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

Abstract

Objective: To determine if daily supplementation with cod liver oil, a low dose vitamin D supplement, in winter, prevents SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections in adults in Norway.

Design: Quadruple blinded, randomised placebo controlled trial.

Setting: Norway, 10 November 2020 to 2 June 2021.

Participants: 34 601 adults (aged 18-75 years), not taking daily vitamin D supplements.

Intervention: 5 mL/day of cod liver oil (10 µg of vitamin D, n=17 278) or placebo (n=17 323) for up to six months.

Main outcome measures: Four co-primary endpoints were predefined: the first was a positive SARS-CoV-2 test result determined by reverse transcriptase-quantitative polymerase chain reaction and the second was serious covid-19, defined as self-reported dyspnoea, admission to hospital, or death. Other acute respiratory infections were indicated by the third and fourth co-primary endpoints: a negative SARS-CoV-2 test result and self-reported symptoms. Side effects related to the supplementation were self-reported. The fallback method was used to handle multiple comparisons.

Results: Supplementation with cod liver oil was not associated with a reduced risk of any of the co-primary endpoints. Participants took the supplement (cod liver oil or placebo) for a median of 164 days, and 227 (1.31%) participants in the cod liver oil group and 228 (1.32%) participants in the placebo group had a positive SARS-CoV-2 test result (relative risk 1.00, multiple comparison adjusted confidence interval 0.82 to 1.22). Serious covid-19 was identified in 121 (0.70%) participants in the cod liver oil group and in 101 (0.58%) participants in the placebo group (1.20, 0.87 to 1.65). 8546 (49.46%) and 8565 (49.44%) participants in the cod liver oil and placebo groups, respectively, had ≥1 negative SARS-CoV-2 test results (1.00, 0.97 to 1.04). 3964 (22.94%) and 3834 (22.13%) participants in the cod liver oil and placebo groups, respectively, reported ≥1 acute respiratory infections (1.04, 0.97 to 1.11). Only low grade side effects were reported in the cod liver oil and placebo groups.

Conclusion: Supplementation with cod liver oil in the winter did not reduce the incidence of SARS-CoV-2 infection, serious covid-19, or other acute respiratory infections compared with placebo.

Trial registration: ClinicalTrials.gov NCT04609423.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Orkla Health AS, Oslo University Hospital, and the University of Oslo for the submitted work. During the past three years, KBH has received research grants or personal fees from Olympic Seafood, Amgen, and Sanofi, not related to the content of this manuscript. SMU has received a research grant from Olympic Seafood during the past three years, not related to the content of this manuscript. AS and KTK are employed by Age Laboratories AS, a company developing SARS-CoV-2 diagnostics, and FL-J has received grants from Helse-SørØst for developing SARS-CoV-2 diagnostics, not related to the content of this manuscript. The authors declare; no support from any organisation for the submitted work (except from the funders); no financial relationship with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Fig 1

Consolidated Standards of Reporting Trials (CONSORT) flow diagram of Cod Liver Oil for Covid-19 Prevention Study (CLOC). *Norwegian Covid-19 Cohort Study is a population based open cohort established in March 2020. †Including history of renal failure or dialysis, hypercalcaemia, severe liver disease (cirrhosis), sarcoidosis, or other granulomatous disease (eg, granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)). ‡Vegan, pregnant, ≥75 years old. §Loose compliance: reported consuming >0.1 L of cod liver oil or placebo, consuming cod liver oil or placebo for >0-1 month, or consuming cod liver oil or placebo for >1 day/week. ¶Strict compliance: reported consuming >0.5 L of cod liver oil or placebo or consuming cod liver oil or placebo for >2-3 months

Fig 2

Kaplan-Meier plot of the probability of a positive SARS-CoV-2 test result for participants in the cod liver oil (n=17 278) and placebo (n=17 323) groups during the intervention period