Objective: To systematically review prospective cohort studies and quantify associations between polyunsaturated fatty acids (PUFA) and all-cause mortality, cardiovascular disease (CVD), breast cancer, mental health, inflammatory bowel disease and type 2 diabetes.
Design: Systematic review and meta-analysis of prospective cohort studies.
Data Sources: MEDLINE (from 1946), EMBASE (from 1974), Cochrane Central Registry of Controlled Trials (from 1996), Evidence Based Medicine Reviews (from 1996) and CINAHL (from 1983) were searched through 19 December 2019. Reference lists of retrieved articles and previous systematic and narrative reviews were hand searched.
Eligibility criteria for selecting studies: Prospective cohort studies reporting associations between PUFA and all-cause mortality, CVD, breast cancer, mental health or type 2 diabetes were eligible.
Data extraction and synthesis: Two reviewers independently abstracted design features, participant characteristics, exposures and outcomes, and assessed risk of bias. Multivariable risk ratios were pooled using inverse-variance random-effects models. Heterogeneity was assessed (Q statistic) and quantified (I2). Potential publication bias was assessed (funnel plots) and subgroup analyses were undertaken (meta-regression).
Results: A total of 4015 potentially eligible articles were identified; after full-text review, 170 primary reports of associations between PUFA and the health outcomes in prospective cohort studies (published between 1981 and 2020) provided 719 comparisons. In prospective cohort studies (considered the highest quality observational evidence available), higher intake of total and various subtypes of PUFA, compared with lower intake varied in terms of associations with chronic diseases. Higher intakes of total PUFA were associated with a 14% reduced risk of all-cause mortality (16 studies with 960 538 participants), 9% reduced risk of fatal CVD (13 studies with 907 721 participants) and 27% reduced risk of sudden cardiac death (1 study with 91 981 participants). Total omega-3 fatty acids were associated with a 6% reduced risk of fatal CVD (10 studies with 872 029 participants), 17% reduced risk of fatal coronary heart disease (CHD) (4 studies with 238 990 participants), 35% reduced risk of sudden cardiac death (2 studies with 149 953 participants), 57% reduced risk of myocardial infarction (1 study with 41 578 participants), 15% reduced risk of fatal stroke (2 studies with 82 122 participants), and 21% reduced risk of cognitive decline in older age (1 study with 4809 participants). Higher intakes of long-chain omega-3 fatty acids were associated with a 9% reduced risk of all-cause mortality (15 studies with 1 033 235 participants), 12% reduced risk of fatal CVD (18 studies with 1 070 906 participants), 20% reduced risk of fatal CHD (16 studies with 461 060 participants), 59% reduced risk of fatal myocardial infarction (2 studies with 39 586 participants), 45% reduced risk of haemorrhagic stroke (4 studies with 94 687 participants) and 28% reduced risk of ulcerative colitis (1 study with 170 805 participants). Higher intakes of total n-6 fatty acids were associated with a 9% reduced all-cause mortality (9 studies with 768 475 participants) but a 31% increased risk of postmenopausal breast cancer (6 studies with 174 816 participants). Higher intakes of arachidonic acid were associated with a 5% increased risk of breast cancer (3 studies with 180 342 participants). Higher intakes of linoleic acid were associated with a 16% reduced risk of all-cause mortality (9 studies with 706 400 participants), 17% reduced risk of fatal CVD (7 studies with 692 243 participants), 21% reduced risk of fatal CHD (13 studies with 306 050 participants), 32% reduced risk of sudden cardiac death (1 study with 91 181 participants) and 14% reduced risk of total CHD (14 studies with 267 201 participants), but a 26% increased risk of depression (3 studies with 57 538 participants). Higher intakes of alpha-linolenic acid were associated with a 7% reduced all-cause mortality (10 studies with 714 634 participants), 9% reduced risk of fatal CVD (11 studies with 800 724 participants), 18% reduced risk of fatal CHD (9 studies with 252 010 participants), 46% reduced risk of sudden cardiac death (2 studies with 99 183 participants) and 15% reduced risk of fatal stroke (3 studies with 103 532 participants). A higher polyunsaturated:saturated fat ratio was associated with an 18% increased risk of fatal CVD (3 studies with 65 598 participants) and 86% increased risk of postmenopausal breast cancer (1 study with 910 participants). A high omega-6:omega-3 ratio was associated with a 25% increased risk of cognitive decline and 45% increased risk of ulcerative colitis (1 study with 170 805 participants). A high omega-3:omega-6 ratio was associated with a 26% reduced risk of depression (3 studies with 57 538 participants), The confidence in the estimates for the association between PUFA and all outcomes using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach ranged from very low to moderate.
Conclusions: On balance, higher intakes of PUFA are associated with reduced risks of all-cause and cardiovascular mortality, but the quality of the evidence is mostly very low. The benefits of n-3 fatty acids appear to be specific for CVDs, but few observational studies have directly observed or otherwise modelled the effects of replacing saturated or trans-unsaturated fats with PUFA on health outcomes. The interaction between different types of PUFA requires further research.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)