When COVID-19 disrupted research, a Mass General Brigham multivitamin study kept going

Few clinical trials have shown as much adaptability as COSMOS (COcoa Supplement and Multivitamin Outcomes Study), Mass General Brigham's nationwide study of multivitamins, cocoa extract and health.

The study of 20,000+ men aged 60 years and over and women aged 65 years or over was launched in the mid-2010s as a collaborative effort between investigators at Brigham and Women’s Hospital (BWH) and Fred Hutchinson Cancer Research Center. It is co-directed at BWH by JoAnn Manson, MD, MPH, DrPH, and Howard Sesso, ScD, MPH.

When the COVID-19 pandemic upended research efforts across the country in early 2020, the COSMOS team was still in the process of testing the effects of long-term use of a multivitamin and cocoa extract on risk of heart disease, stroke, and cancer. Rather than pause their work as the world shut down to limit the spread of infection, investigators continued the study while broadening its lens to consider a new question: Could taking a daily multivitamin help protect against COVID-19 or lessen its effects?

For Mass General Brigham scientists Jun Li, MD, PhD and co-director Sesso, the COSMOS trial offered a chance to test a timely hypothesis about multivitamin-mineral supplementation and COVID-19 in a randomized trial that had a large cohort already in place. Indeed, these participants had been receiving the intervention for 2.7 years—a crucial advantage during the COVID shutdown when ongoing research became more of a challenge. COSMOS was also a remote-based clinical trial, providing unique adaptability when in-person assessments were difficult to manage.

"To the credit of our research staff and investigators, we were able to continue collecting and analyzing data through questionnaires sent to COSMOS participants during the first year of the pandemic," says Li, an associate epidemiologist at Brigham and Women's Hospital and lead author of the new study summarizing the team’s findings, which were recently published in The American Journal of Clinical Nutrition.

The study found that older adults who received daily multivitamin supplements did not have a significantly lower risk of SARS-CoV-2 infection, but multivitamin supplements did show promise in lowering the odds of more symptomatic COVID-19, and reducing symptom burden.

Why the study matters now

The findings remain especially relevant today.

Multivitamins, which combine lower amounts of vitamins and minerals considered essential to a balanced diet, are the most common dietary supplement in the United States, with more than a third of adults reporting regular use.

Millions of Americans take multivitamins every day, often with the hope that they can support overall health and help prevent illness.

Prior clinical trials of dietary supplements and COVID-19 have focused on the potential therapeutic effects of high-dose vitamin D, vitamin C, and zinc among hospitalized patients. The results have been mixed.

COSMOS is the first study to examine the effects of long-term multivitamin supplementation on COVID-19 symptoms and risk in generally healthy older adults, a population that’s more vulnerable to severe viral infections. The trial began a few years before the pandemic, with participants randomized to a multivitamin or placebo.

During the pandemic, participants remained randomized to take a daily multivitamin containing more than 30 vitamins and minerals, including vitamin D, vitamin C, zinc, magnesium, and other micronutrients known to play important roles in immune function. The formulation included 1000 IU, or international units, of vitamin D, which has been studied for its role in immune response and possible modest reductions in acute respiratory infection.

What the researchers found

As the Mass General Brigham researchers reported in their published work, a daily multivitamin supplement did not significantly reduce COVID-19 incidence among older men and women in the study.

However, among participants who became infected, researchers observed an encouraging signal that those who consistently took their multivitamin appeared to experience fewer disease symptoms.

"While we didn't see a statistically significant effect of multivitamin use on COVID-19 risk, we did find important preliminary evidence that those taking the daily multivitamin reduced symptom burden," says Sesso, associate director of the Division of Preventive Medicine at Mass General Brigham and senior author of the study. "We now need to follow up on this promising signal with other randomized clinical trials."

For Li and Sesso, the study underscores the importance of rigorous clinical research, particularly when public interest in supplements is high. While multivitamins are often marketed as simple solutions for better health, studies like COSMOS help separate promise from proof, providing the evidence needed to guide informed decisions.

"It's an important reminder that while the messaging and advertising on many dietary supplements today might suggest major benefits, those claims are not always borne out by the clinical evidence," says Li.

To be sure, the findings underscore the importance of exercising caution when interpretating clams about dietary supplements, and of conducing randomized clinical trials like COSMOS to vigorously evaluate their health effects and provide reliable evidence to better inform public health.