Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study).
Level 2 - randomized trial
Individual randomized, placebo-controlled trial
PubMed 33184146 · doi:10.1136/postgradmedj-2020-139065
What was done
Forty asymptomatic or mildly symptomatic, vitamin D-deficient (25(OH)D < 20 ng/ml), SARS-CoV-2 RNA-positive individuals were randomized to receive either daily oral high-dose cholecalciferol (60,000 IU oral nano-liquid droplets for 7 days, target 25(OH)D > 50 ng/ml; n=16) or placebo (n=24). Supplementation was continued after day 7 if target 25(OH)D was not met. Patients requiring invasive ventilation or with significant comorbidities were excluded. Outcomes assessed were the proportion of participants achieving SARS-CoV-2 RNA negativity before day 21 and changes in inflammatory markers (fibrinogen, D-dimer, procalcitonin, CRP, ferritin).
What was found
Baseline 25(OH)D levels were 8.6 ng/ml (7.1 to 13.1) in the intervention group and 9.54 ng/ml (8.1 to 12.5) in the control group (p=0.730). By day 14, 25(OH)D was 51.7 ng/ml (48.9 to 59.5) versus 15.2 ng/ml (12.7 to 19.5), respectively (p<0.001). Significantly more intervention participants became SARS-CoV-2 RNA negative before day 21 compared with control (10/16 [62.5%] vs 5/24 [20.8%], p<0.018). Fibrinogen significantly decreased with cholecalciferol (intergroup difference 0.70 ng/ml, p=0.007), whereas other inflammatory biomarkers showed no significant differences.
Why it matters
This trial provides preliminary randomized evidence that short-term high-dose vitamin D supplementation can accelerate viral clearance and reduce fibrinogen in vitamin D-deficient individuals with mild SARS-CoV-2 infection.
Limits
The sample size was very small (n=40), creating high imprecision and risk of random error. The trial was limited to asymptomatic or mildly symptomatic vitamin D-deficient patients without significant comorbidities, precluding generalization to moderate-to-severe COVID-19 or vitamin D-replete populations. Clinical endpoints such as disease progression, hospitalization duration, or symptom resolution were not reported.
Cited by
- supports The SHADE randomized controlled trial in India showed that COVID-19 patients given 60,000 IU/day of vitamin D for 7 days had higher SARS-CoV-2 PCR negativity rates at day 21 (roughly 60% vs 20%) and significantly lower fibrinogen levels.