Evidence Still Lacking That Vitamins Prevent CVD, Cancer: USPSTF

June 21, 2022

There is not enough evidence to recommend for or against taking most vitamin and mineral supplements to prevent heart disease, stroke, and cancer, a new report by the United States Preventive Services Task Force (USPSTF) concludes.

However, there are two vitamins — vitamin E and beta-carotene — that the task force recommends against for the prevention of heart disease, stroke, and cancer. Evidence shows that there is no benefit to taking vitamin E and that beta-carotene can increase the risk for lung cancer in people already at risk, such as smokers and those with occupational exposure to asbestos, it notes.

These are the main findings of the USPSTF's final recommendation statement on vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer.

The statement is published in the June 21 issue of JAMA, along with an evidence report, editorial, and patient page.

"This is essentially the same recommendation that the task force made in 2014," USPSTF member John Wong, MD, professor of medicine at Tufts University School of Medicine, Boston, told theheart.org | Medscape Cardiology.

"We recognize that over half of people in the US take a vitamin supplement of some sort every day and 30% take a vitamin/mineral combination. We wanted to review the evidence again to see if there was any benefit in terms of reducing the risk of cardiovascular disease or cancer or increasing the chances of living longer," Wong explained.

"We looked hard for evidence, reviewing 84 studies in total. But we did not find sufficient evidence in favor of taking or not taking vitamins, with the two exceptions of beta-carotene and vitamin E, which we recommend against taking," he noted.

Although there is evidence of some harm with beta-carotene, the main reason behind the recommendation against taking vitamin E is the consistent evidence of no benefit, Wong explained.

"While the evidence for some other vitamins is conflicting, there is more consistent evidence of no benefit for vitamin E," he said.

The bulk of new evidence since the last review in 2014 was predominately for vitamin D supplementation, but despite the inclusion of 32 new randomized controlled trials and two cohort studies, pooled estimates for all-cause mortality were similar to those in the previous review, with confidence intervals only slightly crossing 1, and point estimates that suggest at most a very small benefit, the task force notes.

"Apart from beta-carotene and vitamin E, after reviewing 84 studies — including 78 randomized controlled trials — in over a million patients, we can find no clear demonstration of benefit or harm of taking vitamins in terms of developing cardiovascular disease or cancer or the effect on all-cause mortality. So, we don't know whether people should take vitamins or not, and we need more research," Wong added.

On the use of a multivitamin supplement, Wong noted that the complete body of evidence did not find any benefit of taking a multivitamin on cardiovascular or cancer mortality. But there was a small reduction in cancer incidence.

However, he pointed out that the three studies that suggested a reduction in cancer incidence all had issues regarding generalizability.

"The recently published COSMOS trial had an average follow-up of only 3.6 years, which isn't really long enough when thinking about the prevention of cancer, one of the other studies only used antioxidants, and the third study was conducted only in US male physicians. So those limitations regarding generalizability limited our confidence in making recommendations about multivitamins," Wong explained.  

But he noted that the task force did not find any significant harms from taking multivitamins.

"There are possible harms from taking high doses of vitamin A and vitamin D, but generally the doses contained in a multivitamin tablet are lower than these. But if the goal for taking a multivitamin is to lower your risk of cancer or cardiovascular disease, we didn't find sufficient evidence to be able to make a recommendation," he said.

Asked what he would say to all the people currently taking multivitamins, Wong responded that he would advise them to have a conversation with a trusted healthcare professional about their particular circumstances.

"Our statement has quite a narrow focus. It is directed toward community-dwelling, nonpregnant adults. This recommendation does not apply to children, persons who are pregnant or may become pregnant, or persons who are chronically ill, are hospitalized, or have a known nutritional deficiency," he commented.

"Any Benefit Likely to Be Small"

In an editorial accompanying the publication of the USPSTF statement, Jenny Jia, MD, Natalie Cameron, MD, and Jeffrey Linder, MD — all from the Northwestern University Feinberg School of Medicine, Chicago — note that the current evidence base includes 52 additional studies not available when the last USPSTF recommendation on this topic was published in 2014.

The editorialists point out that for multivitamins, proving the absence of a benefit is challenging, but at best, current evidence suggests that any potential benefits of a multivitamin to reduce mortality are likely to be small.

They give an example of a healthy 65-year-old woman with a 9-year estimated mortality risk of about 8%, and note that taking a multivitamin for 5 to 10 years might reduce her estimated mortality risk to 7.5% (based on an odds ratio of 0.94).

"In addition to showing small potential benefit, this estimate is based on imperfect evidence, is imprecise, and is highly sensitive to how the data are interpreted and analyzed," they say.

The editorialists recommend that lifestyle counseling to prevent chronic diseases should continue to focus on evidence-based approaches, including balanced diets that are high in fruits and vegetables and physical activity.

However, they add that healthy eating can be a challenge when the American industrialized food system does not prioritize health, and healthy foods tend to be more expensive, leading to access problems and food insecurity.

The editorialists suggest that rather than focusing money, time, and attention on supplements, it would be better to emphasize lower-risk, higher-benefit activities, such as getting exercise, maintaining a healthy weight, and avoiding smoking, in addition to following a healthful diet.

Possible Benefit for Older Adults?

Commenting on the USPSTF statement for theheart.org | Medscape Cardiology, JoAnn Manson, MD, chief, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, who led the recent COSMOS study, said that vitamin and mineral supplements should not be perceived as a substitute for a healthful diet.

"The emphasis needs to be on getting nutritional needs from a healthy diet that is high in plant-based and whole foods that don’t strip the vitamins and minerals through excessive processing," she said. "Although it's easier to pop a pill each day than to focus on healthful dietary patterns, the mixture of phytochemicals, fiber, and all the other nutrients in actual foods just can't be packaged into a pill. Also, vitamins and minerals tend to be better absorbed from food than from supplements and healthy foods can replace calories from less healthy foods, such as red meat and processed foods."

However, Manson noted that the evidence is mounting that taking a tablet containing moderate doses of a wide range of vitamins and minerals is safe and may actually have benefits for some people.

She pointed out that the COSMOS and COSMOS-Mind studies showed benefits of multivitamins in slowing cognitive decline in older adults, but the findings need to be replicated.  

"The USPSTF did see a statistically significant 7% reduction in cancer with multivitamins in their meta-analysis of four randomized trials and a borderline 6% reduction in all-cause mortality," she noted. "Plus, multivitamins have been shown to be quite safe in several large and long-term randomized trials. I agree the evidence is not sufficient to make a blanket recommendation for everyone to take multivitamins, but the evidence is mounting that this would be a prudent approach for many older adults," Manson said.

"Many people view multivitamins as a form of insurance, as a way to hedge their bets," she added. "Although this is a rational approach, especially for those who have concerns about the adequacy of their diet, it's important that this mindset not lead to complacency about following healthy lifestyle practices, including healthy eating, regular physical activity, not smoking, making sure that blood pressure and cholesterol levels are well controlled, and many other practices that critically important for health but are more challenging than simply popping a pill each day."

JAMA. 2022;327:2326-2333, 2334-2347, 2294-2295, 2364. Statement, Evidence report, Editorial, Patient page


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