Should You Take a Multivitamin-Mineral Supplement to Prevent Dementia

Let’s talk about the cosmos today. And cacao beans.

Rather than explore the nature of the universe in this post, we will discuss something slightly more understandable, The COSMOS trial, (Cocoa Supplement and Multivitamin1 Outcomes Study.)

The skeptical cardiologist has been casting aspersions on antioxidants and multivitamins for the last decade. In particular, he notes no high quality evidence that these heavily marketed products improve heart health or prevent heart attacks.

For coronary heart disease we have a broad array of safe and effective medications that can, if used optimally, eliminate heart attacks and strokes.

However, for the prevention of dementia and cancer, there are no equivalent pharmaceuticals.

We have lots of observational studies showing that increased physical activity/exercise, a healthy diet, higher sleep quality and lower stress are associated with a lower risk of dementia and cancer but it is unclear if optimizing these lifestyle components reduces cognitive decline or the development of dementia.

In fact, when the MIND diet, (developed from observational studies) was put to the test in a “gold-standard” RCT it failed miserably.

In addition, Americans surely know by now that they should be optimizing those 4 lifestyle variables for their overall health, happiness, and well-being.

Given this, background it is understandable why Americans are spending billions of dollars to buy nutraceuticals and supplements that claim to slow the cognitive decline associated with aging.

Since I have a family history of dementia and carry the apo E 3/4 phenotype I am particularly interested in ways to prevent or slow my mental decline.

I discussed my decision to take the Shingrix vaccine here. I’ve also decided to lower the evidence bar for chemicals I’ll consume that are very safe even if the evidence for effectiveness is of low quality.2

Which brings us to the COSMOS study.

The COSMOS Study: Cocoa and Multivitamins

Here is the Open-Evidence’s (vetted by the skeptical cardiologist) summary of the COSMOS trial

The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) was a large, randomized, double-blind, placebo-controlled trial (n = 21,442) that evaluated the effects of cocoa extract (500 mg flavanols/day) and a daily multivitamin-multimineral (MVM) supplement on cardiovascular disease (CVD), cancer, cognitive outcomes, and other aging-related endpoints in older adults.

And its summary of the key findings:

• Cocoa extract supplementation did not significantly reduce total cardiovascular events (HR 0.90, 95% CI 0.78–1.02), nor did it reduce the risk of type 2 diabetes or improve cognitive function over 2–3 years. However, there was a statistically significant reduction in CVD mortality (HR 0.73, 95% CI 0.54–0.98), but this was a secondary outcome and should be interpreted cautiously.^[1-3]

• Daily multivitamin-multimineral supplementation did not significantly reduce the incidence of total invasive cancer (HR 0.97, 95% CI 0.86–1.09), major site-specific cancers, total CVD, or all-cause mortality. There was a possible protective effect for lung cancer, but not for other cancer types.^[4-6]

• Cognitive outcomes: MVM supplementation was associated with modest but statistically significant benefits in global cognition and episodic memory, equivalent to delaying cognitive aging by approximately two years. Cocoa extract did not show cognitive benefit.^[7]

• Fracture risk: Neither cocoa extract nor MVM supplementation reduced the risk of clinical fractures in older adults.^[10]

These findings are consistent with the US Preventive Services Task Force (USPSTF) recommendation, which, based on COSMOS and other large trials, concludes that there is insufficient evidence to support routine use of multivitamin or cocoa flavanol supplementation for the primary prevention of CVD or cancer in the general adult population.^[5-6]

Wait a minute, you might be saying, If “MVM supplementation was associated with modest but statistically significant benefits in global cognition and episodic memory, equivalent to delaying cognitive aging by approximately two years” why shouldn’t doctors recommend them to our patients.

(You also may have noted that the cocoa extract lowered cardiovascular mortality by 27% but that is something that requires a deep cocoa dive which I shall have to take later in a post on chocolate and the heart.)

The COSMOS Trifecta

There are 3 published COSMOS MVM cognition trial papers. The first (COSMOS-MIND) was published in 2023 and analyzed the three-year follow-up of patients undergoing telephone evaluation of cognitive function.

The makers of Centrum Silver (the MVM used in COSMOS) were very happy to translate the results into marketing for us

and to trumpet the modest differences between their MVM and placebo.

Of note, cocoa-extract in all COSMOS studies had no effect on cognitive function or cancer risk.

COSMOS-WEB published in 2023 was a web-based RCT that measured ModRey, a 20-item word recall task measuring episodic memory. “The primary outcome measure was the number of words recalled immediately (immediate recall), which is related to hippocampal function. The secondary outcome measure was the ratio of words recalled after a delay to words recalled immediately (retention), which relates to entorhinal cortex function.

The authors concluded that

Daily multivitamin supplementation improved immediate recall memory after 1 year among older adults, above practice effects observed in a placebo group. Examining the change from baseline averaged over 3 years, the effect of multivitamin supplementation on memory was sustained over the 3 years of the COSMOS trial. In contrast, we found that multivitamin supplementation did not significantly affect memory retention, executive function, or novel object recognition.

The authors estimated that “the effect of the multivitamin intervention improved memory performance above placebo by the equivalent of 3.1 y of age-related memory change.”

COSMOS-CLINIC, published in 2024 looked at 573 COSMOS patients who underwent a detailed in -person neuropsychological evaluation.

It found a “modest benefit of MVM compared with placebo on global cognition over 2 years with a significantly more favorable change in episodic memory but not in executive function or attention [mean difference.

This paper also did a meta-analysis of all 3 COSMOS substudies and concluded there was clear evidence of MVM benefits on global cognition and episodic memory.

The authors estimated the magnitude of effect on global cognition was equivalent to reducing cognitive aging by 2 years.

Bottom-Line Conclusions

I asked Open Evidence “Should patients take a multivitamin to reduce cognitive decline based on the COSMOS study?”. Its full answer along with references is available here. It basically answered no:

Broader systematic reviews and guidelines, including those from the US Preventive Services Task Force and Cochrane, conclude that evidence remains insufficient to recommend multivitamin supplementation for prevention of cognitive decline or dementia in the general population, citing small effect sizes, short follow-up, and inconsistent results. The COSMOS findings are promising for cognitive outcomes, but longer-term and more diverse studies are needed before routine multivitamin use can be recommended solely for cognitive protection.

The reviews and guidelines it references were all published before COSMOS was published. Prior to COSMOS, we had one large negative trial so our estimate of prior probability that MVI could reduce cognitive decline was very low. It would be great if we got additional high-quality studies in this area to increase our confidence of a benefit.3

But if I’m going to intervene to stop my age-related cognitive decline I feel like now is the time.

Thus, after looking in detail at the COSMOS trifecta I have decided to hold my nose and start swallowing one of those giant Centrum Silver tablets every day.

Other claims for MVMs appear unsubstantiated. Centrum Silver makes these claims, two of which were disproven by COSMOS.

COSMOS did NOT find any evidence to support MVM for heart health or bone strength.

The quest for the fountain of brain youth shall continue in future posts with an analysis of cocoa and creatinine.

Cosmophilically Yours,

-ACP

1. From the COSMOS authors intro

Multivitamin-multimineral (MVM) formulations, which lack a universal definition but typically provide ≥100% of the recommended daily value of most essential vitamins and minerals , are the most common dietary supplement taken in the United States and other high-income countries. Approximately one-third of US adults report regular MVM use, with an even greater prevalence among older adults, women, and cancer survivors. Many US adults continue to take MVMs for general health and well-being or to reduce the risk of chronic diseases like cancer, cardiovascular disease and dementia despite inconsistency among observational studies examining long-term MVM use and risk of cancer and cardiovascular disease.

2. have started taking creatine, details forthcoming.

3 Large-scale trials testing broad-based MVMs on clinical outcomes remain limited to the Physicians’ Health Study (PHS) II of 14,641 men aged ≥50 y, for which a typical MVM had a modest, significant 8% reduction in total cancer but no effect on cardiovascular disease or dementia.