Vitamin D and COVID-19: evidence and recommendations for supplementation
Source: Royal Society
Vitamin D is a hormone that acts on many genes expressed by immune cells. Evidence linking vitamin D deficiency with COVID-19 severity is circumstantial but considerable—links with ethnicity, obesity, institutionalization; latitude and ultraviolet exposure; increased lung damage in experimental models; associations with COVID-19 severity in hospitalized patients. Vitamin D deficiency is common but readily preventable by supplementation that is very safe and cheap. A target blood level of at least 50 nmol l−1, as indicated by the US National Academy of Medicine and by the European Food Safety Authority, is supported by evidence. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target. Randomized placebo-controlled trials of vitamin D in the community are unlikely to complete until spring 2021—although we note the positive results from Spain of a randomized trial of 25-hydroxyvitamin D3 (25(OH)D3 or calcifediol) in hospitalized patients. We urge UK and other governments to recommend vitamin D supplementation at 800–1000 IU/day for all, making it clear that this is to help optimize immune health and not solely for bone and muscle health. This should be mandated for prescription in care homes, prisons and other institutions where people are likely to have been indoors for much of the summer. Adults likely to be deficient should consider taking a higher dose, e.g. 4000 IU/day for the first four weeks before reducing to 800 IU–1000 IU/day. People admitted to the hospital with COVID-19 should have their vitamin D status checked and/or supplemented and consideration should be given to testing high-dose calcifediol in the RECOVERY trial. We feel this should be pursued with great urgency. Vitamin D levels in the UK will be falling from October onwards as we head into winter. There seems nothing to lose and potentially much to gain.
1. Vitamin D is a hormone that regulates many genes and is dependent on ultraviolet (B) skin exposure for its generation
1.1. Vitamin D synthesis and sources
Vitamin D is derived from 7-dehydrocholesterol in the skin by the action of ultraviolet B (UVB, wavelength 280–315 nm) splitting a carbon to carbon bond (C9–C10) thus opening up its B ring—it is structurally related to other cholesterol-derived hormones such as cortisol, testosterone and oestrogen. Formation of the active hormonal form of vitamin D, 1,25 dihydroxyvitamin D (1,25(OH)2D), requires 25-hydroxylation, performed in the liver, and 1-hydroxylation, performed in the kidneys but also in many immune cells and epithelial cells by the action of the enzyme 1-hydroxylase also referred to as CYP27B1 .
Vitamin D exists in two forms, D2 and D3. Vitamin D2 (ergocalciferol) derives from UVB irradiation of the yeast and plant sterol ergosterol, and vitamin D3 (cholecalciferol) is found in oily fish and cod liver oil and is also made in the human skin. It is very hard to obtain sufficient vitamin D from food. Oily fish is the only substantial dietary source. Other sources that include liver, eggs and mushrooms (the latter only if they have been UV irradiated) provide only modest amounts of vitamin D. The main source of vitamin D is its generation by the action of UVB on the skin .