Greta Goldshtein, PharmD, APh
December 26, 2020
Essential nutrient functions
Vitamin D is a fat-soluble compound that can be made by the human body or can be obtained from diet or supplementation. The vitamin is well known for its role in regulation of calcium and phosphorus balance in the body, bone development and maintenance. However, nearly every tissue in the human body has important vitamin D-related functions; in the immune system, the vitamin plays a role in the function of essential components of the immune response (antigen-presenting cells, T-cells, and B-cells contain vitamin D receptors).
Proposed role in COVID-19*
Vitamin D deficiency has been shown to increases autoimmunity and susceptibility to respiratory infections, particularly in individuals with low levels of 25(OH)D. It has also been linked as a risk factor for COVID-19 infection. A non-peer reviewed survey of supplementations revealed that vitamin D reduced the risk of SARS-CoV-2 by 9% (6-12%) (Louca, 2020)
Vitamin D modulates innate and adaptive immune systems and may improve the body’s response to respiratory viruses, including SARS-CoV-2. The proposed mechanism is inhibition of antigen-presenting cells, antiproliferative effect on T cells, modulating expression and secretion of type 1 interferon, and inhibition of pro-inflammatory cytokine expression (IL-6, TNF-alpha). Additionally, it may also play a basic role in respiratory homeostasis by accelerating expression of antimicrobial peptides or by directly influencing the replication of respiratory viruses. In COVID-19, it may also be potentially protective by binding to the ACE2 receptors, which are also a binding target of SARS-CoV-2.
The human body can produce its own vitamin D, but this synthesis is severely limited when only arms and legs are exposed to sunlight and is further hindered by darker skin, winter months, and northern latitudes.
Vitamin D is found in foods such as dairy products, cereals, oily fish (sardines, mackerel, and salmon) and in some mushrooms and yeast. Dietary intake from an average American diet is inadequate, however. National Health and Nutrition Examination Survey data from 2009-2012 found that around 95% of Americans consume less than the estimated average requirement for Vitamin D. Other surveys have found that approximately 40% of US population are deficient, especially in winter months.
Vulnerability to vitamin D deficiency is increased in elderly, limited sunlight exposure, gastric bypass surgery, inflammatory bowel disease, liver disease, cystic fibrosis, obesity, severe burns, and kidney disease. Some medications can predispose to deficiency by hindering fat absorption (cholestyramine, colestipol, orlistat, mineral oil, olestra, etc.) or by altering enzymatic action (anti-seizure medications).
While there is disagreement in the medical community regarding the level of serum Vitamin D level that is required for optimizing health, it is generally well established that supplementation should be targeted to maintain serum 25(OH)D levels in the 30-90 ng/mL range.
Supplementation is usually via Vitamin D3 (cholecalciferol), which is superior to Vitamin D2 (ergocalciferol) in terms of ability to increase serum 25(OH)D levels.
Daily doses of vitamin D up to 2,000 IU are safe and could protect against acute respiratory tract infections, especially in people with vitamin D deficiency, though doses in 3,000 – 5,000 IU range are usually necessary to maintain optimal serum levels (30-88 ng/mL). Loading doses (short-term supplementation with higher doses such as 50,000 IU weekly for 2-3 months or three times a week for 1 month) may be needed to quickly raise serum levels to the desired range. For prevention/treatment of COVID-19, serum levels >30-40 ng/mL have been suggested.
Potential for toxicity is technically possible with long-term, high-dose supplementation (e.g. >50,000 IU per week); consequently, it is recommended to periodically check serum 25(OH)D levels to maintain levels below 100 ng/mL.
* To date, there are no rigorous scientific studies affirming the role or defining best treatment protocols of any vitamins or supplements for prevention or treatment of COVID-19. The information in this section is based on expert opinion and data available to date. Best protection against COVID-19 is socially distancing, wearing a mask, and avoiding congregating indoors with people outside of immediate household members, practicing good hygiene, and receiving vaccination when available.
Bauer SR, Kapoor A, Rath M, Thomas SA. COVID-19 Curbside Consults: What is the role of supplementation with ascorbic acid, zinc, vitamin D, N-acetylcysteine for prevention or treatment of COVID-19? Cleveland Clinic Journal of Medicine, June 2020 https://doi:10.3949/ccjm/87a.ccc046
Guilliams TG. Supplementing Dietary Nutrients: A Guide for Healthcare Professionals, 2nd Edition. Point Institute, 2020
Louca, Panayiotis (2020). Dietary supplements during the COVID-19 pandemic: insights from 1.4M users of the COVID symptom study app – longitudinal app-based community survey. medRxiv preprint server. Doi: https://doi.org.10.1101/2020/2020.11.27.20239087, https://www.medrxiv.org/content/10/1101.2020.11.27.20239087v1
Sahebnasagh A, Saghafi F, et al. The prophylaxis and treatment potential of supplements for COVID-19. European Journal of Pharmacology, September 2020. https://doi.rog/10.1016/j.ejphar.2020.173530