Evolution of hypothesis April 1998

Dennis Argall's paper, April 1998

copyright Dennis Argall 1998

A Response to "ASK YOUR DOCTOR" - Autumn issue

B Hypothesis

CFS AS A FAILURE OF MITOCHONDRIAL HEALTH

 AND DISREGULATION OF THE ENDOCRINE SYSTEM

I wrote this article in response to a piece of advice from a doctor 

in a CFS support group's newsletter,

which gave the writing a focus - but the ideas involved have been longer in development.

The paper represents where my ideas stand on some broad issues of health. 

These ideas are substantially influenced by the writing of Raymond Peat, 

an endocrine physiologist specialising in aging and stress. 

Peat's ideas contradict a lot of conventional medical doctrine, 

which led me to start reading into basic biochemistry, 

where I found more support for his propositions 

than for some current medical and popular health obsessions, 

notably those relating to avoidance of cholesterol and sugar. 

These substances are critical to our metabolism, 

our hormonal balance and our energy supply and protein assembly. 

If our bodies are not absorbing them sensibly 

the task is surely to correct the process of their use, 

not to avoid such fundamental substances or take inappropriate or dangerous substitutes.

Having been sick, for most of the time disablingly sick, since 1985, 

with a 'stress related' illness which has defied conventional 

- or indeed 'alternative' - medical management

and which has seen my persistent downward slide into weakness and pain, etc,

I can only be impressed by a shift to a treatment approach  

which is designed to be physiologically constructive

 and which has since the beginning of 1998 produced substantial health benefits.

I am nonetheless aware that in recent years my greatest difficulty has been 

in getting through winter without serious decline in health. 

So the real test will be this [southern hemisphere] winter, especially July-September.

While this article was addressed to a CFS-interested audience, 

the kinds of adjustment proposed are of much wider relevance 

and in the end may take away much need for illness or syndrome labelling.

The CFS label, like many others, may have some value 

in social or legal explanation of one's health circumstance, 

but this treatment makes such labelling of declining relevance.

I am concerned about the answer provided in the autumn 1998 issue of Chameleon [Journal of the ACT ME/CFS Society] regarding the relationship between depressed thyroid hormone secretion, low body temperature, menstrual problems, low progesterone and CFS. And addressing that gives me an opportunity to set out a different perspective on CFS and related illness which seems to be working for me.

The questioner asked "could low progesterone be a problem and a marker and should we be being treated for low progesterone levels?"

Some problems in the answer may arise from the complexity of the question. Yet the question was undoubtedly based on the breadth of overlap between the symptoms of hypothyroidism and those of CFS and other unexplained syndromes. 

The answer stated that "depressed thyroid hormone secretion (called hypothyroidism) is due to failure (or removal) of the thyroid gland."

The situation is a bit more complex than that. As Teitelbaum observed in his 1996 book on CFS "My impression, and that of many other physicians, is that the current method of  testing still misses many people with underactive thyroids. Therefore the physician must treat the patient, not the blood test." 

There are a number of things that can diminish thyroid function, including the adequacy of uptake of iodine by the thyroid, the adequacy of response by the hypothalamus to need for thyroid hormone, etc... reducing availability of T3 when required. These are more subtle forms of functional 'hypothyroidism' than "failure (or removal) of the thyroid gland". One such cause is estrogen dominance, which is of direct relevance to the question of progesterone levels. But mercury and cabbages and peas and other simple things also depress thyroid.

The thyroid has a sophisticated way of maintaining available hormone, balancing its dual obligations for hormone manufacture and in energy supply. The two principle thyroid hormones are T4 and T3. T4 is mainly a reserve store, with a half life of several weeks in humans; T3 is produced on demand from T4, is far more active in promoting metabolism and has a half life of a day or so. So the organisational process involves building a sufficient base store of T4, parked all over the body, and then converting that into an operational supply of T3 on short notice. I like to compare this to a house in the country, with its own water supply, a tank in the ground for storage of collected water, and a small pump to keep the right amount of water in the pipes to the house. Anyone who has ever had a shower while someone flushes a toilet will know the difficulty of maintaining the right pressure to the house. In my analogy, the tank storage is T4, the water between the pump and the house is T3. The analogy also indicates how such a system can be disregulated at a number of points and identification and solution of the problem may be difficult.

The next wrinkle in thyroid treatment is that if you take supplements of T4 [Thyroxine] your thyroid will decide it does not need to work itself and may in time atrophy. The same adjustment problem does not arise with small doses of T3. Yet it is T4, not T3, which is more widely used in Australia for thyroid treatment. T4 may be 'safer' than T3 to take, in terms of the possible immediate effects of taking a lot of directly acting T3 - but T3, taken only occasionally and then only at less than the normal hourly human production rate (<5 micrograms) is of more immediate benefit, without long term complications.

Cholesterol, in the presence of thyroid and vitamin A, is converted by mitochondria to pregnenolone, all over the body (notably in the brain, which in a healthy person is 30% cholesterol). Pregnenolone is the base substance from which other steroid hormones are made, including progesterone and DHEA and from them testosterone, estrogens, cortisol and cortisone, aldosterone and is thus involved with regulation of norepinephrin and epinephrin. Among all these, progesterone is the great harmoniser and protector and should be present in about 10 times the abundance of estrogens.  

It is a common error to state that the medical profession has had "many years experience of giving progesterone to women of all ages (alone or in combination with oestrogen). It is used in the contraceptive pill and hormone replacement therapy...". A glance at the index of  the doctors' dispensing bible, MIMS, lists only one prescribable form of progesterone, an injectable form, under the trade name of  Proluton, rarely used - and a painful injection. All other substances often but mistakenly described as progesterone are synthetic 'progestins', which mimic (and often at many times the strength of natural progesterone) some of the reproduction-related functions of natural progesterone, while lacking progesterone's protective and hormone balancing functions. In short, a progestin is 'any compound able to sustain the human secretory endometrium' - or rather, as Lee [see below] says, any such substance other than natural progesterone.  Compare the warnings associated in MIMS with Proluton on the one hand and Provera [commonly prescribed progestin - long list of warnings] on the other. What has occurred with this substitution of progestins for progesterone is a failure to see women as whole people and a focus solely on reproductive systems.

Progesterone, a natural substance not controlled by the Federal Drug Administration in the United States, did indeed have to be injected (and unpleasantly) until the 1970s, when it was established that it could be absorbed through the skin or under the tongue when dissolved in Vitamin E. This progesterone in vitamin E is not a substance easily obtained in Australia. It is not in MIMS, or within the normal ambit of conventional medical practice because the patent is not held by a pharmaceutical company. (Note also that Wild Yam Cream, though it is sold widely in health food stores with some claims to be a source of progesterone, is a base for manufacture of whole progesterone in factories, but not in the human body.)

Progesterone deficiency in women can arise severely in puberty, or if the monthly cycle is disturbed  (by whatever stress, bodily or social - progesterone is normally produced in the second half of the cycle and this can fail) and for ten or more years before menopause. A brief failure, or persistent inadequacy of progesterone production can precipitate estrogen dominance and estrogen dominance will upset the whole chain of hormonal production and balance (see above) - i.e. upset and weaken the endocrine system generally - and will directly suppress thyroid.  Women can of course suffer disregulation before puberty or after menopause;  men are vulnerable, but less so, and  their hormonal cycles are more mysterious.  But the circumstances of women's fertile years as suggested above seem likely to be points of great vulnerability, likely to contribute to the statistical preponderance of women as sufferers from CFS and like illness. One factor which may contribute to the incidence of the illness in men is the possibility of thyroid deficiency during fetal and early neonatal periods, which "may lead to the development of motor and cognitive disorders". [Sher ES; Xu XM; Adams PM; Craft CM; Stein SA, "The effects of thyroid hormone level and action in developing brain are these targets for the actions of polychlorinated biphenyls and dioxins?" Toxicol Ind Health, 14(1-2)121-58 1998 Jan-Apr.]

Whether a test of progesterone levels will identify such a weakness I do not know. I suspect again that more subtle levels of deficiency may cause widespread problems. One nice aspect of the use of pregnenolone and/or progesterone as therapy is that they would appear not to have excess dosage complications as with estrogen. But note that an identified progesterone weakness will not be treated entirely appropriately or effectively with progestins, if one has regard for the whole person.

Estrogen's preoccupation would seem to be with the next generation - among other things, it releases calcium from bone and promotes rapid cellular division - great for uterine preparation and reproduction, also great for osteoporosis and cancer. It is not estrogen, but an appropriate level of progesterone which protects the whole hormonal cycle, including by provision of an adequate and balanced amount of estrogen. Note also that estrogen causes fluid retention and weight gain - part of the mystique it enjoys in HRT, by puffing the cheeks, etc.

While women (or rather the mitochondria in women) produce progesterone in the corpus luteum (in the ovary, after ovulation), in both men and women it is also produced by the mitochondria in the adrenals, in the presence of adequate vitamin E, from pregnenolone. Men and women need progesterone for production of testosterone;  estrogens are largely derived from testosterone. (A lot of confusion arises from the popular perception that 'men are testosterone, women are estrogen'. Note, for example that male blood carries no less than two thirds the level of estriol that women carry; note also that the earliest industrial source of estrogen was horses' urine, and stallions' urine comes out tops.)

Estrogenic substances [xenoestrogens] are also widely available from the environment, for men and women, in some plastics, in agricultural chemicals, in cosmetics and, in heavily-pharmaceutical-consuming societies, in the downstream waters from users of synthetic hormones, which are typically not at 'hormone replacement' levels but many times any such level. 

As a result of a lot of reading and correspondence in the past half year or so I have come to the view that Chronic Fatigue Syndrome, Fibromyalgia Syndrome, Post-Traumatic Stress Disorder, Multiple Chemical Sensitivity - whatever label you like in this package of suspect syndromes of general disregulation - are best seen as involving a failure of mitochondrial health and a disregulation of the endocrine system.

The failure of most conventional 'treatments' of this general disregulation is, in my view, that they seek to manipulate the nervous system (that is, they deal with nervous system symptoms like pain or sleep deprivation, or to correct neural disregulation) rather than the endocrine system and they have no regard for mitochondrial health. There is a striking coincidence between the symptoms of CFS and those of hypothyroidism. Clarifying that coincidence is not helped by taxonomic rules which say that if it's hypothyroidism it can't be CFS and that it can't be hypothyroidism unless you meet standard test criteria - when that test is over-simple. That is playing with boxes, not pursuing wellness. 

It is understandable that, for clinical practice "[t]he definition of CFS requires the exclusion of other known causes of fatigue" - among other symptoms. However, what I am suggesting is that if we begin to address the problem of endocrine regulation and mitochondrial health, seeking to improve basic physiology, then our bodies, which have no knowledge of the taxonomy of disease (any more than the mitochondria know whether they have a Greek or Latin name) and will not respect concepts of differential or exclusionary diagnosis, may cure more than the mystery syndromes. 

Note, along the way, that some of the diagnoses to be excluded are suspect too - depression is often 'clearly' diagnosed on the basis of medication response. I am sure there are disorders of the nervous system which arise in the nervous system; but I am also sure that the nervous system rides on the back of the endocrine system, and that the nervous system has a very imprecise knowledge of how the endocrine system manages the body and can itself contribute to endocrinal derangement. I am also aware that I am saying, as with such depression diagnosis, that it may be a better test of endocrinal deficiency, not to check blood, but to observe response to treatment - in this case diet change, T3, pregnenolone and progesterone. Moreover, I think these are much safer steps than taking antidepressants, whose effects on the endocrine system are manifold and scarcely appreciated. 

I have mentioned the role of the mitochondrion several times. We are told little in school and rarely anything by doctors about mitochondria. They are beyond the reach of church and state too, but without these quasi-independent organisms life on earth would stop instantly; they are the basis of survival in an oxygen atmosphere. Mitochondria are microorganelles which live inside all cells with nuclei, that is, in all organisms larger than bacteria. They have their own DNA, which derives from the DNA of the mitochondria in any person's mother; that is, travelling with the ovum. They have their own life cycle and we depend on them for the following

[1] production of pregnenolone, and thus our whole hormone system, from cholesterol, in the presence of thyroid and vitamin A, as discussed above

[2] conversion of oxygen and sugar into adenosine triphosphate [ATP] ( let's call them energy packages, noting that ATP is also critical to the construction of proteins from amino acids in the body) and carbon dioxide as discussed briefly below. (We often take a narrow view of carbon dioxide as a 'waste product', but it is the major balance against oxygen and protectant of cells from oxidants.) 

When I look at these two mitochondrial functions it becomes evident to me that without mitochondrial health, I can have no health myself. As I begin to think about the health of the mitochondria within my cells, some of the smugness of my human-species-pride is eroded, and I wonder who really is here for whose benefit. I am beginning to think that when my mitochondria despair, so will I. It's nice to feel part of a team, all wearing the same skin!

Mitochondria will die in the darkness of winter and night; hence I need sun or artificial light (red light goes deeper in the skin - hold your hand over a light, it's the red light that gets through). Mitochondria will die if unemployed - they need thyroid and cholesterol and vitamin A. Mitochondria will also be in trouble if they are in muck like loose calcium, which they will shove into bone [spurs], blood vessels [arteriosclerosis], muscles [calcifications]. Cellular life would seem also to be a constant struggle with an oxygen-dominated environment. There is a desperate need for adequate carbon dioxide to dispose of free radicals, notably, again, calcium. Conditions have to be just right for 'respiration' to burn sugar and oxygen and produce ATP. Otherwise, problems arise as the alternative ways of processing sugar are by yeast (which can get out of hand, producing runaway candidiasis and contributing to hypoglycemia) or fermentation (producing lactic acid, which means muscle pain, and demanding many times more energy for the liver to break down than it took to make the lactic acid). Only a modest amount of ATP is produced by fermentation or yeast. Large amounts are produced by 'respiration' or oxidative metabolism, along with carbon dioxide.

A shortage of ATP not only means low energy but also will mean less-than-best-practice blood and there will be a failure to convert amino acids to proteins. Wider, hard-to-predict symptoms which confuse patient and doctor, will follow - not at levels which conventional tests for seriously diseased organs will measure, but seriously enough in combination to derange and disable the individual and profoundly annoy many doctors.

With this perspective, I am not at all sure of the value of a lot of the professional medico-scientific hunt for cause and solution in CFS; it seems to be in the wrong place and too much focussed on finding a target to shoot at in ways relevant to germ theory and conventional medical practice, but at a distance from the idea of disregulation as above, and the objective of natural strengthening of physiology. Please compare my perspective with the report of the delegates to the Sydney conference [Autumn issue, page 9] "As to achieving a definitive diagnostic test and a standard treatment pathway for ME/CFS - it was very clear that such a goal may not be achievable. There is general agreement among researchers that we are dealing with a collection of illnesses, and the impetus is towards identifying subgroups for whom appropriate treatment can be instigated."

A major factor in this endocrine disregulation is that there is a major pathway from the endocrine to the nervous system in the role of adrenal hormones. Norepinephrine and epinephrine (=noradrenalin and adrenalin) have major functions as neurotransmitters. In hypothyroidism a major symptom is adrenal levels 10 to 40 times 'normal' (which is probably also the base of the hyper-vigilance and disturbed sleep in CFS); cortisol levels (cortisol and cortisone are also adrenal products) are correspondingly low (which means pain will be high).  The hypothalamus, part of the limbic system of the brain, is responsible both for norepinephrin production and thyroid regulation. But before making judgments about the hypothalamus alone, I am impressed by the observation, under Limbic System in The Oxford Companion to the Mind of "the importance of considering the interaction of connected brain areas rather than the activity within particular 'centres', as effectors of functions."

In the course of treating myself (under medical supervision) since the beginning of this year with very small doses of T3, pregnenolone and progesterone (along with a shift to coconut oil and butter from unsaturated oils; soda water for carbon dioxide, vitamin E, carrot salads, simple rather than complex carbohydrates, epsoms salts/carb soda baths, etc - see below) I have experienced very rapid improvement equanimity, exercise tolerance, muscle gain, less pain, very few headaches, very little brain fog (reversible dementia), improvements in bowel and bladder performance. 

NOTE the question in the Autumn issue also asked about low body temperature. This was not addressed in the doctor's answer. For whatever reasons, the core of the medical profession is not impressed by the work of those doctors who diagnose and treat thyroid problems on the basis of measuring Basic Metabolic Rate [BMR]. Broda Barnes argued that a basal temperature of 36.6 or below indicated functional hypothyroidism. (A basal temperature - a measure of BMR - is taken first thing in the morning when you wake up. Women who are cycling monthly must measure it at the beginning or end of the cycle, away from their peak.) Raymond Peat argues that dementia is reversible above 37.0.  I can report that since this treatment began, my oral temperature has risen from around 35.7c to 36.3 to 36.6c which is amazingly cozy and comforting, allowing real rest. (Endurance athletes have low body temperature, but this too is arguably a reversible functional hypothyroidism, which ends when they cease the marathon routine.) I was previously able to identify feeling relatively good with a temperature approaching 36.0c, whereas feeling confused, irritable and about to be blown off my feet with exhaustion, I found last October, coincided with an oral temperature of 35.5 or less. Hypothermia begins at 35.0.

I have, however, continued to have some difficulty with 'adrenal alerts' waking me - brain alert, waking from tense dreams, bladder or bowel tension. It seems to me that there is a big hole in the fence between the endocrine and nervous systems around the adrenals, and it seems also that my nervous system is continuing to make inappropriate withdrawals from the endocrine through that hole - a gaping hole, in my case, after over a decade of stress-related illness.  This comes back to the proposition suggested earlier, that the nervous system has an imperfect knowledge of the endocrine, particularly in homo sapiens - a major problem is undoubtedly our adaptation to having a grossly more complex brain, which has allowed a passage to cultural life, placing varied and repeated stresses on the nervous system at large and some derangement/alteration of lower brain functions (I realise that this is a whole separate issue, no room to be developed here, but I am influenced by Edward O. Wilson, On Human Nature, Cambridge, Mass, 1978) which leads the nervous system to ring and ring the bell on the door to the endocrine system which it knows best - 'give me adrenal support, now!' The limbic system is caught in the crossfire.

In my case, work and other stress was the major contributor to my illness, but it is now evident to me that the widening damage done over the years was via the exhaustion of the endocrine system, failure to address the problem at an endocrine level - plus damage caused by inappropriate treatment of the nervous system. (There is some experimental evidence that elevated serotonin levels may also depress thyroid function.) 

In other people, 'syndrome' symptoms may arise quite differently, but with entrenchment of mysterious disability and with the failure of efforts to identify and treat it, causes and effects will be of declining significance. In my own case I could hunt through considerations of childhood illness, genetic predisposition, disease exposure living in different countries, vaccinations, etc, but I would still tend now to see that there is more future for me in allowing my body to rebuild physiological health based on endocrinal balance and mitochondrial health than there is in hanging around, feeling strung out like a fox-skin on a dunny door, waiting for a magic bullet.

How to repair that hole draining endocrine resources into the nervous system, and return it to sensible size is the next, very interesting, question. Here, it seems to me, is the major remaining weakness in my approach to treatment since the beginning of the year. There may be a place for rational and other behaviour therapies (simple things like goal setting, positive ideas, imagery, etc, and just simply thinking constructively about the nature of this torn hole that needs sewing up properly) in this adrenal-calming task; but I now think I understand why such things are useless without prior and concurrent effort to re-regulate the endocrine system. 

I set out below some reading, and my dietary changes and 'medication'. Please look at the latter not as medicine to overturn a disorder, but as extra amounts of natural substances to help my own physiology correct itself. As my doctor puts it "This is not a long term treatment. It is not even intended to get you back on the rails. It is to get you pointed in the right direction so your own system can find the rails."

I have been working on these ideas with help from one other member of the Society. I would be very happy to have the support of others for discussion and research.

Dennis Argall

grargall@alphalink.com.au

02 6288 2958

References

White Handler Smith Principles of Biochemistry a major text, through various editions, for medical undergraduate teaching of biochemistry. Not so much like a 1000 piece jigsaw as a description of most of the parts of such a jigsaw. Not easy to derive a sense of what comes first in hormonal mechanisms.

Raymond Peat From PMS to Menopause 1997, Mind and Tissue Russian Research Perspectives on the Human Brain 1976, 1994 etc, see internet site http//www.efn.org/~raypeat/  ;

other newsletter material and books from Ray Peat, available or orderable from that web site; 

personal correspondence with Ray Peat, accessible from me.

John R. Lee, MD with Virginia Hopkins What Your Doctor May Not Tell You About Menopause Warner Books 1996, widely available from health food stores. Lee's work follows Peat's.

Broda Barnes Hypothyroidism the Unsuspected Illness 1976 provides an account of both research and clinical practice. Peat and others draw on Barnes; Peat carries the functional account of the whole endocrine system further than others.

There is also an interesting discussion of thyroid at the internet site 

http//www.alternativemedicine.com/digest/issue22/i22-a54.shtml [sic - my copy shows the 's' before html in the url] 

with links to articles on chronic fatigue and thyroid, etc.

Jacob Teitelbaum From Fatigue to Fantastic Avery Publishing New York 1996 has a readable but not, to my mind, very orderly discussion of hormones at pages 25-39.

for interesting discussion of mitochondria, see

Lynn Margulis and Dorion Sagan Microcosmos 1986 [several copies in Canberra Public Library Service]

I have also referred to Edward O Wilson On Human Nature Cambridge Mass 1978

and The Oxford Companion to the Mind [ed] Richard L Gregory, OUP 1987

'Medication' and Diet

I have embarked upon the following, since early January 1998, with monthly medical supervision and support.

We use coconut oil for making chips or cooking crumbed cutlets, etc - delicious! Copha is coconut oil which has been increased from 96% to 100% saturation. It is solid below 22 degrees celcius. We heat the oil in a wok - harder to boil over, and before it cools we decant to a saucepan through a fat/oil filter made by Pearsons, sold through Woolworths/Big W [I think]. A move to saturated oil should be embarked upon with knowledge of your cholesterol level. A high level cholesterol may be better treated with thyroid and vitamins A and E (to enhance conversion to pregnenolone) than with unsaturated oils which 'rancidify' [White, Handler Smith] in the body and cause endotoxin problems [Peat]. Olive oil and butter OK. Grass fed animals, avoid e.g. pork made lean with unsaturated oils.

I use tiny fragments of T3 [2 or 3 micrograms each] once or twice a day, or rather when I wake at night, or when I use an exercise bike. On each occasion with milk and and orange [protein/sugar]. Back to warm sleep at night, warming easily, pulse rising, while exercising. T3 [liothyronine] is marketed as Tertroxin, private script $86 recommended for 100 tabs 20mcg [which I break into eighths, makes 800 doses, say 400 days, price gets better looking!]. My chemist sells for $70 - not generally instantly available straight away in Canberra; ask your pharmacist to try Fauldings in Sydney for supply. This dose level I am using is below normal hourly production, once or twice a day; the whole bottle is probably a very dangerous dose, but the effect of treatment includes sensible thinking. I do not use T4 as it suppresses natural thyroid function.

Unfortunately legumes and brassicas [peas, beans and the cabbage/broccoli family] suppress thyroid function, so if you are determined to raise thyroid function, you are doomed to steak, eggs, chips, salad, fizzy drinks and  some morning real coffee [provides manganese, also caffeine supports thyroid]. (Chocolate continues to have bad effects on me, though far less severe than hitherto, when it was a major source of depression and perturbation). Carrot salad is important especially in the early stages of correction. In reply to questions about why this is so, Ray Peat advised in May 1998 that 

It's something special about carrot fiber, the root contains things that

retard rotting, so it's unlike the fiber in cereals and leaves, which are

easily converted to gas and irritants by intestinal bacteria.  The

enterohepatic circulation permits the recycling of bile-excreted estrogen

over and over when there isn't quick elimination and/or a binding substance

in the intestine.  And besides blocking estrogen reabsorption, the reduced

absorption of bacterial endotoxin allows the liver to function more

vigorously, eliminating even more estrogen.  The increased progesterone and

decreased cortisol that so often result from using the carrot salad

apparently indicate that stress produced by endotoxin has decreased.

We use a Soda Stream drink maker with a quarter teaspoon of carb soda [buy it from the cake making section of the supermarket] per litre bottle for carbon dioxide [add the carb soda to the water first, not after!]. We buy epsoms salts for around $1-70 for 350gms at larger supermarkets - near the bandaids or the Mylanta  - and use half a packet in a warm bath before bed. Get into a warm bed in a towelling gown, straight from the bath, for good sleep and muscle pain reduction, cramp avoidance. Add carb soda to the bath too. Both these simple substances help with calcium management and other requirements for optimising cellular circumstances for the mitochondria. (And the carb soda in the mix cleans the bath wonderfully!)

I started using pregnenolone a month before T3 and while I was almost instantly aware of equanimity effects on the brain and clearer thought, energy etc, big doses were necessary to get any control over night time adrenal alerts. Using T3, I dropped pregnenolone to below normal bodily production, 200mg per week. Pregnenolone can be ordered from Raymond Peat. It cost me $US35 for 10gms bulk, including postage to Australia, delivery 5-7 weeks. (Buying bulk means that does measurement is haphazard, but it is not difficult to take, being a tasteless white powder. There are no negative effects from large doses. Peat reports that rats fed very large doses suffered no more than loss of appetite while their stomachs were stuffed with the powder [e-mail to me January 1998]) I obtained a script from my doctor which may or may not be necessary but avoids any Customs hassles. There is no toxic dose; a weekly amount stays in the system with T3 support. Check price by e-mail to raypeat@efn.org   Payment to R.Peat, PO Box 5764 Eugene, Oregon, 97405 USA. These details are not here for promotion - this seems the best way to obtain pregnenolone in Australia. It is widely sold in the USA. Internet marketing folk sell pregnenolone with wild claims and much higher prices in 10mg capsules as a daily dose, which is a ridiculous proposition  - you need 30mg at least and it needs to be used in the context set out here.

I use 2 x 1000mg Vitamin E capsules per day. Vitamin E enhances thyroid uptake of iodine and an abundant supply of vitamin E will ensure maximum conversion of pregnenolone to progesterone. Vitamin E is fat soluble like vitamins A and D, but there is no toxicity problem as with A and D. (For A, a diet of eggs and dairy should suffice; D is made by exposing cholesterol to UV radiation - i.e. time in the sun.)

I have used a few doses of progesterone, say 3 drops once or twice a week now and then, under the tongue or on skin; don't swallow, it will be broken down. This seems to promote rest more for me - makes me sleepy more than does the pregnenolone, and seems to reduce the night adrenal alerts a bit more. While progesterone may be more suitable for women than men, it has had no adverse or feminising effects - remember testosterone is made from progesterone. Progesterone in vitamin E is sold by Ray Peat as a cosmetic oil, $US35 including postage to Australia. Check price by e-mail to raypeat@efn.org  Payment to R.Peat, PO Box 5764 Eugene, Oregon, 97405 USA.  [NO, YOU SHOULD NOW, IN 2019, GOOGLE PROGEST-E]

Women taking pregnenolone or progesterone should have in mind that if they are making up after a long deficit there may be some symptom shocks and there may be low serum progesterone levels for some time, as the deficit in fat is corrected [progesterone is fat soluble].

Supplementary substances in the foregoing are all equivalent to natural body products or normal physiological inputs. There are no 'medications' among them, allopathic, homeopathic, whatever, although T3 must be prescribed and used sensibly.

I think adequate rest and wise, modest, low-stress use of the exercise tolerance that develops is essential.

If it is the case that elevated neurotransmitter levels are going to depress thyroid, then my approach is inconsistent with sustained use of anti-depressants or some other substances, such as Xanax. Rivotril [clonazepam] in infrequent, tiny doses may help with sensitivity attending withdrawal from antidepressants, but avoid habituation - it's hard to get off, like Xanax, and can lower neurotransmission to levels causing anxiety and pain sensitivity.

I use very occasional aspirin for pain - note that the anti-estrogenic, antihistamine, pro-thyroid, anti-inflammatory benefits of aspirin are a drug equivalent of the whole regime set out above. The main pain I use it for is from sitting typing too long ---huh! But not so long ago I was unable to get relief from pain by any means.