"Chronic Fatigue Syndrome"
- a fresh approach
(c) Dennis Argall 1998
If we look back 150 years, to the paradigms and practices of that time, we are likely to smile indulgently. Many of us can see clearly that the belief systems then operating were inadequate to explain events, and have been overtaken. But too many of us lack a capacity to learn from that observation about our current paradigms. If we go forward 150 years in our imagination and then look back it seems likely that practitioners of that day will smile again at our belief systems. There is nothing wrong with this - we are using the best paradigms we have. They are not perfect and they will be overtaken. We need to be relaxed and ready - and not be prisoners of the paradigms of today.
The Tasks of Medicine
An Ideology of Care
Why we have to discuss methodology
Chronic Fatigue Syndrome - the perils of disease classification
Reason and Reductionism and The Tasks of Medicine
The need to look at systems
New Perspectives  Evolution
Nervous or endocrine system? Whos in charge here?
How little we know
Proposition: That the nervous system is a disruptive passenger,
and not as in charge as we think
What is a mitochondrion
Gene theory sells us short
Mitochondrial functions - the chart
Mitochondrial Task 1 - respiration
Mitochondrial Task 2 - steroidogenesis
Mitochondrial Task 3 - apoptosis
Another evolutionary issue - calcium
How does this relate to CFS
The consequences of respiratory inefficiency
Unopposed, unrelieved catabolism
The thoughts and needs of the mitochondrion
Free radicals and antioxidants
The exercise problem - fundamental turnaround and recovery
Appetite, cravings, eating disorders, ADD and psychiatric disorders
Saturated and unsaturated oils
Blind trials of single substances v. synergistic packages
The 80% rule - self-recovery
An individual, subjective report
What do I do
The synergistic package
Why we have to discuss methodology
Last month, a team from the University of Adelaide visited Canberra and spoke of CFS as involving a defect of energy metabolism. While the findings of the team were encouraging and consistent with what I am proposing to say now, I was disappointed by the methodological limits to these professors' inquiries.
Last April I wrote a paper, published in the Winter issue of Chameleon, in reply to which the Anonymous Doctor has written with some concern for methodology in addressing new approaches or using new substances.
I agree that it is important to have a coherent intellectual framework and methodology and that in what was a quick, work-in-progress note in Winter Chameleon, the science base of my approach was not set out explicitly.
So I must begin here with some such discussion.
I was trained in anthropology and my truncated career was in the foreign service and policy areas of government and working for the parliament. I thus presume nothing, other than that all perceptions are culturally based, that they reflect community ontology - the way we explain life; all ideas of fact and truth are similarly culturally based. I advance nothing based on faith or mystery or unprovable, un-disprovable propositions, as in some areas of 'alternative medicine', and in some attitudes to and expectations of conventional medicine. Having spent a working lifetime looking at whole cultures and their major institutions, my own view of my own society has to be affected.
Let me state it again, more directly: the practice of medical science, the nature of medical practice - and the way in which Chronic Fatigue Syndrome is dealt with either by doctors or support groups - has no intrinsic truth; it is cultural behaviour. To think otherwise is to grant the status of religion.
Edward O. Wilson, Harvard naturalist, gives us two very handy words for defining characteristics of the cultural evolution of Homo sapiens1 . They are: autocatalysis and hypertrophy. Autocatalysis is the tendency among humans for doing something to facilitate the doing of ever more of the same thing. Hypertrophy is the tendency to develop any aspect of culture to the extreme. A moment reflecting on the complexity of modern urban life, compared to basic human needs, allows us to see the value of those two propositions. I suggest that the conformation of medical science and the complex and ritualistic processes and expectations surrounding medical careers, medical practice and patient expectations are more easily reviewed or seen critically, when we recognise just how autocatalytic and hypertrophic they are. As I write, the ABC News reports AMA support for increased tax incentives for private health insurance. There is a seamless web of sustaining power and intellectual support for maintaining things as they are, even when they begin to crumble.
I began my current line of research a year ago with, I think, the characteristic focus of sufferer or doctor: "What can I do, what can I take, to fix me up, to make me feel better". You know and I know how keen we become to try anything new. It would take me a very long time this evening to catalogue all the treatments and approaches I have tried.
Different conventional doctors have offered me a wide range of medications and other routines. And I've tried any number of alternative remedies.
I have found it necessary, in the last half year, to put aside that pressing "whaddo I do?" question and address some broader questions, and I feel that is essential for understanding of the approach I now take. It has been a difficult thinking and writing process; I am grateful for this opportunity to bring it together.
You have to step away from the mendicant relationship of patient to medication to get benefits from what follows.
"Chronic Fatigue Syndrome"?
- the perils of disease classification
Let me make another basic point, express another strong, perhaps contentious opinion: I believe that the diagnosis "Chronic Fatigue Syndrome" has some psychological, social and legal values, but such a diagnosis will not in my opinion contribute to solving the cluster of health problems to which it is attached.
The critical problem is that the labelling tends to encourage the effort to isolate CFS as a disease phenomenon, or set of phenomena, which in turn encourages differentiation and dissociation from other health problems. The diagnostic criteria are differential: exclude this, exclude that and (if you believe in it) you may have CFS. So we have then this fragile little disease classification, a little box of identity, from which effort goes into identifying cause or cure.
Neither Gods nor Gaia know the names of diseases. They are intellectual constructs of the classificatory approach in recent medical research and practice, replete with the most dreadful vanity that the odder the illness the greater the enthusiasm of the 'discoverer' to give his name to it.
Short of finding cause or cure, there seems to be a preoccupation with finding a 'marker'. I look around at a number of diseases for which markers have been found and find no great comfort. The incidence of diabetes has risen since it was identified and insulin was made readily available; there is no 'cure' and the treatment brings problems. Alzheimer's Disease has markers, I believe, but is 'incurable' and what is the significance of putting a boundary between that order of dementia and the 'reversible' dementia (politely known as 'fog') in CFS. Sure there's a difference between reversible and progressive, but how secure is the fence and what's the point? Are there no common considerations? I can assure you that until this year I had many periods - progressively more of them - of feeling profoundly senile, incoherent, incompetent, forgetful, irritable and stupid. Time spent earlier this year as a 'moderator' with an internet discussion group of 1400 people with Chronic Fatigue and Fibromyalgia impressed me with the pervasiveness of such symptoms.
Alzheimer's and diabetes are 'modern' diseases, and both are now regarded as diseases of mitochondrial DNA - but in my view are in the same field of ill health as this concept of 'CFS'; the same issues of mitochondrial fitness and abundance arise, it's not just a question of disparate genetic time bombs, but a question of how we care for our cells.
Dr Burnet, from Adelaide, spoke of wanting to use bicarbonate, just to raise pH, in response to a lactic acid state arising in CFS. That simple approach to symptom treatment is exactly the kind of destructive consequence to marker-discovery that would make CFS diagnosis very dangerous indeed, in my view. You cannot solve this kind of problem by correcting little aspects in isolation.
If you are a woman, if you have CFS-ish symptoms and especially if your mother did so too, if you see the right doctor and he catches a thyroid deficiency in tests, you may be diagnosed with Hashimoto's Thyroiditis and be prescribed T4 which will shrink your thyroid and make the illness proof of its identity and its incurability, and you will have all the symptoms of CFS. But you won't have CFS, because of the prior differential diagnosis.
If you have undergone adrenal stress or for whatever reason present yourself to a doctor with CFS-ish symptoms, and the doctor assays your adrenal hormones and finds a lack of cortisol, you may be diagnosed with Addison's Disease (an American friend said to me: "I just have CFS, but my sister has Addison's") and you may be given cortisone supplements which will reinforce and entrench the CFS-ish state, at cellular level. It can't be CFS, because of the principle of differential diagnosis. I had a shot of cortisone in mid-year, for multiple bee stings. I promptly got the puffy cheeks and other signs of Cushing's Disease (excess cortisol, especially in over-supplementation), as well as the return of every symptom I have ever had of CFS. The Cushing's phenomena went away pretty soon, but the cognitive, fatigue, gut and other symptoms persisted. I will speak later of how I got them to go away again, as I had earlier in the year.
If you fight ferociously against the fatigue and neurological and gut symptoms and the pain and then present yourself to a doctor, with anxiety or eventually feeling despairing and depressed, or perhaps with a bit of substance abuse, legal or otherwise, then you will almost certainly be precluded from CFS diagnosis, by differential diagnosis.
If you are woman and the disability hits you most desperately locally, in reproductive areas and is perhaps worse at times, then you may be the butt of jokes or prejudice ("The problem with her is that she has PMS 12 months of the year" - I have heard it said) and you will certainly have available a professional-industrial panoply of medication, surgery and psychiatric advice and counselling. But that won't be CFS, of course. This is a tragic subject. I am sure that there are very substantial links between CFS and women's problems, but too often the women's problems are far progressed, perhaps dealt with surgically, before the 'CFS' becomes an issue. The losses are so profound and the taboos and sensitivities so great as to make taking a fresh view difficult, and the weight of professional specialist opinion is against the connection.
I am less hormonally vulnerable as a man, but I am pleased that this approach to treatment I have adopted this year took away, unexpectedly, a prostate enlargement and discomfort (weight for age not a major problem, in professional opinion, not cancerous but uncomfortable). And that has nothing to do with CFS either, of course, because medicine's meaning is based on discrete disease classification.
So, be wary of disease classification and 'markers'; and be wary that success for the CFS label may lead to compound problems arising from fragmentary treatment.
A Russian physicist friend with CFS recently wrote, reflecting on the state of Russia, socially and especially environmentally, that doctors in Leningrad now tended to define a well person as a person not yet aware of what was wrong. In other words, perhaps, a person not yet fitted into the taxonomy of disease.
Certainly, CFS is a disease with a place and time: that correspondent had her diagnosis in Israel. The problems related to CFS will not be solved by assigning the label to people with similar symptoms in Leningrad or Bangladesh or Ouagadougou. The chronic fatigue, in my view, is in the disease classification approach to medicine.
Reason and Reductionism and
"The Tasks of Medicine"
It seems to me that the nature of this illness is such that it cannot have a settled, comfortable place in Cartesian, reductionist medical science - unless that cozy marker comes along. I would prefer, however, to see change in the parameters of conventional medicine.
That's just my view, you say.
Of more importance is a book edited this year by Peter Baume, former Federal Health Minister, former Senator, now Professor of Community Medicine at the University of New South Wales and Chancellor of the Australian National University, entitled The Tasks of Medicine: an Ideology of Care.2 It brings together some writers with leading roles in thinking about medical practice.
Miles Little, a published poet who is also Emeritus Professor of Surgery and Founding Director of the Centre for Values, Ethics and Law in Medicine at Sydney University, provides a critique of "Cartesian Thinking in Health and Medicine". We derive from Descartes, writing in the early seventeenth century, much of our contemporary approach to reasoning, just as much of our thinking about physics and, indeed, about our bodies is derived from Newton. Little notes Descartes' understandable fear that he could fall into the hands of the inquisition, like his contemporary Galileo. We cannot know just how much that fear coloured Descartes' arguments; everyone has lost sight of the fact that Cartesian reasoning was based on a reasoned explanation of the existence of God which reads rather strangely today.
Descartes was preoccupied with analysis rather than synthesis, which led to the 'reductionist' preoccupation of contemporary medicine. The Oxford Companion to the Mind says that:
For a long time reductionism remained the generally accepted philosophical aim of the natural sciences... It was supposed that the basic goal of science is to reduce complex phenomena to separate simple parts, and that such reduction provides significant explanations of phenomena.
... there are grounds to suppose it may be false.
To study a phenomenon, or an event, and to explain it, one has to preserve all its basic features... It can easily be seen that reductionism may very soon conflict with this goal3
Descartes, writes Little, also established 'dualism', the idea of the separation between mind and body, which also plagues modern medicine and our 'western' way of thought generally. Anyone seeking a CFS diagnosis and seeking to avoid the outer darkness of being passed to the shrinks, knows that!
A lot of Descartes' ideas were subjected to criticism near his own time, but as is the case with many evolving social institutions, they have become set in concrete and and become rigid rules. Reductionism, though it has not intrinsic truth, is at the heart of modern medical research and practice. Little says:
Ontological reductionism (meaning how we understand the world around us) is expressed in the devotion to the structural explanation of disease; methodological reductionism by the search for further explanations at the level of the molecule and the gene; and theory reductionism by the way in which we assimilate teleological explanation into genetic explanation...4
Teleology being 'the doctrine of final causes, especially as related to the evidence of design or purpose in nature'5. That is - my words - the current tendency to focus obsessively on genetics, in ascribing functions to body/cell bits in accounts of research. Little continues:
Medicine in practice and in research is reductionist and reductionism has enabled the extraordinary developments of scientific medicine over the last 200 years.
But reductionism has its weaknesses. Reductionism in science assumes 'bottom-up' causation - that is, it assumes that ultimate causes can be found at the lowest levels of physical structure, the molecule, the fundamental particle.6
Little takes the view that:
Reductionism and dichotomous thinking have worked to disengage medicine from its foundations. The whole health endeavour is justified in Western societies by the high valuation we place on human life. But it is the whole human whose health we defend or restore, not her liver or heart alone.7
I think that among things that commit medical research and practice to its reductionist trench are:
(1) The high volume of graduate research and the obligation on every researcher to find virgin ground. And that virgin research ground, like farmland in China a century ago, gets smaller and smaller, generation after generation. Will a revolution come?
(2) I suspect that supervisors are chronically anxious that young students do their basic graduate work in conformity with established big pictures and methodologies. Apprenticeships are done within the dominant paradigms; research funding is largely within such paradigms. See also Richard Lewontin's less charitable view, under (4).
(3) Fear of litigation for malpractice, fear of professional discipline, keeps doctors within one standard deviation of orthodoxy.
(4) Reductionist research goes through fads and phases of power in pursuing fundamental causes. Genetics is just the latest fad focus. Richard Lewontin in his Canadian Broadcasting Corporation Massey Lectures 19918 criticises [chapter 3] the ideological prejudice in modern biology particularly as relates to causes, or rather the tendency to seek THE cause of an effect. This he says is "nowhere more evident than in our theories of health and disease". In discussing pursuit of the 'cause' of cancer he runs through the history of cancer research, pursuing a viral cause, an environmental cause and more recently in the human genome project, of which he is sharply critical. He asks (or, in 1991 asked, but the question remains valid):
Why, then, do so many powerful, famous, successful, and extremely intelligent scientists want to sequence the human genome? The answer is in part, that they are so completely devoted to the ideology of simple unitary causes that they believe in the efficacy of the research and do not ask themselves more complicated questions. But in part, the answer is a rather crass one. The participation in and the control of a multibillion dollar, 30- or 50-year research project that will involve the everyday work of thousands of technicians and lower-level scientists is an extraordinarily appealing prospect for an ambitious biologist...9
(5) Legal and commercial pressures focus on an allopathic pharmacopoeia and mind set.
Baume himself writes:
The prevailing orthodox paradigm derives from allopathy - 'the treatment by opposites' - in spite of contrary protestations from many well-trained, present-day practitioners. Allopathy arose from the view that disease was caused by noxious influences within people. In accordance with that view it made sense to purge and bleed people to reduce the amount of noxious substances. That paradigm continues to affect practice today - the pharmacopoeia contains antibiotics, anti-hypertensives, antipyretics, ... and many more agents which are grouped by what they are against, and whose desired action is to oppose something.10
Doctors are constantly dealing with patients whom, they know, will go to alternative practitioners and pay out of their own pockets for treatments of mixed and uncertain value, treatments which, it seems to me, are increasingly or even more than conventional drug industries, driven by commercial promotion. There is a lot of expensive nonsense in health food stores. But there is much unease and despair among health service consumers, which drives them to the health food store.
It may be understandable that doctors find it convenient therefore, to retreat to arguing the need for reductionist testing and approval for things people want to take. But that is a self-defeating approach in the end.
Moreover, some of the reductionist-approved procedures seem to contribute to systemic health problems. I think I can say that nothing I have bought from a health food store has done me prompt damage; the same cannot be said for some things carefully prescribed for me.
Among the things we do, on reductionist allopathic principles, are these:
- we respond to difficulties with sugar metabolism not by improving that metabolism but cutting back or adding the chemical to oppose the sugar. If I took my car to the garage and said there seemed to be something wrong with the way it used petrol, and if the mechanic said I should instead put diesel fuel in the tank, I would think the mechanic a fool; but we soak up the complex carbohydrate argument...
- we respond to difficulties with cholesterol metabolism (steroidogenesis) not by fixing that problem but by telling people to stop using the body-essential substance cholesterol and instead use readily oxidised paint thinners (unsaturated fats). If I took the car to the garage and told the man the car was huffing badly on the hills and he came back to me and said there was oil on the spark plugs but it would be all right now because he'd taken out the sump oil and replaced it with kerosene, we'd know the man was a fool - but we live in terror of cholesterol in the blood vessels and will replace it with anything...
- we respond to pain not with efforts to resolve the source of pain, not as an important warning, but with powerful chemicals which slow cellular processes and compound underlying problems
- we deal with symptoms of despair with antidepressants which also interfere with cellular processes and reduce respiration and steroidogenesis; those same potent substances are used for 'side effects' in CFS, or as someone on an internet discussion transferred such use to a different reality, "antidepressants work differently in people with CFS". Hah!
- we treat acid stomachs with H2 blockers, which interfere with cytochrome P450 in the liver11 . Cytochrome P450 is fundamental for thyroid hormone to get to the mitochondrion and allow respiration and steroidogenesis12 .
- when liver weakness leads to enterohepatic weaknesses and bowels become irritable, we add grain fibres which add gas and increase bacterial endotoxin levels
- the same grains are thought by some to be good for sugar problems as they are complex carbohydrates, but they impose further work on the pancreas and they have a high glycemic index and themselves contribute to hypoglycemia.
The key point I want to make is that these are fragmented responses to problems identified fragmentarily, with the reductionist blinkers on. When we try to put the brakes on problems in the body, we also seem to put brakes on the most fundamental important processes. AZT interferes with mitochondrial DNA (mtDNA) replication; the new wonder treatment for impotence, Viagra, promotes the blood vessel dilating functions of nitric oxide, a free radical implicated, among other things, in nerve cell death after heart attack13 . What can we say? Lucky stiffs?
On 8 November the Associate Professor of Pharmacology and Toxicology at Canberra Hospital, David LeCourteur was quoted in the Canberra Times warning that "half the new drugs that come onto the market could turn out to have serious side effects... Every new drug costs about $300 million to develop and there are enormous pressures for drug companies to make a profit."14
The need to look at systems
The need to look at whole systems rather than fragments was expressed perhaps most elegantly by the physiologist Albert Szent-Gyorgyi, after whom a university is now named in Hungary:
Or, at more length:
One particle, plus one particle, put together at random, are two particles, 1+1=2; the system is additive. But if two particles are put together in a meaningful way then something new is born which is more than their sum: 1+1>2. This is the most basic equation of biology. It can also be called organisation.15
The word holistic has become very popular in medicine and elsewhere. Baume et al are discussing the importance of holistic medicine in The Tasks of Medicine, but the term has been hijacked to some extent by some alternative practitioners. Baume states the key problem thus:
Without science modern medical practitioners are dangerous. Without humanity they are monsters. Some alternative practitioners have no science; some orthodox practitioners have no humanity. 16
* * *
When I scribbled that piece for Chameleon in April I was preoccupied by 'what to do to fix me up?' In the half year since, I have been very much more preoccupied by the broader issue of trying to achieve some systemic understanding of what is going on in CFS and the like.
I had set out to get myself well, no more than that. I had not imagined that this would lead to a critique of the state of contemporary medicine. Whether my naivete and lack of education in the 'rules' of science is an advantage or a disadvantage is for others to judge.
The news of recent days in relation to public health in Australia are indicative of crisis. Costs accelerate, while results are marginal and relate to running repairs of human degeneration rather than its prevention or correction. We are trapped in a vicious circle.
* * *
New perspectives -
My own new perspective is influenced by evolutionary biology. I have been profoundly influenced by consideration of the role and status of mitochondria in our cells. That is, I have come to appreciate that there is a holistic world at the level of the cell; at conception, we are just one cell, for most organisms on the planet, that's as good as it gets.
We happen to be made up of large numbers of differentiated cells. But the cell remains a fundamental whole unit of life, and there is a critical social contract involving the cell and the mitochondria.
We are a vain species, and nowhere is that vanity greater than among the Middle Eastern and European cultures which have produced both the most rapid advances in mathematics, science, technology and industry and the religions which are most species-centric. A great deal of our cultural focus on medicine is shaped by presumptions of species superiority and especially by our infatuation with the defining brain development of Homo sapiens. This cerebral feature, perhaps acquired, as Edward O.Wilson would argue, in evolving to become the dominant carnivore on the African plain, and enhanced by the nutritional advantages of the use of fire to cook meat, produced the cultural evolution of the species which has run
ahead of our physiological evolution.
This disparity between cultural and physiological evolution is a major factor in stress. When I refer to stress, I mean whole organism stress, not just mental stress as in the word's most common use.
Stress can manifest itself in our minds and behaviour, of course, but that says nothing about where it comes from.
Nervous or endocrine system?
Who's in charge here?
Our front brain infatuation is evident in the tendency of medications, and other healing techniques to give great emphasis to cerebral and other brain processes. In earlier years with this illness, I used medications and was encouraged with other techniques to resolve issues at brain level.
During 1997, with my doctor, I went through a number of substances in the Goldstein protocol, to attempt to reorder a neurological disregulation, especially of the limbic system17. A number of these substances had prompt benefits but the benefits turned out to be transitory18.
When I began reading, then, about the endocrine system and especially about the steroidal hormone system, I began to have a sense of a whole new world, both of body management and communication, of which we have far less understanding.
How little we know
Last week, Philip Adams was interviewing the Director of the Royal Observatory at Greenwich on Late Night Live. The latter noted that we only understand what 10% of the matter is in the known [external] universe.
I think we should regard our knowledge of our internal universe as probably comparably limited. Like the astrophysicists we really don't know all that is in our internal universe. The reductionist mind set of our research inhibits systemic understanding and the making of deductions. Our ability to know what is going on inside is also limited because our tools are so largely confined to electromagnetic readings, pictures and measurements.
That the nervous system is a disruptive passenger, and not as in charge as we think
The nervous system is central to our ability to deal with the external environment and stimuli from it. But it is not the only, and probably the less smart system for communicating within and managing the organism itself, though we presume to give it primacy. There is room for dispute about such a proposition, but rather than be sidetracked to that, I would hope one key proposition could be accepted: is it reasonable to regard the performance of the nervous system as dependent on a more basic system of endocrine19 management, that the nervous system, grown so large, so self-opinionated, so dominating in Homo sapiens is really a passenger, albeit a disruptive passenger claiming ownership, on endocrine systems? That leads to the important proposition that if there is endocrine disruption or disregulation or perturbation, problems at that level will give rise to problems which are more easily detected neurologically and in behaviour. But it will not fix the problem just to address it neurologically or psychologically. You have to go back to the source of the problem.
At the same time, it allows us to recognise that when social and cultural pressures - work, relationship, travel, car accident, iatrogenic, whatever - impinge on our nervous systems, there can be an impact back into disregulation of endocrine systems. So if you are going to fix the problem at the endocrine level, then you also have to make sure that the organism you are fixing (the person) doesn't have to keep going in a socially-culturally-environmentally toxic environment.
What is a
photo of mitochondrion from this website... hardly a vision likely to encourage the average student to see it it the meaning of life!
I interrupted writing this Saturday for several hours while a retired professor of history visited.
I asked him what a mitochondrion was. He, like most of the human race, did not know. I said I thought our ignorance of mitochondria extraordinary, as if the Czar, in 1912, had remarked: "Serfs? What are serfs? Do we have serfs? What do they do?"
There is now widespread acceptance in evolutionary biology that about 1.2 or 1.3 billion years ago, when the bacteria populating this planet had ruined the atmosphere by adding their waste product oxygen to it, one bacterium attacking another failed to kill its target and instead was coopted to remain in the cell and undertake key tasks.
This allowed the development of a nucleus in the cell, with the mitochondria undertaking key tasks. The contract has been around for a long time. you don't have to buy that theory in detail to accept that. And any sense of history, rather than mechanical Newtonian physics, alerts us to the prospect that there will have been a few problems with the contract over time and that some of these will persist. The fantastic longevity of the mitochondrial contract has to make us sit up and remark on its importance - contrast the failure of the apparently useful Australian Conciliation and Arbitration Commission to last a century; or say the failure of Egyptian civilisation or the British empire; or the departure of most species in the fossil record.
While my historian friend, intent on writing a centenary history of the Department of Defence, did not know what mitochondria were, it is even more interesting to listen to scientists speak of them. There seems to me at times to be, shall we say, an ontological nervousness. There is an odd, awkward dismissiveness in some scientist's attitudes.
Partly it may be that mitochondria slip down educational cracks. Their role in energy processes comes under physiology; their role in steroidogenesis is almost entirely skipped over or muddled in biochemistry and endocrinology; their role in apoptosis is only just becoming appreciated particularly because of cancer and AIDS research.
As the chart above shows, the human mitochondrial genome has been mapped in its entirety and it is now possible to assert that specific disease problems arise from specific mtDNA.
Gene theory sells us short
My own view is that this sells the mitochondria short, just as reducing our whole selves to an eventual, somewhat bigger DNA map will sell us short. There is more to life than that. The gene allocation of disease neglects the prospect that mtDNA can be cared for, and that they aren't just ticking down; it also distracts from the reality that mitochondrial inefficiency is responsible for ill health, whatever the state of the DNA.
Excising the segment marked on the diagram by the clock hands at 6:15 apparently will do something for Kearns-Sayer Syndrome/progressive external ophthalmoplegia; but I would be inclined to think life a bit more complicated than that. There was far more enthusiasm for corrective brain surgery in the 1950s than now. What's the difference? A magnitude of cleverness, of technological innovation?
- the chart
If I have done anything original in my writing, it is to combine on the one little chart two of the key things that mitochondria (ten, a hundred or a thousand to the cell, the numbers vary particularly with the level of activity of the cells involved, as well as with health, season, etc) actually do - respiration and steroidogenesis. There is a very important third task below, which I have not been able to depict in the same way.
Mitochondrial Task 1
The horizontal process in the diagram, oxidative phosphorylation or intramitochondrial respiration is amply discussed and illustrated in many places, many texts.
Mitochondrial Task 2
There is no dispute about the steroidogenic process. Let's make clear, by the way, that the word 'steroid' is hopelessly confused in both common parlance and some medical use. The ster in cholesterol and the ster in steroid are the same. A steroidal hormone is one made from cholesterol. It is described in various places, though textbooks seem not to be greatly interested in cholesterol's foundation role in the steroidal system.
Here's a handy statement of the process, albeit written by an undergraduate:
The precursor of all body steroids is cholesterol. This is first converted to pregnenolone in the mitochondria of the cell, via hydroxylation and the removal of six carbon atoms from the hydrocarbon side chain at C17.20
Ray Peat21 , endocrine physiologist specialising in stress and aging, who has written extensively on functional hypothyroidism, pregnenolone and progesterone, has a diagram in several books22 from which I derive the vertical process in my diagram. There is a more extensive account of downstream hormones (testosterone, estrogen, cortisol, aldosterone) in Dr John Lee's book on natural progesterone. Lee's approach to progesterone is derived from Peat, but he rejects Peat's views on cholesterol and sugar use, which may reflect the fact, as Lee reports, that in his sixties he is the first male in his family for several generations to live past 4023 .
My own debt to Peat is substantial; the development of my ideas was facilitated by an almost daily e-mail dialogue until Ray went to Mexico for a sabbatical from June to October. It has actually been very worthwhile for me to move on since then, developing my ideas independently and validating information and ideas from a wider range of sources. This wider research has tended to validate much of Peat's views - if one takes the results of Medline research on details and relates them to a broader perspective.
It was from reading Peat earlier in the year that I derived the propositions in my article in Winter Chameleon regarding hypothyroid states and chronic fatigue and the uses of T3, pregnenolone and progesterone. Let's be absolutely clear about this: the conventional medical requirement is that hypothyroidism be precluded as a diagnosis before CFS be diagnosed. This arises because of the common symptom patterns.
The critical issue is whether the processes in the mitochondrion, for which T3 is essential, take place. Here it is put another way:
Since mitochondrial energy production accounts for the vast majority of total energy production, mitochondrial function is a necessary and essential aspect of the regulation of basal metabolic rate. In other words, either decreased thyroid hormone or mitochondrial dysfunction can lower basal metabolic rate and induce the symptoms of hypothyroidism (cold hands and feet, sensitivity to cold weather, psychological depression, cognitive difficulties, dry skin, scaly scalp, brittle hair, menstrual problems, constipation, diminished stomach HCl production, etc.). Non-thyroid-related mitochondrial insufficiency could easily account for the high incidence of hypothyroid symptoms in individuals with otherwise-normal thyroid hormone levels. Perhaps a significant amount of subclinical hypothyroidism is really mitochondrial insufficiency.
Regardless of what it is called, decreased mitochondrial energy production reduces the capacity of the cell to function. Depending on the cell populations affected, this may decrease body temperature, lower immune function, impair growth, decrease DNA repair, impair hearing, weaken muscles, decrease steroid and neurotransmitter synthesis, and lower nervous system electrical potentials. These are all factors which are associated with both mitochondrial diseases and hypothyroidism.24
Mitochondrial Task 3 - Apoptosis
A third key function of the mitochondria is less well understood and still the subject of research. That is, the role of mitochondria in 'apoptosis'.
An information paper from the Apoptosis Interest Group at the U.S. National Institutes of Health says this:
Unlike most terms used in biomedical science, the term apoptosis is not simple to define, and this has led to some confusion and controversy. The proper pronounciation [sic] is also controversial (if in doubt try ap-a-tow'-sis). In any case there is intense current interest in this area, with a recent exponential expansion in Medline textword citations. There are exciting and powerful ideas emerging from these studies...
The term apoptosis was coined in a now-classic paper by Kerr, Wyllie, and Currie (Brit J. Cancer 26:239) in 1972 as a means of distinguishing a morphologically distinctive form of cell death which was associated with normal physiology. Apoptosis was distinguished from necrosis, which was associated with acute injury to cells...25
There are some firm views emerging about the role of mitochondria in apoptosis:
mitochondria appear today as the central executioner of programmed cell death
write two French researchers, who add:
We discuss the possibility that the mechanism originally involved in the maintenance of the symbiosis between the bacterial ancestor of the mitochondria and the host cell precursor of eukaryotes, provided the basis for the actual mechanism controlling cell survival26.
I do not wish to get into detail of this here, and my own knowledge is rudimentary, but it is of enormous importance that we see the mitochondria not only as doing the critical work of respiration and steroidogenesis but also controlling life in the organism more broadly by apoptosis.
Apoptosis would seem to occur in normal body changes, as in the loss of tails by tadpoles and in the alterations to the breast after weaning.27
It also appears to occur where the cell's DNA is interfered with, as in cancer or viral attack. The capacity of the mitochondrion to shut down cells under such attack is obviously closely related to health, immunity and disease resistance.
This not only involves mtDNA but the health of mitochondria generally.
And we can begin to see links to issues of immunity and some reasons why the issues of 'viral cause' or 'post-viral onset' in CFS may in fact reflect problems at this level. The susceptibility to viral infection, the apparent devastating effects of a viral infection - especially if the sufferer ploughs on and makes high exercise demands of the mitochondria during that infection - are usefully seen at this intimate level of the general health and wellbeing of the mitochondria and their ability to do all the things they would like to do (I started to write 'assigned tasks' but that assumes they are not in charge or not voluntarily acting wisely).
This is speculative, but it seems a more fruitful line of inquiry than search for a viral cause. [note 10 years later... you will begin to find now medline research in these areas... D]
Another evolutionary issue - calcium
One of the most significant elements on the planet and in living organisms is calcium. Calcium does some very important things in the body, in bones, blood and so on, but elevated levels of calcium in the mitochondrion depress mitochondrial functions and have potentially much wider impacts.28
The fossil record indicates a major achievement in evolution some six or seven hundred million years ago, with the first appearance of calcium based skeletal structures. This gave rise to all the higher organisms of which we are proudly the finest.
But what do the mitochondria think. I think they were pleased to get rid of the calcium dust storm and get on with life as a mitochondrion would wish to know it.
Especially as we face more stresses as life expectancy increases, we see in a variety of health problems that this little issue of getting the free calcium out of the way of the mitochondria has not gone away.
A crucial consideration: high levels of estrogen are associated with high levels of cortisol; these are catabolic and have other disturbing effects. They draw calcium from bones. The free calcium will interfere with mitochondrial function. Production of progesterone will fall; a vicious cycle of estrogen dominance is established; mitochondrial performance falls further.
It's really quite interesting, to consider that an array of health degeneration issues may be best understood in terms of these very very ancient issues within the cell.
I don't believe it is unscientific to adopt deductive approaches to developing an overview of this situation, and plans for action to assist natural processes to correct themselves.
How does this relate to CFS?
All the symptoms in CFS can in my view be related to problems that arise from inadequate mitochondrial performance. Up at the top of those symptoms are persistent fatigue, neurological deficits and autonomic dysfunction.
Scroop et al in Adelaide are examining the issue of defective energy metabolism and lactic states. That is a mitochondrial problem. Scroop expressed uncertainty about exactly where the blockage was occurring. It could be in many places, and hence a holistic approach to enhancing mitochondrial performance is appropriate.
Deficits of ATP diminish neurological functions; adequate pregnenolone is essential for the stability and myelination of nerve tissue.
The Adelaide findings regarding energy metabolism fit with this proposition, as do sugar problems, both the hyper- and hypoglycemia. Same with the hormonal-reproductive problems which seem anecdotally a significant co-factor, underreported for reasons mainly of disease classification thinking.
Intestinal problems can be related both to autonomic deficits and liver burden due both to lactic acid and estrogen clearance problems. While these do not amount to sufficient for liver pathology to be significant, the enterohepatic cycle is disturbed, the wrong things are retained and excreted, gut flora is down, and the liver has difficulty with tasks like alcohol clearance.
It is possible to continue through symptoms; what should be evident is that here we have a way of understanding:
- why the onset circumstances vary so much
- why individuals have different symptom patterns
- why some escape and others don't
- and ways all may seek to escape.
of respiratory inefficiency
My little diagram is deceiving, in that it is idealised. It actually represents a process which is, in a really healthy person, no more than 80% efficient - much better than an open fire (10%) or a car (20% or so) but still not 100%. These processes in the mitochondria involve large volumes of electron transfer between atoms and molecules. The net result of inefficiency is free radicals - reactive oxygen species (ROS) or active oxygen forms (AOF).29
In a person with diminished mitochondrial performance there may well be a heightened level of such inefficiency. A first consequence of such free radical production is even greater inefficiency, greater free radical production.
Mitochondrial DNA is vulnerable to free radicals:
Nuclear DNA is far more stable than mitochondrial DNA (mtDNA). Nuclear DNA has better protection from free radicals, it is associated with structural protective proteins called histones, and it has active and robust repair mechanisms. mtDNA is directly exposed to the high free radical flux within the mitochondrion, it has no protective histones, and it has minimal repair mechanisms. As a result of these differences, mtDNA mutates more than ten times more rapidly than nuclear DNA.30
There is a very important issue here, expressed by researchers in Sweden thus:
Mitochondria are the power-houses of both plant and animal cells, and contain electron transport chains and genes ("mtDNA"). Electron transport - redox chemistry - is bad for genes, causing mutations that increase the proportion of electron transfers that do genetic damage; these mutations are their own cause and effect. This "vicious circle" is now widely discussed as an explanation of ageing. Whatever the reason for the persistence, in evolution, of genes in mitochondria and chloroplasts, it had better be a good one - these are the wrong places to keep a delicate genetic apparatus.31
Elevated levels of free radicals also hasten cell apoptosis.32
It's easy to see how a vicious cycle of chronic debility develops. How do we protect ourselves against this?
Unopposed, unrelieved catabolism
My doctor sketched out this little diagram for me last year.
I find it now fits very well with the ideas in this paper. To be healthy, a person has to be able to draw on resources to be active (catabolism), and then restore the body later (anabolic recovery). The wider curves are the considerable 'withdrawals' and 'deposits' that can be undertaken by a healthy person. The shallow lines show the limited give and take of the debilitated person. The little zig-zag of catabolic expenditure is my doctor's view of the person with Chronic Fatigue Syndrome trying to do a bit of this and that in the morning before falling over.
I am now of the view that a number of disease categories with symptom patterns overlapping with CFS and with diverse onset circumstances probably share a common foundation of a 'crisis of unopposed catabolism', brief and intense or prolonged and unrelieved, or one leading to the other, which entrenches a vicious cycle of inadequate mitochondrial function, dragging people down in a diversity of ways.
In simple language, the demineralising, catabolic state sees the mitochondrion working in a 'dust storm' with all sorts of things going wrong, free radicals proliferating, longer term damage accumulating.
The 'thoughts' and needs
of the mitochondrion
We speak of bacteria developing resistance to antibiotics, which these days we see as a process of natural selection. But that was not apparently, quite as it was always seen. In a report on 21 September, ABC Radio National's Health Report quoted Alexander Fleming, who discovered penicillin, as follows:
Alexander Fleming: And I have a fear that when penicillin can be bought over the counter, patients will indulge in self-medication and in many cases they will not take large enough doses. If the dose is too small, the microbes will not be killed and there is a danger that they will be educated to resist penicillin. Once a microbe has been thus educated to resist a drug, it does not lose this property very quickly. We might then have someone who has a simple sore throat, treating himself inadequately with penicillin and educating his microbes to resist the drug.33
Did Fleming mean that or was he a bit of a goose with words? I suspect the former, though it's not the way we tend to think these days.
How unnerving to think that our mitochondria are educated, that they know us each very intimately, in the sort of 'god is watching' way that small children are warned about. But how interesting and, really, how satisfying to think that a bit of thought might go into the provision of staples for my mind and body and decisions about euthanasing my cells.
I think it is appropriate to think about what the mitochondrion needs to live a good life in the cell. Nothing less than that is required for my whole health as an organism. If my mitochondria are happy and thriving I can be happy and thrive as I will have an abundance of the materials I need which the mitochondria produce. But we presume too much if we think only of the things we treat as important.
In my diagram above are the products ATP, carbon dioxide and pregnenolone. The ATP is the focus of much human energetic interest. The carbon dioxide and the pregnenolone are probably of greater value to the mitochondria.
Anyone who has ever managed a fuel stove or other fire knows the complexities of getting the balance of oxygen supply right, especially when the fire is in trouble. The mitochondria need oxygen but they need the protection first of carbon dioxide. Remember that they have been taking refuge for over a billion years from the oxygen in the atmosphere.
I started explaining this relevance of carbon dioxide in the cell to an Inspector in the New South Wales Rural Fire Service last week - I didn't have to say much. He knew very well the value of carbon dioxide as protection against against fire.
I was brought up thinking that fresh arterial blood was the top value thing, blue venous blood was just taking away waste. We still have a 'waste' view of carbon dioxide in many attitudes. In fact it is at venous blood concentrations that carbon dioxide is most value as a protectant.
Carbon dioxide (CO2) also diminishes production of free radicals in the form of active oxygen species.34
Tess Graham, a Buteyko breathing therapist last week gave me a paper setting out the symptoms of hyperventilation (which might also be thought of as symptoms of hypocapnia, under-supply of carbon dioxide) - which are essentially the symptoms of CFS, among other things.
I mentioned early in this paper the different perspectives of Russian science35 , and the last footnote shows some of that. Buteyko was a Russian and his major work was in the 1950s, not the best time in terms of percolation of ideas between Russia and the English-speaking world:
...Buteyko was able to lay down the theoretical foundation for this idea - hyperventilation causes a depletion of carbon dioxide; low levels of carbon dioxide in the organism cause blood vessels to spasm and also cause oxygen starvation of the tissues. This results in a whole range of "defence mechanisms" that have been previously misunderstood and labelled as diseases. It was not difficult to surmise that vessel spasming occurring in hypertension could occur also with other types of diseases, for example: stenocardia (angina pectoris) with the resultant myocardial infarction (heart attack): end arteritis (inflammation of the innermost coat of an artery, usually occurring in legs) or ulcerative stomach disease.36
Pregnenolone has two values to the mitochondrion at home: the use of steroidal molecules in building the structure of cells, and their use in communication. We know that hormones travel around the body with signalling roles, but our knowledge is very vague indeed.
So far as wider importance in the organism is concerned, Peat states the following, which I quote at length because this substance seems so little understood:
Pregnenolone, which is the raw material for producing many of the hormones of stress and adaptation, was known as early as 1934, but for several years it was considered to be an "inert" substance. A reason for this belief is that it was first tested on healthy young animals. Since these animals were already producing large amounts of pregnenolone (in the brain, adrenal glands, and gonads), additional pregnenolone had no effect.
In the 1940s, pregnenolone was tested in people who were sick or under stress, and it was found to have a wide range of beneficial actions, but the drug industry never had much interest in it. Its very generality made it seem unlike a drug, and its natural occurrence made it impossible to patent. Thus, many synthetic variants, each with a more specialized action and some serious side effects, came to be patented and promoted for use in treating specific conditions. The drug companies created an atmosphere in which many people felt that each disease should have a drug, and each drug, a disease. The side effects of some of those synthetic hormones were so awful that many people came to fear them. For example, synthetic varieties of "cortisone" can destroy immunity, and can cause osteoporosis, diabetes, and rapid aging, with loss of pigment in the skin and hair, and extreme thinning of the skin.
Natural pregnenolone is present in young people of both sexes at a very high concentration, and one reason for the large amount produced in youth is that it is one of our basic defenses against the harmful side effects that an imbalance of even our natural hormones can produce. In excess, natural cortisone or estrogen can be dangerous, but when there is an abundance of pregnenolone, their side effects are prevented or minimized.
In a healthy young person or animal, taking even a large dose of pregnenolone has no hormone-like or drug-like action at all. It is unique in this way. But if the animal or person is under stress, and producing more cortisone than usual, taking pregnenolone causes the cortisone to come down to the normal level. After the age of 40 or 45, it seems that everyone lives in a state of continuous "stress," just as a normal part of aging. This coincides with the body's decreased ability to produce an abundance of pregnenolone.
When aging rats are given a supplement of pregnenolone, it immediately improves their memory and general performance. Human studies, as early as the 1940s, have also demonstrated improved performance of ordinary tasks. It is now known that pregnenolone is one of the major hormones in the brain. It is produced by certain brain cells, as well as being absorbed into the brain from the blood. It protects brain cells from injury caused by fatigue, and an adequate amount has a calming effect on the emotions, which is part of the reason that it protects us from the stress response that leads to an excessive production of cortisone. People feel a mood of resilience and an ability to confront challenges.
Many people have noticed that pregnenolone has a "face-lifting" action. This effect seems to be produced by improved circulation to the skin, and by an actual contraction of some muscle-like cells in the skin. A similar effect can improve joint mobility in arthritis, tissue elasticity in the lungs, and even eyesight. Many studies have shown it to be protective of "fibrous tissues" in general, and in this connection it was proven to prevent the tumors that can be caused by estrogen.
Pregnenolone is largely converted into two other "youth-associated" protective hormones, progesterone and DHEA. At the age of 30, both men and women produce roughly 30 to 50 mg. of pregnenolone daily. When taken orally, even in the powdered form, it is absorbed fairly well. One dose of approximately 300 mg (the size of an aspirin tablet) keeps acting for about a week, as absorption continues along the intestine, and as it is "recycled" in the body. Part of this long lasting effect is because it improves the body's ability to produce its own pregnenolone. It tends to improve function of the thyroid and other glands, and this "normalizing" effect on the other glands helps to account for its wide range of beneficial effects. 37
Free Radicals and Antioxidants
I have mentioned free radicals and the primacy of carbon dioxide as a protectant. Free radicals are active forms of oxygen, arising in the electron transfer processes in the cell. Their existence is fundamental to all those processes, like flame is essential to a fire. It is when they are out of place, or in excess, that they are a problem. They include:
singlet oxygen (O),
hydrogen peroxide (H2O2),
hydroxyl (OH-) - for whose production iron is a catalyst, and nitric oxide (NO).
Fire is a process of oxidation. That is what free radicals do. What goes on in our cells is inherently dangerous, inherently at risk of going bung - there is a prompt circular effect on healthy mitochondrial processes, increased as damage to mtDNA occurs. The products of oxidation are themselves more often than not problems. Some effects may be direct: we know that unsaturated oils are good for painting; their oxidation results in the formation of membranes. These are unlikely to be useful in our cells. The indirect effects arise as the body's defence systems respond to the presence of such substances. Allergic and chemical sensitivities, gut reactions to grains, processed foods, etc., ought, in my view, to be seen as a flag of elevated free radicals/oxidant products: use of coconut oil, simple sugars (these in reason, see notes at end), CO2, pregnenolone and progesterone would seem more likely in the end to achieve the right results than doses of antihistamine, estrogen or cortisone.
There is a dual problem - how to keep free radical production to useful amounts; how to provide enough antioxidants to deal with those that arise.
There are three most important vitamins which act as antioxidants: A, C, and E. While A is critical in the steroidogenic process, E also is important in protecting the integrity of A. Enough A may be available from eggs and milk; the supply of C and E in food is probably far from sufficient in a person with problems. The avoidance of processed foods will help reduce supplement needs.
The warning flag for problems with free radicals is the scale of problems with post-exertional fatigue, food intolerances, allergies, chemical sensitivities.
The Exercise Problem - Fundamental to Turnaround and Recovery
If a person is debilitated and it is suspected that defective mitochondrial performance is a factor, that would mean an efficiency problem with respiration and a tendency to generate free radicals.
Such a person would have problems made worse by exercise. The problem will be how to get out of that situation.
It will be necessary to help the cell at the outset by supplementing those things that provide protection, allowing an exercise start up without excess oxidation. The objective will be to assist cellular processes along, while they restore key mitochondrial functions, until, for example, the liver has enough capacity to handle lactic problems, the gut is getting back to normal, the nervous system is more robust and acts more sensibly. My judgment and personal experience is that providing such a protective framework produces a desire for and tolerance of exercise.
The question arises: what is the purpose of exercise?
Does the single cell and its mitochondria want exercise so as to feel good or to build muscle or to achieve condition or cardiovascular tone or lose weight or get the right fat:muscle ratio, etc?
I don't think so. Those are are our intellectual overlays, and are associated with problems of complex organisms - quite real, but not in any sense essential to the fundamental issues of concern to the single cell and its mitochondria.
I think these parties to a very old contract want to achieve a satisfactory cellular circumstance, with a sensible, comfortable amount of CO2, ATP and steroidal hormones, simulating inside the cell the blissful, open air circumstances before the oxygenation of the earth's atmosphere one to two billion years ago, when simple organisms could make ATP while skinny-dipping.
Because of the oxygenation of the atmosphere, this now has to be done in confined circumstances, to exclude and meter oxygen, inside structures that have brought on a host of ancillary questions.
For the chronically debilitated person, a bath with Epsom Salts (MgSO4) and Baking Soda (NaHCO3), then going to bed with a combination of nutrients and antioxidants - a glass of milk, an orange, 1000mg of Vitamin E, a Berocca and a crumb of T3 can produce profound exercise effects - warmed, heart rate up, pulse strong, good sleep, later awake cheerful with increased exercise capacity/tolerance. Such 'simulated exercise' produces increased intramitochondrial respiration, with less risk of extra-mitochondrial 'anaerobic' respiration, with high ATP output, low work demand, leaving the ATP for anabolic restoration and altering the CO2 state significantly.
The anecdotal evidence is, though, that some folks get exercise intolerance even from that salts bath, so it is a routine to be respected - resting promptly is essential, as is the adequacy of the antioxidant-protectant routine.
People with CFS notably have disturbed sleep and dreaming patterns. This year some publicity has been given to an argument that 'REM sleep' is not something generated by the brain, tidying up or fantasising overnight, but is an action by the eye itself, anxious for oxygen supply, giving itself a bit of a jiggle.38
So REM sleep would have the purpose of circulating O2 and the movement of the eye would give rise to dreaming in this hypothesis.
Note also that "Lactic acid excess is typically found in eyes with cataracts".39
The eye does not use mitochondrial respiration. The brain, however, does, and the relationship between the brain and the eye is very intimate.
Discussion of exercise and going lactic focuses on muscles; it's a big thing in sports physiology. It has to be recognised, however, that the brain is stuffed with mitochondria, should also have huge stores of cholesterol and should produce vast amounts of pregnenolone. The definition of death is brain death; the brain needs vast amounts of blood supplying vast amounts of oxygen.
I haven't seen research on the lactic brain, but I think from past experience that I know what a lactic brain feels like. The kind of exercise issues addressed in that rethink of REM can also be undertaken in relation to the brain itself. Sleep disturbance, and other neurological problems surely would follow from brain mitochondria underperformance.
Leg twitching, also common in CFS, may similarly be an attempt to improve peripheral O2 and CO2 movement. Leg twitching seems diminished by the treatment proposed - in my experience - and sleep is improved so that you wake refreshed.
Appetite, Cravings, Eating Disorders,
ADD and Psychiatric Disorders
Once we begin to think about the problems faced by the brain in diminished mitochondrial performance, as touched on in the last section, some very broad issues arise.
People with CFS suffer disturbed appetite and cravings.
While my doctor regards me as unusual in my sensitivity to, or awareness of, reactions to substances and medications, I think that this is the result of years of sensitivity and awareness of minor changes, in a life stripped of a lot of the busyness that keeps most people from observing themselves. Conventional medical practice may think of this as obsessive behaviour, but all observant people are obsessive, and when life becomes pretty empty, some pretty small things, like disturbing food effects, assume a significance they would not have otherwise have.
But the cravings and food reactions do not arise, in my view, in a psychological defect, but because our bodies are in a real state of confusion about what to stuff down the hole to deal with the malaise of metabolic processes in the cell.
I suspect that there are lines of inquiry open from here to investigate eating disorders more generally in this context, noting their tendency to arise, especially in young women, at times of hormonal change. There is no particular reason why all brains should adapt to mitochondrial underperformance in one way; they are neither that bright, nor that consistent.
A person with Attention Deficit and Hyperactivity problems is almost certainly going to have an imbalance between anabolic and catabolic activity and may so acquire 'chronic fatigue' problems. Or the need/anxiety/compulsion to be active may be seen as a maladaptation by the brain to the underlying deficiencies in mitochondrial performance.
A real chicken and egg problem exists. The brain may not be all that bright, but it can be very determined, and maladaptations can persist.
A writer going by the pen name P.R.Celsus has written some exhaustingly long-winded papers under the title "The Cerebellum Synthesis" arguing that the most common first report symptoms in depression are also the most common first report symptoms in CFS; the separate diagnoses arise, in his/her view, because of the artificial distinctions of diagnoses. He says
In a modern medicine divided by specialty, guided by elaborate nosology, trained in "differential diagnosis", and made overly-cautious by the apprehension of "peer review", there has arisen a disabling dearth of unifying or synthesizing (synthetic or "global") hypotheses.
In the ever-burgeoning and, indeed, now exponentially-ballooning literature, there is more than a hint that the time has become ripe -- become more than ripe -- for a pause, and a present attempt at such a synthetic effort.
A bit wordy, and hard to read as a result, but his argument is that the common factor in depression, CFS and other disorders is a cerebellum disregulation.40
My own view is that the cerebellum and the limbic system generally may be disregulated, but that this arises for the more fundamental reason of mitochondrial problems.
As regards brain problems, I think it makes sense to point to
the importance of considering the interaction of connected brain areas rather than the activity within particular 'centres', as effectors of functions.41
That is also consistent with my view that underlying and pervasive problems may have disparate consequences.
Saturated and unsaturated oils
Among the things free radicals react very easily with, creating serious problems, are unsaturated oils. The term 'unsaturated' indicates a molecular structure vulnerable to oxidation. In nature unsaturated oils are normally in company with antioxidants, notably vitamin E, but processing of oils breaks down that association. Peat also argues42 that these grain seed oils have evolved to protect grain seeds from loss over hard winters and thus are inappropriately unstable at higher temperatures and contain toxins to reduce losses to pests. Leave aside such problems, however, and it remains that unsaturated oils may compound free radical problems and by their slowing of mitochondrial performance, actually impede conversion of cholesterol, increasing blood cholesterol problems.
Blind trials of single substances
v. synergistic packages
I loiter around BMW dealerships, waiting to see a doctor drop in to collect a brown paper bag, which may or may not contain a rear wheel from a new 5-Series BMW, so that he can carry out a blind trial. Nothing much happening so far!
There are a lot of strong opinions about whether individual substances are of value in treating CFS. My view is that it is unrealistic to treat this health circumstance other than with a whole package.
The 80% rule - self-recovery
Baume notes that:
...it may not matter a lot what treatment is given for the 80% of patients with self-limited disease - provided always that the treatment does no harm.43
There are undoubtedly people who recover 'spontaneously' from CFS, or whose flirtation with its symptoms self-corrects. My argument, overall, is that the whole approach to treatment should be one which facilitates self correction.
It is not an allopathic approach but one which is intended to provide synergy and to enable cellular processes to get back on their feet. This may take time. We are not discussing wonder drugs.
It will also mean that what you get back from the 'treatment' ain't necessarily grand. You get, in my self-observation:
-the same person as got sick, who may have habits that need correction or who may still have difficulty coping with circumstances that led to illness, if those circumstances persist
-that same person is older, and
-regrettably, some damage may have been done by the period of debility that has elapsed.
Hence, the quicker the start, the easier the self recovery, the better the prospective outcome.
We wish doctors to be more aware; so do the Tasks of Medicine team. We, too, have to be more aware.
Self-awareness, or mindfulness, is something emphasised by Buddhists as fundamental to meditation. In my words, we are talking about something quite different from concentration. Mindfulness arises not in concentration but from awareness of concentration. Mindfulness is the basis from which it is possible to observe thoughts passing through the mind, as a step towards achieving a circumstance in which we are not driven by passing thoughts, but have a calmness.44
Some such basis for calmness is essential to recovery.
"...meditation helps to prolong the body's anabolic process of growth and repair, and to reduce the catabolic or decaying process. Ordinarily the anabolic process predominates until the age of 18. From 18 to 35 there is balance between the two, and after 35 the catabolic process dominates. Meditation can significantly reduce the catabolic decline. This is because of the innate receptivity of the body cells."45
But there is, I think, a real catch. Many people with this kind of illness are simply not capable of meditation. They do not have the energy or nerve strength. My own capacities to address these issues and acquire some calmness has arisen in the first instance from use of pregnenolone and T3, and some progesterone. Only with that endocrine underpinning can we be calm.
An individual, subjective, report
I have been disablingly sick on and off since 1985.
From the outset, the symptom package included nausea, vertigo, inappropriate fatigue, memory problems, listening problems, difficulties with coherent argument, loss of confidence, palpitations, headaches, gut pains and back pains.
I deteriorated desperately on psychoactive medications 1985-87, but with a severe diet - no grains, sugar avoidance, nystatin - I was able to do a masters degree in 1988 and get back to work for a couple of years 1989-91. But to do that I accepted a lot of pain, an enormous sense of 'restraint' (just making it by holding myself together in a wet paper bag, may explain it metaphorically) and a tendency only to go to work or to bed. By the end of 1990 I was, as my doctor put it, 'in spasm', and attempts to resume work part-time in 1991 collapsed as even a few hours work caused total fatigue and days feeling like I had an enormous hangover, getting back to work on a minor research project with no idea of the merit of anything I had written to that point.
I don't propose to set out all the horrors of years that followed.
On ABC Radio National's Health Report 9 November, Len Syme, Chair, Research Committee, Canadian Institute for Work and Health, and Emeritus Professor of Epidemiology, University of California at Berkeley spoke46 of the impact of social and work circumstances on physical health. He advanced the idea of a demand latitude ratio, the extent to which a person has control over circumstances, latitude to deal with issues sensibly.
There is a severe demand latitude problem in this kind of illness, with its perverse punishment for almost anything you try to do.
The treatment I have embarked upon this year seems to have given me some demand latitude and provides a base for widening that. Obviously, achieving that at a physiological level, if it allows improvements also in life, means a lot.
I can run through symptom changes. Mostly upwards, in terms of how I feel. Starting with a brain and autonomic nervous system that seem to work reasonably well, a gut that is back to how it worked in the 1970s. Overall, it seems a bit like having the sun come out.
A year ago or so, I had the experience of meeting a friend and spending half an hour in social conversation, and then having a hangover for days. A year ago, my doctor's advice, in the context of that little anabolic-catabolic diagram, was to eat at 4pm and go to bed. I went out only once or twice at night during 1997. If I was at the dinner table at the beginning of dinner at home, I was seldom there at the end.
This year, I have been able to think and write and I have spent not just dinner but whole evenings with the family and been good company, I think. I have had few headaches, although I'm damn tired now and I have a bit of a headache at 5pm with 24 hours to finish this and three hours work lost this afternoon when the word processor crashed. I used to use maybe 8 Panadol in a day and get no benefit. Now, an occasional aspirin.
I have put on muscle; I have been doing a fair amount of physical work. My body wants exercise, an odd sensation. There is quite a lot of muscle pain, and tendon pain, and also odd sensations from old wounds, from the eighties and all the way back to a sensitised fingertip which has not troubled me for years; the tip was chopped off in 1957. My interpretation of all this is one of coming out of mothballs; I hope it means there is a lot of cellular resurrection taking place, with a certain amount of muck being stirred up.
I still have some thoracic outlet (spinal) nerve problems, affecting arms and hands, which tangle with the muscle and tendon pains mentioned. The thoracic outlet problems arose, I think, from inactivity and loss of muscle support to the spine. The extent of possible recovery remains to be seen.
My chemical sensitivities have reduced. Other members of the family are falling down with allergic reactions at the moment. I no longer have lots of difficulty putting fuel in the car.
Since early in 1998 I have used no sleep medication, no medication to deal with weather changes, etc.
I sleep at more normal hours, I awake more refreshed. I may be woken by the bladder not at all or once or twice, but not half a dozen times.
I have not experienced neurally mediated hypotension (falling down) and I have not had that terrifying sensitivity in which voices are loud, conversation impossible, walking down stairs impossible, travelling in a car deeply disturbing.
I learned a year ago that the latter problem occurred when I had a very low body temperature (35.4c or so). I have kept my temperature up this year, over 36.0 most of the time, except during the relapse that occurred after cortisone treatment in June.
My weight has risen about 3kgs; my blood sugar and blood cholesterol have risen very slightly, such as they should in a more active person, according to my doctor, and are within normal range.
I am still wary of using chocolate or alcohol. My appetite is, however, reasonable, and I rarely am desperate to eat. I do not have cravings unless I run myself right out of steam and that is harder to do. I not only eat with the folks, I also do lots more cooking now.
Without a shadow of doubt, feeling better makes me feel a lot better, provides enthusiasm and the confidence of having more control over my life. That does not, in my view, make the whole thing a placebo response and take away the underlying propositions about health.
What do I do?
This too is a personal account; its relevance to others is for others to establish. I have emphasised the individual nature of symptoms and ways into and out of this illness. I have noted the 80% rule.
I have advanced the hypothesis that this and other illnesses arise from inadequacy of circumstances at cellular level and in mitochondrial well-being and performance.
I do not have any suggestions of genes to rip out or replace, or allopathic substances to go bombing with.
My concern has been to clean the kitchen, check the fridge is stocked and the gas bill has been paid, and let the mitochondria do the cooking.
Always, always, flatter the cook. As the Director of the Diplomatic Service Bureau of the Chinese Foreign Ministry said to me in 1984, when I entertained him royally to seek a new cook: "Ambassadors are easy to find, but it's hard to find a good cook." Never trust a skinny mitochondrion, to paraphrase something else.
What I have done, I have done in consultation with my doctor.
Some people have expressed puzzlement that I tell my doctor things. How culturally ingrained we are with the notion that our relationship to our doctor is simply mendicant, begging. Welcome a doctor who appreciates new knowledge, respect his distrust of hokum. My doctor's advice has been invaluable in the development of these ideas, as also it has been invaluable as a trust-caring-support relationship.
The Synergistic Package
Do not read this section without at least reading the preceding section. You can't benefit from any of this without an awareness of the conceptual context and an awareness of yourself.
The task is to contribute to cellular life those things that will support energetic performance.
Tests are not necessarily useful. They are of necessity gross. Keep them in perspective.
In particular, be conscious that, say, a reading which indicates that you are losing density from bone does not mean that taking big doses of calcium will help. The loss of mineral reflects a catabolic circumstance. You have to shift the balance in your system back toward bone making; then your body will probably find all the calcium without great supplementation.
This is just a package as I have derived it from various sources, with substantial debt to Peat, and my impressions of how it works, for me.
A central criterion has been to distinguish between those things that produce effects of some kind, often by shock, or by suppressing symptoms, and those things that contribute to our systemic capacity to balance and stabilise. Sure someone may find that, say, there is a testosterone deficit in someone, but it's better to take other steps to allow for the appropriate production of testosterone, rather than take an inherently provocative hormone.
Running down the steroidogenic pathway, my judgment is as follows:
Cholesterol (versus unsaturated oils) - I have since January used butter, coconut oil (Copha) and olive oil and abandoned use of unsaturated oils. This is entirely contrary to all advice from the Heart Foundation, Rosemary Stanton, Don Burke and Meadow Lea. But I find that eating potatoes cooked in coconut oil, for example, simply makes me feel better. It has been no easier for me that anyone else to make this shift, although I have had a good blood cholesterol reading historically. There is obviously no point in adding more cholesterol if you are not using it. Any suggestion that using cholesterol (or sugar) is healthy has to be seen in the context of overall dietary quantity and activity. We modern urban folk tend to overeat (see also notes on appetite and craving above). The critical issue, in my view, is whether you have enough cholesterol in your brain and elsewhere to make pregnenolone. Without that, and without the shift away from unsaturated oils, I don't see the point of any of the following. See also footnote to pregnenolone, below.
Vitamin A - is available in eggs and milk (along with cholesterol and protein, etc). These are my main sources. Fish oils are unsaturated, but the fish oil capsules arguably have a high vitamin A to oil ratio and may be useful.
T4 - thyroxine - is an inappropriate supplement as it is a 'reserve' form of thyroid hormone. Supplements of it will reduce your thyroid performance. This advice is modified by observing that a little T4, briefly, in the context also of using T3, can have positive effects for some people.
T3 - triiodothyronine, industrially available as liothyronine sodium, brand name Tertroxin, has been a useful supplement for me, using an eighth of a 20 microgram tablet (about 3 micrograms) zero to three times daily. T3 helps stabilise demand for pregnenolone when it is also used as a supplement. Be conscious that T3 is a very active substance and that high natural levels of T3 have been found in interesting circumstances, e.g. the Swedish study showing that:
Increased levels of T3 were found to be associated with a more than three times increased risk for persistent criminality.47
You can't be a lively lad without a bit of T3, I guess.
T3 enhances vascular contractility, and works in a manner opposed to calcium channel blockers, so a medical context for its use is fundamental.
Pregnenolone is in my experience a remarkable supplement in terms of prompt effects of providing equanimity and exercise enthusiasm and capacity.
The new energy did bring with it some effects that needed dealing with. I still woke in an 'alert state' once or twice at night, though this was not the kind of waking in agitation or despair I been familiar with hitherto (as I would describe it) inadequate nerve resources. Ray Peat's advice on this as on other matters, was very valuable indeed. The following also deals with T4, T3 and cholesterol, and is a very useful indication of the importance of weaving a comprehensive approach with a personal understanding and self-awareness:
"There's almost no context [wrote Peat] 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, 200mg 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."48
Natural progesterone I have used a little of, although my doctor was uneasy about this. It shrank my prostate and had other adjacent benefits. It gave me wonderful sleep, waking refreshed, in an early period of correction, when I had been having the adrenal alert problems with pregnenolone.
While progesterone is predominantly a female hormone, men produce about 15mg a day, women 20 to 30, placentas may produce 200mg. It's easy to see how the association with gestation arose. Nevertheless, progesterone is a precursor of testosterone as testosterone is a precursor of estrogen. It is also a precursor of cortisol and aldosterone. There is an 'alternative' body of opinion that argues the safety of natural progesterone, and its capacity to provide the right balance among hormones. It also promotes bone growth (putting calcium back where it belongs) and healthy cells.
Because progesterone is an unpatentable substance, drug companies have developed 'progestins' which mimic some of the progestational roles of progesterone, but which have substantial negative side-effects, acknowledged in MIMS. The idea of such function-limited mimicry of a fundamental hormone is in my view anti-feminist and reflective of a failure to see women as whole people.
In the respiratory pathway, my impressions are:
Sugar is as contentious as cholesterol, and the fundamental need is there for people with modern suburban lifestyles - especially those who are unable to be active - to avoid overconsumption. There is no doubt that many people with CFS crave sugar; whether this is statistically very different from such craving in the whole community I don't know. I respect taste and appetite, but am suspicious of craving, and believe it is important to distinguish between these sensations. Craving sugar may (I speculate) reflect a problem in sugar metabolism, something crying out. But it is critical to relate consumption of sugar to capacity to use it - to actual energy consumption. The pancreas has major responsibility for sugar management and the fact that people with CFS teeter between hypoglycemia and hyperglycemia seems to me to reflect muddled pancreas performance; exhaustion and inefficiency. For that reason particularly, I am puzzled by the notion that hypoglycemia can be dealt with by taking more complex carbohydrates and avoiding simple sugars (I notice that some such advocates then speak highly of the orange, which contains simple sugars). Breaking down complex carbohydrates is another task imposed on the tired pancreas. It makes more sense to strengthen the mitochondrial processes to improve utilisation of sugars than to impose another burden.
Large amounts of fruits are ideal; there are not only sugars but vitamins and a host of enzymes deemed in some research to be critical to communication between cells.
High quantities of grain add to bacterial endotoxin problems in the bowel and apparently have a high glycemic index anyway.
Good, fresh coffee, with lots of milk and sugar has real value, with its combination of thyroid stimulus (caffeine), manganese (in the coffee, also for thyroid), protein, cholesterol (full milk), and sugars. A synergistic combination indeed, and interesting to watch people who use it in moderation, in the course of this cure, find that it is calming and drowsy making.
Oxygen is of fundamental importance, noting that carbon monoxide, a major gas in cigarette smoking, displaces the oxygen molecule in the blood. Dr Charles Lapp, with a large American CFS practice, remarked that a first step with patients is to teach them to breath properly. Various practitioners have made points to me about breathing, to a point of considerable confusion on my part. I think there is a breathing problem, but its a carbon dioxide problem.
Carbon dioxide: someone suggested that you could get enough carbon dioxide into your system by holding your breath or running upstairs. This hits the nail on the head. Those things only work if you have effective intramitochondrial respiration. I take the view, like Ray Charles, that "you've gotta have somethin' before you can get somethin'". Until you lift carbon dioxide levels, you cannot have efficient intramitochondrial respiration and you cannot make the right amount for yourself. So how to get out of that vicious circle: I am prepared to be promiscuous in finding ways to lift carbon dioxide levels, however marginal the benefits: in drinks, in baths, at altitude, etc.
While I have given attention in the foregoing to some key items, I have put together this more comprehensive list. It in fact was initially devised as a way of trying to get results without resort to any non-food substances at all.
In my own case, it has continued to be important to use T3 and pregnenolone.
These are my thoughts, of relevance to me. There are references to things like insulin and HRT, which I do not have to address personally. My concern is that people think about 'illness' more broadly, and not just accept that, "ah, well, now I have another disease".
NOT TO DO list - avoid these things
A unsaturated oils
B brassica (cabbage family) and legume (peas and beans) - at least while starting recovery. These are anti-thyroid.
C insulin - I make no suggestion that anyone ignore medical advice, but urge rather that taking insulin should not be regarded as an easy fix for sugar problems. A host of problems attend insulin use, among them being depressed respiration. Good supply of thyroid hormone T3 helps manage sugar. The key issue is whether you are able to manage you health upwards so as not to fall into a diabetes regime.
D estrogen; read the substantial literature AGAINST HRT and in favour of natural progesterone
E cortisone - if use is necessary to cope with trauma, be aware of the prospect that syndrome symptoms will be exacerbated. Consider using natural progesterone at the same time as and after the cortisone, to help adjust the system back to sense
F prolonged stress; drugs which interfere with neurotransmission
G histamines and chemically closely related narcotics
H avoid using pesticides, be careful with food products which may be contaminated
I calcium supplements. If your bones are losing calcium, you have to fix the mechanism, not just chuck dust at it.
TO DO list
1 Mitochondria die in darkness, so get yourself enough time in the light; use the summer to prepare for winter. Get all the light in summer you can.
2 Vitamin D is made from cholesterol by exposure to U-V radiation -- now, back out in the sun again!
3 Vitamin A is available from milk and eggs.
4 If your body is able to use cholesterol, use coconut oil and olive oil and butter. If you lift thyroid performance, you should consume cholesterol and levels should reduce. A high cholesterol level may indicate failure to convert to pregnenolone. A low cholesterol level will mean you just won't be able to make pregnenolone.
5 Take supplements of vitamin E. Say 2 gms a day. As you achieve more cellular respiration, it will still be inefficient, and the prospect is of needing more antioxidant protection during the recovery period than while inactive.
6 Walk and exercise to a point where there is no exacerbation of symptoms - happy exercise. See the anabolic-catabolic diagram. Take extra antioxidants after exercise (see 5)
7 To deal with aches, and routinely after exercise, bath with half cup Epsom Salts, 4 tablespoons Baking Soda; take extra antioxidants after this simulated exercise.
8 Use CO2 [as carbonated drinks, in bath].
9 Do not lose appetite and stop eating under stress but ensure you have access to good protein and sugar. Milk and oranges are easy to use if you wake at night - make sure you have something available that is healthy and not a great digestive burden.
10 Walk or drive to high vantage points to enjoy the altitude. Altitude (air pressure - the Bohr-Haldane Effect) enhances retention of carbon dioxide; see  above regarding carbon dioxide. Also can be good for the soul, and involve more sunlight.
11 Take care of your posture and activity - avoid sitting or lying in one position for a long time. Concentration and desk work are profoundly catabolic, demanding much energy without adequate exercise.
12 If legs twitch, they need exercise; if dreams substantial, the eye is trying to exercise. Use the bath at 7 above, use eyebath with tiny bit of salt and Baking Soda
13 Adopt whatever suits you best as mechanisms for your big front brain to try to calm itself and send calming messages to the lower brain. Some people do well on yoga, some with relaxation techniques, some with meditation. If you just can't, look at the Sections on Awareness and Exercise in the text.
14 Breathing. Make sure your posture is open, but allow your body to breath when it has the capacity to use more oxygen. Consider Buteyko training.
15 Raw carrot salads. You will need to give strong support to bowel and liver as you get rid of toxins, including excess estrogen. Carrot roots contain an ingredient that resists rotting, so it becomes the fibre of choice, reducing gassiness and bad chemical reactions.
16 Sugar: conventional wisdom says use complex carbohydrates to slow sugar impact, but we know that our pancreases are weak and it's a lesser burden in the end to use simple sugars. Cutting down on the bread, etc, will have benefits... What you will need, as your system cleans up, is a good sense of matching protein and simple sugar doses, when you know that you have the right cholesterol and a reasonable pulse and some exercisability
17 real coffee, with sugar, boosts thyroid; in moderation it can calm and produce drowsiness
18 Having cut down on the complex carbohydrates and altered the oils, ensure that protein intake is high. That is a different matter for vegetarians and meat eaters. If eating meat, try to stick with the range-fed animals if you can. Avoid meat from birds and animals that have been fed abnormal diets or antibiotics (intensive-raised chickens, most pork, lot-fed cattle).
19 Provide yourself with mineral and vitamin adequacy. I use a daily Berocca and 2 x 1000mg Vitamin E, more when exercising.
20 These points add up to these thoughts about diet:
[i] the purpose of a diet is not to lose weight, but to enhance physiology and thus health and fitness, from which a happier body and mind will follow;
[ii] be careful about saying "I just need to eat a good balanced diet", because their are traps of conventional wisdom to be avoided;
[iii] fresh food, and a minimum of processed foods and cans and bottles with preservatives will reduce the need for vitamin and mineral supplements.
1 On Human Nature, Cambridge, Mass, 1978
2 The Tasks of Medicine: An Ideology of Care, Peter Baume [ed] Sydney 1998.
3 A.R. Luria, "Reductionism in Psychology " in Richard L Gregory [ed] The Oxford Companion to the Mind, Oxford 1987, p. 675. This article deserves attention; Luria was Professor of Neuropsychology at Moscow University. Russian thinkers have not been obsessed with reductionism; their intellectual inheritance is from Aristotle, the Orthodox church, Pavlov (in full, not as bowdlerised in English-speaking behaviourism) and Marx - all synthesisers, in contrast to Socrates, Descartes, the Western Christian churches and the pharmaceutical industry.
4 Miles Little, "Cartesian Thinking in Health and Medicine and Health", in Baume 1998, p 89.
5 The Australian Reference Dictionary, Oxford University Press, 1991, p 794.
6 Little, p 89.
7 Little, p 91.
8 R.C. Lewontin, The Doctrine of DNA, Penguin Books 1993
9 Lewontin p. 51.
10 Baume 1998, p 34.
11 Pattichis K; Louca LL "Histamine, histamine H2-receptor antagonists, gastric acid secretion and ulcers: an overview" Drug Metabol Drug Interact, 12(1):1-36 1995
"...Furthermore, due to their ability to bind to cytochrome P-450, these compounds have the potential to interfere with the hepatic clearance of other drugs which are also metabolised by the mixed-function oxidase system in man."
12 "Cytochrome P-450scc (Side-Chain Cleavage) is a steroidogenic enzyme associated with the inner-mitochondrial membrane of steroid producing tissues. It catalyses three oxidative reactions resulting in the cleavage of the side chain of cholesterol to produce pregnenolone. This step is important in steroid biosynthesis, since it is the first and rate-limiting step, and occurs in all steroidogenic tissues" "EXPRESSION OF CATALYTICALLY ACTIVE HUMAN CYTOCHROME P-450scc IN ESCHERICHIA COLI" Stephen T. Woods , Tristan M. Downs and Robert C. Tuckey, Department of Biochemistry, The University of Western Australia at http://www.general.uwa.edu.au/u/swoods/p450.html
13 "Oxidative stress, calcium overload and NO-production have also been implicated in neuronal damage following ischemia" Doctor´s Thesis from Karolinska Institutet, Ankarcrona, Maria, "Mechanisms of apoptosis in secretory and neuronal cells: role of oxidative stress and calcium overload" 1996, http://diss.kib.ki.se/1996/91-628-1867-8/
14 "Warning on Medication Cocktails" Canberra Times, 8 November 1998, p. 1.
15 Albert Szent-Gyorgyi, Bioelectronics: A Study in Cellular Regulations, Defense, and Cancer, Academic Press New York, 1968, p 4.
16 Baume, p 31.
17 Jay A Goldstein MD, CFS: The Limbic Hypothesis, 1994; Betrayal by the Brain 1996.
18 For me, naphazoline (in eye drops) helped in seconds with bran clarity; glycine helped with sleep; nitroglycerine (one sixteenth of a 600mcg Anginine tablet daily) helped reduce irritable bowel problems but then gave rise to increased tendency to faint. Goldstein emphasises, however, that responses to his protocol are individual and vary over time.
19 Endocrine glands are 'ductless glands' which produce a wide range of substances to manage the body. For general research on the internet, go to http://endocrineweb.com/ but be aware that this site, written by doctors for the information of patients, is focussed on gross disorders and opportunities for messy intervention and surgery.
20 Julia Graham, Napier University (U.K.) Student, Bsc Biomedical Sciences honours project on Atopic Eczema, at http://www.biol.napier.ac.uk/bws/courses/projects/eczema/STERCHEM.HTM
See also, for a more complex account, including of the role of the Steroidogenic Acute Regulatory protein (StAR), see Miller WL, "Mitochondrial specificity of the early steps in steroidogenesis. J Steroid Biochem Mol Biol, 55(5-6):607-16 1995 Dec: "...the mitochondrial environment is absolutely required for the conversion of cholesterol to pregnenolone".
21 various papers available at http://www.efn.org/~raypeat
22 Raymond Peat Progesterone in Orthomolecular Medicine, 1993, PO Box 5764, Eugene Oregon 97405, USA, page 21, also in From PMS to Menopause 1997
23 John R. Lee, MD with Virginia Hopkins What Your Doctor May Not Tell You About Menopause Warner Books 1996
24 Steven W. Fowkes, Ward Dean M.D. and Thomas H.Nufert, "Mitochondria, Hypothyroidism and Weight Loss", at http://www.ceri.com/mito2.htm (Both text and diagram) I am for the most part reluctant to use material from www sites promoting products, but this statement is clear and coherent and seems sound.
25 See http://www.nih.gov/sigs/aig/Aboutapo.html
26 Mignotte B; Vayssiere JL, "Mitochondria and apoptosis" Eur J Biochem, 252(1):1-15 1998 Feb 15
27 Claudio Vallan, Zhiwei Feng and Rolf Jaggi, MORPHOLOGICAL CHANGES DURING PROGRAMMED CELL DEATH (PCD) IN THE INVOLUTING MOUSE MAMMARY GLAND, at http://mammary.nih.gov/reviews/apoptosis_(Jaggi).html
28 Sheehan JP; Swerdlow RH; Miller SW; Davis RE; Parks JK; Parker WD; Tuttle JB "Calcium homeostasis and reactive oxygen species production in cells transformed by mitochondria from individuals with sporadic Alzheimer's disease" J Neurosci, 17(12):4612-22 1997 Jun 15
Richter C; Gogvadze V; Laffranchi R; Schlapbach R; Schweizer M; Suter M; Walter P; Yaffee M "Oxidants in mitochondria: from physiology to diseases"
Biochim Biophys Acta, 1271(1):67-74 1995 May 24
Yamazaki T; Kowluru R; McNamara BC; Jefcoate CR "P450scc-dependent cholesterol metabolism in rat adrenal mitochondria is inhibited by low concentrations of matrix Ca2+" Arch Biochem Biophys, 318(1):131-9 1995 Apr 1: "Ca2+ entry into the matrix is, therefore a necessary step prior to inhibition of cholesterol metabolism by several mechanisms, including the consequences of changes in inner membrane permeability. "
29 A Brief History of Free Radical Biology University of Colorado Health Sciences Centre, at http://www.uchsc.edu/sm/waring/webpages/history.htm;
Research Field Monographs, Biochemistry of Oxidative Stress, Institut fur Physiologische Chemie, Heinrich Heine Universitat, Dusseldorf, at http://www.uni-duesseldorf.de/WWW/MedFak/PhysiolChem/oxygen.shtml
30 Fowkes et al
31 Paper from Department of Cell Biology, Lund University Sweden, at http://plantcell.lu.se/Research/redox.html with links to papers by John Allen
32 Barroso MP; G´omez-Diaz C; Lopez-Lluch G; Malag´on MM; Crane FL; Navas P "Ascorbate and alpha-tocopherol prevent apoptosis induced by serum removal independent of Bcl-2" Arch Biochem Biophys, 343(2):243-8 1997 Jul 15
33 "Howard Florey Part Two " Radio National with Norman Swan on Monday 21/09/1998 at http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s12820.htm.
34 Boljevi¨c S; Kogan AH; Gra¨cev SV; Jelisejeva SV; Daniljak IG "Carbon dioxide inhibits the generation of active forms of oxygen in human and animal cells and the significance of the phenomenon in biology and medicine" Vojnosanit Pregl, 53(4):261-74 1996 Jul-Aug (A Yugoslav journal; Kogan also working with another team in the same field and publishing in Russia.) "It was established that CO2 in concentrations similar to those in blood (5.1%, pCO2 37.5 mmHg) and at high concentrations (8.2%, pCO2 60 mmHg; 20%, pCO2 146 mmHg) showed pronounced inhibitory effect on the AOF generation in all the studied cells (usually reducing it 2 to 4 times). Those results were obtained not only after the direct contact of isolated cells with CO2, but also after the whole body exposure to CO2. Besides, it was established that venous blood gas mixture (CO2 - 45 mmHg, +O2 - 39 mmHg, + N2 - 646 mmHg) inhibited the AOF generation in cited cells more than the arterial blood gas mixture (CO2 - 40 mmHg, + O2 - 95 mmHg, + N2 - 595 mmHg). Carbon dioxide action mechanism was developed partially through the inhibition of the OAF generation in mitochondria and through deceleration of NADPH oxidative activity. Finally, it was established that CO2 led to the better coordination of oxidation and phosphorylation and increased the phosphorylation velocity in liver mitochondria. The results clearly confirmed the general property of CO2 to inhibit significantly the AOF generation in all the cell types. This favors the new explanation of the well-known evolutionary paradox: the Earth life and organisms preservation when the oxygen, that shows toxic effects on the cells through the AOF, occurs in the atmosphere. The results can also be used to explain in a new way the vasodilating effect of CO2 and the favorable hypercapnotherapy influence on the course of some bronchial asthma forms. The results are probably significant for the analysis of important bio-ecological problem, such as the increase of CO2 concentration in the atmosphere and its effect on the humans and animals.
35 See also Ray Peat, Mind and Tissue: Russian Research Perspectives on the Human Brain, 1973; see http://www.efn.org/~raypeat/sub.html
36 See potted history at http://www.buteyko.com/doctor_buteyko.html
see also the immediately preceding footnote. Russian science retains a larger interest in these matters.
37 Raymond Peat, "Three Youth-Associated Hormones" downloadable from http://www.efn.org/~raypeat/sub.html
38 David Maurice, "The Von Sallmann Lecture 1996: an ophthalmological explanation of REM sleep" Experimental Eye Research Feb 1998 Vol 66, p 139 "The hypothesis is advanced that the purpose of the eyeball movements during REM sleep is to stir the aqueous humor behind the closed lids and so avoid the risk that its stagnation could cause corneal anoxia. The relevance of the hypothesis to evolutionary biology and intensive care nursing is discussed."
39 Ray Peat's Newsletter "The transparency of life: Cataracts as a model of age-related disease" p 3 [supporting citations in text], August 1998.
41 O.T Phillipson, "Limbic System", in The Oxford Companion to the Mind, 1987.
42 Raymond Peat, "Toxicity of Unsaturated Oils", downloadable from http://www.efn.org/~raypeat/nutri.html
43 Baume, 1988, p 34.
44 While these are my words, I am indebted for the ideas to the English-Tibetan nun, Anila Tenzin Palmo, who visited Canberra in 1998.
45 Some useful papers on meditation and yoga are available from http://www.sivananda.org/ - see paper entitled Meditation (Dhyana);
also see http://www.dharma.org/
including for schedule of meditation courses at Blackheath
46 I write this from memory. Transcript should be available from http://www.abc.net.au/rn/talks/8.30/helthrpt/index/hrchronoidx.htm
by the time you read this.
47 Doctor´s Thesis from Karolinska Institutet, Alm, Per Olof Juvenile and adult criminality: Relationships to platelet MAO activity, triiodothyronine, ADHD, conduct disorder and psychopathy Friday, April 19, 1996
48 Personal e-mail received from Ray Peat, January 27, 1998
Dennis Argall Chronic Fatigue Syndrome... a fresh approach November 1998 page #