A Multivitamin Mystery

May 18, 2007 - Millions of Americans take multivitamins as part of their daily regimen and assume that they are getting some health benefits. But a recent study by the National Cancer Institute found that men who consume too many multivitamins might be upping their risk of a particularly aggressive form of prostate cancer, especially men with a family history of the disease. NEWSWEEK's Alexandra Gekas spoke with Dr. Michael Leitzmann, senior author of the study. Excerpts:

NEWSWEEK: What was the goal of the study?
Dr. Michael Leitzmann: To assess the association between the use of multivitamins and prostate-cancer risk. About 35 percent of U.S. adults use multivitamins on a regular basis.

What motivated the study? Was there previous evidence that multivitamins might increase the risk of prostate cancer?
The little data available to us indicated that there might be a positive association between multivitamin use and prostate cancer. We're basically the third study. An American Cancer Society study and a French trial both seemed to indicate that if prostate cancer was pre-clinically present in the body, that in those men, the use of multivitamins could possibly have an adverse effect. This was just speculation, so we went into our data and found that there's no association with overall prostate cancer. And when we split the men with organ-confined prostate cancer there was also no association, which was reassuring because that means the vitamins don't do anything in terms of harm for most cases. But when we looked at men with advanced prostate cancer, when the cancer had metastasized beyond the organ itself, we found that the risk of developing that type of cancer increased by one third with excessive multivitamin use. Then we had a third group that died of prostate cancer and among those men we saw that the risk had actually doubled with excessive multivitamin use. So it appeared that the multivitamin use was not affecting the early stages and it was not affecting the moderate disease but it was affecting the advanced or aggressive disease.

An epidemiological study like this one doesn't prove cause and effect. How confident are you that there really is a causal relationship?
In a study that is designed like ours, there is no basis for concluding that there is a causal relation. So what we did was observe an association. A rigorous study would assign people certain doses of vitamins and then give a control group a different type or a placebo, which our study didn't do. So if you ask me point blank, our study cannot establish causality. It just raises concern, enough concern to publish because of the perceived health benefits of multivitamins. People think they are doing themselves good, but in the best case nothing happens and in the worst case it actually causes harm. So our study should be seen as raising concern and prompting further research.

At excessive levels of intake, antioxidants can become harmful pro-oxidants. Is something similar going on with multivitamins?
It's not unthinkable that if you drastically increase the level of one single item that it may have an adverse effect on the body's function or inhibit the absorption of another substance. There are hints that it effects this balance. For example we know that beta carotene, which is a corotinoid, has about 600 isoforms, in other words there is not just one type. There are many forms which are very similar but differ in small respects. It appears that the whole spectrum might be important for the body's health, so if you grab one of those and you multiply the body's consumption manyfold, without the other kinds, who knows if the others aren't equally important. These multivitamins contain synthetic substances that have been isolated and are not in their natural forms, as in fruits and vegetables, which contain all their isoforms. So it might be the combination of having an isolated substance and administering it in ultra-high doses with unexplored effects. We don't know what that does to the body.

You specifically mention selenium, zinc and beta carotene. Is part of the problem that people are taking those supplements in addition to the multivitamins?
It always goes back to this basic notion, people do this because they think it's good for them. But what people are taking needs to be addressed carefully. There's a notion that selenium might protect against prostate cancer. There's a whole literature on the possible beneficial effects of these substances on cancer, and specifically prostate cancer, and that is probably true. But additional research is needed in parsing down what is the actual dosage and what is the relationship between the actual dosages. Can you actually overdose? Not like a drug overdose but a chronic overdose or excessive use or over-supplementation.

So from your evidence, what do you recommend people take away from this study?
I think it's wise to adhere to the RDA of multivitamins and I would be cautious to exceed the RDA by any magnitude. Taking a multivitamin for insurance, there's nothing to suggest that's bad for you. I think it would be safe to say that. But I would caution against the excessive use of multivitamins until more research comes. In our study the bottom line is not the multivitamins, per se, what we're worried about is unknown consequences of excessive uses of these substances.