Women Taking Vitamin Supplements May Have Slightly Lower Risk of SARS-CoV-2 Infection

A new observational study published in BMJ Nutrition has analyzed self-reported data from the COVID-19 Symptom Study on dietary supplement usage in the first wave of the COVID-19 pandemic. The results suggest a modest association between use of multivitamin, probiotic, omega-3 fatty acid or vitamin D supplements and lower risk of testing positive for SARS-CoV-2 in women. ¹

COVID-19 and supplements

Our knowledge of how SARS-CoV-2 virus behaves and how infection impacts the human body continues to evolve as we live through the global pandemic. Naturally, as our understanding has grown, scientists have explored various research avenues in the search for effective preventives and treatments against the virus. This has included pharmacological agents, such as chemically synthesized drugs, biopharmaceuticals, such as vaccines and antibody-based therapeutics and also multivitamins and supplements, such as vitamin D.

Micronutrients, dietary supplements and vitamins have become "buzzwords" that can have negative connotations due to their association with growing "wellness" trends. Endorsements of supplements – which lack rigorous scientific testing to support their use – by high-profile individuals and "influencers" has received much criticism.

However, there is some evidence to suggest that micronutrients may have a positive impact on our immune system, says Professor Sumantra Ray, executive director at the NeedPro Global Centre for Nutrition and Health: “We know that a range of micronutrients, including vitamin D, are essential for a healthy functioning immune system. This, in turn, is key to prevention of, and recovery from, infections." However, whether micronutrients reduce the likelihood or severity of COVID-19 infection specifically remains to be conclusively determined.

In spite of the uncertainty, the sales of multivitamins boomed in 2020, at least in the UK: market shares rose by 19.5% in the time period leading up to "lockdown number one" in March 2020. Specifically, sales of vitamin C increased by 110% and multivitamins by 93%.

Evidence to support any role for vitamins and minerals in preventing SARS-CoV-2 infection would need to be robust, and this means accounting for a number of different factors including ethnicity, occupational exposure to the virus and socioeconomic status, in a large number of people.

A collaborative research study involving the Department of Nutritional Sciences at King's College London has utilized self-report data from the COVID Symptom Study, an epidemiological research mobile app developed in the UK, to test the hypothesis that individuals taking dietary supplements were at a lower risk of testing positive for SARS-CoV-2.

The COVID Symptom Study

The COVID Symptom Study app was first launched in the UK on March 24 2020, before release in the US on March 29 and Sweden in April 2020. Initially, users were asked to self-report their location, age and health risk factors. Continued use required daily input regarding any symptoms users experienced, healthcare visits and SARS-CoV-2 test results. If users tested positive for the virus, they were asked to share whether they were self-quarantining or seeking healthcare interventions. If so, what was the level of intervention and what was the subsequent outcome?

From June 2, users were asked to retrospectively record whether they had been consuming any supplements regularly, which was defined as a period of over three weeks for a minimum of three months. In the study published in BMJ Nutrition, the researchers analyzed data that was collected on July 31.

Between the period of May-July, 175,652 UK app users reported that they regularly took dietary supplements, and 197,068 did not.

"We initially examined whether supplement use was associated with SARS-CoV-2 infection among 372,720 UK participants who reported having been tested for SARS-CoV-2 using a reverse transcriptase-PCR (RT-PCR) or serology-based test," the authors write in the paper.

Protective associations only in women

The study found that taking the following micronutrients and supplements were associated with a lower risk of SARS-CoV-2 infection by the respective percentages:

• Probiotics – 14%
  
  
• Omega-3 fatty acids – 12%
  
  
• Multivitamins – 13%
  
  
• Vitamin D – 9%
  
  

These percentages were determined after accounting for influential factors, such as underlying conditions and "typical" diet. The "protective" associations were observed in women of all ages and weight, but not in men.

The researchers then used data from 45,757 US and 27,373 Swedish app users that had also reported tests for SARS-CoV-2, to replicate the findings. The equivalent figures for the US and Sweden were:

• Probiotics ­– US (18%), Sweden (37%)
  
  
• Omega-3 fatty acids – US (21%), Sweden (16%)
  
  
• Multivitamins – US (12%), Sweden (22%)
  
  
• Vitamin D supplements – US (24%), Sweden (19%)
  
  

Limitations of the study

In a press release, the authors of the study emphasize that the work has a number of limitations and it is not recommended to take – or equally, to not take – the dietary supplements that were studied.

Firstly, the work is observational, meaning it cannot determine causation. These data do not prove that the studied supplements contributed to the fact certain individuals did not test positive for SARS-CoV-2. Kevin McConway, professor of applied statistics at The Open University, who was not involved in the study, explains, "The big problem with any study like this is that there will be a great number of other differences between people who take and don’t take a supplement, apart from the difference in supplement use. One or more of those other differences might have been the cause of the difference in the rate of testing positive, and not the supplements at all." Furthermore, the study collected self-reported data, which is susceptible to a range of biases and often is poor in validity. 

The next steps for this area of research, the study authors say, is randomized controlled trials of selected supplements to determine whether there is a causal relationship. "The randomness ensures that, on average, the two groups don’t differ at all except in whether they take the supplement or not, so if the infection rates did turn out to differ, it would be pretty clear that the difference was actually cause by the supplements," says McConway. There are trials of this kind underway already; for example The CORONAVIT trial.

However, McConway recognizes that this research area is challenging, and is cautious to say that randomized controlled trials will produce clear results: "The success of vaccinations, and other interventions, mean that infection rates are now pretty low. A trial to compare the infection rate in people who do and do not take supplements would have to be very large indeed, given that this study has indicated that the reductions in infection from using supplements are not likely to be very large, and given that you would need reasonably substantial numbers to become infected to estimate the size of the reduction properly."

Reference: Louca P, Murray B, Klaser K, et al. Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app. BMJ Nutrition. 2021:bmjnph-2021-000250. doi:10.1136/bmjnph-2021-000250.