Ray Peat (1936–2022) Complete Collection of Ray Peat's articles from website raypeat.com and raypeatforum.com

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Ray Peat (1936–2022) Complete Collection of articles from his website.

Ray Peat (1936–2022)
Ray Peat's BACKGROUND

Concerning my background, Ray Peat has a Ph.D. in Biology from the University of Oregon, with specialization in physiology. The schools I have taught at include: the University of Oregon, Urbana College, Montana State University, National College of Naturopathic Medicine, Universidad Veracruzana, the Universidad Autonoma del Estado de Mexico, and Blake College. I also conduct private nutritional counseling.

I started my work with progesterone and related hormones in 1968. In papers in Physiological Chemistry and Physics (1971 and 1972) and in my dissertation (University of Oregon, 1972), I outlined my ideas regarding progesterone, and the hormones closely related to it, as protectors of the body's structure and energy against the harmful effects of estrogen, radiation, stress, and lack of oxygen.

The key idea was that energy and structure are interdependent, at every level.

Since then, I have been working on both practical and theoretical aspects of this view. I think only a new perspective on the nature of living matter will make it possible to properly take advantage of the multitude of practical and therapeutic effects of the various life-supporting substances--pregnenolone, progesterone, thyroid hormone, and coconut oil in particular.

"Marketing" of these as products, without understanding just what they do and why they do it, seems to be adding confusion, rather than understanding, as hundreds of people sell their misconceptions with their products. The very concept of "marketing" is at odds with the real nature of these materials, which has to do with the protection and expansion of our nature and potential. A distorted idea of human nature is sold when people are treated as "the market."

It seems that all of the problems of development and degeneration can be alleviated by the appropriate use of the energy-protective materials. When we realize that our human nature is problematic, we can begin to explore our best potentials.

---- Ray Peat

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W E L C O M E Although we removed the page for ordering books several months ago, there's still a backlog of orders, so there can be a very long delay, but the orders are still being filled. This website currently reports on my research in aging, nutrition, and hormones. You will find this information in the ARTICLES section. A variety of health problems are examined (eg., infertility, epilepsy, dementia, diabetes, premenstrual syndrome, arthritis, menopause), and the therapeutic uses of progesterone, pregnenolone, thyroid, and coconut oil are frequently discussed. My approach gives priority to environmental influences on development, regenerative processes, and an evolutionary perspective. When biophysics, biochemistry, and physiology are worked into a comprehensive view of the organism, it appears that the degenerative processes are caused by defects in our environment. As a supplement to this web site, I've also included examples of my artwork, specifically some of my paintings, which you will find in the ART GALLERY. As I've discussed in my books, I see painting as an essential part of grasping the world scientifically. For a few years, I taught art and painted portraits. I have shown my work in both the US and Mexico. BACKGROUND Concerning my background, I have a Ph.D. in Biology from the University of Oregon, with specialization in physiology. The schools I have taught at include: the University of Oregon, Urbana College, Montana State University, National College of Naturopathic Medicine, Universidad Veracruzana, the Universidad Autonoma del Estado de Mexico, and Blake College. I also conduct private nutritional counseling. I started my work with progesterone and related hormones in 1968. In papers in Physiological Chemistry and Physics (1971 and 1972) and in my dissertation (University of Oregon, 1972), I outlined my ideas regarding progesterone, and the hormones closely related to it, as protectors of the body's structure and energy against the harmful effects of estrogen, radiation, stress, and lack of oxygen. The key idea was that energy and structure are interdependent, at every level. Since then, I have been working on both practical and theoretical aspects of this view. I think only a new perspective on the nature of living matter will make it possible to properly take advantage of the multitude of practical and therapeutic effects of the various life-supporting substances--pregnenolone, progesterone, thyroid hormone, and coconut oil in particular. "Marketing" of these as products, without understanding just what they do and why they do it, seems to be adding confusion, rather than understanding, as hundreds of people sell their misconceptions with their products. The very concept of "marketing" is at odds with the real nature of these materials, which has to do with the protection and expansion of our nature and potential. A distorted idea of human nature is sold when people are treated as "the market." It seems that all of the problems of development and degeneration can be alleviated by the appropriate use of the energy-protective materials. When we realize that our human nature is problematic, we can begin to explore our best potentials. ----Ray Peat

Critical MAS

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Dec 16, 2022

Ray Peat Died. Now What? Recently, nutritional pioneer Ray Peat died at the age of 86. I have several posts on this blog that reference his work. I’m not a strict follower, but I have borrowed some of his ideas. This post will not be about Ray’s contribution to our understanding of nutrition. It will be about preserving the digital legacy of someone that has passed away.

Dead Men Can’t Pay For Web Hosting When I heard that Ray had passed away, my first thought was what was to become of his website. Ray did a great job with his site. He published his articles and he left them alone. Unlike so many in the nutritional space, he kept his site going, and he didn’t move links. I run a broken link checker on this site and I’ve never once had to fix a broken link to RayPeat.com. I hope Ray has an assigned backup for his domain registration and if so, I hope they maintain his website.

But I am doubtful. Many of his most popular followers have demonstrated the inability to keep their own websites up and running. See my 2017 post titled The Digital Graveyard of My Health and Fitness Mentors for examples. Whois hides the registrar information for RayPeat.com, but it does say the domain is expiring on March 1, 2023. If it is not renewed, bots are far more likely to capture the domain faster than a fan the second it becomes available. If that happens, all of Ray’s writing will be taken down and replaced with spammy affiliate links. There are thousands of inbound links to RayPeat.com. That makes it worth the effort to capture the domain.

Screenshot of RayPeat.com

My Story

In 2010, a popular Miami-based radio personality died. Then a few months later, the man running his website died. From the post My Tribute to Radio’s Neil Rogers:

”

Just when I was about to reach out to Eric, I discovered he had recently died. Young man too. I believe he was in his 40s. Eric was a one-man operation. At this point, I realized it was just a matter of time before the NeilRogers.com site went dark. Servers need human intervention and they also need someone to pay the electric bill. Using a download program I was able to grab all the audio from the site, which were the bits he played. A few months later the site went dark. There was no backup name on the domain registration. No one knew anyone associated with Eric. To this day the data on that server or any backups remain lost.

The rest of the post describes the other steps I took to successfully preserve that digital legacy.

My Advice I hope I’m wrong and someone out there continues to renew the registrar and hosting. But if not, here is what I would do. 1. Copy every article off of RayPeat.com

2. Create a bare-bones HTML mobile-friendly (responsive website). No server code (WordPress, Drupal, etc). Static HTML and CSS only. 3. Go to GitHub.com and create a repo for the site. Make the repo public. This allows anyone the ability to download or copy (fork) Ray’s work. 4. Once the repo is set up, use the GitPages feature in the repo to create a free website. 5. If RayPeat.com is lost, buy a new domain. I bought NeilRogers.org when NeilRogers.com was lost. Map the domain to the GitPages and then set the payment to the registrar to auto-renew annually. The good news is the effort to save Ray’s content is far less than the work I had to do to save thousands of hours of audio. All of RayPeat.com could be saved in a weekend, but the clock is ticking. Some might argue that the Wayback Machine on Archive has snapshot copies of RayPeat.com, so all my outlined steps are unnecessary. That is true today, but not necessarily true in the future. I love the Wayback Machine and have even donated money to them, but whoever owns a domain can request that their domain be removed from their search results. This means if someone that doesn’t care about Ray’s work acquires the domain, they can have the domain scrubbed from the Wayback Machine.

I briefly poked around the Ray Peat Forums and Reddit page. I didn’t see anyone mention preserving his website. I hope I missed the post and someone has already taken a leadership role. Please leave a comment if you are that person or if you need my assistance. I expect I will have to update some broken links to Ray’s site next year. UPDATE August 2023: Stef B alerted me that there is now a mirror for all Ray Peat’s articles.

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9 Comments

Add yours

Christian Dec 17, 2022 — 3:34 am

RayPeat.com doesn’t have a ton of content, so archiving was really fast, actually.

If anyone else wants to crawl and download the page, this command in a shell will do: $ wget \ --recursive \ --no-clobber \ --page-requisites \ --html-extension \ --convert-links \ --restrict-file-names=windows \ --domains raypeat.com \ --no-parent \ http://raypeat.com

One could drop the

--html-extension

flag; then

the articles will download as .shtml instead of .shtml.html. This could be desirable to keep existing links working. I left this in for reference because in other archival processes, I was happy to have the .html extension to make it possible to inspect files in a local browser quickly. The header image in rotation will be stored as ‘rotate.php’ even though it’s an image. Now someone figure out how to get the domain for posterity

MAS

🙂

Dec 17, 2022 — 6:56 am

@Christian – Nice. I haven’t touched Wget in years.

russ cox Dec 24, 2022 — 6:23 am

please contact danny roddy ,i feel sure he would like to help

CB Dec 25, 2022 — 8:59 pm

the other person who might help is Georgi D. @haidut http://haidut.me and it’s Danny Roddy @dannyroddy I’m hoping his estate will be willing to publish more (maybe all?) of his work. I will help with preserving his site and the domain. contact me, please. I’ve been a Peat student since ’99!

Andrew Wiguna Dec 29, 2022 — 8:46 pm

As an aspiring author and small content creator myself (nutritional-humility.me) [currently under rebranding], I too am saddenned by this news. Another way people can still read and/or access his materials, particularly, his newsletters is visiting the Archive.org. The link (hopefully if I’m allowed to post URLs in comments) is here https://archive.org/details/mega-master-raynewsletter ^ Warning: massive PDF. 320 Megabytes. This PDF is curation of every release. Whilst my dietary / sustenance philosophy is in many ways stark opposite to Ray’s (Cyclical Keto + IF) ~ he nonetheless implore selfexperimentation, and never be afraid to challenge authoritarianism. The latter, is pretty much what everyone should ably relate. Live-it-forward, AW. nutritional-humility.me

MAS Dec 30, 2022 — 7:33 am

@Andrew – best of luck on your site and rebranding. I love Archive – however – it is not ideal for those of that have deep links to specific

articles. Archive is great if you already know about Ray and know what to look for. @All – I’m not going to take a leadership role on preserving Ray’s articles. I have too many projects more important to me. This means I’m not reaching out to anyone at this time. If by March, the Peat community (of which I am not a member), hasn’t set up a proper backup, I *may* step in at that time. I think that the fans of Ray have a DUTY to set up the article backup themselves, not an outsider like myself. I am happy to assist, but I’m not stepping forward to lead. My motivation is to not have links break on this blog.

MAS Jan 12, 2023 — 9:36 am

@All – I found a Ray archive, which includes articles from his site. https://wiki.chadnet.org/ray-peat If and when Ray’s site goes dark, I will update my links to this resource.

Stef B Aug 15, 2023 — 2:02 am

Another mirror is up here: https://expulsia.com/health/peat-index There is also some other content on the site that you may or may not agree with. However, the Ray Peat mirror is excellent in my opinion. I much prefer the formatting to Ray Peats original site. Also, I think I heard Georgi and Danny say that Ray’s family will continue the website

MAS Aug 16, 2023 — 8:49 am

@Stef B – This is great news. I added a link to the mirror at the end of the post. Thank you for sharing!

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Physiology texts and the real world

Ruolo Fisiologico del Sale (Na-Cl +)

El problema de la enfermedad de The dark side of stress Alzheimer como una pista para la (learned helplesness) inmortalidad

Cancer: Disorder and Energy Mitochondria and mortality www.RayPeat.com ©2006-16 Ray Peat All Rights Reserved

Heart and hormones The Cancer Matrix Serotonin: Effects in disease, aging and inflammation Cataracts: water, energy, light, and aging Fatigue, aging, and recuperation Estrogen Receptors - what do they explain? Meat physiology, stress, and degenerative physiology Multiple Sclerosis and other hormone related brain syndromes Prostate Cancer Growth hormone: Hormone of Stress, Aging, and Death? Phosphate, activation, and aging Rosacea, inflammation, and aging: The inefficiency of stress Hot flashes, energy, and aging Multiple Sclerosis and other hormone-related brain syndromes When energy fails: Edema, heart failure, hypertension, sarcopenia, etc. Cancer: Disorder and Energy Fats, functions & malfunctions Radiation and Growth: Incoherent imprinting from inappropriate irradiation (pdf file) (this may take some moments to load) Sugar issues Glucose and sucrose for diabetes Cascara, energy, cancer and the FDA's laxative abuse Osteoporosis, aging, tissue renewal, and product science Regeneration and degeneration: Types of inflammation change

with aging Pathological Science & General Electric: Threatening the paradigm Protective CO2 and aging Genes, Carbon Dioxide and Adaptation Serotonin, depression, and aggression: The problem of brain energy NEWER ARTICLES Academic authoritarians, language, metaphor, animals, and science Adaptive substance, creative regeneration: Mainstream science, repression, and creativity Calcium and Disease: Hypertension, organ calcification, & shock, vs. respiratory energy Cholesterol, longevity, intelligence, and health. Estrogen, memory and heredity: Imprinting and the stress response Estrogen, progesterone, and cancer: Conflicts of interest in regulation and product promotion Natural Estrogens Tissue-bound estrogen in aging Suitable Fats, Unsuitable Fats: Issues in Nutrition The Great Fish Oil Experiment Gelatin, stress, longevity Glycemia, starch, and sugar in context How do you know? Students, patients, and discovery Intelligence and metabolism Intuitive knowledge and its development Lactate vs. CO2 in wounds, sickness, and aging; the other approach to cancer Milk in context: allergies, ecology, and some myths Membranes, plasma membranes, and surfaces Multiple sclerosis, protein, fats, and progesterone Progesterone Summaries Progesterone Deceptions Preventing and treating cancer with progesterone. Protective CO2 and aging RU486, Cancer, Estrogen, and Progesterone Salt, energy, metabolic rate, and longevity Stem cells, cell culture, and culture: Issues in regeneration Thyroid, insomnia, and the insanities: Commonalities in disease

TSH, temperature, pulse rate, and other indicators in hypothyroidism Water: swelling, tension, pain, fatigue, aging Unsaturated fatty acids: Nutritionally essential, or toxic? Aging, estrogen, and progesterone. Aging Eyes, Infant Eyes, and Excitable Tissues Altitude and Mortality. Alzheimer's: The problem of Alzheimer's disease as a clue to immortality - part 1. Alzheimer's: The problem of Alzheimer's disease as a clue to immortality - part 2. Aspirin, brain and cancer. Autonomic systems. Bleeding, clotting, cancer. Blocking Tissue Destruction. Bone Density: First Do No Harm. Breast Cancer. BSE ("mad cow"), scrapie, etc.: Stimulated amyloid degeneration and the toxic fats. Caffeine: A vitamin-like nutrient, or adaptogen. Questions about tea and coffee, cancer and other degenerative diseases, and the hormones. Coconut Oil. Diabetes, scleroderma, oils and hormones. Eclampsia in the Real Organism: A Paradigm of General Distress Applicable in Infants, Adults, Etc. Epilepsy and Progesterone. Estriol, DES, DDT, etc. Estrogen - Age Stress Hormone. Estrogen and Osteoporosis. Fats and degeneration. Food-junk and some mystery ailments: Fatigue, Alzheimer's, Colitis, Immunodeficiency. Immunodeficiency, dioxins, stress, and the hormones. Iron's Dangers. Leakiness, aging, and cancer. Menopause and its causes. Oils in Context. Osteoporosis, harmful calcification, and nerve/muscle malfunctions. Progesterone Pregnenolone & DHEA - Three Youth-Associated

Hormones. Progesterone, not estrogen, is the coronary protection factor of women. Thyroid: Therapies, Confusion, and Fraud. The transparency of life: Cataracts as a model of age-related disease. Tryptophan, serotonin, and aging. Unsaturated Vegetable Oils: Toxic. Vegetables, etc. - Who Defines Food? Vitamin E: Estrogen antagonist, energy promoter, and antiinflammatory William Blake as biological visionary. Can art instruct science?

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Painterly Science Painting and science have been closely associated historically, because both used to involve close, intense examination of their subject, generalization based on experience, and imaginative consideration of the possibilities. That has changed but not because of any intrinsic change in knowledge. Knowledge always changes through time, but vested interests try to permit only those changes that are good for them. Authoritarian education derives its authority from political and economic power, and generally not from the quality of the knowledge it inculcates. As education became more important economically in the twentieth century, it became more specialized, in the sense that each teacher devoted his full time to an increasingly narrow topic. In this state, the specialist loses his authority when he ventures to evaluate the big picture. In the 19th century, biologists were usually competent painters, but as specialization took over at the beginning of the 20th century, both science and painting became "abstract." Mathematics came to be called the language of science, and a science was considered to be more scientific when it was more mathematical. The mathematical habit of mind inclines biologists to see organisms as disembodied information, ultimately as the information contained in the genetic code. Change (they are likely to say) is random, "chaotic," ultimately unknowable. There is no place in this system for a radical critic of the purpose and direction of the system. If physicists and biologists learn to see the world in a lively way by exercising the power to paint, they will learn to prevent the atrophy of their critical powers.

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Home / Wellness / Food / What Is the Ray Peat Diet?

What Is the Ray Peat Diet? Explore the ins and outs of the Ray Peat Diet in a U.S. News in-depth review.

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By Elaine K. Howley

Reviewed by Dietitian Vandana Sheth, RDN, CDCES, FAND

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March 10, 2023

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This article is based on reporting that features expert sources.

For anyone who’s ever had a chronic, difficult-to-diagnose health condition, the search for answers can lead to years of frustration. Where medical science sometimes fails to offer a definitive answer, anecdotal evidence and experimentation can occasionally lead to a sustainable solution for some people.

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That’s been true for Benedicte Lerche, a biochemist, nutritional counselor and thyroid specialist who struggled with a low-thyroid disorder in her 20s before finally finding the Ray Peat diet. She now offers counseling and support featuring the Ray Peat diet via her service, BiochemNordic, based in Copenhagen, Denmark. Lerche came across the Ray Peat diet concept when she was working as an au pair in Paris. She was living in a “very moldy, dark apartment,”where she says she was always sick. She assigned all of her various, nonspecific symptoms – headaches, digestive issues, menstrual problems, rashes, blood sugar issues and repeated colds and fevers – to her environment, and when she returned to Denmark, she expected that the symptoms would resolve.

But they didn’t. Thus, she began seeking help from the medical system, but all of her tests came back as being within normal levels. She says her thyroid function levels were a little on the low side “but not alarmingly low,” so the doctors thought the issue might be something else. Still experiencing symptoms and frustrated with the lack of answers from the medical establishment, Lerche turned to alternative medicine. A dentist in the alternative community suggested that she had low thyroid function and recommended vitamin supplements to address it. She began researching low thyroid conditions and ways to boost function of this important hormone-secreting gland that resides in the neck. She soon came across information about Ray Peat’s sometimes counterintuitive approach to food and health. She found a phone number and dialed. “Very luckily, he just grabbed the phone,” she says. The two stuck up a correspondence where Peat explained his theories for overcoming hypothyroidism. His recommendations helped Lerche resolve her symptoms. “It was such a relief in a lot of ways,” she says of finally finding the answer to her problems and feeling better. Inspired by the improvement in her health and overall well-being, Lerche pursued a PhD in biochemistry. Today, she counsels other people struggling with low thyroid conditions to better health via her BiochemNordic platform and a slew of online resources including ebooks, recipes and blog posts.

See: Top Foods for Thyroid Health

What Is the Ray Peat Diet? The thing about the Ray Peat diet is that there isn’t really a set Ray Peat diet. Erin Holley, a registered dietitian at the Ohio State University Wexner Medical Center in Columbus, says that “apparently the Ray Peat diet works to correct hormonal imbalances and improve metabolism through ‘pro-metabolic’ dietary changes.” If that term seems unfamiliar, you’re not alone. “I’m not quite sure what this means because even the people that follow his diet can’t explain it,” Holley says. U.S. News reached out to Peat for an interview but did not hear back. Peat hasn’t published a book that outlines all the ins and outs of eating to improve thyroid function, and he’s not offering a monthly membership program, cookbooks, recipe lists or simplified lists of

foods to eat or avoid in prescribed amounts, like so many other diets out there. Instead, finding the essence of the Ray Peat diet takes a lot of digging and reading into various online networks and forums, some of which include unconventional alternative medicine advice alongside mainstream nutritional and health advice. Nevertheless, the Ray Peat diet has many staunch followers, such as Lerche, who’ve found freedom and relief in his unconventional ideas. This eating concept draws from the Peat’s research and, to a certain degree, is open to interpretation by the user. According to information posted on the website raypeat.com, which is attributed to Peat himself, he holds a PhD in biology from the University of Oregon, with specialization in physiology. He has taught at the University of Oregon, Urbana University, Montana State University, National University of Naturopathic Medicine, Universidad Veracruzana, the Universidad Autonoma del Estado de Mexico and Blake Austin College. He has also offered private nutritional counseling. Peat’s biography notes that he started his work with progesterone and related hormones in 1968. “In papers in Physiological Chemistry and Physics (1971 and 1972) and in my dissertation (University of Oregon, 1972), I outlined my ideas regarding progesterone, and the hormones closely related to it, as protectors of the body's structure and energy against the harmful effects of estrogen, radiation, stress and lack of oxygen," he writes. "The key idea was that energy and structure are interdependent, at every level.” Holley says that while there’s a lot of information online about the Ray Peat diet, most of it comes from people other than Peat himself, and they aren’t always reliable sources. “The info I found online came from non-credible people, such as wellness coaches, functional nutrition therapy practitioners and other followers of his works.”

See: What Are Early Warning Signs of Thyroid Problems?

What to Eat on the Ray Peat Diet If there can be a codification of the Ray Peat method, it would seem to include eating: Healthy fats, such as coconut oil and butter. Dairy products, with a strong emphasis on milk, cheese and ice cream. Lots of fresh fruit and fruit juices.

Root vegetables. Protein from muscle and organ meats. Collagen, a protein the body uses to keep bones, tendons and muscles strong and support skin health. Eggs. Shellfish. Lerche says there’s plenty of fruit and meat in the Ray Peat diet and that while most dietitians and doctors these days warn people against the use of sugar, “Ray Peat is not afraid of sugar. That’s because the liver needs sugar to activate the thyroid hormones.” She says by consuming simple sugars, you can support your liver in its efforts to stabilize your hormones. For this reason, she says that “completely normal, white sugar is actually not dangerous. Sugar is basically from nature,” as it’s present in fruits, honey, dairy products and so on. “Natural sugar promotes cellular energy,” she adds, since it’s the fuel that cells run on; the body takes glucose from the foods we eat to fuel cellular function. Lerche cautions that a more welcoming attitude toward white sugar doesn’t give you a free license to “go out right now and drink gallons of Coca-Cola every day. Because the problem with doing that is that it's only sugar.” With sweet things like fruit and honey instead, you’re getting some other health-supporting vitamins and minerals. As such, orange juice is “very big in the Ray Peat diet. There’s always juice with everything,” Lerche says, though she recommends rinsing your mouth out with plain water after drinking orange juice as the sugars can lead to tooth decay. For her part, Holley says that as a dietitian, she finds this emphasis on simple sugars such as juice and white table sugar “fascinating. These are certainly easy-to-digest sugars and do not cause harm in moderation. But some followers report that Peat has been known to drink a quart of orange juice at a time. I would not recommend that,” as a quart of orange juice can contain more than 450 calories and 83 grams of sugar.

See: Questions to Ask an Endocrinologist

How Much You Can Eat on the Ray Peat Diet Portion size doesn’t really enter the conversation for many proponents of the Ray Peat diet, and this approach doesn't typically

have weight loss as its primary aim. Fundamentally, followers of this diet have different goals than those trying to lose weight; most of them are seeking relief from underdiagnosed or difficult-topinpoint thyroid or other hormone problems.

Focus on Red Light Light therapy is also a component of the Ray Peat method, with a focus on red light as a possible anti-stress mechanism that can support longevity and reduce the cellular deterioration that comes with aging. Red light, which is a component of sunlight, can penetrate tissues easily and support healing, Peat has suggested. Living in a dark environment without much sunlight can be detrimental to health, he argues. Lerche adds that if you live in a climate where you can’t get enough sunlight daily, it may be worth investing in a light therapy machine to boost your levels.

Eat the Right Kind of Fat A key tenant of the Ray Peat diet centers around the type of fat you should be consuming if you have a hypothyroid condition. Polyunsaturated fats, also called polyunsaturated fatty acids or PUFAs, are a type of fat that’s liquid at room temperature. In conventional nutritional circles, PUFAs are considered heart healthy because they contain omega-3 fatty acids, which have been shown to reduce the risk of heart attack and heart disease. Vegetable oils, nuts, seeds and fatty fish like salmon and mackerel are all good sources of polyunsaturated fats. However, proponents of the Ray Peat diet say that PUFAs are detrimental to health because they inhibit thyroid function. PUFAs also contain omega-6 fatty acids, which can have negative effects on heart health when consumed in excess. One of the omega-6 fatty acids, called linolenic acid, is converted in the body to arachidonic acid, which can promote inflammation and vascular problems, such as blood clots and narrowing of blood vessels. In addition, Ray Peat diet followers, citing PUFAs' low melting point, say that it is an unstable type of fat; the claims are that PUFAs can easily oxidize, which causes the oil to go rancid and become toxic. Oxidation creates free radicals, which can cause damage to cells throughout the body. Examples of PUFAs include: Vegetable oil. Canola oil.

Corn oil. Soybean oil. Walnut oil. Cottonseed oil. Peanut oil. Flaxseed oil. Margarine. PUFAs also show up in many packaged and prepared foods including: Energy or granola bars. Potato chips. Commercially raised poultry, beef and eggs. Animals that consume a diet that’s high in corn and soy will have high levels of PUFAs in their products. Fast foods and fried foods. Fish oil and seafood. Lerche says that while PUFAs do appear to lower the levels of cholesterol in the blood, which is why conventional nutritional science says they’re heart-healthy, they do so by “actually poisoning the liver in some way so that the cholesterol doesn’t show up in the blood.” There is some limited evidence that PUFAs could increase the liver’s burden, though the issue seems to come down to the ratio of helpful omega-3 fatty acids to potentially damaging omega-6 fatty acids, and the scientific research has so far been mainly conducted in animals. Instead of using PUFA-heavy cooking oils, the Ray Peat approach advocates for using more stable, saturated fats for cooking such as: Coconut oil. Butter or ghee (clarified butter). Tallow. Opting for pasture-raised or grass-fed animal products is another way to remove PUFAs from your diet. However, because these sources of fats are saturated fats, which are solid at room temperature, conventional dietary advice says to avoid them. Saturated fats can elevate the level of LDL cholesterol – that’s the “bad” kind in the blood, and it may increase the risk of heart disease and stroke.

Other foods to avoid include: Nuts, seeds and nut and seed butters because of their PUFA contents. Low-quality, highly processed foods, such as packaged or fast foods, also because of PUFAs. Beans, lentils and other legumes because they are high in fiber, which Lerche says the body isn’t designed to digest readily and can tax the system, leading to reduced thyroid function.

Is There Science to Back Up the Ray Peat Diet? As a scientist himself, Peat has performed studies of hormones and how diet can influence them. There is some evidence hinting at these ideas, but generally speaking, the concept lies outside the bounds of conventional nutritional advice. It’s also unclear whether the anecdotal results some believers have found with this eating method are actually a result of the diet. Holley says that while there’s little scientific research to support some of the claims made by devotees of the Ray Peat method, “I do not believe these foods to be harmful either.” As with many other off-the-beaten-track diets, there’s a mix of good advice and questionable nutritional ideas that have been ascribed to Peat. One that Holley points to is the Ray Peat carrot salad, which recently became a viral sensation on TikTok. Followers claim that the salad balances hormones, such as estrogen. Holley, however, says, “Please do not fall for this. Yes, it’s good to eat carrots, but carrots do not balance hormones.”

Should I Try the Ray Peat Diet? Bottom line, this approach isn’t necessarily bad or wrong, but if you have thyroid issues, it’s important to seek advice from a medical provider. While it’s true that some thyroid disorders can be difficult to diagnose and that diet can be a powerful tool to support individuals with health conditions, there are treatments available for hypothyroid conditions that don’t require completely revamping your diet or vastly upping your intake of orange juice. That said, Holley adds, “I really don’t think any of these foods are bad or wrong to include in your diet. But I would not recommend limiting oneself to only the foods that are part of this diet."

In the end, she says that “the best thing for us is truly getting as much variety as possible. This is how we get more vitamins, minerals, phytochemicals, antioxidants, fiber (and a) variety of prebiotics and probiotics.”

The 40 Easiest Diets to Follow

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Updated on March 10, 2023: This story was previously published at an earlier date and has been updated with new information.

SOURCES The U.S. News Health team delivers accurate information about health, nutrition and fitness, as well as in-depth medical condition guides. All of our stories rely on multiple, independent sources and experts in the field, such as medical doctors and licensed nutritionists. To learn more about how we keep our content accurate and trustworthy, read our editorial guidelines.

Erin E. Holley, MS, RD, LD Holley is a registered dietitian with the Ohio State University Wexner Medical Center in Columbus. Benedicte Lerche, MSc, PhD Lerche is a biochemist, nutritional counselor and thyroid specialist offering the Ray Peat diet via her service, BiochemNordic, based in Copenhagen, Denmark.

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" I intend to show you how neo-Darwinism has been invalidated within science itself, as an explanation of how life on earth has evolved and is evolving. It is nevertheless still perpetrated by the academic establishment, if only because it serves so well to promote genetic engineering, a technology that has the potential to destroy all life on earth. Furthermore, neo-Darwinism reinforces a worldview that undermines all moral values and prevents us from the necessary shift to holistic, ecological sciences that can truly regenerate the earth and revitalize the human spirit." Mae-Wan Ho http://www.i-sis.org.uk/paris.php =========================== More than 50 years have been wasted in one of the most important and fundamental branches of science and medicine, for reasons that are highly ideological and political. Rather than studying the regeneration of organs and tissues, and recognizing its obvious importance in healing as well as in understanding the nature of life, much of the last century was devoted to the defamation of the researchers who were making real process in the field. Despite many demonstrations that regeneration can occur in adult mammals, students were taught that it happens only in lower vertebrates. I think it's important to look closely at the ideology responsible for this great loss. Warburg and Szent-Gyorgyi, in thinking about cancer, emphasized that growth is the primordial function of all cells, and that the differentiated functions of complex organisms involve restraints of that primitive function, imposed by a system that has developed through time. Seen with this orientation, regeneration is the spontaneous result of the disappearance of restraint. The reproduction of a whole plant from a twig, or clone, was a process known for thousands of years. Any part of the plant contains the information needed for making a whole plant. More than thirty years ago, cells from a tumor were added to the cells of a normal embryo, and the animal that matured from the embryo-tumor mix was normal, and had traits of both lineages, showing that the tumor cells had retained the genetic information of a complete healthy organism, and just needed a different environment in which to realize their full potential. O n e of the currents of medical thinking, from classical times through Paracelsus to homeopathy and naturopathy, has been a confidence in the capacity of the organism to heal itself. But "modern" medicine has arrogated to itself the "healing power," with terrible results, mitigated only by their occasional reluctant acceptance of fragments of sane organismic thinking, such as recognizing the importance of nutrition, or of keeping sewage out of the drinking water. Research into methods to support the organism's natural restorative powers has been ridiculed and suppressed. We are immersed in the propaganda of modern medicine, and part of that propaganda involves the confabulation of a history of science that supports their practice and their ideology. The real history of science won't be found in science textbooks. "I intend to show you how neo-Darwinism has been invalidated within science itself, as an explanation of how life on earth has evolved and is evolving. It is nevertheless still perpetrated by the academic establishment, if only because it serves so well to promote genetic engineering, a technology that has the potential to destroy all life on earth. Furthermore, neo-Darwinism reinforces a worldview that undermines all moral values

and prevents us from the necessary shift to holistic, ecological sciences that can truly regenerate the earth and revitalize the human spirit." Mae-Wan Ho http://www.i-sis.org.uk/paris.php Mainstream medical treatments are based on some fundamentally absurd scientific ideas. The advent of experimental animal cloning and the industrialization of genetic engineering have undercut the most important biological doctrines of the 20th century, but the processes of critical thinking haven't made headway against most of the traditional medical stereotypes. Cloning shows that all cells are potential "stem cells," but this fact co-exists with the Hayflick doctrine, that says, essentially, that no cell is a stem cell. The ideology of culturally significant "intellectuals"--scientists, professors, neurobiologists, linguists, philosophers, oncologists, geneticists--in the US is deeply influenced by the dualism and mechanistic materialism of Rene DesCartes. The denial that animals can think or understand language, the claim that babies or animals don't feel pain, or that heart cells and brain cells can't divide, or that somatic cells lack the genetic capacity to be cloned, or that they are intrinsically mortal, limited to a maximum of 50 cell divisions-these absurdities of 20th century biology and medicine all resulted from an abject commitment to the mechanistic doctrine of matter and life promoted or invented by DesCartes. I doubt that DesCartes really invented anything, because, by the evidence of his writing, he wasn't an intelligent man, but he placed himself politically in such a way that his arguments were acceptable to many influential people, and they continue to be acceptable to authoritarian and elitist factions even today. In the 16th and 17th century the cultures of England, Holland, and France were increasingly dominated by business interests. People who had money to invest wanted to see the world as an orderly, predictable place, and they found that many of the ideas of the ancient Greeks were useful. Mathematics was needed to calculate interest rates, insurance premiums, and, for the military, the trajectories of missiles. In an orderly world, allowance for a little random variation helped to save the perfection of the general rule. In this environment, theological thinking began retrenching its doctrine, to make it more acceptable to the increasingly powerful commercial people. The clockwork universe of DesCartes' time, in which a perfect world that operated according to perfect natural laws had been divinely created, gradually became theologically acceptable during the 18th and 19th centuries. In the 18th century, the Deists were the most famous embodiment of the idea, and then in the 19th century their place was taken by the Catastrophists, who claimed that the fossils which seemed to show evolutionary change of species actually represented species that had been created along with those now existing, but that had been destroyed by catastrophes, such as Noah's flood. By the end of the 19th century, the president of an American university recognized that theological compromises could prevent his undergraduates from rejecting religion entirely, and forbade sermons against evolution. There were many biologists who insisted that evolution of new species was analogous to the development of an individual, and that both revealed an adaptive capacity of the living substance. In this view, the adaptive growth of an individual in a new environment revealed novel solutions to new problems, and showed an innate inventiveness and intelligence in the process of growth and adaptation. The appearance of new species was thought to represent the same sorts of adaptive processes. Erasmus Darwin (grandfather of Charles) was an evolutionist of this sort, but because of political and theological pressure, he kept relatively quiet about his beliefs. There was an underground culture, in which an evolutionary view of the world was accepted, but these views were seldom published, because of increasingly stringent censorship. Because of censorship, poetry, letters, and diaries, rather than academic and scholarly works, give us the true picture of 18th century and early 19th century scientific culture.

The scientists who wanted their work to be acceptable to those in power found ways to work with the Cartesian mechanical view of the world, building on the Deists' compromise, which had succeeded in removing the supernatural from nature. As the fossil evidence of evolution became inescapable, around the time of Charles Darwin's work, those who wanted to bring evolution into the mainstream of culture found that the Catastrophism of the creationists could be adapted to their purposes, with only slight modification. The doctrine of Thomas Malthus, who argued that war, famine, and disease were beneficial for those who survived, by decreasing the competition for limited resources, became a near equivalent to the catastrophic floods that the creationists had invoked to explain the geological record that contained evidence of many extinct animals. The doctrine of Malthus, like that of the Catastrophists, made loss, deletion, and destruction into a central device for explaining the history of the world. Both of the Darwins had accepted the idea that many biological changes were adaptive, rather than random, but the new practical compromise doctrine introduced the idea that changes were just "random variations." The essentially mechanical nature of the world was preserved, because "chance" occurrences could be dealt with, and didn't involve anything supernatural. The function of the environment wasn't to add anything to life (that would have been to assert that there were creative powers other than those of the Creator), but simply to eliminate the inferior individuals that appeared as the result of random changes. Gregor Mendel applied the principle of chance to explaining the inheritance of certain traits, and showed that "traits" were passed on unchanged, even when they weren't visible. His ideas were published and were acceptable to the scientific mainstream of his time. Traits were determined by "factors" that were passed on, unchanged, from parents, and biological variation was explained by varied mixing of factors which in themselves were unaffected by the organism or the environment. Genetic determinism was safely compatible with creationism. Shortly after Mendel's death, August Weismann began a campaign to put a stop to the claims of those who, like the Darwins and Lamarck, saw adaptive development of organisms as an essential part of the evolution of species. Weismann was essentially a propagandist, and his first fame was the result of "disproving" Lamarck by cutting the tails off more than 1500 mice, and observing that their offspring were born with tails. The reason the inheritance of acquired traits was impossible, he said, was that the "germ line" was perfectly isolated from the rest of the organism. The differentiated tissues of the body were produced by the selective loss of information from the nuclei of cells in the embryo. The cells of the germ line were immortal and contained all the information needed to produce an organism, but no other cell of the organism was complete. Complexity was produced by deletion, and this was the basis for arguing that, if even the development of an individual was nothing but a passive unfolding of inherited properties, much like unpacking a trunkful of clothes, then there could be no adaptively acquired traits, and certainly no inheritance of something which didn't exist. Changes in an individual were simply accidents, such as having a tail amputated, and so the whole issue of the origin of complexity was safely left to a primordial creation. Weismann and his arguments were famous in Europe and the US, and formed the background for the ideas known as neo-Darwinism. His "isolation of the germ line" was the earliest version of the Central Dogma of molecular biology, namely, that information flows only from DNA to RNA to protein. His doctrine, of complexification through deletion, is the epitome of the greatest dogma of modern times, expressed in doctrines from Catastrophism through the second law of thermodynamics and the theory of the Big Bang, down to Hayflick's Doctrine of the mortality of somatic cells. All these are consequences of the Cartesian and Deistic separation of intelligence from matter. Regeneration is one of the most vivid examples of the intelligence of living substance.

Given a natural tendency of cells to multiply, the interesting thing about regenerative healing is the question of why the new growth of tissue sometimes differentiates to fit appropriately into its surroundings, but sometimes fails to differentiate, becoming a tumor. With aging, the regenerative process declines, and the process of tissue rebuilding slows. Against a background of reduced regenerative ability, tissue growth sometimes produces tumors, rather than renewed healthy tissue. When tumors are grafted onto the amputated tail stump of a salamander, which has good regenerative ability, the tumor is transformed into a tail, by its envirornment, or morphogenic field. The "cancer problem" is essentially the problem of understanding the organizing forces of the organism. The aging problem is another aspect of the same problem. Traditionally, biologists had studied anatomy, physiology, embryology or development, and taxonomy or the classification of organisms. The growth of knowedge early in the 20th century was suddenly seeming to confirm the physiological, adaptive view of organisms that Lamarck had held. C.M. Child, Joseph Needham, Alexander Gurwitsch, and L.V. Polezhaev were demonstrating the primacy of a formative process in biology. Polezhaev and Vladimir Filatov were studying practical means of stimulating regeneration as a medical technique. Until the beginning of the second world war, the study of regeneration and the pattern-forming processes in embryology were the liveliest parts of biological research. Gestalt psychology was being developed at the same time, with a similar emphasis on patterns and wholes. But Weismannism and neo-Darwinism, largely embodied in the person of the geneticist T.H. Morgan, deliberately set out to kill that line of biological research. Gestalt psychology was similarly eliminated by the Behaviorists. O n e of Morgan's closest associates, his student and colleague A.H. Sturtevant, said that "Morgan's objectives, what he was trying to get at in general in his biological work was to produce mechanistic interpretations of biological phenomena. One of the things that irritated him most was any suggestion of purpose in biological interpretation. He always had some reservations about the idea of natural selection, because it seemed to him to open the door to interpretations of biological phenomena in terms of purpose. He could be talked into the conclusion that there was nothing that wasn't strictly mechanistic about this interpretation, but he never liked it. And you had to talk him into it again every few months." (Sturtevant, A. H., Genetics, Vol. 159, 1-5, September 2001, Copyright 2001, Reminiscences of T. H. Morgan.) Whatever his motives, Morgan was known to have prevented his students (including C.M. Child) from publishing work that supported a holistic view of the organism. After Morgan's death, there was an intense and widespread campaign to suppress any approach to biology other than the "new synthesis," neo-Darwinism, with its doctrine of mechanistic genetic determinism and its doctrine of random variation. A developmental biologist, J.M. Opitz (1985), commented that "in one of the most astounding developments in Western scientific history, the gradient-field, or epimorphic field concept, as embodied in normal ontogeny and as studied by experimental embryologists, seems to have simply vanished from the intellectual patrimony of Western biologists." Formative processes are necessarily multidimensional, and that makes calculation and analysis very complex. To a great extent, the geneticists were motivated to study bacterial genes, rather than vertebrate embryos, by the principle that motivated the drunk to look for his car keys under the street lamp, even though that wasn't where he lost them, because the light made it easier to look there. Bacteria are easy to study because they lack the complexity that makes it hard to study an embryo or an animal. The language used in genetics textbooks shows not only that bacteria are treated by geneticists as if they were one or two dimensional, but that the concepts developed for bacterial genetics have been extrapolated to use in describing complex organisms: "Genes interact to establish the body axis in Drosophila. Homeotic Genes control pattern formation along the anterior-posterior body axis." (Essentials of Genetics, M. Cummings and W. Klug, Prentice Hall, 2004.)

One of the basic distinctions in embryology is in the way the cells divide after the egg is fertilized. Oysters and earthworms have spiral cleavage, sea urchins and people have radial cleavage. Several decades ago an experimenter was transferring a nucleus from an egg of an animal with radial cleavage, I think a sea urchin, into the enucleated egg of a snail, with spiral cleavage. The nucleus transplanted across such a great difference in phyla didn't sustain maturation of the animal, but it did permit development to proceed for several rounds of cell division, and the pattern of cell division, or cleavage, and embryonic development always followed the pattern of the phylum to which the egg cytoplasm belonged, never the pattern of the phylum from which the nucleus was derived. The genes in the nucleus, obviously, weren't directing the basic pattern formation of the embryo. One-dimensional bacterial genetics can be used to "explain" multidimensional systems, but it can't be expected to make useful predictions. The idea of complexity, or of multidimensionality, has often been analyzed in terms of "fields," by analogy with a magnetic field, as some property, or properties, that extend beyond any individual part, giving some coherence to the parts. Lamarck was concerned with understanding ensembles of particles and cells, but in his time electricity and heat were the only principles that physics provided that helped to illuminate the nature of living organisms. At the end of the 19th century, though, the physicist J.C. Bose was noticing that all of the properties of life that had interested Lamarck and Buffon--irritability, sensation, contraction, memory, etc.--had their close analogs in non-living substances. Bose, who invented the radio detector that was the core of Marconi's apparatus, found that, in the presence of an electromagnetic field, particles of a substance, such as finely powdered metal filings, cohered into a unified whole. An otherwise invisible, undetectable "field" which in Lamarck's time might have been known as one of the "subtle fluids," was able to organize a myriad of inert particles into a unified whole. I n the early 1920s, Bungenberg de Jong and A.I. Oparin showed how solutions of organic substances could spontaneously organize themselves into complex systems, with differentiated parts. A Russian embryologist, Alexander Gurwitsch, found that the parts of an organ or embryo could exert their stimulating or organizing influence on other cells even through a piece of glass, and by using different types of filter, he identified ultraweak ultraviolet rays as a medium of communication between cells. F.-A. Popp and others are currently studying the integrating functions of ultraweak light signals. Guenter Albrecht-Buehler (who has an interesting website called Cell Intelligence) is investigating the role of pulsed infrared signals in cell communication. Electrical fields produced by cells, tissues, and organisms have been shown t o influence cellular metabolism and physiology, and to influence growth patterns. Closely associated with cellular electrical fields are fields or gradients of pH and osmolarity, and all of these fields are known to affect the activity of enzymes, and so to create environments or fields of particular chemical concentrations. A phenomenon that was well known in the 1930s, when developmental fields were still a familiar part of scientific discussion, was the "cancer field." Before a cancer developed in a particular area, the area showed progessive changes, away from normal function and structure, toward the cancer physiology. I n the embryonic state, damaged tissues regenerate quickly. The metabolism of an embryo or fetus is highly oxidative, converting glucose rapidly to carbon dioxide and water. Both carbon dioxide and water are important regulators of cellular metabolism and function, and the concentrations of both of them decrease systematically with maturity and aging. Both are involved with the most basic aspects of cellular sensitivity, responsiveness, and organization. T o resume the scientific tradition that has "simply vanished," I think we have to recover our ability to think about organisms generally, leaving aside as many of the concepts of genetics as possible (such as "gene," "operon," "receptor"; "the gene" has never been more than an ideological artifact), because they so often falsify the most important issues. The organization of

tissues and organs, and their functional properties, should be the focus of attention, as they were for Lamarck around 1800, and for Johanes Muller, who in 1840 saw cancer as a problem on the level of tissue, rather than cells. For Lamarck, sensitivity and movement were the essential properties of the living substance, and J. C. Bose showed reasons for believing that the characteristics of life were built on related properties of matter itself. Sensitivity, the ability to respond appropriately to the environment, is probably a missing factor in the development of a tumor. The ability to become quiescent, to quietly participate in the ensemble of cells, is an essential feature of the sensitivity and responsiveness of the cells of complex organisms. The factors that support organized appropriate functioning are the factors that help cells to inhibit the excitatory state. If the keys of an accordion or organ didn't spring back after the musician pressed them, the instrument would be unplayable. In extreme physiological states, such as epilepsy or malignant hyperthermia, nerves or muscles become incapable of relaxing. Insomnia and muscle cramps are m i l d e r degrees of a defective relaxation process. Excitoxicity and inflammation describe less generalized cases of a similar process, in which there is an imbalance between excitation and the restorative ability to stop the excitation. Prolonged excitation, resulting in excessive fatigue, can cause a cell to disintegrate, in the process of cell death called apoptosis, "falling away." I n the experiments of Polezhaev and Filatov, the products of cell disintegration were found to stimulate the birth of new cells (possibly by blocking a signal that restrains cell division). This process has been found in every organ that has been examined appropriately. It amounts to a "streaming regeneration" of the organism, analogous to the progressive creation of Lamarck's view. G. Zajicek has demonstrated an orderly "streaming" renewal in several organs, and even the oocytes (which in the Weismannian dogma were formed at a very early stage during embryonic development, and were perfectly isolated from the cells of the mature body) have recently been shown to be continually regenerated in adult ovaries. "Stem" cells turn out to be ubiquitous, and the failure of regeneration and restoration seems to be situational. In the 1950s a magazine article described the regeneration of a finger-tip when the wound was kept enclosed. Decades later, friends (one a child, the other a man in his forties) had accidental amputations of a finger-tip, down to the cuticle so that no visible nail remained. The boy's mother fitted his finger with the tube from a ballpoint pen, and the man used an aluminum cigar tube as his "bandage." Within a few weeks, their fingers had regenerated to their normal shape and length. I think the closed environment allows the healing tissues to be exposed to a high concentration of carbon dioxide, in equilibrium with the carbon dioxide in the capillaries, and to a humid atmosphere, regulated by the osmotic or vapor pressure of the living tissues. Under ordinary conditions, the creation of cells and the dissolution of cells should be exactly balanced. The coordination of these processes requires a high degree of coherence in the organism. Simple increase of water in the vicinity of a cell increases its tendency to multiply, as well as its excitability, and hypertonicity restrains cell division, and reduces excitability. Carbon dioxide, besides helping proteins to release water, appears to increase the ability of proteins and cells to respond to morphogenetic fields. Carbon dioxide is the most universal agent of relaxation, restoration, and preservation of the ability of cells to respond to signals. Progesterone is another very general agent of restorative inhibition. T h e study of regeneration and "stem cells" is helping to illuminate the general process of aging, and to provide very practical solutions for specific degenerative diseases, as well as providing a context for more appropriate treatment of traumatic tissue injury. In aging, the growth and regenerative processes are slowed. There is some evidence that even cell death is slower in old age, at least in some tissues. Since animals with the highest metabolic rate live the longest, the slowing rate of metabolism during aging probably accounts for those changes in the rate of cell renewal. The continually streaming regeneration of tissues is part of the adaptive process, and it is probably intensified by stress. T h e ability to sleep deeply decreases in old age, as a generalized

inflammatory, excitatory state of stress develops. With progressive weakening of restorative cellular relaxation (inhibition), cells become more susceptible to disintegration. It's well established that bone loss occurs almost entirely during the night, and since the catabolic hormones generally affect soft tissues as well as bones, the atrophy of soft tissues ("sarcopenia") of aging is also probably a process that occurs mostly during the night. Mediators of inflammation are at their highest during the night (Cutolo and Masi, 2005). But during the period of growth, the length of bones seems to increase mostly during the night (Noonan, et al., 2004). My interpretation of this is that the stress of darkness accelerates biological processes, whether the process is mainly constructive or mainly destructive. The effect of light supports efficient oxidative energy production, which supports the protective inhibitory processes, by increasing ATP and CO2, and decreases the inflammatory mediators that intensify stress. If organized cellular luminescence is required for a proper balance, then the random luminescence produced by lipid peroxidation (which may be more intense at night--Diaz-Munoz, et al., 1985), might be an important factor in disrupting the balanced streaming of regeneration. Free radicals, whatever their source, absorb a broad spectrum of radiation, and would block luminous signals of all frequencies. Isoprene, produced mainly at night (Cailleux and Allain, 1989), is another ultraviolet absorber that might account for nocturnal regulatory disorders. T h e age pigment, lipofuscin, is known to contribute to degenerative diseases, but the nature of its toxicity has never been established. Its absorptive and fluorescent properties would be very likely to interfere with mitogenetic and morphogenetic radiation. Polyunsaturated fats are the main component of lipofuscin, and these fats in themselves can absorb ultraviolet light. When those fats are present in the skin, exposure to ultraviolet light accelerates the aging of the skin. Free fatty acids often increase during the night, under the influence of hormones such as adrenaline and growth hormone. A single night of poor sleep probably causes significant anatomical damage to the streaming cellular systems that will be repaired over the next few days if a high level of energy metabolism can be combined with a sufficient amount of deep sleep. The things that optimize energy and sleep form the background for supporting the restorative processes. Salt, glycine, carbon dioxide, progesterone, thyroid hormone and sugar all contribute to preserving the organism's energetic reserves by reducing inappropriate excitation. Lamarck's idea that organs developed or regressed according to their use or disuse was often attacked by followers of the Weismann-Morgan genetic dogma. In their view, the influence of the environment was limited to either preventing or permitting the realization of "the genetic potential." Once that predefined potential had been unfolded, the finite and mortal nature of the somatic cells didn't allow for any significant changes, except for depletion and death. One of the high points of Weismannian biology came with the publication of an article in Science, around 1970, that proposed to explain learning in terms of the lifelong loss of brain cells, beginning in humans around the age of 18 months, with a daily loss of 100,000 cells, which would record experience by selective deletion, the way punching holes in cards had been used to enter data into computers. I was present to witness "world class biologists" taking that idea very seriously. A s Sturtevant mentioned in the quotation above, T.H. Morgan couldn't accept any attribution of purposefulness to organisms. In his genetic dogma, changes were only random, and people who denied that were denounced as "teleological" (or metaphysical) thinkers. Changes occurred by deletion, not by meaningful addition. O n e of Pavlov's students, P.K. Anokhin, developed the concept of the Functional System in the 1930s, to explain the purposive behavior of animals. In the 1950s, Anokhin integrated the endocrinology of stress and adaptation into the concept, and F.Z. Meerson continued the work, concentrating on the metabolic and structural changes that protect the heart during stress. The simplest view of the conditional reflex involves the adaptation of an animal to an external signal, identifying it as the occasion for a particular action. Analyzing the Functional System starts with the need of the animal, for example for food, and examines the processes that are involved in satisfying that need, including nerve cells, a sense of hunger,

knowledge of what things are edible, the muscles needed to get the food, and the digestive apparatus for assimilating it. When an understanding of stress physiology is combined with the idea of functional systems, the adaptive meaning of the use or disuse of certain organs is given a concrete basis. Cortisol mobilizes amino acids from muscles that are idle, and makes them available for the synthesis of proteins in the muscles, nerves, or glands that are activated in adapting to the stress. The London taxi drivers whose hippocampus grows as they learn the locations of the streets are very good examples of the processes described by Meerson, Anokhin, and Lamarck, in which the use of an organ in meeting a need contributes to the development of that organ. The balance between growth and regression is shifted during adaptive behavior. Exercise physiologists, without mentioning functional systems, have recently discovered some principles that extend the discoveries of Meerson and Anokhin. They found that "concentric" contraction, that is, causing the muscle to contract against resistance, improves the muscle's function, without injuring it. (Walking up a mountain causes concentric contractions to dominate in the leg muscles. Walking down the mountain injures the muscles, by stretching them, forcing them to elongate while bearing a load; they call that eccentric contraction.) Old people, who had extensively damaged mitochondrial DNA, were given a program of concentric exercise, and as their muscles adapted to the new activity, their mitochondrial DNA was found to have become normal. There are probably the equivalents of constructive "concentric" activity and destructively stressful "eccentric" activity in the brain. For example, "rote learning" is analogous to eccentric muscle contraction, and learning by asking questions is "concentric." "No bird soars too high, if he soars with his own wings." Any activity that seems "programmed" probably stifles cellular energy and cellular intelligence. When activity is meaningful, and is seen to be meeting a felt need, the catabolic and anabolic systems support and strengthen the components of the functional system that has been activated. Everything we do has an influence on the streaming renewal of the adaptive living substance. T h e r e are many therapeutic techniques that could be improved by organized research, for example, investigating the interactions of increasing carbon dioxide, reducing atmospheric pressure, supplementing combinations of salt and other minerals, balancing amino acids and sugars, and varying light exposure and types of activity. The dramatic results that have occasionally been demonstrated (and then suppressed and forgotten) are just a hint of the possibilities. I f we keep our thoughts on the living substance, the pervasive ideologies lose their oppressive power. REFERENCES Chronobiol Int. 2004;21(6):937-47. Postprandial metabolic profiles following meals and snacks eaten during simulated night and day shift work. Al-Naimi S, Hampton SM, Richard P, Tzung C, Morgan LM. "We have previously shown that both simulated and real shift workers showed relatively impaired glucose and lipid tolerance if a single test meal was consumed between 00:00-02:00 h (night shift) compared with 12:00-14:00 h (day shift). The objective of the present study was to extend these observations to compare the cumulative metabolic effect of consecutive snacks/meals, as might normally be consumed throughout a period of night or day shift work." "There was a trend toward an effect of shift for plasma glucose, with higher plasma glucose at night (p = 0.08), and there was a time-shift interaction for plasma insulin levels (p < 0.01). NEFA levels were unaffected by shift." "These findings confirm our previous observations of raised postprandial TAG and glucose at night, and show that sequential meal ingestion has a more pronounced effect on subsequent lipid than carbohydrate tolerance." Anokhin P.K. System mechanisms of higher nervous activity. Moscow, Nauka, 1979. (In Russian). Life Sci. 1989;44(24):1877-80. Isoprene and sleep. Cailleux A, Allain P. Isoprene is one of the main constituents of endogenous origin in exhaled human breath. The concentration of isoprene seems to vary with states of sleep and wakefulness, increasing during sleep and decreasing sharply just after awakening. Thus, isoprene may be involved in in sleep upholding. Exp Neurol. 1978 May 15;60(1):41-55. Evidence of normal mitosis with complete cytokinesis in central nervous system neurons during sustained depolarization with ouabain. Cone CD Jr,

Cone CM. Nat New Biol. 1973 Nov 28;246(152):110-1. Stimulation of DNA synthesis in CNS neurones by sustained depolarisation. Stillwell EF, Cone CM, Cone CD Jr. J Natl Cancer Inst. 1971 Mar;46(3):655-63. Intercellular transfer of toxic components after laser irradiation. May JF, Rounds DE, Cone CD. J Theor Biol. 1971 Jan;30(1):151-81. Unified theory on the basic mechanism of normal mitotic control and oncogenesis. Cone CD Jr. Oncology. 1971;25(2):168-82. Control of somatic cell mitosis by simulated changes in the transmembrane potential level. Cone CD Jr, Tongier M Jr. A c t a Cytol. 1969 Oct;13(10):576-82. Autosynchrony and self-induced mitosis in sarcoma cell networks. Cone CD Jr. Ann N Y Acad Sci. 1980;339:115-31. Ionically mediated induction of mitogenesis in CNS neurons. Cone CD Jr. Science. 1976 Apr 9;192(4235):155-8. Induction of mitosis in mature neurons in central nervous system by sustained depolarization. Cone CD Jr, Cone CM. DNA synthesis and mitosis have been induced in vitro in fully differentiated neurons from the central nervous system by depolarization with a variety of agents that produce a sustained rise in the intracellular sodium ion concentration and a decrease in the potassium ion concentration. Depolarization was followed in less than 1 hour by an increase in RNA synthesis and in 3 hours by initiation of DNA synthesis. Apparently normal nuclear mitosis ensued, but cytokinesis was not completed in most cells; this resulted in the formation of binucleate neurons. The daughter nuclei each contained the same amount of DNA as the diploid preinduction parental neurons; this implies that true mitogenic replication was induced. A n n N Y Acad Sci. 1974;238:420-35. The role of the surface electrical transmembrane potential in normal and malignant mitogenesis. Cone CD Jr. Ann N Y Acad Sci. 1974;238:451-6. Panel discussion: The role of electrical potential at the cellular level in growth and development. Becker RO, Cone CD, Jaffe LF, Parsegian VA, Pohl HA, Weiss L. J Cell Physiol. 1973 Dec;82(3):373-86. Contact inhibition of division: involvement of the electrical transmembrane potential. Cone CD Jr, Tongier M Jr. J Theor Biol. 1971 Jan;30(1):183-94. Maintenance of mitotic homeostasis in somatic cell populations. Cone CD Jr. Oncology. 1970;24(6):438-70. Variation of the transmembrane potential level as a basic mechanism of mitosis control. Cone CD Jr. T r a n s N Y Acad Sci. 1969 Apr;31(4):404-27. Electroosmotic interactions accompanying mitosis initation in sarcoma cells in vitro. Cone CD Jr. R h e u m Dis Clin North Am. 2005 Feb;31(1):115-29, ix-x. Circadian arthritis. Cutolo M, Masi AT.

rhythms and

Neuroscience. 1985 Dec;16(4):859-63. Day-night cycle of lipid peroxidation in rat cerebral cortex and their relationship to the glutathione cycle and superoxide dismutase activity. Diaz-Munoz M, Hernandez-Munoz R, Suarez J, Chagoya de Sanchez V. Lipoperoxidation, glutathione cycle components and superoxide dismutase activity show a day-night rhythm in the cerebral cortex of the rat. The highest lipoperoxidative activity is observed during the night (20.00-04.00 h). The enhancement in lipoperoxidation occurs concurrently with a decrease in glutathione peroxidase activity, an increase in superoxide dismutase activity and an increase in the double bonds in the brain cortex lipid fraction. The changes described in this paper seem to be related to a succession of light and dark periods, or to fasting and feeding periods. We propose that those fluctuations could act as a physiological oscillator with an important role in modulating the membrane properties of the nerve cell. Brain Res. 1977 Mar 4;123(1):137-45. Daily variations of various parameters of serotonin metabolism in the rat brain. II. Circadian variations in serum and cerebral tryptophan levels: lack of correlation with 5-HT turnover. Hery F, Chouvet G, Kan JP, Pujol JF, Glowinski J. Rats submitted to regular 12 h cycles of light and darkness for three weeks were sacrificed at various times of the day. 5-HT, 5-HIAA and tryptophan levels were estimated in the fronto-parietal cerebral cortex. Tyrosine and free and total tryptophan levels in serum were estimated in parallel. Significant circadian variations in 5-HT and 5-HIAA levels were found in cerebral tissues. The peaks of 5-HIAA levels were dectected during the lignt and dark periods respectively, the maximal fluctuations being seen between 17.00 h and 21.00 h, two times separating the light off. Important significant circadian variations in free and total serum tryptophan levels were also observed. In both cases, the maximal levels were found during the middle of the dark phase after the peak of 5-HIAA levels. The circadian rhythm of tyrosine levels in serum was in opposite phase with that of tryptophan (free or total). The diurnal changes in tryptophan content in cerebral tissues seemed thus related to those found in serum. Taking in consideration results obtained in previous studies 16,17 carried out in similar experimental conditions, it was concluded that the parallel increase in serum free tryptophan and in tissues 5-HIAA levels seen during the night were not related to a stimulation of 5-HT turnover. Indeed 5-HT synthesis is minimal at this time16.

Kryukov V . I . An attention model based on the principle of dominanta // Proceedings in Nonlinear Science. Neurocomputers and Attention. I: Neurobiology, Synchronization, and Chaos. 1989. Ed. by A.Y. Holden and V.I. Kryukov, pp. 319-351. Endocrinol Exp. 1976 Jun;10(2):131-7. Diurnal variation in the effect of melatonin on plasma and muscle free fatty acid levels in the pigeon. John TM, George JC. Pigeons maintained on standard diet and held under 12 h daily photo-period in a controlled environmental room, were given intravenous injections of melatonin. A low dose (1.25 mg/kg body weight) of melatonin when given in the middle of the scotophase, produced a significant increase in plasma FFA when estimated at 20 min and 90 min post-injection, whereas no significant change was seen with injections given in the middle of the photophase. No significant change in muscle FFA level was obtained either during the photophase or the scotophase when estimated at 90 min postinjection. With a higher dose (5 mg/kg body weight) of melatonin given in the scotophase, on the other hand, a significant increase in both plasma as well as muscle FFA levels was obtained at 90 min post-injection but there was no effect on plasma FFA at 20 min or 90 min postinjection in the photophase and at 20 min in the scotophase. It is concluded that melatonin has a lipid mobilizing action in the pigeon when administered during the scotophase. Exp Brain Res. 2001 Feb;136(3):313-20. Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat. Kee NJ, Preston E, Wojtowicz JM. "Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60% of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60% of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia." "The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain." A m J Cardiol. 1998 Dec 17;82(12A):24U-28U; discussion 39U-41U. Clinical profiles of plain versus sustained-release niacin (Niaspan) and the physiologic rationale for nighttime dosing. Knopp RH. Niacin is the oldest and most versatile agent in use for the treatment of dyslipidemia. It has beneficial effects on low-density lipoprotein cholesterol; high-density lipoprotein cholesterol; the apolipoproteins B and A-I constituting these fractions; triglyceride; and lipoprotein(a). Together, these benefits lead to a diminished incidence of coronary artery disease among niacin users. The chief constraints against niacin use have been flushing, gastrointestinal discomfort, and metabolic effects including hepatotoxicity. Time-release niacin has been developed in part to limit flushing, and now a nighttime formulation (Niaspan) has been developed that assists in containing this untoward effect. In a pivotal metabolic study, bed-time administration of 1.5 g time-release niacin was shown to have the same beneficial effects as 1.5 g plain niacin in 3 divided doses and to be well tolerated. Previous studies suggest that bedtime niacin administration diminishes lipolysis and release of free fatty acids to the liver; this, in turn, leads to an abolition of the usual diurnal increase in plasma triglyceride, which may result in diminished formation and secretion of triglyceride in the very-low-density lipoprotein fraction. J Pediatr Orthop. 2004 Nov-Dec;24(6):726-31. Growing pains: are they due to increased growth during recumbency as documented in a lamb model? Noonan KJ, Farnum CE, Leiferman EM, Lampl M, Markel MD, Wilsman NJ. Cell Tissue Kinet. 1977 Nov;10(6):557-68. Circadian rhythms of presumptive stem cells in three different epithelia of the mouse. Potten CS, Al-Barwari SE, Hume WJ, Searle J. Physiol Res. 1995;44(4):249-56. Circadian and circaannual oscillations of tissue lipoperoxides in rats. Solar P, Toth G, Smajda B, Ahlers I, Ahlersova E. Circadian and circaannual oscillations of tissue lipid peroxides (LPO) were studied in young male Wistar rats. The concentration of malondialdehyde, one of LPO degradation products, was measured at 3-h intervals during 24 hours in rats, adapted to light:dark 12:12 h regimen in the course of the year. LPO in the liver, thymus and bone marrow oscillated rhythmically in the course of the day and year. Circadian oscillations in all tissues were two-peaked, with zeniths at various times of the light and dark parts of the day. In the liver and thymus, the highest mesors were found during the winter, in the bone marrow during the spring. The same holds for amplitude values, with the exception of the bone marrow which exhibited the highest values during the summer. The reason for the LPO oscillations is probably resulting from the changing ratio of pro- and anti-oxidative capacities in various tissues during the day and the year. B i o f i z i k a . 1976 Jul-Aug;21(4):688-91. [Circadian rhythms of ultraweak chemiluminescence of bean roots] Sul'tsman FM, Petrusevich IuM, Tarusov BN. Circadian rhythms of ultra-weak chemoluminescence of bean roots were investigated. It was found that under periodical change of light and darkness and without subsequent

illumination a periodical change of spontaneous chemoluminescence of bean roots was observed. (The study of antiradical activity of the substances extracted from the root showed the dependence of this activity on illumination conditions. Ukr Biokhim Zh. 1977 Sep-Oct;49(5):64-9. [Effect of "carbostimulin", vitamin D 3 and their mixture on bone tissue regeneration] [Article in Ukrainian] Taran TT, Guly MF, Mykhajlovskyj VO, Dvornykova PD, Fanak MM, Vorobjov NA. "Healing of the bone injury in rabbits was studied as affected by carbostimulin and its mixture with vitamin D3. Some biochemical indexes: the content of sialic acids, calcium and citric acid in blood serum of the animals, intensity of 14C incorporation from NaH14CO3 into the regenerated bone tissue and its proteins as well as histological studies, data, evidence for a positive effect of the mentioned preparations on the bone substance regeneration in the animals under experiment." Biofizika. 1961;6(4):490-2. [Study on ultra-weak spontaneous luminescence of animal cells.] Tarusov BN, Polivoda AI, Zhuravlev AI. Biofizika. 1961;6(4):83-5. Study of the faint spontaneous luminescence of animal cells. Tarusov BN, Polivoda AI, Zhuravlev AI. V o p r Med Khim. 1977 May-Jun;(3):375-81. [Free fatty acids and cholesterol as possible participants in lipid oxidation radical reactions in animal tissues] [Article in Russian] Terekhova SF, Burlakova EB, Elizarova TI. Alterations in concentration of free fatty acids, free cholesterol, native antioxidants as well as in the antioxidative activity were studied in lipids of mice liver tissue and small intestinal mucosa. The intensity of free radical reactions in lipids of animal tissues was affected directly by administration of synthetic inhibitors of the reactions. The inverse correlation was observed between the alteration in concentrations of native antioxidants and free fatty acids as well as between the antioxidative activity of lipids and amount of free cholesterol in them. Free fatty acids appears to be the constant participants in the system of free radical oxidation of lipids, while cholesterol can center the system under distinct level of these reactions intensity. Ukhtomsky A.A. Dominanta as factor of behavior // Collected works. Leningrad, 1950. Vol.1, pp.293-315. Biofizika. 1974 Mar-Apr;19(2):295-9. [Formation of pigments of lipid nature in animal tissues during neoplastic growth and irradiation] Vertushkov VT, Ivanov II, Tarusov BN. Biofizika. 1967 Jul-Aug;12(4):739-41. [Antioxidative activity of blood serum fractions during malignant degeneration studied by inhibition of chemiluminescence] Zakarian AE, Tarusov BN. Biofizika. 1966;11(5):919-21. [Inhibition of chemiluminescence of the blood plasma in malignant growth] [Article in Russian] Zakarian AE, Tarusov BN.

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A R T I C L E Aging, estrogen, and progesterone HOME ARTICLES ABOUT RAY PEAT ART GALLERY LINKS

“Estrogen” refers not just to a family of steroids but to a class of substances that can produce approximately the same effects as estradiol and its metabolites. Even before the pure substance was isolated in the 1930s, the effects of fluid from ovarian follicles were studied. It was soon discovered that many chemicals could produce similar effects. B y the middle of the century, many toxic effects of the estrogens were known, and more are being discovered.

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Cancer, abnormal blood clotting, and infertility were known to be caused by estrogen before 1940, but at the same time the drug companies began calling estrogen “the female hormone,” and claiming that it would improve fertility. Since the 19th century, some people argued that aging was caused by hormonal deficiency; for example, the symptoms of thyroid deficiency resembled aging. The estrogen industry exploited this idea to create the “hormone replacement” business. Some hormones do decrease with aging, but others increase. All of the unpleasant consequences of estrogen excess happen to resemble some of the events of aging. If aging involves the same processes that are created by estrogen, then our knowledge of how to protect ourselves against estrogen can be used to protect ourselves against aging. Estrogen steals oxygen from mitochondria, shifting patterns of growth and adaptation. The balance between what a tissue needs and what it gets will govern the way that tissue functions, in both the short term and the long term. When a cell emits lactic acid and free radicals and the products of lipid peroxidation, it's reasonable to assume that it isn't getting everything that it needs, such as oxygen and glucose. With time, the cell will either die or adapt in some way to its deprived conditions. In aging, tissues generally atrophy, with loss of both substance and activity. Ordinarily, organisms react to stress with increased activity of the appropriate functional system, but when the stress is inescapable, organisms adopt the strategy of decreasing their demands, as in hibernation o r the defensive inhibition that has been called parabiosis, the state of being “not fully alive.” In many situations, serotonin (which is closely associated with estrogen) seems to be an important inducer of this state. There are many indications that estrogen is a factor [e.g., Shvareva & Nevretdinova, 1989, Saltzman, et al., 1989] in functionally suppressed states such as hibernation, social subordination, learned helplessness and depression. Social subordination in animals often involves high estrogen and reduced fertility. In good health, an animal's systems are designed so that certain tissues will be intensely but briefly stimulated by estrogen. This stimulation by estrogen doesn't produce the normal amount of carbon dioxide, so the tissue experiences oxygen deprivation, leading to swelling and cell division. (Along with the reduced carbon dioxide production, there is increased lipid peroxidation). Any similar stimulaton, whether it's produced by soot, or suffocation, or irradiation, will produce the broad

range of estrogen's effects, beginning with inflammation but ending with atrophy or cancer if it is too prolonged. Although, as the 21st century begins, the US government hasn't decided whether to classify estrogen as a carcinogen, it was identified as a carcinogen in the first half of the 20th century--and a variety of carcinogens were found to be estrogenic. Many people studying estrogen's biological effects observed that certain of its effects resembled the changes seen in aging, such as fibrotic changes of connective tissues, accelerated accumulation of age pigment, a tendency to miscarry, or the production of degenerative changes in various organs. But as far as I know, I was the first one to suggest that aging itself involves increased estrogen dominance. (Taking this perspective suggests many specific things to do for aging. And, if radiation injury, and stress, are “estrogenic,” it suggests that specific anti-estrogenic treatments could be appropriate.) I based my argument on the identity of the biochemical and tissue effects produced by aging and by estrogenic excess. At that time, techniques for the accurate measurement of very small amounts of estrogen hadn't been fully developed. I felt that the situation should have been clear, because of the previous decades of research, and I used that as the context for arguing that the reason for age-related infertility was the same as for estrogen-induced infertility or stress-related infertility, namely, the inability to deliver oxygen to the embryo. I thought of the developing embryo as a sensitive indicator of processes that occur throughout the body during aging and stress, and that the destruction of the embryo by the excessive estrogen of the birth control pill was closely analogous to the progressive loss of function that occus in so many tissues during normal aging. After I wrote my dissertation, Terry Parkening, who had worked in the same lab, sent me data from rats, showing that his measurements confirmed the increase of estrogen with aging. Since then, many others have shown that either the absolute levels of estrogen, or the ratio of estrogen to the antiestrogens, increases with aging in a wide variety of organisms of both sexes, including humans. In the 1970s, the claims about estrogen curing osteoporosis apparently had been debunked. At the time, that appeared to be the last of the major claims for the therapeutic properties of estrogen. Studies in dogs were starting to show that estrogen was an important cause of degenerative bone disease, as well as kidney disease, liver disease, thyroid disease, etc. Hormones used in contraceptives were producing cancer in dogs, as well as many other diseases, so dog research was widely abandoned by the drug industry/FDA, in favor of animals that were less sensitive, or differently sensitive, to the hormones. The claims that the industry was making were contradicted by the dog research, so they sought new animal “models” that wouldn't so clearly contradict their claims. A great advantage, for the drug industry, of using rats instead of dogs is that expensive, and often embarrassing, long-term experiments aren't possible in such short-lived animals. Rats die when their tissues still appear to be relatively young. Although excess prolactin (resulting from excess estrogen) in humans is an important cause of osteoporosis, in rats at a certain age and on a certain diet, hyperprolactinemia can stimulate bone growth. [Piyabhan, et al., 2000, Yeh, et al., 1996] This trait of rats could be very advantageous to the estrogen industry. All of the maladies caused by estrogen excess appear to develop in the same way that it interferes with pregnancy, by driving the tissue to require more energy and oxygen than can be delivered to it. Necrosis, the death of sections of tissue, was produced acutely by extreme overdoses of estrogen, or gradually by less extreme overdoses, and if the estrogenic stimulation was milder but very prolonged, the result would usually be tumors, sometimes developing in the midst of atrophy or necrosis. An overdose of estrogen was used to shrink breasts and prevent lactation, and an even larger dose was used to kill breast tissue in treating cancer. A recent study (Toth, et al., 2000) shows that, at least in women, estrogen is closely associated with the general loss of fat-free tissue with aging. This shows a close association between the generalized atrophy of aging and the amount of estrogen in the tissues. I n the case of the embryo that can't implant in the aged or estrogenized uterus, it is because oxygen is being consumed so fast by the uterus that very

little is available for the embryo. The uterus is, effectively, in an inflamed state, and the embryo is in a state that requires abundant oxygen. The general loss of tissue that Toth associated with increased estrogen follows many of the same steps that occur in the failure of the embryo to implant in the uterus: Glycogen is depleted in futile oxidative cycles, protein synthesis is inhibited, lipid peroxides and free radicals accumulate, cellular defensive and repair processes replace normal functioning. (With aging, the loss of glycogen in the brain has serious consequences, including insomnia. Estrogen's depletion of glycogen in other tissues is probably important for their functioning, and thyroid and progesterone are known to help maintain the glycogen stores.) In the last several years, according to the medical literature estrogen would seem to have outgrown nearly all of its bad traits. It protects the brain, the heart, the blood vessels, even the fetus, and it prevents many kinds of cancer, and improves memory, mood, and immunity. And it would still seem to be of great promise in treating breast cancer and prostate cancer, if we took some medical journals seriously. It achieves many of these nice things by functioning as an antioxidant and by increasing circulation, often acting through nitric oxide and serotonin or melatonin. Even though I have read thousands of the articles that said otherwise, the near unanimity of the current research literature can almost give me the feeling that things might not be exactly as they had seemed. In fact they aren't, but the change is in what passes for science, rather than in the way organisms respond to estrogen. Many little pictures are being presented, that seem to add up to a very different big picture. It is clear that this new picture is being painted by those who fund the research, and by some of those whose careers depend on that funding. The people who do the odd little studies of estrogen and cytokines, nitric oxide, regulatory genes, and so on, are usually getting the data they claim to get, and if they draw speculative conclusions about what their study means medically, that's their privilege. But hundreds of these little publications that would be harmless individually, add up to national policy endorsed by the FDA and other powerful agencies--they add up to the same sort of criminal conspiracy that the tobacco industry and its researchers perpretrated throughout the twentieth century. Journals that are considered to be the best in their field publish many papers that simply misrepresent some of the basic facts, while interpreting experimental results that would otherwise have unpleasant commercial implications. For example, the follicular phase is a time of low steroid production by the ovary, until near the end of the phase, just before ovulation, when estrogen rises. The luteal phase is a time of high estrogen and high progesterone synthesis. Many publications describe the follicular phase as a time of high estrogen, and the luteal phase as a time of low estrogen, roughly the opposite of the actual situation. And an even larger number of studies get the results they want by using a short exposure to estrogen to study something which takes a long time to develop. In the last few years, one of the most common tricks of estrogen promotion is to argue that estrogen protects against heart disease and Alzheimer's disease because it relaxes blood vessels, by increasing the formation of nitric oxide. It does generally increase the formation of nitric oxide, but nitric oxide is a toxic free radical that plays a major role in degenerative diseases. And the inappropriate relaxation of blood vessels, coupled with increased clottability of the blood, is a major cause of pulmonary embolisms and venous disorders. In studies of tendons, excess estrogen, aging, and cooking (the phenomenon of the curling pork chop) all caused hardening and contraction of the collagen. When people get to be 90 or 100 years old, the opening between their eyelids is sometimes contracted, presumably because of this process of collagen shrinkage. If this shrinkage of connective tissue affects the large blood vessels, they become narrower and stiffer, so that the blood has to travel faster if the same amount is to be delivered in the same time. Ultrasound can be used to measure the velocity of the blood flow, and increased velocity will correspond to constriction of the channel, if the same amount of blood is being delivered. But many people praise estrogen's

vascular benefits on the basis of tests showing increased blood velocity in large arteries such as the aorta, without evidence that more blood is being circulated. With aging, as arteries become constricted, increased blood velocity is taken as evidence of the pathology. Velocity measurements have to be interpreted in the contexts of tissue perfusion, cardiac output, etc. When the diameter of the artery is considered along with the velocity of the blood, the volume of flow can be determined, and then it appears that progesterone increases blood flow, while estrogen can decrease it. [Dickey and Hower, 1996.] This would be consistent with the known ability of an estrogen excess to cause retarded growth of the fetus, as well as specific birth defects. Estrogen does increase the blood flow to particular organs, but apparently less than it increases their oxygen demand, as can be seen from the color change of estrogenized tissues, toward purple, rather than pink. Measurements of oxygen tension in the tissue show that estrogen decreases the relative availability of oxygen. And when the level of estrogen is very high, metabolically demanding tissues, such as the kidney and adrenal cortex, simply die, especially under conditions that restrict blood flow. [E.g., Kocsis, et al., 1988, McCaig, et al., 1998, Yang, et al., 1999.] When estrogen's effects overlap with the stimulating effects of other hormones, such as pituitary hormones, particular organs undergo something similar to “excitotoxicity.” When estrogen overlaps with endotoxin (as it tends to do), multiple organ failure is the result. The simple need for more oxygen is a stimulus to increase the growth of blood vessels, and estrogen's stimulation of non-mitochondrial oxygen consumption with the production of lactic acid stimulates blood vessel formation. Progesterone, by increasing oxidative efficiency, opposes this “angiogenic” (neovascularization) effect of estrogen. Szent-Gyorgyi spent most of his career studying muscles--from the anal sphincter to pigeon breast to tense goats. One of his most interesting experiments investigated the effects of estrogen and progesterone on the heart muscle. He showed that estrogen excess prevents the increase of stroke volume as the speed increases, but that progesterone increases the stroke volume as the heart accelerates, making pumping more effective without unnecessary acceleration of the heart rate. These effects are parallel to Selye's observation that estrogen imitates the shock reaction. I n shock, the blood pressure decreases, mainly because the blood volume decreases. Water is taken up by the tissues, out of the blood. Much of the remaining blood volume is accumulated in the relaxed veins, and little is returned to the heart, yet the increased need for circulation accelerates the heart, causing each stroke to pump only a small amount. The reduced blood pressure caused many people to think that adrenaline would help to improve the circulation, but actually the “resistance arteries,” small arteries that provide blood to the arterioles and capillaries, are constricted in shock, (Lin, et al., 1998,) and adrenaline usually makes the situation worse. When tissue is poorly oxygenated (or is exposed to estrogen) it takes up water, swelling and becoming more rigid, turgid. (It also takes up calcium, especially under the influence of estrogen, causing muscles to contract.) This swelling effect will be much more noticeable in small arteries than in major arteries with very large channels, but when the effect is prolonged, it will affect even the heart, causing it to “stiffen,” weakening its ability to pump. There is some evidence that estrogen can make large arteries stiffen, over a span of a few months. (Giltay, et al., 1999) Estrogen, by creating an oxygen deficiency, stimulates first swelling, and then collagen synthesis. Collagen tends to accumulate with aging. In shock, the cells are in a very low energy state, and infusions of ATP have been found to be therapeutic, but simple hypertonic solutions of glucose and salt are probably safer, and are very effective. The low energy of cells causes them to take up water, but it also causes the veins (which always receive blood after most of its oxygen and nutrients have been extracted) to lose their tone, allowing blood to pool in them, instead of returning to the heart. (Abel and Longnecker, 1978) This contributes to varicose veins (Ciardullo, et al., 2000), and to orthostatic hypotension, which is seen in women who are exposed to too much estrogen, and very frequently in old people. The energy failure resulting from estrogen excess has been remarkably well

characterized (but the meaning of this for the cell hasn't been explored). The electron transfer process of the mitochondria is interrupted by the futile redox cycling catalyzed by estrogens. G o o d sleep requires fairly vigorous metabolism and a normal body temperature. In old age, the metabolic rate is decreased, and sleep becomes defective. Protein synthesis declines with aging, as the metabolic rate slows. At least in the brain, protein synthesis occurs most rapidly in deep sleep. [Nakanishi, et al., 1997; Ramm and Smith, 1990] In old age, the catabolic hormones such as cortisol are relatively dominant [Deuschle, et al., 1998], and even in youth, cortisol rises during darkness, reaching its peak around dawn. Even in young women, bone loss occurs almost entirely during the night, when cortisol is high. The hormones that are commonly said to prevent bone loss, estrogen and growth hormone, are high at night, rising along with cortisol. Estrogen causes growth hormone to increase, and in the morning, young women's growth hormone has been found to be 28 times higher than men's.[Engstrom, et al., 1999] The growth hormone response to estrogen is probably the result of the changed use of glucose under estrogen's influence, making it necessary to mobilize free fatty acids from tissues. While estrogen is usually highest at night, progesterone is lowest during the night. These observations should suggest that progesterone, not estrogen, is the bone protective substance. The disappearance of water from the blood, as it moves into the tissues during the night, makes sleep resemble a state of shock or inflammation. Since rats, that are active at night, experience the same blood thickening, it's actually the darkness, rather than sleep, that creates this “inflammatory” state. Estrogen increases, and acts through, the inflammatory mediators, serotonin and histamine, to increase vascular leakiness, at the same time that it causes cells to take up water and calcium. The formation of lactic acid, in place of carbon dioxide, tends to coordinate these effects. I n sleep, as in shock, hyperventilation is common, and it sometimes produces extreme vasoconstriction, because of the loss of carbon dioxide. Since glucose and salt are used to treat shock (intravenous 7.5% salt solutions are effective), it seems appropriate to use carbohydrate (preferably sugar, rather than starch) and salty foods during the night, to minimize the stress reaction. They lower adrenalin and cortisol, and help to maintain the volume and fluidity of blood. Thyroid, to maintain adequate carbon dioxide, is often all it takes to improve the blood levels of salt, glucose, and adrenalin. Temperature falls during sleep. Recent experiments show that hypothermia during surgery exacerbates the edema produced by stress, and that hypertonic (hyperosmotic or hyperoncotic) solutions alleviate the swelling. It is possible that light's action directly on the cells helps them to prevent swelling, and that the body's infrared emissions have a similar function. Whatever the mechanism is, adequate temperature improves sleep, and an excessive nocturnal temperature drop probably increases edema, with all of its harmful consequences. At least some of the redox cycles involving NAD/NADH and NADP/NADPH keep electrons from moving beyond ubiquinone (coQ10) and energizing the mitochondria. The cycle that makes nitric oxide is one of these, but some forms of estrogen participate directly as catalysts in this energy-stealing process. One of the effects of blocking electron transfer in the mitochondria is to lower the energy charge of the cells, mimicking the function of the agedamaged mitochondria. Glutathione and protein sulfhydryls are oxidized, because the normal energy pathways that maintain them have been disrupted. Estrogen directly lowers the temperature, while progesterone raises the temperature. Estrogen sets the brain's temperature regulator lower, but, acting through serotonin and other mediators, it can actually lower the metabolic rate, too. F a r from being just the “hormone of estrus,” estrogen, in the form of estradiol and the related steroids, plays a role in organisms as diverse as yeasts, worms and mollusks, and in modifying the function of practically every type of animal cell--skin, nerve, muscle, bone, hair, gland, etc. But, as more and more of its functions come to be understood, it turns out that

many toxic chemicals and stressful physical processes can activate the same functions, and that estrogen's association with the functions of stress makes it a kind of window into some universal biological functions. When Hans Selye brought it to our attention that “stress” was a general life process, he began a process of generalization that led people to be able to see that the changes of aging were also the result of complex interactions between organisms and their environment, rather than some genetic program that operates like a clock running down. When W. Donner Denckla demonstrated that the removal of an animal's pituitary (or, in the case of an octopus, its equivalent optic gland) radically extended the animal's life span, he proposed the existence of a death hormone in the pituitary gland. But the case of the octopus makes it clear that the catabolic, death-inducing hormone is produced by the ovary, under the influence of the optic gland's gonadotropins. This sacrifice of “the old” (the individual) for “the new” (the progeny) is analogous to the tissue wasting we see under the influence of estrogen, as it stimulates cell division. I n Selye's classical stress, the destruction of tissues by the catabolic hormones makes sense in terms of the “functional system” described by Anokhin, in which the hormones of adaptation dissolve one tissue for use by the system which is adaptively functioning, with the production of carbon dioxide by the functional tissue, stabilizing it and regulating the adequate delivery of blood. Progesterone is both an anticatabolic hormone and an antiestrogenic hormone, and in both cases, it protects the functional systems from atrophy. The extreme generality of the phenomenon of “estrogenicity” that was built up during the twentieth century has taken the concept beyond the specific functions of estrus, and reproduction, and the activation of genetic programs of the female animal, to make it necessary to see it as a way that living substance responds to certain kinds of stimulus. And these ways of responding turn out to be involved in the complex but coherent ways that organisms respond to aging. Selye gave various names to the biology of stress, but the “general adaptation syndrome” expressed the idea accurately. But the biology of estrogenicity, like the biology of aging, is so central that any name is likely to be misleading. The historical accident of naming a hormone for estrus shouldn't keep us from thinking about the way estrogen affects our energetics and structure, and how those processes relate to aging, atrophy, cancerization, etc. While progesterone is probably the most perfect antiestrogenic hormone, and therefore an anti-stress and anti-aging hormone, the recognition of a wide variety of estrogen's effects has made it possible to adjust many things in our diet and environment to more perfectly oppose the estrogenic and age-accelerating influences. REFERENCES A d v Shock Res 1978;1:19-27. Alterations in venous compliance in hemorrhagic shock. Abel FL, Longnecker DE “Nine dogs and one primate were placed on total cardiopulmonary bypass and subjected to a simulated hemorrhagic shock procedure.” “These results are interpreted as indicating a different response of the two vascular beds, particularly an increase in IVC [inferior vena caval] arteriolar resistance with a decrease in venous tone. To the extent that the splanchnic bed contributes to the IVC system changes, they are contrary to the concept of a maintained venous tone and decreased arteriolar tone after hemorrhagic shock.” Acta Physiol Scand 1990 Sep;140(1):85-94. Effects of hypertonic NaCl solution on microvascular haemodynamics in normo- and hypovolaemia. Bouskela E, Grampp W, Mellander S. “The aims of this study were to investigate possible resuscitation effects of a single, 10-min, 350-microliters intravenous infusion of 7.5% NaCl in hamsters in hemorrhagic shock and to compare the effects of such infusion with an identical one of 0.9% NaCl on the hamster cheek pouch microcirculation during normovolaemia and after acute bleeding to a hypotension level of about 40 mmHg. No significant differences could be detected between the effects of either infusion given to normovolaemic normotensive hamsters. In the animals subjected to haemorrhage, upon bleeding, arterioles larger than 40 microns constricted, arterioles smaller than 40 microns dilated and venular diameter did not change, while blood flow decreased in all vessels.” “Central nervous and/or reflex excitation of the sympathetic nervous system could account for the constriction of venules and larger arterioles, while a direct effect of hyperosmolarity could explain the dilatation of the smaller arterioles. The study can therefore help to explain some of the mechanisms underlying the reported resuscitation effect of 7.5% NaCl infusion in animals

during severe haemorrhagic hypovolaemia.” Medicina (B Aires) 1998;58(4):367-73. [Physiopathologic effects of nitric oxide and their relationship with oxidative stress]. [Article in Spanish] Carrizo PH, Dubin M, Stoppani AO. Nitric oxide (NO.) is produced from L-arginine, as result of a reaction catalyzed by the enzyme nitric oxide synthase (NOS). The reaction is the sole source of NO. in animal tissues. NO. can control physiological processes (or systems) such as (a) blood pressure; (b) relaxation of arterial smooth muscle; (c) platelet aggregation and adhesion; (d) neurotransmission; (e) neuroendocrine secretion. NO. contributes to the killing of pathogenic microorganisms and tumoral cells by phagocytes. NO. reacts with superoxide anion thus producing peroxynitrite, a cytotoxic ion capable of destroying many biological targets. The superoxide/peroxinitrite balance determines the ONOO- production and, accordingly, is essential for the development of hypertension, atherosclerosis, neurodegenerative diseases, viral infections, ischemia-reperfusion injury, and cancer. Stress 1998 Dec;2(4):281-7. Effects of major depression, aging and gender upon calculated diurnal free plasma cortisol concentrations: a re-evaluation study. Deuschle M, Weber B, Colla M, Depner M, Heuser I. “Depression, aging and female gender are associated with increased diurnal concentrations of total plasma cortisol.” “This finding is in line with the observation that in both conditions medical problems triggered and/or maintained by glucocorticoids (e.g. osteoporosis) are frequently seen.” Adv Exp Med Biol 1975;53:359-69. The effect of nutritional regimes upon collagen concentration and survival of rats. Deyl Z, Juricova M, Stuchlikova E “It has been demonstrated that food restriction put upon animals at any stage of the individual's life, if chronic, produces a distinct increase in the lifespan.” “Collagen starts to accumulate in the kidneys and liver of experimental animals roughly ten months before 90 percent of the population dies out. Thus an increase in collagen concentration can be indicative of involutional changes in the organ (and perhaps organism).” Early Pregnancy 1996 Jun;2(2):113-20. Relationship of estradiol and progesterone levels to uterine blood flow during early pregnancy. Dickey RP, Hower JF. “After correction for gestational age, estradiol was negatively related to uterine artery flow volume (p < 0.05), diameter (p < 0.05), pulsatility index (p < 0.05) and resistance index (p < 0.01) for weeks 5-16 and to diameter (p < 0.05) after week 9. Progesterone was positively related to volume (p < 0.05) and velocity (p < 0.01) for weeks 5-16 and to volume (p < 0.05) for weeks 5 to 9. Spiral artery indices of resistance were unrelated to hormone levels. These results indicate that before the 10th gestational week, uterine blood flow volume is related to progesterone, but not estradiol levels, and suggest that high estradiol levels during and after the 10th week may be associated with decreased uterine blood flow volume.” A n n Surg 1998 Jun;227(6):851-60. Microvascular changes explain the "two-hit" theory of multiple organ failure. Garrison RN, Spain DA, Wilson MA, Keelen PA, Harris PD “Acute bacteremia alone results in persistent intestinal vasoconstriction and mucosal hypoperfusion. Little experimental data exist to support the pathogenesis of vascular dysregulation during sequential physiologic insults.” “Acute bacteremia, with or without prior hemorrhage, caused significant large-caliber A1 arteriolar constriction with a concomitant decrease in blood flow. This constriction was blunted at 24 hours after hemorrhage but was restored to control values by 72 hours.” “These data indicate that there is altered endothelial control of the intestinal microvasculature after hemorrhage in favor of enhanced dilator mechanisms in premucosal vessels with enhanced constrictor forces in inflow vessels.” A m J Physiol 1998 Jul;275(1 Pt 2):H292-300. Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. Geary GG, Krause DN, Duckles SP. “Gender differences in the incidence of stroke and migraine appear to be related to circulating levels of estrogen; however, the underlying mechanisms are not yet understood. Using resistance-sized arteries pressurized in vitro, we have found that myogenic tone of rat cerebral arteries differs between males and females. This difference appears to result from estrogen enhancement of endothelial nitric oxide (NO) production.” Free Radic Res 1999 Feb;30(2):105-17. Inactivation of myocardial dihydrolipoamide dehydrogenase by myeloperoxidase systems: effect of halides, nitrite and thiol compounds. Gutierrez-Correa J, Stoppani AO. “The summarized observations support the hypothesis that peroxidase-generated "reactive species" oxidize essential thiol groups at LADH catalytic site.” Medicina (B Aires) 1998;58(2):171-8. [Myeloperoxidase as a factor of oxidative damage of the myocardium: inactivation of dihydrolipoamide dehydrogenase]. Gutierrez Correa J, Stoppani AO. “Myocardial dihydrolipoamide dehydrogenase (LADH) is inactivated after incubation at 30 degree C, with myeloperoxidase (MPO)-dependent systems.” J Natl Cancer Inst 1981 Aug;67(2):455-9. Synergism of estrogens and X-rays in mammary carcinogenesis in female ACI rats. Holtzman S, Stone JP, Shellabarger CJ. Br J Exp Pathol 1988 Apr;69(2):157-67. Effect of the anti-oestrogen tamoxifen on the development of renal cortical necrosis induced by oestrone + vasopressin administration in rats. Kocsis J, Karacsony G, Karcsu S, Laszlo FA. Bilateral renal cortical necrosis was observed after vasopressin administration in rats pretreated with oestrone acetate. Histochemical (succinic dehydrogenase, trichrome, periodic acid Schiff) and electronmicroscopic methods were used to examine how the anti-oestrogen, Tamoxifen,

influences the development of this renal cortical necrosis. The experiments revealed that in most rats vasopressin did not induce renal tubular necrosis if the anti-oestrogen was administered simultaneously, even during oestrogen pretreatment. The results suggest that oestrogen receptors in the kidney are involved in the induction of renal cortical necrosis by vasopressin.

B r J Exp Pathol 1987 Feb;68(1):35-43. Histochemical and ultrastructural study of renal cortical necrosis in rats treated with oestrone + vasopressin, and its prevention with a vasopressin antagonist. Kocsis J, Karacsony G, Karcsu S, Laszlo FA. Renal cortical necrosis was induced by the administration of vasopressin to oestrogen-pretreated rats. Histochemical (succinic dehydrogenase, trichrome, perjod acid Schiff) and electronmicroscopic methods were applied to examine how the vasopressin antagonist d(CH2)5Tyr(Met)AVP influences the development of this renal cortical necrosis. The experiments revealed that vasopressin did not induce hypoxia or necrosis in the renal tubules if the antagonist was administered simultaneously, even after oestrogen pretreatment. The conclusion is drawn that this pressor antagonist may be of value for the prevention of renal cortical necrosis in rats or in human beings. Invest Radiol 1979 Jul-Aug;14(4):295-9. Serioangiographic study of renal cortical necrosis induced by administration of estrin and vasopressin in rats. Kocsis J, Szabo E, Laszlo FA. We report a serioangiographic method in rats which permits assessment of the course and dimensions of the renal arteries, the durations of the arterial and venous phases, and the intensity and uniformity of the renal parenchymal filling. The procedure was employed to study the mechanism by which administration of vasopressin to rats pretreated with estrin leads to renal cortical necrosis. The pathogenetic significance of the spasm localized on t h e larger renal arteries was proved directly; the possible role of the arteriovenous shunt in the development of the renal ischemia was excluded. Contrib Nephrol 1981;28:1-216. Renal cortical necrosis. Experimental induction by hormones. Laszlo FA. Morphol Igazsagugyi Orv Sz 1974 Jan;14(1):8-12 [The effect os estrogen, ACTH and cortisone administration, as well as hypophysectomy on histological changes in unilateral renal hilus ligation]. [Article in Hungarian] Laszlo F, Monus Z. Eur J Neurosci 1997 Feb;9(2):271-9. Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta. Nakanishi H, Sun Y, Nakamura RK, Mori K, Ito M, Suda S, Namba H, Storch FI, Dang TP, Mendelson W, Mishkin M, Kennedy C, Gillin JC, Smith CB, Sokoloff L. Can J Physiol Pharmacol 2000 Oct;78(10):757-65. Changes in the regulation of calcium metabolism and bone calcium content during growth in the absence of endogenous prolactin and during hyperprolactinemia: a longitudinal study in male and female Wistar rats. Piyabhan P, Krishnamra N, Limlomwongse L “Since endogenous prolactin has been shown to enhance food consumption, calcium absorption, and bone calcium turnover in the pregnant rat, the role of endogenous prolactin in the regulation of calcium metabolism was investigated in 3-day balance studies of female Wistar rats from the age of 3 to 11 weeks.” “Results showed that rapid growth occurred between 3 and 6 weeks with maximum fractional calcium absorption and calcium retention at 5 weeks of age in both sexes. The data also showed a physiological significance of endogenous prolactin in enhancing calcium absorption and retention in 5 week old rats. In an absence of prolactin, peak calcium absorption was delayed in 7-week old animals, and vertebral calcium content of 11-week old animals was reduced by 18%. Hyperprolactinemia in the AP group was found to enhance fractional calcium absorption and calcium retention at 7, 9, and 11 weeks and increased the femoral calcium content by 16%. It could be concluded that a physiological role of prolactin is the stimulation of calcium absorption and maintainance of bone calcium content during growth and development.” Physiol Behav 1990 Nov;48(5):749-53. Rates of cerebral protein synthesis are linked to slow wave sleep in the rat. Ramm P, Smith CT. Using L-[1-14C]leucine autoradiography, rates of cerebral and local cerebral protein synthesis were studied during wakefulness, slow wave sleep (SWS) and REM sleep in the rat. In the cerebrum as a whole, the rate at which labelled leucine was incorporated into tissues was positively correlated with the occurrence of slow wave sleep. We failed to observe a significant correlation of protein synthesis rate with either wakefulness or REM sleep. As in the cerebrum as a whole, most discrete brain regions showed moderate positive correlations between the occurrence of SWS and rates of protein synthesis. There were no brain regions in which rates of protein synthesis showed striking correlations with sleep-wake states. Thus, the occurrence of SWS is associated with higher rates of protein synthesis throughout the brain. These data suggest that SWS sleep favors the restoration of cerebral proteins. Surgery 1991 Oct;110(4):685-8; discussion 688-90. The effect of hypertonic saline resuscitation on bacterial translocation after hemorrhagic shock in rats. Reed LL, Manglano R, Martin M, Hochman M, Kocka F, Barrett J. “Recent work suggests that

moderate hypovolemia causes gut arteriolar constriction, which is ameliorated by hypertonic saline resuscitation. Bacterial translocation should, therefore, be reduced when hypertonic saline (HS) is used as the resuscitative fluid.” “Compared to autotransfusion, hemodilutional resuscitation from hemorrhagic shock with hypertonic saline resulted in a significant reduction in bacterial translocation (p values were 0.03 and 0.04 for 3% and 7 . 5 % hypertonic saline, respectively). The reduction in translocation after hypertonic saline resuscitation may be the consequence of microcirculatory alterations preventing gut hypoperfusion.” A m J Physiol 1999 Feb;276(2 Pt 2):H563-71. Changes in resistance vessels during hemorrhagic shock and resuscitation in conscious hamster model. Sakai H, Hara H, Tsai AG, Tsuchida E, Johnson PC, Intaglietta M. “The unanesthetized hamster dorsal skinfold preparation was used to monitor diameters and blood flow rates in resistance arteries (small arteries, A0: diameter, 156 +/- 23 micrometers) and capacitance vessels (small veins, V0: 365 +/- 64 micrometers), during 45 min of hemorrhagic shock at 40 mmHg mean arterial pressure (MAP) and resuscitation. A0 and V0 vessels constricted significantly to 52 and 70% of the basal values, respectively, whereas precapillary arterioles (A1-A4, 8-60 micrometers) and collecting venules (VC-VL, 26-80 micrometers) did not change or tended to dilate. Blood flow rates in the microvessels declined to