Vitamin D3 supplementation shows no therapeutic benefits in severe COVID-19 patients, study finds

Vitamin D has gained immense popularity amid the coronavirus disease 2019 (COVID-19) pandemic. Several studies have tied vitamin D deficiency to the severity of COVID-19. Health experts are investigating if taking vitamin D may help protect against severe COVID-19.

A team of researchers at the University of São Paulo in Brazil aimed to determine if vitamin D3 supplementation reduces length of stay in hospitalized patients with severe COVID-19.

The researchers found that taking vitamin D3 was safe and effective in increasing 25-hydroxyvitamin D levels but did not reduce hospital length of stay or yield any other clinically-relevant outcomes compared with a placebo.

The study

In the current study, which appeared on the preprint server medRxiv*, the team wanted to determine if vitamin D supplementation can reduce the hospital length of stay and improve clinical outcomes in hospitalized COVID-19 patients.

The team conducted a multicenter, double-blind, randomized and placebo-controlled trial in two centers in Sao Paulo, Brazil. The trial included 240 hospitalized patients with severe COVID-19.

The team randomly assigned patients to receive either a single oral dose of 200,000 IU of vitamin D3 or a placebo.

The team wanted to determine the effects of vitamin D3 supplementation on the hospital length of stay, defined as hospital discharge or death. Other recognized outcomes were mortality, mechanical ventilation requirement, admission to the intensive care unit (ICU) and serum levels of 250-hydroxyvitamin D, calcium, creatinine, D-dimer and C-reactive protein.

Study outcomes

The team has found that of the 240 randomized patients, vitamin D supplementation markedly increased serum 25-hydroxyvitamin D levels compared to placebo.

The supplement increased the serum vitamin D levels in 86.7 percent of the patients, compared to 11 percent in the placebo group.

"There were no changes in any health-related laboratory markers following the intervention. Vitamin D3 supplementation was well tolerated, and no severe adverse events were reported throughout the trial," the researchers noted.

However, vitamin D3 supplementation is ineffective in improving hospital length of stay or any other clinical outcomes among hospitalized patients with severe COVID-19.

The single dose of 200,000 IU of vitamin D3 supplementation could not promote any clinically relevant effects among the study participants.

"Thus, this trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19," the team concluded.

The study has several limitations, however. The sample size was too small to detect significant changes for secondary outcomes. Further, the patients had comorbidities or coexisting diseases and so were using diverse medication regimens which might have impacted the researchers ability to gauge the supplementations efficacy.

Lastly, the proportion of patients with vitamin D deficiency enrolled in the study was lower than those reported in other cohorts.

Vitamin D and COVID-19

A growing body of evidence has shown that vitamin D may enhance innate and adaptive immunity. Vitamin D supplementation could improve macrophages and dendritic cell function, strengthening, and overall immune response.

Inadequate vitamin D levels in the body have been suggested as a possible risk factor for acute respiratory tract diseases, including viral infections. Health experts said that optimal vitamin D levels play an imperative anti-inflammatory role, thereby benefiting COVID-19 patients.

Several studies have explored the potential benefit of vitamin D supplementation on COVID-19 health outcomes.

Observational studies have shown that 25-hydroxyvitamin D levels are linked to better clinical outcomes in respiratory diseases. In one trial, administering boluses of vitamin D3 before the infection was associated with better prognosis and less severe illness among older and frail COVID-19 patients.

The elderly and those with comorbidities are at a higher risk of severe illness and death. Finding potential therapies to avert severe COVID-19 illness is crucial amid the coronavirus pandemic.

Globally, the COVID-19 pandemic has caused over 1.34 million deaths, with more than 55.76 million cases.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.


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  1. Costa Conn Costa Conn Australia says:

    Why report on such a seriously flawed paper? Someone there needs to select better quality work to report on.

  2. James Simpson James Simpson United Kingdom says:

    "a brief overview of the most catastrophic flaws in its design:

    The doctors gave patients a single dose, one that barely qualifies as a high dose despite the study description, that earlier research on Vitamin D, conducted four years ago, proved doesn’t work. In other words, they designed a study that was entirely unnecessary because the outcome was known beforehand. The research was a complete waste of everybody’s time and a betrayal of the patients who took part because nothing could be learnt from it.

    Even worse, the form of Vitamin D the researchers gave the patients needs 10 days to become available in their bodies, far too late to help these seriously ill patients in their battle against Covid. Another form, calcifediol, which is available for use by the immune system immediately, should have been given instead, as it was in the Spanish study.

    In addition, not only was the wrong form of Vitamin D given but it was administered to patients 11 days after the onset of their symptoms – a huge time lag that, as Dr Vasquez observes, would ensure that many established drug treatments – for illnesses such as influenza, for example – would be guaranteed to fail too.

    The combined delay in treatment and the delay in the Vitamin D becoming active meant the patients had to wait three weeks before their Covid was being treated in any meaningful way. But that was the point at which the study ended and an assessment was drawn about Vitamin D as an ineffective treatment."

  3. Chris Hartley Chris Hartley United Kingdom says:

    Anyone with even a basic knowledge of how calcitriol (activated Vit D) is created in the kidneys from calcifediol (pre-activated D3), itself created in the liver, and the length of time taken to achieve activation would be aware that taking a bolus dose of Vitamin D3 (cholecalciferol) would be ineffective in substantially altering the serum level of calcitriol in sufficient time to affect the outcome of the progression of the disease.

    The average length of time from admission to discharge seems to be 7 days, with or without administration of the bolus dose. Considering that this is less than the average time for conversion of cholecalciferol to calcitriol, should it really come as a surprise that the length of stay was unaffected? Yes, the serum level of calcifediol was increased at the time of discharge, but it needed to be raised at the time of admission.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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