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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  
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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. c19early.org Maghbooli et al., Endocrine Practice, Oct 2021 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,000+ studies for 104 treatments. c19early.org
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 [28‑43%] from meta analysis of the 69 mortality results to date.
Meta analysis shows that late stage treatment with calcitriol / calcifediol (or paricalcitol, alfacalcidol, etc.) is more effective than cholecalciferol: 69% [47‑82%] lower risk vs. 39% [27‑49%] 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 30 COVID-19 RCTs for vitamin D, which collectively show efficacy with p=0.0000032.
This is the 56th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 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.
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.
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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.
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