June 1998: Mitochondrial function

As noted elsewhere, these are papers exploring issues, written in 1998.

Nothing for sale, nothing recommended.

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The Significance of Mitochondrial Function

copyright Dennis Argall 1998

On an internet discussion list, a chiropractor, seeing titles but not text of my papers, made the observation

"I suppose one of the obvious questions would be how does one go aboutassessing the health/function of mitochondria ?"

I replied:

Actually this is a very very interesting question,  but I think that the way you have expressed the thought - pinpointing what should be an 'obvious' question, when it is actually one of the scarcely-likely-to-be-asked questions - probably also reflects the fact that you are already committed, in chiropractic, to searching for holistic and systemic patterns rather than local organ functions. You bring to the fore another question "Why is it not an obvious question in general medical practice?"

There is a preference for speaking about thyroid gland function, and particular organs, rather than holistic circumstances. Many of the symptoms generally associated with suspicion of hypothyroidism are in fact indicators of mitochondrial performance, because of the dependence of mitochondria on thyroid hormone (see diagram). At the same time, however, the standard pathological tests for thyroid performance are not going to be reliable measures of mitochondrial performance, because they do not measure other inputs or outputs from the mitochondria. For example, in the absence of sufficient supply of  'steroidogenic acute regulatory (StAR) protein' (which seems to be affected by stress, particularly via corticosteroids) cholesterol will not get into the mitochondria, and the conversion to pregnenolone will not take place. I have not seen research evidence on the point, but it would seem logical, for example, that in fact a high or normal reading in a serum thyroxin test may be less useful (sure, if you can't make thyroxin, you may have a dud or cancerous thyroid, and that will need attention, but what reading will there be if the thyroid is healthy but thyroid hormones can't be used?) than a high serum cholesterol reading, or yellow patches (of vitamin A) on the skin.

CHART TO INDICATE THE TWO MAIN FUNCTIONS OF MITOCHONDRIA 

IN MAINTAINING LIFE IN THE ORGANISM - 

STEROIDOGENESIS [VERTICAL] AND OXIDATIVE METABOLISM [HORIZONTAL]

(These are the healthy pathways for consumption of these inputs in the body. Failure of these pathways will cause problems with managing any of the inputs, and will mean lack of outputs.)

           cholesterol

                                            \ /

                            plus thyroid hormone [mainly T3]

                                     and vitamin A

                                            \/

                                _______________

sugar + oxygen  -->   MITOCHONDRION  -->ATP + carbon dioxide

                                _______________

                                           \/

                                  pregnenolone

                                      /            \

                                    + vitamin E

                                     /              \

                             progesterone    DHEA

On the input side, you also have sugar and oxygen. Our old Readers Digest Family Health Guide [we have the 1977 edition] says that a "less convenient and less reliable [thyroid]  test involves measuring the rate at which the body uses oxygen (see Basal Metabolic Rate [BMR])". When you look up BMR, you get an explanation of "The rate at which a person uses energy to remain alive..." and of measurement of heat produced by the body or "how much oxygen a person at rest uses in a short time" - [obviously not as easy to do in clinical circumstances as taking a bit of blood - my comment]. The BMR entry concludes

"The results of a BMR test can be influenced, however, by factors such as pregnancy, diabetes, various drugs, the presence of food in the stomach and particularly by emotion (anxiety) during the test."

A lot of money is being made in the vitamin and herbal medications industries selling anti-oxidant substances when the core of the problem is unused oxygen. If mitochondria are healthy enough and in sufficient number, the 'need' for such ill-focussed intervention - such supplements - evaporates or is greatly reduced (the fact that people are subjected these days to strange diets and destructive lifestyle and environmental challenges needs to be taken into account too, though).

I suggest that problems related to sugar metabolism should be looked at the same way (again acknowledging that some people may have highly destructive disease problems in the pancreas, etc),  but we tend to deal with hypoglycemia and hypoinsulinism and candidiasis, 'leaky gut', etc., in little boxes, rather than arising from failure to consume sugar through the healthy mitochondrial pathway.

I suggest that abnormal cholesterol readings should be looked at in the same light if you have low cholesterol, steroidogenesis will be impossible or reduced; if you have high cholesterol then surely it deserves consideration to take steps to see that cholesterol gets used before you cut off the supply. Again, I am not suggesting an avoidance of conventional analysis related to high cardio-vascular risk or event, but suggesting that correction or avoidance need to be seen in this broader physiological context.

On the output side we have adenosine triphosphate (ATP), carbon dioxide, pregnenolone.

If you don't have enough of these

[1] inadequate ATP lack of energy, lactic states and muscle pain; neurological dysfunction; failure/disruption of liver and digestive processes; and failure of conversion of protein foods to amino acids, recombination of amino acids to proteins.

[2] inadequate CO2 decline in cellular health, and of intercellular space; dislocation of calcium - arteriosclerosis, bone spurs, muscle calcifications.

[3] inadequate pregnenolone means no satisfactory hormonal system and thus for men and women but especially for women, there will be an array of problems related to the reproductive system. Most importantly, inadequate supply of progesterone and a tendency to estrogen dominance. Estrogen dominance washes out calcium from bones and disrupts the whole process by depressing thyroid function. Hormonal weakness will also derange the adrenals, contributing to psychological and social problems and more pain and loss of sleep and more thyroid disruption. Inadequate pregnenolone also directly impacts on brain function. The greater vulnerability of women to disruption down these pathways has to be linked to the greater vulnerability to this kind of illness.

Combine such deficiencies and a variety of behavioural and eating disorders and obsessions may also come into focus for consideration of their correction at this level.

I think one reason why mitochondria get less attention than they deserve is because some general subconscious embarrassment, hurt pride, that we only live because semi-autonomous organisms in all cells with nuclei in all living things provide our basic needs, moment to moment. How embarrassing that we do not have charge of such a fundamental thing, in a species obsessed with control. Animals have mitochondria, plants have both mitochondria and chloroplasts - the latter allow them to use solar energy more directly than we can. But mitochondria also depend on light, and they can be assumed to be lower in number and function in the darkness of night and especially winter.

There is fairly wide acceptance in evolutionary biology (if the reader doesn't accept evolution, see note below) of Lynn Margulis's concept of 'symbiogenesis', that is, that great advances have been made in evolution when organisms come together to cooperate. She argues that the great divide in living things is not between plants and animals but between cells with no nucleus (including bacteria) and those cells with a nucleus. And she argues (Devin mentioned this several months ago, sending me off to study the subject) that the rise of cells with nuclei, and the consequent vast complexity of cellular life, came about when one bacterium attacked by another managed to survive and enclose it and to achieve a symbiosis, between a cellular host and its mitochondria. This occurred around the time when the bacteria, who owned the planet, caused such enormous damage to the environment (in their terms) by filling it with a fiery waste product, oxygen. [Lynn Margulis and Dorion Sagan, Microcosmos, 1986.] So - to live within the cell is a survival need for the mitochondrion, a safe haven in which to convert oxygen into carbon dioxide and cholesterol into hormones, for its protection and that of its cellular host --- just as living within the atmosphere, at acceptable temperature, never far from water and within a gravitational field, while being kept alive by mitochondria, is the basis of our survival as a larger organism. Note too that as a whole complex organism, a healthy human carries a very large weight of other folk trying to keep away from the atmosphere bacteria and fungi as cellular organisms, viruses within our cells and our genetic structure. 

When we start to look at ourselves as such large, complex, symbiotic systems, rather than the perfect machine we see each morning in the mirror, we can begin to think more carefully about approaches to medicine which amount simply to hand grenades aimed at some of these folks who've been riding around for a long long time in us, most of them doing good. Survival is based on cooperation, not competition. That's why we developed big brains, but sometimes it's easy to forget that.

If you start at this point of emergence of cells with nuclei, you see the ongoing billion years or so of organic life as a constant struggle to survive in an oxygen environment, achieved over long periods of time, without a vitamin manufacturing industry, but by the work of the mitochondria. If you come forward in geological time to 600 million years ago, you see organisms making great strides in turning free calcium, another bothersome hindrance to life inside cells, into body structures. This, it would seem, is the other great ongoing struggle, to get calcium out of the way of the mitochondria and into sensible structures. 

I think the increase in this kind of illness now, with its pervasive and diverse effects, is very suggestive indeed of problems with mitochondrial function/health;  in that long historical perspective, and in the context of rapid change in our living environment now.

If your belief systems preclude the evolutionary perspective, a holistic snapshot of what is happening right now inside us still has to focus on the same basic physiology. It is, indeed a good area for study if one has spiritual objections to surgical invasion, etc. 

Chiropractic is wise and effective in saying such things as "there's no point taking something for a headache if your spine is not holding your head up properly"; "there's no point correcting your spine if you are not standing upright", etc. This seems to me exactly parallel to what I am trying to say about life at a cellular level - what point is there in taking pain medications for the long term (I'm not dismissing need in trauma) if they just compound a problem of metabolism if it is the basis of the pain problem. I concede that in the wake of accident or other trauma there may be organ or tissue damage causing pain; I concede that left uncorrected (and you can hear the parallel arguments in chiropractic) a failure of cellular/mitochondrial health will lead to organ and structural damage. But I see it as fundamental to physiological restoration - to whatever modest or grand level, for ongoing life with some stability and happiness - to consider mitochondrial health and enhance mitochondrial performance. 

That's the basis of the suggestions - 11 things to avoid, 19 things to do - in my June paper (Thyroid and Mitochondrial Function). These are basically a practical  framework for thought and action, related to mitochondrial health, which ought, in my view, to become as natural as thinking of washing our hands (we do that because it's sensible, not because of constant monitoring with tests).

I restate here that my early training was in anthropology, that my career has been (or was, until wiped out twice by illness) first mainly in the foreign service and then as head of the research side of our equivalent of the US Congressional Research Service (yes, we were smaller - 40 professional staff - but much admired by the CRS!), and that I thus come from a background not of specialist focus but long experience taking disparate technical issues and advice and trying to bring them into broader focus for analysis and action. I am influenced and informed by the deterioration of my health over a decade and a half, including through drug treatments. I write to the list as a fellow pilgrim who is just too delighted by health progress this year to keep it quiet. If I fail to state my background all the time, it is to try to let my arguments speak for themselves, to try not to sound pretentious, and to be accepted as a friend. 

In a situation where we suffer from a disease which in conventional medical opinion has no known etiology and no known cure, and which is said not to be 'progressive' but which causes a different wheel to fall off a different sufferer most weeks of the year, we owe it to ourselves to recognise that conventional therapies are largely palliative in nature and to go search for a more holistic solution. It has given me no great comfort to conclude that medical research and medical peer opinion on these matters is for the most part mucking around in the wrong paddock. I decline to be tethered in that other paddock. Individual readers will, whatever course they choose, only secure their health if they take charge of it. Weakness, vulnerability, mental confusion and constant defeat by rogue symptoms make this hard to do when sick like this. 

Even at one's best, it can be hard to get new ideas sorted in one's head, let alone discuss them with a doctor. Language is the basis of understanding, and also of power. The film "Lorenzo's Oil" provided an account of the difficulty securing consideration of new ideas even within a support group, those most hurt by illness. I am encouraged to have this week received Ray Peat's June Newsletter (interesting discussion of "Eclampsia... as a paradigm of general distress...", in which he notes, at the outset, that

"Metaphoric thinking - using comparisons, models or examples - is our natural way of gaining new understanding. Ordinary language and culture grow when insightful comparisons are generally adopted, extending the meaning of old categories. Although the free growth of insight and understanding might be the basic law of language and culture, we have no institutions that are amenable to that principle of free development of understanding. Institutions devoted to power and control are naturally hostile to the free development of ideas"

copyright Dennis Argall 1998.