Analgesics
Antiandrogens
Azvudine
Bromhexine
Budesonide
Colchicine
Conv. Plasma
Curcumin
Famotidine
Favipiravir
Fluvoxamine
Hydroxychlor..
Ivermectin
Lifestyle
Melatonin
Metformin
Minerals
Molnupiravir
Monoclonals
Naso/orophar..
Nigella Sativa
Nitazoxanide
Paxlovid
Quercetin
Remdesivir
Thermotherapy
Vitamins
More

Other
Feedback
Home
Top
Results
Abstract
All vitamin D studies
Meta analysis
 
Feedback
Home
next
study
previous
study
c19early.org COVID-19 treatment researchVitamin DVitamin D (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality -124% Improvement Relative Risk Ventilation 25% ICU admission 27% Progression 3% primary Progression (b) 33% Progression (c) -79% Progression (d) 25% Progression (e) 16% Vitamin D  CARED  LATE TREATMENT  DB RCT Is late treatment with vitamin D beneficial for COVID-19? Double-blind RCT 218 patients in Argentina (August 2020 - June 2021) Higher mortality with vitamin D (not stat. sig., p=0.45) c19early.org Mariani et al., PLOS ONE, May 2022 Favors vitamin D Favors control

High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial

Mariani et al., PLOS ONE, doi:10.1371/journal.pone.0267918, CARED, NCT04411446
May 2022  
  Post
  Facebook
Share
  Source   PDF   All   Meta
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020
 
*, now known with p < 0.00000000001 from 120 studies, recognized in 7 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments. c19early.org
Late stage RCT with 115 patients treated with a single dose of 500,000IU cholecalciferol and 103 placebo patients, showing no significant differences. Authors do not explain why they did very late treatment with cholecalciferol instead of calcifediol or calcitriol, which would avoid several days delay in conversion. Baseline vitamin D levels were relatively high, limiting the potential benefit.
Cholecalciferol was used in this study. 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. 39% [26‑49%] 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 15th of 29 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000035.
This is the 82nd of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 226 sextillion).
risk of death, 124.0% higher, RR 2.24, p = 0.45, treatment 5 of 115 (4.3%), control 2 of 103 (1.9%).
risk of mechanical ventilation, 25.0% lower, RR 0.75, p = 0.85, treatment 5 of 115 (4.3%), control 6 of 103 (5.8%), NNT 68.
risk of ICU admission, 27.0% lower, RR 0.73, p = 0.62, treatment 9 of 115 (7.8%), control 11 of 103 (10.7%), NNT 35.
risk of progression, 3.0% lower, OR 0.97, p = 0.82, treatment 115, control 103, Wilcoxon-Mann-Whitney, primary outcome, RR approximated with OR.
risk of progression, 32.8% lower, RR 0.67, p = 0.71, treatment 3 of 115 (2.6%), control 4 of 103 (3.9%), NNT 78, Δ rSOFA 4.
risk of progression, 79.1% higher, RR 1.79, p = 0.30, treatment 10 of 115 (8.7%), control 5 of 103 (4.9%), Δ rSOFA 3.
risk of progression, 25.4% lower, RR 0.75, p = 0.76, treatment 5 of 115 (4.3%), control 6 of 103 (5.8%), NNT 68, Δ rSOFA 2.
risk of progression, 16.0% lower, RR 0.84, p = 0.70, treatment 15 of 115 (13.0%), control 16 of 103 (15.5%), NNT 40, Δ rSOFA 1.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Mariani et al., 27 May 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Argentina, peer-reviewed, mean age 59.1, 33 authors, study period 14 August, 2020 - 22 June, 2021, average treatment delay 7.0 days, dosage 500,000IU single dose, trial NCT04411446 (history) (CARED). Contact: ja_mariani@hotmail.com.
This PaperVitamin DAll
High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial
Javier Mariani, Laura Antonietti, Carlos Tajer, León Ferder, Felipe Inserra, Milagro Sanchez Cunto, Diego Brosio, Fernando Ross, Marcelo Zylberman, Daniel Emilio López, Cecilia Luna Hisano, Sebastián Maristany Batisda, Gabriela Pace, Adrián Salvatore, Jimena Fernanda Hogrefe, Marcela Turela, Andrés Gaido, Beatriz Rodera, Elizabeth Banega, María Eugenia Iglesias, Mariela Rzepeski, Juan Manuel Gomez Portillo, Magalí Bertelli, Andrés Vilela, Leandro Heffner, Verónica Laura Annetta, Lucila Moracho, Maximiliano Carmona, Graciela Melito, María José Martínez, Gloria Luna, Natalia Vensentini, Walter Manucha
PLOS ONE, doi:10.1371/journal.pone.0267918
Background The role of oral vitamin D 3 supplementation for hospitalized patients with COVID-19 remains to be determined. The study was aimed to evaluate whether vitamin D 3 supplementation could prevent respiratory worsening among hospitalized patients with COVID-19. Methods and findings We designed a multicentre, randomized, double-blind, sequential, placebo-controlled clinical trial. The study was conducted in 17 second and third level hospitals, located in four
Conclusions Supplementation with a single, high dose of vitamin D 3 at admission to patients hospitalized with mild-to-moderate COVID-19 did not prevent respiratory worsening as compared with placebo. Supporting information S1
References
Amrein, Schnedl, Holl, Riedl, Christopher et al., Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial, JAMA, doi:10.1001/jama.2014.13204
Anka, Tahir, Abubakar, Alsabbagh, Zian et al., Coronavirus disease 2019 (COVID-19): An overview of the immunopathology, serological diagnosis and management, Scand J Immunol, doi:10.1111/sji.12998
Annweiler, Beaudenon, Simon, Guenet, Otekpo, Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2021.105958
Atef, Vitamin D assays in clinical laboratory: Past, present and future challenges, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2017.02.011
Bergman, Lindh, Bjo ¨rkhem-Bergman, Lindh, Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials, PLoS One, doi:10.1371/journal.pone.0065835
Briggs, Gormally, Li, Browning, Treggiari et al., Early but not late convalescent plasma is associated with better survival in moderate-to-severe COVID-19, PLoS One, doi:10.1371/journal.pone.0254453
Castillo, Costa, Barrios, Alcala ´dı ´az, Lo ´pez 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, doi:10.1016/j.jsbmb.2020.105751
Costagliola, Nuzzi, Spada, Comberiati, Verduci et al., Nutraceuticals in Viral Infections: An Overview of the Immunomodulating Properties, Nutrients, doi:10.3390/nu13072410
Divine, Norton, Baro ´n, Juarez-Colunga, The Wilcoxon-Mann-Whitney Procedure Fails as a Test of Medians, Am Stat, doi:10.1080/00031305.2017.1305291
Ferder, Martı ´n Gime ´nez, Vm, Inserra, Tajer et al., Vitamin D supplementation as a rational pharmacological approach in the COVID-19 pandemic, Am J Physiol Lung Cell Mol Physiol, doi:10.1152/ajplung.00186.2020
Festic, Bansal, Kor, Gajic, US Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). SpO2/FiO2 ratio on hospital admission is an indicator of early acute respiratory distress syndrome development among patients at risk, J Intensive Care Med, doi:10.1177/0885066613516411
Getachew, Tizabi, Vitamin D and COVID-19: Role of ACE2, age, gender, and ethnicity, J Med Virol, doi:10.1002/jmv.27075
Grove, Osokogu, Al-Khudairy, Mehrabian, Zanganeh et al., Association between vitamin D supplementation or serum vitamin D level and susceptibility to SARS-CoV-2 infection or COVID-19 including clinical course, morbidity and mortality outcomes? A systematic review, BMJ Open, doi:10.1136/bmjopen-2020-043737
Heart, Lung ; Ginde, Brower, Caterino, Finck et al., Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients, N Engl J Med, doi:10.1056/NEJMoa1911124
Jovic, Ali, Ibrahim, Jessop, Tarassoli et al., Could Vitamins Help in the Fight Against COVID-19?, Nutrients, doi:10.3390/nu12092550
Kearns, Alvarez, Tangpricha, Large, single-dose, oral vitamin D supplementation in adult populations: a systematic review, Endocr Pract, doi:10.4158/EP13265.RA
Kraus, Medenwald, Ludwig-Kraus, Do extreme summers increase blood vitamin D (25-hydroxyvitamin D) levels?, PLoS One, doi:10.1371/journal.pone.0242230
Leaf, Ginde, Vitamin D3 to Treat COVID-19: Different Disease, Same Answer, JAMA, doi:10.1001/jama.2020.26850
Mariani, Gime ´nez, Vmm, Bergam, Tajer et al., Association Between Vitamin D Deficiency and COVID-19 Incidence, Complications, and Mortality in 46 Countries: An Ecological Study, Health Secur, doi:10.1089/hs.2020.0137
Mariani, Tajer, Antonietti, Inserra, Ferder et al., High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: A structured summary of a study protocol for a randomised controlled trial (CARED-TRIAL), Trials, doi:10.1186/s13063-021-05073-3
Martineau, Forouhi, Vitamin D for COVID-19: a case to answer?, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587%2820%2930268-0
Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ, doi:10.1136/bmj.i6583
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw Open, doi:10.1001/jamanetworkopen.2020.19722
Mora, Iwata, Von Andrian, Vitamin effects on the immune system: vitamins A and D take centre stage, Nat Rev Immunol, doi:10.1038/nri2378
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, doi:10.1001/jama.2020.26848
Osterholm, Preparing for the next pandemic, N Engl J Med, doi:10.1056/NEJMp058068
Pandharipande, Shintani, Hagerman, Jacques, Rice et al., Derivation and validation of Spo2/Fio2 ratio to impute for Pao2/Fio2 ratio in the respiratory component of the Sequential Organ Failure Assessment score, Crit Care Med, doi:10.1097/CCM.0b013e31819cefa9
Peng, Liu, Zheng, Lu, Hou et al., Immunological Aspects of SARS-CoV-2 Infection and the Putative Beneficial Role of Vitamin-D, Int J Mol Sci, doi:10.3390/ijms22105251
Petrelli, Luciani, Perego, Dognini, Colombelli et al., Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2021.105883
Pham, Waterhouse, Baxter, Romero, Mcleod et al., The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587%2820%2930380-6
Rice, Wheeler, Bernard, Hayden, Schoenfeld et al., Institute ARDS Network. Comparison of the SpO2/FIO2 ratio and the PaO2/FIO2 ratio in patients with acute lung injury or ARDS, Chest, doi:10.1378/chest.07-0617
Schulz, Altman, Moher, Group, CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials, BMJ, doi:10.1136/bmj.c332
Seymour, Liu, Iwashyna, Brunkhorst, Rea et al., Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA, doi:10.1001/jama.2016.0288
Silberstein, Vitamin, A simpler alternative to tocilizumab for trial in COVID-19?, Med Hypotheses, doi:10.1016/j.mehy.2020.109767
Stroehlein, Wallqvist, Iannizzi, Mikolajewska, Metzendorf et al., Vitamin D supplementation for the treatment of COVID-19: a living systematic review, Cochrane Database Syst Rev, doi:10.1002/14651858.CD015043
Teymoori-Rad, Shokri, Salimi, Marashi, The interplay between vitamin D and viral infections, Rev Med Virol, doi:10.1002/rmv.2032
Torjesen, Covid-19: Public health agencies review whether vitamin D supplements could reduce risk, BMJ, doi:10.1136/bmj.m2475
Vincent, Moreno, Takala, Willatts, Mendonc ¸a et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine, Intensive Care Med, doi:10.1007/BF01709751
Yisak, Ewunetei, Kefale, Mamuye, Teshome et al., Effects of Vitamin D on COVID-19 Infection and Prognosis: A Systematic Review, Risk Manag Healthc Policy, doi:10.2147/RMHP.S291584
Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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.
  or use drag and drop   
Submit