Review question
We reviewed randomised trials (participants had an equal chance to be assigned to either treatment) examining effects of higher omega-6 fats compared to lower omega-6 fats on deaths and heart and circulatory diseases (cardiovascular diseases (CVD), which include heart attacks and strokes).
Background
Omega-6 fats are essential, we must obtain some from food. They are important for regulating energy production (part of metabolism), bone, skin and hair health. Many foods contain omega-6 fats, particularly vegetable oils and nuts. Omega-6 fats include linoleic acid (LA), gamma-linolenic acid (GLA), dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA).
Some evidence suggests that a higher intake of omega-6 fats, along with a lower intake of saturated fat (from animal sources such as meat and cheese) can reduce coronary heart disease. In contrast, there is concern that high levels of omega-6 fats may worsen cardiovascular risk by increasing inflammation. Overall, there is no conclusive evidence on the benefits or harms of omega-6 fat intake on heart and circulatory diseases or on other health outcomes.
Study characteristics
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.
Key results
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).
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.
Omega-6 fats are polyunsaturated fats vital for many physiological functions, but their effect on cardiovascular disease (CVD) risk is debated.
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.
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.
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.
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.
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).