Based on a review of the evidence, the task force has recommended against the use of beta-carotene or vitamin E supplements for the prevention of CVD or cancer. This is a “D” recommendation, and applies to community-dwelling, nonpregnant adults. It does not apply to children, people who are pregnant or may become pregnant, or individuals who are chronically ill, are hospitalized or have a known nutritional deficiency.
The task force also issued a pair of “I” recommendations. It concluded that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta-carotene and vitamin E) or multivitamins for the prevention of CVD or cancer.
“Because heart disease and cancer are the two leading causes of death in the United States, we want to look at whether taking vitamins and minerals help prevent these important diseases,” said family physician Chyke Doubeni, M.D., M.P.H., a member of the task force, in a press release. “However, there is not enough evidence to know if taking vitamin, mineral and multivitamin supplements prevent these conditions, so the task force is calling for more research.”
When finalized, the recommendation will replace the task force’s 2014 recommendation statement on the topic. The 2014 statement also recommended against the use of beta-carotene or vitamin E supplements for the prevention of CVD disease or cancer, and found insufficient evidence to assess the balance of benefits and harms of single- or paired-nutrient supplements (except beta-carotene and vitamin E) or multivitamins for CVD or cancer prevention. The AAFP supported the 2014 recommendation statement.
To update the existing recommendation, the task force commissioned a systematic evidence review on the efficacy of supplementation with single nutrients, functionally related nutrient pairs or multivitamins for reducing the risk of CVD, cancer and mortality in the general adult population, as well as the harms of supplementation. Trials and systematic reviews published between January 2013 and Aug. 28, 2020, were evaluated for inclusion, as were all studies included in the task force’s prior review.
The review focused on community-dwelling nonpregnant adults without known CVD or chronic disease (other than hypertension, overweight or obesity) or nutritional deficiencies. A total of 78 studies were included.
Beta-carotene, with or without vitamin A, was associated with a 10% increased risk of cardiovascular mortality and a 20% increased risk of lung cancer. More specifically, the task force found increased cardiovascular mortality and increased risk of lung cancer in people who smoke or had workplace asbestos exposure associated with beta-carotene supplementation. Based on these findings, the task force concluded with moderate certainty that the harms of beta-carotene supplementation outweigh the benefits in the prevention of CVD or cancer.
The task force also found clear evidence that vitamin E, with or without vitamin C or selenium, offered no benefit in reducing the risk of all-cause mortality, CVD events or cancer. Evidence for the impact of multivitamins, vitamin A (without beta-carotene), vitamin C, calcium (without vitamin D) and selenium on all-cause mortality, CVD events and cancer was more ambiguous, and data was lacking for the task force to draw conclusions on the benefits or harms of any of the B vitamins, iron, zinc or magnesium.
In comparison, vitamin D, with or without calcium, was associated with a 12% lower risk of cancer mortality and a statistically non-significant 6% lower risk of all-cause mortality compared with placebo.
With regard to harms, the task found weak evidence that certain supplements increased the risk of some other serious harms, such as hip fracture (vitamin A), hemorrhagic stroke (vitamin E) and kidney stones (vitamin C, calcium). The task force also noted that several supplements were associated with an increased risk of minor adverse outcomes such as skin yellowing (beta-carotene) and gastrointestinal symptoms (calcium), but these outcomes could be reversed by discontinuing use.
The investigators also stated that additional studies are needed to address gaps in the current research. Specifically, the task force called for more studies to better understand the effects of vitamin, mineral and multivitamin supplementation on CVD and cancer outcomes; to determine the effects of vitamin D supplementation on cancer mortality; and to understand whether there is heterogeneity across specific populations or by baseline nutrient level in the effects of vitamin, mineral and multivitamin supplementation on CVD and cancer outcomes, especially in people with no known deficiencies and low prevalence of supplement use, and in diverse populations.
The task force has published several additional recommendations related to vitamin and mineral supplementation, addressing topics including
Corey Lyon, D.O., an associate professor in the Department of Family Medicine at the University of Colorado School of Medicine in Denver, said in an email to AAFP News that the evidence review presented some important findings for family physicians.
“The main message is we have a good idea of which vitamins or supplements cause harm, so when patients ask for advice on taking vitamins, we do have some answers for them,” said Lyon. “We are able to say with confidence that beta-carotene or vitamin E supplements are not beneficial, and actually can cause harm with an increase in cardiovascular and cancer risks.
“These recommendations help us understand what we know and what we still don’t have enough evidence to guide us,” Lyon added. “If patients ask, we can confidently advise against beta-carotene or vitamin E supplements. Then, since the evidence is lacking on other vitamins such as multivitamins, vitamin C, calcium and selenium on cardiovascular outcomes or all-cause mortality, individualized discussions with patients are important to discuss what we don’t know.”
As for having those discussions, Lyon said that he tries to talk with patients about topics where more information is available to help patients achieve the best health possible.
“Topics such as appropriate screening for hypertension, diabetes and cancer, and discussing healthy diet and physical activity, are more useful in cardiovascular disease and cancer prevention than the unknown benefits and risk of many of these supplements,” he said.
Lyon added that he hopes the findings will lead to more research in areas where information is lacking so that he and other clinicians can offer patients more guidance when discussing vitamins, dietary supplements and nutrition.
All comments will be considered as the task force prepares its final recommendation.