Are fish oil supplements associated with cardiovascular disease?

By Dr. Sushama R. Chaphalkar, PhD.Reviewed by Lily Ramsey, LLMMay 21 2024

In a recent study published in BMJ Medicine, researchers examined the effects of using fish oil supplements on the clinical progression of cardiovascular disease (CVD) in a prospective cohort of United Kingdom (UK) Biobank participants.

They found that regular use of fish oil supplements was associated with an increased risk of atrial fibrillation (AF) and stroke among healthy individuals but showed benefits in reducing major adverse cardiovascular events and death in participants with existing CVD.

​​​​​​​Study: Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study. Image Credit: Galina Zhigalova/Shutterstock.com

Background

CVD is the leading cause of death globally, responsible for about one-sixth of all deaths in the UK. Fish oil, rich in omega-3 fatty acids, is recommended to prevent CVD, with UK guidelines advising at least one portion of oily fish weekly.

However, the effects of fish oil are controversial. Some studies suggest the benefits of fish oil for ischemic stroke but not for AF or major cardiovascular events.

Conversely, the REDUCE-IT (short for reduction of cardiovascular events with icosapent ethyl–intervention trial) trial found reduced cardiovascular events with icosapent ethyl in patients with high triglycerides.

Previous studies examining the link between fish oil consumption and CVD mostly focused on single health outcomes or specific stages of CVD, and none focused on CVD progression.

This highlights the need for further research on fish oil's varied effects. To bridge this gap, researchers in the present study investigated the impact of using fish oil supplements on cardiovascular outcomes and disease progression in individuals with and without known CVD.

About the study

The present study included 415,737 participants from the UK Biobank. The mean age of participants was 55.9 years, and 55% were female. Patients with missing or outlier data and those with AF, heart failure, myocardial, stroke, or cancer at baseline were excluded.

Regular fish oil supplement use was self-reported using a questionnaire at the baseline, and participants were categorized as users or non-users. Data were collected on covariates, including demographic factors, dietary information, lifestyle, comorbidities such as diabetes mellitus and hypertension, and medication use.

Participants were followed up until death or the end date of the trial or were lost to follow-up, with a median follow-up of 11.9 years. Incident cases were identified using records in various registries. Statistical analysis involved using chi-square test, Student's t-test, multi-state regression models, likelihood ratio test, hazard ratios (HR), and sensitivity analyses.

Results and discussion

About 31.4% of the included participants consumed fish oil supplements regularly. Compared to non-users, regular use of fish oil supplements was found to be more common in older people, White, and female participants, as well as in those consuming higher amounts of alcohol, oily fish, and non-oily fish.

During the study period, 18,367 participants developed AF (transition A) and 17,826 had major adverse cardiovascular events (transition B), while 14,902 participants died without experiencing either (transition C). Among those with incident AF, 4,810 had major adverse cardiovascular events (transition D), and 1,653 died (transition E).

Regular fish oil use was found to be associated with an increased AF risk (HR= 1.13) but had no significant impact on major adverse cardiovascular events or death. In AF patients, it reduced major adverse cardiovascular events and protected slightly against death.

While it marginally increased stroke risk (HR: 1.05), it lowered heart failure risk (HR: 0.92). For AF patients, it decreased myocardial infarction risk, and for heart failure patients, it reduced mortality risk.

Stratified analysis showed that sex, age, consumption of non-oily fish, smoking, prevalent hypertension, and use of antihypertensive drugs and statins influenced the association between regular fish oil use and transition to AF.

Furthermore, the association between fish oil use and transition to major adverse cardiovascular events was found to be stronger in women and non-smokers.

Interestingly, fish oil's protective effect against transition to death was found to be more significant in men and older participants. The results of the sensitivity analysis corroborated the main findings.

The study is strengthened by its large sample size, long follow-up period, complete health outcome data, and use of a multi-state model.

However, the study is limited by its observational design, potential residual confounding, lack of data on fish oil dose and formulation, possible underestimation of AF events, limited generalizability, and unaddressed behavioral changes among different cardiovascular profiles.

Conclusion

In conclusion, the findings suggest that regular consumption of fish oil supplements may potentially increase the risk of AF and stroke in healthy individuals.

However, in persons with existing CVD, the regular consumption of fish oil supplements could be beneficial for preventing the progression from AF to major adverse cardiovascular events and death.

The findings highlight the need for tailored recommendations for using these supplements and warrant further research to understand the underlying mechanisms, ultimately informing better clinical guidelines and patient care.