Healthy Skepticism: Antioxidant "Nutritional Supplements"

by Tim Gorski, M.D.

According to one of several speculative hypotheses about the cause of aging and senescence, cumulative damage to cell structure leads to progressive degradation and impairment of function, as well as disorders which are disproportionately prevalent in old age such as cancer. It has been further postulated that the proximate causes of cell damage at the molecular level are free radicals and oxidizing substances. These, for the most part, are extremely reactive bits and pieces of ordinary moleculeswhich can become disrupted by any number of means.

Although these ideas remain somewhat speculative, there are very good reasons for taking them seriously. There is excellent evidence, for example, that many cancers arise through the cumulative acquisition of cellular mutations. And it appears that the tendency to develop certain cancers consists of the prior possession of such genetic defects, which can be passed along to one's descendants. It also happens that diets high in fruits and vegetables, which contain a variety of antioxidants and other naturally- occurring substances that are capable of quenching free radicals, reduce the risk of some cancers.

These are the facts that have led many to advocate the use of "nutritional supplements" of Beta-Carotene and Vitamins C and E (alpha-tocopherol). Others rely on such ideas to claim that these substances can be depended on to prevent cancer and lengthen one's life span. But, apparently, as is the case so often, things are more complicated than the supplement promoters would like to believe.

Earlier this year, for example, the Alpha-Tocopherol, Beta Carotene Cancer Prevention Study published the results of its 5- to 8-year follow up study of 29,133 male smokers in Finland. These subjects were chosen because, if there are any anti-cancer benefits to be had from taking such supplements, they ought to be most easily discernible among those at highest risk. Surprisingly, no reduction in the incidence of lung cancer was found. Instead, there was a statistically significant 8% excess mortality among those who took the beta-carotene supplement. [The New England Journal of Medicine, 330:1029, 1994.]

A case-control study was also published some years ago which found an increased risk of cervical dysplasia (the abnormality for which pap smears screen) among women with a high intake of beta-carotene. [International Journal of Epidemiology, 20:603, 1991.]

And just last month, the results of a multi-center trial of the same supplements were published in which the incidence of colorectal was studied. Among four groups of 751 individuals taking either placebo, beta-carotene, vitamins C, E, or all three supplements, this research showed no reduction in the occurrence of these precursors of invasive cancer over four years. [The New England Journal of Medicine, 331:141, 1994.]

Now it is possible, of course, to pick apart virtually any research study, and the proponents of "nutritional supplements" have been doing exactly that with both of these published reports. Concerning the Finnish study, for example, it's been argued that the study subjects who developed cancer had already progressed through the earliest stages of carcinogenesis during which antioxidant supplements exert their effects. And, with all such studies, it's possible that the dosages were either too high or, as the most vociferous critics allege, too low. It's also possible that the results in any or all of the studies were due to chance.

None of these are unreasonable criticisms, but it seems that they're seldom made when research results could be construed as supportive of the "nutritional supplement" pushers' claims. Skepticism itself is suspect when it's so selectively employed. For what is more often the case is that the flimsiest connection to what is merely suggested by the most preliminary of scientific studies is seized upon as if it were divinely-inspired scripture by many of the self- proclaimed health and longevity "experts."

But even a far less free-wheeling approach to reporting on scientific research is decried in a Journal editorial accompanying the third of the above-referenced articles. The editors cite the apparent flip-flops over the health benefits of oat bran and margarine, of sugar versus saccharin, and even exercise, in addition to the new findings concerning beta-carotene and vitamins C and E. They quote from a New York Times editorial opining "no wonder health-conscious Americans often feel they just can't win," and paraphrase the general question being asked as: "Why can't researchers get it straight the first time?"

The answer offered by the Journal editors is that "what medical journals publish is not received wisdom but rather working papers. Each of these is meant to communicate to other researchers and to doctors the results of one study. Each study becomes a piece of a puzzle that, when assembled, will help either to confirm or refute a hypothesis. Although a study may add to the evidence about a connection between diet or exercise and health, rarely can a single study stand alone as definitive proof." They then go on to cite a number of confounding factors that can distort the puzzle pieces and remind their readers that even "the now overwhelming evidence that cigarette smoking is extremely dangerous was accumulated bit by bit over many years."

"For this reason," they point out, "the practice of medicine, as well as clinical research, is inherently conservative. ... But because of the public's keen interest in new medical findings, the media may be less conservative. They are serving a public that believes passionately that the more we can learn about what to eat or how to live, the longer we will live." As a result, "the media reports are exaggerated or oversimplified." The Journal editors recommend that the media "pay closer attention" to these four caveats:

They also urge the public at large to "become much more sophisticated about clinical research" but acknowledge that this "is unlikely to happen as long as science education in the United States is so poor."

"Although we would all like to believe that changes in diet or lifestyle can greatly improve our health," the editors note in conclusion, "the likelihood is that, with a few exception such as smoking cessation, many if not most such changes will produce only small effects [which] may not be consistent [and] will almost inevitably involve some sort of trade-off."

An attitude of "moderation," not just towards diet and exercise, but "in our response to news of clinical research" is called for, suggest the Journal editors. "People who feel betrayed when they learn of a new study showing that vitamin E and carotene do not protect against cancer should ask themselves why they so readily believed that antioxidants had this effect in the first place and why they now believe that there is no such effect."

Finally, to muddy the waters just a bit more on the subject of antioxidants, there is the work of researchers at Northwestern University Medical School in Chicago. There, Mark Gurney and colleagues appear to have found an animal model for amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, the same crippling neurological disorder from which cosmologist Stephen Hawking suffers. According to a report in Science [264:1663, 1994], the animal model is a mouse into which a gene for a mutant Cu,Zn superoxide dismutase (SOD) has been introduced. SOD is an enzyme which eliminates superoxide radicals by converting them into hydrogen peroxide, which is, in turn, converted to water and oxygen by another enzyme, catalase.

But, so far, the indications are that the mutant SOD is not simply disabled. Gurney himself has declared that "We now have genetic proof for the mechanism. It's a dominant gain of function." Just what that "gain of function" is remains to be discovered, but there is some evidence already that SOD does more than break down superoxide radicals. Compare that to the recently-discovered fact that nitric oxide, a highly reactive chemical species, actually serves as an important neurotransmitter which is involved in, of all things, penile erection.

All these considerations should serve to remind us that there is still a great deal still to be learned about the metabolism of free radicals and other highly reactive molecules. Anyone who knows anything about chemistry, moreover, should know that many chemical reactions are freely reversible. Thus, although vitamins C, E, and beta-carotene can act as antioxidants, they can also produce free radicals. Thus, there are very good reasons to question the simple-minded supposition that, where these and similar substances are concerned, if a little is good, then a lot must be better.

[Provided by the D/FW Council Against Health Fraud. Dr. Gorski is a practicing physician, chairman of the D/FW Council Against Health Fraud and a North Texas Skeptics Technical Advisor. Reprinted with permission by the North Texas Skeptics.]

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