“The physician should not treat the disease but the patient who is suffering from it.”
– Maimonides, 800 years ago
Simply put, trophology is the study or discipline of nutrition. The expression is lifted from the Greek trophe, meaning nourishment, and logos, word or study. In these fast-moving times, with a veritable flood of newly learned detail about human physiology pouring in on us, there is no shortage of facts. The difficulty lies in making these facts meaningful, in applying them. Thus one who wishes to be a student of applied trophology may take in abundant facts from reliable sources available to him, but more importantly one must learn to put them in perspective. This journal attempts to help the thoughtful health-care professional do just that, always within the basic framework of good balance and common sense, with an eye to the whole person.
THE SPACES FILL IN
The information deluge may be just beginning. The biologic revolution is still young. In his delightful series of essays entitled “The Lives of a Cell,” the accomplished physician and researcher, Lewis Thomas notes: “It is a curious, peaceful sort of revolution, in which there is no general apprehension that old views are being outraged and overturned. Instead, whole, great new blocks of information are being brought in almost daily and put precisely down in what were empty spaces. The news about DNA and the genetic code did not displace an earlier dogma; there was nothing much there to be moved aside. Molecular biology didn’t drive out older, fixed views about the intimate details of cell function. We seem to be starting at the beginning from scratch.”
Reflect on that pioneer of molecular biology, Dr. Royal Lee. Today one can only note the empty spaces are being filled in. We have sound physiological and biochemical rationale to support even those empirical approaches which he found to have clinical validity. Take, as an example, the prostaglandins, first found in the prostate, seminal fluid and vesicular glands. They are now known to be of very wide distribution in marrunalian tissues, in the kidney, thyroid, spleen, endometrium of the uterus, and so on. Dr. Lee anticipated their discovery and arachidonic acid as their precursor by some thirty years! These and other exciting new developments deserve to be given attention in the future. But in this issue we would like to set forth some simple premises on which someone may build who wishes to master the art of applied trophology.
A basic truth is that man is integrally linked to his food supply and intake. His organ systems biochemically respond to changes in intake, but always within the. parameters laid out genetically for the function of the organism. Thoughtful physicians or dentists may wish to avoid introducing foreign or alien substances into their patients unless they cannot avoid it. Drugs simply do not have single effects and may produce a multitude of undesirable effects, known and unknown. One must always remember the whole patient. If this is true with drugs, it must also be true even when one uses so-called natural substances. Let us start our examination of basic concepts by a simple review of vitamin function.
MEGAVITAMINS CONTRADICTION IN TERMS
What is a vitamin? It is an organic substance required in minute amounts to sustain the normal metabolic processes of life, which the body cannot make for itself at least in sufficient quantity. Vitamin function is essentially coenzyme function. That is to say, when a vitamin enters the body as a component of food, it travels to the cells that need it and is converted into a coenzyme form if it is not already in that form. It attaches to a protein made within the cell called apoenzyme. The complete combination of apoenzyme and coenzyme serves the vitamin function of catalyzing metabolic reactions. When the cell is making apoenzyme at maximum capacity, any extra coenzyme cannot possibly serve its vitamin function because it cannot bind to apoenzyme.
A basic fact emerges. By definition, megavitamin therapy is a contradiction in terms. That is not to say it does not have an effect on the organism. It does. But that effect must be a chemical one. Megadosages can serve only as chemicals and not as vitamins. It may achieve certain results, but let us not make the mistake of assuming that result is a natural one or that it will not produce side effects that are undesirable.
EXCESSIVE FAT-SOLUBLE VITAMINS
Once one grasps the concept of megadoses as having chemical rather than vitamin effects, it is not surprising to learn of side effects from excess ingestion of even substances previously thought to have no toxicity. Let us first look at one of the fat-soluble vitamins in that category, vitamin E. With large doses there are reports of inflammation of the mouth, chapping of the lips, muscle weakness and/or cramps, gastrointestinal disturbances, hypoglycemia, increased bleeding tendencies and degenerative changes. In large dosages vitamin E antagonizes the action of vitamin A, perhaps explaining reports of blurred vision in recipients of megadose therapy. Headache, nausea and fatigue are also reportedly side effects of megadose therapy with vitamin E.
This should not be surprising. The vitamin E-deficient animal presents a baffling array of apparently unrelated histopathologic sequelae. Obviously vitamin E is not a substance with single effects. Evidence mounts that it is not simply a biological antioxidant but a component of multiple enzyme systems. Too, interaction between various vitamins has been demonstrated, as with vitamin A compounds and other members of the lipid class. Vitamin A metabolism is linked with that of coenzyme Q, vitamin E, vitamin D, the sterols, and the biosynthesis of squalene (intermediate in cholesterol production). This again emphasizes the fact that a single vitamin has more than one specific function. This is part of the difficulty in researching the exact functions of various substances. Truly Royal Lee was correct in describing vitamin activity as “wheels within wheels.”
Effects of excess vitamin A ingestion are well known, but a review may be helpful. One of the main functions of vitamin A is to maintain membrane integrity by providing cross-linking between the lipids and proteins. Excessive amounts of vitamin A combine with membrane lipoprotein and cause instability. Arctic explorers eating large quantities of polar bear liver experienced such toxicity. The syndrome is characterized by drowsiness, headache, dizziness and diarrhea, caused mainly by cerebrospinal fluid pressure. Increased blood levels of vitamin A are found in persons with lipid nephrosis and glomerulonephritis. These patients are intolerant even to ordinary amounts of this vitamin. Chronic ingestion of inordinate amounts of vitamin A result in a cirrhotic liver syndrome that includes portal hypertension. Other results may be hypercalcemia, swelling over the long bones and premature epiphyseal closure. Early signs may include coarse sparse hair, alopecia of the eyebrows, dry rough skin, and cracked lips. Fatigue and lethargy are common, and there are reports of irregular menses and emotional flare-ups. Joint pains or bone pains may be noted especially in children.
The effects of vitamin D toxicity are also well known. Current thinking suggests this substance could be classified as a hormone rather than a vitamin. The kidney functions as an endocrine organ in converting prohormone vitamin D to at least one active hormone. There is homeostatic control of metabolism of the active metabolite in the liver, depending on the blood level of vitamin D-3 (cholecalciferol), which is formed in human skin by exposure to the ultraviolet radiation of sunlight. Its metabolism in the kidney depends on blood calcium levels. Early signs of toxicity are weakness, fatigue, lassitude, headache, nausea, vomiting or diarrhea. Finally soft tissues show evidence of calcinosis, while bones become osteoporotic. The kidney is especially affected, with polyuria, polydipsia and pruritus present. In such cases, clinicians suggest not just the discontinuance of the vitamin, but putting the patient on a low-calcium diet and keeping the urine acid.
Vitamin K toxicity generally results from the use of water-soluble synthetic analogues. Such derivatives act as oxidants in the body, causing red blood cell instability and hemolysis.
IS IT NATURAL?
One may ask the question as to whether similar amounts of “natural” vitamins would produce the same effects, since ingestion of such large amounts would have to involve synthetic sources. It is an interesting question that leads to another basic concept that should be appreciated.
The reader is doubtless familiar with the pitfalls of assuming something is “natural” just because the label says so, or because the names of natural substances appear on it. For the benefit of the reader not familiar with the practice, we note the following. A person purchases for himself or a patient “natural rose hips vitamin C” tablets. What could be more natural? The fact is rose hips may contain 0.1% vitamin C, up to 2% by some claims. To get milligrams per tablet up to label specifications, the manufacturer adds plain old synthetic ascorbic acid, the same used in standard pharmaceutical tablets. Otherwise one would have to produce a golf-ball size, tennis-ball size, or larger tablet depending upon the label milligrams per tablet.
A similar situation exists with regard to vitamin E / products. The label or product advertising may loudly proclaim the source for its vitamin E is vegetable oils and is therefore not synthetic. That may be perfectly true. Yet the capsule must be made small enough to swallow. And therein lies the rub. To concentrate the amount necessary for the milligrams or international units per capsule on the label, the manufacturer must use various chemical solvents for extraction and separation. On top of this, the capsule itself may contain a preservative so it will not turn rancid. An additional point: the vegetable material used in such “natural” products may be and usually is grown with the usual chemical fertilizers and pesticides.
A complete discussion of the theoretical implications of synthetic or process-adulterated supplements is beyond the scope or space of this journal. Yet the very possibilities must pose some intriguing questions for the thoughtful reader.
EXCESSIVE WATER-SOLUBLE VITAMINS
It is a Mistake to assume that water-soluble vitamins can produce no side effects because they are not stored in the body. Adverse effects may be common, although not always recognized as such. Let us take a few examples to make the point.
Niacin (nicotinic acid) is currently being employed in megadosages.for schizophrenia and other ailments. Aside from the obvious effect of flushing or vasodilatation, there are also reports of its causing tachycardia, fainting, hyperglycemia, skin rashes, itching, nausea, ulcer activation and disturbed liver function, just to list a few such conditions. The medical profession has also used niacin to lower serum cholesterol and to prevent myocardial infarction. A well controlled study was set up on a national level, the Coronary Drug Project. The results were published in a major journal of that profession (JAMA 231:360-381, 1975). The conclusion? Taking megadoses of niacin to lower serum lipid levels had no effect on preventing heart attack. Interestingly, there was a greater incidence of cardiac arrhythmias in the niacin-treated group as compared with the placebo group.
Let us not lose sight of a fascinating point: as do certain drugs, megadoses of niacin may indeed lower serum lipids. The question is, is this good, is it desirable? If at the same time serum lipids are merely driven into the tissues, such action is certainly not desirable. A figure on a blood test may appear to be within so-called normal limits, but what is the net effect to the person? Again, the human organism must be looked at as a complex whole. One must beware the pitfall of looking for even the “natural” agent that will reduce serum A or raise the level of serum B, without considering the possible far-reaching effects on, say, serum C or D not to mention enzyme systems X, Y, Z.
Pyridoxine, vitamin B-6, was once thought incapable of producing side effects. Evidence now indicates it is capable of producing liver disturbances, adding to earlier reports of convulsive disorders in children from pyridoxine excess. Even this surface scratching will doubtless cause the reader to pause before thinking that the B vitamins are incapable of producing adverse effects.
Again, it should be noted that vitamin B products are often formulated in a similar fashion to what we have considered relative to vitamins C and E. That is to say their “natural composition must be open to question. Synthetic products are often added to natural’ bases in order to bring milligrams per tablet to higher levels:, One may also question the source and treatment of the natural base.
Rather than involve ourselves in current controversies over vitamin C, let us again set forth a few simple points. Consider the phenomenon of rebound scurvy, which occurs when large dosages of Vitamin C are abruptly discontinued. If one is ingesting, say, fifty times the amount biologically utilizable, the mechanism for destruction may be operating at fifty times normal. When one stops the megadose, destruction of ascorbic acid continues. Thus rebound scurvy occurs. This may not be dangerous in an adult, but may be serious in the case of a pregnant mother taking it in megadoses. Her infant is born with a catabolic mechanism operating to deal with the excess vitamin C from maternal circulation. When the baby goes on its own diet, the result is rebound scurvy. The principle is possibly applicable to over-ingestion of other vitamins as well.
Megadoses of vitamin C have precipitated gout in patients with high serum uric acid levels. Such doses have untoward effects on bone metabolism in experimental animals and can lead to increased urinary excretion of oxalate in humans, with the danger of renal stone formation. Megadosage has activated hemolytic anemia in predisposed subjects, such as ethnic groups with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
This is not to suggest that larger-than-physiologic doses may not have an effect on such entities as the common cold, the infectious processes, and so on. It merely serves to illustrate the basic concept presented in this issue: megadosages serve chemical rather than pure vitamin functions and this must be recognized for what it is. Some such chemical functions may be desirable; others may be detrimental or obscure the underlying problems of the patient. It is also reasonable to conclude there may be far-reaching unwanted metabolic effects that are as yet unknown.
POTENCY A VALID CONCEPT?
In view of this line of reasoning, it seems sheer folly to look for the label with the highest milligrams or the most ingredients per tablet. As a matter of fact, one has to challenge the usage of the term “potency” in this connection. One cannot accurately refer to an item with lower milligrams per tablet of a substance as being lower in potency than something with a higher figure on the label. It is clear that more is involved. According to Webster, potency refers to the ability or capacity to bring about a particular result. Thus, if a substance or combination of substances has the ability or capacity to bring about a desired result, that substance or combination is potent.
It is noted with some sadness that young physicians fresh out of even non-medical schools will ask supplement manufacturers or suppliers for the highest potency product, with and note the expression “pharmacological” dosages. In the case of the chiropractic or naturopathic physician, this denies their professions’ rich heritage of attempting to care for the human organism without pharmacology. One can only hope such expressions are mere slips of the tongue, and that the seeker of his patient’s health is really looking for a physiological effect. Maimonides’ wise advice echoes through the centuries: “The physician should not treat the disease but the patient who is suffering from
ILLUSTRATIVE THOUGHTS ON ZINC AND COPPER
In the last few years there have been numerous articles published even in conservative medical journals relative to the use of zinc in wound healing, hypogeusia (diminished capacity of taste) sexual maturity, skin lesions, and so on.
An editorial in 7he Lancet (January 28, 1978) called attention to yet another aspect of zinc metabolism, under the heading “A Radical Approach to Zinc.” It stated: “In enzymology zinc already has a venerable past. Carbonic anhydrase, a zinc-protein, was the first metalloenzyme to be identified; and the score of zinc enzymes is now over eighty. Their functions are so varied that they defy categorizing: no metabolic pathway of any importance, from alcohol detoxication (sic) to nucleoprotein synthesis, could exist ‘without them. It is now suggested that, in addition to these varied enzymic roles, zinc also intervenes in non-enzymic, free-radical reactions in particular, that it protects against iron-catalysed free-radical damage. . . . Iron-catalysed free-radical oxidation is known to be inhibited by other trace-metal complexes (notably by ceruloplasmin), by metalloenzymes (catalase, peroxidases, superoxide dismutases), and by free-radical scavenging antioxidants (vitamin E).” (Incidentally, superoxide dismutSse is a zinc-manganese metalloenzyme, just one of many such.) A magic bullet?
The journal observes the first human disease specifically attributed to zinc deficiency was acrodermatitis enteropathica, an inborn metabolic disorder. It notes the possible relevancy of the disorder’s affecting a tissue most continuously exposed to ultraviolet radiation, the skin. Noting that very little can be taken for granted with either trace elements or free radicals, the editorial continues: “In the same speculative vein one may note that of all human organs it is the eye which has the highest zinc content; and that seminal fluid, the body fluid with the highest zinc concentration, is the only one in which cells must survive outside the body if they are to fulfill their physiological function. Zinc may prove to be rather less prominent in protecting against iron-catalysed free-radical damage than has been suggested, but if the suggestion catalyses a ‘radical’ approach. . .it will have served a useful purpose”
Earlier this year the conservative Journal of the American Medical Association published a report entitled “Evidence of Copper and Zinc Deficiencies.”
Using atomic absorption spectrometry, researchers measured copper and zinc intake in hospital patients and made comparisons of twenty diets made from conventional foods. They concluded that hospital and American diets in general seem to be low in copper and zinc “in comparison with current estimates of the respective requirements .” (JAMA 241: 1916-1918 , 1979) Some theoretical implications concluded the report. “Natural and controlled experiments with animals can serve as guides in a search for human disorders. Among the more important abnormalities in animals: produced copper deficiency are (1-) anemias,. (2)- defects in connective tissue leading to abnormalities of arteries and bone, (4) degeneration of brain and spinal cord secondary to abnormal myelinization, and (4) myocardial degeneration. Zinc deficiency has pioduced ‘(1) growth impairment and delayed maturity, (2) skin lesions, andp) reproductive failure and fetal abnormalities. If diets in the United States frequently contain too little copper or zinc, some of the consequences must be common.” Ironically, many current texts flatly state copper deficiency is unknown or impossible.
Our point, however: without careful thought, the unwary physician could start assuming a magic bullet has been found. He might routinely suggest a copper supplement or a zinc supplement for all his patients. He could fall into the trap of looking for a product with the highest potency. Yet uncomplicated deficiencies of single nutrients are usually not found in humans. Once again, one must look at the patient as a whole:The old adage could apply, “A little knowledge is a dangerous thing.”
Sure enough, reports are coming in of side effects following zealous but indiscriminate administration of zinc. Interestingly, zinc is known to produce copper deficiency in experimental animals. Reports have been published of hypocupremia, lowered serum copper levels, produced by administration of zinc. High plasma copper levels with low plasma zinc levels have been reported in zinc-deficient dwarfs from the Middle east and in sickle cell anemia. Thus some researchers suggest a reciprocal relationship between zinc and copper. Both elements may compete for similar binding sites in the tissues.
According to reports by other researchers, a high ratio of zinc to copper in the body may be the basis by which most of the known, risk factors for coronary heart disease exert their influence. High concentrations of zinc (or copper aericiency) have men shown to produce connective tissue abnormalities in the blood vessels of experimental animals. Cirrhosis, apparently protective against coronary heart disease, is reportedly associated with a decreased zinc-copper ratio in the liver.
These facts could either be foolishly ignored or be wisely put to a useful purpose. As an example, the relationship between zinc and copper in humans may suggest that zinc could be beneficial to persons with hepatolenticular degeneration or other conditions associated with the toxic effects of too much copper. It can easily be seen that zinc supplementation by itself, without carefully considering all factors, may produce a number of unwanted effects, however.
A final example of the hazards of not putting all the facts into perspective and applying them: the ill-fated liquid protein diet fad. No one can successfully argue about the need for protein. Proponents of the diet reasoned that if carbohydrate is restricted, then the body must burn up its stores of fat for fuel. Readers are doubtless familiar with the media-publicized furor over this diet. We wish only to take note of an interesting point of physiology. How do researchers produce severe magnesium deficiency in the animal model? High protein diets are used. The resultant magnesium deficiency produces an inevitable loss of potassium not correctable by administration of potassium alone. Also produced is cardiac myopathy characterized by myocardial cell necrosis. Even with vitamin and mineral supplements (excluding magnesium, of course) rats on such a diet die by cardiac arrhythmia or grand mal seizure after ten to fourteen days. Again, there is no magic bullet.
Space does not permit a detailed discussion of theoretical or real problems associated with the administration of large or unbalanced amounts of vitamins, minerals and related substances. It may require a little digging, but such information is available in current texts, published literature and even careful clinical observation. Some basic thoughts should stand out clearly from this discussion, however.
- Megadoses of vitamins do not serve a vitamin function. Rather, they serve as chemicals. Their effects at the organ, cell and sub-cellular level must be recognized as such.
- “Potency” cannot be established by comparing milligrams per tablet as a criterion.
- Aside from the question of synthetic versus natural, the whole concept of what is “natural” is open to question.
- The thoughtful physician must be cautious about looking for the quick, single or simple answer to the patient’s apparent problem. He must wisely look to the organism as a complex whole.
In 1877 the English biologist Thomas Henry Huxley wrote his treatise, “On Elemental Instruction in Physiology.” In it he said: “If a little knowledge is dangerous, where is the man who has so much as to be out of danger?” With the exciting rush of new facts of physiology flowing in daily, the new author of this journal does not presume to be out of danger. Yet as the first-century Latin poet put it, even a dwarf can see far when he stands on the shoulders of giants.