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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality -7% Improvement Relative Risk ICU admission 79% ARDS 28% Vitamin D  Cervero et al.  LATE TREATMENT  RCT Is late treatment with vitamin D beneficial for COVID-19? RCT 85 patients in Spain (June 2020 - March 2021) Lower ICU admission with vitamin D (not stat. sig., p=0.2) c19early.org Cervero et al., Frontiers in Pharmacol.., Jul 2022 Favors high dose Favors low dose

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial

Cervero et al., Frontiers in Pharmacology, doi:10.3389/fphar.2022.863587
Jul 2022  
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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 8 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,200+ studies for 70+ treatments. c19early.org
RCT 85 hospitalized patients in Spain, comparing 10,000IU/day vs. 2,000IU/day cholecalciferol, showing beneficial effects of the larger dose.
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.
risk of death, 7.3% higher, RR 1.07, p = 1.00, treatment 1 of 41 (2.4%), control 1 of 44 (2.3%).
risk of ICU admission, 78.5% lower, RR 0.21, p = 0.20, treatment 1 of 41 (2.4%), control 5 of 44 (11.4%), NNT 11.
risk of ARDS, 28.5% lower, RR 0.72, p = 0.74, treatment 4 of 41 (9.8%), control 6 of 44 (13.6%), NNT 26.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Cervero et al., 4 Jul 2022, Single Blind Randomized Controlled Trial, placebo-controlled, Spain, peer-reviewed, median age 65.0, 10 authors, study period June 2020 - March 2021, average treatment delay 7.0 days, dosage 10,000IU days 1-14. Contact: mcerveroj@me.com, mcoiras@isciii.es, m.torres@isciii.es.
This PaperVitamin DAll
Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial
Miguel Cervero, Daniel López-Wolf, Guiomar Casado, Maria Novella-Mena, Pablo Ryan-Murua, María Luisa Taboada-Martínez, Sara Rodríguez-Mora, Lorena Vigón, Mayte Coiras, Montserrat Torres
Frontiers in Pharmacology, doi:10.3389/fphar.2022.863587
There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D 3 supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53-74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4-13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12-45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D 3 for 14 days in
Adverse Events Treatment Group 2000 UI/day (n = 44) 10,000 UI/day (n = 41) Cytolysis-no. (%) 1 (2%) Diarrhea-no. (%) 1 (2%) Pulmonary embolism-no. (%) 2 (5%) 1 (2%) Neuropathy-no. (%) 1 (2%) Urinary (tract) infection-no. (%) 2 (5%) ETHICS STATEMENT SUPPLEMENTARY MATERIAL The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2022.863587/ full#supplementary-material Conflict of Interest: Drug Cholecalciferol (vitamin D) used in this study was donated by Italfarmaco Group (Cholecalciferol 25,000IU/2.5 ml oral solution). Italfarmaco Group had no role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or the preparation, review, or approval of the manuscript. Publisher's Note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
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{ 'DOI': '10.3389/fphar.2022.863587', 'ISSN': ['1663-9812'], 'URL': 'http://dx.doi.org/10.3389/fphar.2022.863587', 'abstract': '<jats:p>There is now sufficient evidence to support that vitamin D deficiency may predispose ' 'to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested ' 'that vitamin D<jats:sub>3</jats:sub> supplementation may be used prophylactically as an ' 'affordable and safe strategy that could be added to the existing COVID-19 standard treatment. ' 'This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to ' 'evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 ' 'IU/day of cholecalciferol supplementation for 14\xa0days to reduce the duration and severity ' 'of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65\xa0' 'years (Interquartile range (IQR): 53–74), most of them (71%) were men and the mean baseline ' 'of 25-hydroxyvitamin D (25(OH)D) in serum was 15\xa0ng/ml (standard deviation (SD):6). After ' '14\xa0days of supplementation, serum 25(OH)D levels were significantly increased in the group ' 'who received 10,000IU/day (<jats:italic>p</jats:italic> &amp;lt; 0.0001) ' '(<jats:italic>n</jats:italic> = 44) in comparison with the 2,000IU/day group ' '(<jats:italic>n</jats:italic> = 41), especially in overweight and obese participants, and the ' 'higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed ' 'acute respiratory distress syndrome (ARDS). The median length of hospital stay in these ' 'patients with ARDS was significantly different in the participants assigned to the ' '10,000IU/day group (<jats:italic>n</jats:italic> = 4; 7 days; IQR: 4–13) and the 2,000IU/day ' 'group (<jats:italic>n</jats:italic> = 6; 27 days; IQR: 12–45) (<jats:italic>p</jats:italic> = ' '0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group ' '(<jats:italic>p</jats:italic> = 0.049). In terms of blood parameters, we did not identify ' 'overall significant improvements, although the platelet count showed a modest but significant ' 'difference in those patients who were supplemented with the higher dose ' '(<jats:italic>p</jats:italic> = 0.0492). 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J. Med. Sci.', 'key': 'B1', 'volume': '362', 'year': '2021'}, { 'DOI': '10.1016/j.coph.2010.04.001', 'article-title': 'Vitamin D: Modulator of the Immune System', 'author': 'Baeke', 'doi-asserted-by': 'publisher', 'first-page': '482', 'journal-title': 'Curr. Opin. Pharmacol.', 'key': 'B2', 'volume': '10', 'year': '2010'}, { 'DOI': '10.1111/joim.13158', 'article-title': 'The Link between Vitamin D and COVID-19: Distinguishing Facts from ' 'Fiction', 'author': 'Bergman', 'doi-asserted-by': 'publisher', 'first-page': '131', 'journal-title': 'J. Intern. Med.', 'key': 'B3', 'volume': '289', 'year': '2021'}, { 'DOI': '10.1017/S0950268806007175', 'article-title': 'Epidemic Influenza and Vitamin D', 'author': 'Cannell', 'doi-asserted-by': 'publisher', 'first-page': '1129', 'journal-title': 'Epidemiol. Infect.', 'key': 'B4', 'volume': '134', 'year': '2006'}, { 'DOI': '10.1016/j.semcancer.2020.05.018', 'article-title': 'An Update on Vitamin D Signaling and Cancer', 'author': 'Carlberg', 'doi-asserted-by': 'publisher', 'first-page': '217', 'journal-title': 'Semin. Cancer Biol.', 'key': 'B5', 'volume': '79', 'year': '2022'}, { 'DOI': '10.1016/S0140-6736(20)30211-7', 'article-title': 'Epidemiological and Clinical Characteristics of 99 Cases of 2019 Novel ' 'Coronavirus Pneumonia in Wuhan, China: a Descriptive Study', 'author': 'Chen', 'doi-asserted-by': 'publisher', 'first-page': '507', 'journal-title': 'Lancet', 'key': 'B6', 'volume': '395', 'year': '2020'}, { 'DOI': '10.3389/fpubh.2021.736665', 'article-title': 'Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical ' 'Outcomes', 'author': 'Chiodini', 'doi-asserted-by': 'publisher', 'first-page': '736665', 'journal-title': 'Front. 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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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