Can taking cod liver oil reduce the risk of COVID-19? Original paper

Cod liver oil could be considered one of the first dietary supplements in modern history, with records dating back centuries that describe people taking cod liver oil for health reasons. During the 19th century, cod liver oil became more widely available in Europe, Asia, and the Americas and was widely taken to help with various health problems, including rickets, arthritis, and tuberculosis.^[1][2]

Recently, it’s been suggested that the nutritional characteristics of cod liver oil make it a possible intervention for reducing the risk of infection with SARS-CoV-2 (the virus that causes COVID-19), as well as complications from COVID-19. Notably, cod liver oil is a good source of long-chain omega-3 fatty acids, vitamin D, and vitamin A. Because some research suggests that these nutrients can have beneficial effects on the immune system, this study examined whether cod liver oil can lower the risk of COVID-19 or reduce its severity.

This 6-month randomized controlled trial was designed to evaluate whether taking cod liver oil can prevent COVID-19 infection. A total of 34,601 people (ages 18–75, average age of 45) from Norway were assigned to take either 5 mL of cod liver oil or a placebo (corn oil) daily. The trial was quadruple blinded, as neither the participants nor any of the investigators knew who was given cod liver oil.

The cod liver oil contained 400 IU of vitamin D, 1.2 grams of long-chain omega-3 fatty acids, 250 ug of vitamin A, and 3 mg of vitamin E. The corn oil placebo contained 16 ug of vitamin A and 3.8 mg of vitamin E.

Noteworthy nutrients in cod liver oil

The outcomes assessed were SARS-CoV-2 infections (confirmed by PCR testing), serious COVID-19 (based on positive test and self-reported difficulty breathing), and any self-reported acute respiratory infection (ARI). The investigators also assessed the number of participants with at least one negative SARS-CoV-2 test, in case one group tested less often (as this would artificially lower the infection rate in this group).

There were no differences between groups for rates of SARS-CoV-2 infection (cod liver oil: 1.31%, placebo: 1.32%), serious COVID-19 (cod liver oil: 0.7%, placebo: 0.58%), or any self-reported ARI (cod liver oil: 22.94%, placebo: 22.13%). The number of participants with at least one SARS-CoV-2 negative test was also no different between groups (cod liver oil: 49.46%, placebo: 49.44%).

The reported adverse events were all low grade (mild to moderate). The number of participants reporting side effects was lower in the cod liver oil group (10.1%) than in the placebo group (11.3%). The main adverse events were nausea/vomiting (0.4% higher with placebo) and stomach symptoms like stomach pain, diarrhea, and constipation (0.5% higher with placebo).

The cod liver oil group increased their vitamin D levels by 15 nmol/L and increased their omega-3 index (the percentage of long chain omega-3s vs. other fatty acids in the blood) by 1.9%, compared to placebo.

Of participants who developed COVID-19, only 17 (8 in the cod liver oil group and 9 in the placebo group) required admission to the hospital, and none died.

About 36% of participants were vaccinated against COVID-19 during the trial.

The results of this study suggest that taking cod liver oil is not an effective prophylactic measure for preventing COVID-19. Still, it is probably worth contextualizing these results and considering how to interpret them as part of the broader body of literature.

Cod liver oil is a good source of vitamin D. Low circulating levels of vitamin D have been associated with a higher risk of infection with SARS-CoV-2 and a higher risk of developing severe COVID-19. Vitamin D supplementation is likewise associated with a lower risk of developing severe COVID-19.^[3] Still, this evidence is observational, so it can’t be ruled out that other factors, like health conditions and lifestyle habits, are responsible for differences in the risk of COVID-19 and that vitamin D is just a proxy for these factors.

Clinical trials on vitamin D for COVID-19 have had mixed results. On the preventative side, one randomized controlled trial (RCT) of 321 healthcare workers in Mexico City found that taking 4,000 IU per day of vitamin D per day reduced the risk of developing COVID-19.^[4] Conversely, another RCT of 6,200 people from the U.K. found no clear effect of vitamin D supplementation (either 800 IU or 3,200 IU per day) on the same outcome.^[5]

A few clinical trials have also looked at the effect of supplementation of vitamin D among people with active COVID-19, with the results likewise mixed. Two RCTs looked at the effect of vitamin D on health outcomes among people with COVID-19 infection. In one of these studies, taking a higher vs. lower dosage of vitamin D (5,000 vs. 1,000 IU per day) reduced the number of days with a cough from 9.1 to 6.2 days.^[6] However, in the other study using a single large dose of vitamin D (200,000 IU), there was no effect on serious COVID-19 outcomes, like ICU admission and death.

Two RCTs also looked at whether supplementation with high doses of vitamin D can help people clear the virus faster. In an RCT conducted in India, taking vitamin D (60,000 IU per day) seemed to help people with COVID-19 become SARS-CoV-2 negative more quickly.^[7] Additionally, a RCT from Mexico found no apparent effect of vitamin D (10,000 IU per day) on viral clearance rates among people with COVID-19.^[8]

Most participants in the current cod liver oil study did not have vitamin D deficiency as it is typically defined (less than 20 ng/mL). At baseline, participants in the cod liver oil group had average vitamin D levels of 66.9 nmol/L or 26.76 ng/mL, and participants in the placebo group had average vitamin D levels of 73.3 nmol/L or 29.32 ng/mL. If vitamin D is only beneficial in the case of a deficiency, this study would not have been a good test of vitamin D’s potential benefits.

Cod liver oil is also rich in long-chain omega-3 fatty acids. There isn’t much research on the effect of these fats on COVID-19 outcomes, but one large observational study found that supplementation with omega-3s was associated with a lower risk of SARS-CoV-2 infection. However, this effect depended on the population under examination. For example, benefits were observed in women but not men.^[9] The other notable study was an RCT of critically ill COVID-19 patients, which found an increased intake of omega-3s (1,000 mg per day) reduced the risk of death.^[10] Ultimately, neither of these studies provide strong evidence that omega-3s can prevent COVID-19.

Finally, cod liver oil is a good source of vitamin A. There is very little research evaluating how vitamin A status is related to COVID-19 outcomes, but vitamin A has a number of seemingly beneficial effects on the immune system,^[11] and vitamin A supplementation has shown some benefits in the context other viral infection.^[12][13] There has only been one RCT of vitamin A for COVID-19, which found no apparent benefits from vitamin A (50,000 IU per day). However, this study only analyzed 30 participants, so it is far from definitive.^[14]

Finally, it should be noted that the participants in the summarized study did not appear to be especially prone to negative sequelae resulting from SARS-CoV-2 infection, as evidenced by the fact that of the 455 people who became infected, only 17 required admission to the hospital and no one died. Based on this, it may not be appropriate to extrapolate this study’s findings to a population more susceptible to adverse COVID-19 outcomes (e.g., older adults).