Vitamin D deficiency is a global health problem. The negative consequences to skeletal health are well known, but the impact this deficiency has on other systems, and most currently on the COVID-19 pandemic, is less appreciated.
Epidemiologic studies of serum vitamin D (25-OH cholecalciferol) estimate 88.1% of the world’s population have levels below 30 ng/ml,1 (Insufficient) with 37% below 20 ng/ml,2 (Deficient), and 6.7% below 10 ng/ml.1 (Grossly Deficient) Several articles link vitamin D deficiency (20 ng/ml) and insufficiency (30 ng/ml) with higher rates of morbidity and mortality because of viral infections.3-8
The current guidelines for the COVID-19 virus of wearing masks, social distancing, and washing hands has not been adequate to control the pandemic. As of this writing (November 28, 2020), there have been over 260,000 deaths due to COVID-19 in the United States, with even steeper projections for the coming months. COVID-19 has pushed healthcare systems to the limit. Research suggests that the widespread and aggressive prescription of vitamin D may help reduce the current burden. Dosages of vitamin D in excess of the RDA have been safely used to prevent and treat the virus or as part of treatment programs with other viral or respiratory illnesses.9-11
Undoubtedly, lack of vitamin D is not the only factor in this pandemic. Not all people with a vitamin D deficiency contract COVID-19, nor do those with optimal levels escape entirely. However, recent papers demonstrate the plausibility of vitamin D as a beneficial tool in controlling COVID-19.
Reviews
Bilezikian12: This review paper outlines several immune pathways that are either dependent upon or enhanced by vitamin D.
Grant13: “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 5,000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L).”
McCartney14: “We recommend that all older adults, hospital inpatients, nursing home residents, and other vulnerable groups (e.g. those with diabetes mellitus or compromised immune function, those with darker skin, vegetarians and vegans, those who are overweight or obese, smokers and healthcare workers) be urgently supplemented with 20-50pg/d of vitamin D to enhance their resistance to Covid-19, and that this advice be quickly extended to the general adult population.”
Panfili15: “In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.”
Positive, Retrospective
Meltzer16: “The multivariable analysis suggests that persons who are likely to have deficient vitamin D levels at the time of COVID-19 testing were at substantially higher risk of testing positive for COVID-19 than were persons who were likely to have sufficient levels.”
Merzon17: “We concluded that low plasma 25(OH) D levels appear to be an independent risk factor for COVID-19 infection and hospitalization.”
Negative, Retrospective study
This negative study was rebutted in a later analysis.
Hastie18: “Our findings do not support a potential link between 25(OH)D concentrations and risk of severe COVID-19 infection and mortality.”
A rebuttal to Hastie by Meltzer16 states: “However, the vitamin D levels studied were between 10 and 14 years before the COVID-19 diagnosis, and the analysis did not control for treatment after the levels were assessed.”
Randomized Controlled Trial
Castillo19: “Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxy vitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19.”
This randomized trial studied 76 consecutive patients that were hospitalized with COVID-19. All patients received a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days). The study group also received calcifediol (25-hydroxycholecalciferol) on days 1, 3, 7, and then weekly until discharge.
Of the 50 patients treated with calcifediol, 1 (2%) required admission to the ICU. In the control group of 26 patients, 13 required admissions (50%). Of the 13 admitted to the ICU, 2 died.
The above trials clearly do not represent complete data sets with ironclad evidence. The reviews and data presented do represent strong suggestions, high levels of correlation, and preliminary evidence. There were no reported adverse reactions from appropriate vitamin D supplementation. In this time of very limited tools and such dire statistics, waiting for large randomized clinical trials in order to recommend vitamin D supplementation may be negligent.
Suggestions of widespread utilization of vitamin D in doses ranging from 800-5000 IU per day are seen in the literature.13,14 Some authors are suggesting doses of 10,000 IU per day for the short term (until desired serum levels are attained)13. The only risk was shown with extremely large doses; in excess of 100,000 IUs.20
Supplementation with vitamin D (and other compounds) is part of the Marik Protocol for COVID-19.21 This includes the use of 1000-3000 IU/day for prophylaxis, 20004000 IU for home care of mildly symptomatic patients, and a single 20,000-60,000 IU, then 20,000 IU weekly for hospitalized patients.
Since it will be months before there is widespread vaccination availability, we might consider:
• Testing the public for serum vitamin D levels and treating those who are deficient or insufficient.
• Initiating a public campaign for the use of vitamin D supplementation as prevention.
These steps are in addition to continuing current public health preventive measures of masks, distance, and hand washing. This does the most good for the most people in the most cost-effective manner and could be initiated tomorrow.
In a world where there is never enough data, we must make judgment calls using the current body of knowledge to assess risk vs. benefit (or potential benefit). The universal prescription of 2000 IUs (50 meg) per day may be the best immediate step available. No credible reports exist that demonstrate risk at this dose while there is the significant potential benefit of reduced transmission, morbidity, and mortality of COVID-19.
About the Author
Alan Cook, DC has been in practice since 1989. Currently, he is involved in two professional endeavors: 1. Treating patients in a collaborative medical clinic system (Open Door Community Health Center) in Eureka, CA. 2. EasyWebCE; providing chiropractic continuing education in a web-based video format, www.easywebce.com. Reach Dr. Cook at: [email protected] or 707 50270711622 Hyland St. Bayside, CA 95524
1. Hilger J, Friedel A, Herr R, et. al. A Systematic Review of Vitamin D Status in Populations Worldwide. Br JNutr 2014:111:23-45.
2. HolickM. Vitamin D Deficiency. NEngl JMed 200 7:35 7:266-281.
3. Martineau AR, Jolliffe DA, Hooper RL, et. al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017; 356.46583.
4. Zdrenghea MT, Makrinioti H, Bagacean C, et. al. Vitamin D modulation of innate immune responses to respiratory viral infections. Rev Med Virol. 2017; 27(1).
5. Greiller CL, Suri R, Jolliffe DA, 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. 2019; 187:152-159.
6. D ’avolio A, Avataneo V Manca A, et. al. 25-hydroxyvitamin D concentrations are lower in patients Math positive PCR for SARSCoV-2, Nutrients 2020:12
7. Rejnmark L, Bislev LS, Cashman KD, et. al. Non-skeletal health effects of vitamin D supplementation: A systematic review on findings from meta-analyses summarizing trial data. PLoS One. 2017; 12:e0180512.
8. Autier P, Mullie P, Macacu A, et. al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol. 2017; 5:986-1004.
9. Canned .11, Vieth R Umhau JC, et. al. Epidemic Influenza and Vitamin D. Cambridge University Press (online); 07 Sep 2006.
10. Aloia JF, Li-NgM. Epidemic Influenza and Vitamin D. Epidemiology and Infection. 2007; 135: 1095-8.
11. Urashima M, Segawa T, Okazaki M, et. al. Randomized Trial of Vitamin D Supplementation to Prevent Seasonal Influenza A in Schoolchildren. Am J Clin Nutt: 2010; 91: 1255-60.
12. Bilezikian JP, Bikle D, Hewison M, et. al. Vitamin D and COVID-19. Mechanisms in Endocrinol 2020;183:133-147.
13. Grant WB, Lahore H, McDonnell SL, et. al. Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths. Nutrients 2020; 12:988.
14. McCartney DM, Byrne DG. Optimisation of Vitamin D Status for Enhanced Immuno-protenction Against COVID-19. Ir Med J 2020:113:58.
15. Panfili FM, Roversi M, D ’Argenio P, et. al. Possible Role of Vitamin D in COVID-19 Infection in Pediatric Population J Endocrinol Investigation 2020 https://d0i.0rg/l0.1007 540618-020-01327-0.
16. Meltzer DO, Best TJ, Zhang J, et. al. Association of Vitamin D Status and Other Clinical Characteristics With COVID-19 Test Results. JAMA Network 2020;3(9):e2019722. doi: 10.1001 jamanetworkopen.2020.19 722
17. MerzonE, Lworowski D, Gorohovski A, et. al. FEBS Journal 2020;
18. https: doi.org/10.1111/febs.15495
19. Hastie CE, Pell JP, Sattar N. Vitamin D and COVID-19 Infection and Mortality in UK Biobank, Eur J Nutr 2020; https://doi, org/10.1007/s00394-020-023 72-4.
20. Castillo ME, Costa LME, Barrios JMV, 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 Molecular Biology 2020; https://doi. org/10.1016/j.jsbmb.2020.105751
21. The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. N Engl J Med 2019;381:25292540.
22. COVID-19 Management Protocol. Eastern Virginia Medical School, 10/29/2020 update. Evms.edu/covidcare
