Oct 18 2012

Multivitamins and Cancer

Existing evidence does not support a health benefit from taking a routine daily multivitamin. That has been the bottom line conclusion of medical research over the last couple of decades. A recent study published in JAMA, however, is making headlines because it found a small but statistically significant decrease in total cancer incidence in men taking a multivitamin vs placebo. The study raises the question again about the total health effects of a daily vitamin.

First let’s take a look at the study:

A large-scale, randomized, double-blind, placebo-controlled trial (Physicians’ Health Study II) of 14 641 male US physicians initially aged 50 years or older (mean [SD] age, 64.3 [9.2] years), including 1312 men with a history of cancer at randomization, enrolled in a common multivitamin study that began in 1997 with treatment and follow-up through June 1, 2011.

The study found that the total incidence of cancer was 17.0 per 1000 person years in the multivitamin group, and 18.3 per 1000 person years in the placebo group. This difference was statistically significant. The study, however, found no statistically significant difference in any specific cancer (it was only the cumulative incidence that reached significance) and no difference in cancer mortality. Taken at face value this indicates a small but real decrease in total risk of cancer for older men taking a daily multivitamin.

I could not find any glaring flaws in the study, it seems well designed and executed. Individual studies, however, are rarely definitive in their findings. The most reliable studies have rigorous design, clear outcomes, large numbers, with a robust and statistically significant result. The results of this study are suspect mainly because the effect size was very small. Subtle confounding factors can reach statistical significance in very large studies, which is why small effect sizes are always suspect. There also appeared to be multiple comparisons in the study – specific cancers, different subgroups, and various outcomes (incidence and mortality), which creates the opportunity for spurious statistical outcomes.

The fact that this study looked at male physicians has an unclear effect on the degree to which it can be extrapolated to the general population. In general physicians take better care of themselves and are more compliant with treatments than the general population.

The results of this study, therefore, are interesting and plausible – there may be a small benefit in terms of total cancer risk from a daily multivitamin. But we have more than this one study to go by. Previous studies looking at the same question have had different results. The authors of this study summarize previous evidence:

In the Cancer Prevention Study II, which followed up more than 1 million US adults beginning in the early 1980s, multivitamin use was not associated with cancer mortality. The Women’s Health Initiative found that multivitamins had little or no relationship with the risk of breast, colon, or other cancers in more than 160 000 women followed up for a mean of 8 years. Among 35 000 Swedish women, however, multivitamin use was associated with a 19% increased risk of breast cancer (95% CI, 1.04-1.37) during a 10-year period compared with women not using these vitamins.

They further point out that observational studies have shown a protective effect, no effect, and even increased risk from multivitamins. Put into the context of the entire literature on this question, therefore, it remains unclear what the net effect of a daily multivitamin is on cancer risk and mortality. When multiple clinical trials of various designs show inconsistent and small results this could reflect the fact that there is little to no net effect, and we are just seeing random statistical fluctuations among trials. There could also be one or more systematic errors in the way the data is being looked at which is obscuring the real effect (whether positive or negative).

At this point about the only thing we can say with a high degree of confidence is that there is no large risk or benefit from taking a multivitamin. There may be a small benefit, no benefit, or even a small harm. The totality of existing data does not rule out any of those latter interpretations.

The best health recommendation also is not changed by this study, which is that the best advice is to eat a varied diet with lots of fruits and vegetables. If you do this you will very likely get enough vitamins from your diet that a supplement will be redundant. The benefits of having many vegetables in the diet is clear. Perhaps the biggest risk of taking a multivitamin is that it can create a false sense of security and justify other unhealthful behavior.

Meanwhile the question about the health effects of taking a multivitamin remains open. If anything, this study confuses the issue further because it is at odds with prior research.

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