Re: Preventing a covid-19 pandemic: Can vitamin D supplementation reduce the spread of COVID-19? Try first with health care workers and first responders.
There is reasonable evidence that higher 25-hydroxyvitamin D [25(OH)D] concentrations reduce the risk of respiratory tract infections. A meta-analysis of vitamin D supplementation trials found an inverse relationship between vitamin D supplementation and incidence of acute respiratory tract infections, especially for those with 25(OH)D concentrations below 25 nmol/l . Several mechanisms by which vitamin D reduces risk of respiratory tract infections have been identified. One is that cathelicidens and defensins are induced that have antimicrobial and antiendotoxin properties . Another is that vitamin D reduces the production of pro-inflammatory cytokines and increases production of anti-inflammatory cytokines 2. The innate immune system often goes into overdrive during respiratory tract infections, resulting in the cytokine storm that can damage the lining of the lungs . Serum 25(OH)D concentrations have been found to be inversely correlated with development of acute respiratory distress syndrome .
An article tying this and other information together suggests that raising serum 25(OH)D concentrations to 100 – 150 nmol/l should be able to reduce the risk of COVID-19 infection and death . To reach those concentrations rapidly would take large doses of vitamin D for a week or two, followed by several thousand IU/d vitamin D for the duration of the COVID-19 pandemic. Such doses have been found not to have adverse health effects . In addition, vitamin D reduces risk of many chronic diseases such as cancer and diabetes mellitus in secondary analyses of large clinical trials , and observational studies have found inverse correlations between serum 25(OH)D concentration and all-cause mortality rate up to 100 nmol/l .
No results of clinical trials regarding vitamin D supplementation for prevention or treatment of COVID-19 have been reported. Thus, an important question is whether making a public health announcement that taking enough vitamin D to raise serum 25(OH)D concentrations is a good idea. On the pro side, high-dose vitamin D supplementation and 25(OH)D concentrations have very few adverse side effects [6, 9]. It is also very inexpensive in markets that are not regulated, such as in the United States. Also, high 25(OH)D concentrations are associated with many health benefits  (see, also, information at vitaminDWiki.com and Grassrootshealth.net). On the anti side, physicians and health policy makers are reluctant to recommend health interventions that have not been rigorously tested and approved.
In my opinion, supplementation with substantial vitamin D doses is justified based on the enormous health and economic magnitude of the COVID-19 pandemic, the likely benefit in reducing risk of COVID-19 infection incidence and severity, and the preponderance of other health benefits from vitamin D supplementation and higher 25(OH)D concentrations with minimal adverse effects.
In terms of rolling out this recommendation, it is proposed that health care providers and first responders might try it first. Many of them lack adequate personal protective equipment and are contracting COVID-19 as a result. They have the training and motivation to lead the way in evaluating the benefit of vitamin D supplementation to help stem the COVID-19 pandemic. Measuring serum 25(OH)D concentrations at baseline and after supplementing for some time would be useful, especially in terms of evaluating the results in a field study rather than a randomized controlled trial .
1. 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:i6583. doi: 10.1136/bmj.i6583
2. Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients 2020;12(1):E236. doi: 10.3390/nu12010236
3. Guo XJ, Thomas PG. New fronts emerge in the influenza cytokine storm. Semin Immunopathol 2017;39(5):541-50. doi: 10.1007/s00281-017-0636-y
4. Dancer RC, Parekh D, Lax S, et al. Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS). Thorax 2015;70(7):617-24. doi: 10.1136/thoraxjnl-2014-206680
5. 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 doi: 10.20944/preprints202003.0235.v2 [published Online First: 30 March 2020]
6. McCullough PJ, Lehrer DS, 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;189:228-39. doi: 10.1016/j.jsbmb.2018.12.010
7. Grant WB, Boucher BJ. Why Secondary Analyses in Vitamin D Clinical Trials Are Important and How to Improve Vitamin D Clinical Trial Outcome Analyses-A Comment on "Extra-Skeletal Effects of Vitamin D, Nutrients 2019, 11, 1460". Nutrients 2019;11(9) doi: 10.3390/nu11092182
8. Garland CF, Kim JJ, Mohr SB, et al. Meta-analysis of all-cause mortality according to serum 25-hydroxyvitamin D. Am J Public Health 2014;104(8):e43-50. doi: 10.2105/AJPH.2014.302034
9. Grant WB, Karras SN, Bischoff-Ferrari HA, et al. Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects? Dermatoendocrinol 2016;8(1):e1187349. doi: 10.1080/19381980.2016.1187349
10. Charoenngam N, Shirvani A, Holick MF. Vitamin D for skeletal and non-skeletal health: What we should know. J Clin Orthop Trauma 2019;10(6):1082-93. doi: 10.1016/j.jcot.2019.07.004
Competing interests: Disclosure: I receive funding from Bio-Tech Pharmacal, Inc. (Fayetteville, AR).