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Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths

Grant et al., Nutrients, 12:4, 988, doi:10.3390/nu12040988
Apr 2020  
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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.
5,100+ studies for 112 treatments. c19early.org
Review of the evidence that vitamin D supplementation could reduce COVID-19 risk.
Reviews covering vitamin D for COVID-19 include1-35.
Grant et al., 2 Apr 2020, peer-reviewed, 7 authors.
This PaperVitamin DAll
Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths
William B Grant, Henry Lahore, Sharon L Mcdonnell, Carole A Baggerly, Christine B French, Jennifer L Aliano, Harjit P Bhattoa
Nutrients, doi:10.3390/nu12040988
The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D 3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D 3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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Those mechanisms include inducing cathelicidins and ' 'defensins that can lower viral replication rates and reducing concentrations of ' 'pro-inflammatory cytokines that produce the inflammation that injures the lining of the ' 'lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory ' 'cytokines. Several observational studies and clinical trials reported that vitamin D ' 'supplementation reduced the risk of influenza, whereas others did not. Evidence supporting ' 'the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in ' 'winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number ' 'of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency ' 'has been found to contribute to acute respiratory distress syndrome; and that case-fatality ' 'rates increase with age and with chronic disease comorbidity, both of which are associated ' 'with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that ' 'people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a ' 'few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be ' 'to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people ' 'who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized ' 'controlled trials and large population studies should be conducted to evaluate these ' 'recommendations.</jats:p>', 'DOI': '10.3390/nu12040988', 'type': 'journal-article', 'created': {'date-parts': [[2020, 4, 2]], 'date-time': '2020-04-02T15:57:14Z', 'timestamp': 1585843034000}, 'page': '988', 'source': 'Crossref', 'is-referenced-by-count': 1204, 'title': 'Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections ' 'and Deaths', 'prefix': '10.3390', 'volume': '12', 'author': [ { 'ORCID': 'http://orcid.org/0000-0002-1439-3285', 'authenticated-orcid': False, 'given': 'William', 'family': 'Grant', 'sequence': 'first', 'affiliation': []}, {'given': 'Henry', 'family': 'Lahore', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sharon', 'family': 'McDonnell', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6172-2005', 'authenticated-orcid': False, 'given': 'Carole', 'family': 'Baggerly', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-5859-7231', 'authenticated-orcid': False, 'given': 'Christine', 'family': 'French', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jennifer', 'family': 'Aliano', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4909-0065', 'authenticated-orcid': False, 'given': 'Harjit', 'family': 'Bhattoa', 'sequence': 'additional', 'affiliation': []}], 'member': '1968', 'published-online': {'date-parts': [[2020, 4, 2]]}, 'reference': [ {'key': 'ref1', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa2001017'}, {'key': 'ref2', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(03)14630-2'}, {'key': 'ref3', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMoa1306742'}, {'key': 'ref4', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/v11010059'}, {'key': 'ref5', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/resp.13196'}, {'key': 'ref6', 'doi-asserted-by': 'publisher', 'DOI': '10.7189/jogh.09.020421'}, {'key': 'ref7', 'doi-asserted-by': 'publisher', 'DOI': '10.1056/NEJMra070553'}, {'key': 'ref8', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.ecl.2017.07.001'}, {'key': 'ref9', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.jcv.2010.12.006'}, {'key': 'ref10', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/j.1365-2265.2011.04261.x'}, {'key': 'ref11', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7064240'}, {'key': 'ref12', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu7105392'}, {'key': 'ref13', 'doi-asserted-by': 'publisher', 'DOI': '10.1039/c6pp00355a'}, {'key': 'ref14', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/j.clinthera.2017.04.004'}, {'key': 'ref15', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/ijms19082419'}, {'key': 'ref16', 'doi-asserted-by': 'publisher', 'DOI': '10.1155/2018/5813095'}, {'key': 'ref17', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/nu12010236'}, {'key': 'ref18', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/mnfr.201000174'}, {'key': 'ref19', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/cei.13042'}, {'key': 'ref20', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0950268820000151'}, {'key': 'ref21', 'doi-asserted-by': 'publisher', 'DOI': '10.1002/ppul.24699'}, {'key': 'ref22', 'doi-asserted-by': 'publisher', 'DOI': '10.1126/science.1123933'}, {'key': 'ref23', 'doi-asserted-by': 'publisher', 'DOI': '10.4049/jimmunol.0803736'}, {'key': 'ref24', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0029665111003351'}, {'key': 'ref25', 'doi-asserted-by': 'publisher', 'DOI': '10.1517/14712598.7.9.1449'}, {'key': 'ref26', 'doi-asserted-by': 'publisher', 'DOI': '10.5114/ceji.2015.51359'}, {'key': 'ref27', 'doi-asserted-by': 'publisher', 'DOI': '10.1371/journal.pone.0025333'}, {'key': 'ref28', 'doi-asserted-by': 'publisher', 'DOI': '10.3390/ijms20143562'}, {'key': 'ref29', 'doi-asserted-by': 'publisher', 'DOI': '10.1007/s11010-019-03658-w'}, {'key': 'ref30', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S0140-6736(20)30183-5'}, {'key': 'ref31', 'doi-asserted-by': 'publisher', 'DOI': '10.1111/apm.12982'}, {'key': 'ref32', 'doi-asserted-by': 'publisher', 'DOI': '10.1017/S0029665110001722'}, { 'key': 'ref33', 'doi-asserted-by': 'crossref', 'first-page': '3032', 'DOI': '10.4049/jimmunol.134.5.3032', 'article-title': '1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte ' 'activity in vitro', 'volume': '134', 'author': 'Lemire', 'year': '1985', 'journal-title': 'J. 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