No Effect of Multivitamins on Cognition

December 17, 2013

Taking a daily multivitamin was not associated with cognitive benefits over a 12-year treatment period in male doctors aged 65 years or older in the large-scale Physicians' Health Study II (PHS II).

The study, published online December 17 in Annals of Internal Medicine, was conducted by a group led by Francine Grodstein, ScD, Brigham and Women's Hospital, Boston, Massachusetts.

"These data do not provide support for use of multivitamin supplements in the prevention of cognitive decline," the authors conclude. But they add that 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.

They also point out that all the participants in this study had a high level of education and were well nourished, and it might be that multivitamins have more benefits on cognition in those with less education and those with suboptimal nutritional status.

A separate analysis also published online December 17 shows no benefit of a high-dose regimen of 28 different vitamins and minerals given to stable patients with a history of myocardial infarction on their future risk for cardiovascular events.

In an accompanying editorial, an international group of experts led by Eliseo Guallar, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, say they believe that the case for multivitamin use is closed.

"Supplementing the diet of well-nourished adults with (most) mineral or vitamin supplements has no clear benefit and might even be harmful," they write. "These vitamins should not be used for chronic disease prevention. Enough is enough."

Theoretical Benefit

In the paper, Dr. Grodstein and colleagues explain that they wanted to test whether multivitamins would prevent cognitive decline due to observations that vitamins C, E, and β-carotene may protect the brain from oxidative damage. B vitamins are involved in the synthesis of neurotransmitters, DNA, and neuronal membrane and prevent accumulation of homocysteine, which is a risk factor for cognitive decline, and vitamin A plays a role in neuronal survival and synaptic plasticity in the hippocampus.

Previous trials have been inconsistent about potential benefits of multivitamin supplementation on cognitive health, with some finding no effect and others finding modest benefits. But all previous trials have had major limitations, including fairly short treatment durations and small sample sizes. The PHS II addressed these limitations.

The study had a double-blind, placebo-controlled, 2×2×2×2 factorial design, testing β-carotene, vitamin E, ascorbic acid, and a multivitamin (Centrum Silver, Pfizer) for the prevention of chronic diseases in 14,641 male physicians aged 50 years and older. Cognitive function was measured in a specified subgroup of 5947 participants aged 65 or older, with up to 4 repeated cognitive assessments by telephone interview completed for each individual over the 12-year study period.

The main outcome was a global composite score averaging 5 tests of global cognition, verbal memory, and category fluency. The secondary end point was a verbal memory score combining 4 tests of verbal memory, which is a strong predictor of Alzheimer disease.

Results from the β-carotene, vitamin E, and ascorbic acid groups have been reported previously. The current paper addresses the results of the multivitamin vs placebo comparison on cognitive function.

Results showed no difference in any of the cognitive endpoints over time.

Table. Mean Difference in Cognitive Decline Between Multivitamin and Placebo

Score Difference between Multivitamin and Placebo P Value
Global score –0.01 .53
Verbal memory score –0.005 .80
Telephone Interview for Cognitive Status 0.02 .79
Category fluency score –0.07 .59


Further Studies in Elderly and Nutrient-Deficient

The researchers suggest that further studies are needed to clarify whether multivitamin supplementation may be more beneficial in people with less optimal nutritional status or vitamin deficiencies. "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 say.

However, in their editorial, which looks at all the possible indications that have been investigated for multivitamins, Dr. Guallar and coauthors point out that other reviews and guidelines have consistently found null results or possible harms of vitamin and mineral supplements in primary or secondary prevention of chronic disease.

"Evidence involving tens of thousands of people randomly assigned in many clinical trials shows that β-carotene, vitamin E, and possibly high doses of vitamin A supplements increase mortality, and that other antioxidants, folic acid and B vitamins, and multivitamin supplements have no clear benefit."

Despite this, they note that use of multivitamin supplements increased among US adults from 30% between 1988 and 1994 to 39% between 2003 and 2006, and overall use of dietary supplements increased from 42% to 53%. Further, the US supplement industry continues to grow, reaching $28 billion in annual sales in 2010, with similar trends seen in Europe.

"The message is simple," they conclude. "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."

Ann Intern Med. Published online December 17, 2013. Abstract Abstract Editorial


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