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All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Mortality 85% Improvement Relative Risk ICU admission 94% Vitamin D  COVIDIOL  LATE TREATMENT  RCT Is late treatment with vitamin D beneficial for COVID-19? RCT 76 patients in Spain (May - June 2020) Lower ICU admission with vitamin D (p=0.008) Castillo et al., J. Steroid Biochemist.., Aug 2020 Favors vitamin D Favors control

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

Castillo et al., Journal of Steroid Biochemistry and Molecular Biology, 203, October 2020, doi:10.1016/j.jsbmb.2020.105751, COVIDIOL, NCT04366908
Aug 2020  
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RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions.
All patients received standard care including HCQ+AZ. Significantly lower ICU admission with the addition of calcifediol - adjusted odds ratio 0.03 [0.003-0.25]. No deaths for calcifediol (0/50), 2 deaths for SOC (2/26).
For additional analysis see
Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 65% [41‑79%] lower risk vs. 38% [25‑49%] lower risk. 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.
This is the 1st of 27 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.00002.
This is the 3rd of 115 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 30 sextillion).
This study includes vitamin D and HCQ.
risk of death, 85.4% lower, RR 0.15, p = 0.11, treatment 0 of 50 (0.0%), control 2 of 26 (7.7%), NNT 13, relative risk is not 0 because of continuity correction due to zero events (with reciprocal of the contrasting arm).
risk of ICU admission, 94.2% lower, RR 0.06, p = 0.008, treatment 1 of 50 (2.0%), control 13 of 26 (50.0%), NNT 2.1, odds ratio converted to relative risk.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Castillo et al., 29 Aug 2020, Randomized Controlled Trial, Spain, peer-reviewed, 7 authors, study period May 2020 - June 2020, dosage calcifediol 0.5mg day 1, 0.27mg day 3, 0.27mg day 7, and then weekly until discharge or ICU admission, trial NCT04366908 (history) (COVIDIOL).
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This PaperVitamin DAll
Abstract: Journal of Steroid Biochemistry and Molecular Biology 203 (2020) 105751 Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: “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” Marta Entrenas Castillo a, Luis Manuel Entrenas Costa a, *, José Manuel Vaquero Barrios a, Juan Francisco Alcalá Díaz b, José López Miranda b, Roger Bouillon c, José Manuel Quesada Gomez d a UGC de Neumología, Instituto Maimónides de Investigación Biomédica de Córdoba 9 (IMIBIC). Hospital Universitario Reina Sofía, Universidad de Córdoba, Avda. Menéndez 10 Pidal s/n, 14004 11, Córdoba, Spain b Departamento de Medicina Interna. IMIBIC, CIBER de Fisiopatología de la Obesidad y la Nutrición. Hospital Universitario Reina Sofía, Universidad de Córdoba, Fundación Progreso y Salud. Avda. Menéndez Pidal s/n, 14004 14, Córdoba, Spain c Department of Chronic Diseases, Metabolism and Ageing, Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat, ON1/902, 3000, Leuven, Belgium d IMIBIC. CIBER de Fragilidad y Envejecimiento Saludable. Hospital Universitario Reina Sofía, Universidad de Córdoba, Fundación Progreso y Salud. Avda. Menéndez Pidal s/n, 18 14004, Córdoba, Spain A R T I C L E I N F O A B S T R A C T Keywords: COVID-19 SARS-CoV-2 Vitamin D Vitamin D3 or cholecalciferol Calcifediol or 25-hydroxyvitamin D3 1α, 25(OH)2D or 1α, 25-dihydroxyvitamin D or calcitriol Acute respiratory distress syndrome (ARDS) Cytokine/Chemokine storm Renin-angiotensin system Hypercoagulability Hydroxychloroquine Chloroquine Covidiol Neutrophil activity Vitamin D endocrine system Cuboidal alveolar coating cells type II Cathelicidin peptide Defensins TLR co-receptor CD14 Vitamin D receptor Objective: The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly in­ crease serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19. Design: Parallel pilot randomized open label, double-masked clinical trial. Setting: University hospital setting (Reina Sofia University Hospital, Córdoba Spain.) Participants: 76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1). Procedures: All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included..
Late treatment
is less effective
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