I'd mentioned in an earlier post that a relative was prescribed fairly high dose vitamin D by her primary care physician despite a blood test showing that her vitamin D level was in the normal range. Her PCP may not be much of an outlier. Among the residents I work with, I've been encountering a lot of desire to prescribe vitamin D to pretty much everyone.
Why the willingness to administer vitamins? Would these same doctors feel that a drug with similar levels of evidence for safety and efficacy should be administered to tens of millions of generally healthy people?
Somehow patients and providers alike seem willing to treat vitamins as articles of faith -- as substances that must be good for humans based on their very name and nature. Yet the actual track record of vitamins, and particularly the fat-soluble vitamins, should not lead us to be so sanguine.
Based on their antioxidant properties, vitamin A/beta carotene and vitamin E were believed to be good for health before any reasonable studies had been performed. Doctors recommended beta carotene and vitamin E at moderate or high doses, and health-conscious patients took even higher doses. Then the results of randomized trials started to come in:
Two large randomized trials of vitamin A/beta carotene found increased rates of lung cancer in smokers, pretty much putting an end to the notion of using beta carotene to prevent cancer. Then, a meta-analysis of trials of vitamin E found an apparent increase in mortality in patients treated with higher doses of vitamin E, and suddenly vitamin E no longer appeared so benign.
With this as a backdrop, we might expect physicians, at least, to show some skepticism before recommending other vitamins, and particularly other fat-soluble vitamins.
Yet, in their defense, vitamin D has been studied in randomized trials (mainly for prevention of fractures/osteoporosis), and these trials have reported other outcomes including cancer rates and mortality.
Although much larger trials have found no effects of vitamin D on cancer rates, one trial that I've heard people cite did indeed find a reduction in cancer rates in patients supplemented with calcium and vitamin D. The RR was 0.23 -- in other words, the supplementation appeared to reduce cancers by 77%. Since virtually nothing in medicine has an effect that large, and such an effect would be hard to have missed in other trials of calcium and vitamin D, this result seems implausible at best.
With regard to mortality, a meta-analysis of randomized trials found that vitamin D supplementation appeared to decrease mortality by 7%. A concern, though, is that the result was just barely statistically significant, and there could be reporting bias with regard to mortality: trials that found larger differences in mortality (or any other safety endpoint -- these were, after all, not trials designed to look at mortality) would be more likely to report on mortality than trials that found nothing interesting when they looked at their safety data. Given the risk that the results could be due to chance, even a small amount of reporting bias would be worrisome.
So, I've now objected to one trial of vitamin D for having too large an effect to be believable, and a meta-analysis for having too small an effect to convincingly rule out chance plus bias. Am I being fair and true to the evidence?
If we were talking about a therapy for a morbid illness where we were compelled to treat, I'd likely accept the evidence from the meta-analysis as being sufficiently hopeful to make vitamin D worth a try. After all if treatment is required, even if vitamin D eventually turned out to be harmful, we would know that we had needed to do something for the ill patient and so we made our best guess.
But that is not the case here. Instead, we are talking about administering a therapy to enormous numbers of healthy people with the hope of preventing disease, and where causing even small increases in harmful outcomes would have no justification. And remember the history of vitamin E and beta carotene. If that is not sufficient to make you concerned, read what happened to cancer rates and mortality in two trials of folate/B12 supplementation in Norway, published just last week in JAMA.
In such a situation we should wait for (and demand) more convincing evidence before we act. It may turn out that vitamin D really does prevent cancer, decrease mortality, and protect people from everything from influenza to the common cold. But I would rather be late jumping on this bandwagon than jump early and find that I hadn't learned a thing from past mistakes.