New data from the Cocoa Supplement and Multivitamin Outcomes Study (COSMOS) suggests that daily intake of a multivitamin supplement may contribute to preserving the aging brain. However, at least one expert has concerns regarding the methodology of the study and the interpretation of its results.
The meta-analysis of three separate cognition studies provides „strong and consistent evidence that daily intake of a multivitamin supplement containing more than 20 essential micronutrients can help prevent memory loss and slow cognitive aging,“ said study researcher Chirag Vyas, MBBS, MPH, from Massachusetts General Hospital and Harvard Medical School in Boston, as reported in Medical News from Medscape.
„We currently do not recommend the intake of multivitamins, but there is compelling evidence supporting the promise of multivitamins in preventing cognitive decline,“ said Vyas.
The new data from the cognitive sub-studies of COSMOS were published on January 18 online in the American Journal of Clinical Nutrition.
Clinically Significant Benefits?
To summarize, COSMOS was a 2 x 2 factorial trial with cocoa extract (500 mg flavanols per day) and/or a daily commercial multivitamin-mineral supplement (MVM) to prevent cardiovascular disease and cancer in more than 21,000 U.S. adults aged 60 and older.
Neither the cocoa extract nor the MVM supplement had a significant impact on cancer or cardiovascular disease.
COSMOS-Mind was a sub-study with 2,262 participants aged 65 or older without dementia who conducted telephonic cognitive assessments at the time of enrollment and annually over 3 years.
As reported by Medical News from Medscape, in COSMOS-Mind, there was no cognitive benefit from daily cocoa extract, but daily MVM supplementation was associated with an improvement in global cognition, episodic memory, and executive function. However, the difference in global cognitive function between MVM and placebo was small, with an average improvement of 0.07 points on the Z-score after 3 years.
COSMOS-Web was a sub-study with 3,562 original participants who were evaluated annually for three years using an internet-based battery of neuropsychological tests.
In this analysis, those taking the MVM supplement performed better on a test of immediate recall (remembering a list of 20 words), being able to remember an average of 0.71 additional words compared to 0.44 words in the placebo group. However, they did not show improvements on tests of memory retention, executive function, or novel object recognition.
The new data comes from COSMOS-Clinic, an analysis of 573 participants who conducted personal cognitive assessments over a 2-year period.
COSMOS-Clinic showed modest benefits of MVM compared to placebo in global cognition (mean difference 0.06 SD units) over the 2-year period, with a significantly favorable change in episodic memory (mean difference 0.12 SD units) but not executive function/attention (mean difference 0.04 SD units), the researchers reported.
They also conducted a meta-analysis based on the three separate cognitive sub-studies with 5,200 non-overlapping COSMOS participants. The results showed „clear evidence“ of MVM benefits in global cognition (mean difference 0.07 SD units; P = .0009) and episodic memory (mean difference 0.06 SD units; P = .0007). The extent of impact on global cognition corresponded to reducing cognitive aging by 2 years.
JoAnn Manson, MD, DrPH, head of the Division of Preventive Medicine at Brigham and Women’s Hospital, who led the entire COSMOS study, said in a statement, „The finding that daily multivitamin supplementation improved memory and slowed cognitive aging in three different placebo-controlled studies within COSMOS is exciting and supports the promise of multivitamins as a safe, accessible, and affordable approach to safeguarding cognitive health in older adults.“
In an interview with Medical News from Medscape, Christopher Labos, MD, CM, MSc, a cardiologist and epidemiologist based in Montreal, Canada, who was not involved in COSMOS, cautioned that the existing evidence on multivitamins for memory and brain health is „not all that impressive.“
Labos, a columnist for Medscape, and a previous author on the COSMOS study, said, „It is important to note that this ‚meta-analysis‘ of the COSMOS data is not strictly speaking a meta-analysis since the patients all came from the original COSMOS study without the inclusion of additional patients, so you don’t have any more data than you started with.“
„The fact that the results are consistent with the original study is not surprising. In fact, it would be concerning if they were not consistent, as it’s the same population, just assessed differently – by telephone, online, or in person,“ explained Labos.
„It is hard to say what the benefit of multivitamins actually means in terms of hard clinical endpoints that matter to patients. Doing a little better on a standardized test, I guess that’s a good thing, but does that mean you are less likely to get dementia? I’m not sure we are there yet,“ he told Medical News from Medscape.
The bottom line, according to Labos, is that „at this point in time, the evidence does not support the recommendation of multivitamins alone for brain health. Their use is also associated with costs and potential downsides.“
Claire Sexton, DPhil, director of scientific programs and public outreach at the Alzheimer’s Association, also commented on the new analyses from COSMOS, saying that there are now „large-scale, long-term positive studies showing that a multivitamin-mineral supplement is suitable for older adults.“ While adults may slow cognitive aging, the Alzheimer’s Association is not ready to recommend widespread use of a multivitamin supplement to reduce the risk of cognitive decline in older adults.
She noted that multivitamin supplements „are generally easy to find and relatively affordable. With confirmation, these promising results have the potential to significantly impact public health – improving brain health, reducing healthcare costs, lessening the burden on caregivers, particularly in older adults.“
The Alzheimer’s Association, she told Medscape, envisions a future where multiple treatments are available to address the disease in different ways – similar to heart disease and cancer – and can be combined with brain-healthy lifestyle guidelines such as nutrition and physical activity to create powerful combination therapies.
The Alzheimer’s Association is leading a two-year clinical trial called US POINTER to assess whether lifestyle interventions targeting multiple risk factors can protect cognition in older adults at increased risk for cognitive decline.
COSMOS-Clinic and the cognition studies in the meta-analysis were supported by investigator-initiated grants from Mars Edge, a segment of Mars Inc., and the National Institutes of Health. Multivitamin and placebo tablets and packaging were donated by Pfizer, Inc Consumer Healthcare (now Haleon). Disclosures for the COSMOS investigators are available in the original article. Labos and Sexton have no relevant disclosures.
Am J Clin Nutr. Online published January 18, 2024.