Omega-6 fats for the primary and secondary prevention of cardiovascular disease.

Background: Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated.

Objectives: To assess effects of increasing omega-6 fats (linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA)) on CVD and all-cause mortality.

Search Methods: We searched CENTRAL, MEDLINE and Embase to May 2017 and clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform to September 2016, without language restrictions. We checked trials included in relevant systematic reviews.

Selection Criteria: We included randomised controlled trials (RCTs) comparing higher versus lower omega-6 fat intake in adults with or without CVD, assessing effects over at least 12 months. We included full texts, abstracts, trials registry entries and unpublished studies. Outcomes were all-cause mortality, CVD mortality, CVD events, risk factors (blood lipids, adiposity, blood pressure), and potential adverse events. We excluded trials where we could not separate omega-6 fat effects from those of other dietary, lifestyle or medication interventions.

Data Collection And Analysis: Two authors independently screened titles/abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias of included trials. We wrote to authors of included studies. Meta-analyses used random-effects analysis, while sensitivity analyses used fixed-effects and limited analyses to trials at low summary risk of bias. We assessed GRADE quality of evidence for 'Summary of findings' tables.

Main Results: 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, I = 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/m, 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).

Authors' Conclusions: 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.