Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial

Study answer

What this study found

No protective effect observed for cod liver oil on SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections versus placebo. SARS-CoV-2 infection: 1.31% vs 1.32% (relative risk 1.00; 97% CI 0.82–1.22). Serious COVID-19: 0.70% vs 0.58% (relative risk 1.20; 98.2% CI 0.87–1.65). Acute respiratory infections: 22.94% vs 22.13% (relative risk 1.04; 99.9% CI 0.97–1.11). A small substudy showed increases in 25(OH)D3 (+15.0 nmol/L) and omega-3 index (+1.9%) with cod liver oil; baseline 25(OH)D3 ≥50 nmol/L was common. Effects were not modified by sex, age, BMI, sun exposure,…

Study & population

Adults aged ≥18 years in Norway; general population; quadruple-masked, randomized, parallel-group two-arm trial; 34,741 randomized; 34,601 analyzed (17,278 cod liver oil, 17,323 placebo); mean age 44.9 years; 64.5% female; mean BMI 26.1; exclusions included renal failure/dialysis, hypercalcaemia, severe liver disease, sarcoidosis or other granulomatous…

Intervention

Cod liver oil, 5 mL daily for ~6 months during winter 2020-21; lemon-flavoured oil; contains ~10 µg vitamin D3 (400 IU), 1.2 g long-chain omega-3 fatty acids (EPA 0.4 g, DHA 0.5 g), 250 µg vitamin A, 3 mg vitamin E.

Key limitation

Fewer SARS-CoV-2 infections than expected reduced power to detect a modest effect; trial underpowered for the infection endpoint; biomarker analyses (25(OH)D3 and omega-3 index) were available in a small subset; cannot separate vitamin D effects from omega-3 effects; vaccination during the study could confound…

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Original abstract