Polyunsaturated fatty acids for the primary and secondary prevention of cardiovascular disease

Abstract

Evidence on the health effects of total polyunsaturated fatty acids (PUFA) is equivocal. Fish oils are rich in omega‐3 PUFA and plant oils in omega‐6 PUFA. Evidence suggests that increasing PUFA‐rich foods, supplements or supplemented foods can reduce serum cholesterol, but may increase body weight, so overall cardiovascular effects are unclear. To assess effects of increasing total PUFA intake on cardiovascular disease and all‐cause mortality, lipids and adiposity in adults. We searched CENTRAL, MEDLINE and Embase to April 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 with lower PUFA intakes in adults with or without cardiovascular disease that assessed effects over 12 months or longer. We included full texts, abstracts, trials registry entries and unpublished data. Outcomes were all‐cause mortality, cardiovascular disease mortality and events, risk factors (blood lipids, adiposity, blood pressure), and adverse events. We excluded trials where we could not separate effects of PUFA intake from other dietary, lifestyle or medication interventions. Two review authors independently screened titles and abstracts, assessed trials for inclusion, extracted data, and assessed risk of bias. We wrote to authors of included trials 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. We included 49 RCTs randomising 24,272 participants, with duration of one to eight years. Eleven included trials were at low summary risk of bias, 33 recruited participants without cardiovascular disease. Baseline PUFA intake was unclear in most trials, but 3.9% to 8% of total energy intake where reported. Most trials gave supplemental capsules, but eight gave dietary advice, eight gave supplemental foods such as nuts or margarine, and three used a combination of methods to increase PUFA. Increasing PUFA intake probably has little or no effect on all‐cause mortality (risk 7.8% vs 7.6%, risk ratio (RR) 0.98, 95% confidence interval (CI) 0.89 to 1.07, 19,290 participants in 24 trials), but probably slightly reduces risk of coronary heart disease events from 14.2% to 12.3% (RR 0.87, 95% CI 0.72 to 1.06, 15 trials, 10,076 participants) and cardiovascular disease events from 14.6% to 13.0% (RR 0.89, 95% CI 0.79 to 1.01, 17,799 participants in 21 trials), all moderate‐quality evidence. Increasing PUFA may slightly reduce risk of coronary heart disease death (6.6% to 6.1%, RR 0.91, 95% CI 0.78 to 1.06, 9 trials, 8810 participants) and stroke (1.2% to 1.1%, RR 0.91, 95% CI 0.58 to 1.44, 11 trials, 14,742 participants, though confidence intervals include important harms), but has little or no effect on cardiovascular mortality (RR 1.02, 95% CI 0.82 to 1.26, 16 trials, 15,107 participants) all low‐quality evidence. Effects of increasing PUFA on major adverse cardiac and cerebrovascular events and atrial fibrillation are unclear as evidence is of very low quality. Increasing PUFA intake slightly reduces total cholesterol (mean difference (MD) ‐0.12 mmol/L, 95% CI ‐0.23 to ‐0.02, 26 trials, 8072 participants) and probably slightly decreases triglycerides (MD ‐0.12 mmol/L, 95% CI ‐0.20 to ‐0.04, 20 trials, 3905 participants), but has little or no effect on high‐density lipoprotein ( HDL) (MD ‐0.01 mmol/L, 95% CI ‐0.02 to 0.01, 18 trials, 4674 participants) or low‐density lipoprotein ( LDL) (MD ‐0.01 mmol/L, 95% CI ‐0.09 to 0.06, 15 trials, 3362 participants). Increasing PUFA probably causes slight weight gain (MD 0.76 kg, 95% CI 0.34 to 1.19, 12 trials, 7100 participants). Effects of increasing PUFA on serious adverse events such as pulmonary embolism and bleeding are unclear as the evidence is of very low quality. This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all‐cause or cardiovascular disease mortality. The mechanism may be via lipid reduction, but increasing PUFA probably slightly increases weight. Review question We reviewed randomised trials (participants have an equal chance to be assigned to either treatment) examining effects of increasing intake of polyunsaturated fatty acids (PUFA) on deaths and diseases of the heart and circulation (cardiovascular diseases), including heart attacks and stroke. Background We eat PUFA in our usual food, but quantities of PUFA eaten vary. There is some evidence that increasing the amount of PUFA we eat can reduce our blood cholesterol and make us less likely to develop cardiovascular disease, particularly if PUFAs are eaten instead of saturated fats (fats from animal sources such as meat and cheese). But eating more PUFA may increase our body weight, and omega‐6 fats (one component of PUFA) may worsen cardiovascular risk by increasing inflammation. Evidence on the benefits or harms of increasing PUFA intake on diseases of the heart and circulation, or on other health outcomes, is inconclusive. Trial characteristics Evidence in this Cochrane Review is current to 27 April 2017. We included 49 trials randomising 24,272 participants, for one to eight years. These trials assessed effects of eating more, compared to less PUFA, on diseases of the heart and circulation, and deaths. Twelve trials were very trustworthy (had low risk of bias overall). Participants were men and women, some with existing illnesses and some not. Trials took place in North America, Asia, Europe and Australia, and sixteen were funded only by national or charitable agencies. Key results Increasing PUFA probably makes little or no difference (neither benefit nor harm) to our risk of death (moderate‐quality evidence), and may make little or no difference to our risk of dying from cardiovascular disease (low‐quality evidence). However, increasing PUFA probably slightly reduces our risk of heart disease events and of combined heart and stroke events (moderate‐quality evidence). Fifty three people would need to eat more PUFA to prevent one person experiencing a heart disease event, and 63 people to prevent one person experiencing a heart or stroke event. Increasing PUFA may very slightly reduce risk of death due to heart disease, as well as stroke, but harm is possible (low‐quality evidence). PUFA probably slightly reduces fats circulating in the blood (cholesterol, high‐quality evidence and triglycerides, moderate‐quality evidence). Increasing PUFA probably slightly increases body weight (moderate‐quality evidence). The evidence mainly comes from trials of men living in high‐income countries.