Abstract: We included 19 RCTs in 6461 participants who were followed for one to eight years. Seven trials assessed the effects of supplemental GLA and 12 of LA, none DGLA or AA; the omega-6 fats usually displaced dietary saturated or monounsaturated fats. We assessed three RCTs as being at low summary risk of bias. Primary outcomes: we found low-quality evidence that increased intake of omega-6 fats may make little or no difference to all-cause mortality (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.88 to 1.12, 740 deaths, 4506 randomised, 10 trials) or CVD events (RR 0.97, 95% CI 0.81 to 1.15, 1404 people experienced events of 4962 randomised, 7 trials). We are uncertain whether increasing omega-6 fats affects CVD mortality (RR 1.09, 95% CI 0.76 to 1.55, 472 deaths, 4019 randomised, 7 trials), coronary heart disease events (RR 0.88, 95% CI 0.66 to 1.17, 1059 people with events of 3997 randomised, 7 trials), major adverse cardiac and cerebrovascular events (RR 0.84, 95% CI 0.59 to 1.20, 817 events, 2879 participants, 2 trials) or stroke (RR 1.36, 95% CI 0.45 to 4.11, 54 events, 3730 participants, 4 trials), as we assessed the evidence as being of very low quality. We found no evidence of dose-response or duration effects for any primary outcome, but there was a suggestion of greater protection in participants with lower baseline omega-6 intake across outcomes. Additional key outcomes: we found increased intake of omega-6 fats may reduce myocardial infarction (MI) risk (RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low-quality evidence). High-quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little in the long term (mean difference (MD) −0.33 mmol/L, 95% CI −0.50 to −0.16, I2 = 81%; heterogeneity partially explained by dose, 4280 participants, 10 trials). Increasing omega-6 fats probably has little or no effect on adiposity (body mass index (BMI) MD −0.20 kg/m2, 95% CI −0.56 to 0.16, 371 participants, 1 trial, moderate-quality evidence). It may make little or no difference to serum triglycerides (MD −0.01 mmol/L, 95% CI −0.23 to 0.21, 834 participants, 5 trials), HDL (MD −0.01 mmol/L, 95% CI −0.03 to 0.02, 1995 participants, 4 trials) or low-density lipoprotein (MD −0.04 mmol/L, 95% CI −0.21 to 0.14, 244 participants, 2 trials, low-quality evidence). This is the most extensive systematic assessment of effects of omega-6 fats on cardiovascular health, mortality, lipids and adiposity to date, using previously unpublished data. We found no evidence that increasing omega-6 fats reduces cardiovascular outcomes other than MI, where 53 people may need to increase omega-6 fat intake to prevent 1 person from experiencing MI. Although benefits of omega-6 fats remain to be proven, increasing omega-6 fats may be of benefit in people at high risk of MI. Increased omega-6 fats reduce serum total cholesterol but not other blood fat fractions or adiposity.

Plain-language summary: Evidence in this review is current to May 2017. We found 19 studies recruiting 6461 adults. These studies assessed the effects of higher compared to lower omega-6 fat intake on heart and circulatory diseases as well as deaths. We found that three trials were highly trustworthy (with good designs that produce reliable evidence). Studies took place in North America, Asia, Europe and Australia, and eight were funded only by national or charitable agencies. Participants increased their omega-6 fats or maintained their usual fats for at least one year and up to eight years. We found that increasing omega-6 fats may make little or no difference to deaths or cardiovascular events but may reduce risk of heart attacks (low-quality evidence). Evidence was weakened by study design problems, small numbers of events, low numbers of participants from developing countries, and few women. Evidence suggests that increasing omega-6 fats reduces blood cholesterol (high-quality evidence), probably has little or no effect on body weight adjusted for height (all moderate-quality evidence), and may make little or no difference to triglycerides, high-density lipoprotein (HDL, the 'good' cholesterol) or low-density lipoprotein (LDL, the 'bad' cholesterol, low-quality evidence).