This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.
Vitamins. If you are like the majority of American adults, you took a vitamin or supplement recently. Over-the-counter sales of these products in this country amount to over $30 billion a year. That’s more than the market for statins — and vitamins aren’t covered by insurance.
For there to be a $30 billion market, there must be some pretty convincing evidence that vitamin supplements work to improve health, right?
Well, in the most thorough meta-analysis to date, researchers from Kaiser-Permanente crunched the numbers from virtually every randomized trial of vitamin supplements in adults to conclude that, basically, they do nothing.
Or, as we say in nephrology: Vitamins give you expensive pee.
As many of you know, the US Preventive Services Task Force (USPSTF) makes evidence-based recommendations to the American people about a wide variety of health behaviors, from aspirin for primary prevention to screening for lung cancer.
The USPSTF tasked researchers with updating the data on vitamin supplementation with two important outcomes in mind: cancer and cardiovascular death. Why vitamins? Because the observational data are clear and compelling. People with vitamin deficiencies are at higher risk for these bad outcomes.
Even people with lower levels of certain vitamins, not in the deficiency range, are at higher risk for cancer and cardiovascular disease. It stands to reason that if lower levels are associated with bad outcomes, and supplements prevent you from having lower vitamin levels, then supplements could improve those outcomes.
The researchers identified 87 randomized controlled trials of adults where at least one vitamin or a multivitamin was being evaluated. Caveat: These were general-population studies, not studies of people with known vitamin deficiencies. The results should not necessarily be generalized to those with known deficiencies or disease states that promote deficiency.
There are a lot of vitamins so there is a lot to cover, but I’ll hit some of the highlights.
Of all the multiple potential links between vitamins and outcomes, only one — the link between multivitamin use and cancer — showed any signal of benefit.
That’s a bit frustrating since “multivitamin” can mean a lot of things. There were nine randomized trials evaluating “multivitamins” that, when combined, show this effect, but the specific types of multivitamin were diverse, ranging from a customized antioxidant cocktail to Centrum Silver. So no, I don’t know what multivitamin you should take.
To be honest, the effect is not even that impressive: a 7% relative reduction in the incidence of cancer. And relative risks really tend to overstate the effect size. In absolute terms, multivitamins reduced the incidence of cancer by around 0.2%. That means you’d need to treat 500 people with a multivitamin to avoid one case of cancer.
And although these studies didn’t specifically enroll patients with vitamin deficiencies, some of those enrolled might have had them. What we might be seeing is a small population effect based on the benefit accrued to a small number of people who were truly vitamin deficient.
And that’s really the best finding in the whole study if you’re a vitamin lover.
No analyses of individual vitamins — beta-carotene, vitamin A, vitamin E, vitamin D (with a whopping 32 randomized trials), and calcium supplements — showed significant benefit in terms of either cardiovascular disease or cancer. They just don’t seem to do much.
So, what makes the act of taking a vitamin so compelling? Why do so many of us, even knowing that the data don’t really support it, continue to pop a pill on a daily basis? I think there are a couple of reasons.
First, we need to acknowledge the fact that vitamins are generally pretty cheap and have a very low side-effect rate. They don’t make you dizzy or nauseated, tachycardic, or tired. They don’t feel like much of anything.
Given the low risk, something of a Pascal’s wager develops here. Sure, vitamins might not help, but they don’t seem to hurt, and so why not take them — just in case.
Well, the truth is they might actually hurt a little bit. The authors also analyzed the adverse events in all these vitamin trials, though to assess harms they also included observational studies. This may seem unfair — assessing benefit only with randomized trials but harms via randomized trials and observational studies. But I think it’s actually okay, given that the direction of bias in observational studies tends to favor vitamins given the “healthy-user effect.” This is the idea that people who choose to take vitamins tend to make other healthy lifestyle choices, so if you see a harm from taking a vitamin in the observational setting, you probably want to pay attention to it.
Notable findings for the harm analysis included evidence that vitamin A use might increase the risk for hip fracture, that vitamin E use might increase the risk for hemorrhagic stroke, and that vitamin C or calcium use might increase the risk for kidney stones.
Why are the observational data that show lower vitamin levels linked to worse outcomes so powerful, and the randomized trial data of supplementation so weak? This is classic confounding. Basically, healthier people have higher vitamin levels, and healthier people have less cardiovascular disease and cancer. Vitamin levels are a marker of overall health, not a driver of overall health.
But to be fair, there probably isn’t too much harm in taking that daily vitamin. We shouldn’t dismiss the ineffable value of ritual here. Taking a vitamin, though it is a small act, is nevertheless an act of self-care — a moment that we take for ourselves and ourselves alone — a commitment to try to be healthy. A brief moment of positivity in the morning may not reduce heart attacks or cancer rates, but it may have benefit nonetheless.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com.
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