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Two times less likely to test positive for COVID if vitamin D level more than 55ng, etc. – Dec 31, 2021


Vitamin D's Role in Reducing Risk of SARS-CoV-2 and COVID-19 Incidence, Severity, and Death

Nutrients 2022, 14, 183. https://doi.org/10.3390/nu14010183
William B. Grant    Sunlight, Nutrition and Health Research Center, P.O. Box 641603, San Francisco, CA 94164-1603, USA; williamgrant08 at comcast.net; Tel.: +1-415-409-1980

The article by D'Avolio and colleagues [1] on patients with a positive polymerase chain reaction (PCR) test for SARS-CoV-2 was the first to report that 25-hydroxyvitamin D [25(OH)D] concentrations were lower in PCR-positive patients than in PCR-negative patients or in historical controls. As a result, that report has the most citations in its category (201 according to SCOPUS on 17 December 2021). Thus, the article likely helped considerably stimulate investigation of vitamin D's role in reducing risk of SARS-CoV-2 infection and ensuing COVID-19.
A later article on 25(OH)D concentration and risk of SARS-CoV-2 positivity was based on more than 190,000 PCR tests on patients in the U.S. with serum 25(OH)D concentration measurements from the previous 12 months on file by quest diagnostics [2]. According to that report, positivity was inversely correlated with seasonally adjusted 25(OH)D concentration, posing a risk for patients with concentrations of ~55 ng/mL have about half the positivity of those with concentrations of <20 ng/mL.
A recent meta-analysis involving 76 studies reported inverse correlations for COVID- 19 risk with respect to serum 25(OH)D concentrations for risk of developing the disease, its severity, and risk of death [3], thus offering support for the role of vitamin D in reducing risk of COVID-19.
However, because of the concern that having an acute inflammatory illness could lower serum 25(OH)D concentrations [4], observational studies of COVID-19 using 25(OH)D concentrations measured at or near time of diagnosis have been questioned. The data in Figure 3 of reference [3] can be used to address that concern.
The 19 studies can be divided into four categories:

  1. 25(OH)D at time of diagnosis (seven studies);
  2. within 1 year prior (eight);
  3. preceding 10 years (one); and
  4. 10-15 years prior (three).

The mean weighted odds ratios for each time are 2.08,1.76,1.27, and 1.04, respectively. Those values are consistent with a longer interval between blood draw and health outcome, which are associated with worse health outcomes due to changes in 25(OH)D concentrations. That effect is most pronounced for diseases that can develop rapidly, such as breast cancer [5]. Although the present editorial does not rule out reduction in 25(OH)D due to COVID-19, the times before diagnosis are independent of COVID-19 and support the role of vitamin D in reducing risk.
The innate immune system mechanisms by which vitamin D reduces risk of SARS- CoV-2 infection and COVID-19 appear to include reduced viral viability and replication by inducing cathelicidin and defensins as well as reduced production of proinflammatory cytokines and the risk of the cytokine storm [6]. Additional mechanisms were suggested later [7]. The innate immune system is not sensitive to the variant of SARS-CoV-2 involved. That is important because the virus mutates easily, thereby reducing the adaptive immune system's ability to respond effectively. Thus, vitamin D can serve as an extra measure of protection as vaccine effectiveness wanes. The recommended serum 25(OH)D concentration for prevention is 40 to >60 ng/mL, which could be achieved with 5000 to 10,000 IU/d vitamin D3, i.e., a safe dose range [8].
Thus, it seems likely that raising serum 25(OH)D concentrations after SARS-CoV- 2 infection or development of COVID-19 could reduce the progression and severity of COVID-19. Two approaches were attempted with mixed results. The most comprehensive trial of vitamin D3 supplementation with COVID-19 patients was a trial conducted in Turkey [9]. Of 867 COVID-19 patients, 160 patients with initial 25(OH)D concentrations of <30 ng/mL were treated with 224,000 to 500,000 IU over periods from 3 to 7 days to achieve >30 ng/mL. The only clinically significant benefit in comparison with untreated patients with 25(OH)D <30 ng/mL was a reduction in hospital stays over 8 days. However, the length of hospital stay was not significantly different between the two groups. That trial probably failed to achieve significant beneficial effects because the body takes several days to convert vitamin D to 25(OH)D, during which time the disease progresses, and because the achieved 25(OH)D concentrations were only 32 ± 12 ng/mL on day 7 and 36 ± 11 ng/mL on day 14.
An alternate approach is to supplement with calcifediol [25(OH)D], which raises serum 25(OH)D concentrations in hours. A successful pilot randomized controlled trial of calcifediol treatment was reported from Barcelona in 2020 [10]. That trial included 76 consecutive COVID-19 patients with acute respiratory tract infection and a positive PCR test for SARS-CoV-2. In addition to standard hospital care, 50 patients were assigned to receive calcifediol treatment: 0.532 mg on the first day, 0.266 mg on days 3 and 7, and then weekly until discharge or ICU admission. Calcifediol is about 3.2 times more efficient at raising serum 25(OH)D concentrations than vitamin D3 [11]. Thus, 0.266 mg of calcifediol is equivalent to ~34,000 IU of vitamin D3. Only 1 of 50 patients treated with calcifediol required ICU treatment, as opposed to 13 of 26 not receiving calcifediol (2 of whom died).
An observational study in Spain involved 537 patients hospitalized with COVID-19 between 5 February and 5 May 2020, of whom 79 were treated with calcifediol [12]. The odds ratio for mortality within 30 days, adjusted for potential confounders, was 0.16 (95% confidence interval, 0.03 to 0.80).
 Download the PDF from VitaminDWiki

References
  1. D'Avolio, A.; Avataneo, V.; Manca, A.; Cusato, J.; De Nicolo, A.; Lucchini, R.; Keller, F.; Cantu, M. 25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2. Nutrients 2020,12,1359. [CrossRef] PDF
  2. Kaufman, H.W.; Niles, J.K.; Kroll, M.H.; Bi, C.; Holick, M.F. SARS-CoV-2 positivity rates associated with circulating 25- hydroxyvitamin D levels. PLoS ONE 2020,15, e0239252. [CrossRef]
    In VitaminDWiki Rate of COVID-19 test positive is 40 pcnt lower if high vitamin D (192,000 people) - Holick Sept 2020
    Image
  3. Dissanayake, H.A.; de Silva, N.L.; Sumanatilleke, M.; de Silva, S.D.N.; Gamage, K.K.K.; Dematapitiya, C.; Kuruppu, D.C.; Ranasinghe, P.; Pathmanathan, S.; Katulanda, P. Prognostic and therapeutic role of vitamin D in COVID-19: Systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2021, dgab892. [CrossRef]
  4. Smolders, J.; van den Ouweland, J.; Geven, C.; Pickkers, P.; Kox, M. Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause and consequence. Metabolism 2021,115,154434. [CrossRef]
  5. Grant, W.B. Long follow-up time and different sensitivities of cancer types may have obscured the effect of 25-hydroxyvitamin D on cancer incidence and mortality rates. Am. J. Clin. Nutr. 2015,102, 230. [CrossRef]
  6. Grant, W.B.; Lahore, H.; McDonnell, S.L.; Baggerly, C.A.; Franch, C.B.; Aliano, J.L.; Bhattoa, H.P. Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020,12, 988. [CrossRef]
  7. Mercola, J.; Grant, W.B.; Wagner, C.L. Evidence Regarding Vitamin D and Risk of COVID-19 and Its Severity. Nutrients 2020, 12, 3361. [CrossRef] [PubMed]
  8. McCullough, P.J.; Lehrer, D.S.; Amend, J. Daily oral dosing of vitamin D3 using 5000 TO 50,000 international units a day in long-term hospitalized patients: Insights from a seven year experience. J. Steroid Biochem. Mol. Biol. 2019,189, 228-239. [CrossRef] [PubMed]
  9. Gonen, M.S.; Alaylioglu, M.; Durcan, E.; Ozdemir, Y.; Sahin, S.; Konukoglu, D.; Nohut, O.K.; Urkmez, S.; Kucukece, B.; Balkan, I.I.; et al. Rapid and Effective Vitamin D Supplementation May Present Better Clinical Outcomes in COVID-19 (SARS-CoV-2) Patients by Altering Serum INOS1, IL1B, IFNg, Cathelicidin-LL37, and ICAM1. Nutrients 2021,13, 4047. [CrossRef]
  10. Entrenas-Castillo, M.; Entrenas Costa, L.M.; Vaquero Barrios, J.M.; Alcala Diaz, J.F.; Lopez Miranda, J.; Bouillon, R.; Quesada Gomez, J.M. 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. 2020, 203,105751. [CrossRef] [PubMed]
  11. Quesada-Gomez, J.M.; Bouillon, R. Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporos. Int. 2018, 29,1697-1711. [CrossRef] [PubMed]
  12. Alcala-Diaz, J.F.; Limia-Perez, L.; Gomez-Huelgas, R.; Martin-Escalante, M.D.; Cortez-Rodriguez, A.L.; Lopez-Carmona, M.D. Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study. Nutrients 2021,13,1760. [CrossRef] [PubMed]

VitaminDWiki - Calcifediol and Virus studies (7 as of Dec 2021)


VitaminDWiki - some Calcifediol studies (5 as of Dec 2021)


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VitaminDWiki - COVID-19 treated by Vitamin D - studies, reports, videos

As of Jan 10, 2022, the VitaminDWiki page had:  34 trials 6 trial results,   32 meta-analyses and reviews,   64 observations,   36 recommendations,   55 associations,  89 speculations,  58 videos   see related:   Governments,   HealthProblems,   Hospitals,  Dark Skins,   26 risk factors are ALL associated with low Vit D,   Recent Virus pages   Fight COVID-19 with 50K Vit D weekly   Vaccines   Take lots of Vitamin D at first signs of COVID


VitaminDWiki pages with GRANT* but not MIGRANT in title (29 as of Dec 2021)

This list is automatcially updated

Items found: 39
Title Modified
Vitamin D benefits ignored at a time they are most needed - Grant Jan 9, 2022 10 Jan, 2022
Top Vitamin D Papers - Grant 2017 09 Jan, 2022
Top 25 Vitamin D Publications in 2020 - Grant 09 Jan, 2022
Cancer incidence and death reduced by both Vitamin D and UVB – Grant Oct 2021 15 Oct, 2021
Vitamin D and Health video with transcript - Dr. Grant Sept 2021 11 Sep, 2021
Vitamin D and COVID-19: Video and PDF by Dr. Grant (includes recommendations)- Nov 25, 2020 26 Nov, 2020
Preventing a COVID-19 pandemic with Vitamin D – Grant April 2020 02 Apr, 2020
Top Advances in the Understanding of Vitamin D on Human Health - Grant Jan 2019 19 Jan, 2020
Breast, Prostate and Colon Cancers are still strongly associated with low Vitamin D – Grant Jan 2020 01 Jan, 2020
Evidence that Vitamin D prevents Cancer – Grant Feb 2018 29 Jan, 2018
Vitamin D injection helped migrants a bit, but some had poor or even negative responses – Dec 2017 19 Jan, 2018
Vitamin D Video 53 minutes with text and PDFs – Grant Oct 2017 28 Nov, 2017
Canadian grant funding lost for prescribing 50,000 IU of vitamin D – July 2017 23 Jul, 2017
Pregnancy and Vitamin D bibliography - Dr. Grant - March 2017 20 Mar, 2017
Bibliography of Black-White health disparities linked to vitamin D - Dr. Grant March 2017 20 Mar, 2017
Prenancy and Vitamin D biliogrraphy - Dr. Grant - March 2017 20 Mar, 2017
Patent granted for adding vitamin D to sunblock and skin cream - Feb 2011 05 Jan, 2017
Cardiovascular death reduction in dark skin migrants by just 1,000 IU of vitamin D – May 2015 04 Jan, 2017
Dr. Grant on vitamin D and mortality in VitaminDWiki 18 Nov, 2016
Optimum Vitamin D level: Evidence for 30 and 40 ng – Grant Aug 2013 28 Feb, 2016
Low UVB (thus low Vitamin D) is linked to many diseases – Grant Jan 2016 10 Jan, 2016
Migrants from Middle East are slightly more vitamin D deficient than those from Africa - meta-analysis Aug 2015 11 Aug, 2015
Time-release form of active vitamin D granted a patent for chronic kidney disease – July 2014 26 Jul, 2015
Vitamin D2 patent granted to prevent hair loss during chemotherapy – 2002 11 May, 2015
Less sun means more disease -Grant, Holick, Cannell, et al Feb 2015 05 Mar, 2015
Autism and vitamin D: Cannell, Grant – March 2013 05 Jan, 2015
Interview concerning UVA, UVB, and health – Grant Dec 2012 05 Jun, 2014
Evidence that the minimum vitamin D blood level is 30 ng – Grant Nov 2012 21 Jan, 2014
Summary of Vitamin D trials - Grant Nov 2012 18 Jan, 2014
Solar UVB reduces Cancer Risk – Grant, Jan 2013 02 Oct, 2013
First and 2nd generation migrants 2X more likely to have psychotic disorders – Jan 2013 08 Jan, 2013
UK Day-Cares being offered grants to develop vitamin D methods – July 2012 27 Dec, 2012
Getting sunshine improves your health provided you do not sunburn - Grant Dec 2012 11 Dec, 2012
Review of Vitamin D trials - Grant Jan 2012 25 Nov, 2012
Abu Dhabi 2012 - Grant 11 Apr, 2012
Evidence for Vitamin D - Grant Aug 2011 09 Nov, 2011
Some cancer due to low UV – Grant – April 2010 13 Oct, 2011
Recommend 2500-4000 IU per day to reduce all-cause mortality by 18%– Grant Netherlands April 2010 13 Jul, 2011
Vitamin D overview by Grant - Jan 2011 13 Jul, 2011

VitaminDWiki - Vitamin D meta-analyses for Virus


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