Vitamin D and COVID-19: Do Latest Studies Support Supplementation?
To date, research on vitamin D supplementation and COVID-19 outcomes has been limited, so the PEN Team reviewed two recent studies on vitamin D and COVID-19 to see what, if anything, has changed.
Conversations continue on social media about the potential role of vitamin D supplementation in the prevention and treatment of COVID-19. The PEN Team noticed that a common rationale was that patients with COVID-19 tended to have lower vitamin D status (25(OH)D levels). We decided to take a look at two recent studies that reported this connection to determine if the results support vitamin D supplementation to improve COVID-19 outcomes.
First, we looked at an observational study by De Smet et al. that noted that patients with COVID-19 had progressively lower 25(OH)D levels with more severe COVID respiratory disease (1). The study authors also observed that those with vitamin D deficiency were almost four times more likely to die (adjusted odds ratio [OR] 3.87; 95% confidence interval [CI], 1.30 to 11.55). Vitamin D deficiency was prevalent among the patients with COVID-19 infections, more so among the men (67%) than among the women (47%). These researchers adjusted for several variables that are risk factors for COVID-19 mortality (age, ethnicity, chronic lung disease, coronary artery disease/hypertension, diabetes and extent of lung damage).
From other vitamin D research, we know that the marker for vitamin D status (25(OH)D) can be lowered by infections (2). Therefore, low 25(OH)D levels may not reflect poor vitamin D status in a person with an infection. De Smet et al. were not able to determine whether what looked like a vitamin D deficiency was actually a nutritional deficiency or whether the COVID-19 infection lowered the participants 25(OH)D, making these patients appear to have a vitamin D deficiency (1). For this reason, this observational study does not provide evidence that vitamin D supplementation would be helpful for improving outcomes of a COVID-19 infection.
The second study we examined was a randomized control trial of vitamin D supplementation in people with mild symptomatic and asymptomatic COVID-19 infections. Rastogi et al. randomized 40 people with mild COVID-19 infections to 60,000 IU/day of vitamin D3 or placebo for seven days (3). The researchers observed that more participants in the intervention group became COVID-19 RNA negative before day 21 compared to participants in the control arm (62.5% versus 20.8%, P<0.018). Vitamin D supplementation lowered fibrinogen levels significantly but not the other inflammatory markers (SARS-CoV-2 RNA, D-dimer, procalcitonin CRP and ferritin). These researchers only reported differences in indirect markers (3) and did not report World Health Organization-recommended patient-important outcomes (patient survival and patient health care system use over the course of clinical illness) (4). The PEN Team thinks that this trial does not answer the question of whether vitamin D supplementation improves COVID-19 outcomes.
What This Means
After reviewing these studies, the PEN Team has two key questions:
1. What is the relationship between vitamin D deficiency and COVID-19 severity?
2. What is the impact of vitamin D supplementation on patient-important outcomes, such as disease severity, hospitalization and death?
Before dietitians can make recommendations on the use of vitamin D supplementation to improve COVID-19 outcomes, randomized control trials examining the prevention of COVID-19 (including severe COVID-19) and the treatment of COVID-19 with patient-important outcomes are needed.
- De Smet D, De Smet K, Herroelen P, Gryspeerdt S, Martens GA. Serum 25(OH)D Level on Hospital Admission Associated With COVID-19 Stage and Mortality. Am J Clin Pathol. 2020 Nov 25:aqaa252. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717135/
- Hernández-Álvarez E, Pérez-Barrios C, Blanco-Navarro I, Pérez-Sacristán B, Donoso-Navarro E, Silvestre RA, et al. Association between 25-OH-vitamin D and C-reactive protein as a marker of inflammation and cardiovascular risk in clinical practice. Ann Clin Biochem. 2019 Jul;56(4):502-7. Available from: https://pubmed.ncbi.nlm.nih.gov/31043057/
- Rastogi A, Bhansali A, Khare N, Suri V, Yaddanapudi N, Sachdeva N, et al. Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study). Postgrad Med J. 2020 Nov 12:postgradmedj-2020-139065. Abstract available from: https://pubmed.ncbi.nlm.h.gov/33184146/
- WHO Working Group on the Clinical Characterisation and Management of COVID-19 infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis. 2020 Aug;20(8):e192-e197. Abstract available from https://pubmed.ncbi.nlm.nih.gov/32539990/