The research found small but significant decreases in the risk of SARS-CoV-2 infection among females — but not males — who took multivitamins, vitamin D, omega-3 fatty acids, or probiotics.
Researchers at King’s College London, in the United Kingdom, analyzed data from 1.4 million users of the COVID Symptom Study app in the U.K., the United States, and Sweden. The participants answered questions about their regular use of dietary supplements.
The app users also reported results from COVID-19 tests and whether they had experienced symptoms of the illness.
“Our research is an observational study and not a clinical trial, so we can’t make strong recommendations based on the data we have,” cautions senior researcher Dr. Cristina Menni, of the School of Life Course Sciences, at King’s.
“Until we have further evidence about the role of supplements from randomized controlled trials, we recommend following the [National Health Service] guidelines on vitamin usage as part of a healthy, balanced diet,” she adds.
The study, which has not yet been peer-reviewed, has been uploaded to the preprint server MedRxiv.
Female immune defenses
The researchers were surprised to find that only females appeared to benefit from taking the four supplements in question.
They cite, however, several studies that have found that females have more robust immune systems, which may mean that their immune defenses get more of a boost from supplements.
Alternately, females may be more likely to wear masks or wash their hands than males, which could increase the apparent protective effects of taking supplements.
“These are interesting results, but due to the way the study has been conducted, these data absolutely cannot tell us that taking such supplements ‘protects’ against infection [resulting in] COVID-19,” says Naveed Sattar, a professor of metabolic medicine at the University of Glasgow, in the U.K., who was not involved in the research.
“It may be that by being more health-conscious, some women are less likely to become infected, so that it’s the behaviors that explain these results, not the supplements,” he hypothesizes.
Seif Shaheen, a professor of respiratory epidemiology at Queen Mary University of London, adds that the researchers had not accounted for factors such as income and educational attainment in their analysis.
“A major concern is that these findings may be confounded by socioeconomic status, given that individuals of higher status are more likely to take supplements and are also less likely to become infected with SARS-CoV-2,” he cautions.
The results in detail
Out of 327,720 users of the app in the U.K. who had each had a polymerase chain reaction or serology test for SARS-CoV-2, 175,652 reported having used supplements regularly since the beginning of the pandemic. The study sample was predominantly female, at 66.8%.
In total, 10,508, or 6.0%, of the supplement users had tested positive for the novel coronavirus, while 13,013, or 6.6%, of the nonusers had received positive results.
After the researchers had adjusted for other factors that could contribute to COVID-19 risk, they found that four supplements were associated with reduced risk.
Taking probiotics, multivitamins, omega-3 fatty acids, or vitamin D was associated with a 14%, 13%, 12%, and 9% lower risk of COVID-19.
Taking vitamin C, zinc, or garlic supplements was not associated with any reduced risk.
When the researchers broke down the numbers by sex, they found reduced risk associated with probiotics, multivitamins, omega-3 fatty acids, and vitamin D in females only.
After analyzing data from app users in the U.S. and Sweden, the researchers found similar associations between supplement use and confirmed SARS-CoV-2 infections.
Among the 993,365 regular users of the app worldwide who had not undergone testing, 126,556 had reported a loss of smell or taste. This suggests that they likely had COVID-19.
When the researchers analyzed data from these individuals, they found a small but significant reduction in risk among both males and females who regularly took omega-3 fatty acids, multivitamins, vitamin D, or probiotics.
Vitamin D uncertainties
During the ongoing pandemic, vitamin D has attracted a lot of media attention following the publication of studies suggesting that it may have a protective effect. The evidence to date has been mixed and inconclusive, however.
Meanwhile, the researchers behind the present study acknowledge several limitations. For example, all the participants were “self-selected.” They chose to download and use the app and so may not be representative of the general population.
In addition, the information that they provided may be inaccurate. For example, they may have started taking supplements after developing symptoms.
The authors emphasize that, as an observational study, their research cannot provide definitive proof that taking any supplement reduces the risk of COVID-19.
“Large randomized controlled trials of selected supplements testing their protective effects and also possible adverse effects on disease severity are required before any evidence-based recommendations can be made. We eagerly await the result of ongoing trials, including [those investigating] vitamin D and COVID risk.”