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Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review

Wimalawansa, S., Nutrients, doi:10.3390/nu17030599
Feb 2025  
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Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 124 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,300+ studies for 116 treatments. c19early.org
Systematic review examining the evidence for vitamin D deficiency as a causative factor in COVID-19 susceptibility, complications, and mortality, evaluated using Bradford Hill's criteria for causality. Author analyzed 294 studies, finding a strong inverse relationship between serum vitamin D levels and COVID-19 severity, with optimal protection suggested at concentrations >50 ng/mL, associated with ~50% reduction in hospitalization and death. Clinical trials using cholecalciferol or calcifediol demonstrated significant benefits, particularly when administered early, with calcifediol showing faster onset of action. The review notes that 97% of trials reported positive effects, while 11 studies that showed no benefit had major design flaws, such as very late-stage intervention and insufficient dosing. Vitamin D supplementation, estimated at $2 per patient, was highlighted as a cost-effective intervention compared to hospitalization. Author criticizes health agencies for not integrating vitamin D into protocols despite over 300 studies supporting its role in immune resilience, antiviral defense, and cytokine regulation.
Reviews covering vitamin D for COVID-19 include1-37.
Wimalawansa et al., 6 Feb 2025, peer-reviewed, 1 author. Contact: suniljw@hotmail.com.
This PaperVitamin DAll
DOI record: { "DOI": "10.3390/nu17030599", "ISSN": [ "2072-6643" ], "URL": "http://dx.doi.org/10.3390/nu17030599", "abstract": "<jats:p>Clinical trials consistently demonstrate an inverse correlation between serum 25-hydroxyvitamin D [25(OH)D; calcifediol] levels and the risk of symptomatic SARS-CoV-2 disease, complications, and mortality. This systematic review (SR), guided by Bradford Hill’s causality criteria, analyzed 294 peer-reviewed manuscripts published between December 2019 and November 2024, focusing on plausibility, consistency, and biological gradient. Evidence confirms that cholecalciferol (D3) and calcifediol significantly reduce symptomatic disease, complications, hospitalizations, and mortality, with optimal effects above 50 ng/mL. While vitamin D requires 3–4 days to act, calcifediol shows effects within 24 h. Among 329 trials, only 11 (3%) showed no benefit due to flawed designs. At USD 2/patient, D3 supplementation is far cheaper than hospitalization costs and more effective than standard interventions. This SR establishes a strong inverse relationship between 25(OH)D levels and SARS-CoV-2 vulnerability, meeting Hill’s criteria. Vitamin D3 and calcifediol reduce infections, complications, hospitalizations, and deaths by ~50%, outperforming all patented, FDA-approved COVID-19 therapies. With over 300 trials confirming these findings, waiting for further studies is unnecessary before incorporating them into clinical protocols. Health agencies and scientific societies must recognize the significance of these results and incorporate D3 and calcifediol for prophylaxis and early treatment protocols of SARS-CoV-2 and similar viral infections. Promoting safe sun exposure and adequate vitamin D3 supplementation within communities to maintain 25(OH)D levels above 40 ng/mL (therapeutic range: 40–80 ng/mL) strengthens immune systems, reduces hospitalizations and deaths, and significantly lowers healthcare costs. When serum 25(OH)D levels exceed 70 ng/mL, taking vitamin K2 (100 µg/day or 800 µg/week) alongside vitamin D helps direct any excess calcium to bones. The recommended vitamin D dosage (approximately 70 IU/kg of body weight for a non-obese adult) to maintain 25(OH)D levels between 50–100 ng/mL is safe and cost-effective for disease prevention, ensuring optimal health outcomes.</jats:p>", "alternative-id": [ "nu17030599" ], "author": [ { "ORCID": "https://orcid.org/0000-0003-1096-8595", "affiliation": [ { "name": "Endocrinology and Human Nutrition, CardioMetabolic & Endocrine Institute, North Brunswick, NJ 08902, USA" } ], "authenticated-orcid": false, "family": "Wimalawansa", "given": "Sunil", "sequence": "first" } ], "container-title": "Nutrients", "container-title-short": "Nutrients", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 2, 6 ] ], "date-time": "2025-02-06T16:32:32Z", "timestamp": 1738859552000 }, "deposited": { "date-parts": [ [ 2025, 2, 6 ] ], "date-time": "2025-02-06T16:39:30Z", "timestamp": 1738859970000 }, "indexed": { "date-parts": [ [ 2025, 2, 6 ] ], "date-time": "2025-02-06T17:10:02Z", "timestamp": 1738861802987, "version": "3.37.0" }, "is-referenced-by-count": 0, "issue": "3", "issued": { "date-parts": [ [ 2025, 2, 6 ] ] }, "journal-issue": { "issue": "3", "published-online": { "date-parts": [ [ 2025, 2 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 2, 6 ] ], "date-time": "2025-02-06T00:00:00Z", "timestamp": 1738800000000 } } ], "link": [ { "URL": "https://www.mdpi.com/2072-6643/17/3/599/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "599", "prefix": "10.3390", "published": { "date-parts": [ [ 2025, 2, 6 ] ] }, "published-online": { "date-parts": [ [ 2025, 2, 6 ] ] }, "publisher": "MDPI AG", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.mdpi.com/2072-6643/17/3/599" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review", "type": "journal-article", "volume": "17" }
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