India, March 16 -- Researchers at Mass General Brigham conducted one of the largest randomized trials to examine whether vitamin D supplementation could influence COVID-19 outcomes.
The findings showed that high-dose vitamin D3 did not reduce infection severity. However, the results suggested it may have a potential link to fewer long COVID symptoms, pointing to the need for further research.
"There's been tremendous interest in whether vitamin D supplements can be of benefit in COVID, and this is one of the largest and most rigorous randomized trials on the subject," said senior author JoAnn Manson, MD, DrPH, of the Mass General Brigham Department of Medicine. "While we didn't find that high-dose vitamin D reduced COVID severity or hospitalizations, we observed a promising signal for long COVID that merits additional research."
Vitamin D has long been hypothesized to support immune health. However, clinical evidence in the context of COVID-19 has remained mixed. The Vitamin D for COVID-19 (VIVID) Trial aimed to provide clarity by rigorously evaluating high-dose vitamin D3 supplementation among newly diagnosed COVID-19 patients and their household contacts.
Across the United States and Mongolia, 1,747 adults who had recently tested positive for COVID-19 and 277 household contacts were randomized to receive either daily vitamin D3 or a placebo.
Participants in the vitamin D group received 9,600 IU/day for two days followed by 3,200 IU/day. The supplementation continued for four weeks. The U.S. trial ran from December 2020 to September 2022, while the Mongolia trial was conducted from September 2021 to April 2022.
The median time between a positive COVID-19 test and starting supplementation or a placebo was three days.
Alongside Manson, lead authors Davaasambuu Ganmaa, Kaitlyn Cook and team used stratified randomization and statistical weighting. This ensured factors that can affect COVID-19 outcomes-including age, sex, body mass index, race/ethnicity, and vaccination status-were balanced between the groups.
Does Vitamin D Help Ease COVID-19 Symptoms?
The results showed that healthcare utilization rates did not differ between the vitamin D and placebo groups over the four-week study period. This included hospitalizations, clinic visits-both in-person and virtual-and emergency visits. The risk of death also remained similar between both groups.
Researchers also observed no significant difference in symptom severity between participants taking vitamin D and those receiving a placebo.
High-dose vitamin D supplementation did not reduce the rate at which household contacts contracted COVID-19 either.
Could Vitamin D Influence Long COVID Risk?
A deeper analysis revealed an interesting signal among participants who adhered to the vitamin D regimen. These individuals appeared less likely to experience long COVID symptoms at eight weeks compared to those taking placebo pills.
In the vitamin D group, 21% reported at least one persistent symptom. In the placebo group, the figure was 25%. The difference showed borderline statistical significance. "Long COVID, which can include symptoms of fatigue, shortness of breath, brain fog, other cognitive challenges, and more, continues to significantly impact people's lives," said Manson. "We hope to conduct further research in larger populations on whether long-term vitamin D supplementation reduces the risks and severity of long COVID."