A daily multivitamin improves cognitive function in the context of aging Original paper

In this 2-year randomized controlled study, daily multivitamin supplementation improved episodic memory, but not executive function or attention, in a cohort of older adults.

The effects of a multivitamin supplement on cognitive function.

The primary outcome was global cognition. The secondary outcomes were executive function/attention and episodic memory.

A total of 573 older adults (51% men, 49% women; average age of 70).

In this 2-year randomized controlled study, known as the COcoa Supplement and Multivitamin Outcomes Study or COSMOS, the participants received a multivitamin supplement (Centrum Silver) or a placebo daily.

Ingredients in the multivitamin

Global cognition was examined at baseline and at an average follow-up of 2 years using 11 neuropsychological tests: Modified Mini-Mental State; Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) immediate total learning, delayed recall, and recognition; East Boston Memory Test (EBMT) immediate and delayed recall; 2 category fluency tests; Trail Making Tests (TMT) A and B; and Digit Span Backwards. Episodic memory was examined using 4 tests: EBMT immediate and delayed recall, and CERAD immediate total learning and delayed recall. Executive function and attention were examined using 5 tests: 2 category fluency tests, TMT A and B, and Digit Span Backwards.

Global cognition improved in the multivitamin group compared to the placebo group at 2 years, but this difference was not statistically significant.

Episodic memory improved in the multivitamin group compared to the placebo group, but executive function and attention scores weren’t different between groups at the end of the study.

In a meta-analysis that included the results of COSMOS substudies (including the current study, called COSMOS-Mind), multivitamin supplementation improved global cognition and episodic memory compared to the placebo. These analyses included data from two substudies (2,731 participants) for global cognition and 3 substudies (5,203 participants) for episodic memory.

Effects of a daily multivitamin vs. placebo on global cognition, episodic memory, and executive function/attention in COSMOS-Mind

COSMOS was a large, randomized controlled study designed to test whether a cocoa extract supplement and a multivitamin-mineral supplement can reduce the risk of cardiovascular disease and cancer. The study comprised 21,442 participants from the U.S. who did not have self-reported cardiovascular disease or cancer at baseline.^[1] In addition to the outcomes related to cardiovascular disease and cancer, COSMOS also included assessments of cognitive function. The results on the effects of the multivitamin supplement on cognitive function in substudies of COSMOS have since been published.

The substudy COSMOS-Mind administered annual telephone-based cognitive assessments to 2,262 participants for 3 years, during which they took a multivitamin-mineral supplement, cocoa extract, or a placebo. Compared to the placebo, a daily multivitamin — but not cocoa extract — had a statistically significant benefit on global cognition that was most pronounced in participants with a history of cardiovascular disease. The multivitamin supplement also improved memory and executive function.^[2]

Another substudy, COSMOS-Web, administered annual computer-based cognitive assessments to 3,562 older adults for 3 years. The study included only the participants who received the multivitamin supplement or the placebo. The participants who received the multivitamin supplement had better memory at 1 year and during 3 years of follow-up. However, multivitamin supplementation did not affect episodic memory, object recognition, or executive function.^[3]

The only other long-term multivitamin supplementation study — one that wasn’t part of COSMOS — is the Physicians’ Health Study II (PHS-II). PHS-II was a randomized controlled study that included 5,947 male physicians ages 65 and older who received a placebo or a multivitamin supplement for 12 years. Over the course of the study, each participant completed up to 4 cognitive assessments. In contrast to some of the findings from COSMOS, there were no differences in average cognitive performance or memory between the multivitamin and placebo groups at any time point during the 12-year study.^[4]

It’s difficult to say why the results of the PHS-II don’t align with those from COSMOS, but it could have something to do with the study design — 2–3 years in COSMOS compared to 12 years in the PHS-II. In addition, PHS-II only recruited men, whereas COSMOS recruited men and women.

The changes in cognitive outcomes are clinically relevant. Because age is the strongest predictor of cognitive decline, the researchers compared the changes in cognition with multivitamin-mineral supplementation to the estimated change in cognition that might be expected to occur due to aging. Put another way, how much cognitive decline did the multivitamin-mineral supplement prevent during the 2-year study? It was estimated that 2 years of supplementation was equivalent to 4.8 years less aging for episodic memory, but no benefit was observed for executive function or attention.

A similar estimate was conducted for the meta-analysis, revealing that the benefits of multivitamin supplementation on global cognition were equivalent to 2 fewer years of cognitive aging.

Unfortunately, it’s not clear which specific vitamin(s) or mineral(s) in the supplement were responsible for the cognitive benefits in this study. Was it the vitamin D? Was it the zinc? Maybe lutein or lycopene deserves the credit? For now, it’s impossible to say — taking a multivitamin-mineral supplement similar to the one in the study could be beneficial due to any or all of its components. The good news is that multivitamins (in the correct dose) don’t appear to have much downside — there weren’t any supplement-related side effects reported in COSMOS.

Multivitamins are often criticized for having little benefit, and are sometimes called a waste of money, but COSMOS indicates that this may not be true. A one-a-day might provide nutritional insurance and also a brain boost.

COSMOS received partial funding from Mars (who manufactures the cocoa extract supplement used in the study) and Haleon (who manufactures the Centrum Silver multivitamin-mineral supplement used in the study).

Analyses regarding the study’s secondary outcomes (i.e., episodic memory, executive function and attention) were not adjusted for multiple comparisons, so these findings should be considered exploratory.

Several other results from COSMOS, including the effect of cocoa extract on cardiovascular disease risk, the effect of a multivitamin on both cardiovascular disease and cancer risk, and the effect of cocoa extract on the risk of type 2 diabetes have been previously covered in Study Summaries.