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Vitamin D and zinc supplementation to improve treatment outcomes among COVID-19 patients in India: results from a double-blind randomized placebo-controlled trial

Partap et al., Current Developments in Nutrition, doi:10.1016/j.cdnut.2023.101971, NCT04641195
Jul 2023  
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0 0.5 1 1.5 2+ Ventilation -5% Improvement Relative Risk Discharge 6% Recovery, dyspnea, coug.. 10% Recovery, dyspnea 50% Recovery, fever 32% Recovery, cough 12% Recovery, D+Z, dyspnea, c.. 16% Recovery, D+Z, dyspnea 77% Recovery, D+Z, fever 17% Recovery, D+Z, cough 18% Zinc  Partap et al.  EARLY TREATMENT  DB RCT Is early treatment with zinc beneficial for COVID-19? Double-blind RCT 85 patients in India (April 2021 - August 2022) No significant difference in outcomes seen Partap et al., Current Developments in.., Jul 2023 Favors zinc Favors control
Zinc for COVID-19
2nd treatment shown to reduce risk in July 2020
*, now known with p = 0.0000013 from 44 studies, recognized in 17 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments.
Early terminated factorial RCT with 46 vitamin D, 48 zinc, 44 vitamin D + zinc, and 43 placebo patients in India.
The most serious outcome (ventilation) numbers do not seem realistic. Authors do not specify outcomes per group, but with one event for non-zinc, we know that either the vitamin D only or the placebo group had zero events, which does not match the reported RRs. All 7 RRs are close to 1.0: for D vs. non-D, Z vs. non-Z, D+Z vs. placebo, D vs. placebo, Z vs. placebo, D<20ng/mL vs. non-D, and D>20ng/mL vs. non-D. This suggests unreliable data or analysis (e.g., inappropriate use of Poisson regression). We will update when authors respond.
The trial is also unusual in that the primary analyses are unadjusted and compare one treatment with a combination of another treatment and placebo.
There are very large baseline differences, e.g., 35 vs. 15% 60+ for zinc vs. non-zinc. There was only 181 patients recruited from 700 planned.
There is limited room for improvement with the population studied that recovered very quickly within a median of 3 days. Oral cholecalciferol takes 3-7 days for complete conversion into the biologically active 1,25-dihydroxyvitamin D. Authors could have provided treatment with much faster onset of action, e.g., using calcitriol.
There was very little improvement in D/zinc levels with the administration used and the baseline deficiency levels. Only 4% of people went from zinc deficient to sufficient, and only 8% went from vitamin D <30ng/mL to >30ng/mL, and most or all of these improvements may have been after patients already recovered.
Notwithstanding the limitations above, we note that, while small, the effect for most outcomes is positive for vitamin D and zinc, and in most cases, the effect in the combined vitamin D + zinc group is larger.
Data for this study is not available.
Study covers zinc and vitamin D.
risk of mechanical ventilation, 5.0% higher, RR 1.05, p = 0.82, treatment 43, control 42, zinc vs. placebo.
risk of no hospital discharge, 6.0% lower, HR 0.94, p = 0.80, treatment 43, control 42, zinc vs. placebo.
risk of no recovery, 10.0% lower, HR 0.90, p = 0.67, treatment 41, control 42, zinc vs. placebo, dyspnea, cough, or fever, Table S8.
risk of no recovery, 50.0% lower, HR 0.50, p = 0.35, treatment 43, control 42, zinc vs. placebo, dyspnea, Table S8.
risk of no recovery, 32.0% lower, HR 0.68, p = 0.26, treatment 43, control 42, zinc vs. placebo, fever, Table S8.
risk of no recovery, 12.0% lower, HR 0.88, p = 0.63, treatment 43, control 42, zinc vs. placebo, cough, Table S8.
risk of no recovery, 16.0% lower, HR 0.84, p = 0.51, treatment 39, control 42, zinc + vitamin D vs. placebo, dyspnea, cough, or fever, Table S8.
risk of no recovery, 77.0% lower, HR 0.23, p = 0.06, treatment 39, control 42, zinc + vitamin D vs. placebo, dyspnea, Table S8.
risk of no recovery, 17.0% lower, HR 0.83, p = 0.57, treatment 39, control 42, zinc + vitamin D vs. placebo, fever, Table S8.
risk of no recovery, 18.0% lower, HR 0.82, p = 0.50, treatment 39, control 42, zinc + vitamin D vs. placebo, cough, Table S8.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Partap et al., 11 Jul 2023, Double Blind Randomized Controlled Trial, placebo-controlled, India, peer-reviewed, 13 authors, study period 22 April, 2021 - 1 August, 2022, trial NCT04641195 (history). Contact:,
This PaperZincAll
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