Milk and Dairy Foods: Their Functionality in Human Health and Disease [1 ed.] 0128156031, 9780128156032

Table of contents :
Cover
Milk and Dairy Foods:
Their Functionality in Human Health
and Disease
Copyright
Contributors
About the editor
Foreword Persistence: The nature of milk
Preface
Acknowledgements
1
Dairy consumption and cardiometabolic diseases: Evidence from prospective studies
Introduction
Types of dairy foods defined
Dairy consumption in the world
Nutrients context
Epidemiological studies
General principles
Dose-response metaanalyses techniques
Current state of evidence on dairy foods and cardiometabolic diseases
Prospective studies on dairy foods and type 2 diabetes
Prospective studies on dairy foods and coronary heart disease
Prospective studies on dairy foods and stroke
Prospective studies on dairy foods and mortality
Prospective studies on dairy foods in healthy populations vs patients
Mechanisms
Food matrix effects
Summary and conclusions
Conflict of interest
References
2
Dairy fats and health
Introduction
Effects of saturated fat consumption
Dairy consumption and cardiometabolic disease
Evidence from prospective cohort studies
Evidence from measurements of blood pressure and haemodynamics
Food matrix effects of dairy products on blood lipids
Effects of milk proteins on blood lipids
Substitution of dietary saturated fatty acids with unsaturated fatty acids
Partial replacement of saturated fatty acids in milk fat by modifying the diet of the dairy cow
Does replacing saturated fatty acids in dairy products provide health benefits?
Conclusions
Conflict of interest
References
Further reading
3
Does modifying dairy fat composition by changing the diet of the dairy cow provide health benefits?
Introduction
Health issues associated with dairy fatty acids
12:0, 14:0, 16:0, and CVD risk
Monounsaturated and polyunsaturated fatty acids
Ruminant trans fatty acids (differences with industrial trans fatty acids)
Conjugated linoleic acids
Altering dairy fat composition
Changing the saturated fatty acid (12:0, 14:0, 16:0) concentrations
Changing 18:0 concentration
Increasing all cis unsaturated fatty acids
Increasing conjugated linoleic acid and trans-vaccenic acid
Undesirable effects of using unsaturated oil sources in dairy cow diets
Human intervention studies involving modified dairy fats
Reduced saturated fatty acid/increased unsaturated fatty acid proportion in dairy products
Increased conjugated linoleic acid proportion in dairy products
Future work
Dairy matrix-Working with other milk constituents to maximise beneficial impact
References
4
Trans and conjugated fatty acids in dairy products: Cause for concern?
Introduction
Trans isomer distribution in milk fat depends on the production system
Isomers of conjugated linoleic acid
Metabolism of trans-fatty acid isomers
Recommendations and limits of intake
General pathophysiological effects of trans-fatty acids
Physiological and biochemical effects of vaccenic acid
Results from human intervention studies and meta-analyses for cardiovascular diseases
Trans-fatty acids and their impact on cardiovascular disease risk
Association of circulating trans-fatty acids and cardiovascular risk: Evidence from observational studies
Association of circulating trans-fatty acids and cardiovascular risk: Evidence from case-control studies
Trans-fatty acids and cardiovascular risk: Evidence from randomised controlled trials
Effects of dietary interventions with ruminant-derived trans-fatty acids on plasma lipids: Evidence from randomise ...
Trans-fatty acids and their impact on cardiovascular disease risk factors: Evidence from meta-analyses
Trans-fatty acids and their impact on cardiovascular disease outcomes and mortality: Evidence from meta-analyses
Trans-fatty acids, insulin resistance, and incidence of type 2 diabetes mellitus
Overall conclusions
References
Internet
5
Organic milk: Does it confer health benefits?
Introduction
The development of the organic milk production
Current organic milk market and drivers for growth
The aim of this review
Organic production - Principles and standards
Organic standards and production intensity on dairy farms
The impact of dairy management on milk composition
Effect of organic management practices on milk fatty acid profile
Origin of fatty acids in the milk
Effect of organic management practices on milk fatty acid profile
Effect of organic management practices on milk vitamin and mineral profile
Switching to organic milk: Differences to the intakes of nutrients
Other evidence on health implications of organic food, including milk and dairy
Conclusions
References
Further reading
6
Milk proteins: Their role in cardiovascular health
Introduction
Cardiovascular diseases mortality, incidence, and prevalence data
Blood pressure and vascular dysfunction: Holistic markers of cardiovascular diseases
Milk protein bioavailability
Impact of milk proteins consumption on blood pressure
Impact of milk proteins consumption on vascular function
Impact of milk protein consumption on lipid metabolism
Impact of milk protein consumption on inflammation and oxidative stress
Conclusions and future recommendations
References
7
Dairy products and diabetes: Role of protein on glycaemic control
Introduction
Dietary patterns and dietary approaches to manage type 2 diabetes
Dairy products and diabetes: Overview of the evidence
Dairy products and glycaemic regulation
Dairy protein and glycaemic regulation
Amino acids
Whey and casein proteins
Bioactive peptides
Gastrointestinal hormones
Conclusions
References
8
The dairy food matrix: What it is and what it does
Introduction
The concept of the food matrix
Food matrix effects
Dairy food matrices are unique
Protein network/macrostructure
Bioactive components
Studying the health effects of the dairy matrix
Factors related to cardiovascular disease risk: Randomised controlled trials comparing whole dairy foods to dairy ...
Bone health: Randomised controlled trials comparing whole dairy foods to dairy constituents
Cheese as an example of dairy food matrix effects
Summary and conclusions
References
9
The role of dairy products in the development of obesity across the lifespan
Introduction
Markers of obesity risk
Burden of obesity in children and adults (worldwide prevalence and projections)
Diversity in nutritional composition/characteristics of different types of dairy products
Methodology
Evidence from systematic reviews and metaanalyses in adults and children
Evidence from longitudinal and randomised controlled trial studies in children and adolescents not in metaanalyses
Evidence from longitudinal observational studies in adults and older adults
Dairy consumption and risk of developing overweight/obesity in adults and older adults
Longitudinal association between specific types of dairy products and dietary calcium and obesity measures in adul ...
Evidence from human intervention trials on the effects of dairy and type of dairy on body composition in adults and ...
Evidence from intervention studies without energy restriction
Evidence from intervention studies with energy restriction
Putative mechanisms underlying the impact of milk nutrients on obesity and energy balance
Conclusions and future recommendations
References
10
Adverse reactions to cow's milk
Overview
Food allergy: The immune response
Innate immune response
Adaptive immune response
Immune tolerance
Cow's milk allergy
IgE-mediated cow's milk allergy
Mechanisms of IgE-mediated cow's milk allergy
Symptoms of IgE-mediated cow's milk allergy
Diagnosis of IgE-mediated cow's milk allergy
Management of IgE-mediated cow's milk allergy
Prognosis of IgE-mediated cow's milk allergy
Non-IgE-mediated cow's milk allergy
Mechanisms of non-IgE-mediated cow's milk allergy
Symptoms of non-IgE-mediated cow's milk allergy
Diagnosis of non-IgE-mediated cow's milk allergy
Management of non-IgE-mediated cow's milk allergy
Prognosis of non-IgE-mediated cow's milk allergy
Milk intolerance
Lactose intolerance
Mechanism of lactose intolerance
Symptoms of lactose intolerance
Diagnosis of lactose intolerance
Management of lactose intolerance
Conclusions
References
Further reading
11
Dairy foods and bone accrual during growth and development
Important concepts in bone health
Bone turnover and bone mass
Important limitations and considerations in using bone mineral density measurements
Osteoporosis: A life course disease?
Fracture epidemiology
Sex differences in bone growth and development in early life
Dairy-associated nutrients and skeletal growth: Focus on protein and calcium
Dairy as a source of protein and calcium in the diet
Is the recommended intake for calcium achievable without dairy foods?
Protein malnutrition and skeletal growth
Calcium insufficiency and bone growth
Dietary magnesium intakes and association with bone status during growth
Dairy food consumption and bone growth: Data from randomised trials
Compliance
Baseline calcium intakes
Varying maturity levels of participants
Study drop-outs
Potential mechanisms of action of dairy on bone
Dairy intervention study design
Dairy consumption and fracture risk during growth
Conclusions
Conflicts of interest
References
12
Dairy foods as a source of dietary iodine
The relevance of milk to iodine intake
Role of iodine and the effects of iodine deficiency
Assessment of iodine intake and status
Dietary recommendations for iodine
Global iodine nutrition: Focus on United Kingdom and Europe
Milk as a contributor to iodine status and intake in the United Kingdom
Milk as a source of iodine in other countries
Iodine content of UK milk
Iodine content of other dairy products
Knowledge of the importance of milk as a source of iodine
Iodine metabolism and excretion into milk
Factors affecting the iodine content of milk
Iodine content of the feed
Changes to the permitted iodine content of cattle diets in the EU
Iodine antagonists in feed
Farming practice: Organic and conventional milk
Seasonal variation
Iodophor disinfectants
Milk processing
Milk alternatives and iodine content
Alternative sources of iodine for those who do not consume milk and dairy products
Conclusions
References
13
Non-dairy milk substitutes: Are they of adequate nutritional composition?
Introduction
Nutritional composition
Macronutrients
Energy and fat
Protein
Carbohydrate/sugar
Micronutrients, fortification, and bioavailability
Fortification
Calcium
Iodine
Vitamin D
Vitamin B12
Additives
Consumer perceptions and drivers of choice
Health impact
Veganism, plant-based diets, and sustainability
Alternative choices within the dairy category
Allergy
Lactose intolerance
Lactose-free milk
A2 milk
Goat and sheep milk
Conclusions
References
14
Dairy foods and maintenance of muscle mass in the elderly
Introduction
Population ageing
Musculoskeletal ageing
Sarcopenia: Definitions, prevalence, and health-care burden
Sarcopenic Obesity: The confluence of two epidemics
Basic mechanisms of muscle protein regulation
Dietary protein, amino acids, and muscle protein turnover
Age-related alterations in muscle protein turnover
Mechanisms of muscle anabolic resistance in sarcopenia
Dietary protein recommendations for the elderly
Benefits of and barriers to higher protein diets for ageing muscles
Consideration of dietary protein quality for muscle anabolism
Dairy protein nutrition for ageing muscles
Whole-food dairy matrix vs isolated dairy proteins for ageing muscles
Waylaying safety concerns of high-protein diets in the elderly
Practical guidelines for older individuals
References
15
Dairy foods and the risk of cancer
Introduction
The grading of evidence
Dairy consumption and breast cancer
Premenopausal breast cancer
Postmenopausal breast cancer
Dairy consumption and colorectal cancer
Dairy consumption and prostate cancer
Conclusions
Conflicts of interest
References
Index
A
B
C
D
E
F
G
H
I
L
M
N
O
P
R
S
T
U
V
W
Back Cover

Citation preview

Milk and Dairy Foods

Milk and Dairy Foods Their Functionality in Human Health and Disease

Edited by

D. Ian Givens

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom © 2020 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN 978-0-12-815603-2 For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Charlotte Cockle Acquisitions Editor: Anna Valutkevich Editorial Project Manager: Lindsay Lawrence Production Project Manager: Joy Christel Neumarin Honest Thangiah Cover Designer: Greg Harris Typeset by SPi Global, India

Contributors Antonella Baldi Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy Sarah C. Bath Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom Leigh Breen Centre for Musculoskeletal Ageing Research (CMAR), University of Birmingham, Birmingham, United Kingdom Gillian Butler School of Natural and Environmental Sciences, Newcastle University, Newcastleupon-Tyne, United Kingdom Lydia Cooper Dairy UK, London, United Kingdom Christine Dawczynski Junior Research Group Nutritional Concepts, Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Institute of Nutrition, Friedrich Schiller University, Jena, Germany Anestis Dougkas The Institut Paul Bocuse Research Centre, Institut Paul Bocuse, Ch^ateau Du Vivier,  Ecully, France Emma L. Feeney Institute of Food and Health, School of Agriculture and Food Science, University College Dublin, Dublin, Ireland A´gnes A. Fekete Department of Food and Nutritional Sciences; Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom Melissa Anne Fernandez Heart and Lung Institute of Quebec, Laval Hospital; Institute of Nutrition and Functional Foods; School of Nutrition, Faculty of Agricultural and Food Sciences, Laval University, Quebec City, QC, Canada Carlotta Giromini Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy D. Ian Givens Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom Caroline Gunn The National Dairy Council, Dublin, Ireland Jing Guo Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom Tom R. Hill Population Health Sciences Institute and Human Nutrition Research Centre, Newcastle University, Newcastle-Upon-Tyne, United Kingdom Erica Hocking Dairy UK, London, United Kingdom Sandra Iuliano Department of Endocrinology, University of Melbourne/Austin Health, Heidelberg, VIC, Australia xv

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Contributors

Gerhard Jahreis Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Institute of Nutrition, Friedrich Schiller University, Jena, Germany Kirsty E. Kliem Department of Animal Sciences, School of Agriculture, Policy and Development; Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom Julie A. Lovegrove Institute for Food, Nutrition and Health; Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutrition Sciences, University of Reading, Reading, United Kingdom Andre Marette Heart and Lung Institute of Quebec, Laval Hospital; Institute of Nutrition and Functional Foods; Department of Medicine, Faculty of Medicine, Laval University, Quebec City, QC, Canada Oonagh Markey School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough; Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom Michelle C. McKinley School of Medicine, Dentistry and Biomedical Sciences, Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland, United Kingdom Elizabeth A. Miles Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom Luciano Pinotti Department of Health, Animal Science and Food Safety, University of Milan, Milan, Italy Margaret P. Rayman Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom Benoit Smeuninx Centre for Musculoskeletal Ageing Research (CMAR), University of Birmingham, Birmingham, United Kingdom Sabita S. Soedamah-Muthu Center of Research on Psychological and Somatic disorders (CORPS), Department of Medical and Clinical Psychology, Tilburg School for Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands; Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom Sokratis Stergiadis Department of Animal Sciences, School of Agriculture, Policy and Development, University of Reading, Reading, United Kingdom Marianne C. Walsh The National Dairy Council, Dublin, Ireland

About the editor

Professor D. Ian Givens has undergraduate and doctoral training in biochemistry and nutrition and is a UK Registered Nutritionist. He is currently Professor of Food Chain Nutrition and the director of the Institute for Food, Nutrition, and Health at the University of Reading, United Kingdom. His research focuses on the consequences of consuming animal-derived foods, including their contribution to nutrient supply and association with chronic disease risk factors across the key life stages. Current concerns include the inappropriate use of plant-based milk alternatives in the diets of children and the suboptimal intake of bonetrophic nutrients by teenage females, which is likely to increase the risk of reduced bone strength in later life, especially in the postmenopausal period. Current research includes metaanalyses on the association between dairy food consumption and cardiometabolic disease risk and cognition, and the effect of modifying the fatty acid composition of milk fat on markers of cardiovascular disease risk and the effect of milk proteins on blood pressure, haemodynamics, and glycaemic control.

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Foreword Persistence: The nature of milk

Where does milk fit within a big picture of human nutrition? The question remains as provocative today as it was centuries ago, when medical treatments and natural remedies invested hope in the properties of animal milk. Yet we now stand in a very different place in terms of what we know about human bodies, food history, and the development of nutritional science. Consumers search for wholesome and natural foods, but the fit they usually seek has to do with their highly specific personal needs, including their physical profile and their own genetic tendencies. Awareness of lactose intolerance and dietary fats and sugars governs a great deal of public discussion of milk. Compounding the challenge of current recommendations, commercial interests regularly add new products to the mix: why drink cow’s milk, if substitutes like almond, soya, or oat milk offer a promising alternative? Finally, given that dairy production involves natural resources, milk consumers (and researchers) struggle with mounting concerns about the environment and humane treatment of animals. How can we even begin to answer the simple question, ‘Should I drink milk?’ History can serve as a source of reassurance, as many of the issues raised by milk consumption today are familiar and important precisely because of their persistence. Historical perspective draws us into a deeper appreciation of the uncertainties of human judgement in the face of shifting bases of knowledge. In ancient settings, the seemingly mysterious origins of milk inspired worshipful treatment; the milk of certain animals was used for sacrifice or as an accompaniment to conversation with gods. Modern milk generates another form of earnest adherence: think for example of the parents of children with chronic illnesses who have turned to raw milk as a curative, or the rapturous attachment to raw milk demonstrated by high-end urban consumers. A new wave of advocates of grass-fed cow’s milk wants to know if the production of their milk reflects kindness to animals and distance from industrial processes. Their appreciation of the source of their milk is not unlike that of 18th-century British dairy women, who understood the variability introduced to the quality of supplies by different pastures and empathetic milkmaids. xix

xx

Foreword Persistence: The nature of milk

With its genealogy rooted in subsistence labour across extraordinarily different geographical settings, milk has always claimed a semblance of universality in diets around the world. Livestock in the shape of goats, sheep, buffalo, horses, and reindeer have served as basic providers of sustenance throughout human history. This was because milk and cheese constituted cheap sources of protein, understood as a cornerstone of nutrition even before the advent of nutritional science; the term ‘white meats’, applied to dairy products by Northern Europeans, signalled this fact. In premodern western society, such foods were recognised as wholesome, rustic, and, in the eyes of elites, rough on the digestive tract. But even menus for feasting aristocrats fell prey to the richness and textures made possible by dairy fats in cheesecakes and fritters. At both ends of the social spectrum in cuisines around the world, attachment to dairy products hinted at some form of human commonality. Milk had another winning card in its pocket throughout history, revealing a fact that modern nutritional scientists continue to explore: populations incorporating dairy products appear to have flourished in ways fortuitously revealed by the historical record. Archaeologists studying the prehistorical past have argued that the adaptation to lactose digestion in Northern Europe clearly advanced the tide of human survival and reproduction. As populations developed, a genetic variation enabling adults to digest the products of gregarious animals like cows, goats, and sheep helped the human population increase and spread. This tendency of the consumption of dairy products to assist population growth was repeated when Europeans launched their exploration and settlement of the Americas. Migrating Spaniards and Britons hauled cows and cattle across oceans in order to supply themselves with winning nutrients. In the crucially influential Columbian Exchange, Europeans introduced the reproductive might of livestock to new environments of the Americas, along with virulent plagues of disease. Native populations were decimated by the invasion, while the fate of companion livestock could not have been more successful or important: a protein and dairy-rich diet among colonisers in North America manifested itself in reproductive strength and in stature that surpassed populations back at home. Milk has entered an entirely different and more problematic phase of its history in the 21st century. Though not exactly fallen from grace, it is fair to say that milk has suffered disenchantment. Nutritional science, always a faithful handmaiden to the queen of animal products, promoted milk to dietary preeminence after the World Wars. Now, however, scientists and medical professionals must make sense of needs and demands far different from those faced in the 1920s and 1950s. A serious popular critique of dairy products followed up on the discovery of a link between fats and coronary heart disease. Allied with mass production and corporate power, ‘factory milk’ stigmatised all milk. At the same time, wealthy nations entered an era of health problems related to

Foreword Persistence: The nature of milk

plenitude, longevity, and economic inequality. Rising rates of obesity have demanded a careful assessment of the components of milk products and their place in overall eating habits. In the maelstrom of discussion around milk, one thing seems clear: controversy has never extinguished the wish to benefit from the aura of the pure white liquid of mammals. It is very likely that a successive chapter to milk history will lead us to some new incarnation of dairy dietary seduction. Perhaps nutritionists can ensure that whatever form that may take, science can illuminate the choices that lie before us. Deborah Valenze Ann Whitney Olin Professor of History Barnard College, Columbia University, New York, NY, United States

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Preface

As highlighted in Deborah Valenze’s thought-provoking foreword and book (Valenze, 2012), humans have been consuming milk and dairy products for a very long time, providing them with advantage in terms of health and population development. Deborah also identifies that we now live in an age where consumers are more likely to raise questions and concerns about food and challenge traditional beliefs. It is of course the role of nutritionists and other health professionals to ensure that consumers are given the most factual and evidencebased information although this is challenging given the many media sources of information which are not always evidence based. Nowadays humans continue to consume milk and dairy products but despite substantial reductions in consumption over time in some countries, recent data (IFCN, 2018) suggest that between now and 2030, there will be a growth in the worldwide demand for milk and milk products equivalent to three times the level of current US milk production. It is interesting to note that the FAO (2013) reports that while in the past, increased milk demand was primarily a function of population growth, during the period 1981–2005 it was increasingly a response to rising per capita milk consumption in developing countries although population growth was still a key factor. Per capita consumption increased significantly in some highly populated countries, notably China, Indonesia, and Vietnam. The consumption of milk and dairy foods remains high in Western Europe compared with many parts of Africa and Asia although milk consumption in some parts of Europe has declined over the last 50 years and this is particularly the case with certain sections of the population such as adolescents. This is becoming an increasing concern due to the resulting suboptimal intake of key nutrients including calcium and iodine. It is generally accepted that dairy products, including milk, cheese, and yoghurt, are nutrient-dense foods which are key contributors of a range of important nutrients to the diet and which are difficult to adequately obtain from dairy exclusion diets. As noted earlier, there are increasing concerns by some that milk production and related processing have substantial negative impacts on

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Preface

the environment mainly due to the use of animals. Yet, at the same time, there is increasing evidence that dietary patterns which contain higher proportions of dairy foods are associated with reduced risk of key chronic diseases. This is supported by the results from long-term prospective studies which, overall, show either a neutral or beneficial association with the risk of cardiovascular and metabolic diseases. These studies also highlight that it is wrong to assume that all dairy foods are the same, the generally greater beneficial association of fermented dairy products with the risk of type 2 diabetes being a notable example. There is now a much wider range of beneficial effects of dairy products or their components than was known even quite recently. An example includes the neutral or reduced risk of cardiovascular diseases despite many dairy foods being rich sources of saturated fats, an effect which is probably related, at least in part, to the hypotensive effects of milk proteins. These proteins also provide an important anabolic stimulus for muscle protein synthesis, an important feature for certain types of sport and increasingly important for reducing muscle loss in the elderly and may also have important roles in glycaemic control and bone development. An important issue about the various functionalities is that most are not explainable according to traditional nutrition science which is largely nutrient supply driven. The so-called dairy matrix, which for example can influence the extent to which dairy fats are digested and absorbed, is a key factor but there are others, not least a range of so-called bioactive compounds present in milk and released during digestion including some peptides, which can inhibit the angiotensin-converting enzyme leading to vascular relaxation and hence reduced blood pressure. The main aim of this book is to explore recent knowledge on the associations between dairy consumption and health and to highlight functionalities involved. Another result of the many health/disease outcomes that dairy foods have a connection with is the wide range of scientific and clinical expertise that is needed to research these connections. Specialists are needed in such diverse topics as epidemiology, paediatrics, clinical biochemistry, vascular science and related haemodynamics, bone health, muscle physiology, etc. In that sense alone, research on these unique foods and their health effects has progressed a long way in recent times but there remains a lot of unknowns. However, the fact that these foods are very important nutrient suppliers and crucially have very valuable functionality beyond that, means that all of these factors must be taken into account when considering a replacement of these foods by plantbased alternatives. D. Ian Givens Institute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom

Preface

References FAO, 2013. Milk and Dairy Products in Human Nutrition. FAO, Rome. 376 pp. IFCN, 2018. More milk needed by 2030. https://www.dairyglobal.net/Market-trends/Articles/ 2018/6/IFCN-More-milk-needed-by-2030-296786E/. Valenze, D., 2012. Milk. A Local and Global History. Yale University Press.

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Acknowledgements

My thanks go to all the authors who were generous enough to give their time, providing excellent contributions to this book and to my colleague Elena Carp who did most of the chasing of authors as deadlines loomed. I am also so grateful to Lindsay Lawrence, our Elsevier Editorial Project Manager, who guided me through all the complex publication procedures including dealing with the EMSS when it decided not to let me do something!

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CHAPTER 1

Dairy consumption and cardiometabolic diseases: Evidence from prospective studies Sabita S. Soedamah-Muthua,b, Jing Guob a

Center of Research on Psychological and Somatic disorders (CORPS), Department of Medical and Clinical Psychology, Tilburg School for Social and Behavioral Sciences, Tilburg University, Tilburg, The Netherlands, bInstitute for Food, Nutrition and Health, University of Reading, Reading, United Kingdom

Abbreviations CHD SFA RCT

coronary heart disease saturated fatty acids randomised controlled trial

1.1

Introduction

The number of people diagnosed with diabetes worldwide has more than doubled in the past 20 years and will continue to increase in the future. Globally there are 463 million people with diabetes, mostly type 2 diabetes (T2DM) in 2019, and this is projected to rise to 700 million by 2045 (Saeedi et al., 2019). One of the most worrying features of this rapid increase is the emergence of T2DM in young people, increase in undiagnosed diabetes, and highly prevalent prediabetes. Prediabetes is defined according to the diagnostic criteria published by the World Health Organisation in 2006, with fasting plasma glucose levels between 6.1 and 7.0 mmol/L, 2-h glucose levels between 7.8 and 11.0 mmol/L, and HbA1c levels between 6.0% and 6.5%. The number of people with prediabetes is expected to rise worldwide from 374 million in 2019 to 548 million in 2045 according to the International Diabetes Federation 9th edition (Saeedi et al., 2019). T2DM is a leading risk factor for the development of cardiovascular disease, which is the number one cause of death globally (WHO, n.d.). An estimated 17.9 million people died from cardiovascular diseases in 2016, representing 31% of all global deaths (WHO, n.d.). Of these deaths, 85% are due to heart attack and stroke. Dietary strategies to reduce the risk of developing cardiovascular disease include lowering of saturated fat intake. Milk and dairy foods are the major contributors of dietary saturated fats in Western diets. Healthy diet and lifestyle are often recommended as a Milk and Dairy Foods. https://doi.org/10.1016/B978-0-12-815603-2.00001-2 © 2020 Elsevier Inc. All rights reserved.

1

2

C HA PT E R 1 :

Dairy consumption and cardiometabolic diseases

strategy for risk reduction; 80%–90% of type 2 diabetes and cardiovascular disease can be prevented by adopting multiple healthy diet and lifestyle recommendations (Hu et al., 2001; Yang et al., 2012; Long et al., 2015; Lachman et al., 2016; Dong et al., 2018). In a recent study by the Global Burden of Disease Study investigators have revealed that dietary risks account for the greatest loss of global disability-adjusted life years (DALY) due to disease risk factors, overtaking smoking and hypertension (Lim et al., 2012; GBD 2017 Diet Collaborators, 2019). The loss of DALY are predominantly from T2DM and cardiovascular diseases, now often termed as cardiometabolic disease, and this presents a key challenge to nutrition scientists to identify effective dietary strategies and foods that can reduce disease risk and are acceptable and palatable to the population (Lovegrove and Givens, 2016). In this chapter, the latest scientific evidence from epidemiological studies on dairy foods in relation to cardiometabolic health will be described.

1.2

Types of dairy foods defined

Dairy is, according to the Cambridge English Dictionary, used to refer to foods that are made from milk, such as cream, butter, and cheese. In general, all mammalian milks (sheep, goat, camel, etc.) and their related products (cheese, sour cream, etc.) are classified as dairy. This may be confusing because dairy also refers to cattle and dairy farms according to the English Dictionary. Dairy foods are heterogeneous, containing solids, liquids, fermented and nonfermented foods; while milk, cheese, yoghurt are the main dairy products, they also include cream (sour cream) and ice cream, buttermilk, kefir, chocolate milk, butter, etc. Dairy foods contain many different types of products, with different textures and different tastes. The country where produced and feeding of the animals producing the milk and production processes further affect variety in dairy foods. Moreover, many foods contain dairy products, but are sold under different names, such as chocolate, custards, frozen desserts, and porridge. Within each dairy food, there are many variations ranging from high to low fat, with or without added sugars or fruits, to the type of fermentation. There are currently over 1800 different types of cheese, such as Brie, Gouda, Emmental, Roquefort, Camembert, Manchego, Cheddar, Feta, Gruyere, Monterey Jack, Stilton, and Grana Padano coming from different parts of the world. Epidemiological research of associations between dairy products and disease outcomes published prior to 2013 mostly considered dairy foods, combining heterogeneous dairy foods into one category as total dairy, and analyses of total high- and low-fat dairy intake. In various studies, different definitions of total dairy were used, including different combinations of dairy foods, which make comparisons between studies of associations between total dairy and cardiometabolic disease challenging. A shift was made over the past 5 years with more differentiation into different

1.3

Dairy consumption in the world

types of dairy foods, fermentation, and fat content, which enabled analyses of more specific associations between dairy subtypes and disease outcomes.

1.3

Dairy consumption in the world

Dairy foods are recommended in dietary guidelines of several countries (Table 1.1), generally advising milk, yoghurt, and cheese products at 2–3 servings per day. Dairy foods are increasingly consumed as indicated by the International Dairy Federation (Fig. 1.1 and Table 1.2). Dairy consumption is found to be highest in European countries, where most varieties of dairy foods are available on the market. From 2006 to 2013 there was globally a steep increase in per capita dairy product consumption (Fig. 1.1). Increases were limited in Europe (Centre National Interprofessionnel de l’Economie Laitie`re (CNIEL)/International Dairy Federation (IDF), Food and Agriculture Organization (FAO) of the United Nations, Population Reference Bureau (PRB), 2013). Dairy consumption, especially milk, is still low in many countries in particularly African and Asian countries (GBD 2017 Diet Collaborators, 2019) and projected to decline (Kearney, 2010) in many countries. Growth in the sales of dairy foods in Asia where people are generally lactose intolerant may not be biologically, culturally, or environmentally sound (Lee et al., 2015). The prevalence of lactose intolerance indeed varies from 100% in China and Japan to 50% in Mexico down to 15% in the United States white populations and 10% in Sweden (Bayless et al., 2017; Silanikove et al., 2015). The global average consumption of dairy foods is less than one serving per day (Lee et al., 2015). In South Asia, dairy consumption is highest in Pakistan. In North-East Asia, where lactase nonpersistence is most prevalent, the dairy consumption is highest in Japan, followed by Taiwan with intakes less than 1 serving per day. Interestingly, for liquid milk, the upper single dose of lactose tolerance seems to be about 25 g, which is the most that a single serve of dairy food might provide (Lee et al., 2015). In a historical perspective, several indicators were given for humans to overcome limitations imposed by lactose intolerance: (i) mutations, in which carriers of the lactose intolerance gene converted from being lactose intolerant to lactose tolerant; (ii) the ability to develop low-lactose products such as cheese and yoghurt, although not always widely consumed in Asian countries; and (iii) colon microbiome adaptation, which allows lactose-intolerant individuals to overcome its intolerance (Silanikove et al., 2015). Healthy eating guidelines in Asian countries include dairy foods (Table 1.1). Generally low to moderate dairy intake per day is well tolerated in most Asian populations and studies relating dairy intake to cardiometabolic diseases in these populations are rare (Lee et al., 2015).

1.3.1

Nutrients context

Dairy foods such as milk, cheese and yoghurt are energy- and nutrient-dense products (Table 1.3). Dairy naturally contains various nutrients beneficial

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Table 1.1 Country-specific dietary guidelines. Year of publication United States

2015

United Kingdom

2016

Netherlands

2015

Switzerland

2011

Recommendation

Amount

Sources

Fat-free or low-fat dairy, including milk, yoghurt, cheese All milk, including lactosefree and lactose-reduced products and fortified soy beverages (soymilk), yoghurt, frozen yoghurt, dairy desserts, and cheeses. Most choices should be fat-free or lowfat. Cream, sour cream, and cream cheese are not included due to their low calcium content Have some dairy or dairy alternatives (such as soya drinks); choosing lower-fat and lower-sugar options Try to have some milk and dairy food (or dairy alternatives)—such as cheese, yoghurt and fromage frais

3 cup-equivalents are recommended for a diet up to 2000 kcal 1 cup-equivalent is: 1 cup milk, yoghurt, or fortified soymilk; 1½ ounces natural cheese such as cheddar cheese or 2 ounces of processed cheese

https://www.cnpp. usda.gov/2015-2020dietary-guidelinesamericans

Choose three servings each day One serving is defined as: 1 glass (200 mL) milk 1 carton (125 g) yoghurt 1 bottle (200 mL) yoghurt drink 2 thumbs (25 g) hard or semihard cheese such as cheddar or edam 2 thumbs (25 g) soft cheese such as brie or camembert 2–3 portions of dairy foods a day

https://www.gov.uk/ government/ publications/theeatwell-guide

3 portions per day

http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ switzerland/en/

Have some daily dairy foods, such as milk, yoghurt and cheese More details on products recommended: Skimmed and semiskimmed milk, yoghurt, buttermilk, skimmed quark, 20 +, 30 + cheese with less salt, soft goat’s cheese, Mozzarella spread Consume some dairy foods

https://www. gezondheidsraad.nl/ documenten/adviezen/ 2015/11/04/richtlijnengoede-voeding-2015 in English: Kromhout et al. (2016)

1.3

Dairy consumption in the world

Table 1.1 Country-specific dietary guidelines—cont’d Year of publication

Recommendation

Amount

Sources

Finland

2014

Milk products and cheese

France

2016

http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ finland/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ france/en/

Australia

2013

Consume foods that are rich in calcium (mainly dairy foods, in addition to vegetables and mineral water rich in calcium, for those who consume mineral water) Reduced fat dairy foods and/or alternatives

Consume fat-free/low-fat milk products daily (5–6 dL/day) and two or three slices of low-fat cheese 3 portions of dairy per day

Milk, yoghurt, cheese, and/or their alternatives, mostly reduced fat (reduced-fat milks are not suitable for children under the age of 2 years)

http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ australia/en/

New Zealand

1990s

Include milk and milk products in your diet, preferably reduced or lowfat options

Canada

2007

Drink skim milk or select lower-fat milk alternatives

China

2016

A variety of dairy products, equivalent to 300 g of liquid milk, should be consumed per day (Wang et al., 2016)

Drink skim, 1% or 2% milk each day; Have 500 mL (2 cups) of milk every day for adequate vitamin D; Drink fortified soy beverages if you do not drink milk Select lower-fat milk alternatives: Compare the nutrition facts table on yoghurts or cheeses to make wise choices Milk and milk products 300 g/day

http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/newzealand/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ canada/en/

The Chinese Nutrition Society. The Food Guide Pagoda for Chinese Residents. Available from http://dg. cnsoc.org/upload/ images/source/ 20160519163856103. jpg (Accessed on June 20, 2016); 2016 (in Chinese) Continued

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Table 1.1 Country-specific dietary guidelines—cont’d Year of publication

Recommendation

Amount

Sources Ministry of Health, Labour and Welfare and the Ministry of Agriculture, Forestry and Fisheries of Japan. Japanese Food Guide Spinning Top. Available from http://www.maff. go.jp/j/balance_guide/ b_use/pdf/eng_reiari. pdf (Accessed on June 30, 2016), 2005 Dietary Guidelines for Indians- A Manual. Available from http://ninindia.org/ DietaryGuidelines forNINwebsite.pdf. (Accessed on 11 January 2019) http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ malaysia/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ thailand/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ nepal/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ kenya/en/ http://www.fao.org/ nutrition/education/ food-dietary-guidelines/ regions/countries/ south-africa/en/

Japan

2016

Milk and milk products are recommended (Wang et al., 2016)

2 servings milk and milk products per day

India

2011

Choose low-fat dairy foods in place of regular whole fat dairy foods

NA

Malaysia

2010

Consume adequate amounts of milk and milk products

NA

Thailand

1998

Have milk appropriately

NA

Nepal

2012

Consume milk or milk products daily

NA

Kenya

2017

Drink fresh milk, fermented milk or yoghurt every day

NA

South Africa

2012

Have milk, maas or yoghurt every day

NA

1.3

Dairy consumption in the world

FIG. 1.1 Per capita Milk Consumption from 2006 to 2013. https://slideplayer.com/slide/11662620/ @copyrights permission granted CNIEL/IDF, FAO Food Outlook, PRB, n.d. Per Capita Milk Consumption From 2006 to 2012. Annual National Workshop for Dairy Economists and Policy Analysts presented in Boston in May.

for health such as calcium, potassium, phosphorus, different vitamins such as B2, B12, and K2, and also nutrients less beneficial for health such as sodium, saturated fat, and added sugars. Vitamin D levels of dairy vary between countries depending on fortification. High- and low-fat products show comparable nutrient quantities in general. Compared to low-fat cheese, whole milk still contains considerably less fat per 100 g of product. There are small differences in saturated fat content between whole milk and skim milk (as g/100 g product) compared to high- and low-fat cheese. Cheese is relatively high in saturated fat and sodium content compared to the other dairy foods, and therefore not always included in healthy eating guidelines (Table 1.1). There has been controversy in the literature as to whether dairy foods should have a prominent place in healthy diets, with alternating more or less focus on beneficial or potentially harmful nutrients (van Aerde et al., 2013; Tognon

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Table 1.2 Country-specific intake of dairy foods, from national food consumption surveys. Country (year of publication)

Dairy foods

Intake

United States (NHANES 2014) https://search.ers.usda.gov/search?affiliate¼ers& query¼Source%3A+2007-10+National+Health +and+Nutrition+Examination+Survey+% 28NHANES%29%2C+two-day+averages Netherlands (2017) https://www.rivm.nl/voedsel-en-voeding/ rivm-weet-wat-nederland-eet/zuivel Norway (2009) European Nutrition and Health Report (2009) Finland (2009) European Nutrition and Health Report (2009) Austria (2009) European Nutrition and Health Report (2009) Poland (2009) European Nutrition and Health Report (2009) The Czech Republic (2009) European Nutrition and Health Report (2009) Canada (2016) https://www.dairynutrition.ca/data-onconsumption/quantitative-data/milk-productconsumption-per-capita United Kingdom (2012) https://www.gov.uk/government/statistics/ national-diet-and-nutrition-survey-results-fromyears-1-to-4-combined-of-the-rolling-programmefor-2008-and-2009-to-2011-and-2012

Total dairy

0.78 cups/1000 cal (dairy serving 177 g/day, 2000 cal (Gijsbers et al., 2016)) 280 g/day

Total dairy

350 g/day

Total dairy

522 g/day

Total dairy

437 g/day

Total dairy

171 g/day

Total dairy

181 g/day

Total dairy

186 g/day

Total fluid milk Total cheeses Yoghurt

190 mL/day 41 g/day 30 mL/day

Whole milk Semiskimmed milk Total cheeses Yoghurt, fromage frais and other dairy desserts Total dairy

24 g/day 93 g/day 15 g/day 27 g/day

Total dairy Milk

27 g/day 32 g/day

Total dairy Milk

109 g/day 67 g/day

China (1998), Singapore Chinese Health Study N (37,124 Chinese men and women aged 45–74 year) China (2011–12) Chinese Nutrition and Health Surveillance in 2010–12 and the Chinese Nutrition and Health Survey in 2002 (Wang et al., 2017; Liu et al., 2016) Korea (2005, 2009) (Ministry of Health and Welfare, 2005; Ministry of Health and Welfare, 2009) The Korea national Health and Nutrition Examination Survey

28 g/day

Table 1.3 Nutrients in full-, medium- and low-fat milk, cheese and yoghurt using the USDA Table.

Milk

Cheese

Yoghurt

Energy (kJ)

Water (g)

Protein (g)

Carb (g)

Total fat (g)

SAFA (g)

PUFA (g)

Ca (mg)

P (mg)

K (mg)

Na (mg)

Vitamin A (μg)

Vitamin B2 (mg)

Vitamin B12 (μg)

Vitamin D (μg)

Wholea

255

88.1

3.2

4.8

3.3

1.9

0.2

113

84

132

43

46

0.2

0.5

1.3

Medium fatb

209

89.2

3.3

4.8

2.0

1.3

0.1

120

92

140

47

55

0.2

0.5

1.2

Nonfatc

142

90.8

3.4

5

0.1

0.06

0.003

122

101

156

42

61

0.2

0.5

1.2

Cheese Mexicand

1607

40.5

23.5

0.1

32.1

16

0.9

659

438

85

607

174

0.3

1.2

0.5

Fat-free Cheddare

657

57

32.1

7.1

0

0

0

893

484

66

1000

60

0.2

0.5

0.1

Full-fatf

255

87.9

3.5

4.7

3.3

2.1

0.1

121

95

155

46

27

0.1

0.4

0.1

Low-fatg

234

85.2

5.7

7.7

0.2

0.1

0.005

199

157

255

77

2

0.2

0.6

0

g, gram/100 gram product; mg, milligram/100 gram product; μg, microgram/100 gram product; En, energy; Carb, carbohydrates; SAFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; Ca, calcium; P, phosphorus; K, potassium; Na, sodium. a Whole milk 3.25% milkfat with added vitamin D (reference code ¼ 01077). b Milk reduced fat, 2% milkfat, with added vitamin A and D (reference code ¼ 01079). c Milk nonfat, skim, with added vitamin A and D. d Cheese Mexican Blend (reference code ¼ 01085). e 01265 Cheddar Cheese, fat-free, nonfat (reference code ¼ 01265). f Yoghurt plain whole milk (reference code ¼ 01116). g Yoghurt plain skim milk (reference code ¼ 01118). https://ndb.nal.usda.gov/ndb/ (Accessed 4 December 2018).

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et al., 2018; Givens, 2010). Increasing attention in the scientific literature has been given to dairy foods because of controversies and confusion as to whether dairy (subtype) products should be consumed and whether or not these are associated with risk of cardiometabolic diseases and mortality.

1.4 1.4.1

Epidemiological studies General principles

Epidemiology is the study of the distribution of diseases (e.g. T2DM, cardiovascular diseases, infections, allergies, etc.) in populations. Epidemiology is concerned with the frequency (counting disease, prevalence, and incidence) and pattern of health events (by time, place, and demographic characteristics) in a population. The purpose of epidemiological study is to understand what risk factors (aetiology) are associated with a specific disease, and how disease can be prevented in groups of individuals. Due to the observational nature of epidemiology, these studies cannot provide answers to what actually caused a disease, and further evidence on the cause-effect relationship from other types of studies (mechanistic studies, randomised controlled trials) need to be considered to make definite conclusions. Observational studies are an important category of epidemiological study designs. These can be categorised as: prospective cohort studies, retrospective cohort studies, case-cohort studies, (nested) case-control studies, and cross-sectional studies. Each study design has its own advantages and disadvantages. Prospective designs (cohort studies) are preferred for dairy and cardiometabolic diseases research and will be the main focus in this chapter. The main advantages of these prospective study designs are the ability to assess the exposure before the outcome occurs and confounding adjustments can be dealt with in statistical analyses. In an observational study, the investigator does not intervene (unlike in randomised controlled trials), rather simply “observes” and assesses the strength of the relationship between an exposure and outcome variable (Merril and Timmreck, 2006). The incidence of the outcome in the exposed group is directly compared to that of the unexposed group. A relative risk and confidence interval are calculated by dividing the incidence rates by the exposed vs. the unexposed group (adjusted for multiple confounders). If a relative risk is 1.0 then no association is found, if a relative risk is above 1.0 then a positive/higher risk association is found, and if a relative risk is below 1.0 then an inverse/lower risk association is found. A relative risk always has to be interpreted taking into account the confidence interval around the estimate. A wide confidence interval indicates lack of power and unreliable estimates. Residual confounding remains an issue in this type of research, because intake of many dairy foods is known to be related to other healthy or unhealthy behaviours, not always accounted for in adjustment models.

1.4

Epidemiological studies

Dietary intake data are mostly self-reported data using extensive food frequency questionnaires, dietary history methods, 24-h recall methods, or food diaries. It is difficult to estimate exact intake amounts of dairy foods with these methods, but these methods are suitable to rank people in different categories of intake and to compare consumption extremes related to risks of cardiometabolic diseases.

1.4.2

Dose-response metaanalyses techniques

Traditionally, metaanalyses were performed pooling risk estimates from prospective cohort studies for high vs low dairy product intake. The meaning of a pooled risk estimate was not clear, because this was not directly linked to a particular dosage of dairy foods, and high and low dairy consumption varied between studies. Interpretations about the dosage/quantity were impossible to derive from underlying studies because each study used a different questionnaire for food intake, ranking study participants into high and low intake based on a different underlying range of intake for each study. A more sophisticated method, dose-response metaanalysis, includes intake/dose generally expressed in the same unit across studies (e.g. in grams per day) and allows investigation of linear or nonlinear associations. The key to this approach is to first calculate the study specific slopes and then pool results across studies. Assumptions have to be made on how to deal with the lower and upper limits of various dairy intake categories used in the analysis (i.e. tertiles, quartiles, quintiles of dairy intake) and how to obtain grams per day food intake from frequency data (times per week using standard portion sizes or country-specific portion sizes). Choices have to be made as to which result is to be extracted from each article. For example, if studies presented several statistical models, the model that included most confounders is usually chosen. Linearity of associations is investigated using spline analysis and dose-response metaregression (Generalised least-square trend; GLST). Splined variables have to be created in order to select the most appropriate knot points of nonlinear associations based on goodnessof-fit tests and Chi-square statistics. The shape of the associations within individual studies are visualised by means of Ding’s spaghetti plots (SoedamahMuthu et al., 2012; Gijsbers et al., 2016; de Goede et al., 2016; Guo et al., 2017). Dose-response metaanalyses offer more insight on the direct association between for example dairy foods and risk of cardiometabolic disease, taking into account the shape of the association (Gijsbers et al., 2016; de Goede et al., 2016; Guo et al., 2017). Large heterogeneity indicates between-study variation and needs to be explored further by metaregression and subgroup analyses. Generally, subgroup analyses by continent, age groups, sex, study outcome types, follow-up duration, confounder adjustments (optimal confounder adjustments vs. limited confounder adjustments) are carried out. Results always have to be interpreted in the light of observed heterogeneity.

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1.5 Current state of evidence on dairy foods and cardiometabolic diseases 1.5.1

Prospective studies on dairy foods and type 2 diabetes

There is an overwhelming amount of evidence on the association between dairy foods and T2DM from prospective cohort studies, summarised in several metaanalyses (Gijsbers et al., 2016; Soedamah-Muthu and De Goede, 2018; Yu and Hu, 2018; Drouin-Chartier et al., 2016a; Aune et al., 2013; Gao et al., 2013; Tong et al., 2011; Elwood et al., 2008; Chen et al., 2014; Alvarez-Bueno et al., 2019). The results from all metaanalyses showed consistently neutral or inverse associations for intake of total and low-fat dairy foods, with the most striking inverse association between yoghurt intake and T2DM. A very recent pooling of three large USA cohort studies (two Nurses Health Studies and Health Professionals Follow-up Study) confirmed these results with longitudinal exposure data and showed that increasing intake of yoghurt was associated with a moderately lower risk of T2DM (Drouin-Chartier et al., 2019). They also showed opposite results for cheese, with increasing cheese consumption associated with a moderately higher risk of T2DM (Drouin-Chartier et al., 2019). A potential explanation for the discrepancy of this study with existing metaanalyses given by the authors is the way cheese is most often consumed in the USA as an ingredient in mixed dishes (for example pizza, hamburgers, sandwiches) and high in refined carbohydrates. The studies by Soedamah-Muthu and De Goede (2018) and Gijsbers et al. (2016) are the most complete with a total of 26 prospective cohort studies. Total dairy intake (per 200 g/day) was borderline significantly associated with a 3% lower risk of T2DM, and low-fat dairy intake was also borderline significantly associated with a 4% lower risk of T2DM (I2 ¼ 60%) (Soedamah-Muthu and De Goede, 2018). Yoghurt intake had the most striking result, with a nonlinear inverse significant association with T2DM (relative risk (RR) ¼ 0.86, 95% confidence interval (CI): 0.83–0.90, P < .001, I2 ¼ 69%, at 80 g/day compared with 0 g/day) (Fig. 1.2, Ding’s spaghetti plot of yoghurt intake and risk of T2DM). In all these metaanalyses considerable heterogeneity (60%–69%) was present, which could not be explained by metaregression and subgroup analyses (Soedamah-Muthu and De Goede, 2018). Metaanalyses of high-fat dairy, fermented dairy, cheese, and milk intake showed no significant associations with incident T2DM. The differences in associations with T2DM risk for high-fat (null association) compared to low-fat dairy (moderately inverse) intake was also shown in previously published metaanalyses (Drouin-Chartier et al., 2016a). Subgroup analyses of the associations between total dairy intake and T2DM risk by Gijsbers et al. (2016) suggested a nonsignificant inverse association in Asian populations (three studies, RR: 0.85 per 200 g/day; 95% CI: 0.65, 1.12), but no association was observed for European populations (six studies). Only a limited number of studies from Asia (n ¼ 3) were available for these analyses, and

Current state of evidence on dairy foods and cardiometabolic diseases

0.4

0.5

0.6

Relative risk 0.7 0.8 0.9

1

1.1

1.2

1.5

0

25

50

75 100 Yogurt intake (g/day)

125

150

FIG. 1.2 Ding’s Spaghetti plot for the association between yoghurt consumption and risk of type 2 diabetes, summarising data from 13 prospective cohort studies (14 samples).

these country-specific associations should be further investigated in the future. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and type 2 diabetes, but a separate metaanalysis was published. In this metaanalysis by Pimpin et al. (2016) summarised data from four cohorts and found that butter consumption was associated with a lower incidence of T2DM, with a 4% lower risk per daily 14 g (1 tablespoon) serving (RR ¼ 0.96, 95% CI: 0.93–0.99, P ¼ .21), moderate heterogeneity was seen (I2 ¼ 42%). The authors of this study have acknowledged that these were small overall associations, which do not support a need for major emphasis in dietary guidelines on either increasing or decreasing butter consumption, and recommended further research on health effects of butter and dairy fat (Pimpin et al., 2016). All the evidence of the association between yoghurt and butter intake and the risk of T2DM have been derived from observational epidemiological studies, with moderate to large heterogeneity and residual confounding remaining an issue. There is evidence that yoghurt intake is related to healthy behaviours (Tremblay and Panahi, 2017) and although confounder models in all studies included in the metaanalyses adjusted for healthy behaviours, there could still remain residual confounding. The impact of dairy foods on T2DM cannot be fully dissociated from that of the foods it replaces (Tremblay and Panahi, 2017; Lamarche et al., 2016). The background diet and habits are generally not captured in epidemiological studies and is an interesting area for future research.

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1.5.2 Prospective studies on dairy foods and coronary heart disease There is good evidence from prospective cohort studies that investigated the association between dairy intake or specific types of dairy product and risk of coronary heart disease (CHD) (Guo et al., 2017; Soedamah-Muthu and De Goede, 2018; Drouin-Chartier et al., 2016a; Mullie et al., 2016; Chen et al., 2017; Bechthold et al., 2017; Gille et al., 2018; Alexander et al., 2016a; Qin et al., 2015; Soedamah-Muthu et al., 2011; Fontecha et al., 2019). The results from all metaanalyses showed that, based on moderate- to high-quality evidence, total dairy, full-fat dairy, low-fat dairy, milk, cheese, and yoghurt consumption has no association with the risk of CHD. In line with this, the PURE cohort investigators published international data from 21 countries in five continents on total dairy foods intake in relation to risk of myocardial infarction and found no evidence for an association (Dehghan et al., 2018). On the contrary, in 2017, Gille et al. (2018) concluded that there was moderate evidence for an inverse association between CHD risk and the consumption of cheese based on three metaanalyses (Chen et al., 2017; Qin et al., 2015; Alexander et al., 2016b), but this is a selection of the evidence. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and coronary heart disease, but a separate metaanalysis was published. The metaanalysis by Pimpin et al. (2016) found that butter intake (per 14 g/day) was not significantly associated with CHD risk (RR ¼ 0.99, 95% CI: 0.96–1.03; P ¼ .54).

1.5.3

Prospective studies on dairy foods and stroke

There are many metaanalyses of prospective cohort studies which have investigated data on dairy intake or specific types of dairy product and incident stroke (de Goede et al., 2016; Mullie et al., 2016; Soedamah-Muthu and De Goede, 2018; Yu and Hu, 2018; Drouin-Chartier et al., 2016a; Chen et al., 2017; Soedamah-Muthu et al., 2011; Alexander et al., 2016b; Fontecha et al., 2019). In 2016, we pooled 18 prospective cohort studies from 11 countries with 8–26 years of follow-up that included 762,414 individuals and almost 30,000 stroke events based on a search up to October 2015 (de Goede et al., 2016). An increment of 200 g of daily milk intake was associated with a 7% lower risk of stroke (RR ¼ 0.93: 95% CI: 0.88–0.98; P ¼ .004; I2 ¼ 86%). RRs were 0.82 (95% CI: 0.75–0.90) in East Asian (n ¼ 4 studies, 5 samples) and 0.98 (95% CI: 0.95–1.01) in Western countries (n ¼ 3 studies, 4 samples) (median intakes 38 and 266 g/day, respectively) with less, but still considerable, heterogeneity within the continents. Nonsignificant inverse associations between semiskimmed milk intake and stroke were found (four Western studies, median intake: 150 g/day): 0.96 (95% CI: 0.90–1.03) per 200 g/day with heterogeneity (I2 ¼ 68%, P ¼ .01), whereas the association with full-fat milk showed a higher risk

1.5

Current state of evidence on dairy foods and cardiometabolic diseases

of stroke. Based on a limited number of studies, full-fat milk (n ¼ 4 studies, RR of 1.04 (95% CI: 1.02–1.06) per 200 g/day) was positively associated with stroke risk, whereas full-fat total dairy (n ¼ 6) as well as low-fat dairy (n ¼ 7) intake were inversely associated (de Goede et al., 2016; Soedamah-Muthu and De Goede, 2018). Differences in associations between full-fat (null association) and lowfat dairy (weak inverse association) products and stroke were found in prior metaanalyses (Drouin-Chartier et al., 2016a). Cheese intake was marginally inversely associated with stroke risk (RR ¼ 0.97; 95% CI: 0.94–1.01 per 40 g/day). The strongest inverse association with incident stroke was found around 125 g/day for milk intake and around 25 g/day for cheese. No associations were found for yoghurt, butter, or total dairy intake. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and stroke, but a separate metaanalysis was published. The metaanalysis by Pimpin et al. found that butter intake was not associated with stroke risk (RR¼ 1.01; 95% CI: 0.98–1.03, P ¼ .74 per 14 g (1 tablespoon)/day) (Pimpin et al., 2016). Analyses for total dairy and milk were updated with four new cohort studies by Soedamah-Muthu and de Goede, who confirmed similar results, an increment of 200 g/day milk intake was associated with an 8% lower risk of stroke, RRmilk and stroke ¼ 0.92, 95% CI: 0.88–0.97, I2 ¼ 85% (Soedamah-Muthu and De Goede, 2018). RRs were 0.82 (95% CI: 0.75–0.89) in East Asian and 0.98 (95% CI: 0.95–1.01) in Western countries (median intakes of 38 and 266 g/day, respectively) (Fig. 1.3). In the large PURE cohort study including data from 21 countries from five continents, dairy consumption was found to be associated with a lower risk of stroke, RR ¼ 0.66, 95% CI: 0.53–0.82, P ¼ .0003 (Dehghan et al., 2018). It was not clear whether this association was due to milk or cheese intake. All evidence of associations between milk and cheese intake and the risk of stroke has been derived from observational epidemiological studies; large unexplained heterogeneity and residual confounding remain an issue in these studies. As noted earlier, the background diet is not generally captured in epidemiological studies, and therefore, hypothetically, the association of a higher milk intake with a lower risk of stroke could potentially be due to, for example, a lower intake of sugar-sweetened beverages.

1.5.4

Prospective studies on dairy foods and mortality

The association between dairy consumption and total mortality has raised the public attention and uncertainty due to the study by Michaelsson et al. (2014) which reported that higher milk consumption was associated with a doubling of total mortality risk in the cohort of women. The most updated metaanalysis (Guo et al., 2017) summarised evidence from 29 cohort studies, including the study by Michaelsson et al. (2014), and demonstrated neutral associations between dairy foods and total mortality. High-fat/low-fat dairy, milk, cheese, and yoghurt intakes were not associated with total mortality. Interestingly, total

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% Weight

Year

Country

Outcome

Relative risk (95% CI)

Kondo, women

2013

Japan

Fatal stroke

0.71 (0.47, 1.06) 1.37

Lin

2013

China

Total stroke

0.75 (0.52, 1.07) 1.69

Kinjo

1999

Japan

Fatal stroke

0.76 (0.72, 0.81) 9.00

Talaei

2017

Iran

Total stroke

0.81 (0.51, 1.30) 1.10

Kondo, men

2013

Japan

Fatal stroke

0.86 (0.54, 1.38) 1.09

Singapore

Fatal stroke

0.88 (0.78, 0.98) 6.75

Japan

Fatal stroke

0.91 (0.79, 1.05) 5.83

Author Asian

Pan Sauvaget

2003

Subtotal (I2 = 35.8%, P = .155)

0.82 (0.75, 0.89) 26.83

. Western 0.89 (0.74, 1.07) 4.49

Elwood

2004

United Kingdom Total stroke

Iso

1999

United States

Ischemic stroke

0.92 (0.82, 1.04) 6.61

Goldbohm, men

2011

Netherlands

Fatal stroke

0.94 (0.81, 1.09) 5.66

Goldbohm, women 2011

Netherlands

Fatal stroke

0.94 (0.81, 1.10) 5.34

Ness

2003

United Kingdom Fatal stroke

0.96 (0.84, 1.10) 5.86

Praagman

2015

Netherlands

Total stroke

0.97 (0.89, 1.05) 7.98

Dalmeijer

2013

Netherlands

Total stroke

0.97 (0.89, 1.05) 8.09

Sonestedt

2011

Sweden

Total stroke

0.97 (0.93, 1.02) 9.33

Larsson

2012

Sweden

Total stroke

0.98 (0.95, 1.01) 9.84

Larsson

2009

Finland

Total stroke

1.03 (1.01, 1.05) 9.96

Subtotal (I2 = 47.2%, P = .048)

0.98 (0.95, 1.01) 73.17

. Overall (I2 = 85.2%, P = .000)

0.92 (0.88, 0.97) 100.00

Note: Weights are from random effects analysis .5

1

2

Relative risk per 200g/day milk

FIG. 1.3 Forest plot for association between milk intake and stroke risk, split by Asian vs European countries.

fermented dairy intake showed a nonlinear marginal association with lower mortality risk (RR ¼ 0.98, 95% CI: 0.97–0.99 per 20 g/day). Furthermore, subgroup analysis showed an inverse association between milk consumption and mortality in the subgroup of studies from Asia (RR ¼ 0.95, 95% CI: 0.91–0.99), although only two studies were included. Other metaanalyses of dairy or milk intake and mortality confirmed these neutral results (Mazidi et al., 2019; Mullie et al., 2016; Cavero-Redondo et al., 2019; Larsson et al., 2015). A very recent pooling of three USA cohort studies (two Nurses Health Studies and the Health Professionals Follow-up study reported that whole milk with an increasing intake of 0.5 serving per day was associated with a 9%–11% higher risk of total mortality, cardiovascular mortality, and cancer mortality (Ding et al., 2019). The intake of whole milk was relatively low (a maximum intake of approximately 2 servings per week), no adjustments for separate foods were included in the statistical models, even though with increasing dairy intake the diet

1.5

Current state of evidence on dairy foods and cardiometabolic diseases

quality was moderately poor, and no adjustments for other dairy subtypes were performed, which limits the interpretation of the independence of this finding (Ding et al., 2019). In the same study, neutral associations were found for cheese, yoghurt intake, and mortality. A recent publication by Willett and Ludwig in the New England Journal of Medicine (Willett and Ludwig, 2020) advocated more research on milk and health and adjusting current guidelines for milk and dairy foods to an acceptable intake (up to 2 servings for adults instead of 3 servings per day), deemphasize reduced-fat milk as preferable to whole milk, and discourage consumption of sugar-sweetened dairy foods in populations with high rates of overweight and obesity. Restricting portion size depending on the populations and background diet quality is necessary. Butter is nutritionally distinct from other dairy foods and generally not included in analyses of dairy products and mortality, but a separate metaanalysis was published. In this metaanalysis by Pimpin et al. found that butter consumption was weakly associated with a higher risk of all-cause mortality (n ¼ 9 studies, RR ¼ 1.01, 95% CI: 1.00–1.03, P ¼ .045) (Pimpin et al., 2016). Recently, a large multinational cohort study (Dehghan et al., 2018) across 21 countries in five continents including 136,384 people for 9 years of follow-up showed that a higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of all-cause mortality (RR 0.83, 95% CI: 0.72–0.96, Ptrend ¼ .0052). The highest category of dairy consumption in the PURE study was only 2 servings a day, which is not comparable to United States and European dietary guidelines recommending 3 servings a day (Rubin, 2018) (Table 1.1). The large PURE study showed stronger inverse associations than previous literature, and this study was not included in above-mentioned metaanalyses, suggesting that more prospective cohort studies including a wider range of countries should be conducted to further analyse the association between dairy foods and mortality. To conclude, evidence from epidemiological studies suggest that higher milk and dairy consumption showed a neutral or inverse association with total mortality.

1.5.5 Prospective studies on dairy foods in healthy populations vs patients To our knowledge, there is limited epidemiological evidence on the associations between dairy consumption and human health in healthy populations compared with patients with diseases (e.g. prediabetes and cardiovascular diseases). Recently, Hruby et al. (2017) examined the association between dairy intake and long-term risk of prediabetes in initially healthy participants, and also the risk of T2DM among participants with prediabetes at baseline using the Framingham Heart Study Offspring Cohort. The authors concluded that dairy consumption showed null to inverse association with incident prediabetes and progression to T2DM. Specifically, after 12 years of follow-up, in 902

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C HA PT E R 1 :

Dairy consumption and cardiometabolic diseases

prediabetes cases out of 1867 healthy participants, total, low-fat, and high-fat dairy intakes were found to be associated with a 39%, 32%, and 25% lower risk of incident prediabetes, respectively, in the highest dairy consumers (14 servings/week) compared with lowest dairy consumers (