Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study
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  • Published on:
    Misleading Results and Conclusions: The Role of Age as Risk factor for AF

    The study of Chen et al. (2024) presents a prospective cohort study conducted within the UK Biobank, aiming to evaluate the effects of fish oil supplements on the clinical course of cardiovascular disease, including transitions from a healthy state to atrial fibrillation, major adverse cardiovascular events, and death (1). While the study is ambitious and large-scale, involving 415,737 participants with a median follow-up of 11.9 years, several critical issues may compromise the validity of its conclusions.
    One major concern is the potential confounding effect of age, which is not adequately addressed in the study. Age is a well-established and significant risk factor for atrial fibrillation (AF) and other cardiovascular diseases (2). Additionally, it is notable that participants who regularly used fish oil supplements in this study were significantly older than those who did not (p < 0.0001). Given that the risk of AF and adverse cardiovascular events increases with age, differences in age distribution between those who do not regularly use fish oil supplements and those who do could significantly bias the results. This age-related bias likely contributes to the different risks observed, as the older age of supplement users naturally predisposes them to higher rates of AF, independent of fish oil supplement use.
    The reported absolute risk for AF was 4.24% for participants who did not use fish oil supplements and 4.75% for those who regularly used fish oil s...

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    Conflict of Interest:
    None declared.
  • Published on:
    Fish oil supplements: we need an NNH

    To the editors of the BMJ Medicine
    Dr. Emma Rouke and Dr. Sophie Cook

    About the study: Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study

    I read with great interest the article published by Chen G. et al. The supplement industry is a multimillion-dollar business, and the use of supplements without any criteria occurs worldwide. Most supplements are sold without prescription, and many consumers think that using supplements involves no health risks.

    Chen et al. demonstrate that the use of fish oil supplements increases the incidence of atrial fibrillation and stroke in a prospective study conducted in the UK Biobank. It would be very informative to know the number needed to harm (NNH) to better inform the general population and health professionals about the risks of such supplementation.

    This data could also be compared with the number needed to treat (NNT) from another study conducted in the same population (UK Biobank), which shows that habitual fish oil supplementation is associated with a 13% lower risk of all-cause mortality, a 16% lower risk of CVD mortality, and a 7% lower risk of CVD events among the general population.

    Such information could lead to better shared decision-making regarding the use of fish oil supplements.

    Chen et al. Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study. BMJMED 2024;3:e000...

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    Conflict of Interest:
    None declared.
  • Published on:
    Risk with Fish Oil – Clarity or Misplaced Controversy?
    • Jacob Hands, Senior Research Associate The George Washington University School of Medicine

    Chen et al. (2024) find that fish oil supplementation exerts several adverse effects in “healthy” users without baseline history of cardiovascular disease (CVD). In particular, the authors note that the risk of conversion from healthy status to atrial fibrillation (HR 1.13 p<0.001) and stroke (HR 1.05, p=0.05) were increased in healthy users without a pre-existent diagnosis of CVD (1).

    While we applaud the authors for their research, we note several major flaws with their results that warrant further exploration.

    First, the authors claim that stroke risk is increased in “healthy” users of fish oil. The definition of “healthy” user is heterogenous and misleading as the authors use a mix of electronic medical records and self-reported survey data to derive this definition. Further, fish oil use is not a randomized allocation. Consequently, fish oil users may have some indication for elevated CVD or stroke risk at baseline that prompts its consumption, which would indicate reverse causation. Therefore, the reliability of survey data for such indications is weak at best and cannot be used to extrapolate a truly CVD risk-free state. Moreover, although hypertension is the most significant modifiable risk factor for stroke, family history, inflammatory parameters, and polygenic risk scores may inform personalized CVD risk to a similar or greater extent, and were not adequately controlled in this analysis (2).

    Second, the reports of stroke risk in healthy...

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    Conflict of Interest:
    None declared.
  • Published on:
    Fish Oil Supplements and Cardiovascular Disease: Commentary on Recent UK Biobank Findings
    • William S. Harris, Researcher Fatty Acid Research Institute
    • Other Contributors:
      • Dariush Mozaffarian, Dean and Cardiologist

    In Chen and colleagues’ observational report of use of fish oil supplements (FOS) and cardiovascular outcomes in the UK Biobank study (1), their stated conclusions suggest equipoise of observed relationships, i.e., relatively balanced risks vs. benefits. However, only one adverse association achieved statistical significance - onset of atrial fibrillation (AF) - while five protective associations did so, including onset of heart failure, mortality after heart failure, and (after onset of AF) risk of myocardial infarction, major adverse cardiovascular events, and death (Figure 1). While important, AF also remains a relatively less severe clinical outcome compared with heart failure and myocardial infarction. These new findings provide evidence to support general cardiovascular benefits of FOS use.

    Ten prior studies - all from UK Biobank - have assessed observational relationships between FOS use and health conditions, ranging from fractures to liver cancer to CV disease to dementia to death (2-11). Across these, 18 relationships were both statistically significant and favorable for FOS users (including total mortality); and only 1 showed an adverse association (AF). Thus, consistent with the new report, the overall findings from the UK Biobank support important net health benefits of FOS use.

    These observational studies have advantages of large, fairly generalizable populations and extended follow-up, allowing an assessment of potential long-term effects of...

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    Conflict of Interest:
    WSH holds an interest in OmegaQuant Analytics, a laboratory that offers blood fatty acid testing.
  • Published on:
    Poor design, poor inference
    • Natalia Ortega, PhD student Institute for Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
    • Other Contributors:
      • Conor J MacDonald, Karolisnka Institutet,

    In a recent publication, Chen et al. (1) show the potential negative effects of fish oil supplementation on incident atrial fibrillation (AF) and subsequent effects on cardiovascular events (CVE) and death in the UK Biobank. Even though the authors start with a well-defined question (i.e., risk of AF had everyone taken taking fish oil supplements for primary prevention vs. had they not), moving into the conclusion, they state: “Regular use of fish oil supplements […] could be beneficial for progression of cardiovascular disease from AF to major adverse CVE, and from AF to death”. We reflect on the aspects for which the study was not fit for this conclusion.

    To illustrate the point, imagine that the authors had instead conducted a randomized trial to estimate their well-defined question – ‘Does fish oil supplementation reduce the incidence of AF and CVE?’. The investigators would recruit a population free of AF and CVE at baseline, and randomly assign them to regular fish oil supplement or placebo. Follow-up would then start until AF, CVE, or death. The investigators would determine if the intervention prevented AF, CVE or death by counting the number of cases at the end of the follow-up period, or by comparing survival curves.
    Now suppose the investigators of this trial conduct a secondary analysis, among those who develop AF during the first half of the follow up period. Among these individuals, the investigators then count the incidence of further CVE and st...

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    Conflict of Interest:
    None declared.