USPSTF: No Evidence of CVD Benefit With Multivitamins

February 24, 2014

WASHINGTON, DC — The current clinical evidence is insufficient to assess the benefits and risks of taking multivitamins or single or paired nutrient supplements for the prevention of cardiovascular disease or cancer, according to a new statement by the United States Preventive Services Task Force (USPSTF). The evidence against the use of beta-carotene or vitamin E is stronger, however, and the agency said these supplements should not be used for preventing cardiovascular events or cancer.

"A critical gap in the evidence is the lack of studies of multivitamin combinations in groups generalizable to the US population," the USPSTF concludes. "Targeting research toward individuals who can be identified as high risk for nutrient deficiency rather than the general population may be more productive."

Published February 24, 2014 in the Annals of Internal Medicine and chaired by Dr Virginia Moyer (Baylor College of Medicine, Houston, TX), the vitamin review included four randomized, controlled trials and one cohort study of multivitamin supplementation. Although the trials varied with the nutrients and dosages, there was no effect on all-cause mortality and no effect on cardiovascular outcomes. One trial showed a borderline significant reduction in MI.

The reviewers also analyzed 24 studies of individual vitamins, minerals, or paired nutrients. As the USPSTF notes, "There was no evidence of beneficial effect on cardiovascular disease, cancer, or all-cause mortality. However, there are only a limited number of studies for most individual nutrients, and differences in study designs make it difficult to pool effects across supplements. Therefore, the USPSTF is not able to conclude there is no effect."

For beta-carotene and vitamin E, though, there is evidence sufficient to estimate the overall net benefit. Given the higher lung-cancer risk with beta-carotene in smokers, there is evidence of net harm, while "there is a large and consistent body of evidence" showing that vitamin-E supplements have no effect of cardiovascular disease, cancer, or all-cause mortality. The USPSTF concludes with "moderate certainty" the net benefit of vitamin-E supplementation is zero.

And regarding the use of minerals or multimineral combinations, the USPSTF makes similar recommendations.

Complex Pharmacology

Commenting on the USPSTF statement for heartwire , Dr Gervasio Lamas (Mount Sinai Medical Center, Miami Beach, FL) agreed with the conclusions of the reviewers and said their recommendations were fair, if a little cautious. He said numerous clinical trials with single vitamins, including vitamins A, C, D, and selenium have all been negative, or as is the case with vitamin A, have shown the potential to cause harm.

He pointed out, however, that multivitamin pharmacology is complex and it remains a difficult-to-study area of medicine. In contrast with these other vitamin and mineral studies, patients in the Trial to Assess Chelation Therapy (TACT) undergoing chelation were given large doses of oral vitamins and minerals, nearly all of which exceeded the daily recommended values. For example, 1200 mg of vitamin C, 25 000 IU of vitamin A, 400 IU of vitamin E, 200 mg of niacin, and 800 µg of folate were prescribed.

"These were vitamins used at levels far beyond what was needed to replete a nutritional deficiency," said Lamas, the lead investigator of TACT.

Given the hint of benefit at very large doses in TACT—there was a nonsignificant 11% reduction in the risk of cardiovascular outcomes—Lamas said other high-dose multivitamin and multimineral studies might be worth a second look. He said the pharmacologic properties of aspirin change when used at different doses. At 81 mg, aspirin is used an antiplatelet agent, at 650 mg as a treatment to reduce fever, and when 1 to 2 g per day are prescribed it can be used to treat rheumatoid arthritis.

That said, Lamas believes the recommendation to stay away from over-the-counter (OTC) multivitamins and multiminerals to reduce cardiovascular disease is a good one. He points out the multivitamin combination used in Centrum Silver (Pfizer) even failed to reduce the risk of MI, stroke, or cardiovascular mortality in one study, yet the company still advertises it as a heart-healthy supplement.

"Overall, this is a good statement from the USPSTF, but they don't have the advertising dollars of the vitamin industry," said Lamas.

In the US, spending on dietary supplements is a big business, with Americans spending $28.1 billion in 2010 alone. In fact, the USPSTF notes that surveys conducted by the vitamin industry have found that many physicians and nurses have recommended multivitamins to their patients for health and wellness.

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