Multivitamins and Multiplication

As has likely come to your attention by now, a new study shows that daily multivitamin use is associated with a reduction in the overall rate of cancer. These findings are intriguing and promising, but far from the proverbial slam-dunk.
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As has likely come to your attention by now, a new study shows that daily multivitamin use is associated with a significant reduction in the overall rate of cancer. This is clearly important, and warrants careful consideration in the context of what we already knew, or thought we knew, about multi-nutrient supplementation.

For a long time, the prevailing view of multis -- which as a rule contain a mix of vitamins and minerals, most at or above the level of recommended daily intake -- was that they could and probably should help, and couldn't hurt. Nutrient levels were based on the Dietary Reference Intakes of the Institute of Medicine, and in general all or nearly all of the micronutrients known to be essential were in the mix.

There was always a sound rationale for such supplementation. Average intake in the U.S. of quite a few nutrients is lower than recommended, and intake of quite a few more is lower than optimal. In particular, as people get older, there is a tendency for both calories and dietary variety to fall -- resulting in a rising risk for nutrient deficiencies. Few of these are bad enough to present as overt deficiency syndromes, but even nominal deficits of key nutrients may compromise health. And some cases of overt deficiency -- notably of vitamins B12, folate, iron, and calcium -- are seen.

This all seemed to make a robust argument for routine supplementation, in particular by those over age 50. Most doctors recommended the practice routinely, as did I. And, of course, the supplement industry made hay predictably, providing a wide array of products that competed for attention with claims about nutrient quality, quantity, variety, and customization.

But then the notion that multis could help but "couldn't hurt" started to take a beating. First came a long line of clinical trials suggesting lack of benefit and potential harm from high doses of select nutrients. Then came studies showing associations between multivitamin use and adverse outcomes -- in particular, a higher rate of breast cancer among women.

Since we never had clear evidence of a benefit, even a hint of potential harm from multis was enough to argue pretty powerfully against their routine use. I stopped taking one, and stopped recommending them to my patients in the absence of a clear reason.

I never abandoned supplementation entirely, of course. In general, my clinic recommends supplements to do a particular job. So, for instance, we use omega-3s routinely to reduce inflammation, probiotics to improve gastrointestinal health and immune function, and vitamin D whenever levels are low. We use a wide range of other supplements when there is a specific case for doing so.

As for multis, I switched over to recommending them only when there was a meaningful likelihood of dietary deficits and, for whatever reason, an inability to fix them with food. I also switched form conventional multis to "whole-food-based supplements." I still think those are a good idea, and here's why:

If multis do harm, there must be a reason -- and the most plausible one is a problem of "nutritional noise." Imagine, for instance, that a great electric guitar player from a rock band, a great sax player from a jazz ensemble, and a virtuoso cellist from a symphony orchestra play their own brand of music all at once. No matter how good each is when in the his/her native context, the result of this mishmash would be unpleasant noise.

In putting together multis, we -- not nature -- have chosen the dose, preparation, and variety of nutrients, and taken them all out of their native context in food. We know that nutrients, like musicians, work best in concert with one another. If we have assembled them wrong, they might clash. Nutritional noise could be harmful.

Whole-food-based supplements avoid this potential danger because they preserve the native context of nutrients in foods. This may facilitate the work of nutrients in concert with one another, and make far more beautiful music in our metabolism. It's theoretical, but makes good sense.

But now we have the new study, and it does invite some reconsideration of the traditional multi. The findings, reported in JAMA, are based on a randomized, blinded, placebo-controlled intervention among nearly 15,000 U.S. male physicians followed for more than 10 years. There were 8 percent fewer cancers overall in those who took the multivitamin, and this was statistically significant, although barely so. There were no significant effects on any particular cancer, none on cancer mortality, and none on all-cause mortality.

So the findings are intriguing and promising, but far from the proverbial slam-dunk. And they are limited to a population of male doctors age 50 and older. How they pertain to women, younger people, or populations who behave differently on average than doctors, is unknown.

So where does it leave us?

We had seen the gradual accumulation of evidence for potential harm from multivitamins. This study does not eradicate that, but it does suggest that in some populations at least, there is potential for net benefit. Judicious use of multivitamins by men age 50 and older is, if not obviously advisable, perfectly reasonable given what we do and don't know at present.

The theoretical case for whole-food-based supplements remains valid, and absence of evidence is not evidence of absence. We don't have a trial like this using supplements like that, so we are left to speculate about the potential for greater benefits.

We once thought multis could do good and couldn't do harm. We then learned they could do harm, and developed doubts about them doing any good. Our current understanding is far from perfect, but it seems to suggest some potential for both. This invites discussion between patients and doctors, and customized decisions based on personal circumstance. That may not be an entirely satisfying resolution, but anything else would run ahead of the evidence we've got. This study revises our risk/benefit assessment, it is not a basis to renounce it.

But the most important take away here has to do with the size of effects, rather than their direction. A relative reduction of 8 percent in the overall rate of cancer is better than nothing -- but it is a small effect. In contrast, studies from 1993, 2004, 2009, 2010, and 2011 -- just to name a few -- show that the combination of not smoking, eating well, and being active can reduce the risk of all chronic disease, cancer included, and premature death from any cause by as much as 80 percent. That is a tenfold multiplication of the best effect of multivitamins yet shown. You certainly want that math on your side!

So whether you choose to take a multi or not, remember it's a supplement, not a substitute. There is no substitute for the profound health benefits of a daily dose of well-chosen lifestyle as medicine.

-fin

For more by David Katz, M.D., click here.

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