Vitamin D supplements don’t cut COVID health care use, symptom severity, trial shows

COVID-19
Vitamin D gel caps

areeya_ann / iStock

While a randomized controlled trial of vitamin D3 supplementation in COVID-19 patients didn’t yield a significant reduction in monthly related health care use or disease severity, the authors say its role in reducing persistent symptoms warrants further study.

Mass General Brigham (MGB) researchers led the parallel two-group trial in adults in the United States and Mongolia, publishing the findings last week in The Journal of Nutrition. The US trial was conducted from December 2020 to September 2022, and the Mongolia trial ran from September 2021 to April 2022. 

Inconsistent findings from previous studies

A total of 1,747 index patients with a new COVID-19 diagnosis were cluster-randomized with 277 household contacts to receive either oral vitamin D3 (loading dose of 9,600 international units per day [IU/d] for two days, followed by 3,200 IU/d for a month) or a placebo. 

Participants completed weekly questionnaires on health care use (hospitalization, emergency department visits, and in-person or virtual clinic visits), symptom severity, long-COVID symptoms (index patients), and any new household-contact infections. The primary outcome was at least one health care visit (including hospitalization) or death within a month among index patients.

The median age of index patients was 38.0 years, 65.6% were women, 4.2% were Black, 4.8% were Hispanic, 43.2% were Asian, 44.3% were White, and 44.9% had vitamin D deficiency or insufficiency (less than 20 nanograms per milliliter). The characteristics of the household contacts were comparable.

“Though some small trials primarily done among highly-exposed healthcare workers or hospitalized patients have suggested prophylactic [preventive] or treatment benefits, concerns have been raised about randomization balance, and several larger trials have had null results,” the authors wrote. “Meta-analyses of randomized controlled trials (RCTs) have produced unclear findings, with some, but not all, suggesting clinical benefit from vitamin D.”

No reduction in household-contact infections

The median time between a positive COVID-19 test and the start of vitamin D3 supplementation or placebo was three days. The monthly cumulative incidence of health care use in index patients didn’t differ significantly between the 863 vitamin D3 and 884 placebo recipients (cumulative incidence, 0.28 vs 0.29, respectively; odds ratio [OR], 0.97). Likewise, supplementation didn’t lower the household-contact infection rate. 

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.

JoAnn Manson, MD, DrPH

Per-protocol analyses, however, suggested a nonsignificant trend toward a lower prevalence of long COVID at two months (OR, 0.78). Among vitamin D recipients, 21% reported at least one lingering symptom at that time point, compared with 25% in the placebo group, a difference of borderline statistical significance. No safety concerns were reported.

Vitamin D may help mitigate COVID-19 infection and its outcomes by boosting the immune system or through anti-inflammatory effects, the authors said. “Vitamin D metabolites are known to regulate adaptive immune response and possess anti-inflammatory effects; the metabolites suppress the production of proinflammatory cytokines while promoting the production of anti-inflammatory cytokines,” they wrote. 

In a news release, senior author JoAnn Manson, MD, DrPH, of MGB, said, “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. 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.”

This week's top reads

  1. Hantavirus outbreak grows to 11 cases, 9 confirmed

    So far no cases have been identified in anyone other than passengers on the Dutch cruise ship.

    Stephanie Soucheray

  2. Osterholm on hantavirus: We’re missing ‘main point of this outbreak’

    "Respiratory person-to-person transmission is not new with the Andes hantavirus," Osterholm points out.

    Stephanie Soucheray
    Mike Osterholm

  3. At least 8 sickened in suspected hantavirus outbreak; Andes strain confirmed

    Among the 8 suspected cases, only 3 have been confirmed by laboratory testing.

    Stephanie Soucheray
    princess cruise

  4. Cruise ship at center of hantavirus outbreak to dock in Spain Sunday

    Public health staff from the Centers for Disease Control and Prevention will meet passengers in Tenerife, Spain as they deboard a cruise ship that has been at the center of a hantavirus outbreak.

     

    Liz Szabo
    A cruise ship makes its way through the ocean.

  5. More hantavirus cases emerge as passengers debark cruise ship

    Among those who debarked yesterday are 18 Americans, 1 of whom has tested positive for the virus. 

    Stephanie Soucheray
    MV Hondius

  6. WHO officials on hantavirus cases: ‘This is an outbreak on a ship, not another COVID-19’

    US officials sought to reassure Americans that they are responding to the outbreak.

    Stephanie Soucheray
    cruise ships

  7. Cancer patients seek unproven antiparasitic treatments after actor's podcast appearance

    Study finds that prescriptions of ivermectin and benzimidazole surged in the first 6 months of 2025.

    Sarah Boden
    Ivermectin tablets seized by the Austrian Federal Ministry of Finance Customs agency.

  8. New research chips away at COVID-19 blood clot mystery

    Patients are at higher risk of heart attack and stroke if COVID spreads to the bloodstream, according to a new study. 

    Sarah Boden
    View of red blood cells traveling down a blood vessel toward a clot.

  9. CDC: Risk to general public from hantavirus is low

    A French patient’s condition worsened overnight.

    Stephanie Soucheray
    cleaning contamination

  10. Many older adults who died of COVID weren’t close to death before infection, study suggests

    In fact, 28% would likely have lived at least another 5 years if they hadn't contracted the virus. 

    Mary Van Beusekom

Our underwriters

Unrestricted financial support provided by

Become an Underwriter