Ray Peat newsletter, 2000. From The Collected Works of Ray Peat.

Ray Peat, "Progesterone: Essential to Your Well-Being", p. 1289

T he hormone progesterone participates in practically every physio logical process, in both men and women. Its tremendous increase during pregnancy serves to stabilize the organisms, both mother and child, during that crucial time. At levels reached just before delivery, progesterone produces anesthesia and contributes to tissue elasticity. The fetus requires large amounts of glucose, and progesterone makes it possible to be provided in abundance for ideal brain growth, by promoting the mother’s ability to use fat for her own energy. It is this efficient use of fat which gives women greater long-range endurance than men. When progesterone is deficient, there tends to be hypoglycemia, often combined with obesity. The stabilizing action of progesterone is especially visible in muscle tissue, such as the uterus, blood vessel walls, the heart, the intestines and the bladder. Less visibly, progesterone stabilizes and normalizes nervous, secretory and growth processes. Biochemically, it provides the material out of which all the other steroid hormones (such as cortisone, testosterone, estrogen and salt-regulating aldosterone) can be made as needed. Progesterone’s simple molecular structure allows it to balance either an excess or deficiency of those other hormones, even when there is a defect in their synthesis. Many factors, including poor nutrition, climate, emotional or physical stress (even excessive running) and toxins, can cause a progesterone deficiency. Use of estrogens, birth control pills and even IUDs can also bring about a deficiency. Animal studies and clinical experience suggests that the prenatal hormonal environment (a mother’s excess of estrogen during pregnancy) can incline a person toward a deficiency of progesterone relative to estrogen. Recent studies show that progesterone prevents stress-induced coronary blood vessel spasms in aged hearts-probably explaining women’s relative freedom from heart attacks, so long as they retain functioning ovaries. Other studies suggest that progesterone has a role in regeneration of damaged brain cells and prolonged growth of the brain. Delayed aging and longer life span have been very clearly related to extra progesterone. Many types of tumors have been prevented and helped

with progesterone. Excessive blood cloning caused by excess estrogen alleviated by progesterone. Pregnancy toxemia and tendency to miscarry or to deliver prematurely are often corrected by progesterone. When epilepsy occurs premenstrually, or first appears around puberty, it is often stopped by progesterone therapy. The hormone has been used successfully in suicidal depression, Reynaud phenomenon, Meniere’s disease, agoraphobia (especially when associated with porphyria, an abnormality of liver metabolism), Bright’s disease (a kidney disorder) and, used as a lotion, in a variety of genital skin problems in children, adults and postmenopausal women. Hot flashes and other menopause problems respond to progesterone therapy. Since progesterone normalizes the immune system (it causes thymus regeneration, for example) it is very effective in autoimmune diseases (which result from adverse reactions to one 5 own tissues) and in those degenerative disease which have an autoimmune component. In several ways both progesterone and thyroid hormone can be considered primary regulatory hormones. Both of them regulate metabolism directly at the energetic and synthetic levels: both have a normalizing, anti-stress action on the pituitary gland; and each has a promoting action on the other. Both are blocked (and consumed) by stress and promoted by light and good nutrition. Both are nutrients in cultures that eat the whole animal, including ovaries and thyroid, butter, cream and milk contain small amounts of progesterone and shellfish seems to be a good source. Disregarding most of the information promoted by pharmaceutical companies and the medical texts and journals which for 30 years have reflected the opinion of those companies (especially regarding the patented synthetic estrogens and glucocorticoids), we can trace a line of research and ideas on the sex hormones, from pioneers such as Loeb, Korenchevsky, and Selye, through a generation that continued to demonstrate the toxicity of estrogen, and the value of progesterone including people like Lipschutz, Dalton and Soderwall. In my dissertation research under Soderwall, I had the opportunity to collect and assimilate data indicating an increased estrogen effect in aging animals and recently, with newer techniques, I have seen similar changes in many menopause women. My research showed that the probable mechanism by which estrogen excess causes infertility is through limiting the availability of oxygen. I showed that anti-estrogenic

substances, such as progesterone or vitamin B, increased the oxygen content of the uterus. This anti-oxygen effect of estrogen suggests a convergence of reproductive aging research with Warburg’s theory that damaged respiration is the primary defect in cancer and also with Selye’s observation that estrogen’s effect resembles the first shock phase of stress reaction. Early research had also shown that estrogen diminishes liver glycogen storage while progesterone increases both blood sugar and liver glycogen. It is well known that hypoxia (oxygen deficiency) damages the fetal brain, but probably less well known that hypoglycemia—either chronic or acute—can cause brain damage and retardation. Oxygen deficiency, by lower metabolic efficiency, will cause hypoglycemia. Estrogen causes hypoxia at every imaginable site, from lung, through vascular fibrin (clot material lining blood vessels and red cells) and extracellular collagen (a glue-like part of connective tissue) and edema, to intracellular metabolism. Estrogen is also a promoter of insulin release and action, lowering blood sugar and promoting fat synthesis. Estrogen and another common anti-oxygen material, excessive unsaturated fats (vegetable or fish oils) have both been demonstrated to cause the birth of small-brained, retarded animals. Recent studies imply that about half the children identified as hyperactive have experienced prenatal stress. The most urgent need for progesterone therapy, I think, is preventing a continuing epidemic of brain damage. Beyond that, many studies have found that the use of natural progesterone increases a child’s IQ, typically by around 35 points and produces personalities that are more “independent, individualistic, self-assured, self-sufficient and sensitive.”1

Progesterone vs. Hypoglycemia Protection against hypoglycemia is probably the main mechanism. Diabetic mothers often have precocious children, if they aren’t damaged by drugs and irrational diets. 10 g to 15 g per pregnancy, at increasing dosage, seems to be the optimal amount, when there is some sign of excessive estrogen or unexpected toxemia. The American Medical Association Department of Drugs, which warns against certain sex hormones being used during pregnancy, has specifically excluded progesterone from those others which are “now contraindicated in early pregnancy.”2

Hypoglycemia (which can result from any respiratory defect) can produce malfunction of any tissue, but brain dysfunction and immune dysfunction are very common effects. Adamkiewics has shown that allergic reactions to a given substance will decrease from 100 % to 0 %, when the blood glucose increases from, for example, 50 mg to 150 mg or more. Soviet research shows a similar involvement of blood sugar level in various “psychosomatic” ailments. Progesterone (and thyroid) will help in most allergic diseases, including the autoimmune and “collagen diseases,” because it helps to maintain blood sugar (promoting respiration and improving use of fat-sparing glucose) and also because it stabilizes lysosomes (enzyme packets in cells, which are involved in inflammation processes). The group of enzymes known as superoxide dismutase (SOD) are probably involved in the protective effects of progesterone, since one of my assays to determine the action of estrogen turns out to be an inverse indicator of SOD-that is, progesterone would seem to turn on this protective enzyme. Although progesterone and cortisone both raise blood sugar and stabilize lysosomes, their effect on the brain is very different. In large doses, progesterone is sedative and anesthetic, while cortisone is stimulating and causes changes in the brain, which resemble aging. An excess of cortisone also tends to elevate estrogen, which was found (in animal experiments) to interfere with memory. High estrogen traits can be acquired by environmental stress and can be passed on to offspring, as discovered by L.C. Strong in his mice, and as confirmed recently in rats that were stressed during pregnancy. It has been observed that the ratio of brain weight to body weight corresponds directly to longevity. The brain has a nourishing, trophic influence on other tissues. A stable, efficient brain is an anti-stress agent. The hormones of stress age various tissues, including connective tissue. Good nutrition, including the anti-stress substances found in certain foods, will simultaneously optimize intelligence and increase the healthy life span. Congenital defects are increased by stress and poor nutrition during pregnancy and, conversely, reduced by good nutrition hormone supplementation and stress reduction. An excessive estrogen/progesterone ratio is more generally involved than either a simple excess of estrogen or a deficiency of progesterone, but even this ratio is conditioned by other factors, including age, diet,

other steroids, thyroid and other hormones. The relative estrogen excess seems to act by producing tissue hypoxia. Symptoms in cycling women are most common around ovulation and in the premenstrual week, when the estrogen/progesterone ratio is normally highest. The early 20’s, late 30’s and menopause are the periods when the ratio is most often disturbed. These are also the ages when thyroid disorders are commonest in women. I have observed the use of progesterone transdermally (applied to the skin) in about 400 women suffering from the full range of perimenstrual symptoms, including migraine, acne, depression, mastalgia (breast pain), edema (water retention and swelling), and lethargy. I found that nearly all the women who apply the lotion themselves, are able to find the appropriate dosage for controlling their symptoms. Occasionally, thyroid therapy, weight reduction: or change in some aspect of lifestyle is necessary for complete relief from symptoms. When some women said the progesterone had no effect, it turned out that they were applying it as sparingly as they would a rare perfume-just touching it to their wrists. Anesthesia (or drunkenness) from a very large overdose is the only negative side effective reported in the literature. Experimenting with very large doses of natural progesterone on myself, for migraine, I found that there is a temporary antagonism to testosterone, causing small symptoms, including a slight sense of gregariousness, an urge to socialize. However, synthetic progestins do have harmful side effects including breast tumors. Unfortunately, most physicians do not yet know the difference between natural progesterone and synthetic progestins. At our health resort/clinic, we’re finding that most women respond dramatically to progesterone support, but don’t remain chronically dependent on it. During their stay, clients are provided specialized, indulgent care, along with progesterone and other therapies. We consider it essential, as well, to teach them the principles of maintaining optimum health through good nutrition. Results are impressive and usually permanent.

Repairing Immunodeficiencies Townsend Letter for Doctors, November, 1989

L ast summer’s death of most of Europe’s seals from viral diseases suggests the possibility that their immune systems were weakened. The coincidental publication last spring of a study of the relatively remote Arctic seals of Spitzbergen,1 which found surprisingly high levels of dioxins and other toxins in the animals, suggests that the aquatic carnivores closer to the sources of pollution might simply have been the first large group of animals to reach an intolerable level of chemical immunosuppression. The people who eat the same fish that the seals eat, and breathe the same air, might also be experiencing some degree of increased susceptibility to infections. For several decades, the death rate from some kinds of opportunistic infection has been increasing,2 and as bacterial infections came under control in the 1960’s they tended to be replaced by less common infections such as Pneumocystis carinii.3 Acquired (or secondary) immune deficiency has been a familiar phrase in immunology for at least a generation, and the recognition of the condition itself, under different terms, has been part of medical knowledge for many generations. Before 1981, typical textbooks listed cancer, chemotherapy, ionizing radiation, malnutrition, aging, parasites, fungal infections, and viral infections among the known causes of acquired immune deficiency.4 After 1981, the term “acquired immune deficiency syndrome” was appropriated by the molecular virologists, who were familiar with the ability of viruses to cause immunosuppression, and who, with impressive speed, determined that the “new” syndrome was caused by a certain new virus, the human immunodeficiency virus (HIV) or the human T-cell lymphotropic virus type III (HTLV-III). Peter Duesberg was one of the few molecular virologists who doubted that a virus of that sort, all by itself, could cause disease.5 An important implication of the identification of the HIV as the cause of AIDS has been—for the molecular virologists who ignore Duesberg—that a specific vaccine or genotoxic chemical should be able to destroy the specific pathogen. Very little attention has been given to the question of whether a person’s good health can be maintained despite the presence

of the “viral gene.” And the lingering effects of the “central dogma” of molecular genetics still discourage serious investigation of the question of whether such genes can be cleared from the genome under certain conditions without destruction of the cell. Since human exposure to known immunosuppressants has been increasing during the years that the incidence of opportunistic infections has been growing, a real investigation of the cause or causes of AIDS will involve doing some scientific epidemiology, to learn whether some factor other than the HIV has a crucial role. Some of the factors that I have given attention to, in working with “ordinary” (i.e., complex, traditional) immunodeficiency—viz., a deficiency of the anti-glucocorticoid hormones, a dietary excess of iron and unsaturated fats,6 a nutritional deficiency of vitamin A, folic acid, copper, and protein, an exposure to pediculocides and other chlorinated hydrocarbons including dioxins, etc.—should probably be included in such an epidemiological study. Even if such factors turn out not to be crucial in AIDS-HIV, my informal studies and observations since 1973 indicate that examining and correcting as many of them as possible can, inexpensively and safely, promote recovery from many chronic infections and other diseases associated with some degree of acquired immunodeficiency. Whatever the cause of AIDS associated with viral infection may be, it is likely that an appropriately designed supportive treatment will at least slow the progress of the disease. In spite of a few virologists who still claim that there is no such thing as an immune stimulant, hundreds of immune-promoting substances have been studied and described, and a few of them (e.g., levamisole, inosiplex) are well-known. Although more meaningful tests are now available, skin tests have been used for several decades to demonstrate that immune stimulants or improved nutrition7 can reliably shift the immune system from anergy to reactivity. Anything that intensifies metabolism tends to be an immune stimulant, other things being equal. A subnormal temperature is a common feature of chronic infection and early cancer, until a late stage of intense catabolism with fever. Since most of the immune stimulants are harmless, compared to the genotoxins, the reluctance to test them is ideological, rather than scientific. My Stedman’s Medical Dictionary (23rd edition) illustrates the psycho-linguistic environment: “immunodeficiency” and “immunodepressant” and “immunosuppressant” are defined in a way that any

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native English speaker would understand. However, “immunological enhancement” (p. 464) is explained as involving the suppression of cellmediated immunity (to prevent rejection of a tissue allograft). A major part of the history of medicine seems to have dropped out of medical English. In one line of thinking a variety of malfunctions of immunity can be created by a single factor, such as energy deficiency, acting within the organism’s special history or constitutional individuality. Allergies, autoimmune disorders, and chronic infections or skin-test anergy, can be seen as aspects or phases of a generally impaired reactivity of the organism, shaped by many trophic influences of nerves, hormones, nutrition, and by toxins, temperature, radiation, etc.8 Accordingly, I have recommended the use of techniques of immunity-promotion (or normalization) for allergies, auto-immune disorders, and chronic infections or immune deficiencies, taking into account the person’s history of environmental insults, nutritional deficiency, family traits, and present hormonal, nervous, and metabolic status as far as possible. Beginning in 1973, a clinic in Eugene, Oregon (a city which is notorious for allergies, because of the surrounding grass-seed farms which produce pollen in the spring, and smoke from field-burning in the summer and fall) had very good results with their allergy patients when they gave them supplements of vitamin A, pantothenic acid, and vitamin C. Later, thyroid extract or triiodothyronine and magnesium were added to the other supplements for patients who had problems more serious than ordinary allergies. We found that many people with acne, bladder or kidney infections, periodontitis and sinusitis seemed to be deficient in both thyroid and vitamin A even when they were taking supplements of those materials. At higher doses of both, many of those people quickly got over their infections. Many people with colitis, myositis, bursitis and arthritis had sudden relief from their symptoms on this, or a similar program. We have assumed that some toxin might be interfering with the biological effects of thyroid and vitamin A. If thyroid and vitamin A can’t be used efficiently to form steroids, a steroid imbalance is likely. Unopposed cortisol is immunosuppressive in several ways, including thymic hypoplasia,9,10 depression of the histaminolytic activity and mono-oxygenase activity of the liver, contributing to chronic allergies,11 and it can induce the expression of some types of retrovirus.12

Although one of the important functions of vitamin A is its involvement in the formation of the steroids pregnenolone and progesterone (both of which moderate the effects of cortisol), it also has some hormone-like actions directly on the cells of the immune system, and it stimulates production of interleukin-2 and both inhibits generation of specific suppressor cells and limits the intensity of activation of suppressor cells.13 The possibility of vitamin A toxicity is reduced by using the thyroid hormones and vitamin E. Pregnenolone and progesterone have a vitamin A-sparing effect, besides their direct protective action for the thymus, and they also have the very general protective action which Selye called “catatoxic.” Both of these hormones have been effectively used to treat various auto-immune ailments. They tend to raise the body temperature and metabolic rate, yet they are anti-catabolic. Vitamin A, thyroid, progesterone, and the related steroid, dehydroepiandrosterone, all oppose estrogen, which has several immunosuppressive effects, including a cortisol-like thymic atrophy, hypoactivity of T cells, and reduced production of gamma-interferon and interleukin-2, reduced natural killer cell activity, and it probably has a role in the development of some auto-immune diseases.14 Subnormal body temperature promotes estrogen secretion. AIDS, which has been called “slim disease” in Africa, often ends with extreme wasting. Many physicians are horrified at the thought of treating immunodeficiency with thyroid, because they associate hyperthyroidism with weight loss. Two young women, who were diagnosed as having “allergies” and supposedly auto-immune pituitary hormone deficiency, and who each weighed around 70 pounds and was considered to be “terminal” (though they both ate normal amounts of food), recovered quickly with a thyroid supplement and a diet emphasizing eggs and fruit. About 80 years ago, when surgery was first being done to remove goiters, the whole gland was removed, no supplementary thyroid hormone was given, and the patients often died of a wasting syndrome, which was named “cachexia strumipriva.” Thyroid function is essential to all cell processes, including protein assimilation and synthesis, formation of growth hormone, etc. Without thyroid hormone to sustain respiration, inefficient glycolysis wastes energy; unoxidized lactate provokes catabolism of liver protein. Hypoglycemia stimulates secretion of glucocorticoids, which maintain blood sugar at the expense of rapid catabolism of protein. It

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is characteristic of people dying with AIDS to have no thymic tissue, as well as having other signs of extreme stress. It seems clear that a safe anti-stress, anti-cachexia, thymus-protecting program would have prolonged their life. Triiodothyronine is often the essential factor in reversing a cachectic state. Although optimal thyroid function can increase the metabolic rate, it is not catabolic because it maximizes bioenergetic efficiency. Adamkiewicz demonstrated the importance of blood glucose in anaphylaxis and allergy.15 In a vicious circle, histamine tends to exacerbate hypoglycemia (e.g., by its acetylcholine-like actions) and it is directly immunosuppressive in many ways. It inhibits lymphocyte proliferation in response to stimulation, it inhibits antibody formation and lymphocytotoxicity, it suppresses cutaneous delayed hypersensitivity and release of lymphokines, and it suppresses both the generation of T-helper cells and their effector functions.16–19 Besides the ordinary antihistamines and receptor blockers, the release of histamine can be inhibited by many other substances which are immunoprotective, such as epsilon-aminocaproic acid, and by the saturated fatty acids, from pentanoic to dodecanoic.20 These fatty acids are known to be assimilated as quickly as glucose, and so it seems likely that part of their antihistamine effect is similar to the glucose effect demonstrated by Adamkiewicz, and that both effects could be largely the result of increased availability of metabolic energy. Since tumors often contain very large quantities of mast cells, immune therapy for tumors should take histamine into account. Since 1970 I have experimented with some unconventional anti-inflammatory substances, including some of the local anesthetics, which seem to have a safe and effective antihistamine action. I think some of the anti-cholinergics which have “anti-viral” activity (e.g., amantadine) are analogous in their mechanisms of activity. Around 1960, ammonia was found to have an “anti-viral” effect, apparently by altering the host cell’s structure or function, rather than by a direct virucidal action.21 Following that discovery, many amines were found to have some anti-viral activity. Local anesthetics, anticholinergics, and the anti-viral amines can be thought of as a pharmacological family. Inosiplex apparently takes advantage of some of those properties, and it too acts on the cell, rather than on the virus.22 The central inhibitory system regulated by gamma-aminobutyric acid, the GABA-ergic system, is protective against stress,23–25 and ap-

pears to protect immunity by limiting the organism’s recourse to cortisol, and by supporting the synthesis of alternative steroids.26,27 Gammahydroxybutyrate and its lactone are closely related to GABA metabolic pathways, and have anesthetic and anti-stress protective effects which appear to result mainly from central inhibition, and from an antiglucocorticoid effect. The lactone has been found to have a strongly protective effect against intra-cerebrally inoculated viruses,28 and it is remarkably non-toxic. The anesthetic and anti-convulsant effects of progesterone probably synergize with and reinforce the GABA-ergic system. Many other substances of low toxicity have beneficial effects on the immune system or on some other aspect of resistance, and might be considered in an integrated approach to immune restoration. Just as optimal nutrition must take age and other factors into account, an integrated therapy for immune deficiency must be sensitively designed for the needs of the individual. In many places where AIDSHIV patients are treated, a panic mentality has taken over, and ordinary supportive therapies are neglected or rejected because they are outside of someone’s “treatment protocol.” A stereotyped protocol can be appropriate when therapy is directed toward the mechanistically understood elimination of a pathogen, but in therapy to strengthen immunity, individualization, alertness, and judgment are more appropriate. The complex nature of every patient should be recognized, in deciding what materials to use and how to use them.