Few purported medical interventions have such wide appeal or such an entrenched reputation for being benign and beneficial as vitamin supplements. Vitamins are chemicals (yes, they are, though you can call them “compounds” or even “essential nutrients” if it sounds nicer) that are required for normal health in minute quantities and cannot be made internally but must be obtained from the diet. Different species have different vitamin requirements, of course, so the defining characteristic is dependent on the organism, not the chemical. Vitamin C, for example, is a dietary requirement for primates and guinea pigs, but all other mammals can make enough on their own from other chemicals that they don’t require it in the diet, so it is not truly a vitamin for them.
Part of the reason vitamins are so widely believed to be good for us is the vague memory (at least in developed nations, though it is still ordinary reality in many parts of the world) of a time when vitamin deficiencies were common due to inadequate diets. Correcting such deficiencies has the kind of tangible, dramatic impact on health that antibiotics or polio vaccine can have, so it is easy to see such things as miraculous. And in America, where more is always better, the idea that it is a good idea to give vitamin supplements even to people with an adequate diet and no obvious signs of deficiencies is a naturally appealing one.
Unfortunately, the grim naysayers of science such as myself are often stuck with the thankless job of dispelling even appealing misconceptions, and recent editorial in the American Journal of Epidemiology has done that for some the proponents of vitamin supplements most hoped to be of benefit in preventing one of the major classes of illness that has replaced nutritional deficiencies and infectious diseases, cancer.
Byers T. Anticancer Vitamins du Jour—The ABCED’s So Far. American Journal of Epidemiology 2010;172:1–3.
The editorial surveys the history of anti-cancer vitamins from early reason for hope seen in observational and animal model studies through disappointing and often frightening clinical trials. In alphabetical order, then (citations are omitted and can be found in the full text of the article):
Animal experimental models led us to the notion that cancer risk might be ‘‘materially’’ reduced by supplementation with beta-carotene, a retinol precursor. Although that idea was seductive, we were all disappointed when 2 large randomized controlled trials that began in 1985 in Finland and the United States reported an 18% increased risk of lung cancer caused by high-dose beta-carotene supplementation and a 28% increased lung cancer risk caused by a combination of beta-carotene and retinol. The vitamin A era was over.
Again, based on animal experimental evidence and supported by epidemiologic evidence of connections between diets low in B vitamins and increased cancer risk, a large randomized controlled trial was begun in 1985 in central China, where micronutrient deficiency was common and where rates of cancers of the stomach and esophagus were extraordinarily high. Nonetheless, several years of supplementation with a combination of riboflavin (vitamin B2) and niacin (vitamin B3) had no effect on incidence of upper gastrointestinal cancers. Interest in folic acid (vitamin B9) persisted, though, in part because of its striking effect on neural tube birth defects, coupled with speculation about possible benefits of food fortification for diseases such as colorectal cancer that were inversely associated with diets rich in folate-containing foods and supplements. However, a 7-year randomized controlled trial found that high-dose folic acid supplements actually increased risk of colorectal adenomas. The vitamin B era was over.
Next came vitamin C, a popular charge led by none other than Linus Pauling, the brilliant and charismatic 2-time Nobel laureate. Of all the cancers thought to be related to vitamin C deficiency, gastric cancer led the way, and of all the places on Earth where a vitamin C deficiency correction trial might yield benefits for gastric cancer, Linxian, China, would be the best. Indeed, vitamin C was tested in the Linxian trial, but just as for the B vitamins, vitamin C produced no change in gastric cancer rates .
Over 2 decades of searching for an anticancer vitamin, we had seemed to skip over vitamin D in its proper alphabetical sequence…the International Agency for Research on Cancer conducted a comprehensive review of the evidence for vitamin D and cancer prevention, concluding that vitamin D may play a protective role in colorectal cancer, but not for prostate cancer, and that the evidence is weak for breast cancer. The conclusion by the International Agency for Research on Cancer about the weakness of the evidence for breast cancer has been a source of controversy among vitamin D protagonists, but subsequent nested cohort studies have found no relation between breast cancer risk and circulating levels of vitamin D. Nonetheless, vitamin D remains the cancer-preventing vitamin du jour.
…An outstanding set of papers in this issue of the American Journal of Epidemiology reports on findings about the relation between circulating levels of vitamin D and subsequent cancer risk…These studies found no suggestion of an inverse association between vitamin D levels in the circulation and later incidence of 6 types of cancers (upper gastrointestinal, ovary, endometrial, pancreatic, kidney, and non-Hodgkin lymphoma)… The only association observed in this set of 6 analyses was a troubling one: that risk of pancreatic cancer was doubled for those in the highest quintile of circulating vitamin D levels.
…many ongoing randomized controlled trials are now using quite high doses of vitamin D. As we await clearer evidence of benefits from those trials, we will also need to be prepared to be vigilant about their individual and collective power to assess any potential harms.
In 1993, we launched headlong into a love affair with vitamin E fueled by compelling observations that those who chose to take vitamin E supplements were at lower risk of heart disease. Vitamin E supplementation became the rage as several large, randomized controlled trials were mounted. When those results finally came in, the findings were again disappointing: vitamin E supplementation offered no benefit for heart disease, and it slightly increased overall mortality. In the meantime, though, because of a secondary observation that prostate cancer incidence was lower in the vitamin E arm of the same Finnish trial that tested beta-carotene (vitamin E had also been included as a factor), a large factorial trial of vitamin E (and selenium) was carried out for reducing prostate cancer incidence. Disappointment again: there was no effect of either selenium or vitamin E on incidence of prostate cancer. The vitamin E era ended in a whimper.
Of course, alternative medicine proponents often dispute this evidence, and it is easy to find claims of efficacy for all of these vitamins in preventing or treating cancer: Vitamin A, Vitamin B, Vitamin C, Vitamin D, Vitamin E.
Given the ease with which the evidence can be ignored, cherry-picked, or distorted, the underlying conclusion of this editorial is even more salient and important than the specifics of the failed promise of vitamin supplementation to prevent:
It is timely for us to now reflect on the history of the past 25 years of our alphabetical approach to studying single vitamin deficiency states as causal factors for cancer. We have learned some hard lessons along the alphabetical way. We now know that supernutritional levels of vitamins taken as supplements do not emulate the apparent benefits of diets high in foods that contain those vitamins, and we now know that taking vitamins in supernutritional doses can cause serious harm. In short, we have found that the reality of human biology is far more complex than is suggested by our simple ideas.
Let me emphasize again these key points:
1. Supernutritional levels of vitamins taken as supplements do not emulate the apparent benefits of diets high in foods that contain those vitamins.
2. Taking vitamins in supernutritional doses can cause serious harm.
3. The reality of human biology is far more complex than is suggested by our simple ideas.
Point 3 is one of the most important principles of science-based medicine. The understandable search for simple answers and the inevitability and challenges posed by complexity and uncertainty naturally drive us to accept simple, clear explanations and recommendations and make us shy away from the messiness and limitations of reality. But unfortunately we must accept that reality is more complex than our ideas, and that as a consequence we will often be wrong and our understanding and ability to control our health will always be limited and incomplete. The best chance we have of actually doing good is to strive for this acceptance and to deal with reality as it is rather than as we would wish it to be.
Alternative medicine often relies on the idea that belief is enough and that reality can be forced into our simple models of one cause/one cure for disease. Science can, and should do better, and though the process is slow, cumbersome, and often not psychologically comforting, the truth is that it just works better. 25 years of scientific research has shown us what supplementation of some vitamins can and cannot do for some diseases, and this information is worth the wait and the effort, and it will serve us better than the false hope and comfort of simplistic theories and wishful thinking.