Summary: The debate over Vitamin D’s role in the pandemic has reached a major milestone with the VIVID Trial, one of the largest and most rigorous randomized studies to date. Researchers found that while high-dose Vitamin D3 supplements did not reduce the severity of acute COVID-19 infections or prevent hospitalization, they revealed a significant “signal” for preventing Long COVID.
Participants who strictly adhered to the Vitamin D regimen were less likely to report persistent symptoms like brain fog, fatigue, and cognitive challenges eight weeks after infection. The findings suggest that while Vitamin D isn’t a “cure” for the initial virus, it may play a critical role in how the brain and body recover long-term.
Key Facts
- No Acute Impact: High-dose Vitamin D3 (3,200 IU/day) did not lower the risk of hospitalization, death, or symptom severity during the first four weeks of infection.
- Long COVID Signal: Among those who followed the regimen, only 21% reported persistent symptoms at eight weeks, compared to 25% in the placebo group—a promising reduction for neurological and physical recovery.
- Rigorous Testing: The study involved 1,747 COVID-positive adults across the U.S. and Mongolia, using stratified randomization to account for vaccination status, BMI, and age.
Source: Mass General
In a large, randomized trial, researchers at Mass General Brigham have found that high-dose vitamin D3 did not reduce COVID-19 infection severity, but may impact long COVID outcomes.
Results of the study are published in The Journal of Nutrition.
“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 been hypothesized to boost immune health, but clinical evidence in the context of COVID-19 has been 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 (9,600 IU/day for two days followed by 3,200 IU/day) or daily placebo for four weeks.
The U.S. trial was conducted from December 2020 to September 2022 while the Mongolia trial ran from September 2021 to April 2022. The median time between the participants’ positive COVID-19 tests and the initiation of vitamin D supplementation or placebo was three days.
Alongside Manson, lead authors Davaasambuu Ganmaa, Kaitlyn Cook and team used stratified randomization and statistical weighting to ensure factors that can affect COVID-19 outcomes (including age, sex, body mass index, race/ethnicity and COVID-19 vaccination status) were balanced between the two groups.
The rate of healthcare utilization (including hospitalizations, in-person or virtual clinic visits, and emergency visits) or death did not differ between the vitamin D and placebo groups over a four-week period. Similarly, no significant differences were found in symptom severity. Taking high-dose vitamin D also didn’t reduce the rate at which household contacts contracted COVID-19.
However, an analysis of the participants who adhered to the vitamin D regimen demonstrated a signal that they were less likely to experience long COVID symptoms at eight weeks than those who took placebo pills. In the vitamin D group, 21% reported at least one persistent symptom, compared to 25% in the placebo group, a difference of 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.”
Authorship: In addition to Manson and Ganmaa, Mass General Brigham authors include Allison Clar, Michael Rueschman, Aditi Hazra, Howard D. Sesso, Valerie E. Stone, Patricia Copeland and Georgina Friedenberg. Additional authors include Cook, Polyna Khudyakov, Dorjbal Enkhjargal, Tsolmon Bilegtsaikhan, Kenneth H. Mayer, Raji Balasubramanian, Douglas C. Smith, Quanhong Lei, Todd Lee, Emily G. McDonald, Tserenkhuu Enkhtsetseg, Erdenebaatar Sumiya, Yansanjav Narankhuu, Myagmarsuren Erdenetuya, Dalkh Tserendagva, Rikard Landberg, Niclas Roxhed and Susanne Rautiainen.
Disclosures: Roxhed is a founder and shareholder of Capitainer AB, a company commercializing the blood collection devices used in this study. All other authors declare no conflicts of interests.
Funding: The study received anonymous foundation support and philanthropic support from Jon Sabes of Minneapolis, Minn. The authors also acknowledge support from the Tishcon Corporation, which donated the vitamin D and placebo study capsules; Takeda; and Capitainer cards. The authors have not declared a specific grant for this research from any funding agency in the public, commercial or nonprofit sectors.
Key Questions Answered:
A: The “immune boost” theory didn’t hold up for the initial fight. In this study, Vitamin D didn’t stop people from getting infected, and it didn’t keep them out of the hospital once they were sick. However, it seems to help with the “cleanup” after the battle is over, potentially preventing the lingering inflammation that leads to Long COVID.
A: It’s looking that way. Brain fog and cognitive fatigue are major hallmarks of Long COVID. While the study calls for more research, the data showed that people taking the supplements had fewer persistent cognitive and physical symptoms two months later. It might act as a neuroprotective buffer during the recovery phase.
A: The study used 3,200 IU/day, which is higher than the standard daily allowance but was administered under medical observation. While the results are promising, the researchers emphasize that this is a “signal” that needs further testing in even larger populations before it becomes a standard clinical recommendation for Long COVID prevention.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this cognitive decline and long-COVID research news
Author: Alexandra Pantano
Source: Mass General
Contact: Alexandra Pantano – Mass General
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The VIVID Trial” by Davaasambuu Ganmaa, Kaitlyn A. Cook, Polyna Khudyakov, Dorjbal Enkhjargal, Tsolmon Bilegtsaikhan, Kenneth H. Mayer, Allison Clar, Michael Rueschman, Raji Balasubramanian, Aditi Hazra, Howard D. Sesso, Valerie E. Stone, Patricia Copeland, Georgina Friedenberg, Douglas C. Smith, Quanhong Lei, Todd Lee, Emily G. McDonald, Tserenkhuu Enkhtsetseg, Erdenebaatar Sumiya, Yansanjav Narankhuu, Myagmarsuren Erdenetuya, Dalkh Tserendagva, Rikard Landberg, Niclas Roxhed, Susanne Rautiainen Lagerström, and JoAnn E. Manson. Journal of Nutrition
DOI:10.1016/j.tjnut.2026.101398
Abstract
A Randomized Trial of Vitamin D Supplementation and COVID-19 Clinical Outcomes and Long COVID: The VIVID Trial
Background
Data from randomized controlled trials of vitamin D3 supplementation in modifying the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse.
Objectives
We evaluated the effect of vitamin D3 supplementation on healthcare utilization and other clinical outcomes among adults with coronavirus disease 2019 (COVID-19) and their close contacts.
Methods
We conducted a parallel 2-group randomized controlled double-blinded trial targeting free-living adults in the United States and Mongolia. Index participants with newly diagnosed COVID-19 were cluster-randomized with up to one of their cohabiting contacts either to an oral vitamin D3 loading dose of 9600 IU/d for 2 d followed by 3200 IU/d for 4 wk or to placebo. Participants completed weekly questionnaires on healthcare utilization, disease severity, and long COVID (index participants) or new SARS-CoV-2 infection (household contacts). The primary outcome was ≥1 healthcare visits (including hospitalization) or death within 4 wk among the index participants.
Results
Index participants (n = 1747) were a median of 38.0 y old (IQR: 31.1–47.0), 65.6% female/other sex, 4.2% Black non-Hispanic, 4.8% Hispanic/Latinx, 43.2% Asian, 44.3% non-Hispanic White, and 44.9% vitamin D deficient or insufficient (25-hydroxyvitamin D3 <20 ng/mL). Baseline characteristics for the household contacts (n = 277) were similar.
The 4-wk cumulative incidence of healthcare utilization in index participants did not significantly differ between the vitamin D3 (n = 863) and placebo (n = 884) groups [cumulative incidences, 0.28 compared with 0.29; odds ratio (OR), 0.97; 95% confidence interval (CI): 0.75, 1.24]. Similar nonsignificant results were observed for the prespecified secondary treatment and prevention outcomes, though per-protocol analyses showed a nonsignificant trend toward benefit of vitamin D3 on the prevalence of long COVID at 8 wk (OR, 0.78; 95% CI: 0.59, 1.03). No safety concerns were identified.
Conclusions
Among adults with newly diagnosed SARS-CoV-2 infections, vitamin D3 supplementation did not significantly change the 4-wk cumulative incidence of healthcare utilization or COVID-19-related outcomes compared with placebo. Promising results for long COVID warrant further study.
This study was registered at clinicaltrials.gov as NCT04536298. First registered on 1 September, 2020.
