Omega-6 fatty acids and the risk of cardiovascular disease: insights from a systematic review and meta-analysis of randomized controlled trials and a Mendelian randomization study
Abstract
Introduction Omega-6 polyunsaturated fatty acids (PUFAs) represent almost 15% of the total energy intake in Western countries. Their effects on the cardiovascular (CV) risk factors are still controversial. Thus, we performed a systematic review and meta-analysis of randomized control trials (RCTs) as well as a Mendelian randomization (MR) analysis to evaluate the links and possible causality between supplementation or serum levels of omega-6 PUFA, CV disease (CVD) and cardiometabolic risk factors. Material and methods Selected databases were searched until September 2019 to identify prospective studies investigating the effects of omega-6 PUFA supplementation on CVD events/mortality. Random-effects model meta-analysis was performed for quantitative data synthesis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 20% reduction in outcomes after administration of omega-6 PUFAs. The inverse variance weighted (IVW) method, weighted median-based method, MR-Egger and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied for MR. Results The pooled estimate risk ratio (RR) of omega-6 PUFA supplementation was 0.94 for any CVD event (95% CI: 0.77–1.15, I2 = 66.2%), 1.06 for CVD death (95% CI: 0.73–1.55, I2 = 66.2%), 0.84 for coronary heart disease (CHD) events (95% CI: 0.61–1.16, I2 = 79.4%), 0.87 for myocardial infarction (MI) (95% CI: 0.74–1.01, I2 = 2.3%) and 1.36 for stroke (95% CI: 0.45–4.07, I2 = 55.3%). In contrast, MR showed that…
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