please read this as an old paper, put here to show evolution of ideas.
Copied and pasted here October 2019, without review.
Health. illness and prospective recovery hypothesis February 1998
Dennis Argall
Background
I was born in 1943. Since 1985 I have suffered varying degrees of disablement with what I would now call general disregulation. I caught a number of infectious diseases as an infant, as a child was poorly coordinated, had frequent headaches and respiratory infections and these continued into adult life. In a very successful but sedentary career, working in a number of countries, I fought increasingly against allergic and chemical sensitivities, the persistent colds and headaches. From a shy and protected background, I learned assertiveness and was influential. I was aware at times of 'just running on adrenalin', performing magnificent 'campaigns' of unrelieved activity because I knew if I stopped I would lose threads. In 1983 I had some bigger than usual antibiotic treatment.
In 1984 I was in a most extraordinarily interesting, influential job and doing it to wide satisfaction, openly expressed. As the year ended and as 85 developed however, I ran out of steam daily, I was dizzy at times by 9am, with more and more physical pains. Batteries of tests found no pathology. I withdrew from work late that year, and further deteriorated, being deemed to have a psychosomatic disorder. After several very bad years of disabling pain and distress and very disturbing symptoms associated with anxiolitic and antidepressant drugs, an allergist's diet excluding grains and yeasts and with daily nystatin got me back through a masters degree to get my memory back, and then into another senior job. I was still in persistent pain, however, and went home from work to bed. This lasted less than two years. I found myself totally unable to continue, with pains, overwhelming tiredness, dizziness, palpitations; the exclusion diet seemed irrelevant, just an extra burden. An experiment with a minor research project working a few hours, no more than 10 hours a week, lasted only a few weeks; I would enjoy a few hours at work, then say, no I won't go on, I'll go and rest and be scarcely able to walk arriving home, then have an almighty hangover for several days. I lost track of the line of research; I lost confidence in my judgment.
The period since 1991 has been a blizzarded trail of false hopes and lost tracks, occasional improvements, general decline in many departments, the worst related to prescription drugs, especially antidepressants. Intermittent demands for rehabilitation and constant forensic review neither produced work fitness nor any self confidence, with the need to constantly tell people how appalling I felt. In late 1996 I obtained invalidity retirement and income security. This has at least removed a major stressor, but contrary to the expectations of some, it did not see me get well.
The Search for the Top of the Stream
In early 1997 my doctor started going through the Goldstein [Jay A Goldstein, CFS: The Limbic Hypothesis 1994, Betrayal by the Brain 1996] protocol with me and this produced some very good improvements in energy, in clarity of thought, in largely bringing to an end [or at least under sensible management] two decades of irritable bowel syndrome. See also Jay A Goldstein "The Neuropharmacology of Chronic Fatigue Syndrome" at prairie.lakes.com/~roseleaf/fibro/cfs-1.html.
In July 1997, after some overexertion and at mid-winter in Australia, I went down with a respiratory infection, which saw a general resurgence of all the array of familiar symptoms, in the course of recovery from which I started looking at the internet again. This led me for the first time to the Fibromyalgia Discussion Group Fibrom-L, [to join send the message SUB FIBROM-L [your first name][your surname] to LISTSERV@MITVMA.MIT.EDU]. where I obtained not only the relief of communicating with people who understood my state, but also found there were some very interesting new perspectives being aired. Some of these came from the Newsgroup, the link to which from Fibrom-L was cut in September or so, as Fibrom-L, probably because of the growing intensity of internet activity, saw an upsurge in heated discussion.
Among the new [to me] ideas about were:
- Johns Hopkins research and advice on neurally mediated hypotension, which helped explain some of my odd balance, vertigo and fainting or near fainting experiences. But it did not tell me really how to fix the neural disregulation that caused it. Just diet changes, including more salt, to compensate and reduce impact.
- Dave Williams's ideas about the role of nitric acid in Chronic Fatigue Syndrome, which he has continued to elaborate [see www.serve.com/licorice/]. While this work seems to unearth some very interesting ideas about the role of nitric oxide, and about the way some effective-for-some medications and remedies and supplements work, via nitric oxide, it seems to me that one might almost just as well say that CFS is caused by oxygen or carbon dioxide disregulation. These are very pervasive substances in body processes, the sexiness of NO is that its role has only begun to come to light in this decade. And Dave's regime seems to me to involve too much scaffolding, testing testing and more chemical scaffolding. As I observed to him last month, I am looking something even closer to the 'top of the stream' whose re-regulation might snap into line functions of the organism which sustain stability; if we really needed such constant checking and scaffolding we'd still just be slime in a Precambrian puddle.
- Dr StAmand's ideas about disregulation of phosphate metabolism, with a regime for recovery using large doses of guaifenesin over an extended period. [see eg www.sunflower.org/~cfsdays/misconce.htm] Without guaifenesin readily available, and with other things to try that did not take such an achingly long time, I put this to side. But not before finding that a guaifenesin dose in a cough medicine was very helpful in dealing with lingering wheezing associated with the recovery from the respiratory problems, and along the way getting me restful sleep and thus more strength. I feel at the moment that the StAmand thesis is too narrow. It may very well pinpoint an aspect of disregulation, correction of which for some may be sufficiently burden-easing for more general re-regulation to occur. The StAmand requirement to cut down on a range of pharmaceutical and herbal treatments may also of itself be helpful.
- Dr John Lowe, in chiropractic research, while studying the role of thyroid hormone deficiency in treatment resistance, he found that hypothyroid fibromyalgia patients usually recovered from their fibromyalgia symptoms when treated in one of two ways: 1) with a thyroid hormone dosage greater than the amount thought to be necessary to maintain a normal metabolic rate, and 2) with T3 rather than the typically prescribed T4. In addition, he found that many fibromyalgia patients who were not hypothyroid (those with normal thyroid hormone blood levels) also improved or recovered without overstimulation when given relatively high dosages of T3. Dr Lowe says that his hypothesis is "that the underlying disease process in FMS is impaired metabolism due to a specific faulty mechanism. That mechanism is inadequate regulation....by thyroid hormone of DNA transcription." [Join the Lowe Recovery discussion group by sending the message SUB LOWE-RECOVERY [Your names] to LISTSERV@MAELSTROM.STJOHNS.EDU or get the document quoted by sending to the same address the message GET LR PENDUKE. Dr Lowe's website is at http://members.aol.com/jlowe55555/drlowe.htm ]. I could not come to terms easily with this, it seemed something down a narrow microscope, like the StAmand and Williams hypotheses, a fractional insight, with some positive results, but complicated by the way the principals involved took fairly obsessive views of their own exclusive correctness.
- From various sources, I found interesting the observations that most of my symptoms could be found in people with low body temperature. This connects with Lowe (above), with Broad Barnes [Broda Barnes and Lawrence Galton Hypothyroidism: The Unsuspected Illness Harper and Row 1976] , with Wilsons Syndrome [www.mall-net.com/mcs/coldbody.html]. My attention was focussed when Raymond Peat (next para) wrote in a note circulate to Fibrom-L on 19 September 1997 on 19 September, saying , somewhat startlingly, that "Low thyroid, causes low blood flow everywhere, including the brain, and I have tried to redirect the framework of interpretation away from the various mystifications we see fro example in dementia research, by identifying the simple "cold brain syndrome". The clearest case of dementia, even with a long history of some condition that would supposedly explain it, can disappear in a day or so when metabolism is restored enough to get the brain temperature up to 98.6F [37.0C]. Thyroid is essential for producing carbon dioxide and carbon dioxide relaxes and opens blood vessels, delivering oxygen and nutrients to the tissues in proportion to their level of functioning/formation of CO2, an automatic control system of the simplest and most basic type. Since the carbon dioxide blocks the formation of free radicals, even some of those produced by nitric oxide [he was commenting on Dave Williams's stuff ], as long as there is adequate thyroid and nutrients, the metabolism rises to meet the challenge of stimulation, and there is no stress or excitotoxic damage; it is only when one of the essential factors for respiration (usually T3) is missing that the emergency adaptive systems come into action, and in the absence of energy and carbon dioxide these systems produce collateral damage, besides intrinsic adaptive change they cause directly. Sometimes, when stress has caused a metabolic shut-down of a region of brain cells, the delivery of carbon dioxide, which opens the blood vessels, can be all it takes to restore the whole normal metabolism, and CO2 is unique in having no harmful side effects. Intervening with drugs at various points in the adaptive systems is not only less effective, but it will always produce undesirable side effects." This seemed vividly relevant to me. I knew that my experience was of drug interventions acting just as described; over the next few weeks, I took my body temperature and found it always low, never much above 36.0 and likely to get that high when I had had acupuncture, just then resumed after some years. I found that at truly awful moments, when I was confused in mind by simple things, unable to do anything sensibly, feeling ready to be blown over, my temperature was down below 35.5. So not only was it relevant, but it seemed to relate to broad and basic body processes.
- This American endocrine physiologist, Raymond Peat was responding to individual enquiries from another Fibrom-L subscriber, now running the Lowe Recovery Discussion Group. Then I found he would reply to the naive questions I might send. His website is at www.efn.org/~raypeat. I ordered all the books advertised there and downloaded newsletter samples. The reading load, the learning curve has not been easy; the problems of cognitive disarray, 'fibro-fog' etc, really a modest intermittent kind of dementia, made it harder. Now, in January-February 1998, using pregnenolone from Peat, which has given me equanimity and much greater clarity of thought, I marvel at how I can re-read things of Peat's which I had read several months ago and find I had forgotten them or that I had not understood them as is possible now.. Ray's original qualifications are in anthropology and linguistics, which would seem to provide useful degree of detachment and perspective to current medical science culture; his masters was on Blake's poetry, which led him to reflect on variations on brain activity in history, which led him to a doctorate in brain physiology. The introduction to his newsletter on The Problem of Alzheimer's Disease as a Clue to Immortality begins with this:
"The toxicity of estrogen and of the unsaturated fats has been known for most of the twentieth century, and much has been learned about their interactions in the aging process. The body during this time, has been understood as a dynamic interaction of cellular trophic influences which govern both form and function. My argument here will be that some of our adaptive, protective regulatory processes are over-ridden by the excessive supply of unsaturated fats - supprted by a few other toxins - in our diet, acting as a false-signal system, and that cholesterol, pregnenolone and progesterone which are our main long-term defenses, are overcome by the effects of the unsaturated fats and that the resulting cascade of ineffective and defective reactions (including various estrogen-stimulated processes) leads to lower and lower energy production, reduced function, and death...
If we look at the human organism form one perspective, it seems coherent and intelligible, but form the perspective of established academic biological doctrine, it seems appallingly complex, lacking any visible integrating principle, and as result simplistic, mechanical, pharmaceutical, or religious ideas are increasingly offered to fill the gap. But experimental data can be taken out of the muddle, and put to coherent human use. In what follows [and in his writing generally - DA] I am acting as though the doctrines of genetic determination and regulation by membranes were mere historical relics. The emerging control systems are now clear enough that we can begin to reverse the degenerative diseases... I think many people experience regenerative age-regressing when many circumstances are just right; for example taking a trip to the mountains in the spring with friends can optimize several basic regulatory systems"
I do not propose to try to set out in depth Peat's scheme of things. Thre is a lot of reading and it is worthwhile trying some of it for oneself. I have concluded that it is appropriate act as follows.
Current Treatment Regime
Under my doctor's supervision I am currently taking pregnenolone, imported from Peat [$US35 for 10 gms, notional minimum three month supply], with some diet modifications, with a review of the appropriateness of adding thyroid treatment in a month or so. I am also in frequent contact with Ray by email. This is not some internet money-making racket. Pregnenolone is not a substance approved by the Australian Therapeutic Goods Administration (thus I have obtained a script before ordering), but is sold in health food stores in the USA. I had discussed the question of thyroid supplementation and the significance of my low temperature with my doctor last October. He was not much moved then, I think that the arguments on this may be clearer soon.
Pregnenolone fits in thus, in crude summary [with apologies to Peat]:
- Pregnenolone, a protective steroid hormone is manufactured in the mitochondria (especially in the brain) from cholesterol, in the presence of sufficient thyroid and vitamin A.
- In the presence of sufficient vitamin E and in circumstances of adequate mitochondrial respiration, pregnenolone manufactures progesterone, the mother of all protective hormones, and DHEA
- Progesterone manufactures estrogen, testosterone, aldosterone etc. Progesterone promotes hormonal balance. Supplements of pregnenolone and progesterone, unlike supplements of the corticosteroids, do not suppress bodily production of themselves but promote their own production by the body.
- Derangement of this steroidal chain as I understand it, is readily brought about by stress, by environment, by diet; in women by cycling out of whack or by iatrogenic estrogen derangement. Diet contributes. Sub-clinical, or clinical hypothyroidism contributes.
- I would note that women get chronic fatigue or fibromyalgia, boys are more culturally adequately categorised with PTSD, or expected to soldier on [such an appropriate metaphorical noun-verb].
Working Hypothesis
My working hypothesis is that as a result of a combination of factors, precipitated by traumatic stress and aggravated since, steroidal imbalance and inadequacy form the base of a fundamental poverty of mitochondrial respiration, precipitating an array of somatic and psychological symptoms regularly listed in the symptomology of (take your pick) PTSD, anxiety disorder, somatoform disorder, CFS, FMS, hypothyroidism, Wilsons Syndrome, etc, etc. Intervention with pregnenolone is intended to correct the steroidal imbalance and breath life into mitochondrial respiration, adreno-corticoid and energy and sugar processes, reducing the liver burden, etc.
The pregnenolone treatment is accompanied by some diet change, notably: the avoidance of unsaturated fats [see Peat papers on fats and oils and on osteoporosis and Alzheimers at world wide web site www.efn.org/~raypeat/ - if you can't get to them or download them let me know], of vegetables tending to suppress thyroid; and using vitamin E, coconut oil, carbon dioxide (SodaStream fizz with a pinch of carb soda added to the water), magnesium (Epsoms Salts bath before bed). These serve various purposes, including promoting circulation cellular integrity and more satisfactory management of calcium. It should help deal with what have been disabling symptoms, and also (or rather in the course of) achieving better health in a number of broader areas. As the research evidence is that excess pregnenolone is inert or excreted and as supplements enhance rather than impede normal bodily actions, this is a very low risk intervention. (I will be working on a separate paper on my diet soon.)
Observations after 3 weeks
In the three weeks since starting the pregnenolone, I am able to observe the following changes:
- In the first couple of days I was very tired, which Peat explained as resulting from adjustment of adrenal system.
- In the same period, there was a shift in appetite and a lasting reduction in hypoglycemia symptoms.
- Decline in intermittent dementia state, more clarity of thought, less conversational confusion and agitation.
- Complexion warming, slight tingling and sense of vasculars returning to the face, after long history of chilly pallor, immobilised features, deadness of expression (perhaps contributed to by past work cultural requirements).
- Exercise tolerance and indeed enthusiasm, able to use an exercise bike without agitation or vertigo or lactic discomfort overwhelming me. Rising from 4 minutes first day to 26 minutes yesterday (fan load only, bike's registration of notional performance yesterday 8kms at about 18km/hr, ear lobe pulse meter actually able to register a pulse at about 15 minutes). Not feeling lactic on waking in the morning helps, but waking up keen to exercise is a very novel attitudinal change. There is some reduction in the tight guitar-string quality of some muscles. This paragraph drafted after the first week, I find myself less inclined to leap out and exercise, but I have more endurance than hitherto.
- Alteration of gut behaviour; previous use of Anginine seems irrelevant. Bowel not settled entirely, but works more calmly and surprisingly easily. (Since I drafted that there have been some problems, but again I have specific advice from Peat on it, see Annex A)
- Alteration of sleep. Not as heavy as at outset, but refreshing, relatively brief, waking cheerful during night or in the morning. Dreaming; frivolously, unstressfully.
- I have had a problem, begun when I went on a cardiac testing exercising machine in 1993 (passed that test brilliantly) of numbness/pins and needles in part of the right hand, which has persisted and spread in that arm and a little in the other, also with pain in the related spine outlet areas. This seems to have moderated a bit, and I am conscious of a new sensation (only part of the time) through this whole area a bit like the feeling you get when you've had a leg go to sleep and the blood starts, rather uncomfortably, to return. But that is really in the category of long term damage that is unlikely to be eased swiftly.
- My basal temperature [in bed first thing] has risen a bit, from under 36.0, to a bit above.
- Reduction of chemical sensitivities, consistent with the reduction of psychological sensitivity - but a very different reduction in sensitivity to that offered by psychopharmacological substances. I feel very comfortably conscious, in no way like a slater under a brick.
- I am still fairly easily tired, but I feel I have a more satisfactory base for restoring condition. And I know that I can rest and or use pregnenolone to feel brighter.
- Leaving aside all the somatic stuff, however, I find most enjoyable an unexpected sense of equanimity and problem (my problems, family problems, whatever) manageability; reduction of anxiety.
I have had periods of symptom remission before. I hope this is more durable. I shall use attitude and allow any placebo element as much room as possible, but I am conscious that there is more than placebo going here, when the response to use of the substance is prompt and feels so physical.
There is more to this than waiting for a drug to cut in. The purpose of the pregnenolone (perhaps with T3) is to re-set the steroidal balance. The purpose of the diet is to alter the balance of essential fatty acids and otherwise enhance mitochondiral respiration. These processes take time. They involve also the elimination of toxins, which imposes burdens on liver and kidneys and on the bowel; that requires time and efforts to keep the bowel moving at a sensible pace. I continue with very modest acupuncture treatment every 2 weeks or so, to help the process along.
ANNEX A
From: Raymond Peat <raypeat@efn.org>
To: Argall Family <argalls@atrax.net.au>
Subject: Re: Peat advice/pregnenolone
Date: Tuesday, January 27, 1998 1:30
There's almost no context in which I would speak of "an appropriate dose of
T4," since thyroxin is so effective as an antithyroid substance. It's
appropriate if you are also taking T3, or if you want to shrink your thyroid.
Thyroid will dependably correct your pregnenolone production, if you have
enough cholesterol, vitamin A, and protein. The cholesterol will be
consumed to make pregnenolone and progesterone and bile acids. If
cholesterol is below 160, fruit sugar helps to raise it. The protein is
needed to detoxify estrogen, unsaturated oils, etc, and to maintain the T3.
Protein deficiency gives antithyroid signals, and T4 will be used to make
reverse T3 to inhibit T3's effects.
About 3 mcg of T3 especially if it's taken with milk or gelatine-rich
salty soup is effective for stopping the nocturnal alarm reaction.
The first couple of years that I took pregnenolone, I suppose I ate more
than a kilogram of it, but when I realized how much it was costing, I found
the minimum that's effective, which is very similar on a weight basis for
rats and humans; about 30 mg per day is the adequate normal maintenance
dose, but it can generally be taken spaced as much as ten days apart, 200
mg per 7 days, 300 mg per ten days. A rat given thousands of milligrams in
a single dose shows no side effects, except a loss of appetite while its
stomach is full of the powder.
Diuresis is an effect of thyroid, pregnenolone and progesterone, as
antagonists to estrogenic edema. The alarm reaction that happens at night
has its effects in every organ; for the brain, it's similar to epilepsy;
for the intestine and bladder, the effect can be either adrenergic or
cholinergic, ie, too little or too much muscle tone; the blood becomes more
concentrated. The bowel reaction causes absorption of endotoxin, which is
a broad-spectrum poison; carrot salad, laxatives, etc., are especially
important during the adjustment time.
Cholesterol has a long history as a protectant against many toxins; I
think this relates to the fact that people with very low cholesterol have
such a high incidence of endotoxin-related symptoms. It might also relate
to the therapeutic effects of eggnogs, though it takes a lot of eggs to
raise the cholesterol a little.
At 10:53 AM 1/27/98 +1100, you wrote:
>I said
>>>I seem to have good results after starting pregnenolone Tuesday last week,
>>>but I'm using a fair bit. Say about a 3mm cube per day.
>and Tesa said
>>I don't know how what we were taking measures up against the 3mm cube.
>>We took 200 mg once weekly, which is the Ray Peat suggested to us.
To which I reply
>I haven't been able to measure by weight, I have a little plastic container
>from which I take by volume. Hence the volume guess above. But given that
>the container was a brimful 10gms, and and I have used almost a sixth in two
>weeks, I must be using about three times that amount. My local friend Dick
>Windsor got no result on a small dose, now finds benefits taking 'about half
>a small pea' twice daily. I woke this morning from shallow sleep at 3.45am,
>alarm bells ringing for some reason, thought it was the fact that daughters
>were not home [they turned up cheerful and well a bit later] but then found I
>was, after modest activity, desperately cold, not relieved by sugary snack
>or putting on heavy tracksuit in mid summer might, found that my temperature
>was 35.3, took 3mm cube of pregnenolone [having taken none, I realised,
>during previous day] got to sleep feeling warm sometime later, now feeling
>well warmed, indeed headache from having head double wrapped. As I'm getting
>reaction to the pregnenolone quickly I wonder why a weekly modest dose - at
>least to start, I have presumed that I'm making up a deficit.
>
>Ray, I also am having a clearly related bladder pain effect. Sometimes with
>something to produce, sometimes little, but definitely a sensitivity which
>comes on swiftly after taking pregnenolone, lasts depending on amount used.
>Have you observed that before? Is it indicative of excess dose? Linked also
>to general weakness lower back.
>
>Ray, are there short term and long term responses to be expected: I'm
>finding a desire to take more to maintain gains I seem to have made. Is that
>realistic. Or is the swift fall off indicative of need for thyroxin. I do
>not get from your texts, a sense of your approach to thyroid treatment.
>
>I have moved my diet fairly comprehensively to what I understand to be your
>recommendations. I presume, however, that the change will take quite some
>time to wash through the system and that there may be some adjustment
>sensitivities. My liver feels pretty sore, is there an EFA change load going
>on? Or is it because I am doing a bit more, maybe putting a bit more lactic
>load on it? Or a combination of the foregoing? Or are these stupid
>questions?
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