Supplements Kill

Curious to see what we know about the health benefits of vitamin supplements, I went looking with my assistant David Ortiz.  We found this fantastic 2007 JAMA meta-analysis of 385 publications regarding 232,000 subjects. Bottom line: on average supplements increase an ordinary adult’s chance of dying by 7%. While selenium reduces death rates by 0.2%, beta carotene increases them by 9%, vitamin C and E by 6%, and vitamin A by 20%.  Maybe you should take selinium, but mostly just stay away from supplements. From now on, I’ll avoid multivitamins. Quotes:

We searched electronic databases and bibliographies published by October 2005. All randomized trials involving adults comparing beta carotene, vitamin A, vitamin C (ascorbic acid), vitamin E, and selenium … were included. … Randomization, blinding, and follow-up were considered markers of bias in the included trials. … We included 68 randomized trials with 232 606 participants (385 publications). When all … were pooled together there was no significant effect on mortality.

Multivariate meta-regression analyses showed that low-bias risk trials (RR, 1.16; 95% CI, 1.05-1.29) and selenium (RR, 0.998; 95% CI, 0.997-0.9995) were significantly associated with mortality. In 47 low-bias trials with 180 938 participants, the antioxidant supplements significantly increased mortality (RR, 1.05; 95% CI, 1.02-1.08). In low-bias risk trials, after exclusion of selenium trials, beta carotene (RR, 1.07; 95% CI, 1.02-1.11), vitamin A (RR, 1.16; 95% CI, 1.10-1.24), and vitamin E (RR, 1.04; 95% CI, 1.01-1.07), singly or combined, significantly increased mortality. Vitamin C and selenium had no significant effect on mortality. …

The pooled effect of all supplements vs placebo or no intervention in all randomized trials was not significant (RR, 1.02; 95% CI, 0.98-1.06). … Univariate meta-regression analyses revealed significant influences of dose of beta carotene (RR, 1.004; 95% CI, 1.001-1.007; P = .012), dose of vitamin A (RR, 1.000006; 95%CI, 1.000002-1.000009; P = .003), dose of selenium (RR, 0.998; 95% CI, 0.997- 0.999; P = .002), … on mortality. None of the other covariates (dose of vitamin C; dose of vitamin E; single or combined antioxidant regimen; duration of supplementation; and primary or secondary prevention) were significantly associated with mortality. …

In trials with low-bias risk mortality was significantly increased in the supplemented group (RR, 1.05; 95% CI, 1.02-1.08). … In high-bias risk rials (low-methodological quality in >=1 of the 4 components) mortality was significantly decreased in the supplemented group (RR, 0.91; 95% CI, 0.83-1.00). …

At event rates below 1%, the Peto odds-ratio method appears to be the least biased and most powerful method when there is no substantial imbalance in treatment and control group sizes within trials. … When we applied Peto odds ratio, we found even stronger support for detrimental effects of the supplements (for all 68 trials: 1.05; 95% CI, 1.02-1.08; for the 47 low-bias risk trials: 1.07; 95% CI, 1.04-1.10; after exclusion of high-bias risk trials and selenium trials, for beta carotene: 1.09; 95% CI, 1.06-1.13; for vitamin A: 1.20; 95% CI, 1.12-1.29; for vitamin C: 1.06; 95% CI, 0.99-1.14; and for vitamin E: 1.06; 95% CI , 1.02-1.10).

Added 9:30p: I’m reminded that Phil Goetz complained the study should have tried to fit higher order moments in dose-response estimates, becuase “mean values used in the study of both A and E are in ranges known to be toxic.” Well not only is it hard to believe that authors of 385 studies chose to test dosage levels known to be deadly, it has been three years since this JAMA paper and no critic has yet bothered to redo the analysis with higher order moments, or restricted to low-dose studies. Really, for any stat analysis, you can always complain that they didn’t try some particular variation you like.  If you think some further analysis would be insightful, it should usually be up to you to try it, not up to them to try all possible variations you can imagine.