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Vitamin D failed to stop COVID and other respiratory infections

Vitamin D supplements did not prevent COVID-19 or other respiratory infections, two randomized controlled trials showed.

Among 6,200 participants in a phase III study from United Kingdom2.6% of those in the control group developed COVID-19 compared to 3.6% of those given 800 IU of vitamin D daily (OR 1.39, 95% CI 0.98-1, 97) and 3.0% who received 3,200 IU daily (OR 1.13, 95% CI 0.78-1.63) during 6 months of follow-up, reported Adrian Martineau, PhD, of Queen Mary University of London , and his colleagues.

For other acute respiratory tract infections, 4.6% of participants in the control group developed at least one infection from any cause compared to 5.7% in the lowest dose group (OR 1.26 , 95% CI: 0.96-1.66) and 5.0% in the higher dose group group (OR 1.09, 95% CI 0.82-1.46).

In a second trial outside Norway which looked at daily supplementation with cod liver oil (which contains low doses of vitamin D, vitamin A, and omega-3 fatty acids) during the winter months, a similar proportion of participants who took the supplement or placebo for a median of 164 days tested positive for SARS-CoV-2 (1.31% vs. 1.32%; relative risk [RR] 1.00, 97% CI: 0.82-1.22), reported Arne Søraas, MD, PhD, of Oslo University Hospital, and colleagues.

Both studies were published in The BMJ.

“There is no strong evidence that nutritional supplements affect susceptibility to COVID-19,” Martineau said. medpage today in the email. “If people want protection, the most effective thing they can do is get vaccinated.”

UK researchers had previously found immunomodulatory effects “with 2 weekly large bolus doses” of vitamin D in patients with pulmonary tuberculosis. “These effects were largely anti-inflammatory, although in theory that could also be good for COVID-19 … we were reasonably optimistic that it would also show protection against COVID-19,” Martineau said.

in the accompanying editorialPeter Bergman, PhD, of the Karolinska Institute in Stockholm, noted that while observational studies have shown that patients with low vitamin D levels may be at risk for more severe COVID-19, “this association could be due to reverse causality.” or confusion.”

“Both COVID-19 and vitamin D deficiency are independently associated with obesity, older age (>65 years), and male gender,” he added.

These two new randomized trials add “much needed evidence to this important question,” he continued. While “both research teams are to be commended for completing large, well-designed clinical trials during the COVID-19 pandemic with its unforeseen logistical challenges,” most trial participants were healthy and a “highly effective vaccine” was deployed. effective”. during the trial.

Bergman also raised concerns about the effects that the vitamin A in cod liver oil may have had as an immunomodulator on vitamin D-mediated effects on the immune system.

As for the Norwegian researchers, they were “extremely disappointed,” Søraas said. medpage today in the email.

“The trial was a huge effort, especially from the 35,000 participants who took 5 ml of cod liver oil or placebo (corn) oil every morning for 6 months,” he noted. “This is a costly result in many ways. We, and our sponsor who produces cod liver oil, would of course have liked a different result, but when it turned out that way, we were pleased that it was so final.”

With nearly 8,000 respiratory infections in each of the cod liver oil and placebo groups, “we could have detected even minimal effects of vitamin D on those infections, but we didn’t,” he added. “This is contrary to many observational studies.”

“Our study is a very good example of how the results of observational studies need to be confirmed in randomized trials before anything can be recommended to everyone,” he said. “It’s not enough to have a good theory and some observations before saying that the entire population should take something.”

study details

For their study, Martineau and colleagues included 6,200 participants (median age 60.2, 67% women) who were not taking vitamin D supplements at the start of the study. Of the 2,674 participants with a blood 25-hydroxyvitamin D concentration <75 nmol/L, 1,328 were randomized to 800 IU of vitamin D per day and 1,346 were randomized to 3,200 IU of vitamin D per day; 2949 participants received placebo.

Apart from similar results for the primary outcome, no beneficial side effects were seen either. “We looked at related outcomes, including COVID-19 severity (that is, whether or not the illness precipitated hospital admission) and risk of prolonged COVID, but we didn’t see an effect on any of these outcomes,” Martineau said. .

The Norwegian study, which took place between November 2020 and June 2021, randomly assigned 34,601 participants (mean age 44.9, 64.5% women) who were not taking vitamin D supplements at baseline to 5 mL of essential oil. of cod liver or 5 ml of corn oil (placebo) every day for 6 months.

Four co-primary endpoints were predefined: a positive SARS-CoV-2 test determined by RT-PCR; Severe COVID-19 defined as self-reported dyspnea, hospital admission, or death; a negative SARS-CoV-2 test result; and self-reported symptoms.

Severe COVID-19 was identified in 0.70% of participants in the cod liver oil group and 0.58% in the placebo group (RR 1.20, 98.2% CI: 0 .87-1.65), while 49.46% and 49.44%, respectively, had one. or more negative SARS-CoV-2 test results (RR 1.00, 99.9% CI 0.97-1.04), and 22.94% and 22.13% reported one or more respiratory infections acute (RR 1.04, 99.9% CI 0.97-1.11).

Bergman pointed out that the COVID vaccination may have masked any effect of vitamin D in these studies, which was a limitation.

  • Ingrid Hein is a staff writer for MedPage Today, covering infectious diseases. She has been a medical reporter for over a decade. To follow


The UK study was supported by the Barts Charity, Pharma Nord, the Fischer Family Foundation, DSM Nutritional Products, the Exilarch Foundation, the Karl R Pfleger Foundation, the AIM Foundation, Synergy Biologics, Cytoplan, the National Institute for Clinical Research UK Health and Care. Research Network, HDR UK BREATHE Hub, UK Research and Innovation Industrial Strategy Challenge Fund, Thornton & Ross, Warburtons, Hyphens Pharma, and a personal donation from Matthew Isaacs (a philanthropist with no potential conflicting financial interests).

The Norwegian study was funded by Orkla Health AS, the manufacturer of Möller’s Tran, the cod liver oil used in the trial.

Bergman reported having lectured for Takeda on the subject of vaccination in patients with primary immunodeficiency.


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