Multivitamins ineffective, not justified, studies conclude

Most multivitamin supplements are ineffective and do not prevent chronic disease or death, and their use is not justified, concluded 3 studies and an editorial in the Dec. 16 Annals of Internal Medicine.

In the first study, a substudy of The Physicians' Health Study II, long-term use of a daily multivitamin did nothing to slow cognitive decline among men 65 and older.

Researchers randomly assigned 5,947 male physicians aged 65 and older to take either a daily multivitamin or placebo for 12 years. After an initial cognitive assessment, the men were given an average of 5 tests of global cognition, verbal memory, and category fluency by telephone 3 more times at approximately 2, 6, and 10 years. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer's disease.

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 assessments. Specifically, the mean difference in cognitive change over follow-up was −0.01 standardized unit (SU) (95% CI, −0.04 to 0.02 SU) when treatment was compared with placebo. Similarly, cognitive performance did not differ between the multivitamin and placebo groups on the verbal memory score (mean difference in cognitive change over follow-up, −0.005 SU; 95% CI, −0.04 to 0.03 SU).

A second study found that high doses of multivitamins and minerals did not protect against secondary cardiovascular events in stable patients receiving appropriate care after myocardial infarction (MI).

Researchers at 134 U.S. and Canadian academic and clinical sites conducted a double-blind, placebo-controlled, 2×2 factorial, multicenter, randomized trial of 1,708 patients aged 50 years or older who had had an MI at least 6 weeks earlier and had serum creatinine levels of 176.8 µmol/L (2.0 mg/dL) or less. For a median of 31 months, patients were randomly assigned to an oral, 28-component, high-dose multivitamin and multimineral mixture or placebo with a primary end point of time to total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina.

The primary end point occurred in 230 (27%) patients in the vitamin group and 253 (30%) in the placebo group. The Kaplan–Meier 5-year event rate estimates were 34.2% for the vitamin group and 37.0% for the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.21). The composite of cardiovascular death, MI, or stroke occurred in 94 (11%) patients in the vitamin group and 115 (13%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.62 to 1.07; P=0.142).

Serious adverse events occurred in 124 (15%) vitamin recipients and 103 (12%) placebo recipients (difference, 3 percentage points; 95% CI, −0.7 to 5.7 percentage points). Adverse events included 12 (1.4%) incident neoplasms in the vitamin group and 11 (1.3%) in the placebo group (difference, 0.1 percentage point; 95% CI, −0.8 to 1.3 percentage points). No evidence suggested harm from vitamin therapy in any category of adverse events, although researchers cautioned that a considerable nonadherence and withdrawal rate limited the study's ability to draw firm conclusions, particularly about safety.

The third article was previously published online Nov. 12. A review by the U.S. Preventive Services Task Force of 26 studies (24 randomized, controlled trials and 2 cohort studies) examined the benefits and harms of using vitamin and mineral supplements for primary prevention of cardiovascular disease (CVD), cancer, or all-cause mortality in healthy individuals without known nutritional deficiencies. It found insufficient evidence that multivitamins prevent cancer, cardiovascular disease or death.

Two large trials (n=27,658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.94; 95% CI, 0.89 to 1.00). The study that included women showed no effect in them. 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.

Editorialists responding to the studies urged adults to stop using dietary supplements. First, the editorial stated, other reviews and guidelines have consistently found null results or possible harms from dietary supplements. Despite this, multivitamin supplement use among U.S. adults has been increasing.

The editorialists wrote, “The message is simple: Most supplements do not prevent chronic disease or death, their use is not justified, and they should be avoided. This message is especially true for the general population with no clear evidence of micronutrient deficiencies, who represent most supplement users in the United States and in other countries. ... Although available evidence does not rule out small benefits or harms or large benefits or harms in a small subgroup of the population, we believe that the case is closed—supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful. These vitamins should not be used for chronic disease prevention. Enough is enough.”