Viewpoint: To D or not to D in Covid?

Clinical

Viewpoint: To D or not to D in Covid?

In Clinical

Vitamin D deficiency is associated with increased severity of Covid-19 and greater risks of hospitalisation and death — so should vitamin D supplements become routine?

There is growing evidence associating vitamin D deficiency with Covid-19 severity, including links with ethnicity, obesity, institutionalisation, latitude and ultraviolet exposure, increased lung damage in experimental models and disease severity in hospitalised patients. Many researchers now regard the evidence in favour of vitamin D supplementation as overwhelming.

By October 2020 there were more than 40 studies showing optimal blood levels of 25(OH)-vitamin D (75-150nmol/L) were linked to reduced Covid-19 risks, including lower risks of severe disease and death.1 A meta-analysis later confirmed the association2 and called for prospective trials to examine whether there is a causal link between low vitamin D levels and poor Covid-19 outcomes.

Other commentators have argued that the risks of supplementing vitamin D are low – the drug is cheap, available and non-toxic – and the potential benefits huge, and therefore it should be done.3,4

The UK Government has implicitly acknowledged the benefits of vitamin D by mandating the supply of the vitamin to the “clinically extremely vulnerable” (starting in January 2021). At the same time further reviews and a trial (‘Coronavit’) were commissioned to determine whether being vitamin replete can reduce the risk of dying from Covid-19 infection.5 The estimated completion date for the Coronavit trial is the end of June 2021.

It is noteworthy that Dr Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases in the US, takes 6000 IU of vitamin D daily.

Deficiency common

Vitamin D is made in the skin by the action of sunlight (UVB) on cholesterol. During the winter months in the UK (from October to April) there is insufficient sunlight for this to occur and vitamin D deficiency is common – even without a lockdown. A small amount of vitamin D also comes from the diet – oily fish, red meat, liver, egg yolks and some fortified foods are good sources.

Vitamin D is a hormone that acts on many genes expressed by immune cells. A target blood level of at least 50nmol/L is recommended by the US National Academy of Medicine and by the European Food Safety Authority. This would require supplementation with 800 IU/day (not 400 IU/day as currently recommended in UK) to bring most people up to target, according to a detailed review of the evidence.4

Adults who are likely to be deficient (e.g. those who have been confined indoors for months) should consider taking a higher dose; for example 4000 IU/day for the first four weeks before reducing to 800-1000 IU/day.

The current NICE guideline on vitamin D recommends daily supplementation with 400 IU (10mcg) to maintain bone and muscle health during the winter and all year round for people who have little exposure to sunshine. The guideline also says that vitamin D should not be offered solely to prevent or treat Covid-19. NICE says that there is insufficient evidence for these indications so far but the guidance will be updated as additional evidence becomes available.

The Frontline Covid-19 Critical Care Alliance is a group of intensivists in the US who have devised protocols for prophylaxis and treatment of Covid-19. Both protocols contain vitamin D3, 1000-3000 IU per day for prophylaxis and 4000 IU per day for treatment of Covid-19.6

It is hard to escape the conclusion that vitamin D supplementation in doses of 400-4000 IU per day (depending on circumstances and needs) should be offered not only for bone and muscle health but also to optimise immune function.

References

  1. Brown RA. Vitamin D mitigates Covid-19 say 40+ patient studies – yet BAME, elderly, care-homers and obese are still ‘D’ deficient, thus at greater Covid-19 risk — why? BMJ 2020; 371 (rapid response) bmj.com/content/371/bmj.m3872/rr-5
  2. Pereira M, Damascena AD, Azevedo LMG et al. Vitamin D deficiency aggravates Covid-19: systematic review and meta-analysis. Critical Reviews in Food Science and Nutrition. 2020. doi.org/10.1080/10408398.2020.1841090
  3. Haug EG, de Lalouviere D, Isharc L. Vitamin D and Covid-19: Is there a lack of risk/reward understanding among health authorities? Preprint November 2020 DOI: 10.13140/RG.2.2.13972.12164
  4. Griffin G, Hewison M, Hopkin J, Kenny R, Quinton R, Rhodes J, Subramanian S, Thickett D. 2020 Vitamin D and Covid-19: evidence and recommendations for supplementation. R. Soc. Open Sci. 7: 201912.doi.org/10.1098/rsos.201912
  5. CORONAVIT trial: qmul.ac.uk/media/news/2020/smd/clinical-trial-to-investigate-whether-vitamin-d-protects-against-Covid-19.html
  6. Front Line Covid-19 Critical Care Alliance. covid19criticalcare.com.

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