Tools for Practice


#283 COVID-19 and Vitamin D: Partners in Crime, or Simply Associates?


CLINICAL QUESTION
Does Vitamin D help prevent or treat COVID19?

BOTTOM LINE
While observational evidence suggests an association between low vitamin D levels and COVID-19 infection, it is unclear if this is simply reflective of overall health status. There are no randomized, controlled trials (RCTs) assessing vitamin D for prevention of COVID-19 infections. The highest quality RCT of vitamin D treatment during hospitalization did not demonstrate benefit for clinical outcomes.


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EVIDENCE
3 RCTs assessed treatment in hospitalized patients with COVID-19, all received standard care in addition to oral:
  • Cholecalciferol 200,000 IU once versus placebo (240 patients, unpublished preprint).1
    • No difference in length of stay (both 7 days).
    • No difference mortality, ICU admission or ventilation.
  • Calcifediol (~21,000 IU) on day 1, (~10,000 IU) days 3 and 7, then once weekly versus usual care (76 patients, pilot study). Study length not reported.2
    • Vitamin D group showed:
      • Significant reduction ICU admission 1/50 (2%) versus 13/26 (50%).
      • Mortality 0/50 versus 2/26 (8%), not statistically different.
    • Limitations: Unbalanced randomization (more diabetes and hypertension in control), patients and physicians not blinded.
  • Cholecalciferol 60,000 IU daily x 7 days versus placebo in 40 patients with mild or no COVID-19 symptoms and Vitamin D deficient [25(OH) D <20ng/ml].3
    • Significantly more patients tested negative for COVID-19 within 21 days with vitamin D supplementation.
    • Limitations: Unclear randomization concealment and blinding, clinical outcomes not reported.
  • There are no published RCTs evaluating the use of Vitamin D for prevention of COVID-19.
  • Systematic reviews of observational studies generally demonstrate an association of low Vitamin D levels with COVID-19 infection and severity of infection, although included studies are often at high risk of bias.4-6
Context:
  • Low vitamin D is associated with poor health7 and it is unclear if low vitamin D levels are causative or simply reflect health status.
  • Additional confounders linked to COVID-19 severity and low vitamin D levels7 include higher body mass index, diabetes, older age, and Black race/ethnicity (versus non-Hispanic white).8
  • Current guidelines recommend against Vitamin D supplementation solely for prevention or treatment of COVID-19.9
February 8, 2021

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Author(s):

  • Christina Korownyk MD CCFP
  • Justin Weresch MD CCFP

1. Murai IH, Fernandes AL, Sales LP, et al. Effect of Vitamin D3 Supplementation vs Placebo on Hospital Length of Stay in Patients with Severe COVID-19: A Multicenter, Double-blind, Randomized Controlled Trial. MedRxIv preprint. https://www.medrxiv.org/content/10.1101/2020.11.16.20232397v1Accessed January 20, 2021.

2. Entrenas Castillo M, Entrenas Costa LM, Vaquero Barrios JM, et al. J Steroid Biochem Mol Biol. 2020; 203:105751.

3. Rastogi A, Bhansali A, Khare N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomized, placebo-controlled, study (SHADE study). Postgrad Med J. 2020 Nov 12:postgradmedj-2020-139065 (online ahead of print).

4. Pereira M, Dantas Damascena A, Galvão Azevedo LM, et al. Crit Rev Food Sci Nutr. 2020; 1- 9.

5. Liu N, Sun J, Wang X, et al. Int J Infectious Disease. 2021; 104:58-64

6. Yisak H, Ewunetei A, Kefale B, et al. Risk Management Healthcare Policy. 2021; 14:31-38.

7. Parva NR, Tadepalli S, Singh P, et al. Cureus. 2018; 10(6):e2741.

8. Wingert A, Pillay J, Gates M, et al. Risk factors for severe outcomes of COVID-19: a rapid review. MedRxiv preprint. https://www.medrxiv.org/content/10.1101/2020.08.27.20183434v1 Accessed Jan 18, 2021.

9. NICE COVID-19 rapid guideline: Vitamin D https://www.nice.org.uk/guidance/ng187/chapter/Recommendations Accessed January 18, 2021.

Authors do not have any conflicts of interest to declare.