Abdelhamid Asmaa S, Brown Tracey J, Brainard Julii S, Biswas Priti, Thorpe Gabrielle C, Moore Helen J, Deane Katherine Ho, Summerbell Carolyn D, Worthington Helen V, Song Fujian, Hooper Lee
University of East Anglia, Norwich Medical School, Norwich Research Park, Norwich, Norfolk, UK, NR4 7TJ.
University of East Anglia, MED/HSC, Norwich Research Park, Norwich, UK, NR4 7TJ.
Cochrane Database Syst Rev. 2020 Feb 29;3(3):CD003177. doi: 10.1002/14651858.CD003177.pub5.
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.
To assess the effects of increased intake of fish- and plant-based omega-3 fats for all-cause mortality, cardiovascular events, adiposity and lipids.
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.
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.
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.
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.
来自油性鱼类的ω-3多不饱和脂肪酸（长链ω-3（LCn3）），包括二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），以及来自植物的α-亚麻酸（ALA）可能有益于心血管健康。指南建议增加富含ω-3的食物摄入量，有时也建议进行补充，但近期试验尚未证实这一点。
评估增加鱼类和植物来源的ω-3脂肪摄入量对全因死亡率、心血管事件、肥胖和血脂的影响。
我们检索了截至2019年2月的Cochrane系统评价数据库、MEDLINE和Embase，以及截至2019年8月的ClinicalTrials.gov和世界卫生组织国际临床试验注册平台，无语言限制。我们手工检索了系统评价的参考文献和书目，并联系了试验作者。
我们纳入了至少持续12个月的随机对照试验（RCT），这些试验比较了补充或建议增加LCn3或ALA摄入量，或两者同时增加，与常规或较低摄入量的情况。
两位综述作者独立评估试验是否纳入、提取数据并评估有效性。我们对ALA和LCn3干预分别进行了随机效应荟萃分析，并通过荟萃回归评估剂量反应关系。
在本次综述更新中，我们纳入了86项RCT（162,796名参与者），发现其中28项的偏倚汇总风险较低。试验持续时间为12至88个月，纳入了心血管风险各异的成年人，主要来自高收入国家。大多数试验评估了用胶囊补充LCn3的情况，但也有一些试验使用富含LCn3或ALA的食物或强化食物，或饮食建议，与安慰剂或常规饮食进行比较。LCn3的剂量范围为每天0.5克至超过5克（19项RCT每天给予至少3克LCn3）。荟萃分析和敏感性分析表明，增加LCn3对全因死亡率几乎没有或没有影响（风险比（RR）0.97，95%置信区间（CI）0.93至1.01；143,693名参与者；45项RCT中有11,297例死亡；高确定性证据）、心血管死亡率（RR 0.92，95%CI 0.86至0.99；117,837名参与者；29项RCT中有5658例死亡；中等确定性证据）、心血管事件（RR 0.96，95%CI 0.92至1.01；140,482名参与者；43项RCT中有17,619人发生事件；高确定性证据）、中风（RR 1.02，95%CI 0.94至1.12；138,888名参与者；31项RCT中有2,850例中风；中等确定性证据）或心律失常（RR 0.99，95%CI 0.92至1.06；77,990名参与者；30项RCT中有4,586人发生心律失常；低确定性证据）。增加LCn3可能会略微降低冠心病死亡率（额外有益结果的需治疗人数（NNTB）334，RR 0.90，95%CI 0.81至1.00；127,378名参与者；24项RCT中有3,598例冠心病死亡，低确定性证据）和冠心病事件（NNTB 167，RR 0.91，95%CI 0.85至0.97；134,116名参与者；32项RCT中有8,791人发生冠心病事件，低确定性证据）。总体而言，在预先计划的亚组分析或荟萃回归中，效应在试验持续时间或LCn3剂量方面没有差异。几乎没有证据表明吃鱼有效果。增加ALA摄入量可能对全因死亡率几乎没有或没有影响（RR 1.01，95%CI 0.84至1.20；19,327名参与者；5项RCT中有459例死亡，中等确定性证据）、心血管死亡率（RR 0.96，95%CI 0.74至1.25；18,619名参与者；4项RCT中有219例心血管死亡；中等确定性证据）、冠心病死亡率（RR 0.95，95%CI 0.72至1.26；18,353名参与者；3项RCT中有193例冠心病死亡；中等确定性证据）和冠心病事件（RR 1.00，95%CI 0.82至1.22；19,061名参与者；4项RCT中有397例冠心病事件；低确定性证据）。然而，增加ALA可能会略微降低心血管疾病事件的风险（NNTB 500，RR 0.95，95%CI 0.83至1.07；但在偏倚汇总风险较低的RCT中RR为0.91，95%CI 0.79至1.04；19,327名参与者；5项RCT中有884例心血管疾病事件；低确定性证据），并且可能会略微降低心律失常的风险（NNTB 91，RR 0.73，95%CI 0.55至0.97；
