Conv. Plasma
Nigella Sativa
Peg.. Lambda

All vitamin D studies
Meta analysis
Home COVID-19 treatment researchVitamin DVitamin D (more..)
Melatonin Meta
Bromhexine Meta Metformin Meta
Budesonide Meta
Cannabidiol Meta Molnupiravir Meta
Colchicine Meta
Conv. Plasma Meta
Curcumin Meta Nigella Sativa Meta
Ensovibep Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Peg.. Lambda Meta
Fluvoxamine Meta Quercetin Meta
Hydroxychlor.. Meta Remdesivir Meta
Ivermectin Meta
Lactoferrin Meta

All Studies   Meta Analysis   Recent:  
0 0.5 1 1.5 2+ Mortality 79% Improvement Relative Risk Mortality (b) 48% ICU admission 87% Vitamin D for COVID-19  Nogués et al.  LATE TREATMENT Is late treatment with vitamin D beneficial for COVID-19? Prospective study of 838 patients in Spain Lower mortality (p=0.001) and ICU admission (p<0.0001) Nogués et al., The J. Clinical Endocr.., Jan 2021 Favors vitamin D Favors control

Calcifediol Treatment and COVID-19-Related Outcomes

Nogués et al., The Journal of Clinical Endocrinology & Metabolism, doi:10.1210/clinem/dgab405
Jan 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
Quasi-randomized trial with 930 hospitalized patients, 447 treated with calcifediol, showing significantly lower ICU admission and death with treatment. Note that the randomization in this trial is by ward. Authors report that patients were allocated to empty beds available at admission time regardless of patient conditions, and that staff in all wards followed the same protocol.
The earlier preprint for this article was censored by the Lancet. The Lancet reportedly requested a review from a Twitter user that posted negative comments The review provides useful feedback for the authors to improve the reporting of the cluster nature of the RCT, and to explain the delay in registration, however it is highly unusual to censor a preprint in this way. Authors responded to the issues raised here:
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 19th of 116 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 38 sextillion). 28 studies are RCTs, which show efficacy with p=0.0000081.
risk of death, 79.0% lower, RR 0.21, p = 0.001, treatment 21 of 447 (4.7%), control 62 of 391 (15.9%), NNT 9.0, adjusted per study, ITT.
risk of death, 48.0% lower, RR 0.52, p = 0.001, treatment 500, control 338, adjusted per study, including patients treated later.
risk of ICU admission, 87.0% lower, RR 0.13, p < 0.001, treatment 20 of 447 (4.5%), control 82 of 391 (21.0%), NNT 6.1, adjusted per study, ITT.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Nogués et al., 22 Jan 2021, prospective quasi-randomized (ward), Spain, peer-reviewed, 16 authors, dosage calcifediol 0.5mg day 1, 0.27mg day 3, 0.27mg day 7, 0.27mg day 15, 0.27mg day 30.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperVitamin DAll
Calcifediol treatment and COVID-19-related outcomes
X Nogues, D Ovejero, J M Quesada-Gomez, R Bouillon, D Arenas, J Pascual, J Villar-Garcia, A Rial, C Gimenez-Argente, M L Cos, J Rodriguez-Morera, I Campodarve, R Guerri-Fernandez, M Pineda-Moncusí, PhD Natalia Garcia-Giralt
Background COVID-19 is a major health problem because of acute respiratory distress syndrome, saturation of intensive care units (ICU) and mortality. Methods Our study aims to elucidate the effect of calcifediol [25(OH)D 3 ] treatment on ICU admission and mortality, in patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 participants were included. Participants (n=551) were randomly assigned to calcifediol treatment (532 ug on day one and 266 ug on day 3, 7, 15, and 30) at the time of hospital admission or as controls (n=379). Findings ICU assistance was required by 110 (11.8%) participants. Out of 551 patients treated with calcifediol at admission, 30 (5.4%) required ICU, compared to 80 out of 379 controls (21.1%; p<0.0001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25(OH)D levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (RR 0.18 [95% CI 0.11;0.29]). Baseline 25(OH)D levels inversely correlated with the risk of ICU admission (RR 0.53 [95% CI 0.35;0.80]). Overall mortality was 10%. In the Intention-to-treat analysis, 36 (6.5%) out of 551 patients treated with calcifediol at admission died compared to 57 patients (15%) out of 379 controls (p=0.001). Adjusted results showed a reduced mortality for more of 60%. Higher baseline 25(OH)D levels were significantly associated with decreased mortality (RR 0.40 [95% CI 0.24;0.67]). Age and obesity were also predictors of mortality. Interpretation In patients hospitalized with COVID-19, calcifediol treatment at the time of hospitalization significantly reduced ICU admission and mortality. Implications of all the available evidence Vitamin D deficiency is common and even more so in COVID-19 patients compared to the general population. Rapid correction of such deficiency by calcifediol is easy, cheap, and appears as highly effective to control disease severity and avoid fatal outcomes in the setting of SARS-CoV-2 infection.
Adorini, Penna, Dendritic cell tolerogenicity: a key mechanism in immunomodulation by vitamin D receptor agonists, Hum Immunol
Amrein, Scherkl, Hoffmann, OH)D deficiency 2.0: an update on the current status worldwide, Eur J Clin Nutr
Baktash, Hosack, Patel, Vitamin D status and outcomes for hospitalised older patients with COVID-19, Postgrad Med J
Beigel, Tomashek, Dodd, Remdesivir for the Treatment of Covid-19 -Final Report, N Engl J Med
Boban, Novel coronavirus disease (COVID-19) update on epidemiology, pathogenicity, clinical course and treatments, Int J Clin Pract
Bouillon, Marcocci, Carmeliet, Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions, Endocr Rev
Carpagnano, Lecce, Quaranta, Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, J Endocrinol Invest
Castillo, Costa, Barrios, 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
Channappanavar, Perlman, Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Semin Immunopathol
Group, Horby, Lim, Dexamethasone in Hospitalized Patients with Covid-19 -Preliminary Report, N Engl J Med
Guan, Ni, Hu, Clinical Characteristics of Coronavirus Disease 2019 in China, N Engl J Med
Hastie, Pell, Sattar, Vitamin D and COVID-19 infection and mortality in UK Biobank, Eur J Nutr
Helming, Bose, Ehrchen, 1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation, Blood
Ilie, Stefanescu, Smith, The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality, Aging Clin Exp Res
Jordan, Adab, Cheng, Covid-19: risk factors for severe disease and death, BMJ
Kalil, Patterson, Mehta, Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19, N Engl J Med
Maghbooli, Sahraian, Ebrahimi, Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection, PLoS One
Martineau, Jolliffe, Hooper, Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data, BMJ
Meltzer, Best, Zhang, Vokes, Arora et al., Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results, JAMA Netw Open
Nair, Venkatesh, Center, Vitamin D deficiency and supplementation in critical illness-the known knowns and known unknowns, Crit Care
Nirula, Shen, Skovronsky, Neutralizing Antibody LY-CoV555 for Outpatient Covid-19. Reply, N Engl J Med
Panagiotou, Tee, Ihsan, Original publication: Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity, Clin Endocrinol (Oxf)
Pizzini, Aichner, Sahanic, Impact of Vitamin D Deficiency on COVID-19-A Prospective Analysis from the CovILD Registry, Nutrients
Quesada-Gomez, Bouillon, Is calcifediol better than cholecalciferol for vitamin D supplementation?, Osteoporos Int
Radujkovic, Hippchen, Tiwari-Heckler, Dreher, Boxberger, Vitamin D Deficiency and Outcome of COVID-19 Patients, Nutrients
Russo, Pitter, Da Re, Tonon, Avossa et al., Epidemiology and public health response in early phase of COVID-19 pandemic, Veneto Region, Italy, 21 February to, Euro Surveill
Xu, Shi, Wang, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, Lancet Respir Med
Ye, Tang, Liao, Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study, J Am Coll Nutr
Late treatment
is less effective
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.
  or use drag and drop