All Studies Meta Analysis Recent:

The effect of high-dose parenteral vitamin D3 on COVID-19-related inhospital mortality in critical COVID-19 patients during intensive care unit admission: an observational cohort study

Güven et al., European Journal of Clinical Nutrition, doi:10.1038/s41430-021-00984-5

Jul 2021

Post
Facebook

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 8 countries.

Lower risk for mortality, ICU admission, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19early.org

Retrospective 175 ICU patients, 113 treated with a single dose of 300,000IU intramuscular cholecalciferol, showing lower mortality with treatment, but not reaching statistical significance. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage.

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 42nd of 120 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 248 sextillion).

29 studies are RCTs, which show efficacy with p=0.0000024.

This study is excluded in the after exclusion results of meta analysis: very late stage, ICU patients.

Important missing comments or errors? Let us know.

risk of death, 24.8% lower, RR 0.75, p = 0.32, treatment 43 of 113 (38.1%), control 30 of 62 (48.4%), NNT 9.7, odds ratio converted to relative risk.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

Güven et al., 23 Jul 2021, retrospective, Turkey, peer-reviewed, 2 authors, dosage 300,000IU single dose.

This Paper Vitamin D All

The effect of high-dose parenteral vitamin D3 on COVID-19-related inhospital mortality in critical COVID-19 patients during intensive care unit admission: an observational cohort study

Mehmet Güven, Hamza Gültekin

European Journal of Clinical Nutrition, doi:10.1038/s41430-021-00984-5

BACKGROUND: In many studies, vitamin D has been found to be low in COVID-19 patients. In this study, we aimed to investigate the relationship between clinical course and inhospital mortality with parenteral administration of high-dose vitamin D 3 within the first 24 h of admission to patients who were hospitalized in the intensive care unit (ICU) because of COVID-19 with vitamin D deficiency. METHODS: This study included 175 COVID-19 patients with vitamin D deficiency [25(OH) D <12 ng/mL] who were hospitalized in the ICU. Vitamin D 3 group (n = 113) included patients who received a single dose of 300,000 IU vitamin D3 intramuscularly. Vitamin D 3 was not administered to the control group (n = 62). RESULTS: Median C-reactive protein level was 10.8 mg/dL in the vitamin D 3 group and 10.6 mg/dL in the control group (p = 0.465). Thirty-nine percent (n = 44) of the patients in the vitamin D 3 group were intubated endotracheally, and 50% (n = 31) of the patients in the control group were intubated endotracheally (p = 0.157). Parenteral vitamin D 3 administration was not associated with inhospital mortality by multivariate logistic regression analysis. According to Kaplan-Meier survival analysis, the median survival time was 16 d in the vitamin D3 group and 17 d in the control group (log-rank test, p = 0.459). CONCLUSION: In this study, which was performed for the first time in the literature, it was observed that high-dose parenteral vitamin D 3 administration in critical COVID-19 patients with vitamin D deficiency during admission to the ICU did not reduce the need for intubation, length of hospital stay, and inhospital mortality.

COMPETING INTERESTS The authors declare no competing interests. ADDITIONAL INFORMATION Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41430-021-00984-5. Correspondence and requests for materials should be addressed to M.G. Reprints and permission information is available at http://www.nature.com/ reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

Abraham, Dowling, Florentine, Can optimum solar radiation exposure or supplemented vitamin D intake reduce the severity of COVID-19 symptoms?, Int J Environ Res Public Health, doi:10.3390/ijerph18020740

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

Asan, Üstündağ, Koca, Şimşek, Sayan et al., Do initial hematologic indices predict the severity of COVID-19 patients?, Turk J Med Sci, doi:10.3906/sag-2007-97

Atkins, Masoli, Delgado, Pilling, Kuo et al., Preexisting comorbidities predicting COVID-19 and mortality in the UK Biobank Community Cohort, J Gerontol A Biol Sci Med Sci, doi:10.1093/gerona/glaa183

Bilezikian, Bikle, Hewison, Castro, Formenti et al., MECHANISMS IN ENDOCRINOLOGY: vitamin D and COVID-19, Eur J Endocrinol, doi:10.1530/EJE-20-0665

Brockman-Schneider, Pickles, Gern, Effects of vitamin D on airway epithelial cell morphology and rhinovirus replication, PLoS ONE, doi:10.1371/journal.pone.0086755

Calder, Nutrition, immunity and COVID-19, BMJ Nutr Prev Health, doi:10.1136/bmjnph-2020-000085

Castillo, Costa, Barrios, Díaz, 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

Charoenngam, Holick, Immunologic effects of vitamin D on human health and disease, Nutrients, doi:10.3390/nu12072097

Chen, Zhang, Ge, Du, Deb et al., Vitamin D inhibits nuclear factor κ B activation by interacting with IκB kinase β protein, J Biol Chem, doi:10.1074/jbc.M113.467670

Conti, Ronconi, Caraffa, Gallenga, Ross et al., Induction of proinflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies, J Biol Regul Homeost Agents, doi:10.23812/CONTI-E

Ebadi, Montano-Loza, Perspective: improving vitamin D status in the management of COVID-19, Eur J Clin Nutr, doi:10.1038/s41430-020-0661-0

Fig, 2 Survival of the groups according to Kaplan-Meier analysis

Gombart, Borregaard, Koeffler, Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3, FASEB J, doi:10.1096/fj.04-3284com

Gonçalves, Gonçalves, Guarnieri, Risegato, Guimarães et al., Prevalence of obesity and hypovitaminosis D in elderly with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin Nutr ESPEN, doi:10.1016/j.clnesp.2020.10.008

Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients, doi:10.3390/nu12040988

Greiller, Suri, Jolliffe, Kebadze, Hirsman et al., Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells, J Steroid Biochem Mol Biol, doi:10.1016/j.jsbmb.2018.11.013

Guan, Liang, Zhao, Liang, Chen et al., Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis, Eur Respir J, doi:10.1183/13993003.00547-2020

Güven, Gültekin, Could serum total cortisol level at admission predict mortality due to coronavirus disease 2019 in the intensive care unit? A prospective study, Sao Paulo Med J, doi:10.1590/1516-3180.2020.0722.R1.2302021

Han, Jones, Tangpricha, Brown, Brown et al., High dose vitamin D administration in ventilated intensive care unit patients: a pilot double blind randomized controlled trial, J Clin Transl Endocrinol, doi:10.1016/j.jcte.2016.04.004

Hastie, Pell, Sattar, Vitamin D and COVID-19 infection and mortality in UK Biobank, Eur J Nutr, doi:10.1007/s00394-020-02372-4

Hughes, Norton, Vitamin D and respiratory health, Clin Exp Immunol, doi:10.1111/j.1365-2249.2009.04001.x

Kaufman, Niles, Kroll, Bi, Holick, SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels, PLoS ONE, doi:10.1371/journal.pone.0239252

Maghbooli, Sahraian, Ebrahimi, Pazoki, Kafan et al., 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, doi:10.1371/journal.pone.0239799

Martineau, Forouhi, Vitamin D for COVID-19: a case to answer?, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587(20)30268-0

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

Merzon, Tworowski, Gorohovski, Vinker, Cohen et al., Low plasma 25(OH) vitamin D level is associated with increased risk of COVID-19 infection: an Israeli population-based study, FEBS J, doi:10.1111/febs.15495

Mitchell, Vitamin-D and COVID-19: do deficient risk a poorer outcome?, Lancet Diabetes Endocrinol, doi:10.1016/S2213-8587(20)30183-2

Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J Med Virol, doi:10.1002/jmv.26360

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

Pekar, Worobey, Moshiri, Scheffler, Wertheim, Timing the SARS-CoV-2 index case in Hubei province, Science, doi:10.1126/science.abf8003

Prietl, Treiber, Pieber, Amrein, Vitamin D and immune function, Nutrients, doi:10.3390/nu5072502

Solmaz, Özçaylak, Alakuş, Kılıç, Kalın et al., Risk factors affecting ICU admission in COVID-19 patients; Could air temperature be an effective factor?, Int J Clin Pract, doi:10.1111/ijcp.13803

Tamer, Mesçi, Role of vitamin D in the immune system, Turkjem, doi:10.4274/Tjem.1938

Thomson, Hunter, Dutton, Schneider, Khosravi et al., Clinical characteristics and outcomes of critically ill patients with COVID-19 admitted to an intensive care unit in London: a prospective observational cohort study, PloS ONE, doi:10.1371/journal.pone.0243710

Yang, Ding, Xu, Pu, Li et al., Increased circulating level of interleukin-6 and CD8 + T cell exhaustion are associated with progression of COVID-19, Infect Dis Poverty, doi:10.1186/s40249-020-00780-6

Zumla, Hui, Azhar, Memish, Maeurer, Reducing mortality from 2019-nCoV: host-directed therapies should be an option, Lancet, doi:10.1016/S0140-6736(20)30305-6

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.

Submit

Post

@CovidAnalysis

FAQ

Public domain CC0 1.0