Published: Dec 16, 2013
By Todd Neale, Senior Staff Writer, MedPage Today
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco
- A daily multivitamin failed to improve cognitive function in older men and did not reduce cardiovascular events in patients after a recent MI.
- Note that previously reported guidance from the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against vitamin and mineral supplementation for the primary prevention of cardiovascular disease or cancer in healthy adults.
A daily multivitamin failed to improve cognitive function in older men and did not reduce cardiovascular events in patients after a recent myocardial infarction (MI), two randomized trials showed.
In the first, there was no difference in the change in global cognitive function or in verbal memory between the multivitamin and placebo groups over an average follow-up of 8.5 years, reported Francine Grodstein, ScD, of Brigham and Women's Hospital in Boston, and colleagues.
And in the second, the rate of a composite endpoint that included total death, recurrent MI, stroke, coronary revascularization, or hospitalization for angina was 27% with a high-dose multivitamin and multimineral mixture and 30% with placebo (hazard ratio 0.89, 95% CI 0.75-1.07), reported Gervasio Lamas, MD, of Mount Sinai Medical Center in Miami Beach, Fla., and colleagues.
Both studies, as well as previously reported guidance from the U.S. Preventive Services Task Force that found insufficient evidence to recommend for or against vitamin and mineral supplementation for the primary prevention of cardiovascular disease or cancer in healthy adults, were published in the Annals of Internal Medicine.
"Other reviews and guidelines that have appraised the role of vitamin and mineral supplements in primary or secondary prevention of chronic disease have consistently found null results or possible harms," noted Eliseo Guallar, MD, DrPH, of the Johns Hopkins Bloomberg School of Public Health, and colleagues in an accompanying editorial.
Despite that, the percentage of Americans using multivitamin supplements and other dietary supplements has been growing, with a previous study showing an increase from 42% from 1988 to 1994 to 53% from 2003 to 2006.
"Evidence is sufficient to advise against routine supplementation, and we should translate null and negative findings into action," Guallar and colleagues 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 U.S. and in other countries," they added.
Effects on Cognition
To address inconclusive evidence about the effects of multivitamin supplements on cognitive health, Grodstein and colleagues examined the cognitive function substudy of the Physicians Health Study II (PHS II). Previous results from the trial showed that multivitamins modestly reduced the risk for cancer but did not cut cardiovascular events.
The substudy included 5,947 male physicians who were 65 or older (mean age 71.6). They were randomized to a daily multivitamin (Centrum Silver) or placebo and had their cognitive function assessed up to four times during follow-up.
The primary measure of cognitive function was a global composite score that included five tests of global cognition, verbal memory, and category fluency. Verbal memory was also examined separately as a secondary outcome.
Cognitive function was similar in the intervention and placebo groups at each assessment during the study, and there were no between-group differences in the changes in cognitive health over time.
For the global composite score, the difference in the change during follow-up with the multivitamin versus placebo was -0.01 standardized units (95% CI minus 0.04-0.02). Similarly, the difference in the change in verbal memory was not significant (-0.005 SU, 95% CI minus 0.04-0.03).
The lack of benefit was consistent across various subgroups.
"These data do not provide support for use of multivitamin supplements in the prevention of cognitive decline," Grodstein and colleagues wrote. "However, it is important to consider other health effects of multivitamin supplementation, including modest protection against overall cancer risk in the PHS II with long-term use and any potential effects on other important health outcomes yet to be evaluated."
They added that the effects of multivitamin supplementation in a less well-nourished population still need to be evaluated.
"This is of particular interest in an aging population because older persons are often at risk for nutritional deficiencies due to reduced micronutrient intake, altered absorption, and the metabolic requirements of vitamins," they wrote.
Effects of Cardiovascular Events
Lamas and colleagues reported the results of the multivitamin intervention included in the TACT trial. Prior results released from the trial demonstrated a slight, but significant benefit from chelation therapy for patients after an MI.
The trial, which was conducted at 134 centers in the U.S. and Canada, included 1,708 patients 50 or older (median age 65; 18% female) who had an MI at least 6 weeks before the study started (median interval 4.6 years) and who had serum creatinine levels of 2.0 mg/dL or lower. The patients were randomized to a 28-component high-dose multivitamin and multimineral mixture or placebo.
Median follow-up in the trial was 4.6 years and patients took their assigned treatments for a median of 31 months in the multivitamin group and 35 months in the placebo group.
A composite of cardiovascular events occurred at similar rates in the two groups, with no difference for the individual components or for cardiovascular death (5% versus 7%, HR 0.80, 95% CI 0.54-1.18).
A subgroup analysis suggested that the multivitamin intervention might have been beneficial for patients who were not taking a statin at baseline, although the patient numbers were small.
There was no evidence of harm from the intervention, with serious adverse events occurring in 15% of the multivitamin group and 12% of the placebo group.
Interpretation of the results is complicated, however, by the high rates of nonadherence (46% of patients in each group discontinued their treatment) and study withdrawal (17%), according to the researchers.
But for the editorialists, the message from accumulated evidence regarding dietary supplementation is clear.
"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," Guallar and colleagues wrote. "These vitamins should not be used for chronic disease prevention. Enough is enough."
The study by Grodstein and colleagues was supported by grants from the NIH and an investigator-initiated grant from BASF. Study agents and packaging were provided by BASF and Pfizer, and study packaging was provided by DSM Nutritional Products.
Grodstein reported receiving grants from the NIH. Her co-authors reported relationships with the NIH, BASF, Pfizer, DSM Nutritional Products, and Novartis.
The study by Lamas and colleagues was supported by grants from the National Heart, Lung and Blood Institute and the National Center for Complementary and Alternative Medicine.
Lamas reported relationships with the National Heart, Lung and Blood Institute, the National Center for Complementary and Alternative Medicine, the Patient Centered Outcomes Research Institute, the American Chiropractic Association, Healthwise, the University of Missouri-Kansas City, Kansas City University of Medicine and Bioscience, Quality Insights of Pennsylvania, Palmer College of Chiropractic, the U.S. Army, the U.S. Health Resources & Services Administration, Michigan State University, Prezacor, Boston University, the University of Ottawa, the NIH, Linkoping University, the University of Calgary, Eli Lilly, Medtronic, the Seattle Institute for Cardiac Research, and AstraZeneca.
Guallar reported that he had no conflicts of interest. One of his co-authors reported a relationship with Rubin/Anders Scientific. Another author reported working for Annals of Internal Medicine, a journal that has published systematic reviews and trials related to vitamins and mineral supplements.
Primary source: Annals of Internal Medicine
Source reference: Grodstein F, et al "Long-term multivitamin supplementation and cognitive function in men: the Physicians Health Study II" Ann Intern Med 2013; 159; DOI: 10.7326/0003-4819-159-12-201312170-00006.
Additional source: Annals of Internal Medicine
Source reference:Lamas G, et al "Oral high-dose vitamins and minerals after myocardial infarction: a randomized, controlled trial" Ann Intern Med 2013; 159; DOI: 10.7326/0003-4819-159-12-201312170-00004.
Additional source: Annals of Internal Medicine
Source reference:Guallar E, et al "Enough is enough: stop wasting money on vitamin and mineral supplements" Ann Intern Med 2013; 159: 850-851.