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 40% Improvement Relative Risk Ventilation 60% ICU admission 40% ICU time 36% Hospitalization time 17% Vitamin D  Maghbooli et al.  LATE TREATMENT  DB RCT Is late treatment with vitamin D beneficial for COVID-19? Double-blind RCT 106 patients in Iran Lower ventilation (p=0.44) and ICU admission (p=0.42), not sig. Maghbooli et al., Endocrine Practice, Oct 2021 Favors vitamin D Favors control

Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in patients hospitalized with COVID-19: a pilot, multicenter, randomized, placebo-controlled double blind clinical trial

Maghbooli et al., Endocrine Practice, doi:10.1016/j.eprac.2021.09.016
Oct 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalization, ICU duration, ventilation, and mortality was lower with treatment, without reaching statistical significance with the small sample size. The dosage used in this trial was much lower than other trials.
Although the 40% lower mortality is not statistically significant, it is consistent with the significant 36% lower mortality [27‑43%] from meta analysis of the 66 mortality results to date.
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 7th of 28 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000081.
This is the 56th of 116 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 38 sextillion).
risk of death, 40.0% lower, RR 0.60, p = 0.72, treatment 3 of 53 (5.7%), control 5 of 53 (9.4%), NNT 26.
risk of mechanical ventilation, 60.0% lower, RR 0.40, p = 0.44, treatment 2 of 53 (3.8%), control 5 of 53 (9.4%), NNT 18.
risk of ICU admission, 40.0% lower, RR 0.60, p = 0.42, treatment 6 of 53 (11.3%), control 10 of 53 (18.9%), NNT 13.
ICU time, 36.4% lower, relative time 0.64, p = 0.20, treatment 53, control 53.
hospitalization time, 16.7% lower, relative time 0.83, p = 0.10, treatment 53, control 53.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Maghbooli et al., 13 Oct 2021, Double Blind Randomized Controlled Trial, Iran, peer-reviewed, 12 authors, dosage calcifediol 25μg daily, mean daily dose.
All Studies   Meta Analysis   Submit Updates or Corrections
This PaperVitamin DAll
Treatment With 25-Hydroxyvitamin D3 (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
Ph.D Zhila Maghbooli, M.D, Saeid Mohammad Ali Sahraian, Saeidreza Jamalimoghadamsiahkali, M.D Asma Asadi, Azadeh Zarei, M.D Abolfazl Zendehdel, M.D Tarlan Varzandi, M.S.c Sara Mohammadnabi, Neda Alijani, Mehrdad Mehrdad Karimi, M.D Arash Shirvani, Ph.D Michael F Holick
Endocrine Practice, doi:10.1016/j.eprac.2021.09.016
Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre -including this research content -immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in patients hospitalized with COVID-19: a pilot, multicenter, randomized, placebo-controlled double blind clinical trial
J o u r n a l P r e -p r o o f J o u r n a l P r e -p r o o f Declaration of interests ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare the following personal relationships which may be considered as potential competing interests: Michael F. Holick was a consultant for Quest Diagnostics Inc. is a consultant for Ontometrics Inc and Biogena Inc., received a grant from Carbogen Amcis BV and was on the speaker's Bureau for Abbott Inc. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Alcala-Diaz, Limia-Perez, Gomez-Huelgas, Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study, Nutrients
Annweiler, Hanotte, De L'eprevier, Sabatier, Lafaie et al., None
Barger-Lux, Heaney, Dowell, Chen, Holick, Vitamin D and its Major Metabolites: Serum Levels after Graded Oral Dosing in Healthy Men, Osteoporosis International
Biancuzzo, Clarke, Reitz, Travison, Holick, Serum concentrations of 1,25-dihydroxyvitamin D2 and 1,25-dihydroxyvitamin D3 in response to vitamin D2 and vitamin D3 supplementation, The Journal of clinical endocrinology and metabolism
Bischoff-Ferrari, Hughes, Stöcklin, Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity. Journal of bone and mineral research : the official journal of the American, Society for Bone and Mineral Research
Borges, Pithon-Curi, Curi, Hatanaka, COVID-19 and neutrophils: The relationship between hyperinflammation and neutrophil extracellular traps, Mediators of Inflammation
Bouillon, Marcocci, Carmeliet, Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions, Endocrine reviews
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, The Journal of steroid biochemistry and molecular biology
Cesareo, Falchetti, Attanasio, Tabacco, Naciu et al., Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?, Nutrients
Cesareo, Falchetti, Attanasio, Tabacco, Naciu et al., None
Charoenngam, Holick, Immunologic Effects of Vitamin D on Human Health and Disease, Nutrients
Charoenngam, Kalajian, Shirvani, A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25
Chen, Zhou, Dong, Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study, The lancet
Denman, Lymphocyte function and virus infections, Journal of clinical pathology Supplement (Royal College of Pathologists)
Fa, Neutrophil-to-lymphocyte ratio and lymphocyte-to-Creactive protein ratio in patients with severe coronavirus disease 2019 (COVID-19): a metaanalysis, Journal of medical virology
Goncalves-Mendes, Talvas, Dualé, Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial, Frontiers in immunology
Grant, Lahore, Mcdonnell, Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths, Nutrients
Guan, Liang, Zhao, Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis, The European respiratory journal
Hewison, Vitamin D and the immune system: new perspectives on an old theme. Endocrinology and metabolism clinics of North America
Holick, Binkley, Bischoff-Ferrari, Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline, The Journal of clinical endocrinology and metabolism
Hossein-Nezhad, Holick, Vitamin D for health: a global perspective, Mayo Clinic proceedings
Huang, Berube, Mcnamara, Lymphocyte Subset Counts in COVID-19
Hypovitaminosis, Is It Time to Consider the Use of Calcifediol?, Nutrients
Kaufman, Niles, Kroll, Bi, Holick, SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels, PloS one
Lippi, Plebani, Procalcitonin in patients with severe coronavirus disease 2019 (COVID-19): A meta-analysis, Clinica chimica acta; international journal of clinical chemistry
Maghbooli, Omidifar, Varzandi, Salehnezhad, Sahraian, Reduction in circulating vitamin D binding protein in patients with multiple sclerosis, BMC neurology
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 (Clinical research ed
Mccullough, Lehrer, Amend, expressed as the mean ± SD for parametric tests or median (IRQ) for non-parametric tests and categorical variables were presented as percentages. N=available data for each variable Albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), Body mass index (BMI), calcium (Ca), creatinine (Cr), creatine phosphokinase (CPK), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), bicarbonate (HCO3), potassium (K), lactate dehydrogenase (LDH)
Misra, Agarwal, Gasparyan, Zimba, Rheumatologists' perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets, Clinical rheumatology
Murai, Fernandes, Sales, 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
Navarro-Valverde, Sosa-Henríquez, Alhambra-Expósito, Quesada-Gómez, None
Nogues, Ovejero, Pineda-Moncusí, Calcifediol treatment and COVID-19-related outcomes, The Journal of clinical endocrinology and metabolism
Pereira, Damascena, Azevedo, De Almeida Oliveira, Da et al., Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis, Critical reviews in food science and nutrition
Quesada-Gomez, Bouillon, Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
Sosa Henríquez, De, Romero, Cholecalciferol or Calcifediol in the Management of Vitamin D Deficiency, Nutrients
Wu, Mcgoogan, Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention, Jama
Xu, Shi, Wang, Pathological findings of COVID-19 associated with acute respiratory distress syndrome, The Lancet respiratory medicine
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