A new study by researchers from the Guangdong Academy of Medical Sciences-China, the Southern Medical University, Guangzhou-China, South China University of Technology, Guangzhou-China, Shantou University Medical College-China, University of California Los Angeles-USA and the Veterans Affairs Greater Los Angeles Healthcare System-USA involving a cohort study of data from the UK Biobank has found that regular use of fish oil supplements prevents the risk of severe COVID-19 outcomes.
The study team aimed to investigate the associations of habitual fish oil use with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospital admission, or mortality with Corona Virus Disease-19 (COVID-19) in a large-scale population-based cohort study involving the UK Biobank.
A total of 110 440 participants aged 37 -73 years who completed a questionnaire on supplement use, which included fish oil at baseline were enrolled between 2006 and 2010 and followed up until 2022.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2022.09.14.22279933v1
In this large-scale prospective cohort study, we found that habitual fish oil use was consistently associated with a lower risk of hospital admission and mortality with COVID-19, using fully-adjusted Cox proportional hazard models or logistic regression models. Additionally, no association was found between habitual fish oil use and the risk of COVID-19 infection in the population with more than 12.1 years of follow-up.
Comparison with other studies
To the best of our knowledge, our study is the first large-scale prospective cohort study, utilizing the latest data from the UK biobank, to examine the effects of habitual fish oil use on the risks of SARS-CoV-2 infection, hospital admission and mortality with COVID-19. Our findings are in agreement with the results of several published studies, while their inadequate sample sizes and poor study designs might have limited the power to detect the effects of fish oil, that it plays a protective role in hospital admission and mortality with COVID-191718.
However, we found that there was no association between habitual fish oil use and the risk of SARS-CoV-2 infection, which is different from previous studies. In Louca’ s study, regular fish oil user had a 12% lower risk of SARS-CoV-2 infection in the UK19.
One possible explanation is that it was conducted at a time when the omicron variant did not appear. By Jan 10, 2022, omicron cases represented more than 99% of all sequenced cases in the UK20.
Thus, our analysis of SARS-CoV-2 infection, utilizing the latest COVID-19 data (Version: Feb 2022), found different influences of fish oil use on SARS-CoV-2 infection in different periods. In the earlier stage, fish oil performed a protective function in preventing SARS-CoV-2 infection, which is in accordance with the finding of Louca’ s study.
In contrast, there is no association between habitual fish oil use and SARS-CoV-2 infection in the later stage when the Omicron is the dominant variant causing the pandemic in the UK. With high number of mutations, the omicron has novel biological and epidemiological characteristics of immune evasion and high transmissibility, which may account for the failure of protective effect on SARS-CoV-2 infection derived from fish oil use 21.
Since available prevention approaches, such as vaccines, are less effective against the Omicron variant, early preventive steps should be developed to suppress the Omicron variant22.
As new variants of SARS-CoV-2 will likely continue to emerge, further large-scale randomized controlled trials of habitual fish oil use testing its effects on COVID-19-related outcomes in existing variants are warranted.
There are certain potential mechanisms for the observed benefits for COVID-19-related outcomes derived from fish oil. SARS-CoV-2 infection can cause exaggerated host immune responses, resulting in cytokine storm, the uncontrolled release of proinflammatory cytokines23. n-3 PUFAs, the main component of fish oil, have been shown to have powerful anti-inflammatory properties and play a critical role in regulating inflammatory processes through several diverse mechanisms, including acting as substrates for the synthesis of protectins during viral and bacterial infections24-26.
Moreover, accumulative studies demonstrated that n-3 PUFAs help to attenuate the uncontrolled immune response in the lungs secondary to bacterial or viral infections which could be helpful in the setting of COVID-1927. It is also suggested that the immune modulatory properties of n-3 PUFAs will provide significant effects in improving clinical outcomes of COVID-19, particularly in hospitalized high-risk populations with hypertensive, oncologic, and diabetic patients28.
In the stratified analysis, we found that the protective associations of fish oil use against hospital admission and mortality with COVID-19 were stronger in those with longstanding diseases.
The evidence mentioned below could account for the finding. Several trials found that people with severe underlying conditions, including those pre-existing condition, have disturbed inflammatory components when suffering COVID-19, which may be greatly attenuated by n-3 PUFA2930.
Strengths and limitations of this study
Our study has several strengths. Firstly, a major strength was that we used various methods in statistical analyses, including Cox proportional hazards regression, propensity score-matching analyses, and multivariable logistics regression, to analyze the large-scale cohort with 110,440 participants involved, which demonstrates the effectiveness and adequate statistical power of fish oil use in a real-life setting.
Secondly, continuously updated data from the UK biobank allows us to analyze the role of fish oil in the pandemic caused by new variants. Besides, the records of COVID-19 outcomes of UK biobank were directly taken from test results, inpatient hospital data, and death registers to reduce selection bias 14.
Thirdly, detailed information on baseline characteristics and other covariates was available. Thus, we are able to minimize comprehensive confounding factors through constructing fully-adjusted models during the analyses and performing sensitivity analyses.
Several limitations should also be noted. First, the lack of information on the specific dose and frequency of fish oil use from the UK biobank prevented us from assessing potential causal relationship. Moreover, participants of the UK Biobank could not perfectly represent the UK population while they are more representative of healthier population than average, since the individuals were recruited on the premise of voluntariness31.