PMID- 32114706 OWN - NLM STAT- MEDLINE DCOM- 20200731 LR - 20230204 IS - 1469-493X (Electronic) IS - 1361-6137 (Linking) VI - 3 IP - 3 DP - 2020 Feb 29 TI - Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. PG - CD003177 LID - 10.1002/14651858.CD003177.pub5 [doi] LID - CD003177 AB - BACKGROUND: Omega-3 polyunsaturated fatty acids from oily fish (long-chain omega-3 (LCn3)), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), as well as from plants (alpha-linolenic acid (ALA)) may benefit cardiovascular health. Guidelines recommend increasing omega-3-rich foods, and sometimes supplementation, but recent trials have not confirmed this. OBJECTIVES: To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase to February 2019, plus ClinicalTrials.gov and World Health Organization International Clinical Trials Registry to August 2019, with no language restrictions. We handsearched systematic review references and bibliographies and contacted trial authors. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that lasted at least 12 months and compared supplementation or advice to increase LCn3 or ALA intake, or both, versus usual or lower intake. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and assessed validity. We performed separate random-effects meta-analysis for ALA and LCn3 interventions, and assessed dose-response relationships through meta-regression. MAIN RESULTS: We included 86 RCTs (162,796 participants) in this review update and found that 28 were at low summary risk of bias. Trials were of 12 to 88 months' duration and included adults at varying cardiovascular risk, mainly in high-income countries. Most trials assessed LCn3 supplementation with capsules, but some used LCn3- or ALA-rich or enriched foods or dietary advice compared to placebo or usual diet. LCn3 doses ranged from 0.5 g a day to more than 5 g a day (19 RCTs gave at least 3 g LCn3 daily). Meta-analysis and sensitivity analyses suggested little or no effect of increasing LCn3 on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.93 to 1.01; 143,693 participants; 11,297 deaths in 45 RCTs; high-certainty evidence), cardiovascular mortality (RR 0.92, 95% CI 0.86 to 0.99; 117,837 participants; 5658 deaths in 29 RCTs; moderate-certainty evidence), cardiovascular events (RR 0.96, 95% CI 0.92 to 1.01; 140,482 participants; 17,619 people experienced events in 43 RCTs; high-certainty evidence), stroke (RR 1.02, 95% CI 0.94 to 1.12; 138,888 participants; 2850 strokes in 31 RCTs; moderate-certainty evidence) or arrhythmia (RR 0.99, 95% CI 0.92 to 1.06; 77,990 participants; 4586 people experienced arrhythmia in 30 RCTs; low-certainty evidence). Increasing LCn3 may slightly reduce coronary heart disease mortality (number needed to treat for an additional beneficial outcome (NNTB) 334, RR 0.90, 95% CI 0.81 to 1.00; 127,378 participants; 3598 coronary heart disease deaths in 24 RCTs, low-certainty evidence) and coronary heart disease events (NNTB 167, RR 0.91, 95% CI 0.85 to 0.97; 134,116 participants; 8791 people experienced coronary heart disease events in 32 RCTs, low-certainty evidence). Overall, effects did not differ by trial duration or LCn3 dose in pre-planned subgrouping or meta-regression. There is little evidence of effects of eating fish. Increasing ALA intake probably makes little or no difference to all-cause mortality (RR 1.01, 95% CI 0.84 to 1.20; 19,327 participants; 459 deaths in 5 RCTs, moderate-certainty evidence),cardiovascular mortality (RR 0.96, 95% CI 0.74 to 1.25; 18,619 participants; 219 cardiovascular deaths in 4 RCTs; moderate-certainty evidence), coronary heart disease mortality (RR 0.95, 95% CI 0.72 to 1.26; 18,353 participants; 193 coronary heart disease deaths in 3 RCTs; moderate-certainty evidence) and coronary heart disease events (RR 1.00, 95% CI 0.82 to 1.22; 19,061 participants; 397 coronary heart disease events in 4 RCTs; low-certainty evidence). However, increased ALA may slightly reduce risk of cardiovascular disease events (NNTB 500, RR 0.95, 95% CI 0.83 to 1.07; but RR 0.91, 95% CI 0.79 to 1.04 in RCTs at low summary risk of bias; 19,327 participants; 884 cardiovascular disease events in 5 RCTs; low-certainty evidence), and probably slightly reduces risk of arrhythmia (NNTB 91, RR 0.73, 95% CI 0.55 to 0.97; 4912 participants; 173 events in 2 RCTs; moderate-certainty evidence). Effects on stroke are unclear. Increasing LCn3 and ALA had little or no effect on serious adverse events, adiposity, lipids and blood pressure, except increasing LCn3 reduced triglycerides by 15% in a dose-dependent way (high-certainty evidence). AUTHORS' CONCLUSIONS: This is the most extensive systematic assessment of effects of omega-3 fats on cardiovascular health to date. Moderate- and low-certainty evidence suggests that increasing LCn3 slightly reduces risk of coronary heart disease mortality and events, and reduces serum triglycerides (evidence mainly from supplement trials). Increasing ALA slightly reduces risk of cardiovascular events and arrhythmia. CI - Copyright (c) 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. FAU - Abdelhamid, Asmaa S AU - Abdelhamid AS AD - University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ. FAU - Brown, Tracey J AU - Brown TJ AD - University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ. FAU - Brainard, Julii S AU - Brainard JS AD - University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ. FAU - Biswas, Priti AU - Biswas P AD - University of East Anglia, MED/HSC, Norwich Research Park, Norwich, UK, NR4 7TJ. FAU - Thorpe, Gabrielle C AU - Thorpe GC AD - University of East Anglia, School of Health Sciences, Earlham Road, Norwich, UK, NR4 7TJ. FAU - Moore, Helen J AU - Moore HJ AD - Teesside University, School of Social Sciences, Humanities and Law, Middlesborough, UK, TS1 3BA. FAU - Deane, Katherine Ho AU - Deane KH AD - University of East Anglia, School of Health Sciences, Earlham Road, Norwich, UK, NR4 7TJ. FAU - Summerbell, Carolyn D AU - Summerbell CD AD - Durham University, Department of Sport and Exercise Sciences, 42 Old Elvet, Durham, UK, DH13HN. FAU - Worthington, Helen V AU - Worthington HV AD - Division of Dentistry, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Cochrane Oral Health, Coupland Building 3, Oxford Road, Manchester, UK, M13 9PL. FAU - Song, Fujian AU - Song F AD - University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ. FAU - Hooper, Lee AU - Hooper L AD - University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ. LA - eng GR - MR/K02325X/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200229 PL - England TA - Cochrane Database Syst Rev JT - The Cochrane database of systematic reviews JID - 100909747 RN - 0 (Fatty Acids, Omega-3) RN - 0RBV727H71 (alpha-Linolenic Acid) RN - 25167-62-8 (Docosahexaenoic Acids) RN - AAN7QOV9EA (Eicosapentaenoic Acid) SB - IM UOF - Cochrane Database Syst Rev. 2018 Nov 30;11:CD003177. PMID: 30521670 MH - Adiposity MH - Adult MH - Arrhythmias, Cardiac/epidemiology MH - Cardiovascular Diseases/diet therapy/mortality/*prevention & control MH - Cause of Death MH - Coronary Disease/mortality MH - *Dietary Supplements MH - Docosahexaenoic Acids/therapeutic use MH - Eicosapentaenoic Acid/therapeutic use MH - Fatty Acids, Omega-3/adverse effects/*therapeutic use MH - Hemorrhage/epidemiology MH - Humans MH - *Primary Prevention MH - Pulmonary Embolism/epidemiology MH - Randomized Controlled Trials as Topic MH - Regression Analysis MH - *Secondary Prevention MH - Stroke/epidemiology MH - Treatment Outcome MH - alpha-Linolenic Acid/therapeutic use PMC - PMC7049091 COIS- ASA: none known
 TJB: none known
 JSB: none known
 PB: none known
 GCT: none known
 HJM: none known
 KHOD: none known
 FKA: none known
 CDS: none known
 HVW: none known
 FS: none known
 LH: none known EDAT- 2020/03/03 06:00 MHDA- 2020/08/01 06:00 PMCR- 2021/02/28 CRDT- 2020/03/02 06:00 PHST- 2020/03/02 06:00 [entrez] PHST- 2020/03/03 06:00 [pubmed] PHST- 2020/08/01 06:00 [medline] PHST- 2021/02/28 00:00 [pmc-release] AID - CD003177.pub5 [pii] AID - 10.1002/14651858.CD003177.pub5 [doi] PST - epublish SO - Cochrane Database Syst Rev. 2020 Feb 29;3(3):CD003177. doi: 10.1002/14651858.CD003177.pub5.