Abstract Background Omega-6 polyunsaturated fatty acids (PUFAs) represent almost 15% of the total energy intake in the Western countries. Their effects on several cardiovascular (CV) risk factors are still controversial. Purpose 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 (or possible causality) between supplementation or serum levels of omega-6 PUFA, CV disease (CVD) and cardiometabolic risk factors. Methods Selected databases were searched until 31 August 2019 to identify prospective studies investigating the effects of omega-6 PUFAs 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. Inverse variance weighted method (IVW), weighted median-based method, MR-Egger and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied for MR. Results In the meta-analysis of 9 studies with 4,433 participants we showed that omega-6 PUFAs supplementation was not associated with CVD event risk - RR 0.94 (95% CI: 0.77–1.15, heterogeneity p=0.031; I2=66.2%, n=4 studies). The pooled estimate (RR) of the effect of omega-6 PUFAs supplementation on CVD death was 1.06 (95% C:I 0.73–1.55, heterogeneity p=0.011; I2=66.2%, n=6 studies), on CHD events 0.84 (95% CI: 0.61–1.16, heterogeneity p=0.001; I2=79.4%), on MI 0.87 (95% CI: 0.74–1.01, heterogeneity p=0.381; I2=2.3%) (Figure), and on stroke 1.36 (95% CI: 0.45–4.07, heterogeneity p=0.082; I2=55.3%). In MR analysis we showed that individuals with genetically higher serum adrenic acid (AA; 22:4, n-6) levels had a greater risk of CHD events (IVW=Beta: 0.526, p=0.007), MI (IVW=Beta: 0.606, p=0.017) and stroke (IVW=Beta: 1.694, p=0.009), as well as higher levels of FBG (IVW=Beta: 0.417, p=1.0x10–3), LDL-C (IVW=Beta: 0.806, p=4.9x10–5), HDL-C (IVW=Beta: −0.820, p=4.3x10–17), whereas lower levels of TG (IVW=Beta: −1.064, p=1.2x10–12) and TC (IVW=Beta: −1.064, p=1.2x10–12). Conclusions In the pooled analysis different omega-6 PUFAs supplementation did not affect the risk of MI, stroke and CHD event/mortality or the serum concentration of cardiometabolic parameters (data not presented), however in MR analysis, higher AA levels significantly associated with the risk of CHD, MI and stroke, as well as with elevated levels of FBG, LDL-C and HDL-C and reduced levels of TC and TG. There is probably lack of class effect for omega-6 PUFAs, therefore further studies are needed to assess the effects of omega-6 PUFAs on cardiometabolic outcomes. Funding Acknowledgement Type of funding source: None
Read full abstract