Dietary chemicals vs. dental caries; 9780841201088, 0841201080

Table of contents :
Dietary chemicals in relation to dental caries / Robert S. Harris --
Carbohydrates, fats and dental caries / Ward Pigman --
Amino acids, proteins and dental caries / Abraham E. Nizel --
Vitamins and dental caries / Samuel Dreizen --
Antibiotics and dental caries / Basil G. Bibby --
Other organic compounds and dental caries / Kenneth O. Madsen --
Minerals : fluorine and dental caries / Harold C. Hodge and Frank A. Smith --
Minerals : calcium and phosphorus / Robert S. Harris --
Effect of minerals on dental caries / Juan M. Navia --
Application of chemical agents for the control of dental caries / Robert C. Caldwell and Joe P. Thomas.

Citation preview

Dietary Chemicals vs. Dental Caries

zyxwvutsr

Based on a Symposium on Dietary Chemicals in Relation to Downloaded by 80.82.77.83 on May 24, 2018 | https://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.fw001

Dental Caries sponsored by the Agricultural and Food Chemistry Division at the 1966 Winter Meeting of the American Chemical Society, Phoenix, Arizona January 18, 1966

Robert S. Harris zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP Symposium Chairman

ADVANCES

IN CHEMISTRY

AM ERI CAN

CHEM I CAL

WASHI NGTON, D. C.

SERIES

SOCIETY

1970

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

94

zyxwvutsrqponmlkji

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Coden:

ADCSHA

Copyright © 1970 American Chemical Society A l l Rights Reserved

Library of Congress Catalog Card 71-142197 I S B N 8412-0108-0 PRINTED IN THE UNITED STATES OF AMERICA

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

Advances in Chemistry Series

Robert F. Gould,zyxwvutsrqponmlkjihgfedcbaZYX Editor

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Advisory Board Frank G. Ciapetta Gunther Eichhorn Frederick M . Fowkes F. Leo Kauffman Stanley Kirschner John L. Lundberg Fred W. McLafferty William E. Parham

Jack Weiner zyxwvutsrqponmlkjihgfedcbaZYXWVUT

AM ERI CAN CH EM I CAL SOCI ET Y PU BLI CAT I ON S

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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FOREWORD zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCB A D V A N C E S I N C H E M I S T R Y S E R I E S was founded in 1 9 4 9 by the American Chemical Society as an outlet for symposia and collections of data in special areas of topical interest that could not be accommodated in the Society's journals. It provides a medium for symposia that would otherwise be fragmented, their papers distributed among several journals or not published at all. Papers are refereed critically according to ACS editorial standards and receive the careful attention and processing characteristic of ACS publications. Papers published in A D V A N C E S I N C H E M I S T R Y S E R I E S are original contributions not published elsewhere in whole or major part and include reports of research as well as reviews since symposia may embrace both types of presentation.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

PREFACE zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA T X e n t a l C a r i e s , a s o - c a l l e d "disease of c i v i l i z a t i o n , " seems to b e w o r s e n i n g i n the U n i t e d States a n d appears to b e r e l a t e d to the f o o d that p e o p l e eat. F o r these reasons, it seemed t i m e l y to h o l d a f o r m a l discussion of the factors that b e a r o n the p r o b l e m , a n d the s y m p o s i u m o n " D i e t a r y C h e m i c a l s i n R e l a t i o n to D e n t a l C a r i e s " was o r g a n i z e d a n d p r e s e n t e d at the W i n t e r m e e t i n g of the A m e r i c a n C h e m i c a l S o c i e t y i n 1966.

Plans

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w e r e l a i d f r o m the b e g i n n i n g to p u b l i s h this s y m p o s i u m , b u t absence of a c r i t i c a l p a p e r o n a m i n o acids a n d proteins i n t r o d u c e d delays.

When

A b r a h a m E . N i z e l , of the S c h o o l of D e n t a l M e d i c i n e , T u f t s U n i v e r s i t y , g r a c i o u s l y a c c e p t e d the i n v i t a t i o n to fill this g a p a n d s u b m i t t e d his p a p e r i n the F a l l of 1968, the other authors w e r e i n v i t e d to u p - d a t e t h e i r p a pers. S u b s e q u e n t r e v i e w a n d r e v i s i o n has r e s u l t e d i n u p - d a t i n g most of the papers to e a r l y or mid-1970.

B y the t i m e his p a p e r was r e a d y for

r e v i s i o n , R o b e r t C . C a l d w e l l h a d b e e n a p p o i n t e d D e a n of the S c h o o l of D e n t i s t r y at the U n i v e r s i t y of C a l i f o r n i a , L o s A n g e l e s , a n d his c o l l e a g u e at the U n i v e r s i t y of A l a b a m a S c h o o l of D e n t i s t r y , Joe P . T h o m a s , a g r e e d to supervise the r e v i s i o n . T h e r e s u l t i n g v o l u m e is a c o m p r e h e n s i v e a n d up-to-date s u r v e y of the m a j o r f o o d - r e l a t e d factors that enter i n t o tooth d e c a y a n d its p r e v e n t i o n . W h i l e i t m a y not h a v e a l l the answers, it does present the results o n the major lines of effort o n b o t h c a r i o g e n i c a n d cariostatic influences a n d w i l l serve as a s o u n d base f o r f u t u r e research. R o b e r t S. H a r r i s Massachusetts Institute of T e c h n o l o g y Cambridge, Mass. A u g u s t 1970

vi

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

1

Dietary

Chemicals

in

Relation

to

Dental Caries

ROBERT S. HARRIS

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Massachusetts Institute of Technology, Cambridge, Mass.

The incidence of dental caries and gingival and peridontal diseases is constantly increasing in the United States, although it varies with geographical location. Caries will not develop if the teeth are caries-resistant, if the mouth is kept clear of nutrients which support caries-producing bacteria, or if no caries-producing bacteria are present. Since permanent teeth begin to develop before two months of age, early nutrition may affect the eventual development of sound teeth. Various elements and compounds in food are classified as cariogenic or cariostatic. While caries in experimental animals is similar to that in man, caution is needed in projecting results of such studies.

This symposium on "Dietary Chemicals in Relation to Dental Caries" was scheduled for presentation before the American Chemical Society because (a) the dental caries problem in the United States is serious, (b) many chemicals natural to foods have caries-producing or cariespreventing properties, (c) the caries activity of foods may be modified by processing or supplementation, (d) most of the literature relating to this subject has been published in journals which chemists (including food chemists) seldom peruse, and (e) it is important that chemists be informed of the potential importance of food chemicals in the control of dental decay. More diseases afflict the mouth than any other part of the human body. Almost everyone in the United States is troubled with gingival and peridontal diseases and with dental caries at some time during his life span. In 1962, more than $2 billion was spent for dental services in the United States (9), a sum equivalent to about 1.5% of the national income and to about 15% of the total amount spent for health services (14). Though some 95,000 dentists are serving the U.S. population, less 1 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2

DIETARY

zyxwvutsrqponmlkjihgfe VS. D E N T A L CARIES

C H E M I C A L S

t h a n 5 0 % o f t h e p e o p l e h a v e ever r e c e i v e d d e n t a l carezyxwvutsrqponmlkjihgfed (14). A t least t w i c e as m a n y dentists w o u l d b e n e e d e d m e r e l y t o correct c u r r e n t d e n t a l defects i n t h e p e o p l e . T h e d e n t a l caries p r o b l e m , w h i c h has b e e n c a l l e d a "disease o f c i v i l i z a t i o n , " seems to b e w o r s e n i n g . F o r instance, B a r t h o l d i et al. (1) n o t e d t h a t t h e n u m b e r o f caries-free subjects a m o n g e n t e r i n g f r e s h m e n at t h e U n i v e r s i t y o f M i n n e s o t a decreased f r o m 1.8 to 1 . 3 % b e t w e e n 1929 a n d 1959, a n d t h e i n c i d e n c e o f carious teeth rose f r o m 34.8 to 4 9 . 3 % .

I t is

l i k e l y that s i m i l a r trends a r e d e v e l o p i n g r e l a t i v e t o disorders o f t h e soft tissues o f t h e m o u t h . K i t e a n d S w a n s o n (6) r e c e n t l y r e p o r t e d t h e results Downloaded by 80.82.78.170 on December 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch001

of a s u r v e y o f the m o d e r n d e n t a l care p r o v i d e d t o f r e s h m e n at t h e M a s s a chusetts Institute o f T e c h n o l o g y .

O n e i n f o u r a m o n g t h e 913 students

b e t w e e n 16 a n d 2 0 years o l d e x a m i n e d h a d i n c i p i e n t g i n g i v a l disease, a n d t h e average D M F T 9.6.

Detectable

( d e c a y e d , m i s s i n g , a n d filled t e e t h ) rate w a s

tooth decay was being controlled i n only 4 2 % of the

students, a n d f e w o f these h a d r e c e i v e d n e e d e d p e r i o d o n t a l care. O r t h o d o n t i c care w a s r e c e i v e d b y o n l y 1 8 % o f t h e students, a n d this w a s d u r i n g a n average o f 2.9 years. D e p e n d i n g u p o n t h e c r i t e r i a u s e d , m a l o c c l u s i o n o c c u r r e d i n 61 t o 7 1 % o f those students w h o s t i l l h a d a l l p e r m a nent teeth. T h e g e o g r a p h y o f d e n t a l caries i n t h e U n i t e d States ( F i g u r e 1 ) is interesting (2).

I t is highest i n t h e N o r t h e a s t , next h i g h e s t i n t h e N o r t h -zyxwvutsrqp

J. M . Dunning. " Dental Clinics of North America," Saunders

Figure 1.

Incidence and distribution

of dental caries

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

1.

HARRIS

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Dietary Chemicals 3

west a n d N o r t h - C e n t r a l area, a n d least i n the S o u t h - C e n t r a l area.

The

h i g h e r i n c i d e n c e of caries i n the areas of h i g h e r r a i n f a l l has l e d some to suggest that the l e a c h i n g of m i n e r a l s f r o m the s o i l m a y b e a c o n t r o l l i n g factor i n caries d e v e l o p m e n t i n this country. W h i l e it is true that r a i n w a t e r w i l l s l o w l y r e m o v e m i n e r a l s f r o m the s o i l a n d c o n s e q u e n t l y r e d u c e the m i n e r a l content of l o c a l w a t e r s u p p l i e s a n d of f o o d plants g r o w n o n these soils, the interesting g e o g r a p h y of caries i n the U n i t e d States cannot b e e x p l a i n e d this s i m p l y . F o o d s a n d n u t r i t i o n h a v e i m p o r t a n t effects u p o n o r a l h e a l t h . o b s e r v a t i o n that d e n t a l caries does not d e v e l o p i n germ-free Downloaded by 80.82.78.170 on December 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch001

f e d s t e r i l i z e d diets ( I I ) d e c a y process.

The

animals

indicates that b a c t e r i a are essential to the t o o t h

T h e d e m o n s t r a t i o n that caries does not d e v e l o p i n n o r m a l

a n i m a l s f e d b y gastric i n t u b a t i o n ( 5 )

indicates that residues of f o o d

debris are n e e d e d i n the m o u t h to s u p p l y nutrients for the g r o w t h a n d d e v e l o p m e n t of c a r i e s - p r o d u c i n g bacteria. It is p o i n t e d out i n this s y m p o s i u m that m a n y elements a n d c o m p o u n d s i n foods m a y accelerate or r e d u c e the d e v e l o p m e n t of d e n t a l caries ( 8 ) . flavin,

D i e t a r y deficiencies of v i t a m i n s {e.g., A , B , B i , D , E , r i b o 6

2

n i a c i n ) , m i n e r a l s (e.g., C a , P , F e , M n ) , a n d a m i n o acids

(e.g.,

lysine, t r y p t o p h a n ) interfere w i t h the d e v e l o p m e n t a n d m a i n t e n a n c e

of

h e a l t h y tissues i n the m o u t h . B e c a u s e o r a l tissues are sensitive a n d c o n v e n i e n t f o r o b s e r v a t i o n , n u t r i t i o n a l c l i n i c i a n s r o u t i n e l y e x a m i n e the m o u t h w h e n a p p r a i s i n g the n u t r i t i o n status of h u m a n beings. S o m e m i n e r a l s are c a r i o g e n i c , some are cariostatic, a n d some

are

inert w h e n ingested i n the diet. T h e b r a n layers of cereals c o n t a i n org a n i c c o m p o u n d s that h a v e cariostatic p r o p e r t i e s , yet o n occasion

this

" r o u g h a g e " m a y act as a l o c a l i r r i t a n t to the g i n g i v a . Sucrose is c a r i o genic, glucose is r e l a t i v e l y inert, a n d starch is inert. M a n y other elements a n d c o m p o u n d s m a y b e c i t e d to demonstrate that the presence a n d absence of nutrients a n d nonnutrients i n foods p l a y a major role i n determ i n i n g the h e a l t h of o r a l tissues. N u t r i e n t s a n d other c h e m i c a l s i n foods m a y affect the teeth t h r o u g h three routes: b y r e a c t i n g w i t h the t o o t h surface as the f o o d passes t h r o u g h the m o u t h ( l o c a l a c t i o n ) , b y r e a c t i n g w i t h the t o o t h surface after b e i n g a b s o r b e d f r o m the intestine a n d r e t u r n e d to the m o u t h via the s a l i v a a n d t h e n r e a c t i n g w i t h the t o o t h surface

( s y s t e m i c - l o c a l a c t i o n ) , a n d after

b e i n g a b s o r b e d f r o m the intestine a n d e n t e r i n g the t o o t h i n the c i r c u l a t i n g blood (systemic action). T h e systemic influences of n u t r i t i o n a l factors greatest d u r i n g tooth d e v e l o p m e n t .

u p o n the teeth

are

T h e p e r i o d o n t i u m is c o n t i n u a l l y u n -

d e r the influence of systemic factors f r o m the t i m e of e r u p t i o n o f the first t o o t h u n t i l the d e a t h of the host.

The growth, development, and main-

tenance of o r a l tissues are i n f l u e n c e d b y n u t r i t i o n because c e l l g r o w t h

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4 and

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

m e t a b o l i s m , p r o t e i n synthesis, a n d c a l c i f i c a t i o n processes

are i n -

v o l v e d . D i s t u r b a n c e s i n p r o t e i n m e t a b o l i s m m a y influence m a t r i x f o r m a t i o n i n the e n a m e l a n d d e n t i n of the d e v e l o p i n g t o o t h , as w e l l as the i n t e r c e l l u l a r m a t r i x of the c e m e n t u m , the fibrous p e r i o d o n t a l m e m b r a n e , a n d the a l v e o l a r bone.

F a u l t s i n the m e t a b o l i s m of c a r b o h y d r a t e s

fats m a y alter v i t a l reactions i n the cells of these tissues.

and

Deficiencies

of v i t a m i n A m a y affect the f o r m a t i o n of e n a m e l m a t r i x a n d the m a i n t e n a n c e of the e p i t h e l i u m of the p e r i o d o n t a l tissue; v i t a m i n C d e f i c i e n c y m a y affect the f o r m a t i o n of the c o l l a g e n m a t r i x i n d e n t i n , c e m e n t u m , periodontal membrane,

a n d alveolar bone; v i t a m i n D deficiency m a y

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affect the c a l c i f i c a t i o n of e n a m e l , d e n t i n , c e m e n t u m , a n d a l v e o l a r b o n e , etc.

D e f i c i e n c i e s a n d excesses of m i n e r a l s m a y affect the c o m p o s i t i o n

of the c a l c i f i e d tissues, or m a y alter c e l l m e t a b o l i s m t h r o u g h their role i n co-enzymes

(3).

T h e s e systemic influences are j o i n e d b y l o c a l effects w h e n the t o o t h erupts into the o r a l c a v i t y . I o n exchange reactions w i t h the surfaces the o r a l tissues b y elements

of

a n d c o m p o u n d s present i n the s a l i v a a n d

p u l p fluids b e c o m e i m p o r t a n t .

D e g r a d a t i o n p r o d u c t s of d i e t a r y c a r b o -

hydrates a n d m i c r o b i a l e n z y m e s o n the surfaces of the t o o t h c a n p r o m o t e caries d e v e l o p m e n t . R e c e n t research has d e m o n s t r a t e d that c e r t a i n types of m u c o p o l y s a c c h a r i d e - p r o d u c i n g m i c r o o r g a n i s m s w h i c h r e q u i r e sucrose for t h e i r m e t a b o l i s m m a y be the major cause of d e n t a l caries i n h u m a n beings. A t least three factors ( F i g u r e 2 ) are i n v o l v e d i n the d e v e l o p m e n t of

d e n t a l caries: host a n d teeth, m i c r o f l o r a , a n d substrate i n the m o u t hzyxwvutsrqponmlkji (4). C a r i e s w i l l not d e v e l o p i f the teeth are caries-resistant, i f the m o u t h is k e p t c l e a r e d of nutrients

( e s p e c i a l l y sucrose)

w h i c h w i l l sustain

the

g r o w t h a n d m e t a b o l i s m of c a r i e s - p r o d u c i n g b a c t e r i a , or i f the m o u t h is not infected w i t h caries-producing bacteria.

T h u s , caries c a n b e c o n -

t r o l l e d b y a l t e r i n g o n l y one of these c o n d i t i o n s . T h e age of the t o o t h is i m p o r t a n t .

C a r i e s i n d e c i d u o u s teeth m a y

cause e a r l y tooth loss a n d affect the p o s i t i o n i n g of the p e r m a n e n t w h i c h are d e v e l o p i n g b e l o w .

teeth

D e n t a l caries i n the p e r m a n e n t d e n t i t i o n

is of major i m p o r t a n c e because these teeth are " p e r m a n e n t " a n d i r r e t r i e v a b l e i f lost t h r o u g h neglect.

are

T h o u g h d e c i d u o u s teeth are gen-

e r a l l y lost b y 11 years of age, the p e r m a n e n t teeth b e g i n to d e v e l o p before 2 m o n t h s of age. T h u s , n u t r i t i o n m a y h a v e a n effect u p o n the g r o w t h a n d d e v e l o p m e n t of a s o u n d tooth l o n g before i t has e r u p t e d i n t o the mouth. T h e earliest v i s i b l e s i g n of caries is c h a r a c t e r i z e d b y p o r o u s , c h a l k y w h i t e spots i n the e n a m e l . T h e " s m o o t h s u r f a c e " t y p e of caries shows a w i d e - a n g l e d w e d g e of p e n e t r a t i o n . T h e " p i t - a n d - f i s s u r e " caries d e v e l o p a w e d g e of d e c a y that is sharper a n d i n v e r t e d , w i t h the p o i n t at the surface.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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1.

HARRIS

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Dietary Chemicals 5 zyxwvutsrqp

P. H. Keyes and H. V. Jordan, " Mechanisms of Hard Tissue Destruction," American Association for the Advancement of Science

Figure

2.

Factors

responsible

for caries

activity

I n either case, t h e shape o f the lesion corresponds w i t h t h e d i r e c t i o n o f the e n a m e l rods, i n d i c a t i n g that the p a t h o f p e n e t r a t i o n o f d e c a y f o l l o w s s t r u c t u r a l p a t h w a y s . O n c e the surface o f the e n a m e l has b e e n d e s t r o y e d , the b a c t e r i a l i n v a s i o n proceeds

along a n uneven front following the

enamel r o d pattern. D e n t i n a l caries d e v e l o p s as a d i s o r g a n i z a t i o n o f t h e m a t r i x , a n d i n the d i r e c t i o n o f i n c r e m e n t a l g r o w t h lines, c a u s i n g first a l a t e r a l s p r e a d , a n d later a p r o g r e s s i o n a l o n g the d e n t i n a l t u b u l e s . T h e r a t has b e e n u s e d most w i d e l y i n e x p e r i m e n t a l caries research. T h e deep

fissures

i n t h e m o l a r teeth s h o w t h e highest i n c i d e n c e a n d

extent o f d e n t a l caries d e v e l o p m e n t . W h i l e these carious lesions are v e r y s i m i l a r t o those i n m a n , n o e x p e r i m e n t a l a n i m a l has teeth that c o m p l e t e l y resemble those o f the h u m a n b e i n g . T h u s , t h e results o f caries research c o n d u c t e d w i t h rats, hamsters, a n d even p r i m a t e s cannot b e p r o j e c t e d to the h u m a n b e i n g w i t h o u t reservation. D u r i n g the d e v e l o p m e n t o f caries, m i n e r a l s m a y b e w i t h d r a w n f r o m c o n s i d e r a b l e depths i n t h e t o o t h structure, i n spite o f t h e h i g h d e n s i t y of the e n a m e l (12).

D e m i n e r a l i z i n g agents r e a c h into t h e e n a m e l struc-

ture a l o n g p a t h w a y s r e l a t e d p r i m a r i l y t o t h e striated structure o f t h e enamel. D e n t a l caries has b e e n r e p o r t e d to d e v e l o p i n e x p e r i m e n t a l a n i m a l s w i t h i n f o u r days f o l l o w i n g e r u p t i o n (13). time-sequence

O p d y k e ( J O ) has s t u d i e d t h e

o f lesions p r o d u c e d a r t i f i c i a l l y i n h u m a n tooth

enamel

that is b e i n g e x p o s e d t o a n a c i d i c s a l i v a r y - g l u c o s e - a g a r system in vitro. T h e first r e a c t i o n w a s a release o f free m i n e r a l after f o u r d a y s ' exposure; w i t h i n e i g h t days the lesion h a d a characteristic a c i d r e a c t i o n ( p H 4.2-4.5); after the 10th d a y v a r i o u s a m i n o a c i d fractions w e r e o b s e r v e d , a n d , after 20 days l i p i d substances w e r e f o u n d .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

finally,

6

DIETARY CHEMICALS VS. DENTAL CARIES

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Since the structure of the tooth is important to the pathogenesis of caries, those factors which influence the structure of teeth during development are especially important. Mellanby (7) has been foremost i n promoting the concept that the high susceptibility to caries i n modern man results from the faulty tooth structure caused by diet abnormalities during tooth development. Finally, it should be emphasized that caries development is catalyzed or retarded by the presence of elements and compounds, both nutrients and nonnutrients, which act systemically or locally. These are the subject of this symposium. Acknowledgment Contribution Number 1429 from the Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass. Literature Cited (1) Bartholdi, W. L . , Peterson, E . E., Crawford, W . H . , J. Am. Dental Assoc. 1961, 63, 868-871. (2) Dunning, J. M., "The Dental Clinics of North America," pp. 291-303, Saunders, Philadelphia, Pa., 1962. (3) Harris, R. S., Ed., "The Art and Science of Dental Caries Research," Academic, New York, 1968. (4) Keyes, P. H . , Jordan, H . V., "Mechanisms of Hard Tissue Destruction," R. F . Sognnaes, Ed., pp. 261-283, Pub. 75, American Association for the Advancement of Science, Washington, D . C., 1963. (5) Kite, O. W., Shaw, J. H . , Sognnaes, R. F., J. Nutr. 1950, 42, 89-103. (6) Kite, Owen W., Swanson, Leonard T., J. Am. Dental Assoc. 1965, 70, 1143-1152. (7) Mellanby,M.,"The effect of diet on dental structure and disease in man," Medical Research Council, Spec. Rept. Ser. #191, London, 1936. (8) Nizel, A. E., "The Science of Nutrition and Its Application in Clinical Dentistry," A. E . Nizel, Ed., Saunders, Philadelphia, Pa., 1966. (9) Office of Business Economics, "Survey of Current Business," U . S. Dept. of Commerce, Washington, D. C., July 1963. (10) Opdyke, D . L . , J. Dental Res. 1960, 39, 698, Abst. 129. (11) Orland, F . J., Blayney, J. R., Harrison, R. W., Reyniers, J. A., Trexler, P. C., Gordon, H . A., Wagner, M . , Luckey, T. D., J. Dental Res. 1954, 33, 147-174. (12) Sognnaes, R. F., "Chemistry and Prevention of Dental Caries," Charles C. Thomas, Springfield, Ill., 1962. (13) Steinman, R. R., Hewes, C. G., Woods, R. W., J. Dental Res. 1959, 38, 592-605. (14) Volker, J. F., "Dental Clinics of North America," p. 385, Saunders, Philadelphia, Pa., 1962. RECEIVED October 27, 1969.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2

Carbohydrates, Fats, and Dental Caries

WARD PIGMAN

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Department of Biochemistry, New York Medical College, New York, N . Y. 10029

Dental caries results from attack on the tooth surface by microorganisms, especially in noncleansing areas. Dietary factors may influence this attack by acting on the tooth or the microorganisms. With experimental animals, dietary carbohydrates exert a pre- and post-eruptive cariogenic effect, whereas fats as a whole may mediate the postzyxwvutsrqponmlk -eruptive effect. Comparisons of primitive man with man living under urban conditions have demonstrated a great enhancement in dental caries in modern man. Such studies and those with controlled populations have suggested that some types of carbohydrates are the main origin of the increased incidence of dental decay. In vitro studies using the artificial mouth have shown most common sugars to be potentially cariogenic.

Carbohydrate constituents usually provide the major source of energy in human diets. As starches, modified starches, and sugars, they also have been the dietary products most susceptible to industrial modification and application in products such as syrups, refined sugars, candies, gums, puddings, soft drinks, canned fruits, and other products. Since these products are produced and consumed mainly in highly industrialized countries, which also have high rates of dental decay, much interest has been shown in the relationship of such products to dental caries. Many investigations of various types have been carried out to determine whether a direct relationship exists between dietary carbohydrates and the incidence of dental caries. The number of such investigations is so great that they cannot be considered adequately in this review. As a result, the principal types of investigations w i l l be considered, and except for recent work, reference generally w i l l be given to secondary sources which discuss the subject more adequately and also give the original 7 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

8

DIETARY

literature.

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

A v a l u a b l e b i b l i o g r a p h y o f recent research o n d e n t a l caries

(4). has b e e n p r e p a r e d b y B r i s l i n a n d C o xzyxwvutsrqponmlkjihgfedcbaZYXWVUTSR

U n i v e r s a l agreement seems to exist o n t h e nature of t h e basic process i n v o l v e d i n d e n t a l caries.

I t consists of t h e attack b y t h e p r o d u c t s of

m e t a b o l i s m of o r a l b a c t e r i a

o n exposed surfaces

o f teeth, u s u a l l y o n

e n a m e l , b u t also o c c u r r i n g o n c e m e n t u m a n d exposed d e n t i n . T h e attack is thus b a s i c a l l y external, a l t h o u g h p o s s i b l y m o d i f i e d b y i n t e r n a l m e t a b o l i c influences.

D e n t a l caries i n i t i a l l y is n e a r l y a l w a y s h i g h l y l o c a l i z e d a n d

i n positions w h i c h are n o n c l e a n s i n g .

T h e d i s t r i b u t i o n of lesions i n t h e

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m o u t h has a s i m i l a r p a t t e r n i n most persons, a n d t h e areas most c o m m o n l y affected are t h e pits a n d fissures of molars a n d p r e m o l a r s , i n t e r p r o x i m a l positions, a n d c e r v i c a l m a r g i n s .

T h e s e positions a c c u m u l a t e f o o d p a r t i -

cles, a n d p r e s u m a b l y are t h e best positions f o r t h e establishment of b a c t e r i a l plaques.

T h e c o m b i n a t i o n of f o o d m a t e r i a l a n d b a c t e r i a p r o v i d e

the attack factor i n d e n t a l caries.

T h e attack, h o w e v e r , is m o d i f i e d b y

m a n y factors, some of w h i c h w i l l b e c o n s i d e r e d later. S a l i v a is r e l a t e d to d e n t a l caries as a b i o l o g i c a l fluid w h i c h washes out f e r m e n t a b l e substrates b e f o r e t h e y are m e t a b o l i z e d , d i l u t e s h a r m f u l b a c t e r i a l p r o d u c t s b e f o r e t h e y attack t h e t o o t h surface, p o s s i b l y repairs i n c i p i e n t carious lesions t h r o u g h r e m i n e r a l i z a t i o n , a n d modifies t h e t o o t h surface b y p r o v i d i n g t h e elements n e e d e d f o r t h e s e c o n d a r y c u t i c l e of the

tooth.

I n a d d i t i o n , its i m m u n e b o d i e s

m a y affect t h e b a c t e r i a l

p o p u l a t i o n . zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED

P^re-Eruptive and Systemic Effects R e l a t i v e l y little is k n o w n , except c o n c e r n i n g fluorides, of t h e d i e t a r y effects that take p l a c e d u r i n g t o o t h f o r m a t i o n o r w h i c h result f r o m gene r a l m e t a b o l i c influences.

H o w e v e r , K i t e , S h a w , a n d Sognnaes (23,

30)

s h o w e d that rats f e d o n c a r b o h y d r a t e - r i c h diets d e v e l o p e d caries, b u t a g r o u p to w h i c h t h e same diet w a s g i v e n b y s t o m a c h t u b e d e v e l o p e d n o caries.

T h i s indicates that t h e effect w a s p r i m a r i l y a l o c a l o n e at t h e

t o o t h surface. S e v e r a l studies h a v e b e e n c a r r i e d o u t w i t h different types of a n i m a l s g i v e n h i g h - c a r b o h y d r a t e diets at v a r i o u s stages of t o o t h f o r m a t i o n a n d m a t u r a t i o n (23, 28).

Sognnaes ( T a b l e I ) f o u n d that a n i m a l s f e d s u c h

diets d u r i n g p r e g n a n c y h a d p r o g e n y w i t h h i g h e r caries t h a n those f e d " n a t u r a l " diets.

susceptibility

S i n c e t h e i n d i v i d u a l m o l a r teeth of rats

a n d hamsters are f o r m e d a n d erupt at different p e r i o d s , the effect o f a h i g h - c a r b o h y d r a t e diet d u r i n g t h e p e r i o d of t o o t h f o r m a t i o n a n d subseq u e n t m a t u r a t i o n also c o u l d b e s t u d i e d . T h e s e experiments s h o w e d t h e existence of a p e r i o d of h i g h caries s u s c e p t i b i l i t y f o l l o w i n g e r u p t i o n of

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

P I G M A N

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries 9

the teeth a n d a g r a d u a l m a t u r a t i o n to a less susceptible c o n d i t i o n [ F i n n , Klapper and Volker (28)]. Table I.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM

Comparison of Caries Susceptibility in Hamsters, Rats, and Mice When " B r e d " on Stock DietzyxwvutsrqponmlkjihgfedcbaZYXW vs. Purified D i e t 0

Pregnancy. No, of and Animals Lactation

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Species

Posteruptive

Average Caries

Diet

Period, Months

Molars Affected

Incidence

Areas Affected

Caries Score

Hamsters Rats Mice

6 12 15

Stock Stock Stock

Purified Purified Purified

4 4 4

4.6 0 0

5.3 0 0

6.1 0 0

Hamsters Rats Mice

3 10 21

Purified Purified Purified

Purified Purified Purified

2 2 2

9.0 2.4 0.4

31.6 2.7 0.5

48.0 2.7 0.5

° From Sognnaes (30). Copyright by the American Dental Association. Reprinted by permission. T h e effects o f p r e n a t a l n u t r i t i o n o n t h e o r a l structures h a v e r e v i e w e d b y L a r s o n (19). S h a w a n d G r i f f i t h s (26,27)

been

reported many mal-

f o r m e d t h i r d m o l a r s i n y o u n g rats w h o s e mothers h a d b e e n o n diets w i t h a protein-to-sucrose r a t i o of 8 : 8 3 , as c o m p a r e d w i t h those f r o m mothers h a v i n g a r a t i o of 24:67. H a l l o w a y et al. (15), i n a d d i t i o n t o m o r p h o l o g i c a l changes, f o u n d that t h e y o u n g o f m o t h e r rats o n a high-sucrose d i e t h a d teeth less resistant t o caries. Effects on Mature Teeth T h r e e g e n e r a l p r o c e d u r e s h a v e b e e n u s e d f o r studies of t h e influence of d i e t a r y c a r b o h y d r a t e s a n d fats o n t h e i n c i d e n c e o f t o o t h d e c a y .

These

are h u m a n n u t r i t i o n a l studies w i t h g r o u p s h a v i n g different diets, a n i m a l studies w i t h c o n t r o l l e d diets, a n d in vitro

procedures.

These w i l l be

d i s c u s s e d separately. H u m a n Nutritional Studies (1, 23, 30).

M a n y studies h a v e

been

made using h u m a n populations. These include institutionalized people o n c o n t r o l l e d diets, persons o n restricted diets ( d i a b e t i c s , f o r e x a m p l e ) , a n d p e o p l e l i v i n g u n d e r c o n d i t i o n s n o t affected b y m o d e r n i n d u s t r i a l i z a t i o n (e.g., E s k i m o s , I n d i a n s , e t c . ) . S u c h studies are d i f f i c u l t t o c o n d u c t a n d to i n t e r p r e t i n r e l a t i o n t o c a u s a l relationships. T h e y s h o w that gene r a l l y persons l i v i n g u n d e r p r i m i t i v e c o n d i t i o n s h a v e l o w caries

rates;

the same p o p u l a t i o n types l i v i n g i n u r b a n areas w i t h contact w i t h m o d e r n i n d u s t r i a l p r o d u c t s h a v e m u c h h i g h e r average rates of caries. Since m a n y factors a r e different f o r s u c h u r b a n a n d r u r a l c o n d i t i o n s , a d i r e c t r e l a t i o n to d i e t a r y constituents cannot b e d e m o n s t r a t e d .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

O n e h u m a n s t u d y r e q u i r e s s p e c i a l attention. T h i s s t u d y w a s c a r r i e d o u t at the V i p e h o l m M e n t a l H o s p i t a l at L u n d , S w e d e n , a n d has b e c o m e k n o w n as the V i p e h o l m D e n t a l C a r i e s S t u d y (20, 3 2 ) .

This carefully

c o n d u c t e d s t u d y s h o w e d a f a i r l y clear r e l a t i o n s h i p b e t w e e n c a r b o h y d r a t e p r o d u c t s of some types a n d d e n t a l caries experience.

It w i l l b e d i s c u s s e d

i n m o r e d e t a i l i n a later section. T h e effects of fats i n h u m a n d i e t a r y studies h a v e b e e n s u m m a r i z e d by Volker and Caldwell (35).

T h e g e n e r a l i m p r e s s i o n is that diets r i c h

i n fats are l o w i n c a r i o g e n i c i t y . T h u s , n o m a d i c E s k i m o s o n p r o t e i n - f a t

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diets, c o m p o s e d of as m u c h as 6 5 %

fat, h a d l o w caries i n c i d e n c e .

The

results of several c l i n i c a l studies o n c o n t r o l l e d g r o u p s w e r e i n t e r p r e t e d s i m i l a r l y , b u t , as w i t h most of the studies o n h i g h - c a r b o h y d r a t e diets, t h e interpretations h a v e q u e s t i o n a b l e significance. Animal Studies ( 2 8 ) .

zyxwvutsrqponmlkjihgfedcbaZYXW

M a n y studies of d i e t a r y c o m p o s i t i o n i n r e l a -

t i o n to d e n t a l caries h a v e b e e n c a r r i e d o u t w i t h e x p e r i m e n t a l a n i m a l s . H a m s t e r s a n d rats h a v e b e e n u s e d p r i n c i p a l l y , b u t m o n k e y s a n d other a n i m a l s also h a v e b e e n e m p l o y e d . T h e carious lesions p r o d u c e d i n rats a n d hamsters seem to b e s i m i l a r to those p r o d u c e d i n h u m a n s , a l t h o u g h i n the e a r l y w o r k w i t h rats t h e caries seemed to b e r e l a t e d to coarse diets a n d the f o r m a t i o n of cracks i n the t o o t h structure. T h e caries r a t e c a n b e g r e a t l y i n c r e a s e d b y p r i o r r e m o v a l of the m a i n s a l i v a r y glands. T h e use of " n a t u r a l d i e t s " s u c h as P u r i n a C h o w u s u a l l y r e s u l t e d i n l o w caries rates. W h e n a m a j o r p a r t of the d i e t w a s c o m p o s e d of starches, sucrose, or dextrose, d e n t a l caries w a s extensive, a l t h o u g h some studies h a v e f o u n d starches a n d dextrins to b e less c a r i o g e n i c t h a n sucrose or dextrosezyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA [See F i n n , K l a p p e r , a n d V o l k e r ( 2 8 ) ] . K l a p p e r a n d V o l k e r f o u n d fructose a n d e s p e c i a l l y s o r b i t o l to b e less c a r i o g e n i c t h a n sucrose. M c C l u r e (28)

f o u n d that the c a r i o g e n i c effect of m i l k p r o d u c t s a n d

processed cereals c o u l d b e g r e a t l y i n c r e a s e d b y h e a t treatments.

These

results, a r i s i n g f r o m d e s t r u c t i o n of l y s i n e , e m p h a s i z e the n e e d f o r k n o w l edge of the effects of p r o c e s s i n g treatments o n the possible c a r i o g e n i c i t y of f o o d p r o d u c t s . T h e c a r i o g e n i c i t y of d r y w h e y p o w d e r s also suggests that lactose is p r o b a b l y c a r i o g e n i c i n a n i m a l experiments. Instead of e x p e r i m e n t a l diets, S t e p h a n (31)

a d d e d h u m a n foods

(53

i n a l l ) to b a s i c diets of rats a n d c o m p a r e d the caries experience to that o f a n i m a l s r e c e i v i n g diets of k n o w n c a r i o g e n i c i t y . A s a result, h e classified f o o d p r o d u c t s i n t o five g r o u p s , a c c o r d i n g to the a m o u n t of caries.

The

most extreme g r o u p was c o m p o s e d of foods r i c h i n c a r b o h y d r a t e s , especially fermentable

sugars.

T h e i n t e r p r e t a t i o n of a n i m a l experiments of this t y p e i n terms of h u m a n caries is f r a u g h t w i t h difficulties. T h e caries rate is v e r y h i g h as c o m p a r e d w i t h the u s u a l h u m a n rate.

O n e factor i n c r e a s i n g the rate

is the s m a l l size of r o d e n t teeth a n d the r e s u l t i n g t h i n e n a m e l .

Another

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

P I G M A N

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries 11

is the constant " d i r t y " m o u t h ; s u c h a n i m a l s u s u a l l y h a v e the teeth b u r i e d i n s o l i d f o o d particles.

T h i s f a c t o r is e v e n m o r e d r a s t i c i n d e s a l i v a t e d

a n i m a l s , w h i c h also i n t r o d u c e s the p r o b l e m of c o m p a r i s o n s o f starches w i t h sucrose o r dextrose i n the absence of s a l i v a r y amylases. T h e a n i m a l diets u s u a l l y i n c l u d e starch as u n c o o k e d particles, different f r o m t h e g e l a t i n i z e d starches c o m m o n f o r h u m a n diets.

F o r a n i m a l experiments

of this t y p e , t h e attack forces c o u l d o v e r w h e l m a n y m i l d p r o t e c t i v e forces s u c h as possible s a l i v a c o m p o n e n t s or a n a t o m i c a l relations. T h u s , H a l d i et al. (13)

f o u n d that i n hamsters a h i g h sucrose d i e t p r o d u c e d a l a r g e r

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caries score t h a n a s i m i l a r d i e t w i t h glucose, b u t f o r d e s a l i v a t e d a n i m a l s , the t w o diets gave s i m i l a r results. A n o t h e r m a j o r d i f f i c u l t y is that the v a r i o u s laboratories pass t h r o u g h p e r i o d s d u r i n g w h i c h the u s u a l c a r i o g e n i c diets d o not p r o d u c e

the

e x p e c t e d caries. T h i s v a r i a b i l i t y is p r o b a b l y e x p l a i n e d b y the o b s e r v a t i o n of F i t z g e r a l d a n d K e y e s [ M c D o n a l d ( 2 8 ) ]

that caries-inactive rodents

c o u l d b e c o n v e r t e d to caries-active a n i m a l s b y exposure to caries-active a n i m a l s o r t h e i r feces.

T h u s , a n a p p r o p r i a t e o r a l flora is r e q u i r e d f o r

caries p r o d u c t i o n . E a r l i e r , O r l a n d h a d d e m o n s t r a t e d that germ-free rats d i d not a c q u i r e caries w h e n f e d diets n o r m a l l y c a r i o g e n i c . S e v e r a l studies o f the effects of d i e t a r y fats o n caries i n c i d e n c e i n rats or hamsters h a v e b e e n s u m m a r i z e d b y V o l k e r (34).

T h e fats i n -

c l u d e d w e r e c o r n o i l , l a r d , arachis o i l , a n d h y d r o g e n a t e d arachis o i l . T h e s e studies s h o w e d a r e d u c e d i n c i d e n c e of caries i n c o m p a r i s o n w i t h the c o n t r o l diets.

Since the fats r e d u c e d the other c o m p o n e n t s of the

diet, the effect m a y not h a v e b e e n cariostatic, b u t i n s t e a d t h e result of d i l u t i o n of a c a r i o g e n i c c o m p o n e n t .

T h e u s u a l i n t e r p r e t a t i o n of these

experiments has b e e n that the fats f a v o r e d o r a l clearance, p e r h a p s b y f o r m i n g films o n the teeth.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI

Laboratory Procedures In V i t r ozyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA A n u m b e r of l a b o r a t o r y p r o c e d u r e s h a v e b e e n u s e d to investigate the possible c a r i o g e n i c i t y of c a r b o h y d r a t e s a n d foodstuffs. A c i d Production and Plaque p H ( 3 5 ) .

W h e n h u m a n salivas, s a l i v a r y

d e b r i s , or s a l i v a r y m i c r o o r g a n i s m s are i n c u b a t e d w i t h m a n y sugars, starch p r o d u c t s , or foodstuffs

c o n t a i n i n g these c a r b o h y d r a t e s ,

the

solutions

r a p i d l y b e c o m e a c i d i c ( u s u a l l y p H 4 . 5 - 5 . 0 ) . S t a r c h p r o d u c t s a p p e a r to p r o d u c e a c i d m o r e s l o w l y t h a n the c o m m o n sugars. A m o d i f i c a t i o n of this m e t h o d f o r in vivo studies w a s d e s c r i b e d b y Stephan.

H u m a n subjects w e r e i n s t r u c t e d not to b r u s h t h e i r teeth f o r

several d a y s . T h e p H of t o o t h surfaces w a s t h e n m e a s u r e d b y t o u c h i n g t h e teeth w i t h a t i n y electrode ( a n t i m o n y o r glass) a n d w i t h a c a l o m e l electrode c o n t a c t i n g the s a l i v a i n the floor of the m o u t h . T h e m o u t h t h e n

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

12

DIETARY

zyxwvutsrqponmlkjihgfe VS. D E N T A L CARIES

C H E M I C A L S

was rinsed w i t h a solution containing a carbohydrate or suspended foodstuff. T h e p H o f t h e p l a q u e w a s m e a s u r e d at short t i m e intervals.

With

the c o m m o n sugars, a r a p i d decrease o f p H o c c u r r e d , f o l l o w e d u s u a l l y

b y a s l o w r e t u r n t o t h e o r i g i n a l p H . Results g i v e n b y L u d w i g a n d B i b b y zyxwvutsrqp are s h o w n i n F i g u r e 1 . zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA

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(29)

2 MIN RINSE WITH 20% GLUCOSE. FIG SANDWICH COOKIE. FRENCH FRIED POTATOES. APPLE. COLA BEVERAGE.

IO. 15. 2Q 25. 30. 35. 4Q TIME IN MftJUTES. From Sognnaes, R. F., Ed., " Chemistry and Prevention of Dental Caries," 1962. Courtesy of Charles C. Thomas, Publisher, Springfield, Illinois.

Figure 1. Effect of various foods on plaque pH, based on data by Ludwig and Bibby; taken from Jenkins (29)

T h e a c t u a l results h a v e v a r i e d s o m e w h a t i n v a r i o u s u s i n g different c o n d i t i o n s .

investigations

T h e general p a t t e r n is f o r sugars s u c h as

dextrose a n d sucrose t o s h o w a r a p i d p H d r o p o f several units a n d r a p i d recovery.

S t a r c h p r o d u c t s a n d foods m a y s h o w a less m a r k e d decrease

a n d often a slower recovery. R e c e n t studies o f p l a q u e p H changes b y G . F r o s t e l (2) after ingest i o n o f s o r b i t o l a n d h y d r o g e n a t e d d e x t r i n p r o d u c t s i n d i c a t e that these p r o d u c t s i n d u c e d less p H change t h a n sucrose.

However, Caldwell and

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries

P I G M A N

B i b b y (6)

13

s h o w e d that the p H of carious lesions ( r a t h e r t h a n p l a q u e p H )

i n c r e a s e d w h e n some foodstuffs w e r e taken b y m o u t h . T h e significance of these results i n terms of the r e l a t i o n of h u m a n diets to h u m a n caries experience is u n c e r t a i n . If the a s s u m p t i o n is m a d e that the p r o d u c t i o n of o r g a n i c acids b y o r a l b a c t e r i a is a n i m p o r t a n t feature of the carious process, the results d o p r o v i d e a means f o r d e m o n stration of t h e p o s s i b l e c a r i o g e n i c effects of d i e t a r y c o m p o n e n t s .

How-

ever, as c a r r i e d o u t , the results are at best o n l y s e m i q u a n t i t a t i v e a n d c a p a b l e of d e m o n s t r a t i o n of o n l y gross differences.

They do

suggest,

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h o w e v e r , the i n a d v i s a b i l i t y of m a i n t a i n i n g c o n t i n u o u s l y h i g h levels of f e r m e n t a b l e c a r b o h y d r a t e s i n the s a l i v a .

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ

In VitrozyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE Caries Production (24). T h e e n a m e l c o v e r i n g the c r o w n of h u m a n teeth is w i t h o u t cells a n d is i n c a p a b l e of restoration except b y p u r e l y c h e m i c a l exchange w i t h s a l i v a r y c o m p o n e n t s .

T h e caries process

i n e n a m e l m a y b e r e p r o d u c i b l e b y p u r e l y in vitro p r o c e d u r e s except for s e c o n d a r y effects, s u c h as d e p o s i t i o n of secondary d e n t i n (24).

The many

earlier in vitro experiments b e g u n b y M a g i t o t ( 1 8 7 0 ) a n d other w o r k e r s t e r m i n a t e d i n the d e v e l o p m e n t of the a r t i f i c i a l m o u t h

(24).

T h e o p e r a t i o n of the a r t i f i c i a l m o u t h consists b a s i c a l l y of exposure of m o u n t e d extracted h u m a n teeth to s a l i v a a n d s u b s e q u e n t l y to a bact e r i o l o g i c a l m e d i u m w h i c h m a i n t a i n s the m e t a b o l i s m of the o r a l m i c r o organisms o n the t o o t h surface.

T h e teeth m a y b e b r u s h e d r e g u l a r l y to

s i m u l a t e n a t u r a l lesions, a n d p u r e strains of m i c r o o r g a n i s m s m a y b e u s e d . F o r q u a n t i t a t i v e c o m p a r i s o n s , b l o c k s of h u m a n e n a m e l m a y be

used

i n s t e a d of w h o l e teeth a n d the s o f t e n i n g w h i c h results f r o m the caries

i Journal of the Association

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO

American Dental

Figure 2. Pattern of carious attack on lower left second deciduous molar (24) Al, Occlusal aspect; Bl, buccal aspect; CI, mesial aspect; Dl, distal aspect; and El, lingual aspect before the tooth was put on the standard regime. A2, B2, C2, D2 and E2 show the respective surfaces after 9 weeks on the standard regime. y

Copyright by the American Dental Association. Reprinted by permission.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

14

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedc VS. D E N T A L CARIES

p r o d u c t i o n c a n b e f o l l o w e d b y m i c r o h a r d n e s s measurements.

Typical

lesions p r o d u c e d i n a b r u s h e d m o l a r a r e s h o w n i n F i g u r e 2. T h e f o l l o w i n g c a r b o h y d r a t e s w e r e tested f o r t h e i r a b i l i t y t o cause the s o f t e n i n g of e n a m e l surfaces i n t h e presence o f o r a l m i c r o o r g a n i s m s : dextrose, fructose, galactose, lactose, maltose, sucrose, a n d s o l u b l e starch. T h e s o l u b l e s t a r c h c a u s e d n o s o f t e n i n g , b u t t h e sugars, w i t h t h e p o s s i b l e exception

of maltose,

showed

comparable

rates

of s o f t e n i n g

(25).

3-O-methyl-D-fructose a n d 3-O-methyl-D-glucose were not fermented b y o r a l m i c r o o r g a n i s m s , b u t 3 - O - m e t h y l - D - g l u c o s e w a s a n e u r o t o x i c agent.

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A n interesting relation between

sugar c o n c e n t r a t i o n a n d t h e t y p e

of attack w a s o b s e r v e d w h e n t h e c o n c e n t r a t i o n o f D - g l u c o s e ( d e x t r o s e )

i n t h e b a c t e r i o l o g i c a l m e d i u m w a s s t u d i e dzyxwvutsrqponmlkjihgfedcbaZYXWVUT (24). W i t h sugar a d d e d t o t h e bacteriological m e d i u m , decalcified dentin was attacked b u t not sound e n a m e l o r d e n t i n ; t h e attack w a s thus p r o t e o l y t i c i n nature.

W i t h 0.5%

dextrose i n t h e m e d i u m , s o u n d e n a m e l a n d d e n t i n w e r e extensively d e c a l c i f i e d , b u t n o attack o n d e c a l c i f i e d d e n t i n w a s o b s e r v e d .

F o r 0.2 to

0 . 3 % solutions, d e n t i n a l m a t r i x w a s a t t a c k e d a n d d e c a l c i f i c a t i o n of s o u n d enamel a n d dentin occurred.

T h e s e results suggest i n terms of h u m a n

o r a l c o n d i t i o n s that t h e c o n c e n t r a t i o n of f e r m e n t a b l e sugar i n t h e s a l i v a w i l l d e t e r m i n e t h e n a t u r e of t h e carious attack, w h i c h m a y v a r y at different times d u r i n g t h e d a y . T h e a r t i f i c i a l m o u t h has b e e n u s e d f o r tests o f t h e c a r i o g e n i c i t y of foodstuffs. K o u l o u r i d e s ( u n p u b l i s h e d d a t a ) s u s p e n d e d breakfast cereals ( c o r n b a s e ) i n w a t e r a n d u s e d this as t h e b a c t e r i o l o g i c a l m e d i u m . T h e p r i n c i p a l q u e s t i o n w i t h r e g a r d t o this p r o c e d u r e is w h e t h e r t h e m i c r o b i a l p o p u l a t i o n is t r u l y representative of t h e r e a l flora of t h e o r a l c a v i t y . T h e attack rate is c o n s i d e r a b l y faster t h a n that u s u a l l y o b s e r v e d in the h u m a n mouth.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI

Oral Clearance Studies and Food Retention C l i n i c a l dentists g e n e r a l l y h a v e associated caries lesions w i t h n o n c l e a n s i n g areas of teeth a n d the r e s u l t i n g a c c u m u l a t i o n of f o o d p a r t i c l e s . S u c h areas also w o u l d t e n d t o f a v o r f o r m a t i o n of b a c t e r i a l p l a q u e s . recent years, m a n y l a b o r a t o r y investigations i n t o t h e factors

In

affecting

t h e rate of r e m o v a l of f o o d p r o d u c t s f r o m t h e m o u t h h a v e b e e n c a r r i e d out. T h e s e h a v e b e e n r e v i e w e d b y V o l k e r a n d C a l d w e l l (35).

T h e prin-

c i p a l studies h a v e b e e n c a r r i e d o u t b y d i r e c t measurements of t h e a m o u n t of f o o d residues after v a r i o u s times o f c h e w i n g , b y measurements o f t h e a m o u n t of s a l i v a r y r e d u c i n g sugar d u r i n g a n d after d i g e s t i o n of f o o d , a n d b y measurements o f p r o p e r t i e s of foods ( s u c h as a d h e s i o n ) w h i c h w o u l d b e e x p e c t e d t o affect f o o d r e t e n t i o n .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

15 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries

P I G M A N

Bibby

a n d associates

(35)

have

s t u d i e d the

retention

of

food

p a r t i c l e s i n the m o u t h d u r i n g c h e w i n g a n d h a v e c o m p a r e d v a r i o u s f o o d p r o d u c t s . T h e y also m e a s u r e d the a c i d f o r m e d b y the f o o d s w h e n i n c u bated w i t h saliva, a n d established a "Decalcification Potential" based o n b o t h measurements.

F i g cookies, dates, chocolates, a n d i c e c r e a m w e r e

r e t a i n e d i n h i g h e s t a m o u n t s , a n d p o t a t o c h i p s a n d carrots ( c o o k e d a n d u n c o o k e d ) w e r e c l e a r e d the most r a p i d l y of the foods s t u d i e d . C a l d w e l l (5, 35)

d e v e l o p e d a n a p p a r a t u s to m e a s u r e the a d h e s i o n

o f f o o d p r o d u c t s to t o o t h e n a m e l in vitro.

T h e results f o r a w i d e r a n g e

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of foods s h o w e d t h a t the foods h a d m a r k e d l y different a d h e s i v e p r o p e r ties. C a r a m e l s a n d toffe ( a h a r d c a n d y ) w e r e the most a d h e s i v e f o o d s . V o l k e r a n d P i n k e r t o n ( 1 9 4 7 ) first u s e d s a l i v a r y r e d u c i n g sugar as a m e a s u r e of f o o d r e t e n t i o n b y h u m a n subjects b y L u n d q v i s t (20)

(33).

It w a s u s e d also (32)

as p a r t of the c o m p r e h e n s i v e V i p e h o l m s t u d y

a n d later b y L a n k e (18)

i n a n extension of the V i p e h o l m s t u d y t o o r a l

c l e a r a n c e studies of foods. T a b l e I I f r o m V o l k e r ( 3 3 ) , shows t h e s a l i v a r y r e d u c i n g sugar levels after i n g e s t i o n of several foodstuffs.

zyxwvutsrqponmlkjihgf

Table II. Reducing Sugar (as D -Glucose) in H u m a n Saliva" after Ingestion of Several Foods or Confections b

. . Time of Eating, Min. rT1

Substance

Chewing gum, D e n t y n e , 3.2 grams

No. of Subjects

Av. Glucose Cone, in ma. 0 Time

c

5 Min.

d

15 Min.

d

% 30 Min*

28

30 (chewing)

19

484

147

26

12

4

16

662

131

23

12

9 (av.)

21

377

259

24

11

7

24*

1,909

269

26

12

2.5

16

889

117

18

12

3

25

1,475

149

22

Soft m i n t , B i r c h B i t , 2.5 g r a m s Hard mint, Toronto M i n t , 1.9 g r a m s Chewy candy, C h o c l e t t o , 5.9 grams Cookie, vanilla wafer, 8.2 g r a m s Bread and jam, 76.0 g r a m s

" Reducing substances in saliva calculated as glucose. From Volker (33). Copyright by the American Dental Association. Reprinted by permission. Zero time value is control value taken immediately before beginning the ingestion of the test substances. Time intervening since the beginning of ingestion of the test substances. 6

c

d

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

16

DIETARY

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES zyxwvutsr

C H E M I C A L S

The Vipeholm Dental Caries Study T h e V i p e h o l m D e n t a l C a r i e s S t u d y w a s c e r t a i n l y t h e best d e s i g n e d a n d c o n d u c t e d a n d t h e freest of c r i t i c i s m o f a l l c l i n i c a l studies o f t h e d i r e c t effect of foodstuffs o n caries i n c i d e n c e i n h u m a n s . I n s t i t u t i o n a l i z e d m e n t a l patients principally.

( 4 3 6 ) u n d e r close s u p e r v i s i o n a n d c o n t r o l w e r e u s e d

T w o studies, e a c h of 2 years' d u r a t i o n , f o l l o w e d 2 years of

p r e p a r a t i o n a n d p r e l i m i n a r y studies. S e v e n groups w e r e f o r m e d , a l l w i t h a basic diet plus supplements:

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( 1 ) C o n t r o l G r o u p o n basic d i e t w i t h 150 grams o r 4 0 grams of m a r g a r i n e as c a l o r i c c o m p e n s a t i o n f o r c a r b o h y d r a t e s a d d e d i n other diets. (2)

Sucrose G r o u p g i v e n sucrose i n s o l u t i o n at meals.

(3)

B r e a d G r o u p g i v e n s u g a r - r i c h b r e a d o r rolls.

( 4 ) C h o c o l a t e G r o u p g i v e n sucrose i n s o l u t i o n f o r first 2 years a n d m i l k chocolate f o r t h e last 2 years. ( 5 ) C a r a m e l G r o u p g i v e n s u g a r - r i c h b r e a d t h e first year, caramels the next 2 years, a n d n o s u p p l e m e n t t h e last year. ( 6 ) 8-Toffee G r o u p g i v e n n o s u p p l e m e n t t h e first year a n d 8 toffees ( h a r d c a n d i e s ) d a i l y f o r 3 years. ( 7 ) 24-Toffee G r o u p g i v e n 24 toffees d a i l y f o r 1.5 years a n d n o s u p p l e m e n t f o r t h e last 2.5 years. T h e basic d i e t f o r t h e first 2 years w a s 1800 calories, l o w i n sugars b u t h a v i n g c o n s i d e r a b l e b r e a d a n d potatoes

as c a r b o h y d r a t e

sources.

T h e b a s i c d i e t f o r t h e last 2 years p r o v i d e d 2700 calories, a n d t h e a m o u n t s of b r e a d a n d potatoes w e r e i n c r e a s e d p a r t i c u l a r l y . T h e v i t a m i n a n d m i n e r a l content w e r e s t u d i e d a n d c o n s i d e r e d satisfactory. C a n d i e s , w h e n g i v e n i n a d d i t i o n to t h e basic diet, a p p a r e n t l y c o u l d b e eaten

between

meals. T h e c a r b o h y d r a t e c o n s u m p t i o n b y groups w a s r e c o r d e d . C a r e f u l d e n t a l examinations w e r e c a r r i e d o u t a n n u a l l y , w i t h t w o examinations p r i o r to the s t u d y . Some of the results are as f o l l o w s . W h e n t h e sugar w a s c o n s u m e d o n l y at meals a n d t h e t o t a l a m o u n t c o n s u m e d w a s c o m p a r e d w i t h d e n t a l caries experiences, p r a c t i c a l l y n o r e l a t i o n c o u l d b e d e m o n s t r a t e d , a n d the caries rate w a s l o w . W h e n t h e candies w e r e g i v e n b e t w e e n meals, a m a r k e d e n h a n c e m e n t of rate w a s d e m o n s t r a t e d o v e r t h e c o n t r o l g r o u p . W h e n t h e candies w e r e r e m o v e d , t h e rates d r o p p e d a g a i n i n t h e subsequent period. T h e conclusions of t h e s t u d y a r e : (1)

T h e c o n s u m p t i o n of sugar c a n increase caries a c t i v i t y .

( 2 ) T h e risk of sugar i n c r e a s i n g caries a c t i v i t y is great i f t h e sugar is c o n s u m e d i n a f o r m w i t h a strong t e n d e n c y to b e r e t a i n e d o n t h e surface o f t h e teeth. ( 3 ) T h e risk of sugar i n c r e a s i n g caries a c t i v i t y is greatest i f t h e sugar is c o n s u m e d b e t w e e n meals a n d i n a f o r m i n w h i c h t h e t e n d e n c y to b e

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries 17

P I G M A N

r e t a i n e d o n t h e surface of t h e t e e t h is p r o n o u n c e d , w i t h a t r a n s i e n t l y h i g h c o n c e n t r a t i o n of sugar o n these surfaces. ( 4 ) T h e increase i n caries a c t i v i t y u n d e r u n i f o r m e x p e r i m e n t a l c o n d i t i o n s varies w i d e l y f r o m one p e r s o n to another. ( 5 ) Increase i n caries a c t i v i t y d u e to intake o f s u g a r - r i c h foodstuffs c o n s u m e d i n a m a n n e r f a v o r i n g caries d i s a p p e a r s o n w i t h d r a w a l of s u c h foodstuffs f r o m t h e d i e t . ( 6 ) C a r i e s lesions m a y c o n t i n u e to a p p e a r despite the a v o i d a n c e of r e f i n e d sugar a n d m a x i m u m r e s t r i c t i o n o f n a t u r a l sugars a n d t o t a l d i e t a r y carbohydrates. Downloaded by CORNELL UNIV on August 23, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch002

B y sugar, sucrose w a s meant, a n d t h e s t u d y seemed to evaluate p r i m a r i l y the effects of candies t a k e n b e t w e e n meals. Sugars t a k e n n o r m a l l y at meals h a d l i t t l e influence. S t a r c h p r o d u c t s w e r e n o t c o n s i d e r e d . T h e significance o f t h e s t u d y w a s c o n s i d e r a b l y e n h a n c e d b y a p a r a l l e l s t u d y b y L u n d q v i s t (20)

of t h e same g r o u p s . F o r this s t u d y , t h e s a l i v a r y

r e d u c i n g sugars ( a f t e r a c i d h y d r o l y s i s of s a l i v a s a m p l e s ) w e r e m e a s u r e d at 15-minute p e r i o d s d u r i n g t h e w o r k i n g hours o n t y p i c a l days f o r the seven g r o u p s . T h e s e studies s h o w e d increases b e t w e e n meals, a n d w i t h some persons the salivas almost c o n t i n u o u s l y h a d glucose e q u i v a l e n t s o f 0.3 to 2 % . T h e s a l i v a r y r e d u c i n g sugar profiles f o r t h e v a r i o u s g r o u p s are s h o w n i n F i g u r e 3. T h e figure also gives t h e caries a c t i v i t y o f t h e g r o u p s . T h e i n d i v i d u a l patterns of s a l i v a r y r e d u c i n g sugar w e r e q u a n t i t a t e d b y c a l c u l a t i o n of a clearance t i m e b a s e d o n the r e d u c i n g sugar c o n c e n t r a t i o n a n d percentage of the w a k i n g hours i n v o l v e d .

These

clearance

times f o r the v a r i o u s groups c o r r e l a t e d closely w i t h the caries a c t i v i t y , as s h o w n i n F i g u r e 4. I n a separate s t u d y u s i n g t w o persons, L u n d q v i s t (20,35)

also m e a -

s u r e d the clearance o f a large n u m b e r o f foods b y m e a s u r i n g the s a l i v a r y r e d u c i n g sugar ( a f t e r a c i d h y d r o l y s i s ) o v e r a p e r i o d of t i m e . T h e results d i d n o t correlate a l w a y s w i t h the t o t a l c a r b o h y d r a t e content, a l t h o u g h candies a n d s u g a r - r i c h p r o d u c t s w e r e g i v e n the highest caries p o t e n t i a l i t y index. A l t h o u g h the p h y s i c a l consistency of foods g e n e r a l l y has b e e n r e l a t e d to c a r b o h y d r a t e o r a l clearance, recent w o r k has i n d i c a t e d that the e l i m i n a t i o n of s o l i d foods f r o m diets of rodents r e s u l t e d i n a r a p i d decrease of s a l i v a r y g l a n d f u n c t i o n a n d g l a n d w e i g h t (14).

I n a d d i t i o n to f o o d

clearance a n d s a l i v a r y g l a n d a t r o p h y , a t h i r d factor has b e e n suggested as c o n t r i b u t i n g to h i g h e r t o o t h resistance

against caries.

T h i s is t h e

m e c h a n i c a l effect of m a s t i c a t i o n o n the crystallites of t h e e n a m e l structure (21).

A l t h o u g h d i r e c t e v i d e n c e f o r this factor is l a c k i n g , it m a y b e a n

a d d i t i o n a l m e c h a n i s m r e l a t i n g t h e p h y s i c a l consistency of foods to the d e v e l o p m e n t of d e n t a l caries.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

18

C H E M I C A L S

zyxwvutsrqponmlkjihgfe VS. D E N T A L CARIES

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DIETARY

Ttaw of day

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO Odontologisk Revy zyxwvutsrqponmlkjihgfe

Figure 3. Concentrations of salivary reducing sugar during the waking periods of persons in the seven groups of the Vipeholm Study as given by Lundqvist (20) zyxwvutsrqponmlkjihg

The Place of Sucrose Sucrose is one o f the most i m p o r t a n t i n d u s t r i a l sugars u s e d i n foods. A l t h o u g h most of t h e early studies c i t e d p r e v i o u s l y d i d n o t differentiate sucrose f r o m other c o m m e r c i a l sugars a n d starches, c o n s i d e r a b l e recent w o r k suggests that i t m a y b e m o r e c a r i o g e n i c . T h i s recent w o r k has b e e n

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

P I G M A N

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Carbohydrates, Fats, Dental Caries 19

r e v i e w e d b y N e w b r u n ( 2 2 ) . T h e basis f o r t h e s p e c i a l effect is t h e r e l a tionship of the cariogenicity of streptococci

a n d some

other m i c r o -

organisms t o t h e i r a b i l i t y t o f o r m b a c t e r i a l p l a q u e s a n d e x t r a c e l l u l a r dextrans a n d levans. E x p e r i m e n t a l l y , these p o l y s a c c h a r i d e s a r e f o r m e d f r o m sucrose b u t n o t f r o m glucose o r other c o m m o n sugars. T h e s e p o l y saccharides a p p a r e n t l y a i d p l a q u e g r o w t h b y h e l p i n g t h e m i c r o o r g a n i s m s to a t t a c h themselves to t h e e n a m e l surface. T h e y m a y act also as a storage f o r m o f fructose o r glucose w h i c h m a y b e released s l o w l y b e t w e e n meals. G u s t a f s o n et al. (12) e a r l y s h o w e d that t h e caries a c t i v i t y o f e x p e r i -

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m e n t a l diets f o r hamsters w a s r e l a t e d t o t h e sucrose content. (17)

Krasse

f o u n d that sucrose w a s better t h a n glucose i n i n d u c i n g p l a q u e s o f

c a r i e s - i n d u c i n g streptococci.

T h e i n c l u s i o n o f sucrose i n a n i m a l diets

c a u s e d the p r o d u c t i o n o f b o t h e x t r a c e l l u l a r a n d i n t r a c e l l u l a r p o l y s a c c h a rides, w h e r e a s glucose c a u s e d t h e f o r m a t i o n o f o n l y i n t r a c e l l u l a r m a t e r i a l (9). Rats o r hamsters w h i c h h a d t h e i r i n d i g e n o u s o r a l flora depressed b y the use o f a n t i b i o t i c s w e r e i n o c u l a t e d w i t h c a r i o g e n i c streptococci.

Diets

c o n t a i n i n g 2 5 % o f t h e f o l l o w i n g c a r b o h y d r a t e s w e r e u s e d : sucrose, g l u cose, fructose, maltose, a n d u n c o o k e d starch.

T h e streptococci d i d not

s u r v i v e i n a n i m a l s f e d o n diets l a c k i n g i n sucrose, a n d t h e highest caries experience w a s f o u n d f o r t h e g r o u p g i v e n sucrose (8, 11). I n other s i m i l a r studies, b u t w i t h n a t u r a l o r a l flora, o n rats f e d diets i n w h i c h a n u m b e r o f c a r b o h y d r a t e s w e r e c o m p a r e d w i t h sucrose, t h e results w e r e m o r e e q u i v o c a l . A l l o f t h e sugars p r o d u c e d c o m p a r a b l e caries, at least i n some experiments (10, 26, 27). W i t h m o n k e y s o n c a r b o h y d r a t e - r e s t r i c t e d diets, B o w e n a n d C o r n i c k (3)

f o u n d that the o r a l p o p u l a t i o n o f b a c t e r i a w h i c h f o r m e d p o l y s a c c h a -

rides decreased a n d i n c r e a s e d w h e n c a r b o h y d r a t e s w e r e i n c o r p o r a t e d into t h e diets.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC

Bread

Control Sucrose Chocolate 8 Toffee Caramel 24 Toffee

Odontologisk Revy

Figure 4. Comparison of clearance of reducing sugar from the saliva of persons in the Vipeholm Study (Lundqvist, 20)

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

20

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES zyxwvuts

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG

Present Status

Basis of Variability of Caries Experience. O n e of the c o n c l u s i o n s of

the V i p e h o l m s t u d y w a s that despite a stringent c o n t r o l of the h u m a n e x p e r i m e n t a l subjects, c o n s i d e r a b l e

v a r i a t i o n i n caries

experience

c u r r e d i n e a c h g r o u p . T h i s agrees w i t h g e n e r a l c l i n i c a l experience

ocof

great v a r i a t i o n s b e t w e e n i n d i v i d u a l szyxwvutsrqponmlkjihgfedcbaZYXWVUT (e.g., f a m i l y g r o u p s ) w i t h s i m i l a r environments.

It is also of interest that a b o u t one or t w o persons

per

t h o u s a n d are c o m p l e t e l y caries-free at the age of n a v a l recruits. T h i s v a r i a b i l i t y suggests that at best the r e l a t i o n s h i p b e t w e e n d e n t a l Downloaded by CORNELL UNIV on August 23, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch002

caries experience a n d d i e t a r y factors is not a s i m p l e cause-effect r e l a t i o n , a l t h o u g h m u c h e v i d e n c e exists that m a n y c a r b o h y d r a t e s c a n b e c o n s i d e r e d as c a r i o g e n i c u n d e r some c o n d i t i o n s . T h e v a r i a b i l i t y p r e s u m a b l y arises f r o m a n u m b e r of factors, some of w h i c h c a n b e classified as h e r e d i t a r y factors. T h e most o b v i o u s h e r e d i t a r y factors are the size, shape, a n d arrangem e n t of teeth i n the m o u t h , the a m o u n t a n d c o m p o s i t i o n of the s a l i v a , a n d the r e l a t i o n of the soft tissues to the teeth. w o u l d b e r e l a t e d to self-cleansing

M o s t of these factors

a n d food retention

characteristics,

a l t h o u g h s a l i v a r y effects c o u l d be e v e n m o r e p r o f o u n d a n d i n v o l v e s u c h components

as buffers,

antibacterial

agents, a n d e n a m e l

rehardening

materials. V a r i a b i l i t y not r e l a t e d to genetic factors also c o u l d arise f r o m d i f ferences a n d changes i n the o r a l m i c r o f l o r a .

T h i s factor r e c e n t l y

r e c e i v e d c o n s i d e r a b l e interest i n the w o r k of K e y e s et al.

(29).

has The

m a t u r a t i o n of t o o t h surfaces after e r u p t i o n is another source of v a r i a t i o n , one of the most c r i t i c a l k n o w n factors b e i n g exposure to fluorides i n the d i e t or w a t e r . Controllable Factors. T h e a b o v e causes of v a r i a b i l i t y ( e x c e p t

ride)

are

essentially

innate a n d not subject to d i e t a r y c o n t r o l .

p r o b l e m that remains is to d e t e r m i n e h o w to m i n i m i z e the c a r i o g e n i c effects of most d i e t a r y c a r b o h y d r a t e s .

fluThe

potential

G e n e r a l l y , the p r o b l e m

seems to r e d u c e itself to d e t e r m i n i n g h o w foodstuffs c a n b e k e p t f r o m contact or b e r e m o v e d f r o m the teet h a n d o r a l c a v i t y as r a p i d l y as possible. Sufficient e v i d e n c e n o w exists to s h o w that s t i c k y c a r b o h y d r a t e - r i c h foods s h o u l d be r e m o v e d f r o m the h u m a n diet as m u c h as

possible.

T h i s a c t i o n w i l l r e q u i r e the l i s t i n g of specific items after c a r e f u l c o n s i d e r a t i o n of the e v i d e n c e . h e a l t h agencies.

P r e s u m a b l y , this s h o u l d b e d o n e b y a p p r o v e d

T h e r e s t r i c t i o n of c a r i o g e n i c substances to

mealtimes

also requires emphasis. T h e same c a r b o h y d r a t e i n different p h y s i c a l f o r m s m a y v a r y m a r k e d l y i n c a r i e s - p r o d u c i n g a c t i v i t y . T h i s s i t u a t i o n suggests that

manufac-

turers of foodstuffs c o n s i d e r the r e l a t i o n to p o t e n t i a l c a r i o g e n i c i t y i n

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

2.

PiGMAN

Carbohydrates, Fats, Dental Canes

21

their formulation and processing methods. In general, methods are probably available for making this judgment. Thus, Volker (33) made a preliminary study of an Army F i e l d Ration and showed slow oral clearance.

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In some instances, it may be possible also to substitute a less cariogenic for a more cariogenic component. Mixtures often are used widely in processed foods, but the judgment is mainly on taste and consistency, and not on cariogenicity. A n alternative, possible in some applications, would be to incorporate cariostatic agents. The accumulated scientific knowledge is currently such that the cariogenicity of carbohydrate products can be evaluated reasonably well. W e now should be able to terminate the period in which most of the dental profession condemned carbohydrates of all types in all applications, and the food industry as a whole responded by refusals to consider the possible cariogenicity of its products. B y cooperation of dental and health agencies with a receptive industry, dental caries experience can be reduced greatly. Acknowledgment The preparation of this section was supported by a grant from the American Chicle Co., Division of Warner-Lambert Pharmaceutical Co. I also express my thanks to J. M . Navia for help in revising this manuscript. Literature Cited (1) Bibby, B. G., Shaw, J. H., Intern. Dental J. 1965, 15, 1. (2) Blix, G. (Ed.), "Nutrition and Caries Prevention," Swedish Nutrition Foundation, Almqvist and Wiskells, Uppsala, 1965. (3) Bowen, W. H . , Cornick, D . E., Helv. Odontol. Acta 1967, 11, 27. (4) Brislin, J. F., Cox, G. J., "Survey of the Literature of Dental Caries," Univ. of Pittsburgh Press, Pittsburgh, Pa., 1964. (5) Caldwell, R. C., J. Dental Res. 1962, 41, 821. (6) Caldwell, R. C., Bibby, B. G., J. Dental Assoc. 1958, 57, 685. (7) Csaky, T. Z., Ann. Ν. Y. Acad. Sci. 1965, 131, 868. (8) Frostell, G., Keyes, P. H., Larson, R. H., J. Nutr. 1967, 93, 65. (9) Gibbons, R. J., Socransky, S. S., Arch. Oral Biol. 1962, 7, 73. (10) Green, R. M . , Hartles, R. L., Arch. Oral Biol. 1969, 14, 235. (11) Guggenheim, B., Konig, K. G., Herzog, E., Muhlemann, H . R., Helv. Odontol. Acta 1966, 10, 101. (12) Gustafson, G., Stellings, E., Abramson, E., Brumius, E., Odontol. Tidskr. 1953, 61, 386. (13) Haldi, J., Law, M. L., John, J., J. Dental Res. 1967, 46, 739. (14) Hall, H . D., Schneyer, C. Α., Proc. Soc. Exptl. Biol. Med. 1964, 117, 789. (15) Halloway, P. J., Shaw, J. H . , Sweeney, J., Arch. Oral Biol. 1961, 3, 185. (16) Koulourides, T., Alabama Dental Rev. 1963, 11, 10. (17) Krasse, B., Arch. Oral Biol. 1965, 10, 215, 223. (18) Lanke, L. S., Acta Odontol. Scand. 1957, 15, Suppl. 23.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

22 (19) (20) (21) (22) (23) (24) (25) (26) (27) (28)

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(29) (30) (31) (32) (33) (34) (35)

DIETARY CHEMICALS VS. DENTAL CARIES

Larson, R. H . , J. Am. Dietet. Assoc. 1964, 44, 368. Lundqvist, C., Odontol. Rev. 1952, 3, Suppl. 1. Neumann, H . H . , DiSalvo, N. A., Ann. N. Y. Acad. Sci. 1965, 131, 893. Newbrun, E., J. Dentistry Children 1969, 36, 239. Pigman, W., "The Carbohydrates," p. 807, Academic Press, New York, 1957. Pigman, W., J. Am. Dental Assoc. 1955, 51, 685. Pigman, W., Brasher, J., Koulourides, T., Nature 1962, 195, 190. Shaw, J. H . , Griffiths, D., J. Nutr. 1963, 80, 123. Shaw, J. H . , Krumins, I., Gibbons, R. J., Arch. Oral Biol. 1967, 12, 755. Sognnaes, R. F., Ed., "Advances in Experimental Caries Research," American Association for the Advancement of Science, Washington, D . C., 1955. Sognnaes, R. F., Ed., "Chemistry and Prevention of Dental Caries," Thomas, Springfield, Ill., 1962. Sognnaes, R. F., J. Am. Dental Assoc. 1948, 37, 676. Stephan, R. M., J. Dental Res. 1966, 45, 1551. Vipeholm Dental Caries Study, Acta Odontol. Scand. 1954, 11, 195-388. Volker, J. F., J. Am. Dental Assoc. 1955, 51, 285. Volker, J. F., " A Symposium on Preventive Dentistry," M . K. Hine, J. C. Muhler, Eds., Mosby, St. Louis, Mo., 1956. Volker, J. F., Caldwell, R. C., "Clinical Pedodontics," S. F. Finn, Ed., Saunders, Philadelphia, Pa., 1967.

RECEIVED August 14,

1968.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

3

Amino Acids, Proteins, and Dental Caries

ABRAHAM E. NIZEL

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School of Dental Medicine, Tufts University, Boston, Mass. 02111

Amino acids and proteins have the potential of being classified as anti-caries nutrients, like fluorides and phosphates. Animal and in vitro studies clearly show that natural protein foods like fish flour, purified compounds like casein, or amino acids like glycine have significant caries-inhibitory and cariostatic effects. The major question that needs to be resolved is whether these findings can be extrapolated to man. Also, we need to determine and understand the mechanisms responsible for producing this effect. It is conceivable that enrichment of sugar and sugar products with amino acids or protein concentrates to reduce their cariogenicity may soon be a reality if we expend more research efforts in this direction.

On

the basis of data obtained from in vitro studies and animal-feeding experiments, it appears that amino acids and dietary proteins may have an effect on dental caries development. However, in human subjects, a direct cause and effect relationship between protein and dental caries has yet to be demonstrated. Furthermore, very few of the studies reviewed in this section suggest the mechanism by which proteins and amino acids influence caries development. Both the lack of clinical studies and paucity of animal or in vitro experiments which deal with possible mechanisms of action indicate the urgent need for more research in protein-dental caries relationship, so that the full potential of protein as an anti-caries nutrient for the human may be realized. Influence of Protein on Dental Caries in Human Beings Population Studies. Ockerse (29) noted that dental caries developed in only 20% of the children who were raised in the Northwest Cape Section of South Africa, an area where the intake of both dietary protein and fluoride are relatively high. This was in sharp contrast to a 23 In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

24

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcba VS. D E N T A L CARIES

1 0 0 % i n c i d e n c e o f caries f o u n d i n c h i l d r e n n a t i v e to the S o u t h e r n R e g i o n of t h e C a p e , a r e g i o n w h e r e the i n t a k e of p r o t e i n a n d fluorides w a s correspondingly lower. T o substantiate his i m p r e s s i o n that p r o t e i n foods a n d fluorides w e r e r e l a t e d to this

finding

of l o w e r caries i n c i d e n c e , O c k e r s e c o n d u c t e d a n

a n i m a l - f e e d i n g e x p e r i m e n t i n w h i c h f e m a l e a l b i n o rats w e r e f e d d u r i n g gestation a n d l a c t a t i o n one of the f o l l o w i n g d i e t s : ( 1 ) c o n t r o l d i e t , ( 2 ) h i g h c a r b o h y d r a t e - l o w p r o t e i n diet, ( 3 ) l o w c a r b o h y d r a t e - h i g h p r o t e i n Downloaded by UNIV OF PITTSBURGH on October 15, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch003

d i e t , ( 4 ) c o n t r o l d i e t p l u s 100 p p m F i n w a t e r , a n d ( 5 ) l o w c a r b o h y d r a t e - h i g h p r o t e i n d i e t p l u s 100 p p m F i n w a t e r .

A t 35 days of age,

a l l t h e o f f s p r i n g w e r e c h a n g e d to a coarse c o r n d i e t , a n d c o n t i n u e d o n i t f o r 45 days m o r e . T h e m e a n caries i n d e x f o r e a c h g r o u p w a s ( 1 ) 5.7; ( 2 ) 8.8; ( 3 ) 3.0; ( 4 ) 2.8; ( 5 )

1.3.

Thus, high carbohydrate and l o w

fluorine

intakes r e s u l t e d i n h i g h e r caries, w h i l e h i g h p r o t e i n a n d h i g h

fluorine

intakes r e s u l t e d i n l o w e r caries.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ

Clinical Studies. A t t e m p t s have b e e n m a d e b y i n d e p e n d e n t i n v e s t i -

gators to correlate the l e v e l of p r o t e i n i n the sera a n d s a l i v a of h u m a n s w i t h t h e i r d e n t a l caries experience.

F o r example, Shannon a n d G i b s o n

( 3 5 ) m e a s u r e d t h e t o t a l p r o t e i n , a l b u m i n , a n d g l o b u l i n levels i n the sera of 505 r a n d o m l y - s e l e c t e d h e a l t h y y o u n g m e n . T h e y w e r e f e d a r a t i o n w h i c h w a s a d e q u a t e i n a l l r e q u i r e d nutrients.

N o correlations b e t w e e n

caries i n c i d e n c e a n d the levels of t o t a l p r o t e i n , a l b u m i n , a n d g l o b u l i n i n the sera w e r e f o u n d . M a n d e lzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA et al. (18) s t u d i e d a g r o u p of 63 c a r i e s - i m m u n e adults w i t h a c o m p a r a b l e g r o u p of caries-active a d u l t s b y a n a l y z i n g p a r o t i d s a l i v a f o r content of t o t a l p r o t e i n a n d p r o t e i n - b o u n d hexosamine a n d b y c o m p a r i n g t h e d i s t r i b u t i o n of v a r i o u s p r o t e i n fractions a n d t h e ratios of fucose a n d hexosamine to n i t r o g e n i n the t w o m a j o r c a r b o h y d r a t e - p r o teins.

N o differences w e r e f o u n d .

Stack ( 3 9 ) c o u l d find n o c o r r e l a t i o n b e t w e e n the levels of s a l i v a r y t r y p t o p h a n a n d the D M F indices of 55 patients, e v e n t h o u g h s u c h a correlation h a d been Crowell

(44).

suggested

b y a n earlier r e p o r t of T u r n e r a n d

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ

Influence of Natural

Food Protein on Animal Caries

Cereals. M c C l u r e (22) c o m p o u n d e d diets c o n t a i n i n g 8 0 % cereals w h i c h h a d b e e n either heat-processed, c o o k e d , o r d r i e d at 1 0 0 ° C , a n d f e d t h e m to rats, w h o d e v e l o p e d smooth-surface caries. S i n c e these finely p u l v e r i z e d diets w e r e l o w i n sugar content, h e c o n c l u d e d that the c a r i o g e n i c i t y of this d i e t w a s related to its l o w - q u a l i t y p r o t e i n content rather than the sugar.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

3.

25 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Amino Acids, Proteins

N I Z E L

I n subsequent experiments, M c C l u r e (20)

demonstrated a h i g h i n -

c i d e n c e of smooth-surface caries i n rats f e d w h e a t flour, d r y or toasted b r e a d , or s h r e d d e d w h e a t b i s c u i t .

W h e n these cereal p r o d u c t s

were

a u t o c l a v e d i n the presence of cerelose or starch, the caries p o t e n t i a l w a s i n c r e a s e d a n d supplements of 1 %

lysine counteracted

this effect.

c o n c l u d e d that this a m i n o a c i d ( l y s i n e ) is the k e y cariostatic

He

nutrient

that is i m p a i r e d d u r i n g the p r o c e s s i n g or h e a t i n g of cereals. D o d d s ( 5 ) was u n a b l e to c o n f i r m the report of M c C l u r e that heatDownloaded by UNIV OF PITTSBURGH on October 15, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch003

p r o c e s s i n g of cereals increases their c a r i o g e n i c i t y , p r e s u m a b l y because of r e d u c e d a v a i l a b i l i t y of their l y s i n e content.

She r e p o r t e d that rats

f e d diets c o m p o s e d m o s t l y ( 8 0 % ) of either c o r n , rice, or oats d e v e l o p e d smooth-surface caries, a n d that the relative c a r i o g e n i c i t y of e a c h of these cereals decreases as f o l l o w s : w h e a t > c o r n > r i c e > Dried M i l k .

M c C l u r e a n d F o l k (24)

oats.

zyxwvutsrqponmlkjihgf

f o u n d that diets c o n t a i n i n g

roller-processed s k i m m e d m i l k p o w d e r s w e r e m o r e c a r i o g e n i c t h a n sprayprocessed s k i m m e d m i l k p o w d e r s w h e n f e d i n the diets of rats.

Since

h i g h e r temperatures are u s e d i n r o l l e r - p r o c e s s i n g t h a n i n s p r a y - p r o c e s s i n g , a n d since l y s i n e is p a r t i a l l y i n a c t i v a t e d w h e n d r y casein is heated, they c o n c l u d e d that the increased c a r i o g e n i c i t y of the r o l l e r - d r i e d m i l k p r o b a b l y w a s r e l a t e d to l y s i n e i m p a i r m e n t . M c C l u r e a n d F o l k (23)

f e d to rats diets i n w h i c h the p r o t e i n w a s

s u p p l i e d b y three different nonfat m i l k p o w d e r s (freeze-dried, s p r a y - d r i e d , a n d r o l l e r - d r i e d ) , a n d they d e v e l o p e d smooth-surface

caries.

The inci-

dence of severity of the caries c o r r e l a t e d w i t h the degree of heat p r o c essing.

L e a s t caries d e v e l o p e d i n the g r o u p f e d the f r e e z e - d r i e d m i l k

a n d the most severe caries i n the g r o u p f e d the r o l l e r - d r i e d m i l k p o w d e r . T h e y later (25)

d e m o n s t r a t e d that caries d e v e l o p m e n t c a n be r e d u c e d

b y the a d d i t i o n of l y s i n e to this t y p e of diet. T h e effect of d r y w h o l e m i l k o n e x p e r i m e n t a l caries has also b e e n s t u d i e d b y M a u r o n et al.

(19),

w h o f o u n d , c o n t r a r y to M c C l u r e ,

that

this source of d i e t a r y p r o t e i n was not c a r i o g e n i c , a n d that there was no r e l a t i o n s h i p b e t w e e n the content of u t i l i z a b l e l y s i n e a n d the p o t e n c y of m i l k - c o n t a i n i n g diets.

D r e i z e n et al.

(6)

cariogenic

c a m e to a s i m i l a r

c o n c l u s i o n , because i n their a n i m a l - f e e d i n g e x p e r i m e n t they f o u n d that d r y w h o l e m i l k f e d at a 3 9 % l e v e l i n a c a r i o g e n i c diet h a d n o a p p r e c i a b l e effect o n i n c r e a s i n g c a r i o g e n i c i t y . R e c e n t l y , G r e e n (10)

suggested that the c a r i o g e n i c i t y of s k i m m e d

m i l k p o w d e r was r e l a t e d to its stickiness a n d the f r e q u e n c y w i t h w h i c h it was eaten. N a t u r a l s k i m m e d m i l k p o w d e r h a d a pleasanter taste t h a n casein or a c a s e i n - r i c h s i m u l a t e d s k i m m e d m i l k p o w d e r , a n d therefore w a s p r e f e r e n t i a l l y selected a n d eaten m o r e f r e q u e n t l y .

A l l three diets (nat-

u r a l s k i m m e d m i l k p o w d e r , casein, c a s e i n - r i c h s i m u l a t e d s k i m m e d m i l k

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

26

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

p o w d e r ) w e r e f o u n d b y analysis to h a v e the same p r o t e i n , c a r b o h y d r a t e , a n d fat content.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Fish

Effect of Fish Protein Concentrate on Animal Caries.

flour,

w h i c h is c u r r e n t l y b e i n g u s e d as a n e c o n o m i c a l source of h i g h - q u a l i t y p r o t e i n f o r f e e d i n g c h i l d r e n i n u n d e r d e v e l o p e d countries, is a n a t u r a l f o o d p r o d u c t , consisting of p r o v e n anti-caries a c t i n g nutrients,

fluorides

a n d phosphates, i n a d d i t i o n to p r o t e i n . S t e p h a nzyxwvutsrqponmlkjihgfedcbaZYXWVUTS (40) a n d N i z e l et al. (26)

h a v e f o u n d that a n otherwise extremely c a r i o g e n i c

experimental

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d i e t c a n b e m a d e significantly less c a r i o g e n i c i f the p r o t e i n

component

of the diet is p r i m a r i l y , i f not c o m p l e t e l y , fish flour. W h a t has not b e e n d e t e r m i n e d is h o w m u c h the fish p r o t e i n has c o n t r i b u t e d to this cariesi n h i b i t i n g effect vis-a-vis

the

the fact remains that F . P . C .

fluoride

or the p h o s p h a t e .

Nevertheless,

(fish p r o t e i n c o n c e n t r a t e ) has the

strong

p o t e n t i a l to b e a u s e f u l a n d effective s u p p l e m e n t f o r r e d u c i n g the i n c i dence of d e n t a l decay.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON

Influence of Synthetic Proteins on Animal Caries Casein. S c h w e i g e r t et al.

(33,

34)

content of a diet was r a i s e d f r o m 2 4 % to 5 0 %

o b s e r v e d that w h e n the

casein

( w h i c h is a d e q u a t e n u t r i t i o n a l l y )

( w h i c h is i n excess), the caries i n c i d e n c e w a s h a l v e d . It w a s

suggested that this effect w a s c a u s e d i n part b y r e p l a c e m e n t of sugar i n the d i e t b y e q u a l amounts of casein, a c o m p o u n d w h i c h is less susceptible to f e r m e n t a t i o n

b y t h e a c i d - p r o d u c i n g organisms associated

with

the

d e c a y process. T h e i m p o r t a n c e of the casein-sucrose

ratio of the diet to

caries d e v e l o p m e n t i n the rat was s t u d i e d b y S t e p h a n (41).

dental

D u r i n g 56

days, groups of 20 w e a n l i n g f e m a l e rats w e r e f e d one of three synthetic diets, the major components of w h i c h w e r e (A) (B)

12%

casein, 8 3 %

sucrose, or ( C )

16%

8 % casein, 8 7 % casein, 7 9 %

sucrose,

sucrose.

He

d e t e r m i n e d that o n d i e t A, 19 rats d e v e l o p e d m o l a r caries a n d 14 rats d e v e l o p e d i n c i s o r caries; o n diet B, 15 rats d e v e l o p e d m o l a r caries a n d o n l y one rat d e v e l o p e d a carious lesion o n the i n c i s o r t o o t h ; a n d o n diet C , 5 rats d e v e l o p e d m o l a r caries a n d n o i n c i s o r carious lesions.

Thus,

less caries d e v e l o p e d as the sucrose content of the diets was progressively r e p l a c e d w i t h casein. Losee and V a n Reen

(17)

reported an experiment

in which

68

w e a n l i n g rats w e r e d i v i d e d i n t o three groups a n d f e d one of the f o l l o w i n g diets, the major constituents of w h i c h w e r e 2 0 % casein a n d 6 1 . 8 %

or 4 0 %

casein

and

71.8%

30%

sucrose.

S o m e caries d e v e l o p e d i n a l l rats, a n d there w a s n o significant

difference b e t w e e n the groups.

sucrose;

casein a n d

sucrose;

51.8%

H o w e v e r , w h e n the caries f r o m these

e x p e r i m e n t a l groups w e r e c o m p a r e d w i t h a c o n t r o l g r o u p w h i c h w e r e

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

3.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Amino Acids, Proteins 27

N I Z E L

f e d g r o u n d R o c k l a n d rat pellets, the latter s h o w e d s i g n i f i c a n t l y m o r e carious teeth a n d m o r e severe caries lesions.

This m a y have been

be-

cause the r e l a t i v e coarseness of the R o c k l a n d d i e t w o u l d t e n d to p r o d u c e f r a c t u r e caries, whereas a diet c o m p r i s e d of sucrose a n d casein has a fine consistency, a n d w o u l d t e n d to p r o d u c e caries o n the s m o o t h B a v e t t a a n d M c C l u r e (1)

o b s e r v e d that i n c r e a s i n g the casein c o n -

tent of the diets of rats r e d u c e d caries.

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surfaces.

A similar observation was made

b y S h a p e r n a k ( 3 6 ) , w h o f o u n d that b y e n r i c h i n g a b a s a l d i e t w i t h

15%

casein, the p e r c e n t a g e of carious teeth w a s decreased b y a b o u t 5 0 %

and

the caries i n d e x b y a b o u t

66%.

S e v e r a l other i n d e p e n d e n t investigators r e p o r t e d that casein exerted

( 5 , 28, 30, 43)

a significant cariostatic

have

effect u n d e r

also the

c o n d i t i o n s of t h e i r experiments. Shaw

(38)

has p o i n t e d out that c a s e i n - r i c h diets h a v e

q u a l i t i e s a n d are r e l a t i v e l y i n s o l u b l e i n the o r a l

fluids.

retentive

T h i s stickiness

m a y encourage the f o r m a t i o n of p l a q u e , w h i c h i n t u r n m a y p r o m o t e the d e v e l o p m e n t of smooth-surface caries.

H e n o t e d that w h e n a m i x t u r e of

a m i n o acids w h i c h d u p l i c a t e d casein was f e d to rats, the a m i n o a c i d m i x t u r e p r o d u c e d less smooth-surface caries t h a n casein itself. T h e a f o r e m e n t i o n e d experiments d e a l w i t h the l o c a l effects of casein s u p p l e m e n t u p o n caries d e v e l o p m e n t i n the n e w l y e r u p t e d tooth. w a y et al.

(13)

Hollo-

s t u d i e d the systemic effects of early f e e d i n g of casein

o n d e n t a l caries experience a n d o n t o o t h q u a l i t y b y f e e d i n g a diet deficient

i n casein ( 8 % ) i n c o m p a r i s o n w i t h one a d e q u a t e i n casein ( 2 4 % )

to m o t h e r rats d u r i n g p r e g n a n c y a n d lactation.

T h e y o b s e r v e d that the

p u p s f e d the l o w - c a s e i n diet w e r e m o r e susceptible to caries

develop-

ment. W h e n the p u p s w e r e f e d a p r o t e i n - a d e q u a t e diet b e f o r e w e a n i n g at 21 days of age, f o l l o w e d b y a protein-deficient d i e t , t h e i r caries score was 22.4.

average

C o n v e r s e l y , w h e n the p u p s w e r e f e d a p r o t e i n -

deficient diet b e f o r e w e a n i n g , a n d a p r o t e i n - a d e q u a t e diet after w e a n i n g , the score was 42.0; this w o u l d be i n d i c a t i v e of a m a r k e d systemic effect o n caries d e v e l o p m e n t d u e to the p r o t e i n c o m p o n e n t .

Since the

first

a n d s e c o n d molars of rats e r u p t at 18 to 20 days of age, it is e v i d e n t that the protein-deficient d i e t p e r m i t t e d m o r e caries d e v e l o p m e n t w h e n f e d b e f o r e tooth e r u p t i o n t h a n after e r u p t i o n .

T h e s e authors

commented

that other variables i n a d d i t i o n to the l e v e l of d i e t a r y p r o t e i n , s u c h as i n a n i t i o n a n d the p h o s p h a t e content of the diet, m a y h a v e i n f l u e n c e d these results. S i n c e casein is a p h o s p h o p r o t e i n , it is possible that at least a p a r t of its cariostatic a c t i v i t y is d u e to its p h o s p h o r u s content

(see

p p . 116).

the

E v e n so, the results r e p o r t e d here c l e a r l y i n d i c a t e that

l e v e l of p r o t e i n i n diets f e d to rats d u r i n g t o o t h f o r m a t i o n a n d m a t u r a t i o n c a n influence caries d e v e l o p m e n t p r o f o u n d l y .

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

28

DIETARY

Influence of Individual

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES zyxwvuts

Amino Acid Supplements on Animal

Caries

zyxwvutsrqpo

(22) f o u n d that heat t r e a t m e n t c a u s e d a n increase Lysine. M c C l u r ezyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIH

i n c a r i o g e n i c i t y o f cereals, p r e s u m a b l y b e c a u s e t h e a v a i l a b i l i t y of heatl a b i l e l y s i n e w a s decreased.

M c C l u r e a n d F o l k ( 2 5 ) later s h o w e d that

the a d d i t i o n of L - l y s i n e at levels of 2.5 a n d 0 . 2 5 % to t w o c a r i o g e n i c diets r e d u c e d t h e caries score i n t h e rats s i g n i f i c a n t l y . S i m i l a r l y , B a v e t t a a n d M c C l u r e (1)

c o n f i r m e d t h e cariostatic p r o p e r t i e s o f l y s i n e w h e n t h e y

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fed a cariogenic

diet containing a considerable

p r o p o r t i o n of r o l l e r -

p r o c e s s e d s k i m m e d m i l k p o w d e r to o n e g r o u p o f rats, a n d f e d t h e same d i e t s u p p l e m e n t e d w i t h 0 . 4 % l y s i n e to a s e c o n d g r o u p . T h e l y s i n e s u p p l e ment

s i g n i f i c a n t l y r e t a r d e d caries

these e x p e r i m e n t a l

development, indicating that

c o n d i t i o n s , l y s i n e exerted

a significant

under

cariostatic

action. I n a n a t t e m p t to d e t e r m i n e w h e t h e r this a c t i o n of l y s i n e w a s l o c a l o r systemic, M c C l u r e (21)

designed an experiment i n w h i c h lysine was

administered i n the diet, i n the water, b y intubation, or b y intraperitoneal injection.

S i g n i f i c a n t r e d u c t i o n i n caries o c c u r r e d w h e n L - l y s i n e w a s a d -

ministered b y diet, b y water, a n d b y intubation. Intraperitoneal injection h a d a v a r i a b l e a n d essentially n e g l i g i b l e effect. McClure

(20)

later r e p o r t e d a h i g h i n c i d e n c e of

caries i n rats f e d w h e a t

flour,

smooth-surface

d r y b r e a d , toasted b r e a d , o r s h r e d d e d

w h e a t b i s c u i t . W h e n these c e r e a l p r o d u c t s w e r e a u t o c l a v e d i n the presence of cerelose o r starch, t h e caries p o t e n t i a l w a s i n c r e a s e d .

Supple-

ments of 1 % l y s i n e c o u n t e r a c t e d this effect. Hennon

(12)

f o u n d that a l y s i n e - d e f i c i e n t d i e t f e d to rats u n d e r

his e x p e r i m e n t a l c o n d i t i o n s p r o d u c e d t h e h i g h e s t caries scores. et al. (36)

Sharpenak

s h o w e d that t h e a d d i t i o n o f D L - l y s i n e H C 1 to a caries-pro-

d u c i n g d i e t c a u s e d a decrease of a p p r o x i m a t e l y 5 0 % i n t h e n u m b e r of carious teeth p e r r a t , i n t h e p e r c e n t a g e of carious teeth, a n d i n t h e caries index. O n t h e other h a n d , D o d d s ( 5 ) r e p o r t e d that L - l y s i n e H C 1 a d d e d to a c a r i o g e n i c d i e t of r a w w h o l e w h e a t h a d n o cariostatic effect. L - A r g i n i n e , L - H i s t i d i n e , L - O r n i t h i n e , L -Cadaverine.

McClure and

F o l k (23) h a v e r e p o r t e d that 0 . 5 % L - a r g i n i n e , 1 % L - h i s t i d i n e , a n d 0 . 2 5 % L - o r n i t h i n e a n d L - c a d a v e r i n e d e c r e a s e d caries d e v e l o p m e n t i n rats f e d a n a u t o c l a v e d s k i m m e d m i l k p o w d e r diet. DL -Methionine and D L - T h r e o n i n e . D o d d s ( 5 ) has r e p o r t e d that s u p p l e m e n t a t i o n of D L - m e t h i o n i n e a n d D L - t h r e o n i n e to a r a w w h o l e w h e a t c a r i o g e n i c diet d i d n o t affect t h e i n c i d e n c e of caries.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

3.

29 zyxwvutsrqp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Amino Acids, Proteins

N I Z E L

A c c o r d i n g to D o d d s ( 5 ) , the a d d i t i o n of 1.6% g l y c i n e to

Glycine.

a w h i t e flour ( w h e a t ) c a r i o g e n i c d i e t r e d u c e d t h e caries score b y a b o u t 23.8%. Furthermore, w h e n 0.20% of the glycine was replaced b y 0.40% D L - m e t h i o n i n e , t h e caries score w a s i n c r e a s e d . H a r r i s et al.

(11)

also f o u n d that 4 % g l y c i n e s u p p l e m e n t s c o u l d

exert significant cariostatic a c t i v i t y w h e n a d d e d to a n o t h e r w i s e c a r i o g e n i c d i e t a n d f e d to rats.

I n t w o successive f e e d i n g trials, caries w a s

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r e d u c e d b y 66 a n d 4 3 % b y t h e 4 % g l y c i n e d i e t a r y s u p p l e m e n t . L - G l u t a m i c A c i d and L - A s p a r t i c A c i d . E n g l a n d e r et al. (8)

recently

r e p o r t e d that n e i t h e r L - g l u t a m i c a c i d n o r L - a s p a r t i c a c i d i n f l u e n c e d t h e d e v e l o p m e n t of caries i n hamsters w h e n a d d e d to a d i e t at a 2 % l e v e l . T h e s e hamsters

h a d been

made

h i g h l y susceptibl e

s w a b b i n g w i t h virulent cariogenic streptococci.

to caries

b y oral

T h e diet w a s r i c h i n

q u a l i t y p r o t e i n , w a s n o t deficient i n l y s i n e , a n d c o n t a i n e d a b o u t 6 5 %

sucrose. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC

Protein and Bacteria Associated with Dental Caries

Relationships

S i n c e d e n t a l caries is a c k n o w l e d g e d to b e a c o m p l e x disease i n w h i c h the m e t a b o l i s m of p l a q u e b a c t e r i a p l a y a significant role, t h e n u t r i t i o n a l r e q u i r e m e n t s of t h e o r a l m i c r o f l o r a , e s p e c i a l l y t h e i r p r o t e i n a n d a m i n o a c i d needs, c o u l d b e q u i t e a n i m p o r t a n t c o n s i d e r a t i o n here. proteinaceous

T h e major

constituent of s a l i v a is the g l y c o p r o t e i n , m u c i n , a n d ac-

c o r d i n g to L e a c h ' s postulate

(15)

c o n c e r n i n g t h e c h e m i s t r y of d e n t a l

p l a q u e , t h e p r o t e i n that is s p l i t f r o m t h e g l y c o p r o t e i n b y n e u r i m i n i d a s e c o u l d c o n t r i b u t e to t h e f o r m a t i o n of p l a q u e m a t r i x . A c c o r d i n g to L o e s c h e a n d G i b b o n s (16),

t h e t o t a l q u a n t i t y of a m i n o acids is b e l o w t h e a m o u n t

necessary f o r m a x i m a l g r o w t h of m i c r o - o r g a n i s m s , b u t since b a c t e r i a i n the m o u t h g r o w s l o w l y a n d d i v i d e o n l y a f e w times e a c h d a y , this a m o u n t is o f significance

to t h e n u t r i t u r e of the organisms.

Unfortunately,

there is v e r y l i t t l e m o r e d e t a i l e d i n f o r m a t i o n a b o u t the r o l e of p r o t e i n o n c a r i o g e n i c b a c t e r i a , w i t h t h e e x c e p t i o n of the f o l l o w i n g three studies. D r e i z e n a n d Spies

( 7 ) i n v e s t i g a t e d t h e p r o d u c t s of p r o t e i n p u t r e -

f a c t i o n i n s a l i v a to d e t e r m i n e w h e t h e r some of t h e m m i g h t b e r e s p o n sible f o r t h e decreased i n c i d e n c e of caries c o m m o n l y seen i n m a l n o u r i s h e d p o p u l a t i o n s . T h e y o b s e r v e d that i n d o l e a n d i n d o l e - 3 - a c e t i c a c i d ( w h i c h m a y be p r o d u c e d b y the bacterial

d e c o m p o s i t i o n of t r y p t o p h a n ) d e -

creased a c i d p r o d u c t i o n a n d i n t e r f e r e d w i t h m a x i m u m g r o w t h of a strain of l a c t o b a c i l l u s a c i d o p h i l u s f o u n d i n the carious lesions. Nordh

(27)

c o m p a r e d t h e s e r u m p r o t e i n patterns

of t w o g r o u p s

of p e o p l e w h o h a d different n u m b e r s of l a c t o b a c i l l i i n t h e s a l i v a . T h e

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

30

DIETARY

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

g r o u p w i t h a h i g h c o u n t ( o v e r 1 m i l l i o n /m l o f s a l i v a ) , w h i c h is assoc i a t e d w i t h h i g h caries a c t i v i t y , s h o w e d e l e c t r o p h o r e t i c patterns i n t h e s e r u m , s i m i l a r to those

seen i n i n f l a m m a t o r y disease—i.e.,

decreased

albumin, increased gamma globulin, a n d increased i m m u n o g l o b u l i n concentrations. G r e e n ( 9 ) has suggested that i n n a t e caries resistance i n p e o p l e m a y b e d u e to the presence o f a b a c t e r i o l y t i c agent i n t h e g l o b u l i n f r a c t i o n of t h e s a l i v a . H e c l a i m e d that this agent, w h i c h contains t r y p t o p h a n

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a n d s e v e r a l r e l a t e d c o m p o u n d s , w i l l r e d u c e the g r o w t h o f c a r i e s - p r o m o t i n g bacteria (lactobacilli a n d streptococci).

zyxwvutsrqponmlkjihgfedcbaZYXW

Effect of Protein and Amino Acids on Tooth Solubility

InterestingzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC in vitro studies of t h e effects of a m i n o acids u p o n t h e rate of e n a m e l a n d d e n t i n e s o l u b i l i z a t i o n w h e n a d d e d to d e c a l c i f y i n g buffers h a v e b e e n c o n d u c t e d at t h e E a s t m a n D e n t a l C e n t e r d u r i n g recent years. B u o n o c o r e a n d S o m n e r ( 3 ) c o m p a r e d aspartic a c i d , g l u t a m i c a c i d , a l a n i n e , a n d v a l i n e , a n d r e p o r t e d that aspartic a c i d w a s t h e most a c t i v e i n r e d u c i n g the s o l u b i l i t y of e n a m e l i n t h e presence

of acetic,

l a c t i c , c i t r i c , a n d p y r u v i c acids, w h i c h a r e t h e o r g a n i c acids c o m m o n l y f o u n d i n d e n t a l p l a q u e a n d o n e n a m e l surfaces.

T h i s result suggested

the p o s s i b i l i t y that t h e aspartic i o n m a y f u n c t i o n to r e d u c e t h e rate at w h i c h these acids dissolve t h e t o o t h structure. I n subsequent studies, K o u l o u r i d e s a n d B u o n o c o r e (14) onocore (2)

and B u -

f o u n d l y s i n e to b e a n effective agent i n r e d u c i n g t h e rate

of e n a m e l d e c a l c i f i c a t i o n . T h e y p o s t u l a t e d that s u r f a c e - b o n d complexes are f o r m e d b e t w e e n a m i n o acids a n d t h e e n a m e l p a r t i c l e s , a n d that these act t o r e t a r d t h e d i f f u s i o n of acids. Significant reductions i n enamel solubility were noted b y Weiss a n d B i b b y (45, 46) w h e n casein solutions w e r e a d d e d to d e c a l c i f y i n g buffers. M i l k p r o t e i n concentrates w e r e at least as g o o d as w h o l e m i l k i n r e d u c i n g e n a m e l s o l u b i l i t y . T h i s result m a y i n d i c a t e that n e i t h e r t h e fat n o r the m i n e r a l i n t h e m i l k c o n t r i b u t e to t h e r e d u c t i o n i n e n a m e l s o l u b i l i t y . T h e i m p o r t a n c e of p r o t e i n to this process w a s e m p h a s i z e d w h e n these authors d e m o n s t r a t e d that m u c o p r o t e i n s , s u c h as gastric m u c i n ,

were

e q u a l l y as effective. M o r e r e c e n t l y , P e a r c e a n d B i b b y (31)

r e p o r t e d that e n a m e l absorbs

p r o t e i n , a n d suggested that p r o t e i n b i n d i n g occurs i n areas w h e r e e n a m e l d e s t r u c t i o n is i n i t i a t e d . T h u s , t h e y d e m o n s t r a t e d that there is a r e a c t i o n b e t w e e n p r o t e i n a n d the e n a m e l surface.

A t t he b e g i n n i n g of caries

d e v e l o p m e n t ( t h e w h i t e spot s t a g e ) , d e c a l c i f i c a t i o n is greater b e l o w t h e t o o t h surface t h a n at t h e surface. P o s s i b l y this is because proteins cannot diffuse to subsurface sites.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

3.

NIZEL

Amino Acids, Proteins

31

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Summary and Conclusions (1) It appears that both the amount and quality of protein are important factors in influencing dental caries development in the experimental animal. F o r example, Dodds noted less caries when the level of cereal protein was raised about 16% and when the diets were less deficient in amino acids. A diet which contains limited amounts of poorquality protein w i l l become less cariogenic as the protein content is increased, and/or as the quality of the protein is improved. (2) Dietary additions of casein, a phosphoprotein, appeared to be the most effective of all proteins tested in the reduction of caries development in experimental animals. The relative importance of the phosphate moiety of the casein molecule for exerting this cariostatic action has not been evaluated. (3) Other proteins and amino acids that show some promise as significant cariostatic agents are fish protein concentrate ( F . P . C . ) and glycine. (4) A few in vitro studies seem to show that amino acids can decrease the rate of enamel solubility. (5) N o well-controlled study has been published which proves that dietary supplements of protein can influence the development of dental caries in human beings. (6) The favorable indications that proteins and constituent amino acids may affect caries development should stimulate further search for protein-caries relationships. Literature Cited (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16)

(17)

Bavetta, L . A., McClure, F., J. Nutr. 1957, 63, 107. Buonocore, M. G., J. Dent. Res. 1963, 42, 700. Buonocore, M. G., Somner, B., J. Am. Dent. Assoc. 1957, 55, 781. Buxbaum, J. D., Kolin, H . , Proutt, L . M . , Oster, R. H . , J. Dent. Res. 1957, 36, 173. Dodds, M. L., J. Nutr. 1964, 82, 217. Dreizen, S., Dreizen, J., Stone, R. E., J. Dent. Res. 1961, 40, 1025. Dreizen, S., Spies, T. D., J. Dent. Res. 1947, 26, 409. Englander, H . R., Keyes, P. H . , Fitzgerald, R. J., Arch. Oral Biol. 1965, 10, 599. Green, G. E., J. Dent. Res. 1959, 38, 362. Green, R. M., Helv. Odont. Acta 1967, 11, 32. Harris, R. S., Nizel, A. E., Navia, J. M . , Das, S. K., I.A.D.R. Abstracts, March, 1967. Hennon, D . K., J. Dent. Res. 1960, 39, 681. Holloway, P. J., Shaw, J. H . , Sweeney, E . A., Arch. Oral Biol. 1961, 3, 185. Koulourides, T. A., Buonocore, M . G., J. Dent. Res. 1961, 40, 578. Leach, S. A., Brit. Dent. J. 1967, 122, 537. Loesch, W . J., Gibbons, R. J., "Influence of Nutrition on the Ecology and Cariogenicity of the Oral Microflora" in Nizel, A. E., "The Science of Nutrition and its Application in Clinical Dentistry," W. B. Saunders Co., Philadelphia, Pa., 1966. Losee, F. L., VanReen, R., J. Dent. Res. 1957, 36, 904-910.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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32

DIETARY CHEMICALS VS. D E N T A L CARIES

(18) Mandel, S. D., Zorn, M., Ruiz, R., Thompson, R. H . , Ellison, S. Α., Arch. Oral Biol. 1965, 10, 471. (19) Mauron, J., Kinkel, H . J., Cremer, H . D., Intern. J. Vitaminforsch. 1959, 30, 19. (20) McClure, F. J., J. Nutr. 1958, 65, 619. (21) McClure, F. J., Proc. Soc. Exptl. Biol. Med. 1957, 96, 631. (22) McClure, F . J., Science 1952, 116, 229. (23) McClure, F. J., Folk, J. E . , J. Nutr. 1955, 55, 589. (24) McClure, F . J., Folk, J. E., Proc. Soc. Exptl. Biol. Med. 1953, 83, 21. (25) McClure, F. J., Folk, J. E., Science 1955, 122, 557. (26) Nizel, A . E., King, G., Harris, R. S., Navia, J., I.A.D.R. Abstract #100, 1969. (27) Nordh, F., Acta Odont. Scand. 1965, 23, 187. (28) Onisi, Ozaki, Hamada, Japan. J. Dent. Health 1966, 16, 85. (29) Ockerse, T. S., African Dent. J. 1941, 15, 353. (30) Osborn, M . O., Carey, J. F., Fisken, A . K., J. Dent. Res. 1966, 45, 1564. (31) Pearce, E . J. F., Bibby, B. G., Arch. Oral Biol. 1966, 11, 329. (32) Russell, A. L., White, C. L . , J. Dent. Res. 1961, 40, 594. (33) Schweigert, B. S., Potts, E., Shaw, J. H . , Zepplin, M., Phillips, P. H . , J. Nutr. 1946, 32, 405. (34) Schweigert, B. S., Shaw, J. H . , Zepplin, M . , Elvehyem, C. Α., J. Nutr. 1946, 31, 439. (35) Shannon, J. L., Gibson, W . Α., Oral Surg. 1964, 18, 399. (36) Shapernak, A. E., Bobyleva, V . R., Gorozanina, L . Α., Vop. Piton 1963, 22, 239-244 (Kaf, bohin. Med. stomatol. Inst. Moscow) Russia. (37) Shaw, J. H . , J. Nutr. 1950, 41, 1. (38) Shaw, J. H., J. Dent. Res. 1966, 45, 1810. (39) Stack, M . V., J. Dent. Res. 1954, 33, 316. (40) Stephan, R. M., I.A.D.R. Abstract #365, 1968. (41) Stephan, R. M., I.A.D.R. Abstract 1956, 34, 77. (42) Sweeney, Ε. Α., Guzman, M., Arch. Oral Biol. 1966, 11, 687. (43) Tamura, S., Kizu, K., Ito, H . , Nahai, K., Bull. Tokyo Dent. Coll. 1965, 6, 15. (44) Turner, N . D., Crowell, G. E., J. Dent. Res. 1947, 26, 99. (45) Weiss, M . E., Bibby, B. G., Arch. Oral Biol. 1966, 11, 59. (46) Weiss, M., Bibby, B. G., Arch. Oral Biol. 1965, 10, 49. RECEIVED August 15,

1968.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4

Vitamins and Dental Caries

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SAMUEL DREIZEN University of Texas Dental Science Institute at Houston, Houston, Tex. 77025

Vitamins contribute to both the pathogenesis and prevention of dental caries. During the formative period, vitamins A, C, and D are essential for proper deposition and calcification of tooth structure. Posteruptively, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic microorganisms. The Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most if not all of the oral acidogenic flora. Some strains also require an exogenous source of thiamine and riboflavin. As components of the coenzymes which participate in anaerobic glycolysis, thiamine and nicotinic acid promote acid production by microbial action on locally retained ingested carbohydrates. Unfortunately, none of the Β vitamins can be deleted safely from the diet for caries prevention without impairment of human health.

vitamins are a group of diverse organic compounds which are dietary in origin and indispensable for human health and well being. Most function as integral parts of enzyme systems involved in essential metabolic processes. As such, they are required in relatively small amounts in sharp contrast to the dietary macro-nutrients which contribute primarily to the structural makeup of cells and tissues. Dental caries is a posteruptive disease of the teeth resulting from the action of cariogenic oral microorganisms on susceptible tooth structure in the presence of a suitable substrate and a favorable local environment. Various vitamins have been associated with the pathogenesis and prevention of dental caries. Some are caries-conducive; others cariesdeterrent. Some affect the caries process by their presence; others by their absence. Some have a preemptive influence which is exerted on the size, shape, and structure of the teeth. Others operate posteruptively by influencing the quantity and composition of the saliva and the makeup

The

33 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

34 of

DIETARY

the

oral microbial

flora.

Evidence

r e l a t i o n s h i p is d e t a i l e d i n this report.

Vitamin

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

of

the

vitamin-dental

caries

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF

A

Effects of Deficiency. L a c k of v i t a m i n A w i l l p r o d u c e characteristic

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a b n o r m a l i t i e s i n the shape a n d structure of d e v e l o p i n g teeth, p r o v i d e d the d e f i c i e n c y is c h r o n i c e n o u g h a n d severe e n o u g h . mediated

through

alterations

i n the

T h e effects

highly specialized

are

odontogenic

e p i t h e l i u m l e a d i n g to disturbances i n histo- a n d m o r p h o d i f f e r e n t i a t i o n . I n the rat, avitaminosis A i n d u c e s e n a m e l h y p o p l a s i a , i r r e g u l a r a n d a t y p -

i c a l d e n t i n f o r m a t i o n , a n d e p i t h e l i a l i n v a s i o n of the d e n t a l p u l pzyxwvutsrqponmlkjihg (79). I n m a n the p r i m a r y h i s t o p a t h o l o g y is a m e t a p l a s i a of t h e e n a m e l - f o r m i n g cells a n d a n a t r o p h y of the e n a m e l o r g a n w h i c h is m a n i f e s t e d c l i n i c a l l y as e n a m e l h y p o p l a s i a (11, 23).

A v i t a m i n o s i s A is a rare cause of e n a m e l

h y p o p l a s i a i n the h u m a n , since deficiencies of the degree a n d d u r a t i o n r e q u i r e d to p r o d u c e d e t e c t a b l e d e n t a l defects are u s u a l l y not c o m p a t i b l e w i t h l i f e . B l o c h (10)

s t u d i e d 64 b l i n d D a n i s h c h i l d r e n w i t h gross e v i -

d e n c e of severe v i t a m i n A d e f i c i e n c y d u r i n g i n f a n c y a n d f o u n d neither c o n s p i c u o u s a b n o r m a l i t i e s i n the f o r m , p o s i t i o n , a n d consistency of the teeth n o r a n i n c r e a s e d p r e d i s p o s i t i o n to d e n t a l caries. (85)

Similarly, Shourie

f o u n d no greater i n c i d e n c e of d e n t a l caries i n I n d i a n c h i l d r e n w i t h

s k i n a n d eye lesions suggestive of v i t a m i n A d e f i c i e n c y t h a n i n a d e q u a t e l y nourished ethnically identical children. P a y n t e r a n d G r a i n g e r (71)

successfully m o d i f i e d the genetic

tem-

p l a t e of tooth m o r p h o l o g y b y r e s t r i c t i n g p r e g n a n t rats to a synthetic diet deficient i n v i t a m i n A d u r i n g the t i m e the m o l a r teeth w e r e b e i n g f o r m e d i n t h e o f f s p r i n g . T h e p r o c e d u r e caused the d e v e l o p m e n t of s m a l l m o l a r teeth i n the y o u n g to a degree w h i c h exceeded variation.

T h e size differences

the range of n o r m a l

w e r e not a c c o m p a n i e d b y gross

surface defects, severe h i s t o l o g i c changes,

tooth

m e t a b o l i c derangements,

or

a n increased caries s u s c e p t i b i l i t y . T h e o n l y e v i d e n c e of a d i r e c t r e l a t i o n s h i p b e t w e e n

dental

caries

a n d c h r o n i c v i t a m i n A d e f i c i e n c y is s u p p l i e d b y S a l l e y , B r y s o n , a n d E s h l e m a n (76),

w h o o b t a i n e d a significant increase i n caries i n hamsters

g i v e n a synthetic diet d e v o i d of v i t a m i n A . T h e c a r i e s - p r o m o t i n g p o t e n t i a l of v i t a m i n A d e f i c i e n c y w a s a s c r i b e d to a greatly r e d u c e d s a l i v a r y flow p r e c i p i t a t e d b y the d e f i c i e n c y r e l a t e d loss of secretory a c i n i i n the major a n d m i n o r s a l i v a r y glands. X e r o s t o m i a a t t r i b u t a b l e to a k e r a t i n i z i n g m e t a p l a s i a a n d i n f l a m m a t o r y reaction i n b o t h the s a l i v a r y g l a n d a c i n i a n d ducts has b e e n d e s c r i b e d i n h u m a n v i t a m i n A d e f i c i e n c y (4).

Un-

f o r t u n a t e l y , details of the c a r i o g e n i c i t y of the xerostomia i n these cases are l a c k i n g .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4.

D R E I Z E N

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Vitamins and Dental Caries 35 zyxwvutsrq

Effects of Excess. D i e t a r y s u p p l e m e n t s of v i t a m i n A neither s t i m -

ulate n o r suppress the caries t e n d e n c y i n c h i l d r e n (21, b y D a y a n d S e d w i c k (21)

64).

In a study

at least 6000 U . S . P . units of v i t a m i n A i n -

gested d a i l y i n tablet f o r m together w i t h a d d e d v i t a m i n D f o r 15 m o n t h s not o n l y f a i l e d to h a v e a b e n e f i c i a l effect o n the caries i n c i d e n c e , b u t a f f o r d e d n o m e a s u r a b l e p r o t e c t i o n to the n e w l y e r u p t e d teeth.

I n rats,

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a d d i t i o n of excessive amounts of w a t e r - s o l u b l e a n d f a t - s o l u b l e v i t a m i n s i n c l u d i n g v i t a m i n A d i d not alter s i g n i f i c a n t l y either the average n u m b e r or average extent of carious lesions i n a n i m a l s w h o s e t o o t h d e v e l o p m e n t

Thiamine (Vitamin

zyxwvutsrqponm

(82).

was almost c o m p l e t e w h e n the s u p p l e m e n t s w e r e i n i t i a t e d

Bj)

Effects of Deficiency. I n 1958 S h a r p e n a k (81)

that a d e f i c i e n c y of cocarboxylase

r e v i v e d a n hypothesis

( t h i a m i n e p y r o p h o s p h a t e or d i p h o s -

p h o t h i a m i n e ) is a n i m p o r t a n t cause of d e n t a l caries because of a n acc u m u l a t i o n of p y r u v i c a c i d i n the d e n t a l a n d b o d y tissues.

This concept

lacks s u p p o r t i v e e v i d e n c e a n d is i n d i r e c t conflict w i t h studies b y R u s s e l l (75)

i n South Vietnam and Thailand and b y Afonsky (2)

China.

i n central

T h e y s h o w that c o n s u m p t i o n of a n u t r i t i o n a l l y i n a d e q u a t e t r a -

d i t i o n a l diet, l o w or deficient i n t h i a m i n e , is w h o l l y c o m p a t i b l e w i t h a l o w caries

prevalence. G o l l (34)

Effects of Excess.

tested the s u p p o s i t i o n that t h i a m i n e

d e f i c i e n c y m a y be a n etiologic factor i n d e n t a l caries b y f e e d i n g cakes p r e p a r e d f r o m t h i a m i n e - r i c h ingredients to a s m a l l g r o u p of G e r m a n children.

T h e t h i a m i n e intake p e r c h i l d w a s thus increased b y 0.8 m g

per day.

N o r e d u c t i o n i n caries i n c i d e n c e was n o t e d i n the

p e r i o d of s u p p l e m e n t a t i o n .

A g a p o v a (3)

9-month

o b t a i n e d a decrease i n the

d e n t a l caries attack rate i n some of 75 c h i l d r e n g i v e n a d i e t a r y a d d i t i v e of 2 m g t h i a m i n e d a i l y f o r 2 years.

T h e decrease w a s a t t r i b u t e d to the

suppressive a c t i o n of t h i a m i n e o n the c a r i o g e n i c m i c r o o r g a n i s m s . m i n e has b e e n f o u n d to be bacteriostatic w h e n a d d e d to s a l i v a in

Thiavitro

at a l e v e l of 200 /xgrams per m l . , a c o n c e n t r a t i o n w h i c h far exceeds the 0.2 to 1.4 /ngrams p e r 100 m l . n o r m a l l y present i n h u m a n s a l i v a (8,

30).

I n contrast, w h e n present at a l e v e l of 2 /xgrams p e r m l . i n a c h e m i c a l l y d e f i n e d c o m p l e t e synthetic m e d i u m , t h i a m i n e is g r o w t h - p r o m o t i n g rather t h a n bacteriostatic f o r some strains of o r a l acidogens

Riboflavin

(Vitamin

(25).

B) 2

Effects of Deficiency. A s s h o w n b y d e n t a l surveys i n the U n i t e d States ( 5 5 ) , G u a t e m a l a (46), N i g e r i a (91), S o u t h V i e t n a m a n d T h a i l a n d ( 7 5 ) , a d i e t deficient i n r i b o f l a v i n is not necessarily c o n d u c i v e to d e n t a l

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

36

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

d e c a y . Subjects w i t h s u b s t a n d a r d r i b o f l a v i n intakes a n d c l i n i c a l e v i d e n c e of t h e d e f i c i e n c y state w e r e f o u n d to h a v e a caries p r e v a l e n c e w h i c h was no higher a n d often m u c h lower than i n nutritionally superior cont r o l g r o u p s i n t h e same r e g i o n . A l t h o u g h r i b o f l a v i n is a n u t r i t i o n a l essent i a l f o r some strains of o r a l l a c t o b a c i l l i , most w i l l tolerate a r i b o f l a v i n - f r e e synthetic m e d i u m w h i c h is c o m p l e t e i n a l l other n u t r i t i o n a l

essentials

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( 2 5 , 5 1 ) . zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC Effects of Excess. I n c l u s i o n of r i b o f l a v i n i n t h e d i e t o f rats i n amounts

f a r i n excess of t h e i r n u t r i t i o n a l needs does n o t alter t h e i r s u s c e p t i b i l i t y

to d e n t a l carieszyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC (82). T h e r e h a v e b e e n n o c o m p a r a b l e studies o n t h e h u m a n level.

Nicotinic

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED

Acid

(Niacin)

Effects of Deficiency. R e p o r t s f r o m v a r i o u s parts o f t h e w o r l d i n d i -

cate that e n d e m i c p e l l a g r i n s h a v e a l o w i n c i d e n c e o f d e n t a l caries 49, 74, 77).

(19,

T h e r e is c o n s i d e r a b l e e v i d e n c e that t h e l o w caries p r e v a l e n c e

a n d t h e n i c o t i n i c a c i d d e f i c i e n c y p r o d u c t i v e of p e l l a g r a are i n t e r r e l a t e d rather t h a n fortuitous.

N i c o t i n i c a c i d has p r o v e d to b e a n i r r e p l a c e a b l e

nutritional factor for the oral lactic a c i d - p r o d u c i n g bacteria N i c o t i n i c a c i d a m i d e acts as t h e f u n c t i o n a l g r o u p of

I a n d I I , e n z y m e s necessary f o r c o n v e r t i n g f e r m e n t a b l e to a c i d residues.

(25, 5 1 ) .

codehydrogenases carbohydrates

W i t h i n p h y s i o l o g i c l i m i t s , the a m o u n t of a c i d p r o d u c -

t i o n i n saliva—glucose m i x t u r e s , in vitro, is r e l a t e d d i r e c t l y t o t h e n i c o t i n i c a c i d content of t h e s a l i v a s a m p l e (24).

A d d i t i o n of antimetabolites of

n i c o t i n i c a c i d to s u c h m i x t u r e s c o m p l e t e l y i n h i b i t s a c i d f o r m a t i o n ( 2 5 , 53).

I n c o r p o r a t i o n of a m e t a b o l i c antagonist of n i c o t i n i c a c i d i n a n ex-

p e r i m e n t a l c a r i o g e n i c d i e t f e d w e a n l i n g rats f o r 150 days r e d u c e d t h e caries t e n d e n c y i n these a n i m a l s s i g n i f i c a n t l y (26).

Conversely, deletion

of n i c o t i n i c a c i d f r o m a n u t r i t i o n a l l y b a l a n c e d c a r i e s - p r o d u c i n g hamster d i e t r e s u l t e d i n a r e d u c t i o n i n caries i n c i d e n c e to a p p r o x i m a t e l y half that of t h e c o n t r o l g r o u p

(68).

Effects of Excess. K o s e r a n d K a s a i ( 5 2 ) f o u n d that c o m p a r a t i v e l y

h u g e quantities of n i c o t i n i c a c i d of t h e o r d e r of 10,000 times t h e n u t r i t i o n a l r e q u i r e m e n t w i l l p r e v e n t c o m p l e t e l y t h e g r o w t h of n i c o t i n i c a c i d d e p e n d e n t b a c t e r i a in vitro.

E x p e r i m e n t a l l y , excessive amounts of n i c o -

t i n i c a c i d a n d other B v i t a m i n s increase t h e caries i n c i d e n c e i n hamsters (32)

a n d d o n o t influence caries s u s c e p t i b i l i t y i n rats (82).

Although

massive doses of n i c o t i n i c a c i d are b e i n g u s e d presently i n t r e a t i n g some cases o f h y p e r c h o l e s t e r e m i a i n m a n , there h a v e been n o reports of t h e effect of this t h e r a p y o n t h e h u m a n d e n t i t i o n .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4.

D R E I Z E N

Pyridoxine

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Vitamins and Dental Caries 37 zyxwvutsrq (Vitamin

B) 6

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON

Effects of Deficiency. T h e p o s s i b i l i t y of a r e l a t i o n s h i p b e t w e e n p y r i -

( 73)

d o x i n e a n d d e n t a l caries w a s a d v a n c e d b y R i n e h a r t a n d G r e e n b e r g

w h o o b s e r v e d that m o n k e y s m a i n t a i n e d o n l o n g t e r m p y r i d o x i n e - d e f i c i e n t diets d e v e l o p extensive d e n t a l caries.

The pyridoxine deficiency-dental

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caries axis w a s a p p a r e n t o n l y after a m i n i m u m of 2 years of exposure to the deficient diets, w i t h l i t t l e or n o adverse d e n t a l effects n o t e d d u r i n g the first 24 s t u d y m o n t h s .

Strean a n d c o - w o r k e r s ( 9 0 )

restricted small

groups of hamsters to a c a r i o g e n i c d i e t w i t h a n d w i t h o u t a d d e d p y r i d o x i n e ( 5 0 m g /1 0 0 grams d i e t ) f o r 10 m o n t h s a n d o b t a i n e d a significant r e d u c t i o n i n f r e q u e n c y a n d extent of caries i n the p y r i d o x i n e - s u p p l e m e n t e d g r o u p . L a t e r Strean et al. (89)

subjected hamsters to c a r i o g e n i c

diets l o w i n p y r i d o x i n e (0.5 p p m ) a n d h i g h i n p y r i d o x i n e (10

ppm)

f o r 7 m o n t h s a n d f o u n d a significant p y r i d o x i n e - a s s o c i a t e d d i m i n u t i o n i n caries f r e q u e n c y for the l o w e r teeth b u t not f o r the u p p e r teeth.

The

d i s t i n c t i o n i n the locale of caries p r o t e c t i o n w a s a s c r i b e d to differences i n the p y r i d o x i n e content of the s a l i v a i n various parts of the m o u t h , b u t n o c h e m i c a l e v i d e n c e w a s offered to s u p p o r t this c o n t e n t i o n . Effects of Excess. T h e caries p r e v e n t i v e p o t e n t i a l of p y r i d o x i n e has

b e e n tested i n a n i m a l s a n d i n m a n w i t h e q u i v o c a l results. W y n n , H a l d i , a n d L a w (94)

i n c l u d e d r e l a t i v e l y large amounts of p y r i d o x i n e ( u p to 100

p p m ) i n a s y n t h e t i c h i g h sucrose d i e t o r i g i n a l l y a d e q u a t e i n p y r i d o x i n e content.

T h e a d d e d p y r i d o x i n e f a i l e d to r e d u c e the c a r i o g e n i c i t y of the

test d i e t w h e n f e d to rats of a caries-susceptible S t e i n m a n a n d H a r d i n g e (87)

strain.

In

contrast,

a t t a i n e d a n o t a b l e r e d u c t i o n i n caries i n -

c i d e n c e w h e n rats w e r e g i v e n a r a t i o n representative

of the t y p i c a l

A m e r i c a n d i e t s u p p l e m e n t e d w i t h p y r i d o x i n e to the extent of 16 m g per k g food. I n a s m a l l p i l o t s t u d y , Strean et al.

(89)

achieved a 40%

reduction

i n n e w carious lesions i n 14 c h i l d r e n , 10 to 15 years o l d , g i v e n lozenges c o n t a i n i n g 3 m g p y r i d o x i n e t h r i c e d a i l y f o r 1 year. T h e reference g r o u p w a s c o m p r i s e d of 14 c h i l d r e n g i v e n p l a c e b o lozenges. (18)

Cohen and Rubin

u s e d a n i d e n t i c a l testing p r o c e d u r e i n 120 test c h i l d r e n a n d

129

c o n t r o l c h i l d r e n , 11 to 14 years of age, for 1 year a n d r e p o r t e d a slight suppressive effect of the p y r i d o x i n e lozenges o n d e n t a l caries.

T h e dif-

ference b e t w e e n the caries attack rates i n the p y r i d o x i n e a n d p l a c e b o g r o u p s w a s not, h o w e v e r , statistically significant. I n adults the effects of p y r i d o x i n e s u p p l e m e n t s o n d e n t a l experience has b e e n tested a n d Schenone (45).

caries

i n pregnant w o m e n by H i l l m a n , C a b a u d ,

S t a r t i n g w i t h the 4 t h m o n t h of p r e g n a n c y , 198 r a n -

d o m l y selected p r e g n a n t w o m e n w e r e g i v e n 20 m g p y r i d o x i n e once d a i l y i n c a p s u l e f o r m , 169 w e r e g i v e n a total of 20 m g p y r i d o x i n e t h r i c e d a i l y

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

38

DIETARY

zyxwvutsrqponmlkjihgfedcba VS. D E N T A L CARIES

C H E M I C A L S

i n l o z e n g e f o r m , a n d 173 r e c e i v e d p l a c e b o p r e p a r a t i o n s a n d s e r v e d as controls.

E a c h regimen was f o l l o w e d u n t i l parturition. T h e group not

g i v e n a d d e d p y r i d o x i n e h a d a n average D M F increase of 1.42 c o m p a r e d w i t h 1.22 f o r t h e c a p s u l e g r o u p a n d 0.89 f o r t h e l o z e n g e g r o u p . T h e difference b e t w e e n t h e m e a n D M F i n c r e m e n t s of the c o n t r o l a n d c a p s u l e g r o u p s w a s n o t significant; that b e t w e e n t h e c o n t r o l a n d l o z e n g e g r o u p s

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w a s significant. S t r e a n ( 8 8 ) attributes t h e caries-deterrent a c t i o n of p y r i d o x i n e to a n a l t e r a t i o n of t h e o r a l flora f r o m a p r e d o m i n a n t l y h o m o f e r m e n t a t i v e l a c t i c a c i d - p r o d u c i n g t y p e to a p r e v a l e n c e o f h e t e r o f e r m e n t a t i v e f o r m s w h i c h p r o d u c e less l a c t i c a c i d a n d m o r e v o l a t i l e e n d p r o d u c t s .

Since

h o m o f e r m e n t a t i v e f o r m s d o n o t a n d h e t e r o f e r m e n t a t i v e forms d o u t i l i z e p y r i d o x i n e , t h e a d d i t i o n of p y r i d o x i n e creates a c o m p e t i t i v e system w h i c h eventuates i n s u p p r e s s i n g t h e h e a v y a c i d p r o d u c e r s . P a r t i a l s u p p o r t f o r this c o n t e n t i o n is s u p p l i e d b y P a l a z z o , C o b e , a n d P l o u m i s ( 7 0 ) , w h o showed

that

addition

of p y r i d o x i n e i n concentrations

ranging from

1:2000 to 1:200,000 to s u i t a b l e m e d i a i n h i b i t s h o m o f e r m e n t a t i v e strains of t h e o r a l flora a n d p r o m o t e s g r o w t h o f t h e h e t e r o f e r m e n t a t i v e

types.

A l t h o u g h p y r i d o x i n e has b e e n s h o w n to b e bacteriostatic against

some

strains o f o r a l m i c r o o r g a n i s m s w h e n a d d e d to s a l i v a i n a c o n c e n t r a t i o n of 20 m g p e r 100 m l ( 8 ) , levels of 200 m g p e r 100 m l f a i l e d t o affect a c i d p r o d u c t i o n i n i n c u b a t e d s a l i v a - g l u c o s e mixtures ( 2 8 ) .

A proper

e v a l u a t i o n of t h e role of p y r i d o x i n e i n t h e caries process awaits m o r e intensive microbiologic, chemical, a n d clinical investigation.

zyxwvutsrqponmlkjih

Other B Vitamins O t h e r B v i t a m i n s w i t h a p o t e n t i a l role i n t h e caries process are biotin, pantothenic acid, folic acid, a n d inositol. B i o t i n a n d pantothenic a c i d resemble n i c o t i n i c a c i d i n that t h e y are essential f o r the g r o w t h a n d a c i d p r o d u c t i o n of o r a l l a c t o b a c i l l i , s t r e p t o c o c c i , s t a p h y l o c o c c i , a n d

yeasts i n p u r e a n d m i x e d c u l t u r e ( 2 5 ,zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQP 51). M a k i l a ( 5 4 ) f o u n d that the m e a n f o l i c a c i d content of resting w h o l e s a l i v a i n e d e n t u l o u s d e n t u r e wearers a n d patients w i t h teeth l a r g e l y d e s t r o y e d b y caries is almost three times greater t h a n that i n subjects w i t h slight caries a c t i v i t y . It w a s c o n c l u d e d that either a h i g h s a l i v a f o l i c a c i d l e v e l promotes t h e d e v e l o p m e n t of caries, o r the c a r i e s - p r e c i p i t a t i n g factor leads to a n increase i n saliva folic a c i d concentration.

Significant caries r e d u c t i o n s h a v e

been

o b t a i n e d i n rats f e d c a r i o g e n i c sugar diets c o n t a i n i n g 0 . 0 1 - 0 . 1 % i n o s i t o l (67).

A d d i t i o n of 1.4% p h o s p h o r y l a t e d i n o s i t o l to a b r e a d - g l u c o s e r a t

d i e t decreased t h e i n c i d e n c e o f d e n t a l caries b y a n average o f 7 7 % a n d the caries severity score b y a n average of 9 1 % ( 5 9 ) . Studies b y M c C a n n ,

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4.

D R E I Z E N

39 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Vitamins and Dental Caries

B r a d y , a n d G i l l e n ( 5 8 ) i n d i c a t e that e n a m e l m a y p i c k u p p h o s p h a t e f r o m p h o s p h o r y l a t e d i n o s i t o l b y i o n exchange a n d that the increase i n e n a m e l p h o s p h a t e contributes to the anticaries effectiveness of this c o m p o u n d i n rats.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA

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Vitamin C (Ascorbic

Acid)

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO

Effects of Deficiency. E v i d e n c e that v i t a m i n C is essential f o r n o r -

m a l t o o t h d e v e l o p m e n t is d e r i v e d f r o m h i s t o l o g i c changes i n the c o n t i n u o u s l y f o r m i n g incisors of s c o r b u t i c g u i n e a pigs.

T h e s e range f r o m

d i s t u r b e d h i s t o d i f f e r e n t i a t i o n of the odontoblasts c u l m i n a t i n g i n a m o r p h o u s a n d i r r e g u l a r d e n t i n f o r m a t i o n to a cessation of d e n t i n d e p o s i t i o n a n d o v e r c a l c i f i c a t i o n of the p r e d e n t i n . A t r o p h i c changes i n the

enamel

e p i t h e l i u m m a y o c c u r i n the late stages g i v i n g rise to e n a m e l h y p o p l a s i a (13).

Boyle

(12)

studied deciduous and permanent

t o o t h germs

of

s c o r b u t i c infants a n d f o u n d n o a b n o r m a l i t i e s except f o r some s m a l l cysts a n d m i n u t e hemorrhages

i n a f e w specimens.

Teeth

from

scorbutic

adults s h o w p o r o t i c d e n t i n , p u l p a l h y p e r e m i a a n d e d e m a , a n d a l t e r e d secondary d e n t i n f o r m a t i o n

(93).

D e s p i t e the s t r u c t u r a l changes associated w i t h s c u r v y , W e s t i n w a s u n a b l e to demonstrate

any relationship between

(93)

v i t a m i n C defi-

c i e n c y a n d d e n t a l caries i n the g u i n e a p i g , m o n k e y , or m a n , n o r is there a n y significant c o r r e l a t i o n b e t w e e n

the v i t a m i n C content

of h u m a n

b l o o d , s a l i v a , or u r i n e a n d d e n t a l caries a c t i v i t y (15, 44, 8 0 ) .

Neverthe-

less, O t t (69)

m a i n t a i n s that d e n t a l caries c a n be e q u a t e d w i t h d i s t u r b e d

v i t a m i n C m e t a b o l i s m b u t offers little c l i n i c a l a n d no e x p e r i m e n t a l e v i dence to substantiate

this c l a i m .

H a n k e (39)

s u p p l e m e n t e d the

diets

of 323 c h i l d r e n w i t h a p i n t of orange juice a n d the juice of one l e m o n d a i l y a n d o b t a i n e d a n a u s p i c i o u s r e d u c t i o n i n the i n t e n s i t y of

caries.

A d m i n i s t r a t i o n of 90 m l . of orange juice d a i l y f a i l e d to sustain the r e d u c e d caries a c t i v i t y , c a s t i n g some d o u b t o n the specificity of a d e n t a l c a r i e s vitamin C deficiency relationship. Effects of Excess. V i t a m i n C has been s h o w n to be c a r i e s - p r o m o t i n g ,

caries-neutral, a n d c a r i e s - p r e v e n t i n g — t h e

specific role v a r y i n g w i t h the

p a r t i c u l a r investigator.

regards p h a r m a c o l o g i c a l l y ef-

T h u s , H a f e r (38)

fective doses of v i t a m i n C as c a r i o g e n i c since the a d m i n i s t r a t i o n of s u c h doses is f o l l o w e d i n a f e w weeks b y a rise i n l a c t o b a c i l l u s counts a n d b y a f a l l i n the n e u t r a l i z i n g p o w e r of the s a l i v a .

W h e n incorporated in

c a r i o g e n i c diets i n amounts r a n g i n g f r o m 0 . 5 - 2 . 5 % of the d a i l y r a t i o n , v i t a m i n C is w i t h o u t m e a s u r a b l e effect o n caries i n rats ( 5 0 ) sters ( 3 5 ) .

and in ham-

I n c h i l d r e n , G r a n d i s o n , Stott, a n d C r u i k s h a n k (36)

found

no significant m o d i f i c a t i o n i n the caries course of 20 c h i l d r e n g i v e n 200 m g v i t a m i n C d a i l y for 2 years.

D i e r k s (22)

r e p o r t e d that d a i l y doses

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

40

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

of 100 m g v i t a m i n C are p r o t e c t i v e against the s e c o n d a r y d e c a y w h i c h forms around

filling

m a r g i n s , as no s u c h lesions d e v e l o p e d i n c h i l d r e n

g i v e n v i t a m i n C f o r 1 year. T h e l a c k of a c o n t r o l g r o u p a n d the f a i l u r e to influence p r i m a r y caries l i m i t s the v a l u e a n d a p p l i c a b i l i t y of these findings. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA

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Vitamin

D

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE

Effects of Deficiency.

ficiency

T h e changes i n d u c e d b y a v i t a m i n D

de-

d u r i n g the f o r m a t i v e p e r i o d of the teeth v a r y w i t h the e x p e r i -

m e n t a l a n i m a l . I n a l l v i t a m i n D - d e p e n d e n t species, the first a n d most p r o m i n e n t d e f i c i e n c y c h a n g e is a l i n e of d i s t u r b e d c a l c i f i c a t i o n i n the dentin.

I n the severe cases this is f o l l o w e d b y a r e t a r d a t i o n of d e n t i n

f o r m a t i o n a n d a f a i l u r e of c a l c i f i c a t i o n of the p r e d e n t i n . I n the rat, e n a m e l f o r m a t i o n a n d c a l c i f i c a t i o n are unaffected b y a v i t a m i n D

deficiency,

b u t g u i n e a p i g s , dogs, a n d m a n m a y d e v e l o p h y p o p l a s t i c e n a m e lzyxwvutsrqponmlkjihg (40). M e l l a n b y (61)

was the first to suggest that teeth w i t h i m p e r f e c t i o n s i n

the e n a m e l surface are m o r e susceptible to caries t h a n teeth w i t h o u t T h i s concept has b e e n b o t h s u p p o r t e d (9, 20,

s u c h defects. refuted

(21,

86),

w i t h M i i h l e m a n n (65)

expressing the

63)

and

contemporary

o p i n i o n that w h i l e s t r u c t u r a l irregularities a n d h y p o p l a s i a of the e n a m e l per

se d o not seem to increase caries s u s c e p t i b i l i t y , t h e y d o f a v o r post-

e r u p t i v e p l a q u e adherence a n d p o s s i b l y caries attack o w i n g to increased roughness. W h e t h e r r a c h i t i c c h i l d r e n have a greater t e n d e n c y to d e n t a l d e c a y t h a n n o n r a c h i t i c c h i l d r e n as has b e e n p r o c l a i m e d b y some (27, d i s p u t e d b y others M e l l a n b y (62)

(43,

84)

is s t i l l u n r e s o l v e d .

i m p l y that a n adequate

29)

and

N u m e r o u s studies

by

v i t a m i n D i n t a k e d u r i n g the

p e r i o d of tooth f o r m a t i o n i n c h i l d r e n is associated w i t h a r e d u c e d caries incidence.

A t t e m p t s to establish a r e l a t i o n s h i p b e t w e e n

dental

caries

a n d the v i t a m i n D content of the diet have been u n s u c c e s s f u l (95).

Di-

rect e v i d e n c e that h y p o p l a s i a is caused b y a d e f i c i e n c y of v i t a m i n D or that adequate v i t a m i n D per

se w i l l p r e v e n t h y p o p l a s i a or r e d u c e

i n c i d e n c e of d e n t a l caries is s t i l l l a c k i n g Effects of Excess.

the

(40).

T h e use of v i t a m i n D s u p p l e m e n t s to

control

d e n t a l caries is b e c l o u d e d b y a n inconsistency of results a n d i n t e r p r e t a tions.

C l a i m s for a caries-preventive

a c t i o n of v i t a m i n D range

from

u n m i t i g a t e d effectiveness regardless of age, diet, a n d f o r m a d m i n i s t e r e d (57)

to those t e m p e r e d b y s u c h l i m i t a t i o n s as: ( a ) v i t a m i n D p r o d u c e s

a substantial decrease i n the d e n t a l caries experience of c h i l d r e n w h e n g i v e n b e t w e e n 3 a n d 10 years of age b u t not w h e n g i v e n b e t w e e n a n d 16 years of age ( 5 ) ;

( b ) v i t a m i n D is m o r e b e n e f i c i a l against

w h e n a d d e d to a deficient diet t h a n to a w e l l b a l a n c e d d i e t (78);

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

11

caries (c)

4.

D R E I Z E N

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Vitamins and Dental Caries 41

v i t a m i n D decreases d e n t a l caries s u s c e p t i b i l i t y o n l y w h e n a d m i n i s t e r e d d u r i n g t h e f o r m a t i v e p e r i o d a n d not after a t o o t h has a l r e a d y e r u p t e d (6);

( d ) v i t a m i n D is m o r e effective against caries w h e n t a k e n as c o d

l i v e r o i l t h a n as i r r a d i a t e d ergosterol ( 5 6 ) .

Aebi (J)

reconciles studies

s h o w i n g a caries-deterrent a c t i o n of v i t a m i n D w i t h those w h i c h f a i l e d to c h a n g e the caries p a t t e r n (14,

21, 33, 48)

b y p o s t u l a t i n g that other

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factors i n the caries p i c t u r e m a y s u p p l e m e n t or negate the influence of v i t a m i n D . I n a m o r e p r o s a i c v e i n , S h a w (83)

ascribes the lack of effect

of v i t a m i n D to a l a c k of a n existing d e f i c i e n c y i n the subjects g i v e n the s u p p l e m e n t s . I n contrast, V o l k e r (92)

suggests that the s p e c i a l bene-

fits n o t e d w i t h c o d l i v e r o i l as c o m p a r e d w i t h other p r e p a r a t i o n s

of

v i t a m i n D c o u l d b e e x p l a i n e d b y the l o c a l a c t i o n of the fats c o n t a i n e d t h e r e i n rather t h a n b y the f o r m of the v i t a m i n D .

Vitamin

zyxwvutsrqponmlkjihgfedcbaZY

E

V i t a m i n E is essential for m a i n t a i n i n g the e n a m e l o r g a n of the rat incisor.

A d e f i c i e n c y leads to p r e m a t u r e a t r o p h y a n d e d e m a of

the

p a p i l l a r y layer, d e p i g m e n t a t i o n , h y p o p l a s i a , b i z a r r e a n a t o m i c f o r m s , ret a r d e d e r u p t i o n rate, a n d cyst f o r m a t i o n i n the adjacent c o n n e c t i v e tissue (66,

72).

T h e p a r e n c h y m a of the s a l i v a r y glands is r e p l a c e d b y fat cells

a n d fibrous c o n n e c t i v e tissue (66).

Because of its a n t i o x i d a n t c a p a c i t y ,

v i t a m i n E has b e e n tested against s u l c u l caries i n the rat.

L e v e l s u p to

0 . 5 % a-tocopherol i n the d i e t f a i l e d to i n h i b i t either caries or the g r o w t h of selected c a r i o g e n i c m i c r o o r g a n i s m s

Vitamin

(47).

K

O f a l l presently k n o w n v i t a m i n s , o n l y v i t a m i n K prevents a c i d form a t i o n w h e n a d d e d to s a l i v a - g l u c o s e mixtures in vitro

(28).

The anti-

b a c t e r i a l properties of n a t u r a l a n d synthetic v i t a m i n K stem f r o m t h e i r q u i n o n e structure w h i c h acts as a n e n z y m e p o i s o n a n d not f r o m the v i t a m i n a c t i v i t y (7, 17).

T h e efficacy of v i t a m i n K i n c o n t r o l l i n g d e n t a l

caries b y i n h i b i t i n g the enzymes i n v o l v e d i n the m i c r o b i a l d e g r a d a t i o n of c a r b o h y d r a t e s has b e e n s t u d i e d i n rats, hamsters, a n d m a n . I n rats, p r o l o n g e d a d m i n i s t r a t i o n of synthetic v i t a m i n K i n c o n c e n trations r a n g i n g f r o m 0.005 to 0.8%

of a c a r i o g e n i c d i e t f a i l e d to exert

a m e a s u r a b l e effect o n the caries i n c i d e n c e (41).

I n hamsters, v i t a m i n K

p r e v e n t e d d e n t a l d e c a y w h e n 1 m g was a d d e d to the d i e t every second d a y or w h e n 1 m g w a s injected i n t r a p e r i t o n e a l l y every t h i r d d a y

(31).

I n m a n , c h e w i n g a stick of g u m c o n t a i n i n g 0.75 m g 2 - m e t h y l - l , 4 - n a p h t h o q u i n o n e s o d i u m bisulfite a d d i t i o n c o m p o u n d ( s y n t h e t i c v i t a m i n K )

for

at least 10 m i n u t e s after each m e a l for a p e r i o d of 18 m o n t h s b y 58 sub-

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

42

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

jects r e d u c e d the d e v e l o p m e n t of n e w carious lesions b y f r o m 60 to 8 0 %

d e p e n d i n g o n the basis o f c o m p a r i s o nzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML (16). T h e v a l i d i t y of these c o n clusions has b e e n c h a l l e n g e d b y S h a w (83)

w h o a n a l y z e d the d a t a i n

the absence of a statistical e v a l u a t i o n b y the authors a n d b y a subsequent s t u d y i n w h i c h c h e w i n g a s y n t h e t i c v i t a m i n K - c o n t a i n i n g g u m after i n g e s t i o n of f o o d o r d r i n k h a d no caries-suppressive

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and radiographic examination Vitamin

(60).

effect o n c l i n i c a l

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR

P

Rutin, a compound w i t h vitamin P-like activity, and hesperidin, a n i n t e g r a l p a r t of the v i t a m i n P m o l e c u l e , e a c h w i t h a n t i o x i d a n t p r o p erties, h a v e b e e n i n v e s t i g a t e d f o r possible a n t i c a r i o g e n i c a c t i v i t y . N e i t h e r p r e v e n t e d caries i n rats w h e n i n c o r p o r a t e d i n a c a r i e s - i n d u c i n g d i e t n o r i n h i b i t e d the g r o w t h of selected b a c t e r i a u s u a l l y e n c o u n t e r e d i n the o r a l cavity.

I n a single t r i a l i n w h i c h rats w e r e f e d 0 . 5 %

h e s p e r i d i n , there

w a s a c t u a l l y a statistically significant increase i n caries score

Vitamin

Mixtures

(47).

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ

Effects of Deficiencies. G r e e n a n d H a r d e s (37)

of short t e r m experiments

p e r f o r m e d a series

( 2 0 - 2 1 d a y s ) d e s i g n e d to test the effect of

m u l t i p l e v i t a m i n d e l e t i o n o n caries p r o d u c t i o n w i t h o u t i n d u c i n g f r a n k d e f i c i e n c y states. O m i s s i o n of a l l fat-soluble v i t a m i n s f r o m a c a r i o g e n i c d i e t w a s w i t h o u t effect o n the caries experience of w e a n l i n g a l b i n o rats, whereas a n absence of a l l w a t e r - s o l u b l e v i t a m i n s r e s u l t e d i n a significant decrease i n caries d e v e l o p m e n t .

T h e latter w a s a t t r i b u t e d , i n p a r t , to

a d i m i n i s h e d f o o d i n t a k e a n d d i s t u r b e d eating p a t t e r n since the rats f a i l e d to g r o w o n the w a t e r - s o l u b l e v i t a m i n deficient diet. Effects of Supplements. T h e a n t i c a r i o g e n i c effectiveness of m i x e d

v i t a m i n preparations w a s i n v e s t i g a t e d i n a series of 436 h e a l t h y c h i l d r e n r a n g i n g i n age f r o m b i r t h to 5.5 years (42).

E a c h received a daily dietary

s u p p l e m e n t of 3000 to 4000 units v i t a m i n A , 400 units v i t a m i n D , 60 to 75 m g v i t a m i n C , 1.0 to 1.2 m g t h i a m i n e , 1.2 to 1.5 m g r i b o f l a v i n , a n d 8 to 15 m g n i a c i n a m i d e f o r 36 months. measurable fluoride

cariostatic

T h i s r e g i m e n f a i l e d to exert a

a c t i o n unless 0.5 to 1.0 m g

fluoride

as s o d i u m

w a s i n c o r p o r a t e d i n the d a i l y v i t a m i n s u p p l e m e n t .

Summary and

Conclusions

I n the p r e e m p t i v e p e r i o d , v i t a m i n s A , C , a n d D are essential f o r the p r o p e r d e p o s i t i o n a n d m i n e r a l i z a t i o n of t o o t h structure. A l t h o u g h w e l l f o r m e d teeth are not necessarily s y n o n y m o u s w i t h caries resistance,

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

4.

DREIZEN

Vitamins and Dental Caries

43

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such teeth may provide fewer opportunities for plaque attachment, plaque retention, and caries activity. In the posteruptive period, the vitamin-dental caries relationship is mediated primarily through the oral acidogenic flora. A l l cariogenic microorganisms are, to a certain extent, vitamin-dependent and require an exogenous supply of some or many of these nutrients. The spectrum of need varies with the particular organism. T h e Β vitamins nicotinic acid, pantothenic acid, and biotin are necessary growth factors for most, if not all, lactic acid bacteria. Some strains also require thiamine, riboflavin, and folic acid. As components of the coenzymes involved i n anaerobic glycolysis, thiamine and nicotinic acid facilitate the production of organic acids by microbial action on retained ingested carbohydrates. Diets completely devoid of the vitamins which serve as essential growth factors for the oral acidogenic organisms or as glycolytic coenzyme components are caries-inhibitory. Unfortunately, these vitamins cannot be deleted safely from the diet without disastrous consequences to human health. Conversely, there is, as yet, no clear and uncontestable evidence that dietary supplements of any of the presently known vitamins is protective against human dental caries.

Literature Cited (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19) (20) (21) (22) (23)

Aebi, H . , Nutr. Dieta 1964, 5, 82. Afonsky, D., J. Dental Res. 1951, 30, 53. Agapova, Ο. I., Stomatologiya 1954, 33, 17. Allington, Η. V., Arch. Dermatol. Syphilis 1950, 62, 829. Anderson, P. G., Williams, C. H . M . , Halderson, H . , Summerfeldt, C., Agnew, R. G., J. Am. Dental Assoc. 1934, 21, 1349. Armstrong, W . D.,J.Dental Res. 1948, 27, 376. Armstrong, W . D., Knutson, J. W., Proc. Soc. Exptl. Biol. & Med. 1943, 52, 307. Balogh, K., Petrucz, K., Angyal, J., J. Dental Res. 1960, 39, 886. Bibby, B. G., J. Dental Res. 1943, 22, 218. Bloch, C. E., Am. J. Diseases Children 1931, 42, 263. Boyle, P. E., J. Dental Res. 1933, 13, 39. Boyle, P. E., J. Dental Res. 1934, 14, 172. Boyle, P. E . , Wolbach, S. B., Bessey, Ο. Α., J. Dental Res. 1936, 15, 331. Bruszt, P., Oesterr. Z. Stomatol. 1958, 55, 72. Burrill, D . Y., J. Dental Res. 1942, 21, 330. Burrill, D . Y., Calandra, J. C., Tilden, Ε. B., Fosdick, L. S., J. Dental Res. 1945, 24, 273. Calandra, J. C., Fancher, Ο. E . , Fosdick, L. S., J. Dental Res. 1944, 23, 31. Cohen, Α., Rubin, C., Bull. Phila. County Dental Soc. 1958, 22, 84. Corkill, N. L., Lancet 1934, 1, 1387. Davies, J. N., Brit. Dental J. 1939, 67, 66. Day, C. D . M . , Sedwick, Η. J., J. Nutr. 1934, 8, 309. Dierks, K., Zahnaerztl. Rundschau. 1943, 52, 645. Dinnerman,M.,Oral Surg. Oral Med. Oral Pathol. 1951, 4, 1024.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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44

DIETARY C H E M I C A L S VS. D E N T A L CARIES

(24) Dreizen, S., Reed, A . I., Spies, T. D., Intern. Z. Vitaminforsch. 1951, 22, 396. (25) Dreizen, S., Spies, T. D., J. Dental Res. 1953, 32, 65. (26) Dreizen, S., Spirakis, C. N., Stone, R. E . , Intern. Z. Vitaminforsch. 1963, 33, 321. (27) Eliot, M . M . , Souther, S. P., Anderson, B. G., Arnim, S. S., Am. J. Diseases Children 1934, 48, 713. (28) Fancher, O. E., Calandra, J. C., Fosdick, L . S., J. Dental Res. 1944, 23, 23. (29) Firu, P., Diaconescu, M . , Cristea, M . , Gherga-Negrea, Α., Cristea, I., Stomatologia (Bucharest) 1965, 12, 139. (30) Fujishiro, I., Igaku To Seibutsagaku 1952, 23, 59. (31) Gebauer, H . , Deut. Zahnaerztl. Z. 1955, 10, 555. (32) Gebauer, H . , Plathner, C. H., Deut. Zahnaerztl. Z. 1959, 14, 1693. (33) Goll, H . , Wien. Klin. Wochenschr. 1939, 52, 35. (34) Goll, H . , Med. Klin. 1940, 26, 712. (35) Granados, H . , Glavind, J., Dam, H., J. Dental Res. 1949, 28, 670. (36) Grandison, W . B., Stott, L . B., Cruikshank, D . B., Brit. Dental J. 1942, 72, 237. (37) Green, R. M., Hartles, R. L . , Arch. Oral Biol. 1966, 11, 913. (38) Hafer, H . , J. Dentistry Belge 1959, 50, 187. (39) Hanke, M . T., "Diet and Dental Health," p. 142, The University of Chicago Press, Chicago, 1933. (40) Hartles, R. L . , Slack, G. L., Proc. Nutr. Soc. 1959, 18, 79. (41) Hatton, Ε. H . , Dodds, Α., Hodge, H . C., Fosdick, L . S., J. Dental Res. 1945, 24, 283. (42) Hennon, D . K., Stookey, G. K., Muhler, J. C., J. Dentistry Children 1966, 33, 3. (43) Hess, A. F., Abramson, H . , Dental Cosmos 1931, 73, 849. (44) Hess, W . C., Smith, B. T., J. Dental Res. 1949, 28, 507. (45) Hillman, R. W., Cabaud, P. G., Schenone, R. Α., Am. J. Clin. Nutr. 1962, 10, 512. (46) Hurtate, Α., Scrimshaw, N. S., J. Dental Res. 1955, 34, 390. (47) Jordan, Η. V., Bowler, A . E . , Berger, N. D., J. Dental Res. 1961, 40, 878. (48) Jundell, I., Hanson, R., Sandberg, T., Acta Paediat. 1938, 23, 141. (49) Kniesner, A . H., Mann, A . W., Spies, T. D., J. Dental Res. 1942, 21, 259. (50) Konig, K. G., Mόhlemann, H . R., Helv. Odontol. Acta 1964, 8, 72 suppl. 1. (51) Koser, S. Α., Fisher, B. J., J. Dental Res. 1950, 29, 760. (52) Koser, S. Α., Kasai, G. J., J. Bacteriol. 1947, 53, 743. (53) Krasse, B., Acta Odontol. Scand. 1954, 12, 173. (54) M zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA äkilä, Ε., Arch. Oral Biol. 1966, 11, 839. (55) Mann, A. W., Dreizen, S., Spies, T. D., Hunt, F . M . , J. Am. Dental Assoc. 1947, 34, 244. (56) McBeath, E . C., Verlin, W . Α., J. Am. Dental Assoc. 1942, 29, 1393. (57) McBeath, E . C., Zucker, T. F., J. Nutr. 1938, 15, 547. (58) McCann, M . C., Brady, R. R., Gillen, W . R., New Zealand Dental J. 1962, 58, 244. (59) McClure, F . J., J. Nutr. 1960, 72, 131. (60) Medical Department Professional Service Schools, Bull. U. S. Army Med. Dept. 1946, 5, 265. (61) Mellanby, M., Brit. Dental J. 1923, 44, 1. (62) Mellanby, M . , Med. Res. Council, Spec. Repts. Ser. (London) 1934, 191. (63) Mellanby, M., Brit. Med. J. 1940, 1, 1341. (64) Mellanby, M., Pattison, C. L., Brit. Med. J. 1928, 2, 1079. (65) Mόhlemann, H . R., "Nutrition and Caries Prevention," G. Blix, Ed., p. 9, Almqvist and Wiksells, Upsalla, Sweden, 1965.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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4.

DREIZEN

Vitamins and Dental Caries

45

(66) Nelson, Μ. Α., Jr., Chaudry, A. P., J. Dental Res. 1966, 45, 1072. (67) Novotny, J., Cesk. Stomatol. 1960, 60, 350. (68) Orland, F . J., Hemmens, E . S., Harrison, R. W., J. Dental Res. 1950, 29, 512. (69) Ott, E., Int. Z. Vitaminforsch. 1958, 29, 83. (70) Palazzo, Α., Cobe, H . M . , Ploumis, Ε., Ν. Y. State Dental J. 1959, 25, 303. (71) Paynter, K. J., Grainger, R. M . , J. Can. Dental Assoc. 1956, 22, 519. (72) Pindborg, J. J., J. Dental Res. 1952, 31, 805. (73) Rinehart, J. F., Greenberg, L. D., Am. J. Clin. Nutr. 1956, 4, 318. (74) Roberts, S. R., "Pellagra," p. 109, C. V. Mosby Co., St. Louis, 1912. (75) Russell, A. J., J. Dental Res. 1963, 42, 233. (76) Salley, J. J., Bryson, W . F., Eshleman, J. R., J. Dental Res. 1959, 38, 1038. (77) Sandwith, F . M . , "The Medical Diseases of Egypt," p. 296, H. Kempton, London, 1905. (78) Schoenthal, L . , Brodsky, R. H., Am. J. Diseases Children 1933, 46, 91. (79) Schour, I., Massler, M . , Physiol. Rev. 1945, 25, 442. (80) Shannon, I. L., Gibson, W . Α., Arch. Oral Biol. 1964, 9, 371. (81) Sharpenak, A. E . , Stomatol. Moscow 1958, 37, 3. (82) Shaw, J. H . , Proc. Soc. Exptl. Biol. & Med. 1949, 70, 479. (83) Shaw, J. H . , Natl. Acad. Sci.—Natl. Res. Council 1952, Publ. 225, 415. (84) Shelling, D . H., Anderson, G. M . , J. Am. Dental Assoc. 1936, 23, 840. (85) Shourie, K. L., Indian J. Med. Res. 1942, 30, 561. (86) Staz, J., S. African Med. J. 1943, 17, 1. (87) Steinman, R. R., Hardinge, M . G., J. Dental Res. 1958, 37, 874. (88) Strean, L . P., Schweiz. Monatsschr. Zahnheilk. 1957, 67, 981. (89) Strean, L . P., Bell, F . T., Gilfillan, E . W., Emerson, G. Α., Howe, Ε. E . , Ν. Y. State Dental J. 1958, 24, 133. (90) Strean, L . P., Gilfillan, E . W., Emerson, G. Α., Ν. Y. State Dental J. 1956, 22, 325. (91) Tabrah, F. L., Science 1962, 138, 38. (92) Volker, J. F., " A Symposium on Preventive Dentistry," J. C. Muhler and M . K. Hine, Eds., p. 45, The C. V . Mosby Co., St. Louis, 1956. (93) Westin, G., Dental Cosmos 1925, 67, 868. (94) Wynn, W., Haldi, J., Law, M . L., J. Nutr. 1960, 70, 69. (95) Youmans, J. B., Patton, E . W., Sutton, W . R., Kern, R., Steinkamp, R., Am. J. Public Health 1944, 34, 1049. RECEIVED August 14, 1968.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

5

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA

Antibiotics and Dental Caries BASIL G. BIBBY

zyxwvutsrqponmlkjihgfedcbaZYXWVUT

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Eastman Dental Center, Rochester, Ν . Y . 14603

When

fed in water or diet, penicillin

biotics

consistently

applications Clinical

on animals'

teeth

studies in human

frices or as prophylaxis

in animals.

seem to have

against

rheumatic

to the manner

of use rather than the absence

long-range ecological

an important

ill effects may balance

findings

result

of the oral

are probably of

consideration

from

effect.

in denti-

fever gave

While

properties,

negative

antiTopical

some

subjects using antibiotics

sistent results. cariostatic

The

and some other

limit caries activity

disturbance

inconrelated inherent is of

that the

flora.

i n i t i a l studies o n t h e relationships b e t w e e n a n t i b i o t i c s a n d d e n t a l caries w e r e d e s i g n e d to i n d i c a t e t h e i m p o r t a n c e of b a c t e r i a o r c e r t a i n

b a c t e r i a l g r o u p s i n its e t i o l o g y . T h e r e a f t e r , attempts w e r e m a d e t o establ i s h t h e usefulness

of c e r t a i n a n t i b i o t i c s i n caries p r e v e n t i o n i n m a n .

R e c e n t l y they h a v e b e e n u s e d a g a i n i n caries research f o r e v a l u a t i n g t h e i m p o r t a n c e of specific b a c t e r i a l types a n d testing n e w ideas i n caries etiology. T w e n t y years ago, t h e b e l i e f that g r a m p o s i t i v e b a c t e r i a , s u c h as t h e streptococci,

w e r e t h e a c t i v a t i n g agents of d e n t a l d e c a y w a s n o t as

g e n e r a l l y a c c e p t e d as i t is t o d a y , a n d some d e n t a l investigators b e l i e v e d that i n a d e q u a t e n u t r i t i o n m i g h t h a v e e q u a l i m p o r t a n c e .

O n e w a y of

settling this q u e s t i o n w a s t o a d d a n agent, s u c h as p e n i c i l l i n , w h i c h w o u l d d e s t r o y a c i d - p r o d u c i n g g r a m p o s i t i v e organisms, to a d i e t w h i c h w a s k n o w n to cause d e n t a l d e c a y i n rats, a n d see w h e t h e r i t w o u l d p r o t e c t the a n i m a l s against caries.

I n s u c h a n experiment, i t w a s f o u n d

(29)

that rats e a t i n g a c a r i e s - p r o d u c i n g d i e t w i t h 75 u n i t s of p e n i c i l l i n p e r g r a m of f o o d o r w a t e r d e v e l o p e d n o d e n t a l d e c a y , w h e r e a s a n i m a l s e a t i n g t h e p e n i c i l l i n - f r e e c o n t r o l d i e t d e v e l o p e d caries as u s u a l . T h e l a c t o b a c i l l i , w h i c h at that t i m e w e r e b e l i e v e d to b e causative agents of caries, h a d b e e n e l i m i n a t e d f r o m t h e m o u t h s of t h e p e n i c i l l i n g r o u p . F o l l o w i n g this a p p r o a c h , S t e p h a n et al. (36, 37)

tested t h e effect of p e n i c i l l i n , A u r e o 46

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

5.zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA B i B B YzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Antibiotics and Dental Caries 47 mycin, bacitracin, Chloromycetin, streptomycin, Terramycin,

cephalo-

s p o r i n , a n d p o l y m y x i n o n rat caries for the d o u b l e p u r p o s e of d e t e r m i n i n g the r e l a t i v e effectiveness of these agents i n p r e v e n t i n g caries a n d i n d i c a t i n g w h i c h spectra of m i c r o o r g a n i s m s p l a y e d the most i m p o r t a n t p a r t i n its etiology. T h e i r findings s h o w e d that o n l y c e p h a l o s p o r i n a n d p o l y m y x i n f a i l e d to r e d u c e caries, a n d that n o n e of the b r o a d - s p e c t r u m a n t i b i o t i c s w a s a n y m o r e effective t h a n p e n i c i l l i n i n this respect. T h e f a i l u r e of c e p h a l o s p o r i n , w h i c h is effective against most g r a m p o s i t i v e organisms

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except some s t r e p t o c o c c i a n d l a c t o b a c i l l i , t o r e t a r d caries i n d i c a t e d the i m p o r t a n c e of these b a c t e r i a l types i n caries.

T h e n e g a t i v e results w i t h

p o l y m y x i n l i k e w i s e s h o w e d that g r a m n e g a t i v e organisms h a d n o signific a n c e i n the c a u s a t i o n of rat caries. Fitzgerald and Jordan

(5)

tested 10 units or 10zyxwvutsrqponmlkjihgfedcbaZYXWV   μ ξ p e r g r a m of

several different a n t i b i o t i c s i n c a r i o g e n i c diets i n a rat s t u d y .

A l l the

agents s i g n i f i c a n t l y r e d u c e d the caries score b e l o w that g i v e n b y control diet.

the

P e n i c i l l i n w a s m o s t effective, w i t h o n l y one t h i r d of t h e

a n i m a l s s h o w i n g caries, f o l l o w e d i n o r d e r b y o r y t h r o m y c i n , z i n c b a c i tracin, carbomycin, and neomycin. I n a s t u d y of the m e c h a n i s m s of caries p r e v e n t i o n b y v a r i o u s agents, M c C l u r e et al

(28)

f o u n d that p e n i c i l l i n at 10 u n i t s p e r g r a m of d i e t w a s

m o r e effective i n p r e v e n t i n g caries i n w h i t e rats t h a n 50 p p m of s o d i u m fluoride

o r i o d o a c e t i c a c i d or a h i g h - m i n e r a l diet. T h e y i n t e r p r e t e d this

to m e a n that b a c t e r i a l a c t i v i t y o n the teeth w a s of p r i m a r y i m p o r t a n c e i n c a u s i n g caries. I n e n d e a v o r i n g to d e t e r m i n e w h i c h types of b a c t e r i a p r o d u c e d caries i n t h e i r caries-susceptible

s t r a i n of rats, R o s e n et al

(33)

f o u n d that

w h e n 500 units o f p e n i c i l l i n or 0 . 0 2 5 % T e r r a m y c i n p e r g r a m of d i e t w e r e f e d , n o caries o c c u r r e d i n the p e n i c i l l i n rats, b u t a l l t h e i r T e r r a m y c i n rats s h o w e d caries.

S i n c e b o t h a n t i b i o t i c s are effective

against

g r a m p o s i t i v e organisms, they c o n c l u d e d that some u n r e c o g n i z e d types of b a c t e r i a m u s t b e r e s p o n s i b l e f o r caries i n t h e i r a n i m a l s . S h a w a n d S w e e n e y (34)

u s e d c o t t o n rats, w h i t e rats, a n d d e s a l i v a t e d

w h i t e rats i n a c o m p a r i s o n of the effectiveness of different levels of a v a r i e t y o f a n t i b i o t i c agents o n caries, a n d also c o m p a r e d t h e i r in effectiveness against a h u m a n a n d rat strain of Lactobacillus

P e n i c i l l i n w a s the m o s t effective i n r e d u c i n g caries i n b o t h species. mycin, Chloromycetin, streptomycin, and Terramycin were

vitro

acidophilus.

Aureo-

moderately

effective, whereas p a n t h e n o l , t y r o t h r i c i n , s u b t i l i n , a n d b a c i t r a c i n

gave

o n l y s l i g h t or n o p r o t e c t i o n . N o c o r r e l a t i o n w a s f o u n d b e t w e e n effectiveness i n r e d u c i n g a n i m a l caries a n d the a b i l i t y to p r e v e n t a c i d f o r m a t i o n i n the l a c t o b a c i l l u s cultures.

F a l l a a n d S h a w (4)

s h o w e d that

injected

p e n i c i l l i n w o u l d r e d u c e caries i n rats, b u t to b e effective, levels t w i c e as h i g h as i n the f o o d h a d to b e u s e d .

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

48

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARTES

U s i n g a 15-day, rather t h a n the u s u a l 80- to 100-day,

experimental

p e r i o d , M u h l e m a n nzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA et al. (31) m a d e a n extensive c o m p a r i s o n of d i e t a r y a d d i t i o n s of 0.01 to 0 . 2 %

of a n t i b a c t e r i a l a n d a n t i f u n g a l a n t i b i o t i c s a n d

other a n t i b a c t e r i a l c h e m i c a l a n d cariostatic agents o n the i n i t i a t i o n of rat caries.

T h e a n t i b a c t e r i a l agents u s e d w e r e p e n i c i l l i n , A u r e o m y c i n ,

D e c l o m y c i n , erythromycin, O l e a n d o m y c i n , novobiocin, thiostrepton, bacitracin,

dihydrostreptomycin, and

chloramphenicol.

The

antimycotic

agents u s e d w e r e n y s t a t i n , g r i s e o f u l v i n , a m p h o t e r i c i n B , e c h i n o m y c i n ,

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usnic acid, and penicillin,

flavofungin.

T h e antibiotics w i t h gram positive s p e c t r a —

Oleandomycin, erythromycin, and

novobiocin—were

most

effective i n p r e v e n t i n g e a r l y caries, a n d t h e i r b r i e f l y - p r e s e n t e d

results

c a n b e i n t e r p r e t e d as s h o w i n g caries r e d u c t i o n s of f r o m 85 to 9 0 %

below

t h e w a t e r controls.

Tetracyclines—Aureomycin, Tetracyn, and Declo-

m y c i n — g e n e r a l l y gave r e d u c t i o n s i n the 6 0 % w e r e c o m p a r a b l e i n effectiveness t o s o d i u m

range a n d i n this respect fluoride,

as w e r e the a n t i -

b i o t i c s w i t h b o t h g r a m p o s i t i v e a n d g r a m negative spectra. a n t i m y c o t i c s n o r the disinfectants r e d u c e d caries.

N e i t h e r the

F r o m these results, it

w a s c o n c l u d e d that the a n t i b i o t i c s w e r e the most effective agents against rat caries. T h e o b v i o u s c o n c l u s i o n f r o m a l l of these studies is that a n t i b i o t i c s are c a p a b l e of p r e v e n t i n g d e n t a l d e c a y i n a n i m a l s . S e v e r a l o f t h e m are v e r y potent, a n d t h e i r effectiveness seems to b e r e l a t e d to t h e

capacity

to interfere w i t h the g r o w t h of g r a m p o s i t i v e b a c t e r i a i n g e n e r a l , rather t h a n the l a c t o b a c i l l i i n p a r t i c u l a r . T h e d e m o n s t r a t e d effectiveness of antibiotics i n p r e v e n t i n g a n i m a l caries l e d to a c o n s i d e r a t i o n of their use to c o m b a t d e n t a l d e c a y i n m a n . A s a result, b o t h in vitro a n d a n i m a l caries studies w e r e u n d e r t a k e n , w i t h a v i e w to d e v e l o p i n g p r o p h y l a c t i c p r o d u c t s for h u m a n use. T h e in vitro experiments w e r e b a s e d o n the k n o w l e d g e that d e n t a l caries results f r o m d e c a l c i f i c a t i o n of teeth b y acids f o r m e d b y b a c t e r i a l f e r m e n t a t i o n of c a r b o h y d r a t e s , a n d , therefore, a n y agent w h i c h w o u l d effectively interfere w i t h the p r o d u c t i o n of a c i d w o u l d b e l i k e l y to p r e vent tooth decay.

U s i n g this a p p r o a c h , large n u m b e r s of

antibacterial

agents a n d e n z y m e i n h i b i t o r s h a v e b e e n tested i n several w a y s to i n d i c a t e t h e i r p o t e n t i a l usefulness i n p r e v e n t i n g caries.

Zander and B i b b y

(44)

m e a s u r e d r e d u c t i o n of a c i d f o r m a t i o n f r o m glucose i n s a l i v a , F o s d i c k

(9)

c a l c i u m loss f r o m e n a m e l i n a s a l i v a r y f e r m e n t a t i o n system, a n d M a h l e r a n d M a n l y (27) p a c k e d organisms

acid formation i n an "artificial plaque" composed obtained b y centrifuging m o u t h washings.

In

of our

experiments, a n d F o s d i c k ' s , p e n i c i l l i n w a s the most effective of the m a n y agents tested.

F o s d i c k c o n c l u d e d that since p e n i c i l l i n w a s a b s o r b e d i n

p r o t e i n films, a n d other e n z y m e i n h i b i t o r s w e r e not, i t w o u l d h a v e

a

l a s t i n g effect o n the c a r i e s - p r o d u c i n g a c t i v i t y of the b a c t e r i a l p l a q u e s o n

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

5.

49 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Antibiotics and Dental Caries

BIBBY

the t o o t h surface.

H o w e v e r , i n M a h l e r a n d M a n l y ' s (27)

experiments,

i n w h i c h p a c k e d m i c r o o r g a n i s m s w e r e u s e d rather t h a n

suspensions,

p e n i c i l l i n w a s ineffective i n c h a n g i n g the course of a c i d p r o d u c t i o n . T h i s finding

o n short-term a c i d f o r m a t i o n i n " a r t i f i c i a l p l a q u e " w a s e x t e n d e d

i n t o the m o u t h b y B r u d e v o l d a n d H a w e s ' (3)

finding

that p e n i c i l l i n d i d

not interfere w i t h a c i d f o r m a t i o n i n p l a q u e s o n h u m a n t o o t h surfaces. A different sort of in vitro e v i d e n c e o n the effectiveness of p e n i c i l l i n i n p r e v e n t i n g caries w a s offered b y Z a n d e r a n d B i b b y (44),

w h o showed

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t h a t s a l i v a c o l l e c t e d f r o m h u m a n m o u t h s 2 h o u r s after a p e n i c i l l i n rinse s t i l l l a c k e d the a b i l i t y to f e r m e n t glucose. W h i l e a t t e n t i o n has b e e n c e n t e r e d o n p e n i c i l l i n , other g i v e c o m p a r a b l e i n h i b i t i o n of a c i d f o r m a t i o n i n in vitro Brudevold and B i b b y (2)

antibiotics

tests (2,

29).

f o u n d that a m o n g e x p e r i m e n t a l l y d e v e l o p e d

a n t i b i o t i c s that the m a n u f a c t u r e r s d e e m e d u n s u i t a b l e f o r systemic a d m i n i s t r a t i o n there w e r e some w h i c h w e r e e q u a l l y as effective as p e n i c i l l i n i n reducing acid production b y m o u t h bacteria.

F r o m this, i t m a y b e s u g -

gested that the l o n g - r a n g e p o s s i b i l i t i e s of u t i l i z i n g a n t i b i o t i c s i n caries c o n t r o l m i g h t w e l l d e p e n d u p o n the selection o f types w h i c h w o u l d n o t b e e m p l o y e d f o r a n y other m e d i c a l p u r p o s e . S e v e r a l a n i m a l - f e e d i n g studies d e s i g n e d to s u p p l e m e n t those a l r e a d y c i t e d h a v e b e e n c a r r i e d out to select a n d evaluate a n t i b i o t i c s f o r i n c l u s i o n i n d e n t i f r i c e s i n t e n d e d f o r caries p r e v e n t i o n i n m a n . finding

L o o k i n g towards

the lowest effective c o n c e n t r a t i o n of p e n i c i l l i n w h i c h w o u l d b e

effective against caries, W e b m a n et al.

(40)

s h o w e d that as l i t t l e as 2

units of p e n i c i l l i n a d d e d to a c a r i e s - p r o d u c i n g d i e t r e d u c e d d e n t a l d e c a y i n rats b y almost a t h i r d , a n d that a r e d u c t i o n of l a c t o b a c i l l u s c o u n t a n d a n increase

of g r a m negative organisms also o c c u r r e d i n the

m o u t h s . V o l k e r et al. (38)

animals'

c o m p a r e d the effect of p e n i c i l l i n , a m e r c u r i c

benzoate, a n d a sarcosinate, a l l of w h i c h i n h i b i t e d a c i d p r o d u c t i o n b y s a l i v a r y b a c t e r i a a n d w e r e r e t a i n e d o n the t o o t h surface, o n

hamster

caries. T h e y f o u n d p e n i c i l l i n to b e the most effective u n d e r the t w o test c o n d i t i o n s u s e d . I n another c o m p a r i s o n of the effectiveness of p e n i c i l l i n a n d other cariostatic agents, P i n d b o r g (32)

f o u n d that 20 m g of p r o c a i n e

p e n i c i l l i n p e r k g of d i e t ( t h e e q u i v a l e n t of 20 i n t e r n a t i o n a l u n i t s p e r g r a m of d i e t ) r e d u c e d d e n t a l d e c a y b y 8 1 % , whereas 10 p p m of s o d i u m fluoride

or of stannous

fluoride

a d d e d to the same d i e t gave

caries

r e d u c t i o n s of o n l y 31.6 a n d 28.9, respectively. Another type

of

experiment,

i n w h i c h antibiotic mixtures

were

b r u s h e d o n a n i m a l teeth, has b e e n u s e d to p r e d i c t t h e p o t e n t i a l effectiveness of a n t i b i o t i c dentifrices i n m a n . I n the first e x p e r i m e n t of this sort, Z a n d e r a n d B i b b y (44)

b r u s h e d a s o l u t i o n c o n t a i n i n g 500 u n i t s of p e n i -

c i l l i n p e r c c o n t h e t e e t h of hamsters

w h i c h were kept on a

caries-

p r o d u c i n g d i e t f o r 40 days. I n e i g h t animals w h o s e teet h w e r e b r u s h e d

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

50

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

w i t h p e n i c i l l i n , there was less t h a n one c a v i t y p e r a n i m a l , whereas i n the w a t e r - b r u s h e d c o n t r o l g r o u p , the a n i m a l s h a d a n average of seven cavities. I n another hamster e x p e r i m e n t ( 4 5 ) , solutions c o n t a i n i n g v a r i o u s c o n c e n trations of p e n i c i l l i n , A u r e o m y c i n , a n d t y r o t h r i c i n w e r e b r u s h e d o n the teeth.

P e n i c i l l i n w a s most effective.

testing i n c h i l d r e n , Shiere ( 3 5 )

T o select a d e n t i f r i c e f o r c l i n i c a l

b r u s h e d five different t y r o t h r i c i n d e n t i -

frices a n d a c o n t r o l o n hamster teeth.

T h e one w h i c h gave the m a x i m a l

caries

c o n t r o l , was

reduction, 25.6%

b e l o w the

subsequently

found

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e q u a l l y effective i n m a n . T h e a c c u m u l a t e d e v i d e n c e that p e n i c i l l i n w o u l d interfere w i t h a c i d formation b y salivary bacteria and w o u l d unquestionably prevent dental caries i n a n i m a l s l e d to tests of its caries-preventive effect i n m a n . B e f o r e m e n t i o n i n g the findings i n the c l i n i c a l tests w h i c h h a v e b e e n c a r r i e d o u t u s i n g a n t i b i o t i c dentifrices, it s h o u l d b e p o i n t e d out

that

m a n y v a r i a b l e s b e y o n d that of the agent u s e d c o m p l i c a t e the o b t a i n i n g of r e l i a b l e results i n h u m a n studies.

F o r instance, a n agent w h i c h is

effective i n a n i m a l s m a y not b e of a n y use i n m a n , or one e x a m i n a t i o n a n d r e c o r d i n g p r o c e d u r e m a y f a i l to s h o w differences w h i c h w o u l d a p p e a r i f another w e r e u s e d , b u t m o s t i m p o r t a n t l y , the w h o l e result is g o i n g to d e p e n d u p o n the extent to w h i c h the instructions o n the use of the test d e n t i f r i c e are f o l l o w e d . O b v i o u s l y , n o t h e r a p e u t i c agent c a n b e expected to p r o d u c e benefit as l o n g as it r e m a i n s i n its container. S e v e r a l c l i n i c a l tests o n the effect of a n t i b i o t i c dentifrices o n caries have been reported.

et al. ( 1 5 ) , u s e d a T h e first s t u d y , that of H i l lzyxwvutsrqponmlkjihgfedcbaZYXWVU

p o w d e r c o n t a i n i n g 500 units of p e n i c i l l i n p e r g r a m a n d p r o d u c e d n o a p p a r e n t r e d u c t i o n i n d e n t a l decay, a l t h o u g h a r e d u c t i o n i n s a l i v a r y l a c t o b a c i l l u s c o u n t was o b s e r v e d .

H o w e v e r , since the test subjects w e r e

8- to 16-year-old boys w h o s e u n s u p e r v i s e d b r u s h i n g habits

are

most

u n p r e d i c t a b l e , the negative result c o u l d h a v e b e e n the result of l i m i t e d use of the d e n t i f r i c e .

I n another

study, Zander

(43)

found a

55%

r e d u c t i o n i n d e n t a l d e c a y i n 6- to 14-year-old c h i l d r e n i n the first year, a n d a 57.6%

r e d u c t i o n i n the s e c o n d y e a r w h e n a p o w d e r c o n t a i n i n g

500 units of p e n i c i l l i n p e r g r a m w a s b r u s h e d o n the teet h u n d e r superv i s i o n five times p e r w e e k i n school. I n the t h i r d test of a n a n t i b i o t i c d e n t i f r i c e ( 1 6 ) , 1000 units of p e n i c i l l i n p e r g r a m i n a n a n h y d r o u s c r e a m y base was used under supervised brushing.

It w a s o n l y s l i g h t l y effective i n

r e d u c i n g d e n t a l d e c a y a n d d i d not r e d u c e the l a c t o b a c i l l u s c o u n t i n the s a l i v a . T h e l a c k of success i n this instance c o u l d h a v e b e e n c a u s e d b y the p e n i c i l l i n not b e i n g l i b e r a t e d f r o m the d e n t i f r i c e r a p i d l y e n o u g h i n the m o u t h . I n a s m a l l test ( 3 9 )

w i t h a p o w d e r c o n t a i n i n g 100 units of

p e n i c i l l i n p e r g r a m , o r p h a n a g e c h i l d r e n s h o w e d n o s l o w i n g of the caries attack o r r e d u c t i o n of the

l a c t o b a c i l l u s c o u n t as c o m p a r e d w i t h

the

controls. I n the o n l y d e n t i f r i c e s t u d y w i t h a n a n t i b i o t i c other t h a n p e n i -

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

5.

51 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Antibiotics and Dental Caries

BIBBY

c i l l i n ( 3 5 ) , a t y r o t h r i c i n d e n t i f r i c e w h i c h h a d b e e n s h o w n to b e effective against hamster caries gave a 2 6 %

reduction i n dental decay w h e n com-

p a r e d w i t h a c o n t r o l paste. Using

only lactobacillus

counts

and acid formation by

m o u t h organisms to assess caries a c t i v i t y , L u d w i c k et al

(26)

aciduric compared

different concentrations of several a n t i b i o t i c s a n d other agents over 6- to 7-week p e r i o d s . T h e y f o u n d that a p o w d e r c o n t a i n i n g 0.07%

penicillin

was m o r e effective t h a n p o w d e r s c o n t a i n i n g t y r o t h r i c i n , s t r e p t o m y c i n ,

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g r a m i c i d i n , b a c i t r a c i n , a n d other anticaries agents. T h e effect of a n a n t i b i o t i c i n a m o u t h w a s h o n caries seems to h a v e b e e n tested o n l y o n c e ( 2 3 ) , i n w h i c h a 1-year t r i a l of b a c i t r a c i n i n a m o u t h w a s h f a i l e d to r e d u c e caries.

W h i l e p e n i c i l l i n has b e e n i n c o r p o r a t e d i n t o c h e w i n g g u m a n d

troches f o r other o r a l uses, t h e r e does not seem to h a v e b e e n a n y o r g a n i z e d s t u d y of t h e i r effect o n d e n t a l caries. R e a s o n f o r b e l i e v i n g that p e n i c i l l i n is c a p a b l e of r e d u c i n g d e n t a l d e c a y i n h u m a n subjects has c o m e f r o m another t y p e of use.

Many

c h i l d r e n are p l a c e d o n p r o p h y l a c t i c p e n i c i l l i n f o r the c o n t r o l of r h e u m a t i c fever or as a means of c o m b a t t i n g c h r o n i c p u l m o n a r y

diseases.

S e v e r a l c o m p a r i s o n s h a v e b e e n m a d e of patients u n d e r s u c h t h e r a p y .

In

one of these ( 2 5 ) , r h e u m a t i c f e v e r patients w h o h a d b e e n o n p r o p h y l a c t i c p e n i c i l l i n f r o m the age of 7 years h a d a p p r o x i m a t e l y 4 0 %

f e w e r carious

teeth t h a n c h i l d r e n of c o m p a r a b l e age w i t h o u t a n t i b i o t i c experience.

In

a later s t u d y ( 1 3 ) , 75 a n d 74 c h i l d r e n w h o r e c e i v e d d a i l y o r a l p e n i c i l l i n , r e s p e c t i v e l y , 200,000 u n i t s f o r the p r e v e n t i o n of r e c u r r e n t fever

and

1-3,000,000 units w i t h

occasional

tetracycline

rheumatic for

chronic

r e s p i r a t o r y diseases, s h o w e d o n l y one t h i r d of the caries i n c r e m e n t

of

c o n t r o l subjects. T h e in vitro

a n d a n i m a l studies, together w i t h p r e l i m i n a r y c l i n i c a l

e v i d e n c e of caries r e d u c t i o n i n m a n , r e s u l t e d i n the b r i e f a p p e a r a n c e o n the m a r k e t of t w o p e n i c i l l i n dentifrices. their disappearance.

S e v e r a l reasons c o n t r i b u t e d to

O n e o f these w a s that c o m p e t i n g t h e r a p e u t i c d e n t i -

frices w i t h greater cosmetic a p p e a l w e r e offered at a b o u t the same t i m e . A n o t h e r is that t h e y w e r e treated w i t h s u s p i c i o n b y b o t h the m e d i c a l a n d d e n t a l professions, w h i c h , as experience g r e w , a t t a c h e d i n c r e a s i n g w e i g h t to the dangers of d e v e l o p i n g p e n i c i l l i n - r e s i s t a n t organisms a n d a l l e r g i c states. T h e e v i d e n c e o n this latter subject rests i n some

demonstrations

that the m o u t h s of c h i l d r e n u s i n g p e n i c i l l i n dentifrices c o n t a i n e d i n creased p o p u l a t i o n s of g r a m n e g a t i v e organisms i n t w o studies (14,

42).

C h i l d r e n u s i n g Z a n d e r s 500-unit p e n i c i l l i n p o w d e r f o r 1£ years d i d not s h o w a n increase i n p e n i c i l l i n - r e s i s t a n t l a c t o b a c i l l i (8) a n d s t a p h y l o c o c c i (22),

or

streptococci

b u t after 3 years m o r e p e n i c i l l i n - r e s i s t a n t strep-

t o c o c c i , m i c r o c o c c i , a n d neisseria w e r e f o u n d (21,

41).

I n patients o n

200,000-3,000,000 units of o r a l p e n i c i l l i n p e r d a y , a s l i g h t increase

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

in

52

DIETARY

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

a n t i b i o t i c resistance w a s n o t e d w i t h o u t a n y significant change i n b a c t e r i a l e c o l o g y of the m o u t h ( I I ) .

H o w e v e r , f a i l u r e to establish the safety of

p e n i c i l l i n i n the f a c e of i n d i c a t i o n s of increases i n the n u m b e r of p e n i cillin-resistant b a c t e r i a l types r e s u l t e d i n u n f a v o r a b l e o p i n i o n f r o m a n

A d H o c C o m m i t t e e of the F e d e r a l F o o d a n d D r u g A d m i n i s t r a t i o nzyxwvutsrqponmlkjih (24), a n d l i k e w i s e , the C o u n c i l o n D e n t a l T h e r a p e u t i c s of t h e A m e r i c a n D e n t a l A s s o c i a t i o n offered a c r i t i c a l o p i n i o n ( 1 7 ) , r e c o m m e n d i n g that " p e n i c i l l i n dentifrices

s h o u l d not

be

d i s t r i b u t e d . . . except

on

a

prescription

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basis." I n a n y case, w h e t h e r i t w a s f o r this or other reasons, the p e n i c i l l i n d e n t i f r i c e s d i d not c o n t i n u e o n the m a r k e t . A p a r t f r o m c o m m e r c i a l c o n siderations, this m a y h a v e b e e n a p r e m a t u r e d e v e l o p m e n t b e c a u s e e v e n i f p e n i c i l l i n c o u l d not b e u s e d i n e v e r y d a y d e n t i f r i c e s , a p e n i c i l l i n d e n t i f r i c e m i g h t h a v e h a d some usefulness i n s h o r t - t e r m treatment of patients w i t h o t h e r w i s e u n c o n t r o l l a b l e d e n t a l d e c a y . It is also possible that u s i n g a n t i b i o t i c s i n other w a y s m i g h t b e justified i n p h y s i c a l l y h a n d i c a p p e d or m e n t a l l y deficient patients, w h e r e o r d i n a r y m e t h o d s of caries c o n t r o l cannot be used. T h e last phase of e x p e r i m e n t a t i o n w i t h a n t i b i o t i c s has b e e n d i r e c t e d m a i n l y t o w a r d s i n v e s t i g a t i n g the r o l e of i n f e c t i o n w i t h specific m i c r o organisms i n e x p e r i m e n t a l caries. F o l l o w i n g the finding t h a t t r a n s m i s s i o n of m i c r o o r g a n i s m s w a s i m p o r t a n t i n i n i t i a t i n g a c t i v e caries i n a n i m a l s , i t b e c a m e i m p o r t a n t to establish the s p e c i f i c i t y of the b a c t e r i a l types i n volved.

A f t e r i t w a s f o u n d that the caries seemed to result f r o m o r a l

c o n t a m i n a t i o n w i t h the streptococcus

f r o m the feces, K e y e s (18)

was

a b l e to demonstrate that p e n i c i l l i n a n d e r y t h r o m y c i n w h i c h e l i m i n a t e d s u c h s t r e p t o c o c c a l types f r o m the m o u t h also p r e v e n t e d caries. T o d e m onstrate the s p e c i f i c i t y of specific strains of organisms, test s t r e p t o c o c c i w e r e m a d e streptomycin-resistant so that they c o u l d b e u s e d as m a r k e r s a n d i d e n t i f i e d i n the presence

of other s t r e p t o c o c c a l types

(8).

This

m a d e i t possible to s h o w that the m a r k e d types w e r e t r a n s m i t t e d f r o m one a n i m a l to another (6)

a n d to i d e n t i f y t h e m as t h e i n f e c t i v e agents

w h i c h p r o d u c e caries i n o t h e r w i s e caries-free a n i m a l s . This technique

of d e v e l o p i n g s t r e p t o m y c i n resistance

strains of s t r e p t o c o c c i w a s u s e d b y K r a s s e et al. (20)

i n specific

to s t u d y " i n f e c t i o n "

of h u m a n m o u t h s w i t h exogenous c a r i o g e n i c streptococci.

H e demon-

strated l o n g - t e r m s u r v i v a l of a h u m a n c a r i o g e n i c streptococcus i m p l a n t a t i o n i n m o u t h s i n w h i c h it w a s p r e v i o u s l y absent.

after

Cariogenic

h a m s t e r s t r e p t o c o c c i s u r v i v e d for shorter p e r i o d s . A n o t h e r w a y i n w h i c h the a n t i b i o t i c s h a v e b e e n u s e d t o i n d i c a t e the c a r i o g e n i c i t y of specific b a c t e r i a l types is b y u s i n g t h e m as G u g g e n h e i m et al.

(10)

h a v e d o n e to depress t h e u s u a l o r a l flora to p r o d u c e a

p a r t i a l gnotobiosis so that t h e i n t r o d u c e d test t y p e w i l l f a c e a less c o m p e t i t i v e struggle f o r existence a n d b e c o m e established i n a s i t u a t i o n i n

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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5.

BIBBY

Antibiotics and Dental Caries

53

which it would not otherwise survive. Using a similar approach, Bowen (I) was able to show that an erythromycin-resistant streptococcus from human teeth could be established i n the mouths of monkeys rendered partially gnotobiotic by administration of erythromycin. A further use for antibiotics i n caries research has been to indicate the importance of bacterial polysaccharides i n the sticky masses or plaques which form on the tooth surfaces of rats and hamsters on a sucrose diet (19). Since tooth destruction occurs under these plaques, agents which w i l l inhibit the streptococci responsible for their formation would have potential importance i n the prevention of caries i n man. Keyes (19) has shown that i n rats and hamsters daily short applications of penicillin, erythromycin, streptomycin, tetracycline, and speramycin are very effective i n preventing plaque formation and subjacent tooth decalcification. Vancomycin was somewhat less so, and neomycin, bacitracin, and thiostrepton without effect. W h i l e caution cannot be too strongly emphasized i n projecting animal findings to conditions i n man, Mitchell and Holmes (30) have demonstrated that frequent applications of vancomycin w i l l prevent the development of one type of plaque deposit in human mouths. In conclusion, a final question has to be faced—that is, whether repeated use i n the mouth of a therapeutic vehicle containing a "safe" antibiotic free of a l l medical hazards would be wise. If it killed a wide spectrum of oral bacterial types, its use would not be without danger because elimination of the predominant bacterial types i n the mouth might allow other organisms, such as fungi, to become established, with possible unfortunate pathological effects. The perfect anticaries antibiotic w i l l need to have preferential antagonism for only those types which are particularly important i n caries causation and no effect on other types. Achieving this goal should not be beyond the possibilities of future research.

Literature Cited (1) (2) (3) (4) (5) (6) (7) (8)

Bowen, W., personal communication, 1968. Brudevold, F., Bibby, B. G., unpublished findings. Brudevold, F., Hawes, R. R.,J.Dental Res. 1952, 31, 474. Falla, W . S., Shaw, J. H . , Arch. Oral Biol. 1965, 10, 537. Fitzgerald, R. J., Jordan, H . J., J. Dental Res. 1955, 34, 685. Fitzgerald, R. J., Keyes, P. H . , Am. J. Pathol. 1963, 42, 7. Fitzgerald, R. J., Keyes, P. H . , J. Am. Dental Assoc. 1960, 61, 9. Fitzgerald, R. J., Zander, H . A., Jordan, H. J., J. Am. Dental Assoc. 1950, 41, 62. (9) Fosdick, L . S., Ludwick, W . E., J. Dental Res. 1950, 29, 664. (10) Guggenheim, B., Konig, K . G., Muhlemann, H. R., Helv. Odont. Acta 1965, 9, 121. (11) Handelman, S. L . , Hawes, R. R., Arch. Oral Biol. 1965, 10, 353.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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54

DIETARY C H E M I C A L S VS. D E N T A L CARIES

(12) Handelman, S. L., Hawes, R. R.,J.Oral Therap. Pharmacol. 1964, 1, 23. (13) Handelman, S. L., Mills, J. R., Hawes, R. R., J. Oral Therap. Pharmacol. 1966, 2, 338. (14) Hawes, R. R., Thesis, University of Rochester, Rochester, Ν. Y., 1951. (15) Hill, T. J., Kniesner, A. H . , J. Dental Res. 1948, 27, 267. (16) Hill, T. J., Sims, J., Newman,M.,J.Dental Res. 1953, 32, 448. (17) J. Am. Dental Assoc. 1952, 45, 466. (18) Keyes, P. H . , Arch. Oral Biol. 1960, 1, 304. (19) Keyes, P. H., J. Oral Therap. Pharmacol. 1966, 3, 157. (20) Krasse, B., Edwardsson, S., Svensson, I., Trell, L . , Arch. Oral Biol. 1967, 12, 231. (21) Lind, H . E., Antibiot. Chemotherapy 1954, 4, 161. (22) Lind, H . E., Zander, Η. Α., J. Dental Res. 1950, 29, 667. (23) Law, F . E . , Wallace, D . R., Spitz, G. S., Public Health Rept. 1961, 76, 1094. (24) Lewis, Charles N., M.D., personal communication, 1952. (25) Littleton, N . W., White, C. L., J. Am. Dental Assoc. 1964, 68, 520. (26) Ludwick, W . E . , Fosdick, L. S., Schantz, C. W., J. Am. Dental Assoc. 1951, 43, 285. (27) Mahler, I. R., Manly, R. S.,J.Am. Dental Assoc. 1958, 56, 854. (28) McClure, F . J., Falk, J. E . , Rust, J. D., J. Am. Dental Assoc. 1956, 53, 1. (29) McClure, F. J., Hewitt, W . L., J. Dental Res. 1946, 25, 441. (30) Mitchell, D . F., Holmes, L. Α.,J.Periodont. 1965, 36, 202. (31) Muhlemann, H. R., Meyer, R. W., Konig, K. G., Marthaler, T. M., Helv. Odont. Acta 1961, 5, 18. (32) Pindborg, J. J., Acta Odont. Scand. 1958, 16, 383. (33) Rosen, S., Ragheb, C. Α., Hoppert, C. Α., Hunt, H . R., J. Dental Res. 1956, 35, 399. (34) Shaw, J. H., Sweeney, Ε. Α., J. Dental Res. 1957, 36, 349. (35) Shiere, F. R., J. Dental Res. 1957, 36, 237. (36) Stephan, R. M., Fitzgerald, R. J., McClure, F . J., Harris, M . R., Jordan, H . J., J. Dental Res. 1952, 31, 421. (37) Stephan, R. M., Harris, M . R., Fitzgerald, R. J., J. Dental Res. 1952, 31, 475. (38) Volker, J. F., Apperson, L. D., King, W . J., J. Dental Res. 1955, 34, 733. (39) Walsh, J. P., Smart, R. S., New Zealand Dental J. 1951, 47, 118. (40) Webman, H . , Kniesner, A. H., Hill, T. J., J. Dental Res. 1948, 27, 258. (41) Welsh, H . , Randall, W . Α., Buckman, L . E . , Hendrix, F. D . , Antibiot. Chemotherapy 1952, 2, 249. (42) White, B. J., Kniesner, A . H . , Hill, T. J., J. Dental Res. 1949, 28, 267. (43) Zander, Η. Α., J. Am. Dental Assoc. 1950, 40, 569. (44) Zander, Η. Α., Bibby, B. G., J. Dental Res. 1947, 26, 365. (45) Zander, Η. Α., Lisanti, V . F., Shiere, F . R., J. Dental Res. 1951, 30, 139. RECEIVED October 27, 1969.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

6

Other Organic Compounds and Dental Caries

K E N N E T H O. M A D S E N

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Dental Branch, University of Texas, Houston, Tex.

Caries in experimental animals may be influenced by the dietary administration of a wide variety of organic compounds. Some influences are attributed to physiological or pharmacological effects. Phenolic acids, polyphenols, antioxidants, antienzymes, carbonyl binding agents, and complexing agents as well as organic polymers all affect caries production. Anticaries activity was widespread in the outer coverings of seeds under all conditions studied. Naturally occurring anticariogenicity was also noted in unrefined sugar products, cocoa, and chocolate.

Many

naturally occurring and synthetic organic substances when added to the diet have an influence on caries. Some, including organic phosphates and fluorides, have been reviewed elsewhere in this symposium. Primarily, the results from compounds that influence caries in experimental animals w i l l be discussed in this paper. Most of the compounds tested in clinical studies as components of toothpaste, mouthwashes, and chewing gum have been reviewed in detail elsewhere (48, 146, 149) and w i l l be considered here in summary manner. Thousands of compounds have been screened by a variety of in vitro testing procedures, most involving microbiological assays where microorganisms came from saliva or dental plaque or are strains suspected of being important in the caries process. Usually, the effect of the compound on total acid production, p H , or growth is measured. Shaw concluded i n 1959 in an excellent review of caries-inhibiting agents (149) that "no specific in vitro test procedure has been shown to have a sufficiently good correlation with clinical trials to merit confidence. Such testing, of course, provides one means for finding suitable compounds for subsequent trial at the experimental animal stage prior to clinical evaluation. Although it is appropriate to mention the most likely compounds discovered in screening and in vitro tests, primarily ,,

55 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

56

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

o n l y those c o m p o u n d s tested b o t hzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ in vitro a n d i n e x p e r i m e n t a l caries assays w i l l b e c o n s i d e r e d i n this discussion. T h e c o m p o u n d s c o n s i d e r e d w i l l b e classified a r b i t r a r i l y o n the basis of c e r t a i n of t h e i r c h e m i c a l s i m i l a r i t i e s , o n w h e t h e r or not t h e y a p p e a r to h a v e a specific a c t i o n o n caries, a n d w h e t h e r t h e i r effect o n caries m a y b e a consequence of t h e i r p h y s i o l o g i c a l or p h a r m a c o l o g i c a l a c t i v i t y . T h e a r r a y of factors i n f l u e n c i n g e a c h of the different d e n t a l caries studies c i t e d i n this r e v i e w w a s not o n l y l a r g e b u t often d i f f i c u l t to determine.

A c c o r d i n g l y , the factors i n c l u d e d i n the d e s c r i p t i o n of

each

assay w e r e those c o n s i d e r e d most significant either f o r the p a r t i c u l a r Downloaded by CORNELL UNIV on May 21, 2017 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch006

s t u d y or f o r c o m p a r i n g i t w i t h other studies.

Whenever it appeared

that a substance o r c o m p o u n d h a d h a d a statistically significant or other v a l i d effect o n caries, s u c h has b e e n stated s i m p l y . N o a t t e m p t has b e e n m a d e to d e s c r i b e the extent of the effects—e.g., percentage

inhibition—

since this t y p e of e v a l u a t i o n is h i g h l y relative a n d s o m e w h a t m i s l e a d i n g . If effects c a n b e e s t a b l i s h e d as r e a l , or not, i t is a s s u m e d that t h e y c a n b e m a d e m o r e or less d r a m a t i c b y v a r y i n g assay c o n d i t i o n s .

The

c o n d i t i o n s h a v e b e e n d e s c r i b e d i n d e t a i l w h e n effects w e r e f o u n d .

Materials and

assay

zyxwvutsrqponm

Methods

A l t h o u g h this p a p e r is p r i m a r i l y a r e v i e w , some p e r t i n e n t n e w d a t a f r o m the a u t h o r s l a b o r a t o r y w i l l b e discussed. T h e s e d a t a w e r e o b t a i n e d b y m e t h o d s s i m i l a r to those p r e v i o u s l y d e s c r i b e d (109, 110,

112).

I n the e a r l y studies w i t h or r e l a t e d to seed h u l l anticaries a c t i v i t y (108,110,

111; T a b l e I ) a n d w i t h c e d a r w o o d , c o t t o n rats w e r e p l a c e d o n

the c a r i o g e n i c d i e t as 1 8 - d a y - o l d w e a n l i n g s f o r 14 weeks, after w h i c h caries scores f o r a l l three molars w e r e m e a s u r e d a n d r e p o r t e d . Table I.

Group

1 2 3 4 5 6

zyxwvutsrqponmlkji

Comparison of Caries and Decalcification Inhibiting Abilities of Diets Containing Seed Coverings

Material Studied

None Rice hulls Cottonseed hulls Peanut hulls Pecan hulls R i c e b r a n (solventextracted)

Caries Assay* No. Carious Lesions, Mean zb S.E.M.

In vitro

Assay

Enamel Dissolved, Mg

Acid Produced, Ml, 0 . 0 5 N

1.2 2.2 3.1 3.7 2.3

1.7 1.1 1.0 0.6 0.9

26.4 20.7 28.1 23.8 31.3

19.0 zb 1.7

0.5

28.0

25.8 17.3 20.5 18.2 16.7

zb =b zb ± ±

° Control score significantly reduced by all materials fed; P N a > K

> Ca >

M g ; ( c ) o r g a n i c phosphates s u c h as N a g l y c e r o p h o s p h a t e ,

N a p h y t a t e , o r N a sucrose p h o s p h a t e are e q u a l l y as cariostatic as N a o r t h o p h o s p h a t e , a n d ( d ) s i m i l a r r e l a t i o n s h i p s w e r e f o u n d w h e n the v a r i ous phosphates w e r e c o m p a r e d i n rats, hamsters, o r c o t t o n rats. M c D o n a l d et al. (21) a d d e d 1 % N a H P 0 , 1 % N a H P 0 , o r 0 . 2 5 % 2

NaH P0 2

4

+ 0.25% N a H P 0 2

4

4

2

4

to t h e c a r i o g e n i c diets o f rats to c o m p a r e

the cariostatic actions of a c i d , a l k a l i n e , a n d n e u t r a l f o r m s o f s o d i u m o r t h o p h o s p h a t e . T h e y r e p o r t e d caries r e d u c t i o n s of 61.4, 55.1, a n d 4 2 . 2 % , r e s p e c t i v e l y , after t h e diets h a d b e e n f e d f o r 150 days. T h u s , t h e a c i d p h o s p h a t e w a s t h e most active i n c o n t r o l l i n g caries a n d t h e n e u t r a l p h o s p h a t e m i x t u r e w a s the least effective. of others (14,23)

T h i s c o n f i r m e d the e v i d e n c e

that t h e a c i d i t y of phosphates does n o t interfere w i t h

t h e i r cariostatic a c t i o n . Present e v i d e n c e indicates that the anticaries effects o f phosphates are l o c a l , a c t i n g u p o n t he surface layers o f t h e teeth (22).

A dramatic

cariostatic effect w a s n o t e d w h e n t h e p h o s p h a t e w a s f e d i m m e d i a t e l y after t o o t h e r u p t i o n . T h e m e c h a n i s m of t h e a c t i o n of p h o s p h o r u s is q u i t e different f r o m that of

fluorine.

N a v i a a n d H a r r i s (22)

n o t e d that

p h o s p h a t e delays t h e i n i t i a t i o n of caries, w h i l e fluorine retards the d e v e l o p m e n t o f caries after i t has been i n i t i a t e d . T h e cariostatic actions o f fluorine

a n d phosphates are s y n e r g i s t i c w h e n t h e y are f e d c o n c u r r e n t l y .

T h o u g h the e v i d e n c e is b y n o means c o n c l u s i v e , i t appears

that

p h o s p h a t e s u p p l e m e n t s m a y b e effective i n c o n t r o l l i n g d e n t a l caries i n h u m a n beings. II).

S i x c l i n i c a l studies h a v e b e e n c o n d u c t e d to date

Stralfors ( 2 9 ) , S t o o k e y et al.

(30),

a n d H a r r i s et al.

(8)

(Table added

phosphates to foods, f e d t h e m to c h i l d r e n d u r i n g p e r i o d s of 1 to 3 years,

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

120

DIETARY

C H E M I C A L S

Table II.

zyxwvutsrqponmlkjihgfed VS. D E N T A L CARIES

Effects of Different

Level Fed

zyxwvutsrq

Age at

No. of % % Beginning Test zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Test SubCom-

Substance

CaHP0

pound

Range

Average

Periot

Sugar & flour

163 114

6-15 6-15

-

2 2

Vehicle

0.0 2.0

0.456

CaHP0 • 2H 0

0.0 2.0

0.36

Sugar, bread, & flour

1001 1101

8.5-9.5 8.5-9.5

9 9

2 2

CaHP0 • 2H 0

0.0 2.0

0.36

Bread, cakes, & buns

350 390

7-14 7-14

10.2 10.2

3 3

CaHP0 • 2H,0

0.0 1.125 gm/ day

0.2 gm/ day

Chewing gum

129 138

6-18 6-18

12.4 12.4

2.5 2.5

NaH P0 °

0.0 1.0

0.24

Breakfast cereal

116 84

5-16 5-16

10.1 10.3

2 2

0.0 1.0

0.062

Flour, biscuits, syrup, & jam

632 408

5-17 5-17

-

1 1

4

4

2

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jects

P

4

2

4

2

4

Ca sucrose phosphate

N a H P 0 was replaced by mixture of NaH PO (0.74) and Na*HPO (0.26) at end of first year. a

2

4

2

4

4

a n d n o t e d " s i g n i f i c a n t " r e d u c t i o n s i n t h e d e v e l o p m e n t o f n e w caries, i n c o m p a r i s o n w i t h c o n t r o l g r o u p s o f c h i l d r e n f e d t h e same f o o d s w i t h o u t phosphate supplementation.

F i n n a n d Jamison

(6)

noted a reduction

i n caries d e v e l o p m e n t w h e n c h i l d r e n c h e w e d p h o s p h a t e - e n r i c h e d c h e w i n g g u m d a i l y d u r i n g 2 years, i n c o m p a r i s o n w i t h a c o n t r o l g r o u p that was given a n identical c h e w i n g g u m not fortified w i t h phosphate. O n the other h a n d , A v e r i l l a n d B i b b y ( 2 ) a n d S h i p a n d M i c k e l s e n ( 2 7 ) f a i l e d to observe significant caries effects i n s o m e w h a t s i m i l a r studies i n children. T h e a n i m a l a n d c l i n i c a l studies a r e n o t d i r e c t l y c o m p a r a b l e . I n most studies w i t h rodents, t h e p h o s p h a t e w a s i n c o r p o r a t e d i n t o t h e entire d i e t , a n d w a s c o n s u m e d c o n c u r r e n t l y w h e n e v e r a n y f o o d w a s eaten.

I n the

c l i n i c a l studies, t h e p h o s p h a t e w a s a d d e d t o o n l y a p o r t i o n o f t h e f o o d ( s u g a r a n d flour; sugar, b r e a d , a n d flour; b r e a d , cakes, a n d b u n s ; breakfast c e r e a l ; flour, b i s c u i t s , s y r u p , a n d j a m ; o r i n c h e w i n g g u m ) a n d n o t i n a l l foods. T h u s , t h e c h i l d r e n i n t h e c l i n i c a l studies r e c e i v e d less p h o s p h a t e , p o s s i b l y one-tenth as m u c h , p e r g r a m o f f o o d .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

8.

HARRIS

121 zyxwvutsrq zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Minerals: Calcium and Phosphorus

Phosphates on Dental Caries in Children DMFT

DMFS

DFS

IncreIncreIncre% % % ment ment ReducReduc- ment Reducper per tion over tion over per tion over Ref. Comments Control Child zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Control Child Control Child

5.6 5.0

9.6 9.3

11

(2)

3

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0.27(m) 0.26(f) 0.16(m) 0.14(f)

41 (m) 46(f)

50% & 40% reductions after 1 & 2 yrs., resp.

(29)

-

4.64 4.43

4.5

8.12 7.41

(27) 9 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG

3.12 2.54

19

5.9 4.7

20

4.49 2.86

36.3* 16.8

11.45 6.75

6

6.56 5.47

b e

-

5.60 4.50

41.0 22.2

b

-

(6)

20

-

(SO)

b

Significant reduction in 5 to 12 yrs. age group/

16.6

(U)

Data from two observers. Results were essentially the same at end of two years (S). D i c a l c i u m p h o s p h a t e w a s u s e d i n f o u r o f t h e c l i n i c a l studies, s o d i u m

o r t h o p h o s p h a t e w a s u s e d i n t h e fifth, a n d c a l c i u m sucrose p h o s p h a t e w a s u s e d i n t h e s i x t h . H a r r i s et al. (8, 9,14)

a n d C a g n o n e et al. (4) d e m o n -

strated i n rats that s o d i u m t r i m e t a p h o s p h a t e is a p p r o x i m a t e l y five times as effective as a cariostatic agent as s o d i u m o r t h o p h o s p h a t e , a n d H a r r i s a n d N i z e l ( 12) h a v e s h o w n that p h o s p h o r u s i n t h e f o r m o f s o d i u m o r t h o p h o s p h a t e is p o s s i b l y three times m o r e effective t h a n p h o s p h o r u s i n c a l c i u m orthophosphate.

P h o s p h a t e i n c a l c i u m sucrose p h o s p h a t e is less

effective t h a n p h o s p h a t e i n s o d i u m o r t h o p h o s p h a t e . S o d i u m t r i m e t a p h o s p h a t e is t h e most effective o f a l l phosphates y e t tested i n a n i m a l s , is less t o x i c t h a n o r t h o p h o s p h a t e , a n d appears t o b e t h e c o m p o u n d o f c h o i c e f o r c l i n i c a l trials. C a l c i u m a n d p h o s p h o r u s c a n i n f l u e n c e t h e d e v e l o p m e n t o f caries w h e n a d d e d to t h e d i e t , t o c h e w i n g g u m , o r t o other carriers; p h o s p h a t e is m o r e effective t h a n c a l c i u m as a cariostatic agent, a n d b o t h c a l c i u m a n d p h o s p h a t e are effective e v e n w h e n a d d e d as s u p p l e m e n t s to diets already nutritionally adequate.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

122

DIETARY CHEMICALS VS. D E N T A L CARIES

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Literature

Cited

(1) Agnew, M . C., Agnew, R. S., Tisdall, F. F., J. Am. Dental Assoc. 1933, 20, 193. (2) Averill, H . M., Bibby, B. G., J. Dental Res. 1964, 43, 1150. (3) Beveridge, J., Gregory, G., Schamschule, R. G., Savage, D. C. L . , Med. J. Australia 1968, 2, 256. (4) Cagnone, L . D., Harris, R. S., Navia, J. M . , Proc. Intern. Assoc. Dental Res. 1968, Abst. 364, p. 128. (5) Dahlberg, B., Acta Genet. Statist. Med. (Basel) 1951, II, 57. (6) Finn, S. B., Jamison, H . C., J. Am. Dental Assoc. 1967, 74, 987. (7) Haldi, J., Wynn, W., Bentley, K. D., Law, M. L., J. Nutr. 1959, 67, 645. (8) Harris, R., Schamschula, R. G., Gregory, G., Roots, M . , Beveridge, J., Australian Dental J. 1967, 12, 105. (9) Harris, R. S., Das, S. K., Nizel, A. E., J. Dental Res. 1965, 44, 549. (10) Harris, R. S., Nizel, A. E., J. Dental Res. 1959, 38, 1142. (11) Ibid., 1964, 43, 1090. (12) Ibid., 1965, 44, 416. (13) Harris, R. S., Nizel, A. E., Gardner, D . S., Proc. Intern. Nutr. Congr., 4th, 1957, p. 195. (14) Harris, R. S., Nizel, A. E., Walsh, N. B., J. Dental Res. 1967, 46, 290. (15) Klein, H., McCollum, E . V., Science 1931, 74, 662. (16) Klein, H., McCollum, E . V., J. Dental Res. 1932, 13, 69. (17) Klein, H., Shelling, D . H., J. Dental Res. 1931, 11, 458. (18) Lennox, J., S. African Dental J. 1929, 3, 125. (19) Ibid., 1930, 4, 592. (20) Ibid., 1931, 5, 156. (21) McDonald, J. L . , Stookey, G. K., Muhler, J. C., Arch. Oral Biol. 1968, 13, 903. (22) Navia, J. M . , Lopez, H . , Harris, R. S., Arch. Oral Biol. 1968, 13, 779. (23) Nizel, A. E., Harris, R. S., J. Dental Res. 1964, 43, 1123. (24) Roos, A., "Kulturzerfall und Zahnverderbnis," Hans Huber, Bern, 1963. (25) Rosebury, T., Karshan, M., Arch. Pathol. 1935, 20, 697. (26) Shelling, D . H., Asher, D . E., J. Dental Res. 1933, 13, 363. (27) Ship, I. I., Mickelsen, O. J., J. Dental Res. 1964, 43, 1144. (28) Sobel, A. E., Hanok, A., J. Biol. Chem. 1948, 176, 1103. (29) Stralfors, A., J. Dental Res. 1964, 43, 1137. (30) Stookey, G. K., Carroll, R. A., Muhler, J. C., J. Am. Dental Assoc. 1967, 74, 752. (31) Widdowson, E . M . , Voeding, Neth. J. Nutr. 1962, 23, 62. (32) Wynn, W., J. Nutr. 1959, 67, 645. (33) Wynn, W., Haldi, J., Bentley, K. D., Law, M . L., J. Dental Res. 1960, 39, 1248. (34) Wynn, W., Haldi, J., Bentley, K. D., Law, M . L., J. Nutr. 1956, 58, 325. RECEIVED October 27,

1969.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9

Effect of Minerals on Dental Caries

J U A N M . NAVIA

1

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Massachusetts Institute of Technology, Cambridge, Mass.

Minerals in foods and drinking water have an important role in dental caries. Trace elements can be incorporated preeruptively and posteruptively into tooth enamel and change its physicochemical properties, affect the remineralization processes on the enamel surface, and influence the implantation and metabolism of cariogenic microorganism. Some elements promote caries, such as Se, Mg, and Cd, while others, such as Mo, V, and Sr, are mildly cariostatic. The effect of many other elements on caries is not known clearly owing to experimental limitations of the animal models used to study them. The species of animals used, the type of oral flora, the toxicity effects, and the interrelations between elements have to be evaluated and defined before a clear understanding of the role of trace elements in human caries is achieved.

concept that nutritional deficiencies are related to infection has been documented amply in the literature (166). Attempts to show through epidemiological studies that optimum nutrition inhibits dental caries, an infectious oral disease, have been unsuccessful (157). Caries prevalence is markedly lower in more isolated or primitive areas where the nutritional status is definitely poorer than in sections of the country with access to technical developments characteristic of modern civilization (156). This observation was voiced 30 years ago when Brekhus and Armstrong (21) stated that dental caries is a disease of civilization and that freedom from caries, found in societies less technically advanced, results from other factors besides nutrition. Dental decay is increasing among

The

Present address: Institute of Dental Research, University of Alabama in Birmingham, Birmingham, Ala. 35233. 1

123 In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

124

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

t e c h n i c a l l y d e v e l o p i n g nations a n d is r a p i d l y a p p r o a c h i n g the levels f o u n d i n affluent societies.

severity

A r e p o r t b y B a u m ezyxwvutsrqponmlkjihgfedcbaZYXWV (12) describes t h e

d e n t a l a n d n u t r i t i o n a l status of the s c h o o l p o p u l a t i o n of F r e n c h P o l y n e s i a a n d illustrates the p o i n t .

The

w o r s t d e n t a l c o n d i t i o n s of the

t e r r i t o r y w e r e f o u n d i n the d e v e l o p i n g d i s t r i c t of Papeete.

entire

A m o n g the

i n d i g e n o u s p r e - s c h o o l c h i l d r e n , a n o d o n t o c l a s t i c t y p e of r a m p a n t

caries

p r e v a i l e d , p a r t i c u l a r l y a m o n g those of C h i n e s e extraction. A l m o s t i m m e d i a t e l y after e r u p t i o n of " y e l l o w " p e r m a n e n t teeth, a smooth-surface t y p e of caries " m e l t e d d o w n " these h y p o p l a s t i c teeth so that at age 13 to 15 Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

years the T a h i t i a n s are p r a c t i c a l l y edentulous. T h e teeth of youngsters r a i s e d o n a deficient d i e t are n o t a b l e to w i t h s t a n d the i m p a c t of the c a r i e s - p r o m o t i n g d i e t c o n s u m e d i n u r b a n locations w h i l e the i n h a b i t a n t s of distant i s l a n d s , w h o s t i l l a d h e r e

to

their traditional food habits, maintain good dental health. T h e change i n dietary habits

associated

with

technical

and

economic

development

p r o b a b l y is r e s p o n s i b l e f o r this d e t e r i o r a t i o n i n d e n t a l h e a l t h w h i c h m a y b r i n g r a m p a n t disease to some p o p u l a t i o n groups w i t h i n a generation. O n e factor that has i n t e r f e r e d w i t h efforts to u n d e r s t a n d the nature a n d extent of the i n t e r a c t i o n b e t w e e n n u t r i t i o n a n d d e n t a l caries is the diverse effect of nutrients ( a n d n o n n u t r i e n t s ) i n the d i e t d u r i n g the pree m p t i v e a n d p o s t - e r u p t i v e p e r i o d s of t o o t h d e v e l o p m e n t .

Pre-emptively,

nutrients i n the d i e t c a n influence the m a t u r a t i o n process, the c h e m i c a l c o m p o s i t i o n of teeth, t o o t h size a n d m o r p h o l o g y a n d , to a lesser extent, the t i m e of e m p t i o n . N u t r i e n t s i n the diet also c a n select o u t the c a r i o g e n i c flora b y the process of e n r i c h m e n t a n d thus f a c i l i t a t e the i m p l a n t a t i o n a n d c o l o n i z a t i o n of these m i c r o o r g a n i s m s o n the t o o t h surface once it has e m p t e d i n t o the o r a l e n v i r o n m e n t .

Post-emptively, diet can influ-

ence p l a q u e f o r m a t i o n a n d the m i c r o b i a l m e t a b o l i c a c t i v i t y i n the m i c r o e n v i r o n m e n t of teeth, the c o m p o s i t i o n of s a l i v a b a t h i n g the teeth, a n d the c o m p o s i t i o n of the e n a m e l surface.

T h e pre-emptive a n d post-erup-

t i v e effects of d i e t o n the d e v e l o p m e n t a n d m a i n t e n a n c e

of teeth h a v e

not a l w a y s b e e n c l e a r l y separted i n e x p e r i m e n t a l designs a n d h a v e c o n f u s e d the i n t e r p r e t a t i o n of some results. W h i l e most nutrients m a y h a v e t h e i r major effect o n d e n t a l structures p r e - e m p t i v e l y d u r i n g the process of g r o w t h a n d d e v e l o p m e n t , m i n e r a l s h a v e a p r o f o u n d influence p r e - e m p t i v e l y a n d p o s t - e m p t i v e l y a n d , therefore, p l a y a m a j o r r o l e i n the caries s u s c e p t i b i l i t y or resistance of the t o o t h . T h e i n o r g a n i c p o r t i o n of p r o t e c t i v e foods w i l l c o n t r i b u t e p r a c t i c a l l y a l l of the caries-protective a c t i o n of the f o o d

(14).

F r o m the s t a n d p o i n t of n u t r i t i o n , m i n e r a l elements are either essent i a l f o r the m a i n t e n a n c e

of l i f e processes o r nonessential.

B e c a u s e of

their u b i q u i t o u s n e s s , t h e y m a y enter the tissues i n a n a d v e n t i t i o u s m a n ner w h e n present i n the f o o d a n d w a t e r c o n s u m e d or i n the a i r i n h a l e d .

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

125 N A V I AzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals

T h e m i n e r a l s present i n a n i m a l tissues c a n b e a r b i t r a r i l y d i v i d e d i n t o m a j o r elements o r m a c r o m i n e r a l s , s u c h as C a , P , M g , N a , K , S, a n d C I , a n d trace elements o r m i c r o m i n e r a l s , s u c h as C u , C o , F e , I, M n , M o , Se, a n d Z n , w h i c h are k n o w n t o d a y as t h e e i g h t essential elements.

Another

g r o u p of trace elements w h i c h i n c l u d e s A l , A s , B , B a , B e , F , H g , N i , R b , S i , S r , a n d V m a y b e present, b u t as y e t n o specific f u n c t i o n has b e e n a t t a c h e d to t h e m .

S o m e elements s u c h as V a n d Sr p o s s i b l y m a y b e

s h o w n essential i n f u t u r e investigations. T h e major m i n e r a l elements i n t h e a n i m a l b o d y are d e p o s i t e d i n Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

b o n e a n d teeth, w h e r e t h e y either increase t h e r i g i d i t y of bones o r serve as storage f o r use b y tissue cells w h e n necessary i n o r d e r to m a i n t a i n t h e i n t e g r i t y of m e t a b o l i c f u n c t i o n s . T r a c e elements m a y enter e n z y m e reactions as activators w h i c h b r i n g t h e e n z y m e into a c a t a l y t i c a l l y active state. E n z y m e a c t i v i t y is affected b y t h e presence o r absence of m i n e r a l salts, t h e n a t u r e of t h e ions present, a n d t h e i r concentrations.

Certain

elements s u c h as Z n , C u , a n d M o are essential s t r u c t u r a l c o m p o n e n t s of e n z y m e s s u c h as c a r b o n i c a n h y d r a s e , p o l y p h e n o l oxidase, a n d x a n t h i n e oxidase, r e s p e c t i v e l y , w h i l e others l i k e A g , H g , a n d P b m a y b e h i g h l y inhibitory to enzymes. T h e r e q u i r e m e n t s of a n i m a l organisms f o r trace elements is u n k n o w n to a large extent. T h e y are present i n tissues at e x t r e m e l y l o w c o n c e n t r a tions, a n d because i n t h e i r m e t a b o l i c a c t i v i t y t h e y are r e c y c l e d a n d p o o r l y excreted, t h e i r r e - u t i l i z a t i o n b y t h e tissues is n e a r l y c o m p l e t e .

Examples

of these cycles are t h e m e t a b o l i c r e - u t i l i z a t i o n of i r o n a n d i o d i n e . O n l y i n p e r i o d s of n u t r i t i o n a l stress o r i n c r e a s e d m e t a b o l i c a c t i v i t y s u c h as g r o w t h a n d d e v e l o p m e n t , p r e g n a n c y , o r l a c t a t i o n is t h e r e q u i r e m e n t of these elements increased. E v e n i n these c i r c u m s t a n c e s , t h e b i o l o g i c a l reserves i n organs s u c h as t h e l i v e r o r bones u s u a l l y are sufficient to offset a n u t r i t i o n a l d e f i c i e n c y . T h e w h o l e subject of trace element r e q u i r e m e n t s is i n great n e e d of a serious, d e d i c a t e d e x p e r i m e n t a l s t u d y . T h e t h e o r y that t h e m i n e r a l p o r t i o n s of foods c a n affect d e n t a l caries has b e e n s u b s t a n t i a t e d b y " n a t u r a l " g e o g r a p h i c experiments w h e r e a h i g h o r l o w i n c i d e n c e of caries i n h u m a n s appears to b e associated w i t h a d e f i c i e n c y o r excess of a c e r t a i n element i n t h e s o i l a n d p l a n t s g r o w n i n a l o c a l i t y a n d a n i m a l caries experiments.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ

Geographic Variations in Caries and Trace Elements. A d l e r a n d c o w o r k e r s {2,3)

h a v e r e p o r t e d o n t h e influence of m o l y b d e n u m o n d e n t a l

caries i n H u n g a r y . T h e y s h o w e d that i n areas w h e r e t h e M o l e v e l i n the w a t e r w a s 0.1 p p m there w a s a l o w i n c i d e n c e of caries. I n 1955, H e w a t a n d E a s t c o t t ( 8 5 ) suggested that a p o s s i b l e c o r r e l a t i o n exists b e t w e e n caries i n c i d e n c e a n d soil c o m p o s i t i o n i n N e w Z e a l a n d . I n o r d e r to s t u d y this subject f u r t h e r , L u d w i g et ah (107)

compared the

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

126

D I E T A R Y

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZY VS. D E N T A L CARIES

caries i n c i d e n c e of t w o p o p u l a t i o n s of c h i l d r e n i n t w o adjacent

cities

( N a p i e r a n d H a s t i n g s ) . T h e y f o u n d that the N a p i e r c h i l d r e n h a d c o n s i d e r a b l y less caries t h a n the H a s t i n g s c h i l d r e n of c o m p a r a b l e age years).

(5-8

T h e results of later studieszyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONML (108) i n d i c a t e d that m o l y b d e n u m

m i g h t b e i n v o l v e d , a n d the l o w e r caries experience of N a p i e r c h i l d r e n w a s the result of a h i g h e r M o a v a i l a b i l i t y f r o m the s o i l w h i c h c a u s e d increases i n the m i n e r a l c o m p o s i t i o n of vegetables c o n s u m e d i n the area. A n d e r s o n (5,6)

Recently,

r e p o r t e d first a s t u d y w i t h 270 c h i l d r e n a n d t h e n another

s t u d y w i t h l a r g e r n u m b e r s of c h i l d r e n f r o m the Somerset area i n E n g l a n d . Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

T h i s r e g i o n is one i n w h i c h cattle suffer f r o m m o l y b d e n u m p o i s o n i n g . W h e n the D M F f r o m the c h i l d r e n i n the c o n t r o l areas w a s c o m p a r e d w i t h the D M F f r o m c h i l d r e n i n t h e h i g h M o areas, i t w a s f o u n d t h a t t h e latter h a d better t h a n a 2 0 % r e d u c t i o n i n D M F . O t h e r e p i d e m i o l o g i c a l studies h a v e suggested that h i g h levels of c e r t a i n elements s u c h as s e l e n i u m i n the s o i l m a y b e associated w i t h h i g h (68).

caries i n c i d e n c e

I n this c o u n t r y , N i z e l a n d B i b b y (141) b e t w e e n soils a n d caries p r e v a l e n c e .

d e m o n s t r a t e d correlations

T h e highest p r e v a l e n c e of caries

i n the U n i t e d States is f o u n d i n the N e w E n g l a n d states associated w i t h p o d z o l s . T h e s e soils are g e n e r a l l y s t r o n g l y a c i d a n d of n a t u r a l f e r t i l i t y . T h e l o w e s t i n c i d e n c e of caries is f o u n d i n the s o u t h w e s t e r n states w h e r e the s e m i - a c i d soils are p o t e n t i a l l y h i g h i n m i n e r a l nutrients f o r t h e y h a v e n o t b e e n exposed to the l e a c h i n g a n d erosion a c t i o n f o r l o n g p e r i o d s of time.

F l u o r i d e i n these soils d e f i n i t e l y c o n t r i b u t e s to this l o w caries

p r e v a l e n c e , b u t i n the D a k o t a s w h e r e w a t e r h i g h i n fluoride is c o m m o n , there is a f a i r l y h i g h p r e v a l e n c e of caries. T h i s i n d i c a t e s that factors other t h a n fluoride are i n f l u e n c i n g the caries p i c t u r e . Dietary Minerals, F o o d Ashes, and

zyxwvutsrqponmlkjihgfedcbaZYX

Experimental Dental Caries.

M i n e r a l s i n diets h a v e a p r o f o u n d effect o n the d e n t a l caries experience of e x p e r i m e n t a l a n i m a l s . Sognnaes a n d S h a w (172,

173)

o b s e r v e d m o r e caries lesions w h e n

rats w e r e g i v e n a p u r i f i e d r a t i o n that w a s c o m p l e t e i n k n o w n essentials t h a n w h e n this r a t i o n w a s s u p p l e m e n t e d w i t h 2 % of its o w n ash.

They

suggested

trace

that

p r o t e c t i o n against

elements i n the ash.

I n the

fight

caries

resulted f r o m certain

of w h a t is k n o w n t o d a y a b o u t

the

cariostatic effect of p h o s p h a t e , this also c o u l d b e e x p l a i n e d as a r i s i n g f r o m the P content of the ash. K e y e s ( 96)

o b s e r v e d a n increase i n caries

a c t i v i t y w h e n hamsters w e r e f e d a m i n e r a l - d e f i c i e n t diet. A s i m i l a r effect w a s r e p o r t e d b y G u s t a f s o n (64)

w h o n o t e d a m a r k e d increase i n caries

d e v e l o p m e n t w h e n the a m o u n t of salt m i x t u r e i n the d i e t w a s decreased. T h e ashes of different foods decrease the i n c i d e n c e of caries: c o r n ( 7 5 ) , b o n e (8, 84),

a n d c o c o a (97, 1 5 5 ) .

C o c o a ash has b e e n r e p o r t e d

i n a c t i v e as a cariostatic agent b y W y n n et al. (214),

b u t Stralfors

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

(183,

9.

N A V I A

127 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals

184, 185)

f o u n d activity i n the w h o l e defatted

p o u n d s (186)

cocoa.

Phenolic

com-

present i n c o c o a m i g h t b e i n v o l v e d i n this effect. O f these

foods, c o r n is t h e most i m p o r t a n t since i t is c o m m o n l y eaten b y m a n k i n d . I n 1950 (142),

N i z e l a n d H a r r i s r e p o r t e d t h a t diets c o n t a i n i n g c o r n a n d

m i l k g r o w n i n T e x a s c a u s e d o n l y 4 0 % as m u c h d e n t a l d e c a y i n hamsters as c o r n a n d m i l k g r o w n i n N e w E n g l a n d . T h i s effect w a s n o t c a u s e d b y fluorine fluoride (144)

since t h e F content w a s m a d e e q u a l b y t h e a d d i t i o n of s o d i u m to t h e N e w E n g l a n d diet.

L a t e r , these investigators

reported

t h a t these differences i n d i c a t e t h e presence of a c a r i o g e n i c

factor

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i n t h e N e w E n g l a n d c o r n a n d m i l k rather t h a n t h e presence o f a c a r i o static f a c t o r i n t h e T e x a s c o r n a n d m i l k .

Reasoning that t h e cariogenic (143)

f a c t o r i n N e w E n g l a n d foods w a s a trace element, N i z e l a n d H a r r i s

t r i e d t o m a g n i f y t h e effect b y s u p p l e m e n t i n g t h e N e w E n g l a n d d i e t w i t h its a s h ( 5 5 0 ° C ) . C o n t r a r y t o expectations, t h e caries score of t h e hamsters f e d t h e a s h - s u p p l e m e n t e d d i e t w a s o n l y 3 5 % as h i g h as t h e c o n t r o l g r o u p . T h i s o b s e r v a t i o n l e d to a n i n v e s t i g a t i o n to i d e n t i f y t h e cariostatic factor i n t h e f o o d a s h . T h e c o m p o s i t i o n of this a s h w a s d e t e r m i n e d b y c h e m i c a l a n d s p e c t r o g r a p h i c m e t h o d s , a n d a salt w a s p r e p a r e d c a t i n g t h e 11 m i n e r a l elements that c o u l d b e q u a n t i t a t e d . hamsters,

dupli-

W h e n f e d to

this salt m i x t u r e w a s s i g n i f i c a n t l y m o r e cariostatic

than the

ash w h i c h i t i m i t a t e d ( 7 5 ) . T h i s result c o u l d i n d i c a t e t h a t o n e ( o r m o r e ) of t h e t r a c e elements i n t h e f o o d a s h w h i c h c o u l d n o t b e q u a n t i t a t e d a n d w a s , therefore, o m i t t e d f r o m t h e salt m i x t u r e , is a strong c a r i o g e n i c agent. I n o r d e r to investigate this p h e n o m e n o n f u r t h e r , H a r r i s a n d N i z e l (74)

f e d hamsters five diets c o n t a i n i n g different c o m b i n a t i o n s of the 11

elements s u p p l e m e n t e d to a c a r i e s - p r o m o t i n g diet. W h e n t h e p h o s p h o r u s c o m p o n e n t ( K H 0 P O 4 ) w a s o m i t t e d , t h e caries score rose f r o m 0.7 to 18.4. S i n c e t h e score of the c o n t r o l g r o u p w a s 13.4, i t w a s e v i d e n t that some of t h e 10 m i n e r a l elements i n t h e P-free salt m i x t u r e m i g h t b e a c t u a l l y c a r i o g e n i c . C o n s t a n t et al. (42) c a r r i e d o u t studies c o m p a r i n g w h o l e cereals w i t h processed a n d p u r i f i e d cereals. T h e y f o u n d that w h o l e cereals w e r e less c a r i o g e n i c t h a n t h e p u r i f i e d processed p r o d u c t .

T h e y also

investigated

the c a r i o g e n i c i t y o f a l k a l i n e a s h foods a n d t h a t of a c i d a s h foods a n d f o u n d n o significant difference u n d e r the e x p e r i m e n t a l c o n d i t i o n s u s e d . L a t e r , t h e y s t u d i e d (43,

44)

t h e effect o n caries o f a c i d i c a n d b a s i c

minerals a n d f o u n d that acidic inorganic, basic, or acidic organic

salt

m i x t u r e s gave n o p r o t e c t i o n against t o o t h d e c a y , w h i l e a h i g h l e v e l of b a s i c i n o r g a n i c salts r e s u l t e d i n a m a r k e d decrease i n t o o t h d e c a y . M i l l e r (118)

r e p o r t e d that d o u b l i n g t h e H u b b e l l - M e n d e l - W a k e m a n

salt m i x t u r e f r o m 1.2 grams

to 2.4 g r a m s /1 0 0 grams

gave

a marked

r e d u c t i o n i n the n u m b e r of carious teeth, t h e n u m b e r of carious areas, a n d t h e caries score. T h i s effect w a s v e r i f i e d a g a i n i n a s e c o n d e x p e r i m e n t

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

128

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

b u t the effect w a s n u l l i f i e d w h e n 1 2 % of p o w d e r e d sucrose w a s u s e d i n p l a c e of a n e q u a l a m o u n t of r i c e

flour.

E v e n t h o u g h there is a definite r e l a t i o n b e t w e e n d i e t a r y t r a c e elements a n d d e n t a l caries, there is n o c e r t a i n k n o w l e d g e of the m e c h a n i s m t h r o u g h w h i c h these elements influence caries. Some of the p o s s i b l e w a y s i n w h i c h t h e y c o u l d act are t h e f o l l o w i n g : ( 1 ) I n c o r p o r a t i n g trace elements p r e - e m p t i v e l y i n t o the t o o t h m i n e r a l to c h a n g e its p h y s i c o - c h e m i c a l properties.

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( 2 ) I n f l u e n c i n g the c e l l u l a r e n z y m e systems i n v o l v e d i n the e r a l i z a t i o n of the teeth. ( 3 ) A l t e r i n g p r e - e m p t i v e l y the m a t r i x of the tooth.

nature

of

the

min-

calcifying organic

( 4 ) E n h a n c i n g or i n h i b i t i n g the d e p o s i t i o n of m i n e r a l elements s u c h as fluoride or p h o s p h o m s o n the e n a m e l surface a n d t h e r e b y i n f l u e n c i n g the p o s t - e r u p t i v e m a t u r a t i o n of h y p o r n i n e r a l i z e d e n a m e l areas. ( 5 ) C h a n g i n g t h e p h y s i c a l a n d c h e m i c a l characteristics of s a l i v a . (6)

I n t e r f e r i n g d i r e c t l y w i t h the r e p r o d u c t i o n , m e t a b o l i s m , a n d i m p l a n t a t i o n of the c a r i o g e n i c m i c r o o r g a n i s m s o n the t o o t h surface.

M e t a l Ions as E n z y m e A c t i v a t o r s i n M i c r o b i a l C e l l s . M e t a l s m a y enter e n z y m e reactions as cofactors or activators w h i c h b r i n g the e n z y m e i n t o a c a t a l y t i c a l l y a c t i v e state. T h e a c t i v i t y of enzymes is affected b y the presence or absence of m i n e r a l salts, the n a t u r e of the ions present, a n d t h e i r concentrations. C e r t a i n ions are necessary f o r t h e a c t i v i t y of the

i.e., A g , H g , P b — m a y b e h i g h l y toxic. It is e n z y m e , w h i l e others— zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE +

2 +

2 +

a characteristic of these systems that c e r t a i n ions are poisonous f o r some enzymes a n d activators f o r others.

Some m a y i n h i b i t a n e n z y m e at one

c o n c e n t r a t i o n a n d yet activate the same e n z y m e at another c o n c e n t r a t i o n . T h e effects of metals o n enzymes m a y b e p r o d u c e d b y m a n y m e t a b o l i c routes, a n d i n most cases h a v e not b e e n i d e n t i f i e d . T h e a c t i v a t i n g effect u s u a l l y is not specific. T h e e n z y m e f u m a r a s e m a y be a c t i v a t e d b y several m e t a l ions, yet other e n z y m e s s u c h as i n o r ganic pyrophosphatase specifically require M g

2 +

w h i c h cannot be replaced

b y others. A p p r o x i m a t e l y 16 different m e t a l cations activate one or m o r e enz y m e s ; these are: Al + Ca Cd + Co 3

2 +

2

2 +

Mg

2 +

Cr»+ Cs+ Cu Fe

2 +

2 +

K+ Mg + Mn + Mo+ 2

2

Na+ Ni Rb+ Zn + 2 +

2

is the n a t u r a l a c t i v a t o r of a great m a j o r i t y of the e n z y m e s w h i c h

act o n p h o s p h o r y l a t e d substrates, s u c h as the p h o s p h o k i n a s e s , the s y n -

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

N A V I A

129 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals

thetases, a n d the enzymes w h i c h h y d r o l y z e p h o s p h o r i c a c i d a n h y d r i d e s , b u t not the phosphorylases. I n most cases, M g b u t not b y other metals. and

2 +

can be replaced b y M n

S o d i u m can be replaced b y K

M n , Co , N i , and Z n 2 +

2 +

2 +

+

i n some cases,

m a n y times are i n t e r c h a n g e a b l e

2 +

2 +

among

t h e m . A n t a g o n i s m is f a i r l y c o m m o n , a n d N a m a y act as a c o m p e t i t i v e +

inhibitor for K with M g

2 +

2 +

i n h i b i t s the C a

2 +

Ca

2 +

competes

adenosinetriphosphatase,

a c t i v a t i o n of m y o s i n a d e n o s i n e t r i p h o s p h a -

E n z y m e s also m a y b e affected

c e r t a i n anions. Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

a c t i v a t i o n (i.e., p h o s p h o t r a n s a c e t y l a s e ) ,

to i n h i b i t c e r t a i n e n z y m e s , s u c h as

a n d also M g tase.

+

c o n s i d e r a b l y b y the presence of

S a l i v a r y a l p h a amylases, for e x a m p l e , are affected

greatly b y c h l o r i d e s that this i o n has b e e n

so

natural

(129).

activator of these e n z y m e s M a c D o n a l d (116)

r e g a r d e d as the

has discussed the m i c r o b i o l o g y of caries, stressing

that i t is a b a c t e r i a l l y - i n d u c e d disease c h a r a c t e r i z e d b y a d e c a l c i f y i n g a c t i o n o n the m i n e r a l c o m p o n e n t s a n d a p r o t e o l y t i c a c t i o n o n the o r g a n i c components.

G i v e n energy a n d n i t r o g e n sources, the o r a l m i c r o b i o t a , i n

c o m m o n w i t h a l l m i c r o o r g a n i s m s , w i l l not g r o w i n the c o m p l e t e absence of c e r t a i n m i n e r a l elements.

A s discussed a b o v e , this is b e c a u s e of the

role of metals as i o n activators of the e n z y m e systems essential f o r m e t a b o l i c a c t i v i t y . It w o u l d b e of interest to d e t e r m i n e the specific n u t r i t i o n a l needs f o r trace elements of the c a r i o g e n i c s t r e p t o c o c c i a n d c o m p a r e t h e m w i t h those of the n o n c a r i o g e n i c streptococci.

B o w e n (17)

a t t e m p t e d to

o b t a i n s u c h i n f o r m a t i o n a n d r e p o r t e d that of the three cations tested (manganese, c a l c i u m , a n d m a g n e s i u m ) o n l y manganese is an essential r e q u i r e ment f o r g r o w t h .

A l t h o u g h no q u a l i t a t i v e differences

were

observed

c o n c e r n i n g the r e q u i r e m e n t s f o r g r o w t h of c a r i o g e n i c a n d n o n c a r i o g e n i c organisms, some discrepancies i n t h e i r q u a n t i t a t i v e needs w e r e r e p o r t e d w h i c h w a r r a n t f u r t h e r research. T h e m i n e r a l s f o u n d i n the surface e n a m e l a n d those s u p p l i e d b y the diet, the s a l i v a , a n d d e s q u a m e n t e d

tissue cells m a y influence the o r a l

m i c r o b i o t a i n the f o l l o w i n g w a y s : s t i m u l a t i o n of g r o w t h (increase i n c e l l n u m b e r s ) , f a c i l i t a t i o n of attachment of cells to e n a m e l surface, i n f l u e n c i n g the f o r m a t i o n of m e t a b o l i c e n d p r o d u c t s i n c l u d i n g i n t r a - a n d extracellular

polysaccharides,

inhibition

of

growth

or

metabolic

activity

t h r o u g h p o i s o n i n g of e n z y m e systems w i t h i n the cells, a n d m o d i f i c a t i o n of o r a l e n v i r o n m e n t b y s t i m u l a t i o n of g r o w t h of c e r t a i n types of cells, thus i n h i b i t i n g others.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJ

Mineral Composition of Teeth in Humans and Experimental

Animals

zyxwvutsrqp

Inorganic Composition of Bones and Teeth. B o n e a n d t o o t h m i n e r a l

is m a d e u p m o s t l y of c a l c i u m a n d p h o s p h a t e i n the f o r m of apatite, yet m a n y other elements

are f o u n d w i t h i n its structure.

Bone and tooth

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

130

DIETARY

zyxwvutsrqponmlkjihgfedcbaZ VS. D E N T A L CARIES

C H E M I C A L S

m i n e r a l , therefore, is n o t a single homogeneous c h e m i c a l c o m p o u n d b u t a m i x t u r e w h i c h varies i n c o m p o s i t i o n a n d d i s t r i b u t i o n . O n e of t h e p r o b l e m s i n d e f i n i n g t h e c h e m i c a l b e h a v i o r of t h e i n o r g a n i c p o r t i o n of t h e teeth is t h e d i f f i c u l t y i n d i f f e r e n t i a t i n g b e t w e e n the constituents of t h e b a s i c structure, t h e ions h a v i n g o n l y a surface r e l a t i o n s h i p to t h e crystals, a n d those p o s s i b l y c o m b i n e d w i t h t h e apatite crystals i n a separate phase.

T h e r e f o r e , e v e n t h o u g h t h e structure a n d

c o m p o s i t i o n of t h e m i n e r a l corresponds closely to t h a t of h y d r o x y a p a t i t e , s u b s t a n t i a l amounts of c a r b o n a t e a n d citrate are f o u n d as w e l l as i o n Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

substitutions i n t h e c r y s t a l lattice. T h e m i n u t e crystals a n d interspaces b e t w e e n t h e m expose a large surface area to t h e e n v i r o n m e n t fluids a n d as a result d i s s o l u t i o n a n d r e c r y s t a l l i z a t i o n m a y take p l a c e , m a i n t a i n i n g a d y n a m i c b a l a n c e .

This

large surface area of b o n e a n d t o o t h m i n e r a l s influences its t o t a l c o m p o s i t i o n i n t w o w a y s , b y a d s o r b i n g o r s u b s t i t u t i n g ions as w e l l as i n c o r p o r a t i n g some of t h e m w i t h i n surface u n i t cells w i t h u n s h a r e d sides a n d b y i s o i o n i c o r h e t e r o i o n i c exchange w i t h the fluids b a t h i n g the crystals. I n g e n e r a l , t h e elements w h i c h l o c a l i z e i n b o n e a n d teeth are r e f e r r e d to as "bone-seekers"

b u t t h e t e r m s h o u l d a p p l y also to other o r g a n i c

substances s u c h as m u r e x i d e a n d t h e tetracyclines w h i c h c o m b i n e a v i d l y w i t h b o n e o r t o o t h at n e w c a l c i f i c a t i o n a n d also at carious sites.

zyxwvutsrqponmlkji

Composition of Outer and Inner Enamel of Teeth from Table I. H u m a n Subjects Living in Different Geographic Areas 0

\LMzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM ol. per Gram

Outer

Enamel

Body

Enamel

525-654 Carbonate 350-440 Sodium 310-380 230-360 3.8-44 Fluoride 17-176 60-74 Magnesium 30-60 2.9-14.2 Zinc 6.6-27.5 -1.1 3.5-5.0 Citrate Aluminum 1.1-4.5 1.4-4.8 Strontium 0.7-4.6 0.3-3.7 -1.2 Lactate -2.9 0.1-1.1 Lead 0.4-2.6 Copper tr-0.6 0.1-1.8 Silica 0.1-1.8 0.2-1.5 Silver 0.0-0.5 tr-0.9 0.2-0.4 Iron 0.4-0.6 Tin tr-0.4 0.0-0.3 0.1-0.2 M a n g a n e s e zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONM 0.1-0.4 ° Data from Ref. 24.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

131 9.zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA N A V I AzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerab Table II.

Major Inorganic Constituents of H u m a n Enamel" Thermal Activation

Constituent

-

2

1.16 db 0.40 0.36 db 0.04 0.65 zb 0.30

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Na Mg CI

-

K 0

Data from Ref. 175 and 176. Table III.

Minor Inorganic Constituents of H u m a n Enamel" Thermal Neutron Activation Analysis

Constituent

F 388 276 94 4.9 4.6 0.24 0.26 0.54 0.02 0.0049 0.0027 0.00024

Fe

Zn Sr Rb Br

W Cu Mn Au

Ag Cr Co v Pt 0

33.6-39.4 16.1-18.0 1.92-2.17 1.95-3.66 0.25-0.90 0.25-0.56 0.19-0.30 0.05-0.30

37.4 zb 1.0 18.3 =fc 2.2 2.04

Ca P C a /P

C0

Chemical Analysis

Neutron Analysis

Chemical Analysis

62-650 zb 109 8-218 + 106 152-227 ± 22 50-400 zb 1.6 ± 1.1 zb 0.12 zb 0.11 10-100 zb 0.08 0-18 zb 0.01 zb 0.0012 0-100 zb 0.0016 db 0.00009 zyxwvutsrqponmlkjihgfedcbaZYXW

> 10-

5

>10~

6

Parts per million, dry weight; data from Ref. 175 and 176. T h e chemical composition of enamel, dentin, cementum, a n d p u l p

has b e e n d i s c u s s e d b y Z i p k i n ( 2 1 7 ) , w h o also d i s c u s s e d the c h e m i s t r y o f the s o u n d a n d carious e n a m e l . Brudevold

(24, 30)

reported

o n t h e trace

m i n e r a l content

of

teeth c o l l e c t e d f r o m h u m a n beings l i v i n g i n different g e o g r a p h i c areas. T h e concentrations o f these elements ( / j t M /g r a m ) o f t h e surface e n a m e l a n d the b o d y o f the i n t a c t e n a m e l are p r e s e n t e d i n T a b l e I. T h e a m o u n t s i n t h e outer e n a m e l w e r e often, b u t not a l w a y s , h i g h e r t h a n a m o u n t s i n the i n n e r e n a m e l , a n d the r a n g e o f values is q u i t e w i d e . S o r e m a r k a n d c o w o r k e r s (175, 176), u s i n g n e u t r o n a c t i v a t i o n analysis, r e p o r t e d values f o r t o t a l h u m a n e n a m e l ( T a b l e s II, III).

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

132

DIETARY

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

S t e a d m a nzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA et al. (179) a n a l y z e d the ancient teeth of P u e b l o I n d i a n s (800 years o l d ) a n d I n d i a n K n o l l (5000 years o l d ) f o r the same elements a n d f o u n d that t h e y o c c u r r e d i n greater c o n c e n t r a t i o n i n t h e outer t h a n i n the i n n e r layers of e n a m e l . F l u o r i d e w a s f o u n d i n greatest c o n c e n t r a t i o n i n the external e n a m e l , f o l l o w e d b y Z n , S i , M n , P b , A g , C u , a n d S n . T h e y n o t e d a r e m a r k a b l e s i m i l a r i t y i n the d i s t r i b u t i o n of m a n y trace elements b e t w e e n a n c i e n t a n d c o n t e m p o r a r y A m e r i c a n teeth.

Contrary

to expectations, t h e y f o u n d b u t l i t t l e p e n e t r a t i o n of trace elements i n t o the b u l k of the t o o t h structure, e v e n i n teeth of 5000 years o l d . A s g a r ( 7 ) Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

s t u d i e d differences i n the d e n t i n a n d e n a m e l of ancient G r e e k a n d A m e r i c a n teeth, b u t his samples w e r e too f e w to p e r m i t conclusions. Hadjimarkos a n d Bonhorst (69)

s t u d i e d 27 s o u n d a n d 17 carious

teeth f r o m 2 0 - 4 0 y e a r o l d m o d e r n A t h e n i a n s , a n d 14 s o u n d teeth f r o m the skulls of five w o m e n a n d f o u r m e n w h o l i v e d i n 800 a n d 1100 B . C . ( T a b l e I V ) . H e a t t r i b u t e d the h i g h i m m u n i t y to caries of A t h e n s s c h o o l c h i l d r e n to the h i g h i n t a k e of fluoride a n d p o s s i b l y the l o w e r i n t a k e of

s e l e n i u m . zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Table I V .

Mineral Content of Greek Teeth Modern

Fluorine, p p m Selenium, p p m

Greek

Ancient

Enamel

Dentine

Enamel

178 0.03

0.13

374 0.13

Greek Dentine

0.45

S e v e r a l attempts h a v e b e e n m a d e to correlate v a r i a t i o n s i n t h e m i n e r a l content of d e n t a l tissues w i t h caries sensitivity. P i c a r d et al.

(148)

d i v i d e d 120 h u m a n teeth i n t o three g r o u p s : h e a l t h y , s u p e r f i c i a l caries, a n d d e e p caries.

T h e y f o u n d n o significant difference i n the ash, C a , a n d P

content, or i n the C a /P r a t i o of the e n a m e l of the three g r o u p s . T h e ash, C a , a n d P content of the d e n t i n f r o m d e e p carious lesions w e r e signific a n t l y l o w e r t h a n i n the h e a l t h y teeth. T h e same t r e n d w a s n o t e d i n the teeth w i t h s u p e r f i c i a l caries, b u t the t r e n d was n o t significant. (105)

Lobene

s t u d i e d the i n o r g a n i c constituents of the e n a m e l a n d d e n t i n of teeth

f r o m hamsters, a n d c o n c l u d e d that the C a , P , a n d M g content of the d e n t i n d i d n o t v a r y greatly, w h a t e v e r the source. Z i p k i n a n d P i e z (218)

t r i e d to correlate the c i t r i c a c i d content of

h u m a n teeth w i t h s u s c e p t i b i l i t y to caries i n a s t u d y o f 65 samples of s o u n d d e n t i n a n d 129 samples of carious d e n t i n . T h e y f o u n d 888 ±

103 m g %

a n d 872 ± 105 m g % c i t r i c a c i d i n the s o u n d a n d carious d e n t i n , respect i v e l y , a n d thus n o e v i d e n c e of a c o r r e l a t i o n b e t w e e n c i t r i c a c i d a n d d e n t a l caries. Studies of this t y p e are difficult to i n t e r p r e t , f o r the a n a l y sis is m a d e o n the carious m a t e r i a l left after the disease has p r o g r e s s e d a n d n o i n f o r m a t i o n is a v a i l a b l e as to the c o n c e n t r a t i o n of m i n e r a l s before t h e carious l e s i o n started.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

N A V I A

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals 133 zyxwvutsrq

Trace Element Distribution in Teeth. T h e d i s t r i b u t i o n of i n d i v i d u a l

elements i n h u m a n teeth has b e e n s t u d i e d b y B r u d e v o l d (24) associates.

T h e r a n g e of c o p p e r (47)

a n d his

i n f o u r successive g r i n d i n g s of the

e n a m e l of h u m a n teeth w a s 15 to 30 p p m , a n d its d i s t r i b u t i o n w a s r a n d o m a n d u n a f f e c t e d b y age.

T h e t i n content of p o o l e d samples (28)

of f o u r

successive layers of e n a m e l was 7.0 p p m i n the outer t w o layers a n d n i l i n the t h i r d a n d f o u r t h layers. L e a d (27)

w a s highest (550 p p m ) i n the outer

e n a m e l layers of e r u p t e d teeth a n d decreased to a rather constant l e v e l (90 p p m ) i n t h e i n n e r m o s t layers. Z i n c (31) Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

and

fluoride.

was distributed like lead

It w a s h i g h e r o n the surface ( 4 3 0 - 2 1 0 0 p p m ) , l o w e r i n the

subsurface layers, a n d w a s d e p o s i t e d i r r e g u l a r l y o n the surface. L i t t l e a n d B r u d e v o l d (104)

f o u n d differences i n the C 0

2

content of

t h e s u p e r f i c i a l a n d i n n e r layers of i n t a c t h u m a n e n a m e l i n e r u p t e d a n d u n e r u p t e d teeth.

I n a l l age g r o u p s , the c o n c e n t r a t i o n of c a r b o n d i o x i d e

i n c r e a s e d f r o m the surface t o w a r d the d e n t i n , b u t as the c a l c i f i c a t i o n proceeds d u r i n g d e v e l o p m e n t , t h e c a r b o n d i o x i d e content decreases. (i.e.,

B o n e - s e e k i n g r a d i o a c t i v e isotopes H o l g a t e et al. (87) of r a b b i t s .

Sr)

s t u d i e d the a c c u m u l a t i o n of S r

accumulate 90

i n teeth.

i n the d e n t a l tissues

A n increase i n c o n c e n t r a t i o n w a s o b s e r v e d d u r i n g 30 d a y s

f o l l o w i n g i n t r a v e n o u s i n j e c t i o n , a n d t h e n it f e l l a b r u p t l y . S i n c e t h e teeth of the r a b b i t g r o w c o n t i n u o u s l y , t h e S r

90

d e p o s i t e d i n the teeth m a y h a v e

b e e n lost w h e n the r a d i o a c t i v e z o n e w a s w o r n a w a y .

B u t l e r (33)

s e r v e d a n inverse c o r r e l a t i o n b e t w e e n the c o n c e n t r a t i o n of S r

90

ob-

a n d the

age o f h u m a n b e i n g s . T h e m i n e r a l c o m p o s i t i o n of teeth has b e e n s t u d i e d i n r e l a t i o n to d i s c o l o r a t i o n of the t o o t h substance.

Isaac a n d B r u d e v o l d (89)

studied

the p o s s i b l e s t a i n i n g properties of P b , S n , A g , H g , C u , a n d F e w h e n d e p o s i t e d i n the e n a m e l , a n d t h e n exposed t h e m to a s u l f u r - c o n t a i n i n g medium.

T h e s e m e t a l sulfides are b r o w n or b l a c k , a n d t h e y m a y b e

p r o d u c e d f r o m f o o d or s a l i v a u n d e r o r d i n a r y c o n d i t i o n s . T h e

surfaces

of the c r o w n s a n d roots of i n t a c t teeth w e r e treated w i t h solutions c o n t a i n i n g t h e cations, a n d a l l d e v e l o p e d d i s c o l o r a t i o n w h e n exposed to t h e s u l f u r - c o n t a i n i n g m e d i u m . O n the other h a n d , L a n d i n g et

al.

(101)

n o t e d that the teeth of a p a t i e n t w i t h hemosiderosis w e r e n o t p i g m e n t e d , e v e n t h o u g h t h e y c o n t a i n e d 50.8 / x g % of i r o n rather t h a n t h e 16.1 / x g % i n c o n t r o l patients. It is not k n o w n w h e t h e r the F e w a s d e p o s i t e d i n the teeth b e f o r e or after e r u p t i o n . P o s s i b l y , the l o c a t i o n of t h e F e i n t h e t o o t h determines whether it w i l l be reactive. D u r i n g the last 10 years, investigators h a v e b e e n m a k i n g use of a n a l y t i c a l p r o c e d u r e s b a s e d o n p h y s i c a l p r i n c i p l e s to q u a n t i t a t e elements i n teeth a n d bones.

U s i n g n e u t r o n a c t i v a t i o n analysis, S o r e m a r k a n d

c o w o r k e r s ( 1 0 9 , 1 7 4 , 175,176)

s t u d i e d the e n a m e l c o m p o s i t i o n of n o r m a l

h u m a n erupted and unerupted enamel.

N i x o n et

al.

(138,

139,

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

140)

134

DIETARY

s t u d i e d t h e c o p p e r , arsenic,

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

a n d a n t i m o n y levels i n h u m a n

enamel.

M a n g a n e s e also has b e e n e s t i m a t e d i n h u m a n e n a m e l b y these same

investigatorszyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (137) a n d b y B a t t i s t o n e et al(ll). T h e i n o r g a n i c c o m p o n e n t s of teeth also h a v e b e e n a n a l y z e d b y s u c h m e t h o d s as x-ray e m i s s i o n s p e c t r o g r a p h y s p e c t r o g r a p h y (188).

(38)

a n d spark source

mass

T h i s last m e t h o d continues t o p l a y a n extremely

i m p o r t a n t role i n e l e m e n t a l a n d trace analysis because of great sensitivity f o r metals a n d nonmetals. I n general, these m e t h o d s h a v e b e e n u s e f u l i n d e t e c t i n g a n d q u a n t i Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

t a t i n g trace quantities of elements i n teeth a n d b o n e , b u t t h e d e v e l o p m e n t of t h e electron p r o b e m a d e possible t h e d e t e r m i n a t i o n of t h e d i s t r i b u t i o n of elements i n m i c r o s t r u c t u r e s .

E q u i p m e n t to p r o d u c e beams of ions,

protons, electrons, a n d x-rays is n o w a v a i l a b l e to b e u s e d i n e x p l o r i n g the c r y s t a l l i n e n a t u r e of solids a n d b i o l o g i c a l tissues. T h e e l e c t r o n p r o b e has b e e n u s e d i n m e t a l l u r g y a n d m i n e r o l o g y , b u t its a p p l i c a b i l i t y to b i o l o g i c a l samples has b e e n l i m i t e d b y t h e fact that l i g h t elements w h i c h are of great interest to t h e b i o l o g i s t h a v e n o t b e e n d e t e c t e d easily a n d the p h y s i c a l properties of b i o l o g i c a l specimens are different f r o m those samples n o r m a l l y s t u d i e d i n m e t a l l u r g y . T o d a y , n e w i m p r o v e m e n t s i n e q u i p m e n t a n d m e t h o d o l o g y are m a k i n g p o s s i b l e t h e a p p l i c a t i o n of this v a l u a b l e a n a l y t i c a l t o o l to samples of b i o l o g i c a l o r i g i n (4, 197, 198). T h e m i n e r a l i z e d tissues of the b o d y , s u c h as bones a n d teeth, l e n d themselves to s t u d y b y t h e p r o b e . A n a r r o w b e a m of electrons is f o c u s e d o n a s m a l l area of the s a m p l e (less t h a n 1 m i c r o n i n d i a m e t e r ) , a n d t h e x-rays r e s u l t i n g f r o m t h e electron b o m b a r d m e n t are c o l l e c t e d at a p r e d e t e r m i n e d angle a n d a n a l y z e d i n o n e o r m o r e spectrometers.

These

analyses c a n b e m a d e q u a n t i t a t i v e b y c o m p a r i n g the counts p e r m i n u t e o b t a i n e d w i t h those f r o m suitable standards.

B i r k s (16)

described the

i n s t r u m e n t a n d its use i n a v a r i e t y of a n a l y t i c a l a p p l i c a t i o n s . C a m p b e l l a n d B r o w n ( 3 9 ) r e v i e w e d t h e significant progress m a d e i n t h e last f e w years. U s i n g t h e electron p r o b e , Rosser et al. (154)

studied the C a concen-

tration i n developing enamel, a n d Boyde, Switsur, a n d Fearnhead

(19)

s t u d i e d t h e c a l c i u m a n d i r o n d i s t r i b u t i o n i n rat e n a m e l a n d h u m a n m o l a r enamel.

T h e s e investigators r e p o r t e d a h i g h e r c o n c e n t r a t i o n of c a l c i u m

i n t h e p e r i t u b u l a r area of d e n t i n t h a n i n t h e i n t e r t u b u l a r area. et al. (189),

u s i n g a n electron m i c r o s c o p e w i t h a n x-ray

Takuma

spectrometer

attachment, e x a m i n e d horse d e n t i n p r e p a r e d f o r r o u t i n e electron m i c r o s c o p y (500 A t h i c k ) . T h e y f o u n d t w i c e as m u c h C a a n d P i n t h e p e r i t u b u l a r as i n t h e i n t e r t u b u l a r m a t r i x , a l t h o u g h t h e y c o u l d n o t d e t e r m i n e a statistical difference i n t h e P K a • C a K Z n , a n d T l a l l cause decreased c a l c i f i c a t i o n .

When

Sr

a n d V w e r e absent, caries i n c r e a s e d ; w h e n present, caries w a s c o n t r o l l e d . D e l e t i o n o f Z n , B a , a n d T l f r o m the d i e t h a d n o effect o n d e n t a l caries. T h i s result p r o m p t e d G e y e r  (60)

to test V i n s m a l l groups of h a m -

sters. M a r k e d l y less e n a m e l caries w a s o b s e r v e d i n hamsters f e d d a i l y 0.08 mg V O 2

s

i n c o m p a r i s o n w i t h controls o n the c a r i o g e n i c d i e t , a n d d e n t i n a l

caries also w a s s t o p p e d . H e suggested t h a t . . v a n a d i u m ions, i m b e d d e d i n e n a m e l a n d d e n t i n , c o u l d increase the hardness of the h y d r o x y l apatite as w e l l as the c o h e s i o n b e t w e e n the o r g a n i c a n d i n o r g a n i c m a t t e r . " H e i n a n d W i t s o t z k y  (81)

f o u n d n o i n h i b i t i o n of caries i n hamsters

t h a t h a d b e e n g i v e n 10 p p m V i n the d r i n k i n g w a t e r .

A n increase i n

caries was n o t e d w h e n s l i g h t l y h i g h e r amounts w e r e g i v e n . toxic l e v e l of i n t a k e .

M u h l e r  (121)

T h i s is a

f e d 10, 20, a n d 40  fig of v a n a d i u m

p e n t o x i d e p e r cc i n the d r i n k i n g w a t e r of rats a n d n o t e d n o effect o n caries w h e n these h i g h toxic levels of V w e r e g i v e n .

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals 145

NAVIA

T h e c o n c e n t r a t i o n of V g i v e n seems to b e i m p o r t a n t . W i n i k e r

(208)

f e d a salt of a m m o n i u m m e t a v a n a d a t e to hamsters a n d n o t e d caries i n h i b i t i o n w h e n 0.035 m g /d a y w e r e f e d a n d caries s t i m u l a t i o n w h e n 0.20 m g /d a y w e r e g i v e n . M u n c h (128) given.

o b s e r v e d f a v o r a b l e results w h e n b o t h V a n d M o w e r e

H e p o s t u l a t e d that V acts l o c a l l y o n t h e teeth b y c h a n g i n g t h e

lattice of the h y d r o x y l apatite, w i t h V r e p l a c i n g P . Kruger

(100)

c o r i f i r m e d G e y e r i n a s t u d y o n rats b e g u n

during

amelogenesis i n the rat. R a t m o l a r caries w e r e r e d u c e d s i g n i f i c a n t l y . Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

H o w e v e r , S h a w a n d G r i f f i t h s (168)

o b s e r v e d n o effect w h e n v a n a d i u m

p e n t o x i d e o r v a n a d y l sulfate w a s f e d i n t h e d i e t o r i n t h e d r i n k i n g w a t e r . T h e r e w a s u n c e r t a i n t y i n t h e results w h e n t h e V salts w e r e f e d d u r i n g the d e v e l o p m e n t a l stage. T h e studies b y T a n k a n d S t o r v i c k ( 1 9 0 ) o n c h i l d r e n f r o m seleniferous a n d nonseleniferous areas i n d i c a t e a n i n v e r s e c o r r e l a t i o n b e t w e e n t h e V content of t h e w a t e r a n d caries d e v e l o p m e n t . S o m e studies h a v e b e e n m a d e of t h e i n t e r r e l a t i o n s h i p b e t w e e n

F

a n d V . T e m p e s t i n i ( 191) n o t e d that F a n d V together w e r e m o r e effective i n r e d u c i n g d e n t a l caries t h a n F alone. this

B u t t n e r (36)

d i d not confirm

finding. V deserves f u r t h e r i n v e s t i g a t i o n to d e t e r m i n e its effects o n b o n e a n d

t o o t h c a l c i f i c a t i o n a n d o n d e n t a l caries d e v e l o p m e n t . S T R O N T I U M .

T h i s b o n e - s e e k i n g a l k a l i n e e a r t h m e t a l appears to affect

caries. S h a w a n d G r i f f i t h s (168)

n o t e d n o e v i d e n c e of v a n a d i u m r e d u c i n g

d e n t a l caries i n c i d e n c e . R y g h ( 1 5 8 , 1 5 9 ) n o t e d a h i g h i n c i d e n c e of caries w h e n S r w a s absent f r o m the d i e t of rats. W h e n Sr a n d V w e r e a d d e d i n (94)

p l e n t y , caries w a s c u r t a i l e d . Johansen a n d H e i n 50 p p m of s t r o n t i u m as S r C l

2

c o n c l u d e d that

a d d e d to d r i n k i n g w a t e r h a d n o effect o n

hamsters' caries. B a n k s et al

(10)

r e p o r t e d that 1.0 to 2 . 0 % S r C l

2

a d d e d t o the d r i n k -

i n g w a t e r of w e a n l i n g rats c a u s e d c o n s i d e r a b l e d i s t u r b a n c e s

of t h e

c a l c i f i c a t i o n of t h e d e n t i n a n d c e m e n t u m . P i n d b o r g ( 1 5 1 ) m a d e a s i m i l a r o b s e r v a t i o n , a n d n o t e d a l a c k of p i g m e n t a t i o n of t h e n o r m a l e n a m e l of the rat i n c i s o r . S t e a d m a n et al

(178)

suggested that S r is d e p o s i t e d p r i -

m a r i l y before t h e e r u p t i o n a n d d u r i n g t h e c a l c i f i c a t i o n of t h e t o o t h , t h o u g h a d d i t i o n a l Sr is d e p o s i t e d i n the s e c o n d a r y d e n t i n a n d c e m e n t u m after

tooth

eruption.

a m o u n t s of S r

90

Therefore,

children will

deposit

considerable

w h e n there is h e a v y isotope f a l l o u t . B r y a n t et al

(32)

c o r r o b o r a t e d this c o n c l u s i o n , f o r t h e y f o u n d a n inverse c o r r e l a t i o n w i t h age.

B u t l e r (33)

f o u n d 2.6 ±

0.6 disintegrations o f S r ^/m i n /g r a m i n

teeth o b t a i n e d f r o m c h i l d r e n u n d e r 4 years a n d 0.4 ± 0.2 i n teeth f r o m h u m a n subjects o v e r 31 years of age.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

146

zyxwvutsrqponmlkjihgfedcba VS. D E N T A L CARIES

DIETARY

C H E M I C A L S

YaegerzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA (215) o b s e r v e d b y the use of a n electron m i c r o s c o p e t h a t the m a t r i x of t h e fine structure of the h y p o m i n e r a l i z e d c o m p o n e n t p r o d u c e d by

Sr contained

pools of h e a v i l y stained

material, presumably nonfibrillar collagen.

homogeneous,

interfibrillar

This defect probably could

a c c o u n t f o r the i n h i b i t i o n of m i n e r a l i z a t i o n w h i c h results i n t h e h y p o m i n e r a l i z e d c o m p o n e n t of t h e incisors s t u d i e d . F u r t h e r studies of t h e role of Sr i n c a l c i f i c a t i o n a n d i n d e n t a l caries are n e e d e d . C o p p e r , a n essential element, is a constituent or a n activator

C O P P E R .

Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

of c e r t a i n

enzymes,

a n d i t has a p o s t u l a t e d

role i n b o n e

formation

a n d i n m a i n t e n a n c e of m y e l i n w i t h i n t h e nervous system. C r i p p l i n g b o n e defects o c c u r i n cattle a n d sheep g r a z i n g o n C u - d e f i c i e n t pastures. Brudevold a n d Steadman

(26)

s t u d i e d t h e d i s t r i b u t i o n of C u i n

h u m a n teeth, a n d f o u n d n o c o r r e l a t i o n b e t w e e n C u content a n d t o o t h pigmentation

or caries.

M c C l u r e (113)

found no pronounced

effect w h e n C u w a s g i v e n i n d r i n k i n g w a t e r . S h a w (167)

caries

n o t e d n o effect

w h e n 0 . 5 % N a - C u c h l o r o p h y l l i n w a s a d d e d to t h e d r i n k i n g w a t e r of rats.

H o w e v e r , H e i n a n d S h a f e r ( 8 0 ) , u s i n g a p r e p a r a t i o n of N a - C u

c h l o r o p h y l l i n of 9 3 . 2 % p u r i t y , f o u n d a cariostatic effect i n hamsters. C o n c e n t r a t i o n s of 0.25 m g /1 0 0 grams C u i n sucrose-containing s a l i v a d e f i n i t e l y i n h i b i t e d a c i d f o r m a t i o n w h i l e 3 to 4 m g /1 0 0 grams C u i n s a l i v a c o m p l e t e l y i n h i b i t e d a c i d p r o d u c t i o n (56).

D r e i z e n et al. (52)

found no

r e l a t i o n b e t w e e n the C u content of s a l i v a a n d d e n t a l caries a c t i v i t y i n h u m a n subjects. T h e l e v e l o f C u n o r m a l l y present i n s a l i v a w a s u n a b l e in vitro to p r e v e n t the g r o w t h of L.

Hein

(78)

acidophilus.

o b s e r v e d that C u S 0

r e d u c e d caries as t h e l e v e l w a s

4

i n c r e a s e d : 0, 10, 25, 50 p p m C u . A straight l i n e w a s o b t a i n e d w h e n t h e caries scores w e r e p l o t t e d against t h e l o g a r i t h m of t h e C u c o n c e n t r a t i o n , i n d i c a t i n g that t o o t h d e s t r u c t i o n w a s a n inverse f u n c t i o n o f t h e C u S 0 concentration.

K r u g e r (100)

injected 0.005 to 0.02 m g of C u N 0

3

4

intra-

p e r i t o n e a l l y i n t o rats, a n d n o t e d a caries r e d u c t i o n w h i c h a p p r o a c h e d the 5 % significance l e v e l . B O R O N .

T h i s w a s t h e first element t o b e p r o v e d essential f o r p l a n t

l i f e . It is n o t clear y e t w h e t h e r i t is a n essential e l e m e n t f o r a n i m a l s . W e s s i n g e r (205)

gave 200 m g B /k g b o d y w e i g h t as b o r i c a c i d a n d

o b s e r v e d n o e n a m e l h y p o p l a s i a i n the incisors. H e c o n c l u d e d that B h a d no effect o n amelogenesis K r u g e r (100)

i n contrast t o S r w h i c h has a m a r k e d effect.

gave 0.005 t o 0.025 m g B as b o r i c a c i d i n t r a p e r i t o n e a l l y , a n d

c o n c l u d e d that B is effective i n r e d u c i n g caries d e v e l o p m e n t . (168)

S h a w et al.

n o t e d a modest r e d u c t i o n i n caries w h e n 0.5, 1.0, a n d 2 . 0 % N a

borate were f e d post-developmentally. L I T H I U M .

Wisotzky and Hein

f o u n d n o effect o n a n i m a l caries.

(210)

tested l i t h i u m

sulfate a n d

H o w e v e r , Shaw a n d Griffiths

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

(168)

ΝΑ V I AzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals 147

9.

added a 0.1%

s u p p l e m e n t of l i t h i u m c a r b o n a t e to a rats' d i e t a n d o b -

served a definite p o s t - d e v e l o p m e n t a l influence to i n h i b i t d e n t a l caries. G o l d , i n the f o r m of a u r i c c h l o r i d e , w a s r e p o r t e d b y W i s o t z k y

GOLD.

a n d H e i n (210)

to b e a potent i n h i b i t o r of caries i n hamsters.

Elements W i t h D o u b t f u l Caries Effect.

zyxwvutsrqponmlkj

This alkaline

B E R Y L L I U M .

e a r t h m e t a l has b e e n r e p o r t e d to p r o d u c e changes i n b o t h bones a n d M a y n a r d et al.

teeth.

(112)

f e d w e a n l i n g rats a d i e t c o n t a i n i n g

BeSC>4 or B e C O e a n d o b s e r v e d r a c h i t i c lesions w i t h i n 3 weeks. (204)

fed 3 and 6%

levels of B e C 0

3

5%

Wentz

a n d o b s e r v e d rickets i f the v i t a -

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m i n D i n t a k e w a s l o w , as w e l l as e n a m e l h y p o p l a s i a a n d a p l a s i a , r e t a r d a t i o n i n c a l c i f i c a t i o n a n d i n d e n t i n f o r m a t i o n , a n d d e l a y e d e r u p t i o n of the S h e r m a n a n d S o b e l (169)

teeth.

r e p o r t e d that extremely l o w c o n c e n t r a -

tions (0.01 p p m ) of B e i o n c a n l i m i t c a l c i u m p h o s p h a t e c r y s t a l g r o w t h , and

this m i g h t e x p l a i n the in vivo results.

R y g h (161)

c o n c l u d e d that

w h i l e F is essential to the p r o p e r f o r m a t i o n of t o o t h e n a m e l , B e is of n o significance. L e i c e s t e r et al. 0.02%

BeCl

2

(103)

f o u n d that w h e n m a l e hamsters w e r e g i v e n

i n d i e t or i n d r i n k i n g w a t e r f r o m the date of c o n c e p t i o n

u n t i l 24 days p o s t p a r t u m , a h i g h l y significant r e d u c t i o n i n d e n t a l d e c a y T h e s e authors n o t e d (192)

w a s o b s e r v e d 100 days later. and

that w h e n F e

F w e r e f e d together to m a l e hamsters, there w a s a statistically sig-

nificant r e d u c t i o n i n caries. COBALT.

C o b a l t is a constituent of v i t a m i n B i

f o r m a t i o n , b u t n o definite r e l a t i o n b e t w e e n B been observed.

D r e i z e n et al.

(52)

i 2

2

w h i c h affects b l o o d

d e f i c i e n c y a n d caries has

f o u n d no r e l a t i o n b e t w e e n the C o

l e v e l i n s a l i v a of h u m a n beings a n d t h e i r caries experience. and

F o r s a i t h (82)

Hendershot

f o u n d 3 to 4 times m o r e caries i n m a l e rats f e d a

s u p p l e m e n t of C o - E D T A salt t h a n i n controls. C o b a l t m a y interfere w i t h the m i n e r a l i z a t i o n process, f o r G o l d e n b e r g (63)

n o t e d that the a d d i t i o n of C o (also B e , M n , N i ) to a b a s a l s o l u t i o n

w h i c h contained N a C l , K C 1 , and N a H C 0

3

accelerated

the i n a c t i v a t i o n

of the c a l c i f y i n g m e c h a n i s m of a n e p i p h y s e a l cartilage s u s p e n d e d i n the solution.

B i r d and Thomas

formation

of

apatite

(IS)

crystals

at

found C o unique in preventing concentrations

w h i c h also

the

inhibited

m i n e r a l i z a t i o n of r a c h i t i c cartilage m a t r i x . M A N G A N E S E .

M a n g a n e s e is a n a c t i v a t o r f o r several e n z y m e s s u c h as

b l o o d a n d b o n e phosphatases.

It is a n essential element e v e n t h o u g h there

is n o definite e v i d e n c e that M n d e f i c i e n c y occurs i n m a n . S t e p h a n a n d H a r r i s (180)

n o t e d that d e n t a l caries w a s

somewhat

h i g h w h e n M n was omitted f r o m a synthetic-type diet, a n d reduced w h e n 0 . 1 % M n was a d d e d . W y n n et al Mn

(215)

a d d e d 50, 150, a n d 500 p p m of

to the synthetic t y p e diets of rats a n d n o t e d n o

effect.

caries-reducing

S i m i l a r experiments b y H e n d e r s h o t a n d F o r s a i t h (82)

w i t h the

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

148

DIETARY

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

M n salt of e t h y l e n e d i a m i n e t e t r a a c e t i c a c i d , M n acetate, or M n versenate w e r e also n e g a t i v e . W h e n 0 . 1 5 m g M n , as t h e sulfate, w a s i n j e c t e d i n t r a -

p e r i t o n e a l l y d a i l y into rats, t h e caries i n c i d e n c e d i d n o t decreasezyxwvutsrqponmlkjih (100). N a v i a et al. (131) Mn

2 +

s t u d i e d t h e effect of M n C l

2

supplements ( 2 0 0 0 p p m

) o n a p u r i f i e d c a r i e s - p r o m o t i n g d i e t f e d to rats a n d f o u n d n o effect

o n caries. D r e i z e n et al. (51)

s h o w e d that t h e c o n v e r s i o n of c a r b o h y d r a t e s t o

a c i d residues b y o r a l b a c t e r i a is i n h i b i t e d w h e n M n

2 +

is r e m o v e d b y

c h e l a t i n g c o m p o u n d s . T h e y suggested that t h e M n content of t h e s a l i v a , Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

w h i c h a p p r o x i m a t e s 0 . 0 0 5 f t g /m l , c o u l d b e a n i m p o r t a n t factor i n d e n t a l caries a c t i v i t y . B u t t n e r (36)

f o u n d no interaction between M n a n d F

m e t a b o l i s m , e v e n t h o u g h E l T a n n i r ( 5 3 ) h a d suggested that t h e results of a n e p i d e m i o l o g i c a l s u r v e y i n M e c c a i n d i c a t e d that M n c a u s e d a b r o w n c o l o r a t i o n of t h e m o t t l e d e n a m e l i n h u m a n subjects c o n s u m i n g w a t e r containing 2 p p m F . It is e v i d e n t that t h e caries a c t i v i t y of M n is s t i l l u n c l e a r . TIN.

T i n has b e e n s t u d i e d extensively i n recent years, e s p e c i a l l y i n

r e l a t i o n to F . M u h l e r a n d D a y (124)

supplemented the drinking water

of rats w i t h 1 0 p p m S n F a n d f o u n d i t s u p e r i o r to N a F i n r e d u c i n g t h e i n c i d e n c e a n d severity o f d e n t a l caries, w h i l e S n C l

2

h a d no significant

effect. T h e y o b s e r v e d ( 1 2 5 ) a 7 5 % decrease i n caries i n c i d e n c e w h e n i t w a s f e d i n t h e d i e t of rats. T o x i c effects w e r e n o t e d w h e n 5 0 0 p p m w e r e f e d , as s h o w n b y g r o w t h i m p a i r m e n t . essentially w i t h o u t effect (121),

but S n F

s p o n d e d to its fluoride content.

S n gluconate a n d S n C l 2

M u h l e r (122)

were

suggested that t h e m o s t

significant c l i n i c a l effect of t o p i c a l l y - a p p l i e d S n F lesions, a n d M e c k e l (117)

2

h a d a greater effect t h a n c o r r e 2

is exerted o n i n c i p i e n t

i n d i c a t e d that t i n is h e l d v e r y firmly a n d n o

significant losses take p l a c e f o r p e r i o d s u p to 1 1 3 d a y s . T h e w o r k of H o e r m a n et al. (86) w i t h t h e electron p r o b e m i c r o a n a l y s i s i n d i c a t e s that the m e c h a n i s m o f this l o n g persistence o f t i n m i g h t b e its s p e c i a l b i n d i n g p r o p e r t i e s i n " e n r i c h e d " areas of e n a m e l , f r o m w h i c h i t is l e a c h e d s l o w l y over a l o n g p e r i o d o f t i m e . G i s h et al. (62) of K

fluorostannite

t r e a t e d 4 4 2 c h i l d r e n w i t h a 4 % aqueous s o l u t i o n

and found a 5 3 . 7 % reduction i n D M F T a n d a 3 9 . 2 %

reduction i n D M F S .

B r u d e v o l d et al. (29)

r e p o r t e d that S n

w e r e b o t h t a k e n u p w h e n t h e e n a m e l w a s exposed to S n F

2

2 +

and F"

solutions,

especially w h e n the p H was low. ZINC.

47).

Z i n c is present i n b o n e (194)

a n d is q u i t e h i g h i n d e n t i n (46,

Increased levels h a v e b e e n r e p o r t e d i n t h e d e n t a l tissues o f t u b e r c u -

losis patients.

It is d i s t r i b u t e d w i d e l y i n t h e h u m a n b o d y , e s p e c i a l l y i n

the erythrocytes w h e r e i t is a n essential c o m p o n e n t of c a r b o n i c a n h y d r a s e . Z i n c is also a s t r u c t u r a l c o m p o n e n t of t h e phosphatases, t o w h i c h i t c o n -

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

149 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals

NAVIA

tributes s t a b i l i t y . Z i n c accumulates o n the surface structures of the t e e t h (31),

b u t occurs i n l o w concentrations i n subsurface m a t e r i a l , a n d shows (161).

a d i s t r i b u t i o n p a t t e r n s i m i l a r to F a n d P b . It is a d i e t a r y essential L i t t l e is k n o w n about the effects of Z n o n d e n t a l caries. (113)

n o t e d a c a r i e s - s t i m u l a t i n g effect w h e n Z n S 0

4

McClure

( 250 p p m ) w a s f e d

i n the d r i n k i n g w a t e r of rats. H e n d e r s h o t a n d F o r s a i t h (82, 83)

observed

a p p r e c i a b l y l o w e r caries scores w h e n Z n - E D T A w a s f e d to w e a n l i n g m a l e rats, b u t n o significant effect w h e n Z n acetate was g i v e n . Z n s u p p l e ments as Z n C L (2000 p p m Z n ) offered to rats f r o m b i r t h to 60 d a y s of 2 +

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age w e r e inert i n terms of s m o o t h surface a n d s u l c a l caries ( 1 3 1 ) . B r o m i n e , w h e n f e d as the b r o m i d e , w a s f o u n d b y Sognnaes

B R O M I N E .

(171)

to increase caries i n rats w h e n f e d d u r i n g t o o t h d e v e l o p m e n t , b u t

to r e d u c e caries s o m e w h a t i f f e d after e r u p t i o n . U s i n g serial a u t o r a d i o g (174)

raphy a n d B r , Soremark 8 2

s h o w e d that b r o m i d e ions enter the

d e n t i n a n d that its a c t i o n m a y v a r y , d e p e n d i n g o n the p e r i o d w h e n administered. IODINE.

I o d i n e (0.005 to 0.002 m g )

rats h a d n o effect o n caries (100).

injected intraperitoneally into

S e v e r a l investigators (49, 114,

152)

h a v e f o u n d that c o m p o u n d s l i k e i o d o a c e t i c a c i d cause a significant r e d u c t i o n i n caries w h e n a d d e d to d r i n k i n g w a t e r . U n f o r t u n a t e l y , the L D

5 0

(48)

D a l e and Keyes

o b s e r v e d a n a d d i t i v e effect w h e n i o d o a c e t i c a c i d was g i v e n w i t h of i o d o a c e t i c a c i d is 116

±

fluorine.

12 m g /k g b o d y

w e i g h t , w h i c h gives a safety m a r g i n that is too n a r r o w to p e r m i t its a p p l i c a t i o n as p r o p y h l a c t i c agent f o r caries SILICON.

20%

S i l i c o n oils are c a r i o g e n i c w h e n f e d i n the diet at 10 a n d

levels (20),

fluoridation

(110).

b u t s i l i c o f l u o r i d e salts h a v e b e e n u s e d successfully f o r

of w a t e r s u p p l i e s w i t h o u t a n y a p p a r e n t

effectiveness of the

fluoride

i n r e d u c i n g caries.

r e d u c t i o n i n the

N o e v i d e n c e has

p r e s e n t e d i n d i c a t i n g that S i is c a r i e s - p r o m o t i n g i n h u m a n s . Caries-Inert Elements.

B A R I U M .

W h e n 0.5 or 1.0%

been

zyxwvutsrqponmlkji

of B a C L w a s

f e d i n the d i e t of rats, it h a d n o effect o n the d e v e l o p i n g t e e t h or caries s u s c e p t i b i l i t y (168);

h o w e v e r , some r e d u c t i o n i n caries w a s

observed

p o s t - d e v e l o p m e n t a l l y . N o a l t e r a t i o n i n the rate or degree of c a l c i f i c a t i o n i n these a n i m a l s w a s o b s e r v e d . A L U M I N U M .

T h i s element is a b u n d a n t i n the s o i l , a n d is u b i q u i t o u s

i n foods, b u t is not k n o w n to b e essential to h i g h e r a n i m a l s . Its t o x i c i t y is q u i t e l o w . W y n n a n d H a l d i (213)

n o t e d n o effect o n e x p e r i m e n t a l caries d e v e l -

o p m e n t i n rats w h e n 0.16, 2.0, a n d 20 p p m A l w e r e a d d e d to the diet. K r u g e r (100)

f o u n d n o effect o n rat caries w h e n 0.008 a n d 0.025 m g of

A l w e r e f e d as A l acetate. V a n R e e n et al.

S i m i l a r negative results w e r e r e p o r t e d

(200).

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

by

150

DIETARY

I t appears t o counteract d e n t a l

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

fluorosiszyxwvutsrqponmlkjihgfedcbaZYXWVU (201, 203). T h i s effect is

p r o b a b l y a result of decreased d e p o s i t i o n o f F , since t h e F stores i n bones a n d teet h w e r e r e d u c e d b y c o n c u r r e n t A l f e e d i n g . N I C K E L .

N i c k e l is w i d e l y d i s t r i b u t e d i n p l a n t a n d a n i m a l tissues.

It

acts as a n a c t i v a t o r o f several e n z y m e systems, s u c h as arginase a n d trypsin. F o r b e s a n d S m i t h (56)

f o u n d that N i salts exert a m a r k e d i n h i b i t i n g

a c t i o n o n a c i d p r o d u c t i o n i n s a l i v a . H e n d e r s h o t et al. (83) r e p o r t e d that NiCl

2

c a u s e d a n increase o f caries i n rats, t h a t w h e n N i - E D T A w a s g i v e n ,

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caries w a s i n h i b i t e d i n m a l e b u t n o t i n f e m a l e rats, a n d t h a t N i acetate h a d n o effect o n either sex. IRON.

T h i s element is i m p o r t a n t t o h e m o g l o b i n f o r m a t i o n a n d is a n

essential element.

T h o u g h n o r m a l l y i t is n o t c o n s i d e r e d a p a r t o f t h e

apatite m o l e c u l e , i t appears essential f o r t h e f o r m a t i o n of t h e orangeb r o w n p i g m e n t that is characteristic of t h e e n a m e l of t h e r o d e n t incisors. M c C l u r e (113)

f e d 2 5 0 a n d 5 0 0 p p m f e r r i c citrate i n t h e d i e t o f rats

a n d n o t e d n o d i s t i n c t effect. T h e same result w a s r e p o r t e d b y W y n n et al. (215)

a n d b y H e n d e r s h o t a n d F o r s a i t h (82) w h e n f e d F e - E D T A . T o r e l l

( 1 9 5 ) suggested t h e p o s s i b i l i t y t h a t f e r r i c solutions m a y establish layers of h y d r o l i z e d f e r r i c precipitates o n e n a m e l w h i c h c o u l d increase caries. P A L A D I U M .

P a l a d i u m c h l o r i d e h a d n o effect o n caries

T I T A N I U M .

V a n R e e n et al. (200)

(210).

f o u n d this element t o b e caries-

inert w h e n tested w i t h t h e N M R I - D rats, a l t h o u g h a s m a l l r e d u c t i o n (about 1 0 % ) was observed w h e n A l , T i , a n d M o were f e d together i n the diet.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC

Experimental

Factors Which Contribute

to the Discrepancy in the

Effect of Minerals on Dental Caries T h e r e v i e w e d results of a large n u m b e r of experiments i n h u m a n s a n d a n i m a l s t o investigate t h e r e l a t i o n s h i p b e t w e e n c e r t a i n trace elements a n d d e n t a l caries are c o n f l i c t i n g . T h e reason f o r this a p p a r e n t c o n f u s i o n is p r i m a r i l y that m a n y factors are i n v o l v e d i n this p r o b l e m .

Experiments

i n w h i c h o n l y some of t h e factors are t a k e n i n t o c o n s i d e r a t i o n c a n n o t b e c o m p a r e d w i t h other experiments w h e r e a different set of factors has been controlled. I n o r d e r to c l a r i f y this p o i n t , i t w o u l d b e of a d v a n t a g e t o r e v i e w b r i e f l y the e x p e r i m e n t a l factors w h i c h influence d e n t a l caries

research

w i t h r e g a r d to trace elements. Species. elements

T h e sensitivity o f a n i m a l species to t h e effect of c e r t a i n

has a w i d e v a r i a t i o n , o w i n g p r i n c i p a l l y t o their

anatomical,

b i o c h e m i c a l , p h y s i o l o g i c a l , a n d m i c r o b i o l o g i c a l differences.

These dif-

ferences are n o t o n l y present

w i t h i n a n i m a l species

(rats,

hamsters,

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

N A V I A

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Effect of Minerals 151

m o n k e y s ) a n d e v e n strains, b u t also b e t w e e n a n i m a l species a n d h u m a n beings, m a k i n g the e x t r a p o l a t i o n of results a d i f f i c u l t task.

The animal

is a n e x p e r i m e n t a l m o d e l , w h e r e assumptions h a v e to b e m a d e a n d , therefore, results f r o m this t y p e of s t u d y c a n o n l y b e u s e d to u n d e r s t a n d better the p a t h o l o g y of h u m a n caries, a n d not to e x p l a i n i n its entirety h u m a n caries p h e n o m e n a .

the

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPON

Route of Administration. E l e m e n t s c a n influence the t o o t h a n d its

e n v i r o n m e n t b y e n t e r i n g the o r g a n i s m t h r o u g h diet, w a t e r , air, or cage environment.

E x p e r i m e n t a l l y , elements

also c a n b e

administered

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i n j e c t i o n a n d b y t o p i c a l a p p l i c a t i o n s o n the t o o t h surface

(73).

effectiveness of these different routes i n f a c i l i t a t i n g the effect of

by The the

c h e m i c a l agent is d e p e n d e n t o n the a v a i l a b i l i t y of the c o m p o u n d a n d its p a r t i c u l a r m e c h a n i s m of a c t i o n o n the tooth— i.e., i n c o r p o r a t i o n i n t o e n a m e l , o n the p l a q u e , or surface a d s o r p t i o n , etc. T h e effects of elements, therefore,

c a n b e c o m p a r e d o n l y w h e n the f o r m of a d m i n i s t r a t i o n is

t h r o u g h e q u a l routes. Time (Age)

of Administration. T h e t i m e at w h i c h the element is

g i v e n has a p r o f o u n d influence w i t h r e g a r d to the d e v e l o p m e n t of the a n i m a l a n d the stage of d e v e l o p m e n t of the tooth. C e r t a i n elements m a y e x h i b i t t o x i c properties w h e n f e d to y o u n g i m m a t u r e a n i m a l s a n d , therefore, i n h i b i t t h e i r g r o w t h a n d d e v e l o p m e n t , the result b e i n g a sick a n d a b n o r m a l a n i m a l w i t h u n p h y s i o l o g i c a l responses.

T h e stage of d e v e l o p -

m e n t of the t o o t h is a n e v e n m o r e i m p o r t a n t factor, f o r i f the

element

is to b e i n c o r p o r a t e d or a d s o r b e d b y the t o o t h , this c a n take p l a c e o n l y at the i n i t i a l stages of d e v e l o p m e n t or e r u p t i o n a n d not w h e n the e n a m e l m i n e r a l has m a t u r e d a n d lost its r e a c t i v i t y

(133).

Chemistry and Availability of the Mineral Compound. T h e c h e m -

i c a l structure, v a l e n c e , a n d s o l u b i l i t y are f u n d a m e n t a l factors w h i c h also d e t e r m i n e the a c t i v i t y of the element w i t h r e g a r d to d e n t a l caries.

The

c h e m i c a l properties of a c o m p o u n d b e i n g tested influence t h e i n t e s t i n a l a b s o r p t i o n , the o r a l a n d i n t e s t i n a l flora, a n d the d i r e c t l o c a l u p t a k e b y the t o o t h or p l a q u e .

E x p e r i m e n t s , therefore, e v e n t h o u g h t h e y m a y use

s i m i l a r levels of a c e r t a i n element, are not c o m p a r a b l e i f the c h e m i c a l structure of the c o m p o u n d is different. E x a m p l e s h a v e b e e n c i t e d w h e r e a c h e m i c a l f o r m is effective at a p a r t i c u l a r t o o t h d e v e l o p m e n t stage a n d not at another later stage. Requirement and Toxicity Levels: Biological Reserves. T r a c e

ele-

ments p l a y a p a r t i n m a n y b i o l o g i c a l reactions, a n d some are d e f i n i t e l y essential n u t r i e n t s ; n o n o r m a l d e v e l o p m e n t c a n take p l a c e i n t h e i r absence.

The

amounts

r e q u i r e d are u s u a l l y e x t r e m e l y

v e r y d i f f i c u l t to investigate tions of elements. exists

about the

s m a l l , a n d it is

the p a r t p l a y e d b y s u c h l o w

concentra-

It is not at a l l s u r p r i s i n g , therefore, that u n c e r t a i n t y significance

of some

trace elements

with regard

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

to

152

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

DIETARY

nutrition

a n d dental

health.

Another

C H E M I C A L S

problem

that

confronts

the

investigator is that a l l l i v i n g matter contains trace elements, a n d t h e y store t h e m i n organs s u c h as t h e l i v e r i n vertebrates o r other structures i n the l o w e r f o r m s . T h e e n d result is that i t is q u i t e i m p o s s i b l e to d e p l e t e the

organisms

b i o l o g i c a l reserves

o f nutrients

e n o u g h to observe

a

clear d e n t a l effect o r n u t r i t i o n a l s y m p t o m s o f a trace element d e f i c i e n c y . T h e l o w r e q u i r e m e n t s o f these trace elements

together w i t h t h e

h i g h t o x i c i t y e x h i b i t e d b y m a n y elements f u r t h e r c o m p l i c a t e s t h e i r investigations, f o r s l i g h t l y h i g h e r levels u s u a l l y b r i n g a b o u t t o x i c effects w h i c h Downloaded by UNIV OF PITTSBURGH on May 4, 2015 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch009

influence t h e p h y s i o l o g i c a l status a n d t h e r e b y obscure t h e i n t e r p r e t a t i o n

of experiments, as i s t h e case w i t h s e l e n i u m or m o l y b d e n u m . zyxwvutsrqponmlkjihg Type of Diet. I n d e n t a l caries research, t h e t y p e o f d i e t u s e d deter-

m i n e s to a large extent t h e a m o u n t , t y p e , a n d d i s t r i b u t i o n of carious lesions i n t h e m o l a r s . N u t r i t i o n a l l y , d i e t determines t h e degree o f w e l l being a n d normal development a n d maintenance

of e x p e r i m e n t a l a n i -

m a l s , b u t i n caries research, c e r t a i n diets h a v e b u i l t - i n i m b a l a n c e s , m a i n l y i n t h e amounts of p r o t e i n a n d m i n e r a l s w h i c h are responsible f o r its c a r i o g e n i c i t y . C a r i e s - p r o m o t i n g diets, to b e effective, h a v e to a l l o w t h e d e v e l o p m e n t of different types o f lesions at the same t i m e that t h e y satisfy the r e q u i r e m e n t s f o r n o r m a l d e v e l o p m e n t .

Diets c a n b e d i v i d e d into

n a t u r a l , p u r i f i e d , a n d c h e m i c a l l y d e f i n e dzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQ (130). W o r k w i t h trace elements requires t h e use of p u r i f i e d diets m a d e u p of a c a r b o h y d r a t e a n d p r o t e i n source p l u s some o i l a n d a salt a n d v i t a m i n m i x t u r e . T h i s t y p e o f d i e t has the a d v a n t a g e that its c o m p o s i t i o n c a n b e c o n t r o l l e d a n d the trace elements c a n b e k e p t constant, a v o i d i n g t h e

fluctuations

d u e to variations

i n t h e c o m p o s i t i o n of p l a n t f o o d ingredients u s e d i n n a t u r a l diets. c o m p o s i t i o n , f e e d i n g f r e q u e n c y , p h y s i c a l structure, a n d o r a l

Diet

clearance

are i m p o r t a n t factors i n t h e c o n d u c t of e x p e r i m e n t a l caries research. Interferences from Components of Diet.

T h e n a t u r e of the c a r i o -

g e n i c d i e t influences t h e a v a i l a b i l i t y of trace elements f r o m f o o d m a t e rials, t h e storage of those elements i n t h e tissues, t h e i r i n c o r p o r a t i o n i n t o t h e i r f u n c t i o n a l positions i n t h e c e l l a n d , finally, t h e i r excretion.

The

m e t a b o l i s m of c o p p e r is m a r k e d l y affected b y m o l y b d e n u m a n d that of m o l y b d e n u m b y t h e levels of i n o r g a n i c sulfate i n t h e diet.

T h e zinc

r e q u i r e m e n t a p p a r e n t l y is i n c r e a s e d w h e n i s o l a t e d soy-bean p r o t e i n is u s e d i n s t e a d of casein as a p r o t e i n source i n p u r i f i e d diets. P h y t i c a c i d influences t h e u p t a k e of c a l c i u m a n d i r o n i n c e r t a i n species, s u c h as the p i g . D i e t s u s e d i n caries research s h o u l d b e s t u d i e d c a r e f u l l y a n d screened o u t f o r possible interferences a n d m i n e r a l interactions w h i c h m a y b r i n g a b o u t a d d i t i o n a l a n d u n k n o w n sources of v a r i a t i o n i n t h e experiments. Trace Elements or Contaminants. T h e v e r y l o w r e q u i r e m e n t of trace

elements a n d t h e u b i q u i t o u s presence o f trace elements i n n a t u r e d e m a n d

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

9.

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCB Effect of Minerals 153

N A V I A

a r i g i d c o n t r o l of the e n v i r o n m e n t s u r r o u n d i n g e x p e r i m e n t a l a n i m a l s u s e d i n caries research.

T r a c e e l e m e n t c o n t a m i n a n t s c a n c o m e f r o m the cage,

e s p e c i a l l y i f these are g a l v a n i z e d or h a v e m e t a l parts to w h i c h t h e a n i m a l s h a v e r e a d y access; the w a t e r , i f this is n o t c a r e f u l l y d i s t i l l e d a n d stored i n tanks m a d e of i n e r t m a t e r i a l s ; d i e t i n g r e d i e n t s ; a n d the a t m o s p h e r e , i f a i r is n o t filtered a n d c o n d i t i o n e d to p r o p e r t e m p e r a t u r e a n d h u m i d i t y . Methods of Analysis and Caries Evaluation. T r a c e e l e m e n t

content

of diets a n d w a t e r s h o u l d b e a n a l y z e d c a r e f u l l y i n o r d e r to s t a n d a r d i z e the e x p e r i m e n t a l c o n d i t i o n s . C e r t a i n organs, besides teeth a n d other o r a l

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structures, s h o u l d b e dissected a n d a n a l y z e d f o r trace elements i n o r d e r to u n d e r s t a n d t h e i r effects o n the o r g a n i s m a n d , i n p a r t i c u l a r , o n the d e n t a l structures. T h e l o w levels of elements i n v o l v e d a n d the p o s s i b i l i t y of c o n t a m i n a t i o n d u r i n g p r e p a r a t i o n of samples f o r analysis r e q u i r e t h e use of p h y s i c a l m e t h o d s s u c h as n e u t r o n a c t i v a t i n g analysis a n d

electron

p r o b e m i c r o a n a l y s i s to u n d e r s t a n d their d i s t r i b u t i o n i n m i c r o s t r u c t u r e s . R e c e n d y , the e l e c t r o n p r o b e m e t h o d of analysis has b e e n greatly i m p r o v e d , e n a b l i n g the researcher to scan a t o o t h structure a n d d e t e r m i n e levels of elements s u c h as P a n d C a as w e l l as l i g h t e r elements i n 1 - m i c r o n areas. I n cases w h e r e this is n o t feasible, s p e c t r o g r a p h i c analysis or t h e a t o m i c a b s o r p t i o n s p e c t r o p h o t o m e t r y b e c o m e the m e t h o d s of c h o i c e , f o r t h e y are a b l e to detect elements i n parts p e r m i l l i o n levels. L a r g e n u m bers of analyses c a n be c a r r i e d o u t w i t h the latter m e t h o d , w h i l e the s p e c t r o g r a p h i c p r o c e d u r e is u s e f u l i n that several elements c a n b e assayed readily i n a sample. T h e m e t h o d u s e d i n the e s t i m a t i o n of caries extent a n d severity is i m p o r t a n t , f o r it s h o u l d b e a d e q u a t e f o r t h e t y p e of l e s i o n b e i n g f o r m e d b y the c a r i o g e n i c d i e t u s e d a n d the d u r a t i o n of the experiment.

Caries

s c o r i n g m e t h o d s differ i n t h e i r r e p r o d u c i b i l i t y a n d i n t h e i r specificities, a n d c a r e f u l t h o u g h t s h o u l d b e g i v e n to t h e c h o i c e of m e t h o d a n d to t h e c o m p a r i s o n of e x p e r i m e n t a l results o b t a i n e d i n the different caries s c o r i n g procedures. O t h e r m e t h o d s are u s e d i n caries research, s u c h as hardness tests, s o l u b i l i t y tests, d y e p e n e t r a t i o n tests, etc., w h i c h are u s e d to evaluate the effects of trace elements o n t o o t h structure, b u t t h e y a l l r e q u i r e a h i g h degree of s t a n d a r d i z a t i o n i n o r d e r to o b t a i n m e a n i n g f u l a n d c o m p a r a b l e results.

T h e s e in vitro m o d e l s s h o u l d b e c a u t i o u s l y e v a l u a t e d , f o r t h e y

m a y b e t o t a l l y u n r e l a t e d to the in vivo p h e n o m e n a . Experimental Design. A m u l t i p l i c i t y of factors affect the results of

d e n t a l caries experiments a n d interact

between them, p r e c l u d i n g the

p o s s i b i l i t y of o b t a i n i n g m e a n i n g f u l results f r o m experiments w h e r e one of the factors is v a r i e d a n d the rest are m a i n t a i n e d constant (65,

98).

T h e r e f o r e , i n the d e s i g n of experiments i n w h i c h m a n y factors

are

i n v o l v e d , the s o - c a l l e d f a c t o r i a l e x p e r i m e n t (i.e., a l l c o m b i n a t i o n s of a l l

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

zyxwvutsrq

154

DIETARY CHEMICALS VS. DENTAL

CARIES

levels of all factors) or fractional factorials in which only some of the factors are statistically evaluated w i l l allow estimates of existence of interactions. Factorial analysis has the disadvantage that as the number of factors increases, the experiment becomes extremely large. F o r i n stance, for 6 factors at only two levels, the factorial experiment requires 2 = 64 trials. Statistical designs have been described for reducing the number of runs in large-scale fractional replication studies which enable the experimenter to draw up schedules which permit the examination of results at various stages of the research work. The selection of subsequent trials can be made as the results of the previous trials are obtained. Experimental designs of this type w i l l make dental caries research experiments fruitful and effective.

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6

Conclusion The results of an exhaustive literature review on the effect of trace elements i n dental caries has been presented. Epidemiological data as well as experimental data obtained with animal studies indicate that the mineral portion of foods influences the prevalance of dental caries. Trace elements may act as "bone-seeking" elements and accumulate in the skeleton and teeth to modify their development and composition as well as their chemical-physical properties. This influence, i n the case of those elements in high concentration in surface enamel, may extend into the plaque, the oral flora, and the surrounding environment of the tooth. When the literature is evaluated, a highly tentative classification can be made of the type of effect shown by trace elements with regard to dental caries, in spite of the fact that a large number of experiments present conflicting results. The source of confusion i n these observations can be traced to the multiplicity of factors which enter into dental caries research and its relation to mineral nutrition. Research work in which these factors are taken into consideration should be attempted in order to clarify the influence of mineral elements on dental caries.

Literature Cited (1) Adler, P., Dent. Stomatol. 1965, 15, 96-110. (2) Adler, P., Odontol. Rev. 1957, 8, 52. (3) Adler, P., Straub, J., Acta Med. Acad. Sci. Hung. 1953, 4, 221-227.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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9.

ΝΑVIA

Effect of Minerals

155

(4) Andersen, C. Α., Hasler, M . F., "X-Ray Optics and Microanalysis," p. 310, Herman, Paris, 1966. (5) Anderson, R. J., Brit. Dental J. 1966, 120, 271-275. (6) Anderson, R. S., Proc. ORCA Conf. Advan. Fluorine Res. and Dental Caries Prevent., 11th, 1965, 3, 165-169. (7) Asgar, K., J. Dental Res. 1956, 35, 742-748. (8) Aslander, Α., "Dental Caries: The Bone Meal Method and the Cariogenic Properties of Sugar," Royal Institute of Technology, Division of Agriculture, Stockholm, Sweden, 1960. (9) Bachra, Β. N . , Trautz, O. R., Simon, O. L . , Arch. Oral Biol. 1965, 10, 731—738. (10) Banks, S. O., Bhaskar, S. N . , Weinmann, J. P., Arch. Pathol. 1951, 51, 19-29. (11) Battistone, G. C., Feldman, M . H . , Reba, R. C., Arch. Oral Biol. 1967, 12, 1115-1122. (12) Baume, L . J., Mayer, J., J. Dental Res. 1966, 45, 726-774. (13) Becks, H . , Furuta, W . J., J. Am. Dental Assoc. 1941, 28, 1083-1088. (14) Bibby, B. G., J. Am. Med. Assoc. 1961, 177, 316-321. (15) Bird, E . D., Thomas, W . C., Proc. Soc. Exptl. Biol. Med. 1963, 112, 640-643. (16) Birks, L . S., "Electron Probe Microanalysis," Wiley, New York, 1963. (17) Bowen, W . H., Arch. Oral Biol. 1968, 13, 713-714. (18) Bowen, W . H . , Eastoe, J. E., Caries Res. 1967, 1, 130-136. (19) Boyde, Α., Switsur, V . R., Fearnhead, R. S., J. Ultrastruct. Res. 1961, 5, 201-207. (20) Boyers, C. L . , Shaw, J. H . , Rosenthal, E., Giordana, R., J. Dental Res. 1963, 42, 1517. (21) Brekhus, P. J., Armstrong, W . D., J. Am. Dental Assoc. 1936, 23, 14591470. (22) Briner, W. W., Rosen, S., Arch. Oral Biol. 1967, 12, 1077-1084. (23) Briner, W. W., Rosen, S., Calcified Tissue Res. 1968, 2, 60-66. (24) Brudevold, F., "The Chemistry and Prevention of Dental Caries," p. 32, R. F. Sognnase, Ed., C. C. Thomas, Springfield, Ill., 1962. (25) Brudevold, F., Messer, A. C., J. Dental Res. 1961, 40, 728 (Abstr.). (26) Brudevold, F., Steadman, L . T., J. Dental Res. 1955, 34, 209-216. (27) Ibid., 1956, 35, 430-437. (28) Ibid., 1956, 35, 749-752 (29) Brudevold, F., Steadman, L . T., Gardner, D . E., Rowley, J., Little, M . F., J. Am. Dental Assoc. 1956, 53, 159-164. (30) Brudevold, F., Steadman, L . T., Smith, F. Α., Ann. Ν. Y. Acad. Sci. 1960, 85, 110-132. (31) Brudevold, F., Steadman, L . T., Spinelli, Μ. Α., Amdur, Β. H . , Gron, P., Arch. Oral Biol. 1963, 8, 135-144. (32) Bryant, F. J., Henderson, E . H . , Holgate, W., Brit. Dental J. 1960, 108, 291-294. (33) Butler, F. E., Nature 1961, 189, 848-849. (34) Buttner, W., Advan. Fluorine Res. Dental Caries Prevent. 1965, 3, 19-30. (35) Buttner, W., Arch. Oral Biol. Spec. Suppl. 1961, 6, 40-49. (36) Buttner, W., J. Dental Res. 1963, 42, 453-460. (37) Cadell, P. B., Cousins, F. B., Nature 1960, 185, 863-864. (38) Calonius, P. Ε. B., Visapaa, Α., Arch. Oral Biol. 1965, 10, 9-13. (39) Campbell, W. J., Brown, J. D., Anal. Chem. 1968, 40, 346R-375R. (40) Claycomb, C. K., Sorenson, F. M . , Gatewood, D. C., Jump, Ε. B., Weaver, M . E., J. Dental Res. 1961, 40, 504-510.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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156

DIETARY C H E M I C A L S VS. DENTAL CARIES

(41) Claycomb, C. K., Summers, G. W., Jump, E . B., J. Dental Res. 1965, 44, 826. (42) Constant, M . A., Phillips, P. H., Elvehjem, C. A., J. Nutr. 1952, 46, 271. (43) Constant, M . A., Sievert, H . W., Phillips, P. H., Elvehjem, C. A., J. Nutr. 1954, 53, 17-27. (44) Ibid., 1954, 53, 29-41. (45) Crane, D . B., J. Dental Res. 1960, 39, 704. (46) Cruickshank, D . B., Biochem. J. 1949, 44, 299. (47) Cruickshank, D . B., Brit. Dental J. 1940, 68, 257-271. (48) Dale, P. P., Keyes, P. H . , J. Dental Res. 1945, 24, 194. (49) Dale, P. P., Powell, V. H . , J. Dental Res. 1943, 22, 33. (50) Deakins, M., J. Dental Res. 1942, 21, 429-435. (51) Dreizen, S., Niedermeier, W., Dreizen, J. G., Spies, T. D., J. Dental Res. 1958, 37, 1149-1156. (52) Dreizen, S., Spies, H . A., Jr., Spies, T. D., J. Dental Res. 1952, 31, 137142. (53) E l Tannir, M . D., Am. J. Public Health 1959, 49, 45. (54) English, J. A., J. Dental Res. 1949, 28, 172-194. (55) Ericcson, Y., Acta Odontol. Scand. 1954, 11, 167. (56) Forbes, J. C., Smith, J. D., J. Dental Res. 1952, 31, 129. (57) Francis, M. D., Briner, W . W., Arch. Oral Biol. 1966, 11, 349-354. (58) Frank, R. M., Capitant, M . , Goni, J., J. Dental Res. 1966, 45, 672-682. (59) Frazier, P. D., Arch. Oral Biol. 1967, 12, 25-33. (60) Geyer, C. F., J. Dental Res. 1953, 32, 590-595. (61) Ginn, J. T., Volker, J. F., Proc. Soc. Exptl. Biol. Med. 1944, 57, 189. (62) Gish, C. W., Muhler, J. C., Howell, C. L., J. Dental Res. 1957, 36, 780. (63) Goldenberg, H . , Sobel, A. E., Proc. Soc. Exptl. Biol. Med. 1952, 81, 695-698. (64) Gustafson, G., Stelling, E., Brunius, E., Acta Odontol. Scand. 1963, 21, 297-308. (65) Guzman, M . A., "The Art and Science of Dental Caries Research," p. 131-149, Academic, New York, 1968. (66) Hadjimarkos, D . M., Brit. Dental J. 1967, 123, 201-202. (67) Hadjimarkos, D . M., Experientia 1967, 23, 930-932. (68) Hadjimarkos, D . M., Bonhorst, C. W., J. Pediat. 1958, 52, 274-278. (69) Hadjimarkos, D . M., Bonhorst, C. W., Nature 1962, 193, 177-178. (70) Hadjimarkos, D . M . , Bonhorst, C. W., Oral Surg. Oral Med. Oral Pathol. 1959, 12, 113-116. (71) Hadjimarkos, D . M . , Starvick, C. A., Remmert, L . F., J. Pediat. 1952, 40, 451-455. (72) Hardwick, J. L., "Caries Resistant Teeth," p. 222-237, Ciba Foundation Symp., 1965. (73) Harris, R. S., Navia, J. M . , Ann. N.Y. Acad. Sci. 1968, 153, 240-257. (74) Harris, R. S., Nizel, A. E., Intern. Congr. Nutr., 4th, 1957, p. 195. (75) Harris, R. S., Nizel, A. E., J. Dental Res. 1959, 38, 1142-1147. (76) Head, J., J. Am. Med. Assoc. 1912, 59, 2118-2122. (77) Hein, J. W., "Advances in Experimental Caries Research," p. 197-222, G. R. Sognnaes, Ed., Am. Assoc. Advan. Sci., Washington, D . C., 1955. (78) Hein, J. W., J. Dental Res. 1953, 32, 654. (79) Hein, J. W., Quigley, G. A., Marcussen, H . , J. Dental Res. 1958, 37, 34. (80) Hein, J. W., Shafer, W . C., J. Dental Res. 1951, 30, 510. (81) Hein, J. W., Wisotzky, S., J. Dental Res. 1955, 34, 756. (82) Hendershot, L . C., Forsaith, J., J. Dental Res. 1958, 37, 32-33. (83) Hendershot, L . C., Monselll, E., Forsaith, J., "Metal-Binding in Medicine," pp. 306-311, J. J. Seven and A. L. Johnson, Eds., Lippincott, Philadelphia, 1960.

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9.

NAVIA

Effect of Minerals

157

(84) Herrmann, M . , Rozeik, F., Deut. Zahnaerztl. Z. 1962, 17, 880-885. (85) Hewat, R. E . T., Eastcott, D . F., "Dental Caries in New Zealand," Medical Research Council of New Zealand Publication, 1955. (86) Hoerman, K. C., Klima, J. E . , Birks, L . S., Nagel, D . S., Ludwick, W . E . , Lyon, H . W., J. Am. Dental Assoc. 1966, 73, 1301-1305. (87) Holgate, W., Mole, R. H . , Vaughan, J., Nature 1958, 182, 1294-1295. (88) Irving, J. T., J. Physiol. 1940, 99, 8-17. (89) Issac, S., Brudevold, F., J. Dental Res. 1957, 36, 753-758. (90) Jenkins, G. N., Brit. Dental J. 1967, 122, 435-441. (91) Ibid., 1967, 122, 500-503. (92) Ibid., 1967, 122, 545-550. (93) Johansson, B., J. Dental Res. 1965, 44, 64-70. (94) Johansen, E., Hein, J. W., J. Dental Res. 1953, 32, 703. (95) Johnson, A. R., Singer, L., Arch. Oral Biol. 1967, 12, 389-399. (96) Keyes, P. H., J. Dental Res. 1956, 35, 95-101. (97) Kinkel, H . J., Cremer, H . D., J. Dental Res. 1960, 39, 640. (98) Konig, K. G., "The Art and Science of Dental Caries Research," pp. 201-230, Academic, New York, 1968. (99) Kruger, B. J., J. Dental Res. 1966, 45, 714-725. (100) Kruger, B. J., Univ. Queensland Papers, Dept. of Dentistry 1959, 1, 1-28. (101) Landing, B. H . , Lahey, W . K., Schubert, J., Spinanger, J., J. Dental Res. 1957, 36, 750. (102) Leicester, H . M., J. Dental Res. 1946, 25, 337. (103) Leicester, H . M., Thomassen, P. R., Nicholas, L . W., J. Dental Res. 1954, 33, 670. (104) Little, M . F., Brudevold, F., J. Dental Res. 1958, 37, 991-1000. (105) Lobene, R. R., Burnett, C. W., J. Dental Res. 1954, 33, 487. (106) Losee, F. F., Am. Assoc. Adv. Sci., Publ. 81, 1964, 41-54. (107) Ludwig, T. G., Healy, W. B., Losee, F. L . , Nature 1960, 186, 695-696. (108) Ludwig, T. G., Malthus, R. S., Healy, W . B., Nature 1962, 194, 456458. (106) Losee, F. L., Am. Assoc. Adv. Sci., Publ. 81, 1964, 41-54. 8-11. (110) Lundquist, C., J. Dental Res. 1951, 30, 203. (111) Malthus, R. S., Ludwig, T. G., Healy, W . B., N.Z. Dental J. 1964, 60, 291-296. (112) Maynard, E . A., Downs, W . L . , Scott, J. K., Federation Proc. 1950, 9, 338. (113) McClure, F. J., J. Dental Res. 1948, 27, 34-40. (114) McClure, F. J., Arnold, F. A., J. Dental Res. 1941, 20, 97. (115) McClure, F. J., McCann, H . G., Arch. Oral Biol. 1960, 2, 151-161. (116) McDonald, J. B., "Chemistry and Prevention of Dental Caries," p. 89, R. F. Sognnaes, Ed., C. C. Thomas, Springfield, Ill., 1962. (117) Meckel, A. H . , J. Dental Res. 1962, 41, 1104. (118) Miller, C. D., J. Nutr. 1963, 80, 217-222. (119) Moxon, A. L., Rhian, M., Physiol. Rev. 1943, 23, 305. (120) Muhlemann, H . R., Konig, K. G., Helv. Odontol. Acta 1964, 8, Suppl. 1, 79-81. (121) Muhler, J. C., J. Dental Res. 1957, 36, 787-794. (122) Muhler, J. C., J. Indiana Dental Assoc. 1960, 39, 42. (123) Muhler, J. C., Bixer, D., Shafer, W. C., Proc. Soc. Exptl. Biol. Med. 1956, 93, 328. (124) Muhler, J. C., Day, H . G., J. Am. Dental Assoc. 1950, 41, 528. (125) Muhler, J. C., Day, H . G., J. Nutr. 1951, 44, 413. (126) Muhler, J. C., Shafer, W . C., J. Dental Res. 1957, 36, 895-896.

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158

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(127) (128) (129) (130)

Muhler, J. C., Shafer, W . C., Science 1954, 119, 687. Munch, J., Odontol. Rev. 1957, 8, 52. Myrback, K., Z. Physiol. Chem. 1926, 159, 1-21. Navia, J. M . , "The Art and Science of Dental Caries Research," pp. 245-255, Academic, New York, 1968. (131) Navia, J. M . , Cagnone, L . D., Lopez, H . , Harris, R. S., Proc. Intern. Assoc. Dental Res., 46th, 1968, p. 128. (132) Navia, J. M . , Henry, C. H . , Lopez, H . , Harris, R. S., Federation Proc. 1967, 26, 415. (133) Navia, J. M . , Lopez, H . , Harris, R. S., Arch. Oral Biol. 1968, 13, 779786. (134) Navia, J. M . , Lopez, H . , Harris, R. S., J. Nutr. 1969, 97, 133-140. (135) Navia, J. M . , Menaker, L . , Seltzer, J., Harris, R. S., Federation Proc. 1968, 27, 676. (136) Neuman, W . F., Neuman, M . W., "The Chemical Dynamics of Bone Mineral," University of Chicago Press, Chicago, Ill., 1958. (137) Nixon, G. S., Livingstone, H . D., Smith, H . , Arch. Oral Biol. 1966, 11, 247-252. (138) Nixon, G. S., Livingstone, H . D., Smith, H . , Caries Res. 1967, 1, 327332. (139) Nixon, G. S., Smith, H . , J. Dental Res. 1960, 39, 514-516. (140) Ibid., 1962, 41, 1013-1016. (141) Nizel, A. E., Bibby, B. G., J. Am. Dental Assoc. 1944, 31, 1619-1626. (142) Nizel, A. E . , Harris, R. S., Arch. Biochem. 1950, 26, 155-157. (143) Nizel, A. E . , Harris, R. S., J. Dental Res. 1955, 34, 513-515. (144) Nizel, A. E . , Harris, R. S., N. Eng. J. Med. 1951, 244, 361-362. (145) Parizek, J., J. Endocrinol. 1957, 15, 56. (146) Parizek, J., Nature 1956, 177, 1036. (147) Parma, C., Danek, J., Hanusova, N . , Cs. Stomatol. 1952, 52, 150. (148) Picard, J., Cartier, P., Carties, Α., C.R. Soc. Biol. 1952, 146, 1488-1491. (149) Pigman, W., Cueto, H . , Baugh, D., J. Dental Res. 1964, 43, Suppl. No. 6, 1187-1195. (150) Pindborg, Ε. V., Pindborg, J. J., Plum, C. M . , Acta Pharmacol. Toxicol. 1946, 2, 302. (151) Pindborg, J. J., Oral Surg., Oral Med., Oral Pathol. 1953, 6, 780. (152) Powell, V. H . , Dale, P. O., J. Dental Res. 1943, 22, 257. (153) Ritchie, D . B., Nature 1961, 190, 456-458. (154) Rosser, H . , Boyde, Α., Stewart, A. D . G., Arch. Oral Biol. 1967, 12, 431-440. (155) Rozeik, F., Cramer, H . D., Hannover, R., Deut. Zahnaerztl. Z. 1956, 11, 1104-1109. (156) Russell, A. L., in "Environmental Variables in Oral Disease," pp. 21-39, Am. Assoc. Advan. Sci., Washington, D . C., 1966. (157) Russell, A. L., J. Dental Res. 1963, 42, 233-244. (158) Rygh, O., Bull. Soc. Chem. Biol. 1949, 31, 1052. (159) Rygh, O., Den Norske Tannloegeforeningst Idenc. 1950, 60, 1-19. (160) Rygh, O., Research 1949, 2, 443. (161) Ibid., 1950, 3, 193-194. (162) Schwarz, K., Foltz, C. M., J. Am. Chem. Soc. 1957, 79, 3292. (163) Schwarz, K., Cited in Nutr. Rev. 1958, 16, 149, 174. (164) Schwarz, K., Vitamins Hormones 1962, 20, 463-484. (165) Scott, D . B., Kaplan, H . , Wyckoff, R. W . O., J. Dental Res. 1949, 28, 31-47. (166) Scrimshaw, N. S., Taylor, C. E., Gordon, J. E . , Am. J. Med. Sci. 1959, 237, 367-403. (167) Shaw, J. Η., N.Y. State Dental J. 1950, 16, 503.

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9.

NAVIA

(168) (169) (170) (171) (172) (173) (174) (175) (176) (177) (178)

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(179) (180) (181) (182) (183) (184) (185) (186) (187) (188) (189) (190) (191) (192) (193) (194) (195) (196) (197) (198) (199) (200) (201) (202) (203) (204) (205) (206) (207) (208) (209) (210) (211)

Effect of Minerals

159

Shaw, J. H., Griffiths, D., Arch. Oral Biol. 1961, 5, 301-327. Sherman, B. S., Sobel, A. E., J. Dental Res. 1965, 44, 454. Smith, M. I., Westfall, Β. B., Public Health Repts. 1937, 52, 1375. Sognnaes, R. F., J. Nutr. 1949, 39, 147-157. Sognnaes, R. F., Shaw, J. H . , J. Dental Res. 1953, 32, 685. Sognnaes, R. F., Shaw, J. H . , J. Nutr. 1954, 53, 195-206. Soremark, R., Acta Radiol. Suppl. 1960, 190, 1. Soremark, R., Lundberg, M . , Acta Odontol. Scand. 1964, 22, 255. Soremark, R., Samsahl, K., Arch. Oral Biol. 1961, 6, 275-283. Speirs, R. L . , Caries Res. 1967, 1, 15-31. Steadman, L . T., Brudevold, F., Smith, F. Α., J. Am. Dental Assoc. 1958, 57, 340. Steadman, L . T., Brudevold, F., Smith, F. A., Gardner, D . E., Little, M . F., J. Dental Res. 1959, 33, 285-292. Stephan, R. M., Harris, M. R., J. Dental Res. 1953, 32, 708. Stookey, G. K., Muhler, J. C., J. Dental Res. 1960, 39, 671. Stookey, G. K., Roberts, R. A., Muhler, J. C., Proc. Soc. Exptl. Biol. 1962, 109, 702-706. Stralfors, A., Arch. Oral Biol. 1966, 11, 149-161. Ibid., 1966, 11, 323-328. Ibid., 1966, 11, 609-615. Ibid., 1967, 12, 1375-1385. Suga, S., Gustafson, G., Arch. Oral Biol. Suppl. 1962, 223-244. Swift, P., Brit. Dental J. 1967, 123, 326-327. Takuma, S., Katagiri, S., Ozasa, S., J. Electron Microscopy 1966, 15, 86-89. Tank, G., Storvick, C. A., J. Dental Res. 1960, 39, 473-488. Tempestini, O., Pappalardo, G., Panminerva Med. 1960, 38, 344. Thomassen, P. R., Leicester, H. M . , J. Dental Res. 1959, 38, 670. Ibid., 1964, 43, 346-352. Tipton, I. H . , Foland, W . D., Bobb, F. C., McCorble, W . C., Oak Ridge National Lab. USAEC Report CF-53-8-4, 1953. Torell, P., Odontol. Tidsk. 1956, 64, 165-183. Toth, K., Acta Med. Hung. 1954, 6, 493-500. Tousimis, A. J., Am. J. Med. Electronics 1966, 5, 15-20. Tousimis, A. J., "X-Ray Optics and X-Ray Microanalysis," pp. 539-557, Academic, New York, 1963. Van Reen, R., Ostrom, C. H . , Berzinskas, V . J., Arch. Oral Biol. 1962, 7, 351-359. Van Reen, R., Ostrom, C. A., Berzinskas, V. J., Helv. Odontol. Acta 1967, 11, 53-59. Venkataramanan, K., Krishnaswany, N . , Indian J. Med. Res. 1949, 37, 277. Von der Fehr, F., Advan. Fluorine Res. Dental Caries Prevent. 1965, 3, 83-98. Wadhwani, T. K., J. Indian Inst. Sci. 1954, 36, 64. Wentz, J., J. Dental Res. 1955, 34, 735. Wessinger, G. D., Weinmann, J. P., Am. J. Physiol. 1943, 139, 233-238. Wheatcroft, M . G., English, J. A., Schlack, C. A., J. Dental Res. 1951, 30, 523. Widdowson, E . M . , McCance, R. A., Spray, C. M . , Clin. Sci. 1951, 10, 113-118. Winiker, M . , Odontol. Rev. 1957, 8, 42. Wisotzky, J., Hein, J. W., IADR Meeting, 34th, 1956, No. 36. Wisotzky, J., Hein, J. W., J. Am. Dental Assoc. 1958, 57, 797. Wisotzky, J., Hein, J. W., J. Dental Res. 1955, 34, 735.

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160

DIETARY C H E M I C A L S VS. D E N T A L CARIES

(212) (213) (214) (215)

Ibid., 1955, 34, 768. Wynn, W., Haldi, J., J. Nutr. 1954, 54, 285-290. Wynn, W., Haldi, J., Law, M . L . , J. Dental Res. 1960, 39, 153-157. Wynn, W., Haldi, J., Law, M. L., Bentley, K. D . , J. Dental Res. 1958, 37, 33. (216) Yaeger, J. A., J. Dental Res. 1963, 42, 1178-1182. (217) Zipkin, I., "Art and Science of Dental Caries Research," pp. 29-41, Academic, New York, 1968. (218) Zipkin, I., Piez, K. A., J. Dental Res. 1950, 29, 498.

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RECEIVED October 27, 1969. Contribution Number 1118 from the Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass.

In Dietary Chemicals vs. Dental Caries; Harris, R.; Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10

Application of Chemical Agents for the Control of Dental Caries

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ROBERT C. C A L D W E L L School of Dentistry, University of California, Los Angeles, Calif. 90024 JOE P. T H O M A S School of Dentistry, University of Alabama, Birmingham, Ala. 35233

Vehicles for caries-preventive agents include dentrifices, mouthwashes, chewing gum, drinking water, cereals, flour, milk, table salt, tablets, and concentrated solutions which are applied by dentists. Many chemicals reduce dental caries in experimental animals. Those which have been subjected to clinical trials on humans include NaF, SnF , Na PO F, and other fluorides; CaHPO , anionic detergents, antibiotics, chlorophyll, urea, and vitamins. As a group, the fluorides have been most effective, and no single procedure has yet been as effective at the public health level as water fluoridation. However, several new approaches have promise. For example, topical application of acidulated sodium or stannous fluoride solutions once a year has resulted in a substantial reduction in caries, and fluoride mouthwashes prevent caries more effectively than dentifrices. 2

2

3

4

Many

approaches have been developed to reduce dental caries by chemical means; however, even the most effective procedures cannot yet be expected to eradicate the disease. A complete program of dental caries prevention includes dietary management, good oral hygiene, patient education and motivation, and early treatment of initial carious lesions, as well as the utilization of the various chemical agents. The use of a therapeutic agent is, in some instances, part of the oral hygiene technique, while in other cases it may be in the form of a dietary supplement. Very large caries reductions are possible in individuals who receive complete preventive care, but the 55-65% reduction resulting 161 Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

162

DIETARY

from water

fluoridation

remains

C H E M I C A L S

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

t h e best p r o t e c t i o n a v a i l a b l e

at t h e

p u b l i c h e a l t h l e v e l at this t i m e . T h e most effective r e g i m e f o r t h e c h e m i c a l p r e v e n t i o n of d e n t a l caries p r o b a b l y consists of a c o m b i n a t i o n of p r o c e d u r e s , i n c l u d i n g w a t e r fluoridation

or some other means of fluoride i n g e s t i o n d u r i n g c h i l d h o o d ,

p e r i o d i c a p p l i c a t i o n o f a caries-preventive

agent i n a r e l a t i v e l y h i g h

c o n c e n t r a t i o n t o the t o o t h e n a m e l surface, a n d r e g u l a r a p p l i c a t i o n o f a less c o n c e n t r a t e d booster p r e p a r a t i o n of t h e caries-preventive agent. T h e Downloaded by UNIV OF LIVERPOOL on December 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch010

t i m e i n t e r v a l r e c o m m e n d e d f o r t h e a p p l i c a t i o n o f t h e c o n c e n t r a t e d agent varies s o m e w h a t d e p e n d i n g o n t h e agent b e i n g discussed, w h i l e t h e less concentrated

booster agent is f o r m o r e f r e q u e n t use to m a i n t a i n the

c h e m i c a l at o r i n t h e e n a m e l surface b e t w e e n c o n c e n t r a t e d

applications.

C a r i e s - p r e v e n t i v e c h e m i c a l agents c a n b e i n c o r p o r a t e d i n t o a v a r i e t y of vehicles w h i c h c a n b e d i v i d e d into f o u r m a i n categories. ( 1 ) A g e n t s a p p l i e d b y t h e d e n t a l t e a m : T h e s e i n c l u d e concentrated solutions o f v a r i o u s fluorides f o r t o p i c a l a p p l i c a t i o n , p r o p h y l a x i s pastes c o n t a i n i n g fluoride, v a r i o u s fluoride gels, a n d agents a p p l i e d to i n h i b i t the g r o w t h o f d e n t a l b a c t e r i a l p l a q u e . ( 2 ) T h e r a p e u t i c agents p r e s c r i b e d f o r p e r s o n a l a p p l i c a t i o n : T h e s e i n c l u d e fluoride tablets, lozenges, d r o p s , m o u t h w a s h e s , p r o p h y l a x i s pastes. ( 3 ) P u b l i c h e a l t h measures: T h e s e i n c l u d e w a t e r fluoridation, large scale s u p e r v i s e d s e l f - a p p l i c a t i o n of fluoride-containing agents, a n d t h e use o f m i l k , t a b l e salt, b r e a d , breakfast cereals, a n d flour as vehicles f o r fluoride or other caries-preventive agents s u c h as c e r t a i n phosphates.

(4) Over-the-counter preparations: These include dentifrices, m o u t h w a s h e s , a n d c h e w i n g g u m . zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR Agents Applied by Dental Team T h e c u r r e n t status o f t o p i c a l

fluoride

solutions has b e e n r e v i e w e d

b y H o r o w i t z a n d H e i f e t z ( 4 5 ) . I n g e n e r a l , there appears to b e m e r i t i n the use o f t o p i c a l solutions a n d p r o p h y l a x i s pastes c o n t a i n i n g

fluoride

f o r t h e r e d u c t i o n of d e n t a l caries; h o w e v e r , i n spite o f 25 years of c l i n i c a l investigations i n t o v a r i o u s solutions a n d t e c h n i q u e s , n o c l e a r l y s u p e r i o r s o l u t i o n o r t e c h n i q u e to date has b e e n i d e n t i f i e d . C l i n i c a l testing m e t h ods t o d a y are r e l a t i v e l y u n r e f i n e d w h e n c o m p a r e d w i t h methods a v a i l a b l e i n the p h y s i c a l sciences. T r e a t m e n t effects, therefore, c a n b e o n l y estim a t e d grossly. D e P a o l a has a p p r o p r i a t e l y c o m m e n t e d that i n d e p e n d e n t tests of t h e same or s i m i l a r agents " f r e q u e n t l y s h o w m a r k e d differences i n t h e percentages of r e d u c t i o n i n d e n t a l caries; therefore, w e s h o u l d n o t take p e r c e n t a g e r e d u c t i o n figures too l i t e r a l l y , a n d r e d u c t i o n s f r o m one

s t u d y to another s h o u l d b e c o m p a r e d w i t h c a u t i o n "zyxwvutsrqponmlkjihgfedcbaZYX (16). T h e w e l l - k n o w n m e t h o d of t o p i c a l a p p l i c a t i o n o f s o d i u m

fluoride

to t h e e n a m e l surface d e s c r i b e d first b y B i b b y (7) has b e e n w i d e l y u s e d .

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10.

C A L D W E L L

zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents 163

A N D T H O M A S

T h e p r o c e d u r e w a s d e v e l o p e d b y K n u t s o n a n d c o w o r k e r s ( 3 0 , 3 1 , 54, 56-59),

w h o u s e d a 2 % s o d i u m fluoride s o l u t i o n w h i c h w a s a l l o w e d to

d r y o n t h e teeth f o r 3 to 5 m i n u t e s . T h e 2 % s o d i u m fluoride is a p p l i e d at 4 w e e k l y intervals w i t h a p r o p h y l a x i s b e i n g d o n e at the first a p p o i n t m e n t o n l y . T h i s series o f a p p l i c a t i o n s is r e p e a t e d at age 3, 7, 11, a n d 13.

T h e s e investigators r e p o r t e d r e d u c t i o n s i n d e n t a l caries ( D F T ) o f

39.7, 41.4, a n d 3 6 . 7 % after 1, 2, a n d 3 years, r e s p e c t i v e l y .

T h e majority

of studies u s i n g this t e c h n i q u e h a v e s h o w n d e n t a l caries i n c i d e n c e to b e

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r e d u c e d 30 to 4 0 % i n the p e r m a n e n t teeth o f c h i l d r e n r e s i d i n g i n a n area w i t h

fluoride-deficient

water.

T h e major d i s a d v a n t a g e o f this thor-

o u g h l y s t u d i e d t e c h n i q u e has been the necessity of f o u r p a t i e n t visits over a short p e r i o d o f t i m e . W i t h the a d v e n t of stannous

fluoride,

m a n y dentists s w i t c h e d to t h e

t e c h n i q u e o f M u h l e r ( 7 8 ) . T h e r e c o m m e n d e d p r o c e d u r e i n v o l v e s thoro u g h i n i t i a l p r o p h y l a x i s a n d i n t e r p r o x i m a l flossing a n d the a p p l i c a t i o n o f a fresh 8 % s o l u t i o n o f stannous

fluoride,

k e e p i n g t h e teeth m o i s t w i t h

the s o l u t i o n f o r 4 m i n u t e s . T h i s t e c h n i q u e has the a d v a n t a g e of i n v o l v i n g a s i n g l e v i s i t f o r the i n i t i a l treatment. months

to a year,

of t h e patient.

It requires r e a p p l i c a t i o n i n 6

d e p e n d i n g o n the i n d i v i d u a l

caries

susceptibility

H o r o w i t z a n d H e i f e t z ( 4 5 ) s u m m a r i z e d the extensive

c l i n i c a l investigations

o f stannous

fluoride

solutions

his associates, w h o h a v e r e p o r t e d a range r e d u c t i o n i n D M F surfaces

o f benefit

by Muhler and of 47 to 7 8 %

i n c h i l d r e n . T h i s range of benefit is also

assessed b y Stookey ( 5 1 ) at f r o m 40 to 6 0 % , w h i c h is i n excess of t h e range o f benefit r e p o r t e d f o r the 2 % N a F t e c h n i q u e . A f e w studies h a v e s h o w n negative results w i t h stannous vantages

fluoride

(47, 104, 113),

and disad-

of taste, g i n g i v a l b l a n c h i n g , i n s t a b i l i t y of aqueous

solutions,

a n d unesthetic p i g m e n t a t i o n s h a v e b e e n p o i n t e d o u t ( 5 1 ) . A c i d u l a t e d p h o s p h a t e fluoride has b e e n r e v i e w e d b y D e P a o l a

(16).

T h i s r e l a t i v e l y n e w agent consists of a s o l u t i o n of s o d i u m fluoride a d justed to p H 3 b y t h e a d d i t i o n o f 0.1 M p h o s p h o r i c a c i d . T h e s o l u t i o n contains 1.23% s o d i u m fluoride a n d , i n i n i t i a l c l i n i c a l studies, seemed to surpass agents a l r e a d y i n use (11, 81, 112).

T a b l e I i n c l u d e s representa-

t i v e d a t a s h o w i n g that at the e n d of a t w o - y e a r s t u d y a r e d u c t i o n i n d e n t a l caries ( D M F S ) of 7 0 % (112) B r u d e v o l d , i n a n i n v e s t i g a t i o n (113)

resulted. W e l l o c k , M a i t l a n d , a n d

i n w h i c h h a l f the m o u t h w a s treated

w i t h 2 % N a F a n d half w i t h acidulated phosphate

fluoride

( A P F ) , re-

p o r t e d 5 0 % f e w e r n e w carious lesions o n t h e A P F side o f the m o u t h . T h i s t e c h n i q u e w a s also m o r e successful w i t h subjects w h o m a i n t a i n e d g o o d o r a l h y g i e n e . T h e a d d i t i o n o f a c i d to stannous fluoride w a s s t u d i e d b y M u h l e r , Stookey, a n d B i x l e r (86)

w i t h g o o d results r e p o r t e d . T a b l e I

shows that M e r c e r a n d M u h l e r (74)

a n d Scola a n d O s t r u m (97) reduced

the 4 - m i n u t e stannous

fluoride

treatment

to 15 o r 30 seconds w i t h n o

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

164

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

DIETARY

C H E M I C A L S

Table I. Age Group, Years

Principal Investigator

Recent

Solution

Developments

Used

Acid Phosphate8-11 1 . 2 3 % N a F i n 0.1 M p h o s p h o r i c a c i d 2 % N a F i n 0.15 M p h o s p h o r i c a c i d 4-10 Grade School 1 0 % N a H P 0 plus 8 % S n F

W e l l o c k (112) P a m e i j e r (87) M u h l e r (86)

2

4

2

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15-30-Sec.

M e r c e r (74)

5-12

8 % S n F (4 m i n . ) 1 0 % S n F (30 sec.) S n F p r o p h y paste, t o p i c a l & d e n t i f r i c e : 4 m i n . topical 15 sec. t o p i c a l 8 % S n F 4 m i n . topical 1 0 % S n F 30 sec. t o p i c a l 2

2

S c o l a (97)

17-24

H o r o w i t z (46)

2

7-9

2

2

a p p a r e n t loss o f effectiveness. H o w e v e r , i n a n e v a l u a t i o n of a 30-second a p p l i c a t i o n o f a stannous

fluoride

solution, H o r o w i t z a n d Heifetz

h a d d i s a p p o i n t i n g results w i t h this r a p i d t e c h n i q u e .

(46)

A v e r i l l et al. (2) i n

a 2-year s t u d y o f t h e effects o f three t o p i c a l fluorides ( 2 % aqueous s o d i u m fluoride,

4%

stannous

fluoride,

a n d 2% A P F ) a p p l i e d t w i c e a n n u a l l y i n

c h i l d r e n l i v i n g i n a n o n f l u o r i d a t e d c o m m u n i t y f a i l e d to s h o w c o n c l u s i v e s u p e r i o r i t y o f a n y o n e o f these agents. Caries-reducing

c h e m i c a l agents h a v e b e e n a d d e d to p r o p h y l a x i s

pastes. T h e a d d i t i o n o f stannous fluoride a n d A P F to p r o p h y l a x i s pastes has b e e n s t u d i e d c l i n i c a l l y . A caries r e d u c t i o n of 3 4 % ( D M F S ) w i t h a stannous

fluoride

p r o p h y l a x i s paste w a s r e p o r t e d b y B i x l e r a n d M u h l e r

( 9 ) , w h i l e G i s h a n d M u h l e r (34)

have obtained about a 4 0 % reduction

( D M F S ) w i t h t h e same paste. I n this s t u d y , t h e c o m b i n e d use o f stannous fluoride paste a n d t o p i c a l stannous fluoride w a s m o r e effective t h a n paste alone.

S c o l a a n d O s t r u m ( 9 7 ) r e p o r t e d a caries r e d u c t i o n of 1 2 %

after t h e use o f a stannous fluoride p r o p h y l a x i s paste, w h i c h is p r o b a b l y n o t a significant r e d u c t i o n ; h o w e v e r , t h e paste s e e m e d to e n h a n c e the effect of a t o p i c a l s o l u t i o n a n d a stannous H o r o w i t z a n d L u c y e (48)

fluoride

dentifrice.

i n a 2-year s t u d y o f c h i l d r e n r e c e i v i n g

a n n u a l p r o p h y l a x i s w i t h the stannous

fluoride-lava

p u m i c e paste o b s e r v e d

n o p r o t e c t i o n against caries i n c i d e n c e as c o m p a r e d to controls. a n d others ( 8 9 ) s t u d i e d a n a c i d u l a t e d

fluoride-lava

Peterson

pumice prophylaxis

paste a p p l i e d a n n u a l l y i n c h i l d r e n i n c o m m u n i t i e s w i t h

fluoridated

and

others w i t h n o n f l u o r i d a t e d w a t e r s u p p l i e s , a n d r e p o r t e d m i n i m a l r e d u c t i o n i n d e n t a l caries increments. H o r o w i t z (42-44) and solution.

s t u d i e d t h e c a r i e s - r e d u c i n g effect of a n A P F g e l

A f t e r 3 years, those r e c e i v i n g a n n u a l a p p l i c a t i o n o f t h e

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

zyxwvutsrqp

10.

C A L D W E L L

165 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents

A N D T H O M A S

in Topical Fluoride Therapy Frequency of A pplication

No. in Exptl. Group

Length of Study, Years

1 per y e a r 4 X i n 2 weeks 1 application

115 77 100

2 15 m o . 9 mo.

Caries Reduction (DMFS)

Fluoride

70 50° 75

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Application

2 per y e a r 2 per y e a r 1 1 1 1 1

per per per per

year year year year

135 132

2 2

56 59

200 194 420 421

1 1 3 3

45 54 21 3.8

Compared to effect of 2% N a F .

A P F solution experienced a 24%

r e d u c t i o n i n d e n t a l caries

(DMFS)

w h i l e those r e c e i v i n g s e m i a n n u a l a p p l i c a t i o n of the A P F s o l u t i o n h a d a 4 1 % r e d u c t i o n i n caries i n c i d e n c e . T h e A P F g e l was a p p l i e d i n a w a x r e d u c t i o n as c o m p a r e d w i t h the controls.

tray a n d p r o d u c e d a 2 4 % graham and W i l l i a m s (52)

In-

e v a l u a t e d an A P F g e l a n d s o l u t i o n . A f t e r 2

years, those treated w i t h the g e l d e m o n s t r a t e d a 4 1 % effect as c o m p a r e d w i t h controls.

B e n e f i c i a l results f r o m treatment w i t h the A P F s o l u t i o n

were minimal.

B r y a n a n d W i l l i a m s (12)

reported a 28%

d e n t a l caries

r e d u c t i o n after 1 y e a r u s i n g a n A P F g e l i n a f o a m r u b b e r t r a y i n one a p p l i c a t i o n . O n e r e p o r t s h o w e d n o effect as c o m p a r e d w i t h controls of 1 a p p l i c a t i o n of A P F g e l (102).

Cons, Janerich, and Senning (15), i n a

3-year s t u d y to evaluate the c a r i e s - p r e v e n t i v e effect of f o u r t o p i c a l

flu-

o r i d e p r o c e d u r e s as c o m p a r e d w i t h controls, f o u n d that, statistically, the g r o u p treated w i t h A P F g e l e x p e r i e n c e d s i g n i f i c a n t l y f e w e r n e w carious teeth t h a n the c o n t r o l g r o u p b u t the a c t u a l difference was s m a l l . agents s t u d i e d w e r e s o d i u m fluoride, 2 % ; fluoride

s o l u t i o n , 1.23%

stannous

fluoride,

The

8%;

at p H 3; a n d an A P F fluoride g e l , also

at p H 3. T h e treatments w e r e g i v e n a n n u a l l y . T h e difference

APF 1.23%

between

the other treatments a n d the controls was not statistically significant.

The

t e c h n i q u e f o r a p p l y i n g c h e m i c a l b y the use of a n a p p l i c a t o r tray or m o u t h p i e c e w h i c h h o l d s the active agent against the e n a m e l surface w a s reported by H o r i i and Keyes Stralfors ( 9 9 )

(41).

has d e s c r i b e d a " d i s i n f e c t a n t c a p s p l i n t " c o n t a i n i n g

a t h i n l a y e r of a fine-grained p o w d e r e d d i s i n f e c t a n t s u c h as C h l o r a m i n e - T . T h e s p l i n t c o n t a i n i n g the d i s i n f e c t a n t is w o r n o v e r the teeth for 5 m i n utes, a n d Stralfors r e p o r t e d a n a l m o s t 1 0 0 %

decrease i n the n u m b e r of

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

166

DIETARY

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

s u r v i v i n g b a c t e r i a . A f t e r a b o u t 6 h o u r s t h e b a c t e r i a l count rises, a n d b y 12 hours has almost r e a c h e d t h e o r i g i n a l l e v e l .

Therapeutic

Agents Prescribed for Personal

zyxwvutsrqponmlkjihgfedcbaZY

Application

I n areas w h e r e t h e w a t e r is deficient i n fluoride s u p p l e m e n t s , v a r i o u s o t h e r f o r m s o f fluoride h a v e b e e n p r e s c r i b e d f o r systemic use. A b r i e f d i s c u s s i o n o f c e r t a i n aspects of systemic

fluoride

therapy follows. F o r

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m o r e extensive i n f o r m a t i o n , t h e r e v i e w o f B i r c h ( 8 ) is r e c o m m e n d e d . T a b l e t s u s u a l l y c o n t a i n 2.21 m g o f s o d i u m fluoride ( 1 m g F " ) , w h i c h is e q u i v a l e n t t o t h e average a m o u n t o f fluoride i n g e s t e d d a i l y f r o m w a t e r w h i c h contains 1 p p m fluoride. A p a r t f r o m A r n o l d , M c C l u r e , a n d W h i t e s s t u d y ( I ) i n w h i c h t h e b e n e f i c i a l effect o f fluoride tablets w a s e q u a t e d w i t h that o f

fluoridated

w a t e r , most studies i n d i c a t e fluoride tablets t o

b e n o m o r e t h a n h a l f as effective i n r e d u c i n g d e n t a l caries as

fluoridated

w a t e r . B i r c h states i n h i s r e v i e w that t h e r e d u c t i o n i n d e n t a l caries i n c i d e n c e i n e i g h t studies r a n g e d f r o m 12 to 8 7 % b u t that t h e use o f fluo r i d e i n tablets to r e d u c e caries i n c i d e n c e r e m a i n s to b e p r o v e d f a c t u a l l y i n l o n g - t e r m c l i n i c a l i n v e s t i g a t i o n . T h e use of fluoride i n tablets appears to h a v e great p o t e n t i a l b u t requires f u r t h e r s t u d y . M u l t i p l e v i t a m i n - f l u o r i d e tablets h a v e b e e n p r e s c r i b e d b y p h y s i c i a n s a n d dentists. H e n n o n , Stookey, a n d M u h l e r ( 3 9 ) i n 1967 r e p o r t e d o n a n i n v e s t i g a t i o n o f t h e effect o f the d a i l y use o f fluoride v i t a m i n s b y infants a n d b y c h i l d r e n u p to 5 years of age. A f t e r 48 m o n t h s , a r e d u c t i o n i n t h e p r e v a l e n c e of carious lesions o f 6 8 % ( d e f surfaces) i n p r i m a r y a n d 4 6 % (DMF

s u r f a c e s ) i n p e r m a n e n t teeth h a d r e s u l t e d .

Doherty (17) re-

v i e w e d t h e use o f d i e t a r y fluorides a n d does n o t encourage t h e use o f v i t a m i n - f l u o r i d e s because o f the n e e d to adjust t h e dose w i t h v a r y i n g w a t e r fluoride content a n d t h e n e e d f o r f u r t h e r s t u d y o n t h e effect o n p e r m a n e n t teeth.

A l s o , t h e C o m m i t t e e o n N u t r i t i o n of t h e A m e r i c a n

A c a d e m y ot P e d i a t r i c s questions the r o u t i n e a d m i n i s t r a t i o n o f v i t a m i n supplements. F l u o r i d e passes t h r o u g h the p l a c e n t a a n d is d e p o s i t e d i n t h e bones a n d teeth o f t h e d e v e l o p i n g c h i l d . T h e r e seems to b e a r e g u l a t o r y m e c h a n i s m i n v o l v e d w h i c h l i m i t s t h e a m o u n t c f fluoride t r a n s f e r r e d

because

e v e n i n areas o f e n d e m i c fluorosis one does n o t see m o t t l i n g o f p r i m a r y teeth. T h e effect o f p r e n a t a l exposure to fluoridation has b e e n r e v i e w e d b y H o r o w i t z a n d H e i f e t z ( 4 7 ) , w h o r e p o r t e d n o m e a n i n g f u l benefits to b e d e r i v e d f r o m d i e t a r y s u p p l e m e n t s of fluoride to p r e g n a n t w o m e n . T h e F o o d a n d D r u g A d m i n i s t r a t i o n i n its "Statements interpretation, oral prenatal drugs containing (29), fluoride

of g e n e r a l p o l i c y o r

fluorides

for human use"

banned marketing b y manufacturers of dietary supplements of offered to g r a v i d w o m e n f o r " p r e n a t a l d e c a y p r e v e n t i o n . "

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10.

C A L D W E L L

167 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents

A N D T H O M A S

V a r i o u s U . S . p h a r m a c e u t i c a l c o m p a n i e s a p p a r e n t l y d o n o t adhere to the dosage s c h e d u l e r e c o m m e n d e d b y the A m e r i c a n C o u n c i l o n D e n t a l Therapeutics.

T h e dosages suggested o n the labels o f different m a n u -

facturers o f fluoride tablets a n d d r o p s v a r y , as d o t h e instructions as to w h e n o r w h e n n o t to use systemic fluoride t h e r a p y .

It is n o t s u r p r i s i n g

that there s h o u l d b e some c o n f u s i o n a b o u t fluoride p r e s c r i p t i o n s because there are o v e r 4 0 different k i n d s o f fluoride tablets, lozenges, o r d r o p s on the U . S . market.

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F l u o r i d e m o u t h w a s h e s w i l l b e d i s c u s s e d a l o n g w i t h other m o u t h washes i n t h e section o n over-the-counter p r e p a r a t i o n s .

zyxwvutsrqponmlkjihgfed

Public Health Measures It has b e e n e s t a b l i s h e d b e y o n d a n y reasonable fluoridation

d o u b t that

is a h i g h l y d e s i r a b l e a n d effective p u b l i c h e a l t h

water

measure.

I n this c o u n t r y , t h e state legislature o f C o n n e c t i c u t l e d t h e w a y i n m a k i n g fluoridation

a v a i l a b l e o n a state-wide basis, a n d n o w M i n n e s o t a , I l l i n o i s ,

Delaware, M i c h i g a n , South Dakota, a n d O h i o require

fluoridation

of

p u b l i c w a t e r s u p p l i e s . S e v e r a l other states are c o n s i d e r i n g s i m i l a r legislation. I n Ireland,

fluoridation

has b e e n a p p r o v e d f o r the entire c o u n t r y .

H o p e f u l l y , these actions f o r e t e l l a n a t i o n a l

fluoridation

a c t f o r the U n i t e d

States. K n u t s o n ( 5 5 ) e s t i m a t e d that 7 0 % o f the U . S . p o p u l a t i o n n o w has access to w a t e r

fluoridation.

I n areas w h e r e the w a t e r does n o t

c o n t a i n e n o u g h fluoride, a n u m b e r o f other m e t h o d s h a v e b e e n e m p l o y e d to m a k e fluoride a v a i l a b l e o n a p u b l i c h e a l t h l e v e l .

Supervised Self- Application

of Fluoride

Agents

T h e i d e a o f large n u m b e r s o f c h i l d r e n i n s c h o o l a p p l y i n g fluoride to t h e i r o w n teeth a p p a r e n t l y o r i g i n a t e d i n S w e d e n . B e r g g r e n a n d W e l a n d e r (5)

evaluated a 1 %

solution of sodium

fluoride

w h i c h 568 c h i l d r e n

b r u s h e d o n t h e i r teeth n i n e times over a 2-year p e r i o d , a c h i e v i n g a 2 5 3 0 % r e d u c t i o n i n caries o n the u p p e r teeth. I n the past f e w years, several other studies h a v e b e e n p u b l i s h e d i n w h i c h a v a r i e t y o f solutions h a v e been used (Table I I ) .

S o d i u m fluoride also has b e e n u s e d as a 0 . 5 %

s o l u t i o n o r as 1.23% s o d i u m fluoride i n 0.1 M p h o s p h o r i c a c i d . I n the case of t h e w e a k e r s o l u t i o n , u s e d five times a year, there w a s a 2 9 % r e d u c t i o n i n caries ( D M F T ) ( 6 ) . T h e a c i d u l a t e d 1.23% s o d i u m fluoride u s e d five times a year r e s u l t e d i n a 1 5 % caries r e d u c t i o n ( D M F S ) ( 1 3 ) . G o a z et al

(37)

fluoridated phate.

o b s e r v e d a n a d d i t i o n a l 4 2 % caries r e d u c t i o n i n a c i t y w i t h water b y daily brushing w i t h 6 %

A f t e r 21 m o n t h s , G o a z et al

sodium monofluorophos-

( 3 6 ) , u s i n g a caries i n d e x n o t i n

c o m m o n use a n d h a v i n g a n u m b e r o f reversals i n diagnosis, r e p o r t e d a

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

168

DIETARY

Table II. Age Group, Years

Principal Investigator (5)

Berggren

(94)

Rosenkranz

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Goaz

8-15

(37)

6-14 (6)

Berggren

10

Hunstadbraten B u l l e n (13)

50%

12-14

(50)

7-14 6-8

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES zyxwvutsrq

C H E M I C A L S

Caries Reduction with Fluoride

Solution

Zirconium-citratefluoride ( 0 . 4 2 % N a F ) 6% Sodium monofluorophosphate 0.5% N a F

1 /d a y Unsupervised 5 /y e a r 2 /y e a r 5 /y e a r 2 /y e a r 5 /y e a r 2 /y e a r 4 /y e a r 4 - 5 /y e a r

Z i r c o n i u m fluoride ( 0 . 1 1 % F ~) F e r r i c fluoride (0.36% F - ) 1% N a F 1.23% N a F i n 0.1 M phosphoric acid

r e d u c t i o n i n rate of d e c a y .

A large-scale p r o g r a m a m o n g the m i l i w h i c h consisted of s u p e r v i s e d tooth

b r u s h i n g b y the patient w i t h a n 8 % stannous stannous

5 X 1st y r . , 4 X 2nd y r . 6 /y e a r

1% N a F

tary was r e p o r t e d b y K y e s ( 6 2 ) , a p p l i c a t i o n of 1 0 %

Frequency of Application

Used

fluoride

fluoride-lava

p u m i c e paste,

s o l u t i o n f o r 15 seconds or m o r e ,

a n d the use of a stannous fluoride d e n t i f r i c e . S c o l a (96)

reported a 5 0 %

r e d u c t i o n i n i n c r e m e n t of d e n t a l caries as c o m p a r e d to controls i n this m i l i t a r y p r o g r a m after 1 year. O t h e r studies have b e e n r e p o r t e d r e g a r d i n g the use of s e l f - a d m i n i s t e r e d stannous p h y l a c t i c paste (73, 76, 81).

fluoride-zirconium

It was estimated

(92)

silicate p r o -

that i n 1969

over

1,500,000 a p p l i c a t i o n s b y this m e t h o d w o u l d b e o c c u r r i n g . L a n g et (64)

al.

r e p o r t e d results of f o u r a p p l i c a t i o n s at 6 - m o n t h intervals of a 9 %

stannous

fluoride-zirconium

tained 9 %

m o n o s o d i u m d i h y d r o g e n phosphate.

silicate p r o p h y l a x i s paste w h i c h also c o n A reduction i n dental

caries i n c r e m e n t ( D M F S ) of about 4 0 % was n o t e d . T h e c h i l d r e n s t u d i e d resided in a

fluoridated

c o m m u n i t y . T h e a d d i t i o n of a stannous

fluoride

d e n t i f r i c e r e s u l t e d i n n o significant f u r t h e r decrease i n caries increments. E n g l a n d e r a n d others ( 2 4 ) , u s i n g a custom-fitted u p p e r a n d l o w e r m o u t h p i e c e , s t u d i e d r e p e a t e d a p p l i c a t i o n of a c i d u l a t e d a n d n e u t r a l w a t e r s o l u b l e s o d i u m fluoride gels f o r 21 months. O n e g r o u p a p p l i e d a n a c i d u lated phosphate sodium

fluoride

gel 6 minutes each school day for 2

a c a d e m i c years a n d the s e c o n d g r o u p f o l l o w e d the same p r o c e d u r e w i t h the n e u t r a l s o d i u m fluoride g e l . A t h i r d g r o u p s e r v e d as c o n t r o l . A f t e r 21 m o n t h s , o u t s t a n d i n g results of 75 a n d 8 0 %

r e d u c t i o n i n d e n t a l caries

i n c r e m e n t ( D M F surfaces) o c c u r r e d w i t h the t w o groups as c o m p a r e d

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

zyxwvutsrqpon

10.

C A L D W E L L

A N D T H O M A S

169 zyxwvutsrqp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents

Solutions Brushed on the Teeth No. in Exptl. Group

Length of Study, Years

568

2

25-30

84

1

34

96 Downloaded by UNIV OF LIVERPOOL on December 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch010

Per Cent Caries Reduction (DMFS)

14 m o .

177 174 176 162 167 170 800 235

2 2 2 2 2 2 2 2

42

Comments

M o r e effective o n u p p e r t e e t h t h a n o n lower

D r i n k i n g water fluoridated (1 p p m ) f o r 10 y r

29° 17* 17* 0° 33* 8* "Significant reduction" 15

° D M F T values. w i t h controls (23).

R e c e n t l y , the authors r e p o r t e d that 23 m o n t h s after

the treatments h a d b e e n d i s c o n t i n u e d , the c h i l d r e n a v a i l a b l e f o r reexa m i n a t i o n s t i l l r e t a i n e d the a d v a n t a g e of 55 a n d 6 3 %

fewer new D M F

surfaces t h a n the c o n t r o l c h i l d r e n . I n the s t u d y , the h i g h e r p e r c e n t a g e effect was o b t a i n e d w i t h the a c i d u l a t e d fluoride gel. M u h l e r et al.

(82)

r e p o r t e d o n the c l i n i c a l e v a l u a t i o n of p a t i e n t - a d m i n i s t e r e d stannous o r i d e z i r c o n i u m silicate p r o p h y l a c t i c paste i n c h i l d r e n i n the Islands.

flu-

Virgin

A f t e r one year, c h i l d r e n u s i n g the treatment paste c o n t a i n i n g

9 % stannous fluoride o b t a i n e d a r e d u c t i o n i n n e w D M F surfaces of 6 4 % as c o m p a r e d w i t h c h i l d r e n a p p l y i n g a p r o p h y l a x i s paste c o n t a i n i n g n o fluoride. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA

Fluoridation

of the Diet

U n t i l a l l the w a t e r s u p p l i e s w h i c h c a n b e i n this c o u n t r y h a v e b e e n s u p p l e m e n t e d w i t h

fluoridated

fluoride,

economically

fluoridation

d i e t w i l l b e of s e c o n d a r y i m p o r t a n c e to most p u b l i c h e a l t h g r o u p s . ever, e v e n w h e n a l l of the a v a i l a b l e w a t e r s u p p l i e s h a v e b e e n

of the How-

fluoridated,

a v e r y large n u m b e r of citizens i n r u r a l areas a n d i n s m a l l t o w n s s t i l l w i l l not h a v e the benefits of fluoride unless some m e t h o d other t h a n w a t e r fluoridation

is d e v i s e d . A c c o r d i n g l y , some of the studies w h i c h h a v e b e e n

c o n d u c t e d i n E u r o p e a d d i n g fluoride to the d a i l y d i e t of c h i l d r e n are of c o n s i d e r a b l e

importance.

Table

salt has b e e n

fluoridated

in

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

some

170

DIETARY

Table III. Age Group, Years

Principal Investigator

Reduction in Dental Caries Length of Study, Years

zyxwvutsrqpo

Number in Exptl. Group

214 219 131 257 190 104 M u h l e r (80) 189 2 6-18 156 Peffley (88) 10 m o . 10-19 9-16 2 189 H i l lzyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFED (40) 180 K y e s (63) 17-24 2 M u h l e r (75,77) 165 6-18 3 B i x l e r (9) 219 6-17 1 230 1.5 6-7 461 Z a c h e r l (1/4) 12 1.5 408 6-14 1 206 G i s h (54) G i s h (35) 6-14 207 1 T o r e l l (105) 2 169 10 H e l d (38) 4 66 13-17

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zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES zyxwvutsrq

C H E M I C A L S

(84) (85) (83) (79) (53)

T h o m a s (103) H o r o w i t z (49)

5-15 5-15 17-36 6-15 8-11

1 1 2 1 2

7-16 6-10

2 3

158 288

parts o f S w i t z e r l a n d , r e s u l t i n g i n a r e d u c t i o n i n d e n t a l caries. c u s s i n g these Swiss fluoride

findings,

I n dis-

E r i c s s o n ( 2 5 ) p o i n t e d o u t that too l i t t l e

was a d d e d to the salt a n d that a s u b s t a n t i a l effect o n t h e i n c i -

dence o f d e n t a l caries is possible w i t h the correct f o r m u l a t i o n . I t is gene r a l l y c o n s i d e r e d that t h e d i s t r i b u t i o n p r o b l e m i n t h e U . S . w o u l d b e too great to m a k e

fluoridated

table salt a p r a c t i c a l d e n t a l p u b l i c h e a l t h

measure. F l u o r i d a t i o n o f m i l k is a l o g i c a l i d e a because t h e d i s t r i b u t i o n o f s c h o o l m i l k is a l r e a d y i n effect i n m a n y areas.

F l u o r i d e is c o m p a t i b l e

w i t h m i l k a n d i n t h e s t u d y b y Rossoff et al. (95) fluoride

in Louisiana, 1 m g

i o n as s o d i u m fluoride w a s a d d e d b y 6 - 1 0 year o l d c h i l d r e n to

the h a l f p i n t o f m i l k c o n s u m e d d a i l y . A f t e r 3Vi years, i t a p p e a r e d that caries w a s r e d u c e d b y 7 0 % i n n e w l y e r u p t e d p e r m a n e n t teeth as c o m p a r e d w i t h teeth o f controls. T h i s i n v e s t i g a t i o n a n d others r e v i e w e d b y B i r c h (8)

p o i n t o u t the n e e d f o r f u r t h e r s t u d y o f the effectiveness

of

d i e t a r y s u p p l e m e n t w i t h fluoride i n m i l k . T h e a d d i t i o n o f caries-preventive c h e m i c a l s to flour u s e d f o r b r e a d or b a k e d goods has b e e n t h e subject of studies i n several countries. F l o u r u s e d f o r b r e a d b a k i n g is often e n r i c h e d b y C a H P 0

4

or C a C 0

3

to p r o v i d e

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10.

C A L D W E L L

A N D T H O M A S

171 zyxwvutsrqp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents

with Stannous Fluoride Dentrifices

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Per Cent Caries Reduction (DMFS) 1 yr.

2 yr.

49 36 41 23 34

34

23 57 14 1 19 1° 40 39 34 7 35 a

Comments

8 yr.

21 12 25

-

S u p e r v i s e d b r u s h i n g once d a i l y

Supervised brushing 3 X daily 15 14 19 42 39

22 -

a

Plus S n F Plus S n F 10 a n d 18 10 a n d 18 Plus S n F 0.91 p p m 2

2

2

21° Significant reduction a

p r o p h y l a x i s paste paste a n d t o p i c a l m o n t h results m o n t h results paste a n d t o p i c a l fluoride i n w a t e r

Supervised brushing 2 X daily w i t h N a F - S n F dentifrice Supervised brushing 3 X daily B r u s h i n g at home a n d school 2

17 10

30(DFS) 12

21

° Calculated from authors data. 1

a dietary calcium. With the comprehensive evidence available for a caries-protective effect of various phosphates in experimental animals, Stralfors (100) incorporated 2% C a H P 0 • 2HoO into soft bread, hard bread, wheat flour used for cooking, and sugar in a 2-year study of 2102 children, half of whom ate the phosphate-enriched bread and half of whom ate the bread without phosphate. Although caries was inhibited by 50% in the experimental group the first year and 40% the second year, evaluation was difficult since the dicalcium phosphate used contained 250 ppm fluoride the first year and only 25 ppm fluoride the second year. This made separation of the phosphate effect impossible. Since Averill and Bibby (3) and Ship and Mickelsen (98) failed to find a significant caries reduction with 2% dicalcium phosphate incorporated into bread, pastries, desserts, or sugar, it seems that this approach to caries prevention requires further study. The use of phosphates as a diet supplement to effect dental caries activity has been reviewed by Gilmore (33). The addition of fluoride to bread has been proposed from time to time. Ericsson (25) has reviewed the feasibility of this procedure and points out that in Holland there is less variation in bread consumption 4

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

172

DIETARY

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES

C H E M I C A L S

t h a n i n w a t e r c o n s u m p t i o n . L i k e w i s e , E g e ( 2 0 ) has s h o w n that i n D e n m a r k the c o n s u m p t i o n o f cereals varies less t h a n d r i n k i n g w a t e r . fore, i n these t w o countries at least, the

fluoridation

There-

o f cereals seems

feasible. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCB Over-the-counter

Preparations

D e s p i t e a l l o f the scientific a n d a d v e r t i s i n g f u r o r , n o n e o f t h e d e n t i -

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frices a v a i l a b l e at t h e present t i m e is l i k e l y to r e d u c e d e n t a l caries i n c h i l d r e n u n d e r c o n d i t i o n s o f h o m e use b y m o r e t h a n 2 5 - 3 0 % . w o u l d b e e x p e c t e d i f adults u s e d these p r o d u c t s .

Less

Volker and Caldwell

( 1 0 9 ) , W a l l a c ezyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDC (110), M a n d e l a n d C a g a n (68), Bartelstone et al. (4), a n d H i l l (40)

h a v e r e v i e w e d the e a r l y investigations o f dentifrices c o n -

t a i n i n g t h e r a p e u t i c agents f o r d e n t a l caries r e d u c t i o n . F o r t h e p u r p o s e of this p a p e r , stannous

fluoride

dentifrices w i l l b e r e v i e w e d a n d some

r e c e n t d e v e l o p m e n t s w i t h other agents w i l l b e discussed. T a b l e I I I c o n tains t h e p e r t i n e n t d a t a . T h e U n i v e r s i t y o f I n d i a n a S c h o o l o f D e n t i s t r y a n d the I n d i a n a D e p a r t m e n t o f P u b l i c H e a l t h h a v e b e e n r e s p o n s i b l e f o r the m a j o r i t y of reports d e a l i n g w i t h stannous fluoride dentifrices. U s u a l l y t h e i r results h a v e b e e n f a v o r a b l e , a l t h o u g h t w o reports are d i f f i c u l t to evaluate.

B i x l e r a n d M u h l e r ( 9 ) f o u n d n o d e n t i f r i c e effect after use o f

a stannous

fluoride

p r o p h y paste b u t they o b s e r v e d a 4 0 %

effect f o l l o w i n g stannous

fluoride

t o p i c a l . T h i s contrasts w i t h G i s h a n d M u h l e r ' s (34) no d e n t i f r i c e effect w i t h stannous fluoride

topical.

dentifrice

p r o p h y paste a n d stannous fluoride

finding

fluoride

of little o r

p r o p h y paste a n d stannous

A p a r t f r o m f a v o r a b l e results f r o m t h e m a n y

Indiana

studies, J o r d a n a n d Peterson ( 5 3 ) , H i l l ( 4 0 ) , K y e s , O v e r t o n , a n d M c K e a n (63) h a v e h a d n e g a t i v e results i n studies o f u n s u p e r v i s e d b r u s h i n g , w h i l e

T o r e l l a n d E r i c s s o n ( 1 0 5 ) h a v e o b t a i n e d about a 2 5 % r e d u c t i o n , Z a c h e r l a n d M c P h a i l (114)

a 4 2 % r e d u c t i o n , a n d T h o m a s a n d J a m i s o n (103)

a

3 0 % r e d u c t i o n w h e n t h e teeth w e r e b r u s h e d three times d a i l y . H e l d a n d S p i r g i (38)

i n a study of a N a F - S n F

2

d e n t i f r i c e also h a v e o b s e r v e d a

significant r e d u c t i o n i n caries. A n i n t e r e s t i n g series o f papers o n fluoride d e n t i f r i c e trials a p p e a r e d i n t h e British

Dental Journal

v o l v i n g stannous

fluoride

(10).

F i v e studies w e r e d e s c r i b e d , a l l i n -

dentifrices.

abrasive w a s i n s o l u b l e m e t a p h o s p h a t e .

I n some

studies, t h e d e n t i f r i c e

I n one o f t h e studies, a s o d i u m

m o n o f l u o r o p h o s p h a t e w a s also e v a l u a t e d .

T h e s e w e l l p l a n n e d a n d exe-

c u t e d studies w e r e c a r r i e d o u t u n d e r rigorous c o n d i t i o n s i n v o l v i n g use of t h e d o u b l e b l i n d t e c h n i q u e w i t h a d e q u a t e s a m p l e sizes f o l l o w e d l o n g e n o u g h to demonstrate r e a l differences b e t w e e n g r o u p s .

S o m e general

conclusions c a m e o u t o f t h e five studies. F i r s t , a p p a r e n t l y t h e e a r l y p r o b lem

of i n c o m p a t i b i l i t y b e t w e e n the abrasive i n the d e n t i f r i c e a n d t h e

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10.

C A L D W E L L

A N D T H O M A S

Table IV.

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Type of Active Ingredient

173 zyxwvutsrqp zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG Application of Chemical Agents

Therapeutic Dentrifices for Dental Caries

Mechanism of Action

Chemical Agents Used

General Conclusions about Effectiveness

Detergent

Antienzyme

Urea

Buffering, Dibasic ammonium protein phosphate denaturation Urea

Ineffective i n the low concentrations used

Antibiotic

Antibacterial

Penicillin Tyrothrycin

D o u b t f u l if s u i t a b l e for general use

Fluoride

Antienzyme, decreased enamel dissolution, increased remineralization

A m i n e fluoride S o d i u m fluoride Sodium monofluorophosphate S t a n n o u s fluoride

L i m i t e d effect

Surfacecoating agent

Reduced adhesion of food a n d bacteria to enamel

Tetradecylamine

Ineffective

S o d i u m dehydroacetate L i m i t e d effect S o d i u m l a u r o y l sarcosinate possible; v a r i able results

l a r g e l y o v e r c o m e , a n d stable

products w i t h

fluoride

has b e e n

fluorides

are n o w a v a i l a b l e . S e c o n d , i n a l l five studies, stannous

dentifrices c a u s e d s t a i n i n g of the teeth.

active fluoride

I n one report, the increase i n

s t a i n i n g was d e s c r i b e d as a t r e m e n d o u s increase i n b r o w n stain. u n d e s i r a b l e effect of stannous

fluoride

This

d e n t i f r i c e s indicates that n o n - t i n -

c o n t a i n i n g dentifrices seem to h o l d m o r e p r o m i s e for f u t u r e s t u d y a n d use.

A s o d i u m m o n o f l u o r o p h o s p h a t e d e n t i f r i c e was s l i g h t l y , a l t h o u g h

not s i g n i f i c a n t l y , m o r e effective t h a n stannous fluoride d e n t i f r i c e a n d d i d not stain the teeth.

In a previous study b y F i n n and Jamison (27)

in

the U . S . , i t w a s s h o w n that m o n o f l u o r o p h o s p h a t e was m o r e effective t h a n a stannous fluoride d e n t i f r i c e . A t h i r d finding i n the B r i t i s h studies was that girls benefitted m o r e f r o m the use of the t h e r a p e u t i c d e n t i f r i c e s t h a n b o y s , p r o b a b l y because of t h e i r better o r a l h y g i e n e habits.

It is some-

w h a t d i s a p p o i n t i n g to observe that l i t t l e i m p r o v e m e n t i n o r a l h y g i e n e h a d r e s u l t e d at the e n d of a 3-year p r o g r a m of o r a l h y g i e n e i n s t r u c t i o n a n d r e g u l a r t o o t h b r u s h i n g . T h e r e d u c t i o n i n caries r e p o r t e d r a n g e d f r o m n o r e d u c t i o n i n caries to 3 6 %

r e d u c t i o n i n p r o x i m a l caries of posterior

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

174

zyxwvutsrqponmlkjihgfedcb VS. D E N T A L CARIES zyxwvutsrq

D I E T A R Y

C H E M I C A L S

Table V . Age Group j Years

Principal Investigator

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Reduction in Dental Caries

Solution

W e i s z (111)

5-6 8-9

0.25% 0.25%

T o r e l l (106)

8-9

0.2% N a F 0.2% K F

L u n d s t a m (67)

7-15

0.2%

10

T o r e l l (105) M c C o r m i c k (72)

t o o t h surfaces.

Used

NaF NaF

NaF

0.05% N a F 0.2% N a F C a , P 0 , F " (3 p p m ) F ~ (3 p p m ) F ~ (40 p p m )

6-8

4

W h e n t h e D M F S i n d e x w a s u s e d , t h e r e d u c t i o n i n caries

w a s m a r g i n a l . O n l y b y m a k i n g s p e c i a l c o m p u t a t i o n s o n teeth w h i c h h a d e r u p t e d d u r i n g t h e s t u d y c o u l d t h e observers detect a n y s u b s t a n t i a l effect of t h e fluoride d e n t i f r i c e . T h e s e B r i t i s h studies t e n d t o c o n f i r m t h e o p i n i o n c o n c e r n i n g stannous

fluoride

effect i n r e d u c i n g d e n t a l caries.

d e n t i f r i c e s that t h e y h a v e a m a r g i n a l D u c k w o r t h (19)

reviewed

fluoride

d e n t i f r i c e s , i n p a r t i c u l a r trials i n the U n i t e d K i n g d o m , a n d c o n c l u d e d that dentifrices c o n t a i n i n g stannous fluoride h a d a s m a l l b u t u s e f u l role i n t h e p r e v e n t i o n o f d e n t a l caries i n teen-age s c h o o l c h i l d r e n . T h e greater benefits

s h o w n b y girls d e m o n s t r a t e d

that p r e v e n t i o n d e p e n d s u p o n

conscientious use. T a b l e I V s u m m a r i z e s i n a v e r y g e n e r a l w a y t h e c u r r e n t status o f t h e v a r i o u s dentifrices w h i c h h a v e b e e n f o r m u l a t e d to p r e v e n t d e n t a l caries. T h e most effective dentifrices c o n t a i n

fluoride

i n some f o r m , b u t e v e n

these h a v e a l i m i t e d a b i l i t y to p r o t e c t against d e n t a l caries. S o m e studies h a v e b e e n d e s i g n e d to p r o v i d e a m o r e stable d e n t i f r i c e f o r m u l a t i o n b y u s i n g either n o n - c a l c i u m - c o n t a i n i n g abrasives o r other t h a n stannous

fluoride.

M a n l y (69)

fluorides

a n d E r i c s s o n (24) h a v e d r a w n

a t t e n t i o n t o t h e p r o b l e m of t i n a n d fluoride r e a c t i n g w i t h t h e a b r a s i v e , w h i c h , as m e n t i o n e d earlier, w a s a p r o b l e m w i t h e a r l i e r stannous dentifrices.

fluoride

Dentifrices c a n vary w i d e l y i n the compatibility of the i n -

gredients, m a k i n g i t d i f f i c u l t to c o m p a r e the effectiveness

o f different

d e n t i f r i c e s o r e v e n t h e same d e n t i f r i c e f r o m t i m e to t i m e w h e n s l i g h t modifications i n the f o r m u l a have been made. A n a m i n e fluoride d e n t i f r i c e has b e e n d e v e l o p e d i n S w i t z e r l a n d

(71),

the r a t i o n a l e f o r t h e a m i n e fluoride b e i n g that i t has a n t i e n z y m e a c t i o n a n d is r e t a i n e d better o n t h e e n a m e l surface t h a n other fluorides. M a r -

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

zyxwvutsrqpo

10.

C A L D W E L L

A N D T H O M A S

Application of Chemical Agents 175 zyx zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHG

with Fluoride Mouthwashes

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No. in Exptl. Group

21 11

10 4

912 520

1 1

1 /t w o weeks

2400

1 /d a y 1 /t w o weeks

160 172

1 /d a y 1 /d a y 1 /d a y

Length of Study, Years

90 90 90

S i g n i f i c a n t decrease i n a n t e r i o r p r o x i m a l caries

9 mo.

36

2 2

49 21 45* 0 23*

30 m o . 30 m o . 30 m o .

° Reduction calculated for mesial surfaces of 6-year molar. No effect on occlusal surfaces.

thaler (70)

r e p o r t e d caries i n h i b i t i o n after 7 years of u n s u p e r v i s e d use

of a n a m i n e d e n t i f r i c e .

T h e d e n t i f r i c e c o n t a i n i n g the a m i n e

fluorides

i n h i b i t e d n e w carious lesions b y 3 2 % b a s e d o n n e w D F surfaces. p r o m i s i n g results w e r e o b t a i n e d b y L u d w i g (66)

Less

w i t h a tetradecylamine

d e n t i f r i c e . T h e i d e a of r e d u c i n g f o o d a n d b a c t e r i a l p l a q u e r e t e n t i o n o n the t o o t h surface is l o g i c a l , b u t so f a r n o effective m e t h o d has b e e n d e v i s e d f o r a c h i e v i n g this w i t h a d e n t i f r i c e . It is a m u s i n g to n o t i c e i n H e l d a n d S p i r g i s (38)

a r t i c l e that the n a m e

of one of the dentifrices tested w a s D r a b — a n a m e h a r d l y l i k e l y to excite the U . S . a d v e r t i s i n g c o m m u n i t y . M o u t h w a s h e s h a v e b e e n p o p u l a r f o r centuries because of t h e i r ref r e s h i n g p r o p e r t i e s a n d a b i l i t y to mask m o u t h o d o r . H o w e v e r , n o t u n t i l r e c e n t l y h a v e t r u l y t h e r a p e u t i c m o u t h w a s h e s b e e n f o r m u l a t e d to p r e v e n t d e n t a l caries.

F o r several years, W e i s z (111)

has c l a i m e d that c h i l d r e n

i n his p r a c t i c e h a v e v e r y h i g h resistance to caries w h e n a n 0 . 2 5 %

NaF

m o u t h w a s h is u s e d t w i c e d a i l y . T a b l e V s u m m a r i z e s some of the a v a i l a b l e studies o n fluoride m o u t h w a s h e s . It c a n b e seen f r o m T a b l e V that fluoride

m o u t h w a s h e s offer definite possibilities f o r c o n t r o l l i n g d e n t a l

caries. It is n o t k n o w n w h e t h e r or not these benefits w o u l d b e a d d i t i o n a l to other m e t h o d s of caries c o n t r o l s u c h as t o p i c a l

fluoride

or

fluoride

pastes a p p l i e d b y the dentist, b u t it is q u i t e possible that m o u t h w a s h e s w i l l p r o v e to b e m o r e effective t h a n dentifrices i n r e d u c i n g d e n t a l caries. T h e s i m p l e fact is that n o i n c o m p a t i b l e or i n a c t i v a t i n g agents s u c h as a n a b r a s i v e or b i n d e r n e e d b e i n c l u d e d i n a m o u t h w a s h . A n a p p r a i s a l of T a b l e V indicates that t w o factors i n f l u e n c e the results, the f r e q u e n c y of

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

176

DIETARY

m o u t h w a s h i n g a n d the s t r e n g t h of the

zyxwvutsrqponmlkjihgfedcbaZYX VS. D E N T A L CARIES

C H E M I C A L S

fluoride

solution. A l t h o u g h an

e d i t o r i a l c o m m e n t w h i c h a c c o m p a n i e d one of W e i s z ' s paperszyxwvutsrqponmlkjihgfedcba (111) suggested that a n 0.25%

N a F m o u t h w a s h is too c o n c e n t r a t e d f o r safe h o m e

use, as a p r a c t i c a l matter, n o p r o b l e m s seem to h a v e b e e n b y W e i s z o r other investigators.

encountered

C e r t a i n l y , the d a i l y use of 0.05%

as s t u d i e d b y T o r e l l a n d E r i c s s o n (105)

I n c o m p a r i n g v a r i o u s p r o c e d u r e s , T o r e l l a n d E r i c s s o n (105) a d a i l y m o u t h w a s h of 0.05%

found

N a F was m o r e effective t h a n a 2 %

m o u t h w a s h u s e d once e v e r y 2 weeks. Downloaded by UNIV OF LIVERPOOL on December 19, 2016 | http://pubs.acs.org Publication Date: June 1, 1970 | doi: 10.1021/ba-1970-0094.ch010

NaF

is v e r y safe. NaF

L i k e w i s e , the m o u t h w a s h w a s

m o r e effective t h a n the s t a n d a r d techniques f o r t o p i c a l 2 % N a F or 1 0 % S n F , o r dentifrices c o n t a i n i n g stannous 2

fluoride,

p h o s p h a t e . F j a e s t a d - S e g e r a n d others (28) w i t h 0.2%

or s o d i u m m o n o f l u o r o -

r e p o r t e d that a w e e k l y rinse

n e u t r a l s o d i u m fluoride or a n i r o n

fluoride

solution showed

a significant caries r e d u c t i o n i n c h i l d r e n . T o r e l l a n d S i b e r t (106) m o n t h l y s u p e r v i s e d r i n s i n g of a 0 . 2 %

studied

s o d i u m fluoride s o l u t i o n a m o n g

s c h o o l c h i l d r e n . A s i n the case of the other S w e d i s h s t u d y ( 2 8 ) ,

the

effect was expressed as percentage of c h i l d r e n r e c e i v i n g n e w restorations after one year. U s i n g this less precise assessment, 13 to 2 7 % f e w e r c h i l d r e n r e c e i v e d care after one year. S w e r d l o f f a n d S h a n n o n (101), i n g the f e a s i b i l i t y of the use of a stannous 0.4%

fluoride

study-

mouthwash daily

i n a s c h o o l p r e v e n t i v e d e n t i s t r y p r o g r a m , w e r e a b l e to r e p o r t a

30.5%

r e d u c t i o n i n n e w carious surfaces after o n l y 5 m o n t h s . T h i s t i m e p e r i o d a n d the s m a l l n u m b e r of subjects s t u d i e d m a d e the results not significant other t h a n to l e n d s u p p o r t to the other studies q u o t e d . A n e w d e v e l o p m e n t is the use of a ' r e m i n e r a l i z i n g " m o u t h w a s h . T h e rationale f o r this m o u t h w a s h is b a s e d o n the e v i d e n c e of K o u l o u r i d e s , C u e t o , a n d P i g m a n (60)

a n d K o u l o u r i d e s a n d R e e d (63)

that softened

e n a m e l c a n b e r e h a r d e n e d b y solutions of c a l c i u m a n d p h o s p h o r u s a n d that the process is accelerated b y s m a l l amounts of fluoride. M c C o r m i c k a n d K o u l o u r i d e s (72)

r e p o r t e d that the r e m i n e r a l i z i n g m o u t h w a s h is

c a p a b l e of r e d u c i n g caries o n the m e s i a l surface of the first m o l a r b y 4 5 % . T h e use of c h e w i n g g u m as a v e h i c l e for caries-preventive c o m p o u n d s predates several of the other methods d e s c r i b e d i n this p a p e r .

A good

r e v i e w of the subject has b e e n p u b l i s h e d b y R i c h a r d s o n a n d C a s t a l d i (93).

T a b l e V I s u m m a r i z e s the effect of c h e w i n g g u m o n d e n t a l caries.

T h e first fact w h i c h s h o u l d b e m e n t i o n e d is that i n n o p u b l i s h e d s t u d y h a v e g u m chewers h a d m o r e caries t h a n n o n c h e w e r s . A c t u a l l y , as s h o w n b y D r e i z e n a n d Spies ( 1 8 ) , V o l k e r ( 1 0 8 ) , a n d T o t o , R a p p , a n d O ' M a l l e y ( 1 0 7 ) , o r d i n a r y c h e w i n g g u m seems n e i t h e r to cause n o r p r e v e n t d e n t a l caries. P r o m i s i n g results b y i n c o r p o r a t i n g v i t a m i n K , F u r a d o x y l ( a n i t r o f u r a n ) , or c h l o r o p h y l l i n g u m h a v e b e e n r e p o r t e d b u t none of these has b e e n f o l l o w e d u p . I n a c o u n t r y s u c h as the U . S . A . , w h e r e c h e w i n g g u m is w i d e l y u s e d , this a p p r o a c h has u n t a p p e d p o t e n t i a l .

It has b e e n re-

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

10.

CALDWELL AND THOMAS Table VI.

Effect of Chewing Gum on Dental Caries

Principal Type of Investigator Gum Additive Burrill (14) Dreizen (18) Gerke (32)

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L i n d (65)

177

Application of Chemical Agents

Synthetic vit. Κ Furadoxyl Chlorophyll

Number in Exptl Type of Group Subjects 55 30 102 229

Burrill (14)

Potassium fluoride None

Volker (108) Dreizen (18) Toto (107)

None None None

50 25 275

45

Dental students Age 6-38 Adults (bakers) Age 11 Dental students Age 18-32 Age 8-35 Primary school

Duration of Study

Caries Reduction

18 mo.

60-90%

12 mo. 12 mo. 12 mo.

80% 20% (approx.) None

18 mo.

13-80%

18 mo. 12 mo. 12 mo.

None None None

ported that fluoride or dicalcium phosphate can be released from a gum while chewing (21, 90, 91). In a clinical study of phosphate-containing chewing gum (27), F i n n and Jamison demonstrated reduction of caries incidence in children after a 2-year period of 39.7 to 52.9% considering proximal surfaces of teeth only. Literature Cited (1) Arnold, F. Α., McClure, F . J., White, C. L., Dental Progr. 1960, 1, 8. (2) Averill, H . M . , Averill, J. E., Ritz, A. G., Little, M . F., Am. J. Public Health 1967, 57, 1627. (3) Averill, Η. M . , Bibby, B. G., J. Dental Res. 1964, 43, 1150. (4) Bartelstone, H . J., Mandel, I. D., Chilton, N. W., Ν. Y. Dental J. 1962, 28, 147. (5) Berggren, H . , Welander, E., Acta Odontol. Scand. 1960, 18, 209. (6) Ibid., 1964, 22, 401. (7) Bibby, B. G., Tufts Dental Outlook 1942, 15, 4. (8) Birch, R. C., J. Public Health Dentistry 1969, 29, 170. (9) Bixler, D., Muhler, J. C., J. Am. Dental Assoc. 1964, 68, 792. (10) Brit. Dental J. 1967, 123 (1). (11) Brudevold, F., Gron, P., Spinelli, M . , Trantz, O., Arch. Oral Biol. 1963, 8, 167. (12) Bryan, E . T., Williams, J. E . , J. Public Health Dentistry 1968, 28, 182. (13) Bullen, D . C. T., McCombie, F., Hole, L. S., J. Can. Dental Assoc. 1966, 32, 89. (14) Burrill, D . Y., Calandra, J. C., Tilden, Ε. B., Fosdick, L . S., J. Dental Res. 1945, 24, 273. (15) Cons, N . C., Janerich, D . T., Senning, R. S., J. Am. Dental Assoc. 1970, 80, 777. (16) De Paola, P. F., J. Am. Coll. Dentists 1968, 35, 22. (17) Doherty, J. M . , Wis. Med. J. 1968, 67, 599. (18) Dreizen, S., Spies, T. D., J. Am. Dental Assoc. 1951, 43, 147. (19) Duckworth, R., Brit. Dental J. 1968, 124, 505.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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178

DIETARY CHEMICALS VS. DENTAL CARIES

(20) Ege, R., Tandlaegebladet 1961, 65, 445. (21) Emslie, R. D., Veall, N . , Duckworth, R., Brit.Dental J. 1961, 110, 121. (22) Englander, H . R., Carlos, J. P., Senning, R. S., et al., J. Am. Dental Assoc. 1969, 78, 783. (23) Englander, H . R., Keyes, P. H . , Gestwicki, M., Schultz, Η. Α.,J.Am. Dental Assoc. 1967, 75, 638. (24) Ericsson, Y., in "Caries Symposium Zurich," H . Muhlemann, Ed., Hans Huber, Berne, 1961. (25) Ericsson, Y., in "Nutrition and Caries Prevention," G. Blix, Ed., Almqvist and Wiksells, Uppsala, 1965. (26) Finn, S. B., Jamison, H . C., J. Dental Assoc. 1967, 74, 987. (27) Finn, S. B., Jamison, H . C., J. Dentistry Children 1963, 30, 17. (28) Fjaestad-Seger, M . , Norstedt-Larsson, K., Torell, P., Sveriges Tandlakarforb Tindn 1961, 53, 169. (29) Food and Drug Administration, Federal Register 1966, Oct. 20. (30) Galagan, D. J., Knutson, J. W., Public Health Rept. 1947, 62, 1477. (31) Ibid., 1948, 63, 1215. (32) Gerke, J., Klimt, W., Zahnnaerztl. Rundschau 1955, 64, 499. (33) Gilmore, N. D., J. Public Health Dentistry 1969, 29, 88. (34) Gish, C. W., Muhler, J. C., J. Am. Dental Assoc. 1965, 70, 914. (35) Gish, C. W., Muhler, J. C., Stookey, G. K., J. Am. Dental Assoc. 1965, 71, 60. (36) Goaz, P. W., McElwaine, L . P., Biswell, Η. Α., et al., J. Dental Res. 1966, 45, 286. (37) Goaz, P. W., McElwaine, L. P., Biswell, Η. Α., White, W . E., J. Dental Res. 1963, 42, 965. (38) Held, A. J., Spirgi, M . , Schweiz. Montsschr. Zahnheilk. 1965, 75, 883. (39) Hennon, D . K., Stookey, G. K., Muhler, J. C., J. Dentistry Children 1967, 34, 439. (40) Hill, T. J., J. Am. Dental Assoc. 1959, 59, 1121. (41) Horii, Α. Α., Keyes, P. H . , J. Dental Res. 1964, 43, 152. (42) Horowitz, H . S., IADR Program and Abstracts of Papers, No. 549, March 1969. (43) Horowitz, H . S., J. Am. Dental Assoc. 1969, 78, 568. (44) Horowitz, H. S., J. Oral Therap. 1968 (Jan.), 4, 286. (45) Horowitz, H . S., Heifetz, S. B.,J.Am. Dental Assoc. 1970, 81, 166. (46) Horowitz, H . S., Heifetz, S. B.,J.Dentistry Children 1969, 36, 355. (47) Horowitz, H. S., Heifetz, S. B., Public Health Rept. 1967, 82, 297. (48) Horowitz, H . S., Lucye, H . S., J. Oral Therap. 1966 (July), 3, 17. (49) Horowitz, H . S., Thompson, M . B., J. Am. Dental Assoc. 1967, 74, 979. (50) Hunsfadbraten, V. K., Dent. Zahnaerztl. Z. 1965, 20, 336. (51) "Improving dental practise through preventive measures," Ch. 5, p. 110, J. L . Bernier and J. C. Muhler, Eds., C. V . Mosby Co., St. Louis, 1966. (52) Ingraham, R. Q., Williams, J. E . , J. Tenn. Dental Assoc. 1970 (Jan.), 50, 5. (53) Jordan, W. Α., Peterson, J. K.,J.Am. Dental Assoc. 1959, 58, 42. (54) Knutson, J. W., J. Am. Dental Assoc. 1948, 36, 37. (55) Ibid., 1970, 80, 765. (56) Knutson, J. W., Armstrong, W. D., Public Health Rept. 1943, 58, 1701. (57) Ibid., 1945, 60, 1085. (58) Ibid., 1946, 61, 1685. (59) Knutson, J. W., Armstrong, W. D., Feldman, F . M., Public Health Rept. 1947, 62, 425. (60) Koulourides, T., Cueto, H . , Pigman, W., Nature 1961, 189, 226. (61) Koulourides, T., Reed, J. L., Arch. Oral Biol. 1964, 9, 585. (62) Kyes, F .M.,J. Oral Therap. 1967, 3, 359.

Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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10.

CALDWELL AND THOMAS

Application of Chemical Agents

179

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Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.

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Harris; Dietary Chemicals vs. Dental Caries Advances in Chemistry; American Chemical Society: Washington, DC, 1970.