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HomeCoronavirusVitamin supplementation unlikely to reduce COVID-19 mortality – Toledo meta-analysis

Vitamin supplementation unlikely to reduce COVID-19 mortality – Toledo meta-analysis

A meta-analysis of 26 studies that included more than 5,600 patients hospitalised with COVID-19 has found that taking immune-boosting micronutrients like vitamin C, vitamin D and zinc, do not lessen a patient’s chance of dying from COVID-19.

The latest review of COVID-19 hospitalisation data by researchers at The University of Toledo, Ohio, showed little evidence that these strategies worked.

Early in the pandemic, healthcare providers tried a variety of micronutrients as potential therapies for the new illness. More recently, supplements have been promoted by some as an alternative to the safe and proven vaccines.

However, despite these enduring interest in these options, there has been little confirmation that they are effective.

“A lot of people have this misconception that if you load up on zinc, vitamin D or vitamin C, it can help the clinical outcome of COVID-19,” said Dr Azizullah Beran, an internal medicine resident at The University of Toledo College of Medicine and Life Sciences. “That hasn’t been shown to be true.”

Beran is the lead author on a recent paper that significantly strengthens the emerging medical consensus that micronutrient supplements are not an effective treatment for COVID-19.

He and his collaborators reviewed 26 peer-reviewed studies from around the globe that included more than 5,600 hospitalised COVID-19 patients. Their analysis found no reduction in mortality for those being treated with vitamin D, vitamin C or zinc, compared with patients who did not receive one of those three supplements.

Their analysis did find that treatment with vitamin D might be associated with lower rates of intubation and shorter hospital stays, but the researchers said more rigorous study was needed to validate that finding.

Vitamin C and zinc were not associated with shorter hospital stays or lowering the chance a patient would be put on a ventilator.

While the study predominately looked at patients who were already sick and hospitalised with COVID-19 when given the supplements, researchers also analysed a smaller subset of individuals who had been taking vitamin D before contracting the virus. They found no significant difference in the mortality rate of that population either.

The paper is published in the journal Clinical Nutrition ESPEN.

“It’s important for people to understand that taking a lot of these supplements does not translate into better outcomes,” said Dr Ragheb Assaly, a UToledo professor of medicine and the paper’s senior author. “The other important message is that the answer to this disease is the vaccine. Micronutrient supplements will not offset the lack of vaccination or make you not need the vaccine.”

Researchers caution that the study shouldn’t be interpreted as saying vitamin and mineral supplements are bad or should be avoided, but rather make it clear that they are not effective at preventing COVID-19 deaths.

Beran and Assaly said it’s possible that some COVID-19 patients who are malnourished or otherwise deficient in micronutrients could benefit from taking supplements, but that’s because their bodies already lack essential nutrients – not because vitamin D or vitamin C are effective against the virus.

“What we’re saying is this: if you don’t medically need these supplements, don’t take them thinking they’re protective against COVID-19,” Beran said. “They’re not going to prevent you from getting it and they’re not going to prevent you from dying.”

Study details
Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis.

Azizullah Beran, Mohammed Mhanna, Omar Srour, Hazem Ayesh, Jamie M. Stewart, Majdal Hjouj, Waleed Khokher, Asmaa S. Mhanna, Dana Ghazaleh, Yasmin Khader, Wasef Sayeh, Ragheb Assaly.

Published in Clinical Nutrition ESPEN on 12 January 2022


Background and aims
Micronutrient supplements such as vitamin D, vitamin C, and zinc have been used in managing viral illnesses. However, the clinical significance of these individual micronutrients in patients with Coronavirus disease 2019 (COVID-19) remains unclear. We conducted this meta-analysis to provide a quantitative assessment of the clinical significance of these individual micronutrients in COVID-19.

We performed a comprehensive literature search using MEDLINE, Embase, and Cochrane databases through December 5th, 2021. All individual micronutrients reported by ≥ 3 studies and compared with standard-of-care (SOC) were included. The primary outcome was mortality. The secondary outcomes were intubation rate and length of hospital stay (LOS). Pooled risk ratios (RR) and mean difference (MD) with corresponding 95% confidence intervals (CI) were calculated using the random-effects model.

We identified 26 studies (10 randomised controlled trials and 16 observational studies) involving 5633 COVID-19 patients that compared three individual micronutrient supplements (vitamin C, vitamin D, and zinc) with SOC. Nine studies evaluated vitamin C in 1488 patients (605 in vitamin C and 883 in SOC). Vitamin C supplementation had no significant effect on mortality (RR 1.00, 95% CI 0.62–1.62, P = 1.00), intubation rate (RR 1.77, 95% CI 0.56–5.56, P = 0.33), or LOS (MD 0.64; 95% CI -1.70, 2.99; P = 0.59). Fourteen studies assessed the impact of vitamin D on mortality among 3497 patients (927 in vitamin D and 2570 in SOC). Vitamin D did not reduce mortality (RR 0.75, 95% CI 0.49–1.17, P = 0.21) but reduced intubation rate (RR 0.55, 95% CI 0.32–0.97, P = 0.04) and LOS (MD -1.26; 95% CI -2.27, −0.25; P = 0.01). Subgroup analysis showed that vitamin D supplementation was not associated with a mortality benefit in patients receiving vitamin D pre or post COVID-19 diagnosis. Five studies, including 738 patients, compared zinc intake with SOC (447 in zinc and 291 in SOC). Zinc supplementation was not associated with a significant reduction of mortality (RR 0.79, 95% CI 0.60–1.03, P = 0.08).

Individual micronutrient supplementations, including vitamin C, vitamin D, and zinc, were not associated with a mortality benefit in COVID-19. Vitamin D may be associated with lower intubation rate and shorter LOS, but vitamin C did not reduce intubation rate or LOS. Further research is needed to validate our findings.


Clinical Nutrition article – Clinical significance of micronutrient supplements in patients with coronavirus disease 2019: A comprehensive systematic review and meta-analysis. (Open access)


See more from MedicalBrief archives:


Lancet removes hyped preprint on efficacy of vitamin D for COVID-19


COVID-19: A ready-reference of current and failed treatments


High vitamin D levels may protect against COVID-19, especially for Black people


More evidence of lack of Vitamin D efficacy for COVID-19 — Two studies


Still no definitive answer on Vitamin D3 to treat COVID-19


COVID-19 and vitamin D: 'Insufficient evidence’ as a treatment — NICE Guideline



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