Nov 18 2008

Vitamin E and C Do Not Prevent Cancer

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A new long term study of vitamin E and C supplementation in a group of physicians showed no protective effect for either prostate cancer specifically or cancer in general. This is a disappointing result – it would be nice if a low risk intervention like vitamin supplementation would significantly reduce cancer risk, but it does not appear to be the case.

The results of the study were presented at the American Association for Cancer Research’s Seventh Annual International Conference on Frontiers in Cancer Prevention Research, and the press release states:

The Physicians’ Health Study II is a large-scale, long-term, randomized clinical trial that included 14,641 physicians who were at least 50 years old at enrollment. These physicians were given 400 IU of vitamin E every other day or its placebo, or 500 mg of vitamin C daily or its placebo.

Researchers followed these patients for up to 10 years for the development of cancer with high rates of completion of annual questionnaires, and the confirmation of reported cancer endpoints.

Analyses indicate that randomization to vitamin E did not have a significant effect on prostate cancer. This lack of effect for vitamin E also extended to total cancer. Vitamin C had a similar lack of effect on total cancer.

Vitamins and Disease Prevention

The idea is very appealing, and has gained recent popularity due in part to the larger trend toward “natural” remedies and nutritional therapies. This is turn has been boosted by a deregulated supplement industry that now rakes in billions selling the idea that “supplements” can cure or prevent anything.

But the appeal is more basic – it would be undeniably great if we could live longer and reduce our risk of a dreaded class of diseases simply by tweaking our nutrition.  I have no a priori bias against vitamins as preventives. And, contrary to the ravings of the conspiracy-mongering cranks who want to dismiss any science-based opinion they disagree with – I am not in league with any AMA conspiracy, I am not on the payroll of Big Pharma, and I don’t even treat cancer. In fact I am a salaried academic and do not make money from treating patients.

I simply want to understand the research – what is the evidence really telling us, as opposed to what we would like to be true.

Recently there have been a number of large clinical trials looking at vitamin supplementation to prevent cancer, heart disease, and other common diseases that have all shown no significant benefit. The Physicians Health study is just the latest. Wallace Sampson has summarized and referenced this research recently at Science-Based Medicine.  These include studies that show no benefit from C and E for heart disease (this is the same data set that showed no benefit for cancer), no benefit from the B vitamins for heart disease, and no benefit from E and selenium for prostate cancer. Disturbingly, there are also studies that show an increased risk of some kinds of cancers from specific vitamins.

There seems to be a clear trend in this research. While a number of retrospective or population-based studies have shown a possible correlation between supplementation, certain diets, and a reduced risk of cancer, this correlation does not appear to be holding up with large, placebo-controlled prospective trials. Generally speaking, these large prospective trials are considered a more direct test of the effect of vitamin supplementation, a stronger form of data, and they largely trump the earlier studies.

In this latest study of vitamin C and E, for example, over 14 thousand subjects were followed for 10 years.  That is pretty robust data.

Of course, like all such research, it can’t prove a negative – that there are no specific benefits from vitamins. A lack of statistic correlation shows a specific probability that any effect is smaller than the power of the study to detect. So if there is any effect, it was probably too small to measure by this large study.

Vitamins C and E in particular have garnered a great deal of interest because they are antioxidants – which means they decrease the level of oxygen free radicals which is an important mechanism of cell damage. However, the story of antioxidants has turned out to be much more complex than simply – oxygen bad, antioxidants good. The supplement industry marketing has not caught up to this reality (and probably never will – why should they). Free radicals, for example seem to trigger downstream metabolic effects that are beneficial, therefore while suppressing free radicals you may be reducing cell damage but you are also reducing these beneficial effects.

This is precisely why large clinical trials are needed in order to make reliable clinical conclusions – you cannot simply extrapolate from the basic science. It’s too complex.

Looking at the big picture it seems as if the primary role of vitamins is to treat vitamin deficiencies. There does not appear to be much of a role for supplementation beyond that, except in very specific cases for which there is evidence. For example, women who may become pregnant should take folate supplements to reduce the risk of spinal cord defects. There is reasonable evidence that vitamin B2 may reduce the severity or frequency of migraines. There is mild evidence that B6 may help nerves recovery from injury. It is standard practice to give vitamin C to patients recovering from surgery or trauma. The theme here is that during periods or conditions of particular stress, the metabolic demand for specific vitamins may be needed and supplementation can improve outcome.

There is no compelling evidence for routine supplementation in healthy individuals.

But the story of vitamins and health is far from over. Interest is simply too high – and this is not unreasonable. Again – vitamins are relatively low risk (but should not be considered risk free). They generally have no side effects, except with megadosing, which can be dangerous and should be avoided. Vitmamins by definition are those substances that we are metabolically dependent on but which our bodies cannot make for themselves, so they have to be consumed. It is therefore plausible that they can have a beneficial effect.

Recently there has been great interest in vitamin D. A recent review of studies shows that vitamin D supplementation is associated with lower overall mortality.  Low vitamin D may have a role in MS and other auto-immune diseases (although supplementation does not seem to be a benefit for breast cancer). Recently the RDA for vitamin D was doubled for children. It seems we may still have a lot to learn about specific vitamins and diseases. But to put this in perspective, it may be that there is a relative level of vitamin D deficiency, perhaps brought about by reduced exposure to the sun and UV rays which are necessary for the body to make vitamin D. We may therefore be treating a deficiency, not supplementing above and beyond basic needs.

Also, while this data is compelling we are not yet at the large, controlled, prospective trial level. We will likely not have the final word on vitamin D for many conditions for 10 years – there is no way around that fact that it takes at least10 years to gather 10 year survival data.

Another point to consider is that much of the preliminary retrospective data showing a positive correlation between vitamin intake and health may really be due to other healthful lifestyle factors that correlate with diet or supplementation. One interpretation of this recent negative vitamin data is that supplements are no substitute for a healthful diet. I don’t think this is because of any magical difference between vitamins in food and the same chemicals in pills. But it is plausible that nutritious diets are also healthy in other ways. For example they may contain less bad cholesterol or overall calories. A good diet is also probably a marker for other healthy habits.

Conclusion

The story of vitamins is complex. What we can say now based upon the evidence is that even minor deficiencies of vitamins should be avoided, and physicians needs to test for them and treat them when encountered. A well-rounded and nutritious diet is a no-brainer good idea for everyone. Specific supplementation in specific conditions may be indicated, where supported by the evidence. Megadosing is worthless and may even be harmful.

But the evidence does not support routine supplementation for healthy individuals with a good diet. Vitamins are not a panacea or an elixir of longevity (despite what the supplement industry would like you to believe). And specifically, they do not seem to have a detectable benefit for preventing heart disease or cancer.

Research on vitamins will continue, however, and evidence-based recommendations will change over time. Much of this research is reasonable, even necessary, but some is based upon hype.  We need to clear away the mystique of vitamins and keep our eyes on the science.

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