People who received omega-3 fish oil supplements in randomised clinical trials had significantly lower risks of heart attack and other cardiovascular disease (CVD) events compared with those who were given placebo, according to a meta-analysis from Harvard TH Chan School of Public Health and Brigham and Women’s Hospital. Researchers found an association between daily omega-3 supplementation and reduced risk of most CVD outcomes, including heart attack, death from coronary heart disease, and death from CVD, but did not see benefit for stroke. In addition, higher doses of omega-3 fish oil supplements appeared to provide even greater risk reduction.
“This meta-analysis provides the most up-to-date evidence regarding the effects of omega-3 supplementation on risk of multiple CVD outcomes. We found significant protective effects of daily omega-3 supplementation against most CVD outcome risks and the associations appeared to be in a dose-response manner,” said first author Yang Hu, a postdoctoral fellow in the department of nutrition at Harvard Chan School.
While observational studies have shown an association between fish consumption and lower heart disease risk, results from randomised controlled trials (RCTs) have been inconsistent. Two reviews published last year did not find clear evidence for benefit.
In this new analysis, the researchers did an updated meta-analysis that included three recently completed large-scale trials, which increased the sample size by 64%. The total population analysed by Hu and colleagues included more than 120,000 adults in 13 randomised trials worldwide. The analysis included the VITAL trial, the largest randomised trial of omega-3s to date.
The findings showed that people who took daily omega-3 fish oil supplements, compared with those who took a placebo, lowered their risk for most CVD outcomes except stroke, including an 8% reduced risk for heart attack and coronary heart disease (CHD) death. The association was particularly evident at higher doses of omega-3 fish oil supplementation. This finding may suggest that marine omega-3 supplementation dosage above the 840 mg/day used in most randomised clinical trials may provide greater reductions in CVD risk. Given that several million people experience these CVD events worldwide each year, even small reductions in risk can translate into hundreds of thousands of heart attacks and CVD deaths avoided, according to the researchers.
“Although public health recommendations should focus on increasing fish consumption, having an overall heart-healthy diet, being physically active, and having other healthy lifestyle practices, this study suggests that omega-3 supplementation may have a role in appropriate patients,” said senior author JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s Hospital and professor in the department of epidemiology at Harvard Chan School. Manson is also the director of the large-scale VITAL trial of omega-3s.
Other Harvard Chan School authors included Frank Hu.
Background: Whether marine omega‐3 supplementation is associated with reduction in risk of cardiovascular disease (CVD) remains controversial.
Methods and Results: This meta‐analysis included study‐level data from 13 trials. The outcomes of interest included myocardial infarction, coronary heart disease (CHD) death, total CHD, total stroke, CVD death, total CVD, and major vascular events. The unadjusted rate ratios were calculated using a fixed‐effect meta‐analysis. A meta‐regression was conducted to estimate the dose–response relationship between marine omega‐3 dosage and risk of each prespecified outcome. During a mean treatment duration of 5.0 years, 3838 myocardial infarctions, 3008 CHD deaths, 8435 total CHD events, 2683 strokes, 5017 CVD deaths, 15 759 total CVD events, and 16 478 major vascular events were documented. In the analysis excluding REDUCE‐IT (Reduction of Cardiovascular Events with Icosapent Ethyl‐Intervention Trial), marine omega‐3 supplementation was associated with significantly lower risk of myocardial infarction (rate ratio [RR] [95% CI]: 0.92 [0.86, 0.99]; P=0.020), CHD death (RR [95% CI]: 0.92 [0.86, 0.98]; P=0.014), total CHD (RR [95% CI]: 0.95 [0.91, 0.99]; P=0.008), CVD death (RR [95% CI]: 0.93 [0.88, 0.99]; P=0.013), and total CVD (RR [95% CI]: 0.97 [0.94, 0.99]; P=0.015). Inverse associations for all outcomes were strengthened after including REDUCE‐IT while introducing statistically significant heterogeneity. Statistically significant linear dose–response relationships were found for total CVD and major vascular events in the analyses with and without including REDUCE‐IT.
Conclusions: Marine omega‐3 supplementation lowers risk for myocardial infarction, CHD death, total CHD, CVD death, and total CVD, even after exclusion of REDUCE‐IT. Risk reductions appeared to be linearly related to marine omega‐3 dose.
Yang Hu, Frank B Hu, JoAnn E Manson