Decoding the Mystery Multivitamins and the Aging Brain

Whenever I encounter a supposed practice or supplement that will save or ruin my brain, my first reaction is to roll my eyes – a modus operandi that I, unfortunately, developed in graduate school.

As published in the Lancet, it is expected that by 2050, over 152 million people will be living with dementia. Among these millions, there will be a portion of individuals who, being vulnerable, might resort to unorthodox, not to say fraudulent, therapeutic approaches to delay or 'prevent' cognitive decline — for example, increasing the consumption of grapes or following the advice of Dr. Lair Ribeiro – our Brazilian Joe Mercola.

If this weren't problematic enough, this situation could be further exacerbated by poor journalistic coverage that often uses sensationalist headlines to gain visibility.

However, this assertion does not hold for an article recently published in The New York Times discussing the latest iteration of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS). Researchers observed that adults aged 60 or older who consumed a multivitamin daily for two years demonstrated improved performance on cognitive and memory tests compared to their counterparts who received placebos.

However, before rushing to a pharmacy to purchase a multivitamin, it's important to consider certain aspects of the COSMOS research and its more recent iteration, the COSMOS-Clinic.

Cosmos And Its Children

The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) was a randomized, double-blind, placebo-controlled clinical trial that engaged 21,442 volunteers from the United States, comprising 12,666 women over 65 and 8,776 men over 60. On average, volunteers participated for 3.6 years, encompassing treatment and follow-up.

The primary goal of the research was to examine whether consuming a cocoa extract supplement containing 500mg of flavonoids or a multivitamin could lower the risk of heart disease, heart attack, cancer, or other significant health outcomes.

Neither of the interventions yielded statistically significant reductions in the risk of heart disease or cancer compared to the placebo.

Although the primary objective of the COSMOS research was to assess the impact on cardiovascular disease or cancer, the study also investigated whether the supplements could provide benefits in terms of memory and cognitive decline. This research became known as COSMOS-Mind and COSMOS-Web, two independent studies published in 2022 and 2023,

ACSH has already discussed both - you can access them here and here.

Another child - COSMOS-Clinic:

The most recent report from COSMOS, garnering significant attention in the tabloids, was published in January 2024.

Similar to its predecessor, this is a gold-standard clinical trial lasting for two years, with the participation of 573 individuals averaging 69.6 years of age. The majority were white, well-educated, and maintained a diet ranging from average to good, based on the parameters of the Alternative Healthy Eating Index (AHEI).

The study’s primary outcome was global cognition, evaluated through 11 in-person neuropsychological tests conducted over two years. [1] As a secondary outcome, the researchers emphasized episodic memory, “autobiographical memory” that recalls lived experiences and executive function, actions that require control and direction, such as planning or monitoring.

Compared to the placebo group, participants randomized to the multivitamin group exhibited a modest benefit in global cognition. Moreover, the study also revealed that multivitamin supplementation led to

  • a statistically significant favorable change in episodic memory
  • no significant effects on executive function

These findings were further confirmed by a meta-analysis involving more than 5,000 non-overlapping participants from the three COSMOS studies.

The magnitude of the effect? Two fewer years of cognitive aging compared to the placebo group or as they write:

 “clear evidence of the benefits of daily multivitamin use for both global cognition and memory in older individuals.”

It is noteworthy to mention the low ethnic diversity, which hinders the generalization of findings, and the uncertainty about which specific vitamins or minerals could account for the observed cognitive benefits. Additionally, it remains unclear whether similar benefits could be observed with other brands of multivitamins.

So, Does The Multivitamin Work?

As is often the case, the answer is more complicated than the optimistic conclusion suggests. Remarkably, both the methodological design and the meta-analysis were well-executed. However, delving into the details reveals relevant criticisms that provide context to the observed effects.

  • The effect was relatively modest
  • Multivitamins may be unnecessary for healthy individuals.

It’s possible, for example, that the gains were driven by people who weren’t previously consuming enough of certain nutrients important for brain health, such as vitamin B12, vitamin D and zinc.”

Dr. Hussein Yassine, Associate Professor of Neurology, Keck School of Medicine University of Southern California

This hypothesis appears much more plausible than an assumed cognitive improvement effect resulting from multivitamins. While the authors used the AHEI to assess the quality of participants' diets, they did not measure micronutrient levels in the blood. In other words, despite having a general idea of participants' dietary habits, it may not accurately reflect their actual nutrient levels. This problem is further compounded by response bias when individuals completing a questionnaire like the AHEI tend to exaggerate their consumption of foods they perceive as healthy, omit foods they consider unhealthy, or forget what they have consumed.

"Multivitamins can be useful for certain people, such as those with conditions that affect their ability to absorb nutrients, Dr. Cohen said, but most healthy people don’t need one."

– Dr. Pieter Cohen, Associate Professor of Medicine at Harvard Medical School.

Choosing traditional recommendations with robust scientific support - like maintaining a healthy diet, engaging in physical activity, managing healthy body weight, and avoiding smoking - is a much wiser approach than relying on a multivitamin.  


[1] Among these assessments were the Modified Mini-Mental State (3MS), Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) immediate total learning, delayed recall and recognition; immediate and delayed EBMT recall trials; two category fluency tests (naming animals and vegetables), among others.


Sources: Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050 Lancet Public Health. DOI: 10.1016/S2468-2667(21)00249-8. 

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial. The American Journal of Clinical Nutrition DOI: 10.1093/ajcn/nqac055

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS. The American Journal of Clinical Nutrition DOI: 10.1016/j.ajcnut.2023.12.011