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.com 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 with lower omega-6 fat intakes in adults with or without CVD, assessing effects over ≥12 months. We included full-text, abstracts, trials registry entries and unpublished studies.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 for further data. Meta-analyses used random effects analysis, sensitivity analyses included fixed effects and limiting to low summary risk of bias. We assessed GRADE quality of evidence for Summary of Findings tables.
Main results: We included 19 RCTs randomising 6461 participants for 1 to 8 years duration. Seven trials assessed effects of supplemental GLA, twelve of LA, usually displacing dietary saturated or monounsaturated fats. Three RCTs were at low summary risk of bias.
Primary outcomes: Increasing omega-6 fats may make little or no difference to all-cause mortality (risk ratio [RR] 1.00, 95% 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), low quality evidence, downgraded for risk of bias and indirectness. 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 (MACCEs, 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 all were very low quality evidence (each downgraded for risk of bias, indirectness, and another factor). We found no evidence of dose 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 WHO outcomes: Increasing omega-6 fats may reduce myocardial infarction (MI, RR 0.88, 95% CI 0.76 to 1.02, 609 events, 4606 participants, 7 trials, low quality evidence, downgraded for risk of bias and indirectness). High quality evidence suggests increasing omega-6 fats reduces total serum cholesterol a little long-term (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 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 adiposity (body mass index MD -0.20 kg/m2, 95% CI -0.56 to 0.16, 371 participants, 1 trial, moderate quality evidence plus body weight MD -3.12 kg, 95% CI -12.60 to 6.36, 358 participants, 2 trials with two further RCTs suggesting greater body weight with higher omega-6, very low quality evidence), and may make little or no difference to LDL (MD -0.04 mmol/L, 95% CI -0.21 to 0.14, 244 participants, 2 trials, low quality evidence).
Authors' conclusions: There is no evidence for increasing omega-6 fats to reduce cardiovascular outcomes other than MI, where 53 people would need to increase omega-6 fat intake to prevent one person experiencing a MI. Although benefits of omega-6 fats remain to be categorically proven, increasing omega-6 fats may be of benefit in people with high risk of MI.