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0 0.5 1 1.5 2+ Ventilation -3% Improvement Relative Risk Discharge 14% Recovery, dyspnea, cough.. 11% Recovery, dyspnea 72% Recovery, fever 3% Recovery, cough 17% Recovery, D+Z, dyspnea, c.. 16% Recovery, D+Z, dyspnea 77% Recovery, D+Z, fever 17% Recovery, D+Z, cough 18% Vitamin D  Partap et al.  EARLY TREATMENT  DB RCT Is early treatment with vitamin D beneficial for COVID-19? Double-blind RCT 83 patients in India (April 2021 - August 2022) Higher discharge with vitamin D (not stat. sig., p=0.53) Partap et al., Current Developments in.., Jul 2023 Favors vitamin D Favors control

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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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.
Cholecalciferol was used in this study. Cholecalciferol requires two hydroxylation steps to become activated - first in the liver to calcifediol, then in the kidney to calcitriol. Calcitriol, paricalcitol, and alfacalcidol are active vitamin D analogs that do not require conversion. This allows them to have more rapid onset of action compared to cholecalciferol. The time delay for cholecalciferol to increase serum calcifediol levels can be 2-3 days, and the delay for converting calcifediol to active calcitriol can be up to 7 days. Results may be better with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.).
This study includes zinc and vitamin D.
risk of mechanical ventilation, 3.0% higher, RR 1.03, p = 0.91, treatment 41, control 42, vitamin D vs. placebo.
risk of no hospital discharge, 14.0% lower, HR 0.86, p = 0.53, treatment 41, control 42, vitamin D vs. placebo.
risk of no recovery, 11.0% lower, HR 0.89, p = 0.65, treatment 41, control 42, vitamin D vs. placebo, dyspnea, cough, or fever, Table S8.
risk of no recovery, 72.0% lower, HR 0.28, p = 0.17, treatment 41, control 42, vitamin D vs. placebo, dyspnea, Table S8.
risk of no recovery, 3.0% lower, HR 0.97, p = 0.92, treatment 41, control 42, vitamin D vs. placebo, fever, Table S8.
risk of no recovery, 17.0% lower, HR 0.83, p = 0.51, treatment 41, control 42, vitamin D 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).
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This PaperVitamin DAll
Vitamin D and Zinc Supplementation to Improve Treatment Outcomes among COVID-19 Patients in India: Results from a Double-Blind Randomized Placebo-Controlled Trial
Dr Uttara Partap, Kamal Kant Sharma, Yogesh Marathe, Molin Wang, Sanaa Shaikh, Pradeep D’costa, Gaurav Gupta, Sabri Bromage, Elena C Hemler, Nerges Mistry, Kevin C Kain, Yatin Dholakia, Wafaie W Fawzi
Current Developments in Nutrition, doi:10.1016/j.cdnut.2023.101971
Vitamin D and zinc supplementation to improve treatment outcomes among COVID-19 patients in India: results from a double-blind randomized placebo-controlled trial, Current Developments in Nutrition,
Competing interests All authors declare no conflicts of interest. Summary In a randomized factorial trial in a small population in India, neither vitamin D nor zinc supplementation appeared to improve COVID-19 treatment outcomes. Large-scale data are needed to corroborate findings. J o u r n a l P r e -p r o o f DATA SHARING Data from this study are currently not available to be shared due to regulatory restrictions. J o u r n a l P r e -p r o o f
Abd-Elsalam, Soliman, Esmail, Khalaf, Mostafa et al., Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial, Biol Trace Elem Res
Abdallah, Mhalla, Trabelsi, Sekma, Youssef et al., Twice-Daily Oral Zinc in the Treatment of Patients With Coronavirus Disease 2019: A Randomized Double-Blind Controlled Trial, Clinical Infectious Diseases
Abdelmaksoud, Ghweil, Hassan, Khodeary, Aref, Olfactory Disturbances as Presenting Manifestation Among Egyptian Patients with COVID-19: Possible Role of Zinc, Biol Trace Elem Res
Abioye, Bromage, Fawzi, Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis, BMJ Glob Health
Annweiler, Beaudenon, Gautier, Simon, Dubée et al., COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial, Trials
Batista, Hotez, Amor, Kim, Kaslow et al., The silent and dangerous inequity around access to COVID-19 testing: A call to action. eClinicalMedicine [Internet]
Boro, Stoll, Barriers to COVID-19 Health Products in Low-and Middle-Income Countries During the COVID-19 Pandemic: A Rapid Systematic Review and Evidence Synthesis, doi:10.3389/fpubh.2022.928065
Brunvoll, Nygaard, Ellingjord-Dale, Holland, Istre et al., Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial, BMJ
Cannata-Andía, Díaz-Sottolano, Fernández, Palomo-Antequera, Herrero-Puente et al., A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D-a randomised multicentre international clinical trial, BMC Med
Castillo, Costa, Barrios, Díaz, Miranda et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study, J Steroid Biochem Mol Biol
Cheng, Ma, Witt, Rapp, Wild et al., Face masks effectively limit the probability of SARS-CoV-2 transmission, Science
Dong, Du, Gardner, An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases
Dong, Stallmann-Jorgensen, Pollock, Harris, Keeton et al., A 16-week randomized clinical trial of 2000 international units daily vitamin D3 supplementation in black youth: 25-hydroxyvitamin D, adiposity, and arterial stiffness, J Clin Endocrinol Metab
Elamir, Amir, Lim, Rana, Lopez et al., A randomized pilot study using calcitriol in hospitalized COVID-19 patients, Bone
Fernandes, Murai, Reis, Sales, Santos et al., Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19, Am J Clin Nutr
Greiller, Martineau, Modulation of the immune response to respiratory viruses by vitamin D, Nutrients
Greiller, Suri, Jolliffe, Kebadze, Hirsman et al., Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells, J Steroid Biochem Mol Biol
Hemilä, Fitzgerald, Petrus, Prasad, Zinc Acetate Lozenges May Improve the Recovery Rate of Common Cold Patients: An Individual Patient Data Meta-Analysis, Open Forum Infect Dis
Imai, Ito, Kiso, Yamayoshi, Uraki et al., Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB, N Engl J Med
Jackson, Farzan, Chen, Choe, Mechanisms of SARS-CoV-2 entry into cells, Nat Rev Mol Cell Biol
Jolliffe, Camargo, Sluyter, Aglipay, Aloia et al., Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials, Lancet Diabetes Endocrinol
Jolliffe, Holt, Greenig, Talaei, Perdek et al., Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT), BMJ
Karonova, Chernikova, Golovatyuk, Bykova, Grant et al., Vitamin D Intake May Reduce SARS-CoV-2 Infection Morbidity in Health Care Workers, Nutrients
Kearns, Alvarez, Tangpricha, Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review, Endocr Pract
Kumar, Hameed, Babu, Venkataswamy, Dinesh et al., Descriptive epidemiology of SARS-CoV-2 infection in Karnataka state, South India: Transmission dynamics of symptomatic vs. asymptomatic infections. eClinicalMedicine [Internet]
Kurhade, Zou, Xia, Liu, Chang et al., Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster, Nat Med
Laxminarayan, Cm, Vt, Kumar, Wahl et al., SARS-CoV-2 infection and mortality during the first epidemic wave in Madurai, south India: a prospective, active surveillance study. The Lancet Infectious Diseases
Maghbooli, Sahraian, Jamalimoghadamsiahkali, Asadi, Zarei et al., Treatment With 25-Hydroxyvitamin D(3) (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial, Endocr Pract
Mariani, Antonietti, Tajer, Ferder, Inserra et al., High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial, PLoS One
Maxwell, Sanders, Sabot, Hachem, Llanos-Cuentas et al., COVID-19 Therapeutics for Low-and Middle-Income Countries: A Review of Candidate Agents with Potential for Near-Term Use and Impact, Am J Trop Med Hyg
Menni, Valdes, Polidori, Antonelli, Penamakuri et al., Symptom prevalence, duration, and risk of hospital admission in individuals infected with SARS-CoV-2 during periods of omicron and delta variant dominance: a prospective observational study from the ZOE COVID Study. The Lancet
Misra, Srivastava, Misra, Kant, Kardam et al., Vitamin D status of adult females residing in Ballabgarh health and demographic surveillance system: A community-based study
Mohfw, Clinical Management Protocol for COVID-19 (In Adults) -Version 6 (24.05.21) [Internet]. New Delhi: Ministry of Health and Family Welfare, Government of India
Mohfw, Revised Discharge Policy for COVID-19: Updated on 9th
Murai, Fernandes, Sales, Pinto, Goessler et al., Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial, JAMA
Niet, Trémège, Coffiner, Rousseau, Calmes et al., Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial, Nutrients
Quek, Ooi, Teng, Chan, Ng et al., Zinc and vitamin C intake increases spike and neutralising antibody production following SARS-CoV-2 infection, Clin Transl Med
Rannan-Eliya, Wijemunige, Gunawardana, Amarasinghe, Sivagnanam et al., Increased Intensity Of PCR Testing Reduced COVID-19 Transmission Within Countries During The First Pandemic Wave. Health Affairs
Rastogi, Bhansali, Khare, Suri, Yaddanapudi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study), Postgraduate Medical Journal
Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-Week 5000 IU versus 1000 IU Vitamin D3 Supplementation on Recovery of Symptoms in Patients with Mild to Moderate Covid-19: A Randomized Clinical Trial, Nutrients
Seet, Quek, Ooi, Sengupta, Lakshminarasappa et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: An open-label randomized trial, Int J Infect Dis
Sharma, Partap, Mistry, Marathe, Wang et al., Randomised trial to determine the effect of vitamin D and zinc supplementation for improving treatment outcomes among patients with COVID-19 in India: trial protocol, BMJ Open
Skalny, Rink, Ajsuvakova, Aschner, Gritsenko et al., Zinc and respiratory tract infections: Perspectives for COVID-19 (Review), Int J Mol Med
Stambouli, Driss, Gargouri, Bahrini, Arfaoui et al., COVID-19 prophylaxis with doxycycline and zinc in health care workers: a prospective, randomized, double-blind clinical trial, Int J Infect Dis
Subramanian, Nirantharakumar, Hughes, Myles, Williams et al., Symptoms and risk factors for long COVID in non-hospitalized adults, Nat Med
Telcian, Zdrenghea, Edwards, Laza-Stanca, Mallia et al., Vitamin D increases the antiviral activity of bronchial epithelial cells in vitro, Antiviral Res
Thomas, Patel, Bittel, Wolski, Wang et al., Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial, JAMA Netw Open
Torres, Casado, Vigón, Rodríguez-Mora, Mateos et al., Changes in the immune response against SARS-CoV-2 in individuals with severe COVID-19 treated with high dose of vitamin D, Biomed Pharmacother
Tóth, Fresilli, Paoli, Maiucci, Salvioni et al., D-dimer levels in non-COVID-19 ARDS and COVID-19 ARDS patients: A systematic review with meta-analysis, PLOS ONE
Uraki, Ito, Furusawa, Yamayoshi, Iwatsuki-Horimoto et al., Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB. The Lancet Infectious Diseases
Velthuis, Van Den Worm, She, Sims, Baric et al., +) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture, PLoS Pathog
Villasis-Keever, López-Alarcón, Miranda-Novales, Zurita-Cruz, Barrada-Vázquez et al., Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial, Arch Med Res
Who, Advice for the public on COVID-19 -World Health Organization [Internet]. 2022 [cited
Who, Therapeutics and COVID-19: Living Guideline
Who, WHO Director-General's opening remarks at the media briefing on COVID-19 -11
Please send us corrections, updates, or comments. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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