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

Abstract

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. Methods 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. Results We identified 26 studies (10 randomized 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). Conclusions 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.

Vaccination status, favipiravir, and micronutrient supplementation roles in post-COVID symptoms: A longitudinal study

“…However, there is no specific dose associated with a better prognosis. A meta-analysis revealed heterogeneity in doses and administration of these micronutrients and no significant effect on mortality but the various effect on the need for intubation and length of stay [ 14 ]. Moreover, micronutrient supplementation is not free from side effects.…”

The Variable Nature of Vitamin C—Does It Help When Dealing with Coronavirus?

“…In viral infections, including COVID-19, the positive effect of VC administration has also been reported [ 135 , 136 , 137 , 138 , 203 , 209 ]. The neutral effect of VC has been mentioned in the case of patients with COVID-19 in a few publications [ 47 , 48 , 190 , 191 , 192 , 193 , 194 , 196 , 198 , 199 , 200 ], and the adverse effects of the administration of high doses of VC have been mentioned as an aspect of urinary and kidney stones [ 88 , 89 , 90 ] and nephropathy [ 45 ]. These last effects were found to be neutral.…”

COVID-19: Lessons on malnutrition, nutritional care and public health from the ESPEN-WHO Europe call for papers

“…With regard to oral supplements, a systematic review of 12 randomized controlled trials on use of dietary herbal supplements to increase micronutrient provision [111] showed that high risk of bias makes it difficult to interpret results; the authors conclude that some promising effects were suggested in improving recovery, and zinc supplements could lead to faster recovery from olfactory dysfunction. A meta-analysis focusing on vitamin C, vitamin D and zinc reported beneficial effects of vitamin D supplementation in reducing risk of intubation during COVID-19 illness, whereas no significant impact was detected for vitamin C and zinc on mortality, intubation risk and length of hospital stay [112].…”