Vitamin D, Multivits, Probiotics and Omega-3 Reduce COVID in Women, Not Men

Becky McCall

April 20, 2021

Probiotics, omega-3 fatty acids, multivitamin or vitamin D supplements are associated with reduced risk of coronavirus infection in women but not men, while vitamin C, garlic and zinc show no clear benefit in either, according to the latest findings from users of the COVID-19 Symptom Study app.

The study is the largest observational study of SARS-CoV-2 infection and dietary supplement use to date, drawing on data from more than 400,000 app users from the UK, US, and Sweden. Similar results were found across all three countries and are published today in the journal BMJ Nutrition Prevention and Health.

Cristina Menni, PhD, specialises in gut microbiome and metabolomics at the Department of Twin Research and Genetic Epidemiology, King's College London, and led the study. "We had a very big sample size looking at the correlation between the supplements and COVID-19, and found that vitamin D, probiotics, multivitamins, and omega-3 show a modest reduction in the chances of catching COVID-19," she told Medscape News UK in an interview.

"We can’t make a recommendation based on this alone, but it does however lay the foundations for a larger randomised controlled trial."

Dr Menni adjusted results for diet, which naturally might affect the outcome. However, "it seems the effect of multivitamins, vitamin D, omega-3 is completely independent of diet. The association with probiotics after adjustment remains, but the effect is smaller," she explained.

The risk reduction remained in women across all ages and body mass index (BMI) groups for probiotics, omega-3 fatty acids, multivitamins, and vitamin D. For probiotics the odds ratio (OR) ranged from 0.73 (95%CI: 0.63 to 0.85) in women under 40 years; to OR 0.91 (95%CI 0.86 to 0.96) for vitamin D in women aged 40-60 years.

"We found women to have higher protection," Dr Menni reported. "But women are usually the ones buying supplements for the family, and usually the ones taking them."

Surge in Sales of Multivitamins, Vitamin C and Zinc Since Pandemic

Sales records show a surge in uptake of vitamin supplements with UK market shares of vitamin C increasing by 110% and those of multivitamins by 93% in the period leading up to the first lockdown (March 2020).

In the US, zinc supplement sales rose by 415% in the first week of March, at the height of COVID-19 fears there. Given such a surge in use of supplements, the researchers wanted to find out whether these high sales were justified by their effect on testing positive for SARS-CoV-2 infection.

However, "based on these results we don’t suggest people run to the pharmacy," said Dr Menni.  

The finding on vitamin C, showing no effect on infection rates, might possibly be related to behavioural patterns of consumption, added Dr Menni. "Possibly, people start taking vitamin C when they are already sick rather than routinely, everyday. The pattern of taking vitamin C is different to that of taking vitamin D or multivitamins."

Behavioural factors, specifically health-related ones, might also have an impact on findings. "It’s true that we found that vitamin D, multivitamins, probiotics, and omega-3 reduce the chances of catching COVID-19, but there could be a healthy-user bias in that the people reporting on the app are more health-conscious."

COVID-19 Symptom Study App Provided Data

Data were drawn from the COVID-19 Symptom Study app that collects self-reported information related to SARS-CoV-2 infection including location, age, core health risk factors, daily updates on symptoms, healthcare visits, SARS-CoV-2 test results, self-quarantining, and any healthcare sought. Asymptomatic individuals also used the app. A total of 372,720 users in the UK, 45,757 from the US, and 27,373 from Sweden contributed their data to the app.

Information analysed in this study concerned app users, aged 16–90 years, who regularly (>three times a week for at least 3 months) used dietary supplements throughout May, June, and July 2020 (the first wave of the pandemic), as well as data on any coronavirus swab test results (confirmed by PCR test). Users were asked to self-complete a questionnaire asking about their use of probiotics, garlic, omega-3 fatty acids, multivitamins, vitamin D, vitamin C, and zinc, or if they did not take supplements. The control group comprised users not taking any supplements.

Data were adjusted for age, sex, BMI and health status at sign-up, comorbidities (including type 2 diabetes, cancer, asthma, heart disease, eczema, hay fever, kidney disease and lung disease), index of multiple deprivation (IMD), smoking, ethnicity, health worker/carer status and diet quality.

Modest Protective Effect Overall

Dr Menni and colleagues found that during the first wave, 175,652 UK subscribers regularly took dietary supplements, and 197,068 did not. In total 67% of people taking supplements were women and over half were overweight (average BMI of 27). In all, 23,521 people tested positive for SARS-CoV-2 and 349,199 tested negative over the 3 months.

In UK users specifically, those taking probiotics, omega-3 fatty acids, multivitamins or vitamin D had a lower risk of SARS-CoV-2 infection by 14% (95% CI (8% to 19%)), 12% (95% CI (8% to 16%)), 13% (95% CI (10% to 16%)) and 9% (95% CI (6% to 12%)) respectively, after adjusting for potential confounders.

The risk reduction in testing positive for SARS-CoV-2 with use of omega-3 fatty acids was 21% in the US cohort and 16% in the Swedish cohort. Probiotics modestly protected from infection with a risk reduction of 18% in the US cohort, and 37% in the Swedish data.

With multivitamins, risk for SARS-CoV-2 was reduced by 12% in the US cohort and 22% in the Swedish cohort. With vitamin D, the risk reduction was 24% and 19%, respectively.

Probiotics Improve Gut Microbiome and Boosts Immunity

Commenting on the modest effect of probiotics on risk reduction, Dr Menni said that a healthy diet might have had a confounding effect on the association found.

"A recent study linked the gut microbiome with the immune response in COVID-19 and we also know that the severity of COVID-19 is associated with the gut microbiome."

Regarding probiotics, these improve the diversity of the microbiome, which is good for the immune system and as such, an individual is less likely to get sick, she added.  

"The finding on probiotics opens a lot of potential avenues of research and supports a clinical trial of probiotics."

Professor Sumantra Ray, executive director, NNEdPro Global Centre for Nutrition and Health, which co-owns the journal, commented on the findings. "To date, there is little convincing evidence that taking nutritional supplements has any therapeutic value beyond maintaining the body’s normal immune response.

"What's more, this study wasn't primarily designed to answer questions about the role of nutritional supplements in COVID-19."

The researchers recognise that it is an emerging area of research and warrants further rigorous study including RCTs, investigating possible protective effects on infection and disease severity, as well as adverse effects, before firm conclusions can be drawn about the role of nutritional supplements in preventing infection with SARS-CoV2. They also note that the study relied on self-reported data and a self-selected group. No information was collected on supplement doses or ingredients either.

COI: Dr Menni declares no conflicts of interest. Other authors list a range of interest on the paper.

Published in the 19 April edition of the journal BMJ Nutrition Prevention and Health

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