This week the Annals of Internal Medicine published the results of three studies looking at the health effects of long term use of multivitamins. Two of the studies are placebo controlled trials, both completely negative. The third is a systematic review, which found scant evidence for benefit. Together they are a significant blow to the routine use of multivitamins for health promotion or disease prevention.

This is one of the most common questions I get – “what about vitamins.” That taking your vitamins is healthy behavior has been successfully embedded in our culture. It is something that the vast majority of people take for granted.

There is a superficial sense to it. Vitamins by definition are essential for health, as are minerals. The lack of specific nutrients causes or predisposes to disease. If some is good then more is better, and there seems to be little harm in taking extra nutrients for “nutritional insurance.” It just feels like a wholesome thing to do.

However, the same medical science that taught us about vitamins also taught us other lessons. Biology is complex, and simplistic reasoning such as “more is better” rarely turns out to be true, or at least not the whole picture.

Our bodies also have been finely tuned by evolution to exist in homeostasis (at least for a while), and pushing or pulling on one thread in this intervoven system rarely has the simple effect we expect or intend. Related to this notion, the idea of “it can’t hurt” also turns out to be a naive belief that rarely pans out. If you are affecting the system in a way that can help, then it can also potentially hurt.

In medicine there is also the law of unintended consequences. Taking one health action may take resources away from other more productive interventions, or lull someone into a sense of false security so that they neglect their health in other ways. “I’m taking vitamins, so I don’t have to worry as much about the food I eat.”

For these reasons we need to evaluate risk vs benefit (as well as cost vs benefit) and net health effects of any intervention, even ones that seem benign and seem to make sense.

The three recent studies in the Annals add to years of research looking at multivitamin use. Overall studies have shown little to no benefit of routine supplementation, and some unexpected risks. I have to emphasize the word “routine” – meaning use by the general public. There is a lot of evidence for specific benefits of targeted supplementation – specific vitamins and minerals in specific populations (folic acid and pregnancy, vitamin D and multiple sclerosis, etc.)

The first study is Long-Term Multivitamin Supplementation and Cognitive Function in Men: A Randomized Trial. This was a study of 5947 male physicians aged 65 years or older followed for more than 12 years. They found:

No difference was found in mean cognitive change over time between the multivitamin and placebo groups or in the mean level of cognition at any of the 4 assessments.

No study is perfect, and the authors acknowledge the limitations of this study. Specifically it is possible that the dose of the vitamins was not high enough. It is also possible that the study population (physicians) have good baseline nutrition and therefore did not benefit from supplements. I would add that there may have also been an artifact in that those in the study were motivated to have better nutrition because they feared they might be in the placebo group.

These are generic caveats you can say about pretty much any similar study – the dose wasn’t high enough, or the placebo group was healthy. Still, negative results are negative results. While you can’t absolutely prove a null effect, you can say that the more data we gather without seeing an effect, the smaller any remaining hidden effect is likely to be. In other words, this study rules out any large, or even moderate, cognitive benefit from multivitamin use, even though it is still possible it missed a small effect.

The next study is: Oral High-Dose Multivitamins and Minerals After Myocardial Infarction: A Randomized Trial. This was a study of, “1708 patients aged 50 years or older who had myocardial infarction (MI) at least 6 weeks earlier and had serum creatinine levels of 176.8 µmol/L (2.0 mg/dL) or less.” They found:

High-dose oral multivitamins and multiminerals did not statistically significantly reduce cardiovascular events in patients after MI who received standard medications. However, this conclusion is tempered by the nonadherence rate.

The major limitation of this study was that 46% of subjects in the multivitamin and placebo groups stopped taking their supplements, and 17% of subjects dropped out of the study. This is a high rate which does have the potential to bias the results, although the non-compliance was symmetrical between the two groups. We are left with a similar conclusion – the study makes any large benefit from vitamins unlikely, but cannot rule out a small effect.

The final study was a systematic review: Vitamin and Mineral Supplements in the Primary Prevention of Cardiovascular Disease and Cancer: An Updated Systematic Evidence Review for the U.S. Preventive Services Task Force. They found:

Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor β-carotene prevented CVD or cancer, and β-carotene increased lung cancer risk in smokers.

Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD.

Negative or borderline evidence – once again argues against any large effect but perhaps there is a small effect. Taken together the evidence from these three studies, and prior research into routine vitamin supplementation, finds no clinically significant health benefit. Results tend to be negative to small or equivocal.

Conclusion:

When I write about multivitamin use I typically point out that I test for vitamin levels and prescribe vitamin supplements almost every day I am in clinic. There is solid science behind the role that specific nutrients play in health and the effects of vitamin insufficiency or deficiency. However, I also detect toxic levels of vitamins in some patients (the most common is B6) and have to counsel them to stop any supplementation with the vitamin.

Blind supplementation is overall probably not a good idea. It’s a waste of effort and expense, and you are as likely to be getting excess vitamins than shoring up a deficient vitamin.

The best approach to nutrition seems to be to simply have a well-rounded diet with plenty of fruits and vegetables. There are health benefits to this type of diet that go beyond micronutrients. Overall good nutrition can then be combined with targeted supplementation in people in certain high risk groups or with documented deficiency or insufficiency.

Routine supplementation in healthy individuals does not seem to be of any significant health benefit.