Cod Liver Oil for Covid-19 Prevention Study

A Randomized, Parallel-group Treatment, Quadruple Masked, Two-arm Study, to Assess the Effectiveness of Cod Liver Oil Compared to Placebo in the Prevention of Covid-19 and Airway Infections in Healthy Adults

A randomized, parallel-group treatment, quadruple masked, two-arm study to assess the effectiveness of cod liver oil compared to placebo in the prevention of Covid-19 and airway infections in healthy adults.

In this study, the investigators will investigate whether daily cod liver oil can prevent Covid-19 infections and reduce the severity of such infections. The investigators will also examine whether cod liver oil prevents other airway infections in healthy adults.

Study Overview

• Status: Completed
• Conditions: Respiratory Tract Infections; Covid-19
• Intervention / Treatment: Dietary supplement: Cod liver oil; Dietary supplement: Corn oil (placebo)

Detailed Description

Preliminary evidence from literature and an ongoing study in the investigators' lab suggests that cod liver oil may prevent Covid-19 and complications of Covid-19. In the present study, the investigators will examine whether this is actually the case by randomizing volunteers to take cod liver oil or placebo (corn oil) during the winter months of 2020-2021. The investigators also aim to explore whether cod liver oil can prevent other respiratory tract infections, as well as explore and confirm already known health effects and possible new health effects, in particular rare adverse events associated with cod liver oil use.

Cod liver oil is a traditional source of vitamin A, D, and E and omega-3 fatty acids and the dose administered in the study will contain 250 ug vitamin A, 10 ug vitamin D, 10 mg vitamin E, and 1,2 g omega-3 fatty acids.

• Study Type: Interventional
• Enrollment (Actual): 47210
• Phase: Phase 4

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0424
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any person >18 years with a Norwegian Personal Identity Number

Exclusion Criteria:

• History of renal failure or dialysis, hypercalcemia, severe liver disease (cirrhosis), sarcoidosis or other granulomatous diseases (Wegener)
• Allergy to fish or corn oil.
• Pregnancy or planned pregnancy before summer 2021
• Vegan diet
• Age >75 years old at inclusion based on the Norwegian Personal Identity Number
• Difficulty in swallowing cod liver oil or other oils
• Previous Covid-19 disease
• For Caucasians only: Use of any supplement containing more than trace amounts of vitamin D or omega-3 fatty acids at inclusion (Vitamin D levels in non-Caucasians living in Norway are frequently low even among those self-reporting using dietary supplements). This criterion will be relaxed if too few participants volunteer for the study and only Caucasians that use cod liver oil or an equivalent dietary supplement (with omega 3 and vitamin D) more than 5-7 times per week will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cod liver oil; supplementation for 6 months	Dietary supplement: Cod liver oil; 5 ml of cod liver oil as a source of 10 ug of vitamin D and 1.2 g of long-chained n-3 polyunsaturated fatty acids (DHA 0,6g and EPA 0,4g) per day for 6 months x 1 time/day together with the first meal of the day. 5ml of Cod liver oil also contains 250ug vitamin A and 10 mg vitamin E.; Other Names: 10 ug of vitamin D and 1 g n-3 LCPUFA; Tran
Placebo Comparator: Corn oil (placebo); supplementation for 6 months	Dietary supplement: Corn oil (placebo); 5 ml of corn oil per day for 6 months x 1 time/day together with the first meal of the day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants diagnosed with serious Covid-19	The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following: A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol)	6 months
Number of participants diagnosed with New Covid-19	The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking.	6 months
Number of participants with negative SARS-CoV-2 test	Number of participants with an airway sample negative for SARS-CoV-2 (indicative of another airway infection). *Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.	6 months
Number of participants with self-reported airway infection	The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants hospitalized due to Covid-19	Number of participants hospitalized wholly or partly caused by Covid-19.	6 months
Number of participants in Intensiv Care Unit (ICU) caused by Covid-19	Number of participants with ICU care wholly or partly caused by Covid-19.	6 months
Number of participants with any admissions to hospital	Number of participants with any admissions to hospital based on the Norwegian Patient Registry data.	6 months
Infection with each of the mentioned pathogens	An airway sample positive for a respiratory pathogen* (either PCR or culture) in the period from one week after the start of cod liver oil/placebo taking to the end of this period. *Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.	6 months
Number of visits at GP for infections	Based on The Norwegian Reimbursement Database	6 months
Number of visits at GP	Based on The Norwegian Reimbursement Database	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Cardiovascular disease	Based on self-reporting and Norwegian Registries	6 months
Incidence of Cardiovascular disease	Based on self-reporting and Norwegian Registries	30 months
Incidence of cardiovascular mortality	Based on self-reporting and Norwegian Registries	6 months
Incidence of cardiovascular mortality	Based on self-reporting and Norwegian Registries	30 months
Incidence of cancer	Based on self-reporting and Norwegian Registries	6 months
Incidence of cancer	Based on self-reporting and Norwegian Registries	30 months
Incidence of cancer mortality	Based on self-reporting and Norwegian Registries	6 months
Incidence of cancer mortality	Based on self-reporting and Norwegian Registries	30 months
All-cause mortality	Based on self-reporting and Norwegian Registries	6 months
All-cause mortality	Based on self-reporting and Norwegian Registries	30 months
Incidence of fracture of the hip or forearm	Based on self-reporting and Norwegian Registries	6 months
Incidence of fracture of the hip or forearm	Based on self-reporting and Norwegian Registries	30 months
Incident dementia	Based on self-reporting and Norwegian Registries	6 months
Incident dementia	Based on self-reporting and Norwegian Registries	30 months
Number of participants diagnosed with serious Covid-19	The number of participants with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories in the period from one week after the start of cod liver oil/placebo taking to the end of this period together with any of the following: A) Self-reported dyspnea and fever concurrent (within four weeks) with the positive test OR B) hospitalization caused by Covid-19 concurrent (within four weeks) with the positive test OR C) death where the Covid-19 infection was wholly or partly responsible as judged by the death certificate (see endpoint in the protocol)	12 months
Number of participants diagnosed with new Covid-19	The number of participants diagnosed with first time SARS-CoV-2 positive nasopharyngeal and or pharyngeal swabs (or any other sample used for detection of current disease) analyzed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) nucleic acid amplification test or antigen tests used by accredited Norwegian microbiology laboratories from one week after the start of cod liver oil/placebo taking.	12 months
Laboratory confirmed respiratory tract infection	An airway sample positive for a respiratory pathogen* (either PCR or culture). *Influenza virus (A and B), parainfluenzavirus (1,2,3), metapneumovirus, rhinovirus, coronavirus (non-SARS), Respiratory Syncytial virus, Haemophilus Influenzae, Moraxella Catharralis, Streptococcus Pneumonia, Beta-hemolytic streptococci, Mycoplasma pneumonia, Chlamydophila pneumonia, Enterovirus, Bordetella pertussis. The list can be expanded based on the analyses performed in Norwegian Microbiology laboratories.	12 months
Self-reported airway infection	The number of episodes with any two of the following symptoms: fever, cough, nasal congestion or sore throat	12 months
Number of participants with self-reported cod liver oil related adverse events	Number of participants with self-reported adverse events	12 months
Number of participants with cod liver oil related adverse events	Number of participants hospitalized for major diseases or death in the cod liver oil versus placebo group in Norwegian registries	12 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo; Norwegian Institute of Public Health
• Investigators: Principal Investigator: Arne Søraas, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Brunvoll SH, Nygaard AB, Ellingjord-Dale M, Holland P, Istre MS, Kalleberg KT, Soraas CL, Holven KB, Ulven SM, Hjartaker A, Haider T, Lund-Johansen F, Dahl JA, Meyer HE, Soraas A. 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. BMJ. 2022 Sep 7;378:e071245. doi: 10.1136/bmj-2022-071245.

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2020
• Primary Completion (Actual): June 2, 2021
• Study Completion (Actual): June 2, 2021

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: October 28, 2020
• First Posted (Actual): October 30, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Vitamin D; Cod liver oil; n-3 LCPUFAs; SARS-CoV virus
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Infections; Respiratory Tract Infections; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D; Cod Liver Oil
• Other Study ID Numbers: REK-172796

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: IPD is complicated to share under the European General Data Protection Regulative, however, it is an aim of the study to make such data available within these regulations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes