Also see:
Quotes: Thyroid, Estrogen, Menstrual Symptoms, PMS, and Infertility
Ray Peat, PhD on the Menstrual Cycle
Estrogen Related to Loss of Fat Free Mass with Aging
Fat Tissue and Aging – Increased Estrogen
Estrogen Levels Increase with Age
Ray Peat, PhD on the Benefits of the Raw Carrot
Consult a medical professional regarding all things related to your health.
Despite popular opinion, PMS isn’t normal. It’s akin to a check engine light that goes off monthly. If you’re looking to have an easy menopause, don’t ignore PMS. If you’re looking for easier weight management, it’s recommended to remedy the hormonal imbalances and metabolism suppression associated with PMS. This blog discusses the underlying issues of PMS and provides insight into correction. Correction won’t involve birth control.
The Menstrual Cycle
The menstrual cycle encompasses 26 to 30 days involving cyclical rises in certain hormones. The two steroidal hormones responsible for creating the menstrual cycle are progesterone and estrogen. Both are made from cholesterol in various female tissues but mostly the adrenal glands and ovaries. Fat cells in the overweight are also a chronic source of estrogen. Progesterone and estrogen are antagonistic hormones, each with their own function, that create PMS-free menstrual cycles when balanced.
Estrogen has tightly controlled functions during the cycle and stimulates the release of the egg. Estrogen rises to its highest levels at ovulation which occurs between days 12 to 16. Estrogen in healthy women should only be dominant for a few hours each month. The modern diet, birth control, poor lifestyle, stress, inadequate liver function, gut toxicity, and IUDs are causing women to be estrogen dominant 24/7.
Estrogen is very dangerous if not checked by its opposing hormone, progesterone, which surges from the corpus luteum after ovulation and lowers estrogen and its effects by eliminating it from cells. When progesterone is available, it destroys the estrogen receptor and inhibits the enzymes (sulfatase, aromatase, and glucuronidase) that stimulate estrogen production. Progesterone is very strongly anti-estrogen.
Progesterone stimulates the making of the lining of the uterus. If the egg is fertilized, this “progestational hormone” (progesterone) is produced in very large amounts in healthy mothers to oxygenate the fetus and protect it from stress.
Progesterone is one of the most protective substances the body makes allowing us to handle stress, create energy, offset estrogen, and regulate blood sugar and salt metabolism without the need to produce cortisol and aldosterone respectively. When progesterone is high, it minimizes the stress inducing effects of estrogen, cortisol, and aldosterone.
When progesterone is high after ovulation, PMS doesn’t exist or is minimal at worst. In a progesterone deficient (also know as estrogen dominant) state, the effects of estrogen are unopposed resulting in the common symptoms of PMS – bloating, cramping, heavy bleeding, breast tenderness, acne, mood changes, food cravings, back pain, migraine, fluid retention, etc. The progesterone deficient state is also associated with irregular periods, infertility, and miscarriage as these are the unfortunate effects of unopposed estrogen. So the question is what are some of the factors that lead to this progesterone deficient state?
Thyroid Deficiency and Progesterone
Not many know that the thyroid has a nickname – “the third ovary” – due to its role in producing hormones involved in fertility and the menstrual cycle. High cholesterol was historically used as a diagnostic marker for hypothyroidism. When thyroid is low, cholesterol turnover into bile salts and steroids falls resulting in a rise in serum cholesterol.
The thyroid deficient state is an important factor in estrogen dominance. Thyroid and vitamin A are needed for the conversion of cholesterol into pregnenolone; deficiency in any of these substances decreases steroid synthesis. Pregnenolone is the precursor to both progesterone and DHEA. Progesterone is a protective hormone that offsets or opposes the effects of estrogen (and aldosterone). Low thyroid function, low cholesterol, and/or a vitamin deficiency (particularly Vitamin A) results in a low progesterone. The hypothyroid have a difficult time converting carotene to Vitamin A sometimes resulting in orange calluses on the hands and feet which further feeds the progesterone deficiency. Vitamin A in liver, pastured eggs, and dairy are recommended.
A progesterone deficiency contributes to the overproduction of cortisol and serotonin which further feeds the stress state associated with estrogen dominance. Cortisol is associated with the accumulation of back and belly fat. Until the progesterone deficient state is addressed, weight loss in these areas will prove difficult. Supplemental progesterone from day 14 until the first day of menstruation helps remedy PMS symptoms and sometimes gets rid of them completely. Ultimately though, the health of the thyroid is paramount to improving progesterone production. Anything that contributes to thyroid deficiency will work against your efforts to correct PMS (and fat loss). If progesterone doesn’t help, estrogen removal, nutrition, and thyroid health will have to be ramped up.
“Thyroid is needed to keep the cell in an oxidative, rather than reductive state, and progesterone (which is produced elsewhere only when cells are in a rapidly oxidizing state) activates the processes that remove estrogen from the cell, and inactivates the processes that would form new estrogen in the cell.” -Ray Peat, PhD
Thyroid Deficiency, Bile Salts, and Bowel Regularity
Bile salts are another substance made from cholesterol in the liver and stored in the gallbladder. Bile salts are used to remove toxins and old hormones, excrete excess cholesterol, and breakdown dietary fats that enter the small intestine.
Bile salt production, like steroid synthesis, falls when the metabolic rate decreases. Bile is vital for the removal of estrogen and other toxins through the bowel that have been readied for excretion by a healthy, nourished liver. A toxic bowel can negatively affect this process (glucornidation) if glucoronic acid is stripped off the estrogen leading to estrogen re-absorption back into the body. Bamboo shoots and raw carrots lower gut bacteria and support estrogen removal.
Bowel regularity is needed to reduce estrogen and exposure to endotoxin (lipopolysachharides). A sluggish bowel results in the re-absorption of estrogen back into the bloodstream (enterohepatic recirculation) and increases exposure to endotoxin putting further strain on the liver. Thyroid deficiency is historically related to constipation so once again the health of the thyroid is a vital component to prevent or reverse estrogen dominance. Salt and sugar lower cortisol, adrenaline, and aldosterone and improve gut motility as does a diet that contain foods digestible by humans.
Birth Control
Early in the 20th century, natural dessicated thyroid had been used to correct infertility, menstrual irregularities, delayed or premature onset of puberty (or menopause), and premenstrual syndrome. The medical community at large has forgotten this valuable information and now chooses to poison women of all ages by giving them birth control.
The effects of birth control are due to excess estrogen which inhibit pregnancy. Estrogen has been known as the hormone that causes miscarriage, infertility, and spontaneous abortion. This effect in birth control is intentional and harmful as it manipulates hormones in such a way which promotes age-related degeneration. Did you know that the “morning after pill” is a very high dose of estrogen? For twenty years, this same pill was previously said to “prevent abortions” by the synthetic estrogen industry. The industry was and still is confused about estrogen.
Excess estrogen is associated with osteoporosis, cancer, stroke, heart disease, and serves as a prime player in accelerated aging. Dementia, migraine, chorea, and scleroderma are more dysfunctions promoted by estrogen dominance. Progesterone and high thyroid are protective against all of these.
In much the same way birth control is poisoning younger women, hormone replacement treatment (HRT) is poisoning post menopausal women as the medical community falsely teaches that this population lacks estrogen. Menopause is the prolonged exposure to estrogen. The Women’s Health Initiative Study (2002) was a major showcase of the tragic flaw in allopathic medicine’s methodology. Instead of showing the wonders of estrogen, the study lead to premature death in the estrogen treated group. Gary Null, Phd et al. discusses this in “Death by Medicine.”
“Synthetic hormone replacement therapy (HRT) does not prevent heart disease or dementia, but does increase the risk of breast cancer, heart disease, stroke, and gall bladder attack.
As many as one-third of postmenopausal women use HRT. This number is important in light of the much-publicized Women’s Health Initiative Study, which was halted before its completion because of a higher death rate in the synthetic estrogen-progestin (HRT) group.” -Gary Null, PhD
Menopause occurs not due to lack of estrogen as the estrogen industry would have us believe. The fall in the metabolic rate as aging occurs leads to a fall in progesterone production which leaves estrogen unopposed which further suppresses metabolism, stimulate the pituitary, and promotes stress and aging. The inability to cyclically make progesterone leads to ceasing of menstruation. Progesterone is the hormone that is lacking in menopause NOT estrogen. Pharma’s synthetic progesterone (progestins) acts more like estrogen and cause cancer.
“Since the Women’s Health Initiative study involved the use of Prempro, the emphasis of the industry has been to divert attention from the toxic effects of estrogen, by blaming everything on “progesterone.” An intense campaign is underway to assign all of estrogen’s harmful effects to progesterone.” -Ray Peat, PhD
“Estrogen can be produced in so many different tissues, there’s no deficiency condition that has ever been defined factually. Menopause is exhaustion of the nerves that regulate the pituitary, caused by overexposure to estrogen. Thus, menopause is the result of prolonged exposure to estrogen. In addition to the estrogen produced by many different tissues, other estrogenic substances and xenoestrogens, which are not measured, exacerbate the estrogen dominance condition. These include soy products and other phyto (plant) estrogens (such as black cohosh, sage, pennyroyal, etc.), all unsaturated oils, synthetic estrogens in commercial meat and pesticides.” -Ray Peat, PhD
Menopause and post-menopause is an estrogen dominant state so everything described here for the PMS sufferer would benefit the menopausal woman. This thought makes sense when you consider the dysfunctions associated with menopause like increased risk of osteoporosis, stroke, heart disease, and cancers of the breast and uterus which are all highly correlated with estrogen excess. Progesterone and high thyroid, once again, protects against these conditions. The medical community appears to have the situation backward.
Polyunsaturated Fatty Acids (PUFA)
Digestible seeds don’t stand the test of time. Part of seeds’ and seed oils’ (as well nuts, bean, grains, above ground vegetables) defense mechanism against being eaten is they contain polyunsaturated fatty acids which poison the digestion of the animals that consume them.
In addition to poisoning protein digestion, PUFA promote the production of estrogen in the human body, and estrogen promotes the release of free fatty acids (PUFA) into the blood which block glucose oxidation (Randle Effect) creating a metabolism with an over reliance on fatty acids, which has a myriad of negative effects. Women are more likely to get diabetes as a result of this chronic elevation in free fatty acids. Birth control, because of its estrogen content, has been shown to have this effect.
PUFA and estrogen both block thyroid function at multiple points, decreasing progesterone production, and harming liver function. Because estrogen and PUFA promote each other and both have a metabolism lowering effect, trying to lose weight in an estrogen dominant state can prove very difficult as can correcting hormonal imbalance. Saturated fats, like coconut oil and butter, help offset the affects of PUFA.
One of the effects of excess PUFA on the liver is that it reflexively withholds cholesterol. For those that see cholesterol as harmful, this is a positive effect. However, because cholesterol itself is anti-stress and is the raw material for all of the steroids, vitamin D, and bile salts, this action serves as just another toxic effect. The withholding of cholesterol affects bile salt and steroid synthesis contributing to poor estrogen detoxification and progesterone production.
Liver Health
Digestible proteins from animal-based sources (NOT vegetable sources) are important as they are needed by the liver to detoxify estrogen and other toxins. A healthy liver will destroy all estrogen (and PUFA) that passes through it. A protein deficiency results in thyroid deficiency as estrogen, which is strongly anti-thyroid, is allowed to accumulate. There is a negative feedback loop that occurs here as thyroid hormone activates liver metabolism, but it’s being suppressed due to estrogen accumulation and high free fatty acids in the blood which further lowers thyroid function and thus liver function allowing more estrogen to accumulate.
Remember that PUFA poison the proteolytic enzymes responsible for protein digestion so you can be “eating well” and still have the symptoms of protein deficiency. B vitamins are also a needed component for a healthy liver. Fruit sugars are liver friendly and allow it to store energy (glycogen) for use in detoxification or during times of low blood sugar.
Much of the active thyroid hormones, triiodothyronine (T3), is made in peripheral tissues not the thyroid itself. T4, or thyroxine, is an inactive hormone that cells cannot use and must be converted to T3 to be used. Approximately 70% to 80% percent of this conversion happens in the liver and requires glucose and selenium for the enzymes (deiodinases) involved in the conversion to function. The health of the liver is paramount to correcting hormonal imbalances and maintaining or improving the metabolic rate.
Tryptophan and Serotonin
As the precursor to serotonin, excess dietary tryptophan can be dangerous. Food rich in tryptophan are egg white, muscle and organ meat, and some fruits like kiwis, prunes, plums, pineapple, and bananas. The body can convert tryptophan to vitamin B3 or serotonin, but during stressful times, aging, and malnutrition the preferred pathway is to serotonin. Tryptophan, serotonin, PUFA, and estrogen contribute extensively to age-related degeneration and slowing of the metabolic rate.
Serotonin lowers the metabolic rate and body temperature and has a clear role in hibernation in animals as a function of these effects. Serotonin’s interference with energy metabolism, particularly in the brain, serves as a catalysts for a cascade of anti-thyroid, pro-degeneration effects that involves the production of more inflammatory mediators. It is these harmful anti-metabolic and inflammation promoting effects that cause the adverse symptoms in some SSRI and tryptophan using individuals.
Stress, low metabolism, and aging lead to a rise in the hormone cortisol. Cortisol’s role is to break down proteins from skeletal muscle and other tissues to be made into glucose in the liver to provide the fuel the body needs to meet the demands of the stressor. Skeletal muscle contains high amounts of tryptophan and other anti-thryoid amino acids. Muscle tissue breakdown during times of stress under the influence of cortisol results in high serotonin just as it does when taking SSRIs. Serotonin unfortunately promotes the production of cortisol leading to perpetuation of the issue. Cortisol inhibits the production of T3 in the liver, further suppressing the metabolic rate.
A PUFA-rich diet encourages the production of serotonin as well. PUFA increases the entry and formation of serotonin in the brain; serotonin liberates PUFA from stored fat creating another negative feedback loop. Reductions in the dietary intake of PUFA and tryptophan prolong the healthy life span. Estrogen promotes the release of serotonin (and histamine and prolactin) so it’s imperative that substances that offset the excitatory, stress-promoting effects of estrogen are maximized in order to prevent a serotonin dominant physiology.
PMS symptoms are exacerbated by excess serotonin so reducing dietary tryptophan intake during the entire cycle or during the second half can help diminish or stop unwanted side effects. Optimizing sodium (salt) intake helps lower the production of serotonin, lower adrenaline, improve body temperature, and raise the metabolic rate. Saturated fats, unlike polyunsaturated fats, do not encourage the production of serotonin or its entry into the brain and represent a major part of a protective nutrition plan. Carbohydrate choices like fruit juice, milk, and ripe fruits help spark the thyroid, provide important vitamins/minerals, and balance blood sugar. Carbon dioxide, light exposure, thyroid, caffeine, aspirin, progesterone, and high altitude helps antagonize the anti-metabolism effects of excess serotonin release. Temperature and pulse will provide further insight into whether your metabolism and health enhancing strategy is proving fruitful.
Salt and Sugar
Salt and sugar are your friend. Cravings for salty and sugary treats can occur during the menstrual cycle particularly during and after ovulation. Salt improves circulation, helps improve CO2 production and the elimination of intracellular calcium, lowers stress mediators like cortisol and aldosterone, and assists with cycle-related water retention and puffiness. The hypothyroid tend to lose excess sodium in the urine. Magnesium found in coffee, ripe fruits, and bone broth helps with sodium retention and T3 helps with magnesium retention. Sugars (ripe fruits, milk sugars, and sucrose) also lower cortisol as well as adrenaline, support T3 production, allow the liver to store glycogen, and keep PUFA in storage where their anti-thyroid and degenerative affects described above are not realized. A word from Ray Peat on the matter:
“Many young women periodically crave salt and sugar, especially around ovulation and premenstrually, when estrogen is high. Physiologically, this is similar to the food cravings of pregnancy. Premenstrual water retention is a common problem, and physicians commonly offer the same advice to cycling women that was offered as a standard treatment for pregnant women–the avoidance of salt, sometimes with a diuretic. But when women premenstrually increase their salt intake according to their craving, the water retention can be prevented.
Blood volume changes during the normal menstrual cycle, and when the blood volume is low, it is usually because the water has moved into the tissues, causing edema. When estrogen is high, the osmolarity of the blood is low. (Courtar, et al., 2007; Stachenfeld, et al., 1999). Hypothyroidism (which increases the ratio of estrogen to progesterone) is a major cause of excessive sodium loss.” -Ray Peat, PhD
Excess estrogen stimulates insulin making individuals in such a state prone to low blood sugar (hypoglycemia) and overeating which isn’t ideal with a low metabolic rate. Higher amounts of saturated fat maybe be needed initially in an estrogen dominant state to help balance blood sugar.
Exercise
Exercise is a slippery slope for those with hormonal imbalances. When one cannot lose weight, he/she instantly goes the more, more, more exercise route to lose the weight. This strategy can and will backfire in the stressed individual. More stress means more estrogen because the actions of aromatase enzymes, which convert androgens to estrogens, increase under such conditions. The more you try, the worse it gets. Those will excess fat tissue are even more susceptible to such effects because remember that fat cells are a chronic source of estrogen. Exercise can deplete progesterone because of the increased need for cortisol from exercise. Female athletes are known to get amenorrhea or other menstrual disorders because of the chronic depletion of progesterone from training.
Exercise can lower thyroid hormone. Active thyroid hormone (T3) production tends to halt with exercise. This is likely due to a combination of a decrease in blood sugar, increase in free fatty acids in the blood, and rise in adrenaline and cortisol. A healthy person can restore T3 production following exercise, but the stressed person remains hypothyroid. Low thyroid leads to low progesterone production further feeding the presenting hormone imbalance. Hyperventilation (excessive loss of carbon dioxide) and a rise in lactic acid are two other parameters that can promote cellular stress and synergize with dietary polyunsaturates and estrogen in creating oxygen deficiency, promoting inefficient glycolytic metabolism.
The mindset should switch from “lose weight to get healthy” to “get healthy and correct the underlying imbalances to lose weight.”
Summary
The correction of hormonal imbalances is multifaceted. The body is a systems of systems with each system dependent upon the function of the other. Manipulating one system affects all others. It’s the combination of the right moves within this system that synergistically can make the unit function optimally. PMS and a difficult menopause are signs that your systems are not working well. Will you make the right moves in diet, lifestyle, and in some cases supplementation to help correct the underlying issues at hand?
Synopsis of corrective measures for estrogen dominance
1. Decrease PUFA in the diet. Eat more saturated fat.
2. Support liver health – animal based proteins and B vitamins (beef liver, egg yolks).
3. Bowel regularity is very important.
4. Support thyroid function for improved cholesterol turnover and reduced bodyfat.
5. Supplement with progesterone at the appropriate times if needed.
6. Use sodium, sucrose, milk, OJ and fruit sugars appropriately.
7. Decrease consumption of tryptophan rich foods to decrease serotonin production.
8. Use friendly fibers like carrots and bamboo shoots to assist in decreasing bowel toxicity and estrogen removal.
9. Balance blood sugar – don’t eat protein alone, don’t eat carbohydrate alone.
10. Reduce stress and be very careful with exercise.
Consult a medical professional regarding all things related to your health. FPS coaches a 12 to 16 week nutrition course based solely on the methodology of Ray Peat, PhD. Please click here for more information.
References:
Salt, energy, metabolic rate, and longevity by Ray Peat, PhD
Death by Medicine by Gary Null, PhD et al.
Tissue-bound estrogen in aging by Ray Peat, PhD
Radio Interview – Progesterone v. Estrogen – EastWest Healing Blog Talk
Serotonin, depression, and aggression: The problem of brain energy by Ray Peat, PhD
Ugh! What a viscous cycle it is! I have been suffering with all the above for half my life. I am a personal trainer and have lived a very healthy life-style for many, many, years- (or so I thought)! Regardless of what I’ve done to try to “fix” the problems they have persisted and indeed gotten worse, much to my frustration and dismay. I have been reading these articles and the ones by Dr. Peat for a few days now and am shocked. A lot of the information is so contrary to everything I thought I knew; and yet some of the information (like that on hypothyroidism) I know from my own experience is dead on. You have my attention- keep it coming!
Thanks for your comment, Jessica. Will definitely keep it coming.
I was interested to read your post on a topic I have done a little reading on. However, I must say some of your statements are in conflict with the limited reading I’ve done on the topic. I wouldn’t want to pick it apart piece by piece but two key points stand out I’d love your views on.
You state that PUFAs “decrease” progresterone levels indirectly. Which given your hypothesis that low levels of progesterone cause PMS would suggest that adding additional PUFAs to the diet would make PMS worse? This study appeared to demonstrate the opposite;
Rocha Filho E.A. Lima, J.C. Pinho Neto J.S. and Montarroyos, U., 2011. Essential fatty acids for premenstrual syndrome and their effect on prolactin and total cholesterol levels: a randomized, double blind, placebo-controlled study. Reprod Health, 17, 8(1), 2.
In addition, when I started reading on the topic I too thought that low progesterone levels “caused” PMS symptoms. On searching I personally couldn’t find any support for this. I did find studies cited suggesting that it was caused by an elevated response to circulating hormones.
Berg,a S.L., 1998. Understanding premenstrual syndrome. Lancet, 14, 351 (9101), 465-6
Norlock FE; Benign breast pain in women: a practical approach to evaluation and treatment. J Am Med Womens Assoc. 2002 Spring;57(2):85-90.
Rapkin AJ, Morgan M, Goldman L, et al; Progesterone metabolite allopregnanolone in women with premenstrual syndrome. Obstet Gynecol. 1997 Nov;90(5):709-14.
I’d love to hear your views if you’ve got time.
Thanks for the comment.
When it comes to steroids, it’s a question of balance I feel. Estrogen’s effects should be balanced by progesterone. I think at the center of the issue is not progesterone deficiency but rather low thyroid and all of the dysfunction that occurs as a result of the low energy, alarm state that accompanies it. The prior use of natural desiccated thyroid by the likes of Broda Barnes, PhD, MD shows how correcting the energy deficit can make a big dent in correcting “women’s issues.” But as mentioned in the summary, it’s a multifaceted problem.
Rocha Filho E.A. Lima, J.C. Pinho Neto J.S. and Montarroyos, U., 2011. Essential fatty acids for premenstrual syndrome and their effect on prolactin and total cholesterol levels: a randomized, double blind, placebo-controlled study. Reprod Health, 17, 8(1), 2.
The idea of “essential fatty acids” isn’t valid as I’ve written about. — http://www.functionalps.com/blog/?p=1823
This is a 6 month study. Not long enough. Since cholesterol levels did not vary nor did that of prolactin, the length of the study can be called into question. Usually studies involving PUFA less than a year long will show “benefit,” however, those over a year in duration often begin to show toxic effects. With excitatory mediators, the excitation that occurs with their usage can temporarily relieve symptoms. This is akin to drink a beer after a hangover to feel “sober” or taking SSRI’s to relieve depression or taking estrogen for hot flashes or xrays to reduce inflammation. The symptoms are suppressed in the short term, but eventually come back with vengeance.
You will get research on both side of the spectrum on this topic. Realizing the big picture can help us all realize the small picture. Estrogen’s harmful effects should not be overlooked, and progesterone’s protective function is something that requires more attention in mainstream thought.
Norlock FE; Benign breast pain in women: a practical approach to evaluation and treatment. J Am Med Womens Assoc. 2002 Spring;57(2):85-90.
The abstract says nothing of an experiment or results. Fibrosis and breast tenderness is associated with unopposed estrogen. It is interesting how it mentions bromocriptine (which is a serotonin antagonist) being helpful for PMS sufferers and then talks about using SSRIs in future studies which would have the opposite effect. Evening primrose oil (EPO) is PUFA (omega-6). EPO’s champion was David Horrobin, who died from complications due to lymphoma.
Rapkin AJ, Morgan M, Goldman L, et al; Progesterone metabolite allopregnanolone in women with premenstrual syndrome. Obstet Gynecol. 1997 Nov;90(5):709-14.
The focus here is on allopregnanolone and progesterone not progesterone’s relation to estrogen. Blood or saliva hormone labs do not reflect tissue concentrations of hormones.
I’m not sure if you have dug into Ray Peat’s work, but I encourage you to do so as he has much experience on this topic. I echo his methodology in this blog.
I’m no expert but I believe Bromocriptine is a fairly well established serotonin agonist. http://www.ncbi.nlm.nih.gov/pubmed/10604273
On the essentiality of EFA’s http://www.ajcn.org/content/25/9/897.full.pdf
This highly unethical (in my view) study examined the effects of EFAs on infants. They completely removed them in some cases and gave the patients up to 45% of calories as saturated fat. http://pediatrics.aappublications.org/content/31/1/171.full.pdf+html
The Norlock paper’s a review as I said above, it “cited” studies.
Bromocriptine is an antagonist of serotonin. From Dr. Peat –
“In Parkinson’s disease, the benefits seen from increasing the concentration of dopamine could result from dopamine’s antagonism to serotonin; anti-serotonin drugs can alleviate the symptoms, and 5-hydroxytryptophan can worsen the symptoms (Chase, et al., 1976). Other movement disorders, including akathisia and chorea, can be produced by serotonin. In autism, repetitive motions are a common symptom, and serotonin is high in the blood serum and platelets of autistic children and their relatives. Irritable bowel syndrome, another kind of “movement disorder,” can be treated effectively with anti-serotonin agents. This syndrome is very common in women, with premenstrual exacerbations, when estrogen is highest. One of the side effects of oral contraceptives is chorea, uncontrollable dancing movements. Some research has found increased serotonin in people with Huntington’s chorea (Kish, et al., 1987), and positive results with bromocriptine have been reported (Agnoli, et al., 1977).
The neurosteroid, allopregnanolone, for which progesterone is the precursor, facilitates the inhibitory action of GABA, which is known to be deficient in some disorders of mood and movement. This suggests that progesterone will be therapeutic in the movement disorders, as it is in various mood problems. Progesterone has some specific antiserotonin actions (e.g., Wu, et al., 2000).”
…
“Research on LSD and its derivatives led to drugs such as bromocriptine, which oppose the effects of histamine and estrogen. Some of bromocriptine’s effects are clearly antagonistic to serotonin, though bromocriptine is usually called a “dopamine agonist”; dopamine is pretty generally a serotonin antagonist. Methysergide, a related drug with antiserotonin activity, is effective in protecting the brain from the effects of strokes. But there is a general disinclination to understand the broad biological meaning of these effects. ”
…
“A large carbohydrate meal increases the ratio of tryptophan to the competing amino acids, and it has been proposed that this can shift the body’s balance toward increased serotonin. In an animal study, bromocriptine, which shifts the balance away from serotonin, reduced obesity and insulin and free fatty acids, and improved glucose tolerance.”
…
Eur J Pharmacol 1982 Jul 30;81(4):569-76. Actions of serotonin antagonists on dog coronary artery. Brazenor RM, Angus JA. Serotonin released from platelets may initiate coronary vasospasm in patients with variant angina. If this hypothesis is correct, serotonin antagonists without constrictor activity may be useful in this form of angina. We have investigated drugs classified as serotonin antagonists on dog circumflex coronary artery ring segments in vitro. Ergotamine, dihydroergotamine, bromocriptine, lisuride, ergometrine, ketanserin, trazodone, cyproheptadine and pizotifen caused non-competitive antagonism of serotonin concentration-response curves.. In addition, ketanserin, trazodone, bromocriptine and pizotifen inhibited noradrenaline responses in concentrations similar to those required for serotonin antagonism. All drugs with the exception of ketanserin, cyproheptadine and pizotifen showed some degree of intrinsic constrictor activity. Methysergide antagonized responses to serotonin competitively but also constricted the coronary artery. The lack of a silent competitive serotonin antagonist precludes a definite characterization of coronary serotonin receptors at this time. However, the profile of activity observed for the antagonist drugs in the coronary artery differs from that seen in other vascular tissues. Of the drugs tested, ketanserin may be the most useful in variant angina since it is a potent 5HT antagonist, lacks agonist activity and has alpha-adrenoceptor blocking activity.
I’m not exactly sure what you’re trying to say regardin “EFA deficiency” because you left no commentary. The skin condition associated with “EFA deficiency” is a result of a very high metabolic rate and the requirement of more nutrition (like B6 and zinc for instance) as a result. The “EFA” lower the metabolic rate, decreasing the need for nutrients apparently “curing” the condition yet with a different perspective is just another toxic effect of PUFA.
I will link you to my article on the subject again. – Essential Fatty Acids: Errors in Nutrition — http://www.functionalps.com/blog/?p=1823. The article very thoroughly discusses the benefits of an “EFA deficiency.” Here is what happens when an intentional “EFA deficiency” is induced in humans.
“Inducing an essential fatty acid deficiency in an adult human proved much more difficult than curing one…Each day, he consumed three quarts of defatted milk, a quart of cottage cheese made from it, sucrose, potato starch, orange juice and some vitamin and mineral supplements. His blood lipids became more saturated and their concentrations of linoleic and arachidonic acids were cut in half. He experienced a marked absence of fatigue, his high blood pressure returned to normal, and the migraines he had suffered from since childhood completely disappeared.”(12)
And its effects on animals –
“…a few experimenters were finding that animals which were fed a diet lacking the “essential” fatty acids had some remarkable properties: They consumed oxygen and calories at a very high rate, their mitochondria were unusually tough and stable, their tissues could be transplanted into other animals without provoking immunological rejection, and they were very hard to kill by trauma and a wide variety of toxins that easily provoke lethal shock in animals on the usual diet. As the Germans had seen in 1927, they had a low susceptibility to cancer, and new studies were showing that they weren’t susceptible to various fibrotic conditions, including alcoholic liver cirrhosis.”(10)
I cannot access the last link.
In relation to: Rapkin AJ, Morgan M, Goldman L, et al; Progesterone metabolite allopregnanolone in women with premenstrual syndrome. Obstet Gynecol. 1997 Nov;90(5):709-14.
CONCLUSION:
Subjects with PMS manifested lower levels of the anxiolytic metabolite allopregnanolone in the luteal phase when compared with controls. Diminished concentrations of allopregnanolone in women with PMS may lead to an inability to enhance gamma aminobutyric acid-mediated inhibition during states of altered central nervous system excitability, such as ovulation or physiologic or psychological stress. The lowered metabolite levels could contribute to the genesis of various mood symptoms of the disorder, such as anxiety, tension, and depression.
“In autism, repetitive motions are a common symptom, and serotonin is high in the blood serum and platelets of autistic children and their relatives. Irritable bowel syndrome, another kind of “movement disorder,” can be treated effectively with anti-serotonin agents. This syndrome is very common in women, with premenstrual exacerbations, when estrogen is highest. One of the side effects of oral contraceptives is chorea, uncontrollable dancing movements. Some research has found increased serotonin in people with Huntington’s chorea (Kish, et al., 1987), and positive results with bromocriptine have been reported (Agnoli, et al., 1977).
The neurosteroid, allopregnanolone, for which progesterone is the precursor, facilitates the inhibitory action of GABA, which is known to be deficient in some disorders of mood and movement. This suggests that progesterone will be therapeutic in the movement disorders, as it is in various mood problems. Progesterone has some specific antiserotonin actions (e.g., Wu, et al., 2000).” -Ray Peat, PhD
This study falls in line with the information presented in the blog.
Apologies for the shortness of responses. I genuinely appreciate you taking the time to respond properly. It’s great to see how passionate you are about educating people.
Maybe we have a differing opinion on what an agonist is. Bromocriptine has been shown to stimulate serotonin receptors. I’m not sure how you can refute that.
In the little I’ve read of his and of your writing, there is also a tendency to grossly oversimplify the physiology. Dopamine antagonises serotonin for example. Similalrly, stating that “PUFAs” do … X,Y or Z. Different “PUFAs” have diametrically opposed actions on multiple systems. For example stating that “PUFAs” inhibit the immune system cannot be taken seriously.
The paper I linked to on EFA’s highlights the EFA’s are essential argument and includes references to original research. I just wanted to provide the opposing view to Ray Peats.
I did start to read your article on EFAs, I made it to reference 11. They only managed to reduce linoleic acid by 2.5% over the 6 months. This suggests they may not have actually sufficiently removed EFAs and a longer period may be needed to achieve sufficient EFA loss. I assume you would like to see subjects starved of EFAs till there were no EFAs in the body? or do you think we can synthesise them? The authors own conclusion is,
“In the light of this latter observation, it cannot be as
sumed that the human subject could subsist indefinitely on a
diet completely devoid of the unsaturated fatty acids. ”
This study also suggests your high saturated fat approach may not be ideal for this individual. That however, is what this was, a study on one individual. The studies on multiple children shouldn’t need to be repeated.
With regard to Rapkin. It’s interesting how we all interpret things through our own biases. As I see that paper as refuting your view of low progesterone causes PMS symptoms and so do two reviews on the topic.
I appreciate your passion as well.
I just posted research indicating brompcriptine’s anti-serotonin effects so I suppose painting bromocriptine with the serotonin agonist or antagonist brush doesn’t describe its actions appropriately. It’s probably best described as a dopamine agonist which “antagonises serotonin” as you said.
I can tell you have read little of his writing because the same biases come about from the traditionally schooled and indoctrinated. Refuting something you’ve never read make things difficult.
I think you should take PUFA’s immunosuppression quite seriously as it pervades the literature. PUFA were commonly used after organ transplants to prevent organ rejection because of their immunosuppressive effects. This practice stopped when the transplantees started getting cancer. PUFA are used similarly for autoimmune conditions and inflammatory conditions much the way xrays were previously used. In the case of xrays or PUFA, inhibiting immune function for the sake of “reducing inflammation” has its negative affects clearly.
Research on the immunosuppressive effects of PUFA, use after organ transplants, and use in autoimmune conditions:
Am J Clin Nutr. 2001 Mar;73(3):539-48.
Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y.
Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC.
Source
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Abstract
BACKGROUND:
Animal studies showed that dietary flaxseed oil [rich in the n-3 polyunsaturated fatty acid alpha-linolenic acid (ALA)], evening primrose oil [rich in the n-6 polyunsaturated fatty acid gamma-linolenic acid (GLA)], and fish oil [rich in the long-chain n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] can decrease natural killer (NK) cell activity. There have been no studies of the effect on NK cell activity of adding these oils to the diet of humans.
OBJECTIVE:
Our objective was to determine the effect of dietary supplementation with oil blends rich in ALA, GLA, arachidonic acid (AA), DHA, or EPA plus DHA (fish oil) on the NK cell activity of human peripheral blood mononuclear cells.
DESIGN:
A randomized, placebo-controlled, double-blind, parallel study was conducted. Healthy subjects aged 55-75 y consumed 9 capsules/d for 12 wk; the capsules contained placebo oil (an 80:20 mix of palm and sunflower seed oils) or blends of placebo oil and oils rich in ALA, GLA, AA, DHA, or EPA plus DHA. Subjects in these groups consumed 2 g ALA, 770 mg GLA, 680 mg AA, 720 mg DHA, or 1 g EPA plus DHA (720 mg EPA + 280 mg DHA) daily, respectively. Total fat intake from the capsules was 4 g/d.
RESULTS:
The fatty acid composition of plasma phospholipids changed significantly in the GLA, AA, DHA, and fish oil groups. NK cell activity was not significantly affected by the placebo, ALA, GLA, AA, or DHA treatment. Fish oil caused a significant reduction (mean decline: 48%) in NK cell activity that was fully reversed by 4 wk after supplementation had ceased.
CONCLUSION:
A moderate amount of EPA but not of other n-6 or n-3 polyunsaturated fatty acids can decrease NK cell activity in healthy subjects.
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Chem Phys Lipids. 2008 May;153(1):24-33. Epub 2008 Feb 23.
Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection.
Shaikh SR, Edidin M.
Source
Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, United States. saameshaikh@gmail.com
Abstract
Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.
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Autoimmunity. 2004 Feb;37(1):73-5.
The beneficial and detrimental effects of linoleic acid on autoimmune disorders.
Namazi MR.
Source
Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran. namazi_mr@yahoo.com
Abstract
Type 1, or cellular, immune response is characterized by overproduction of IL-1, IL-2, IFN-gamma and TNF-alpha and is the underlying immune mechanism of some autoimmune disorders such as psoriasis, alopecia areata, rheumatoid arthritis, Crohn’s disease, multiple sclerosis, insulin-dependent diabetes mellitus and experimental autoimmune uveitis. Type 2 immune response is seen in allergic and antibody-mediated autoimmune diseases and is characterized by IL-4, IL-6 and IL-10 overproduction. Linoleic acid is a precursor of prostaglandin E2 (PGE2) and its intake results in tissue production of PGE2, especially in the absence of other polyunsaturated fatty acids (PUFAS) which inhibit this conversion. PGE2 decreases the production of IL-1, IL-2, IFN-gamma and TNF-alpha and proliferation of TH1 cells and increases the production of IL-4, leading to suppression of the type 1 immune response. Taken together, linoleic acid, the major PUFA of maize oil, could have therapeutic efficacy against cellular autoimmune disorders. On the other hand, excessive intake of linoleic acid may aggravate type 2 autoimmune disorders.
—-
Proc Nutr Soc. 1998 Nov;57(4):503-9.
n-3 polyunsaturated fatty acids and immune function.
Wu D, Meydani SN.
Source
Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Abstract
n-3 PUFA have been shown to reduce the risk of cardiovascular and inflammatory diseases. However, they have also been shown to suppress T-cell-mediated immune function, an undesirable effect, especially in immuno-suppressed individuals. Studies have thus far suggested that this immuno-suppression may be in part attributable to increased lipid peroxidation and decreased antioxidant (especially vitamin E) levels, which can be prevented by appropriate vitamin E supplementation. Further well-designed human studies are needed to determine the appropriate levels of n-3 PUFA and vitamin E supplementation to optimize the beneficial anti-inflammatory effect of n-3 PUFA and minimize their suppressive effect on T-cell function.
—
Br J Nutr. 2001 Mar;85(3):251-69.
Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders.
Darlington LG, Stone TW.
Source
Epsom General Hospital, Dorking Rd., Epsom, Surrey KT18 7EG, UK. gdarlington@sthelier.sghms.ac.uk
Abstract
The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-alpha (TNFalpha) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of beta-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include the n-3 compounds, some of which are precursors of eicosanoid synthesis, and the n-6 group which can increase formation of the pro-inflammatory cytokines TNFalpha and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so that n-3 PUFA often oppose the inflammatory effects of some n-6-PUFA. gamma-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich in n-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.
—
Transplantation. 1977 Oct;24(4):263-7.
Immunosuppression with polyunsaturated fatty acids in renal transplantation.
McHugh MI, Wilkinson R, Elliott RW, Field EJ, Dewar P, Hall RR, Taylor RM, Uldall PR.
Abstract
A double-blind controlled trial has been undertaken to assess the value of a preparation containing polyunsaturated fatty acids (PUFA) in human cadaveric renal transplantation. Eighty-nine patients were studied and followed for 6 months after transplantation. Forty-four took the PUFA preparation and 45 the placebo (oleic acid). Other immunosuppression was standardised. Functional graft survival was significantly better in the PUFA group than in those taking the placebo during the first 3 to 4 months post-transplant. At 6 months, however, although the difference between the groups persisted, it was no longer statistically significant. Complications were equally distributed between the groups.
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The “EFA” paper, once again, is the same thought that the Burrs’ had 80 years ago. Dr. Peat’s work and my blog based on his work clearly refute the essentiality of “EFA.” You can’t call something essential when the same skin problem is cured with B6 in the absence of “EFA.” The Burrs’ didn’t know all of the B vitamins in 1929. The consequences of a very high metabolic rate due to “EFA” deficiency are the need for more nutrition. Saturated fats for someone already with a high metabolic rate would further serve to maintain or increase the metabolic rate which wouldn’t be ideal for someone with preexisting nutritional deficiencies being outwardly expressed as dermatitis.
I’m not going to outline all of Dr. Peat’s work on how the body will synthesize its own unsaturated fats (Mead acids) from glucose when deprived of “EFA” and also experiences a very high metabolic rate, correction of existing problems, and remarkable resilience and adaptability to stressors. You’ll have to do the work to relearn the information on the subject just as I did. But if you’re from the “EFA” camp you will have to do the following:
Claiming that certain fatty acids are essential, a scientific approach would require showing what was wrong with the experiments that showed that they were not essential, and especially, those that showed that they were positively harmful. – “Unsaturated fatty acids: Nutritionally essential, or toxic?”-Ray Peat
Thinking that I have a “high saturated fat” approach ultimately corners me into such methodology, however, that is only the goal in the short term to help people stabilize blood sugar and offset the toxic effects of PUFA. Long term, that would not describe what I would recommend for optimal health.
Regarding Rapkin — “Subjects with PMS manifested lower levels of the anxiolytic metabolite allopregnanolone in the luteal phase when compared with controls.” The metabolite of progesterone, allopregnenalone, was beneficial for PMS. Lower allopregnenolone, more PMS and vice versa. Supplementation with progesterone would thus supports my thoughts in the PMS blog and prove beneficial for PMS, movement disorders, and mood problems associated with excess estrogen and serotonin. Since estrogen promotes serotonin, it’s interesting that bromocriptine would proves beneficial for chorea (a side effect of oral contraceptives) since it “only” acts as a serotonin agonist.
““In autism, repetitive motions are a common symptom, and serotonin is high in the blood serum and platelets of autistic children and their relatives. Irritable bowel syndrome, another kind of “movement disorder,” can be treated effectively with anti-serotonin agents. This syndrome is very common in women, with premenstrual exacerbations, when estrogen is highest. One of the side effects of oral contraceptives is chorea, uncontrollable dancing movements. Some research has found increased serotonin in people with Huntington’s chorea (Kish, et al., 1987), and positive results with bromocriptine have been reported (Agnoli, et al., 1977).
The neurosteroid, allopregnanolone, for which progesterone is the precursor, facilitates the inhibitory action of GABA, which is known to be deficient in some disorders of mood and movement. This suggests that progesterone will be therapeutic in the movement disorders, as it is in various mood problems. Progesterone has some specific antiserotonin actions (e.g., Wu, et al., 2000).” -Ray Peat
Thanks very much for your reply. I have to say that although we do not agree. If a client of mine wanted to go down the Ray Peat root I’d send them your way.
I do have doing a thorough review of Ray Peat’s work on my to study list and at some point I’ll get it done. I only hope I can approach his work with an unbiased view and keep my ego quiet enough that I can honestly evaluate it.
Thanks very much for your time and courtesy. I genuinely appreciate it.
Thanks for the discussion.
I feel you and your clients may benefit from Peat’s work. It will definitely take some relearning if CHEK nutrition and CMTA is in your background. I have a similar one to yours in that regard and went through the relearning process. I initially couldn’t wrap my head around what he was saying because of my biases. But as Paul Chek says adapted from Mark Twain, “don’t let your education get in the way of your learning.”
Very true, I find the greatest conflicts with my nutritional therapy background. A lot of the beliefs that I learnt there prior to HLC & CMTA are very well ingrained!
Good quote.
How does one improve bowel regularity?
Thanks!
Nice discussion guys!
In short:
Improve resting metabolism
Balanced, frequent meals to regulate adrenaline
Easily and quickly digested food
Well dissolved gelatin supplement
Broth
Dairy that agrees with you
Shellfish
OJ, ripe fruits
Saturated fats
Raw carrot salad
Bamboo shoots
Aged Cascara sagrada supplement
Coffee with milk and sugar
Best article ever! Thanks
Wow Rob great article and great discussion above. So much information to process, but it makes sence. Thank you for your dedication and passion for this. It’s helping to clear up much of the misinformation out there.