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Vitamin D and covid-19

BMJ 2021; 372 doi: (Published 04 March 2021) Cite this as: BMJ 2021;372:n544

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Rapid Response:

Vitamin D -- dose for prevention and the calcifediol derivative for treatment of COVID-19

Dear Editor

Further to the editorial on Vitamin D and COVID-19 (1) the following points need consideration -


The recent NICE guideline recommends a vitamin D3 dose of only 400 IU (10 micrograms) (2). This is for adults (and perhaps surprisingly also for infants from 1 year of age upwards). Recommendations for higher adult doses of 4000 IU (or at least 2000 IU) have been made by over 200 well known doctors and scientists to combat COVID-19.

Vitamin D toxicity from supplements is rare. It is associated with serum levels higher than 250 nmol/L. (3, 4). A daily dose of 4000 IU (100 micrograms) for three months will not result in levels anywhere near this figure and leaves a wide margin of safety. (5)

Vitamin D is a safe and inexpensive medication. A high incidence of vitamin D deficiency has been reported in the UK (6) and increases the risk of severe COVID-19 infection. The precautionary principle (briefly mentioned in the editorial) makes the point that lack of full scientific evidence does not preclude action if damage would be otherwise serious and irreversible.


Significantly reduced severity of COVID-19 infection has been reported in a randomised controlled trial with a vitamin D derivative (calcifediol) rather than the usual form of vitamin D3 available in the UK (cholecalciferol) (7). Calcifediol is more rapidly effective, better absorbed and 3.2 times more active than cholecalciferol (8). Also, cholecalciferol may take over a week to be fully active and this may be too late for moderately or severely ill patients to respond to treatment. Shouldn’t calcifediol be used for treatment in the UK?

1. Vimaleswaran K S, Forouhi N G, Khunti K. Vitamin D and covid-19 BMJ 2021; 372 :n544 doi:10.1136/bmj.n544
2. NICE. Vitamin D for covid-19: evidence reviews for the use of vitamin D supplementation as prevention and treatment of covid-19. 2020.
3. Jones G. Pharmacokinetics of vitamin D toxicity The American Journal of Clinical Nutrition, Volume 88, Issue 2, August 2008, Pages 582S–586S,
4. Vieth R Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr 2006 Apr;136(4):1117-22.
5. Vieth R, Chan PC, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level Am J Clin Nutr 2001 Feb;73(2):288-94. doi: 10.1093/ajcn/73.2.288
6. Sutherland JP, Zhou A, Leach MJ, Hyppönen E. Differences and determinants of vitamin D deficiency among UK biobank participants: A cross-ethnic and socioeconomic study. Clin Nutr. 2020 Nov 25;S0261-5614(20)30639-7 doi: 10.1016/j.clnu.2020.11.019
7. Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, etal. 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 Mol Biol 2020 ;203:105751. doi: 10.1016/j.jsbmb.2020.105751. pmid: 32871238
8. J. M. Quesada-Gomez & R. Bouillon Is calcifediol better than cholecalciferol for vitamin D supplementation? Osteoporosis International volume 29, pages1697–1711(2018)

Competing interests: No competing interests

09 March 2021
Elizabeth H Price
Retired consultant microbiologist
London NW11