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The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis

Zhang et al., Frontiers in Nutrition, doi:10.3389/fnut.2024.1441847, PROSPERO CRD42024545945
Sep 2024  
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Mortality 28% Improvement Relative Risk Mortality, continuous 47% Mortality, single dose 12% Ventilation 22% ICU admission 42% ICU admission, continuous 56% ICU admission, single dose 21% Vitamin D for COVID-19  Zhang et al.  META ANALYSIS c19early.org 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 109 treatments. c19early.org
Systematic review and meta analysis of 21 studies with 4,553 COVID-19 patients showing significantly lower mortality and ICU admission rates with vitamin D supplementation. Improved results were seen with continuous dosing, total doses less than 100,000IU over 14 days, and in vitamin D deficient patients.
19 meta analyses show significant improvements with vitamin D treatment for mortality1-14, mechanical ventilation1,6,7,12,15,16, ICU admission1,3,6,7,10,12,14-18, hospitalization5,12, severity2,4,6,11,19, and cases8,18,19.
Currently there are 122 vitamin D treatment for COVID-19 studies, showing 36% lower mortality [28‑43%], 19% lower ventilation [-3‑36%], 45% lower ICU admission [28‑58%], 19% lower hospitalization [9‑29%], and 17% fewer cases [9‑24%].
risk of death, 28.0% lower, RR 0.72, p = 0.02.
risk of death, 47.0% lower, RR 0.53, p = 0.005, continuous dosing.
risk of death, 12.0% lower, RR 0.88, p = 0.31, single dose only.
risk of mechanical ventilation, 22.0% lower, RR 0.78, p = 0.14.
risk of ICU admission, 42.0% lower, RR 0.58, p = 0.01.
risk of ICU admission, 56.0% lower, RR 0.44, p = 0.02, continuous dosing.
risk of ICU admission, 21.0% lower, RR 0.79, p = 0.08, single dose only.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Zhang et al., 25 Sep 2024, peer-reviewed, 8 authors, trial PROSPERO CRD42024545945. Contact: shubin007@yeah.net, meixue91@yeah.net.
This PaperVitamin DAll
The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis
Xiangqun Zhang, Junyuan Wu, Hongmeng Dong, Na Shang, Yixuan Li, Ying Zhang, Shubin Guo, Xue Mei
Frontiers in Nutrition, doi:10.3389/fnut.2024.1441847
Objective: To analyze the impact of different methods of Vitamin D administration on the prognosis of COVID-19 patients. Methods: A comprehensive literature search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled trials and cohort studies that compared Vitamin D supplementation with control groups in COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses were performed based on the dosing regimen (singledose vs. continuous-dose), total Vitamin D intake within 14 days (≥100,000 IU vs. <100,000 IU), and baseline serum Vitamin D levels (deficient group: 25OHD < 30 ng/mL vs. non-restricted group). A random-effects model was employed for meta-analysis to account for heterogeneity among studies. Results: A total of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D supplementation significantly reduced the mortality rate (RR = 0.72, 95% CI: 0.54-0.94, I 2 = 54%, p = 0.02), with continuous dosing being more effective (RR = 0.53, 95% CI: 0.34-0.83, I 2 = 55%, p = 0.006) compared to single-dose (RR = 0.88, 95% CI: 0.69-1.12, I 2 = 21%, p = 0.3), and lower total doses (<100,000 IU) showing greater benefit (RR = 0.30, 95% CI: 0.21-0.44, I 2 = 0%, p < 0.0001). Mortality was significantly reduced in the Vitamin D-deficient group (25OHD < 30 ng/mL) (RR = 0.73, 95% CI: 0.59-0.89, I 2 = 0%, p = 0.002) but not in the non-restricted group. Regarding ICU admission, supplementation reduced ICU admission rates (RR = 0.58, 95% CI: 0.38-0.88, I 2 = 74%, p = 0.01), with continuous dosing (RR = 0.44, 95% CI: 0.22-0.90, I 2 = 74%, p = 0.02) being more effective than single-dose (RR = 0.79, 95% CI: 0.61-1.03, I 2 = 22%, p = 0.08), and lower doses (<100,000 IU) providing more significant reduction (RR = 0.31, 95% CI: 0.21-0.47, I 2 = 0%, p = 0.001). ICU admission rates were significantly reduced in the Vitamin D-deficient group (RR = 0.63, 95% CI: 0.42-0.93, I 2 = 0%, p = 0.02) but not in the non-restricted group (RR = 0.59, 95% CI: 0.32-1.11, I 2 = 86%, p = 0.1). For length of hospital stay, no significant differences were observed between Vitamin D and control groups (MD = -1, 95% CI: -2.16 to 0.16, p = 0.13), and subgroup analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no significant differences. Similarly, for
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 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. Supplementary material The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2024.1441847/ full#supplementary-material Frontiers in Nutrition 21 frontiersin.org
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{ 'indexed': {'date-parts': [[2024, 9, 26]], 'date-time': '2024-09-26T04:30:13Z', 'timestamp': 1727325013061}, 'reference-count': 66, 'publisher': 'Frontiers Media SA', 'license': [ { 'start': { 'date-parts': [[2024, 9, 25]], 'date-time': '2024-09-25T00:00:00Z', 'timestamp': 1727222400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': ['frontiersin.org'], 'crossmark-restriction': True}, 'abstract': '<jats:sec><jats:title>Objective</jats:title><jats:p>To analyze the impact of different ' 'methods of Vitamin D administration on the prognosis of COVID-19 ' 'patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A ' 'comprehensive literature search was conducted across four databases: PubMed, Embase, Web of ' 'Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled ' 'trials and cohort studies that compared Vitamin D supplementation with control groups in ' 'COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) ' 'admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses ' 'were performed based on the dosing regimen (single-dose vs. continuous-dose), total Vitamin D ' 'intake within 14\u2009days (≥100,000\u2009IU vs. &amp;lt;100,000\u2009IU), and baseline serum ' 'Vitamin D levels (deficient group: 25OHD\u2009&amp;lt;\u200930\u2009ng/mL vs. non-restricted ' 'group). A random-effects model was employed for meta-analysis to account for heterogeneity ' 'among studies.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total ' 'of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D ' 'supplementation significantly reduced the mortality rate (RR\u2009=\u20090.72, 95% CI: ' '0.54–0.94, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200954%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.02), with continuous dosing being more effective ' '(RR\u2009=\u20090.53, 95% CI: 0.34–0.83, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> ' '=\u200955%, <jats:italic>p</jats:italic>\u2009=\u20090.006) compared to single-dose (RR\u2009' '=\u20090.88, 95% CI: 0.69–1.12, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009' '21%, <jats:italic>p</jats:italic>\u2009=\u20090.3), and lower total doses ' '(&amp;lt;100,000\u2009IU) showing greater benefit (RR\u2009=\u20090.30, 95% CI: 0.21–0.44, ' '<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, ' '<jats:italic>p</jats:italic>\u2009&amp;lt;\u20090.0001). Mortality was significantly reduced ' 'in the Vitamin D-deficient group (25OHD\u2009&amp;lt;\u200930\u2009ng/mL) (RR\u2009=\u2009' '0.73, 95% CI: 0.59–0.89, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.002) but not in the non-restricted group. ' 'Regarding ICU admission, supplementation reduced ICU admission rates (RR\u2009=\u20090.58, ' '95% CI: 0.38–0.88, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200974%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.01), with continuous dosing (RR\u2009=\u20090.44, ' '95% CI: 0.22–0.90, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200974%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.02) being more effective than single-dose (RR\u2009' '=\u20090.79, 95% CI: 0.61–1.03, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009' '22%, <jats:italic>p</jats:italic>\u2009=\u20090.08), and lower doses (&amp;lt;100,000\u2009' 'IU) providing more significant reduction (RR\u2009=\u20090.31, 95% CI: 0.21–0.47, ' '<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.001). ICU admission rates were significantly ' 'reduced in the Vitamin D-deficient group (RR\u2009=\u20090.63, 95% CI: 0.42–0.93, ' '<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, ' '<jats:italic>p</jats:italic>\u2009=\u20090.02) but not in the non-restricted group (RR\u2009' '=\u20090.59, 95% CI: 0.32–1.11, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009' '86%, <jats:italic>p</jats:italic>\u2009=\u20090.1). For length of hospital stay, no ' 'significant differences were observed between Vitamin D and control groups (MD\u2009=\u2009' '−1, 95% CI: −2.16 to 0.16, <jats:italic>p</jats:italic>\u2009=\u20090.13), and subgroup ' 'analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no ' 'significant differences. Similarly, for endotracheal intubation, there was no significant ' 'difference in intubation rates between groups (RR\u2009=\u20090.78, 95% CI: 0.56–1.08, ' '<jats:italic>p</jats:italic>\u2009=\u20090.13), and subgroup analyses confirmed no ' 'significant effect of different dosing strategies or baseline Vitamin D status on intubation ' 'rates.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Vitamin D ' 'supplementation improves clinical outcomes in COVID-19 patients by reducing mortality and ICU ' 'admission rates, particularly when administered continuously with a total dose of less than ' '100,000\u2009IU over 14\u2009days, and among those with baseline Vitamin D deficiency ' '(25OHD\u2009&amp;lt;\u200930\u2009ng/mL). However, there were no significant effects on the ' 'length of hospital stay or endotracheal intubation rates, regardless of the dosing regimen or ' 'baseline Vitamin D levels. 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dendritic cells', 'volume': '44', 'author': 'Kundu', 'year': '2014', 'journal-title': 'Eur J Immunol'}, { 'key': 'ref59', 'doi-asserted-by': 'publisher', 'first-page': '11', 'DOI': '10.1186/s12931-023-02642-9', 'article-title': 'High-dose vitamin D(3) supplementation shows no beneficial effects on ' 'white blood cell counts, acute phase reactants, or frequency of ' 'respiratory infections', 'volume': '25', 'author': 'Wall-Gremstrup', 'year': '2024', 'journal-title': 'Respir Res'}, { 'key': 'ref60', 'first-page': '3675', 'article-title': 'How to optimize vitamin D supplementation to prevent cancer, based on ' 'cellular adaptation and hydroxylase enzymology', 'volume': '29', 'author': 'Vieth', 'year': '2009', 'journal-title': 'Anticancer Res'}, { 'key': 'ref61', 'doi-asserted-by': 'publisher', 'first-page': '46', 'DOI': '10.1002/jbmr.1740', 'article-title': 'Fibroblast growth factor 23 inhibits extrarenal synthesis of ' '1,25-dihydroxyVitamin D in human monocytes', 'volume': '28', 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'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 9, 25]], 'date-time': '2024-09-25T21:21:47Z', 'timestamp': 1727299307000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.frontiersin.org/articles/10.3389/fnut.2024.1441847/full'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 9, 25]]}, 'references-count': 66, 'alternative-id': ['10.3389/fnut.2024.1441847'], 'URL': 'http://dx.doi.org/10.3389/fnut.2024.1441847', 'relation': {}, 'ISSN': ['2296-861X'], 'subject': [], 'container-title-short': 'Front. Nutr.', 'published': {'date-parts': [[2024, 9, 25]]}}
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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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