临床概述

采用

对于降低冠状动脉疾病的风险和减少血清甘油三酸酯的临床益处最大。已经证实，补充至少3年的omega-3脂肪酸可以降低全因死亡率，心源性死亡和突然死亡的风险。美国食品药品监督管理局（FDA）已批准使用鱼油来降低成人极高的甘油三酸酯血症（至少500 mg / dL [5.65 mmol / L]），作为饮食的辅助手段。重症和外科手术患者使用肠胃外鱼油脂质乳剂的证据越来越多。在类风湿关节炎中起作用的证据仍然模棱两可，但很有希望。在食用鱼油与降低中风或维持炎症性肠病风险之间没有一致的关系。需要进一步研究的鱼油治疗用途的其他关注领域包括哮喘和过敏，痛经，精神健康以及促进产后生长发育。

加药

美国心脏协会（AHA）建议每周至少吃2顿脂肪鱼粉。临床试验表明，鱼油在冠心病中每天补充1 g / omega-3脂肪酸，当甘油三酸酯升高时，最小补充2 g / day的omega-3脂肪酸，最多4 g / day。鱼油1,000 mg约等于300至400 mg的omega-3脂肪酸（二十碳五烯酸[EPA] /二十二碳六烯酸[DHA]）。

禁忌症

禁忌活动性出血（例如消化性溃疡，颅内出血）患者。

怀孕/哺乳

潜在的汞摄入。吃汞含量低的鱼，避免食用高汞鱼，例如墨西哥湾的瓦鱼，旗鱼，鲭鱼和鲨鱼。

互动互动

鱼油的摄入可能会增强抗凝药物（包括华法林）的抗凝作用；虽然，病例报告有限。

不良反应

鱼油的EPA / DHA 2至5.4克/天的剂量已被广泛接受和耐受。在临床试验中报告了轻度的胃肠不适。

毒理学

研究显示很少或没有信息。

资源

Omega-3脂肪酸存在于多种动植物中，其中海洋来源的脂肪酸含量最高。牛肉中含有微量的EPA和DHA。与以谷物喂养的牛肉相比，以草喂养的牛肉可增加多不饱和脂肪酸总量的25％。此外，在草饲牛中发现的欧米伽3与欧米伽6脂肪酸（包括EPA和DHA）的比例也高于谷物喂养的同类动物。199EPA和DHA可以从必需的欧米茄中合成，尽管效率很低。 -3脂肪酸α-亚麻酸（ALA）。 ALA不能由人合成，必须从饮食中获得。在亚麻籽，低芥酸菜子，大豆，核桃和小麦胚芽油，坚果和种子以及蔬菜中发现ALA。此外，DHA可以从EPA.1,2,3合成

鱼油主要由omega-3脂肪酸EPA和DHA组成； “鱼油”是经常与EPA和DHA互换使用的术语。含有最高含量的omega-3脂肪酸的海洋来源是脂肪鱼（例如鲭鱼，大比目鱼，鲑鱼，蓝鱼，鱼，黑貂鱼，鲱鱼，an鱼，鲱鱼，湖鳟，银鳕，沙丁鱼），其含量为1 g或更多每100克（3.5盎司）鱼中的欧米茄脂肪酸含量金枪鱼，海豹和贝类（例如牡蛎）是其他海洋来源。1、2、3、4、5

由于海洋鱼类资源有限，并且由于目前许多鱼类资源受到污染物（例如甲基汞，有机氯农药）的污染，因此建议将负责EPA和DHA生产的藻类基因克隆到植物中。6，7转基因油植物将富含EPA和DHA，尽管已经取得了一些成功，但尚未克服高等植物在生物合成途径方面的挑战。8，9

历史

鱼油的大多数用途都是基于EPA和DHA的有益作用，特别是与心血管，炎症，神经和激素支持有关的有益作用。人们对可能的健康益处产生了兴趣，因为有观察发现，饮食中鱼类摄入量较高的人群（例如爱斯基摩人和因纽特人人群）的动脉粥样硬化和血栓形成紊乱以及炎症性疾病的发生率较低。10，11 1789年，一家出版物描述了鳕鱼的有益作用风湿病中使用肝油，据报道在1824年使用相同的油可有效预防of病。12历史上，在以低脂或低脂饮食喂养的婴儿以及长期（例如2至3周）的患者中发现不足）缺乏多不饱和脂肪酸的肠胃外营养配方2，3

化学

EPA和DHA是omega-3长链（20碳或更多）PUFA。 EPA由具有5个双键（20：5）的20碳链组成，而DHA是具有6个双键（20：6）的22碳链。如omega-3命名法所示，第一个双键位于链的甲基（omega）末端的第三个碳上。2，3 C-13核磁共振模式识别已用于分析鱼是从商业鱼油产品中提取的鱼。13已探索鱼油在牛奶中的均质化。14将鱼油掺入其他食品的挑战包括EPA和DHA易于氧化，以及其难闻的味道和气味。因此，充油胶囊是当前优选的补充产品。

用途和药理学

Omega-3脂肪酸代谢成类二十烷酸，具有重要的生理特性，包括前列腺素，前列环素，血栓烷和白三烯。类花生酸是血压，血液凝结，分娩和胃分泌物以及免疫和炎性反应的有效调节剂。脂肪酸链中双键的实际位置会影响其代谢，因此，omega-3衍生的类花生酸的结构和功能与omega-6脂肪酸（例如花生四烯酸）衍生的类花生酸不同。例如，omega-3衍生的类花生酸往往会减少血液凝结和炎症反应。这与花生四烯酸（ω-6）衍生的类二十烷酸相反，后者会增加凝血和炎症反应。2，3，15

消炎（药

在一项随机，双盲，安慰剂对照试验中，261名健康成年人接受了鱼油补充剂（EPA + DHA 1,400 mg）或安慰剂治疗18周，以确定其对慢性全身性炎症的生物标志物的影响。此剂量的鱼油对血清c反应蛋白或IL-6浓度没有影响，也没有基于性别，体重指数，基线IL-6或补​​充后红细胞EPA + DHA的异质性证据。与干预有关的副作用包括鱼腥味或回味，大便稀疏，腹胀或气胀。没有报告严重的不良事件。175

根据2016年更新的Cochrane对成人姑息治疗中瘙痒的药理干预措施的系统评价，Omega-3脂肪酸可能有效地治疗了尿毒症患者的瘙痒。自从之前的2013年审查以来，又确定了另外10项研究，共627名参与者，其中一项研究了omega-3脂肪酸。在这项双盲，随机安慰剂对照的交叉试验中，该试验招募了22名患有终末期肾脏疾病的患者，每天3 g的omega-3s（1 g omega-3s分别为EPA 180毫克和DHA 120毫克，每天3次）在超过20天后口服，并经过14天的冲洗，然后越过。鱼油瘙痒症从基线水平下降了65％，而安慰剂则为15％。尽管差异具有统计学意义，但样本量小且研究方法学质量低189。

心律失常

动物资料

动物研究表明，鱼油具有促心律和抗心律不齐的特性。24，25在实验性心律不齐中，鱼油可预防与缺血有关的心律不齐，但与再灌注损伤无关。24

临床资料

评论已经检查了鱼油在治疗心律不齐中的实用性。保护机制尚不完全清楚，某些类别的患者可能无法受益。26，27，28截至2008年，所有有关室性心律不齐的研究均进行荟萃分析，发现鱼油仅对鱼油有保护作用。首次心室颤动的时间。纳入试验中使用的剂量范围从鱼油900到2,600mg。29，30进一步的荟萃分析发现，心律不齐或各种原因导致的死亡的主要结果无明显降低。对于因心脏原因导致的死亡的次要结果，发现减少了。312003年Diet and Angina随机试验（DART-2）的结果发现，心绞痛患者和植入心脏复律除颤器的患者死亡增加，没有已经发现了对排出风险的总体影响，这可能是因为鱼油可能表现出心律失常的特性。25，32

已经发表了两项评估鱼油对心房颤动（AF）影响的荟萃分析。其中一项来自围手术期鱼油管理研究的有关术后房颤发生率的数据。 8项研究（n = 2687）的证据总和是，鱼油并没有显着降低术后房颤的发生率，住院时间或重症监护病房（ICU）天数，术后死亡率或大出血。进一步的分析发现，使用DHA剂量大于每天1 g的鱼油的研究确实显着降低了术后房颤的发生率和住院时间。147其他荟萃分析着眼于房颤复发的发生率（8项研究， n = 1990）在经历心脏复律或窦性心律有症状持续性/阵发性房颤的成年患者中。来自所有8项研究的数据显示，与安慰剂相比，鱼油AF复发的发生率没有显着降低。随后的分析表明，将来自至少3个在复律前4周开始使用鱼油的研究的数据汇总起来，与对照相比，鱼油的AF复发率明显降低。并合并了至少5个在复律前至少4周未开始使用鱼油的研究的数据，发现鱼油显着增加了房颤复发的发生率。148

哮喘/过敏

临床资料

迄今为止，鱼油在哮喘中的临床益处尚有争议。10、16种Omega-3脂肪酸对嗜酸性粒细胞和肥大细胞没有影响，这可能解释了这种炎症性疾病相对缺乏疗效。10其他鱼油中的成分未知。鱼油对运动性哮喘的作用的证据有限。17有人建议采用含有EPA加γ-亚麻酸的肠内营养配方作为急性呼吸窘迫综合征的临床治疗辅助疗法。18鱼的使用还评估了妊娠和母乳喂养期间补充油以减少婴儿食物过敏的发生率；但是，在怀孕期间补充孕妇鱼油并不能降低患有遗传风险的儿童从出生到3岁的过敏性疾病的风险。 19，159与这些结果相反，由每天接受2.4克n3-LCPUFA的妇女所生的儿童（从出生到3至5岁）患持续性喘息或哮喘的风险降低了三分之一。在这项针对736名孕妇的随机，双盲，安慰剂对照试验中，从出生到5岁的647名儿童得到了随访。发现该有益效果在基线EPA和DHA血液水平为5％至5.5％，母亲在审判前饮食中摄取EPA和DHA的比例最低（<321 mg /天）的母亲中最为明显。谁在rs1535携带G等位基因脂肪酸去饱和酶基因变异（与EPA和DHA含量低相关）。186系统评价和荟萃分析（n = 99,093个人； 3,226例）发现儿童哮喘风险与患者负相关婴儿食用的鱼，母乳中母乳中的n3-LCPUFA水平。然而，在儿童哮喘风险与儿童食用母体鱼或补充鱼油之间没有发现显着关联。此外，在鱼类消费与成人哮喘风险之间没有发现显着关系158。

关于银屑病或特应性皮炎患者补充n-3脂肪酸的临床益处，较早的试验尚无定论。4，20，21，22，23 Cochrane评论指出，对日常生活，受影响的区域和瘙痒的影响有一些积极的结果。进行了一些研究，尽管质量较差；一项更大的试验显示，与安慰剂相比，无益处。145对银屑病替代疗法的系统评价发现，在轻至中度牛皮癣患者中使用鱼油的模棱两可的数据。不支持各种剂量和持续时间的有效性198。

英国国家哮喘管理临床指南（2012年）指出，在没有任何证据表明在怀孕期间使用鱼油补充剂有益处的情况下，不可能将其推荐为预防儿童哮喘的策略。此外，一些对照试验的结果表明，没有足够的证据推荐补充鱼油来治疗哮喘[134]。

癌症

临床资料

炎症与结肠癌之间的明显联系促进了EPA和DHA在癌症预防中的研究。 EPA减少了具有结直肠腺瘤病史的受试者的隐窝细胞增殖并增加了细胞凋亡。89有1篇综述[90]认为对脂质修饰的蛋白质运输的分子作用是一种机制，90而对T细胞功能和亚群的免疫调节作用则被91癌症中n-3 PUFA的其他分子靶点也得到了审查。92在多光谱化患者（N = 352）中进行的为期2年的随机对照试验发现，增加Omega-3脂肪酸（即增加Omega-3脂肪酸）的饮食建议鱼类食用，每天456毫克EPA：DHA鱼油补充，富含ALA的紫苏油和减少omega-6脂肪酸（即植物油，油炸食品）导致血浆，红血球和乙状结肠明显增加与对照组相比，实验组在12和24个月时结肠膜中的omega-3脂肪酸组成降低了omega-6s：omega-3s的比例。但是，在24个月时有或没有肿瘤的参与者的粗略数量没有显着差异。没有观察到不良事件。174

美国临床肿瘤学会预防和管理成年癌症幸存者化疗引起的周围神经病（CIPN）的临床实践指南（2014）没有建议使用Omega-3-脂肪酸预防CIPN无定论的证据（低质量的证据，无定论）.161

心血管疾病

临床资料

鱼油在降低心血管疾病风险中的潜在作用首先来自格陵兰岛因纽特人的观察。尽管摄入高达40％的卡路里的脂肪（大部分来自海洋），但与传统饮食相比，该人群的冠心病发病率较低。33

关于评价鱼油补充对冠心病影响的试验的系统评价和荟萃分析已经发表。已经证实，补充至少3年的omega-3脂肪酸可以降低全因死亡率，心源性死亡和突然死亡的风险。虽然，2013年对9项随机对照试验（n = 32,919）的荟萃分析显示，与安慰剂相比，室性心律不齐或猝死的风险在统计学上无统计学意义的降低。异质性中等。141异质性显着降低的亚分析显示，近期发生心肌缺血事件的患者有获益的强烈趋势。141冠心病（CHD）二级预防的证据大于一级预防的证据，主要是针对的通过3次大型试验； GISSI试验（意大利）和JELIS试验（日本）以及ALA的较早研究。这些荟萃分析的证据尚无定论可预防中风和非致命性心肌梗塞（MI）。28、30、34、35、36日剂量小于2 g EPA（范围从226至1,800 mg）且小于2 g DHA（0到1,700 mg范围），对10例具有先前CHD，中风和/或糖尿病病史的高危CHD高风险随机对照试验（N = 77,917；范围563至18,645）进行荟萃分析发现这些剂量与任何冠心病事件，主要血管事件或全因死亡率均无显着相关性。进入研究的平均年龄为64岁，治疗时间范围为1至6.2年（平均4.4岁）.195

GISSI-Prevenzione试验招募了11,324名冠心病（心梗后）患者，并评估了与维生素E相比omega-3脂肪酸的补充。发现死亡，非致命性MI和中风的综合终点主要终点指标降低了omega-3脂肪酸。34，37来自GISSI心力衰竭试验（n = 7,046）的数据可以计算出56名已有心脏的患者接受omega-3脂肪酸补充治疗3.9年，以避免1例死亡，或44例患者应接受相同时间的治疗，以避免因心脏原因1例死亡或住院。未发现预防中风的益处。对于冠心病的一级预防，GISSI心力衰竭试验发现对omega-3脂肪酸无显着影响。 JELIS试验招募了18,645名高胆固醇血症患者，发现发生重大冠心病（包括猝死和MI）的风险降低，并且发现了针对卒中风险的二级保护证据。30，34随机，双盲，对照一项针对对照组的研究（n = 12,505）使用橄榄油评估了1克/天的鱼油对没有心肌梗死但患有动脉粥样硬化疾病或多种心血管危险因素的患者的5年疗效。鱼油和橄榄油之间因心血管疾病死亡或因心血管原因而入院的情况无明显差异。149有些人在写给编辑的信中质疑选择橄榄油作为“安慰剂”，但首席调查员为他们的选择辩护，通过部分说明，每天1克橄榄油的剂量低于其他研究中发现的有益剂量150。

一项与年龄相关的眼疾研究的辅助心血管结果研究2评估了Omega-3脂肪酸（DHA 350毫克/天+ EPA 650毫克/天）相对于黄斑叶黄素（叶黄素10毫克/天+玉米黄质2毫克/天）的影响天数）与安慰剂2和安慰剂的组合对中位数4.8年的4,203例AREDS患者（中位年龄为74岁）的心血管结局的影响。只有高血压，心血管疾病（CVD）或高胆固醇血症的基线史为阴性的患者才显示出两组补充剂的显着保护作用。发现与omega-3脂肪酸治疗，CVD史以及高血压史之间存在显着的相互作用。一名被认为可能与补充剂有关的严重低钠血症发生在一名76岁患者中，该患者被随机分配到联合补充剂组151。

一项大型的（n = 13,578）较旧的研究发现补充ALA对心血管结局没有影响。30同样，在PREDIMED试验（在西班牙进行的主要预防CVD的一项随机营养干预试验）的纵向研究中， ALA与总死亡率显着降低28％（ P = 0.013）有关，但与心血管疾病死亡率无关。共有7,202名60至80岁年龄段，患有CVD的高风险（但没有CVD）且饮食中海洋n-3脂肪酸含量高（即海鲜）的参与者被随机分配到地中海饮食中，另外加初榨橄榄油（1升/周）或混合坚果（30克/天），或对照饮食。在每天摄入≥500 mg EPA和DHA的人群中，致命性CVD（39％）和CHD（46％）明显降低（分别为P = 0.032和P = 0.046）。此外，分配给MedDiet的橄榄油和特级初榨橄榄油的总死亡率显着降低了42％。在所有原因的死亡率最高还原记录在谁满足两个要求ALA（它们的总能量的0.7％）和长链n-3脂肪酸的要求（≥500毫克/ EPA加DHA的日参与者; P = 0.005）.185在健康的年轻人中（n = 328），每天补充1.6 g / d的DHA可改善4个月的血管功能和某些心血管疾病的危险因素（例如，甘油三酸酯，极低密度脂蛋白浓度）；然而，总的低密度脂蛋白（LDL）和高密度脂蛋白（HDL）胆固醇水平以及血压，空腹胰岛素，葡萄糖和c反应蛋白均未改变。146关于鱼类影响的证据尚无定论。 38，39，40，41，42心率降低，尤其是静息率高于69 bpm的心率降低，在一些（但不是全部）的12周研究中得到了证明。补充鱼油43，44，45补充鱼油对C反应蛋白（冠心病的标志物）的影响是模棱两可的46，47

使用10个月以上特定剂量的长链n-3脂肪酸（即DHA或EPA）单一疗法对10项随机对照试验（N = 550）进行荟萃分析，评估了对动脉僵硬的影响，具有统计学意义与对照组相比，脉搏波速度（ P <0.01）和动脉顺应性（ P <0.001）更高。参与者每天接受640至3,000 mg EPA和DHA胶囊的联合剂量，为期6至105周。 184没有发现异质性或出版偏见的证据。

CNS效应

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包括DHA在内的多不饱和脂肪酸对于大脑的正常发育至关重要，与正常水平的任何偏离都与认知障碍有关。12来自充分控制的临床试验的数据不足以对特定精神健康疾病中补充omega-3脂肪酸做出明确的陈述。 。有限的试验评估了精神分裂症和注意缺陷多动障碍中鱼油的补充效果不明确。12，48，157 OFFER试验是首发精神分裂症中omega-3脂肪酸的随机对照试验，将比较EPA 26周加上DHA作为橄榄油安慰剂的附加疗法，可改善症状和复发率173。

8至16岁有反社会和攻击行为问题的儿童（N = 200）被随机分配到每日补充饮料中，该饮料包含omega-3 1,000 mg（DHA 300 mg，EPA 200 mg，DPA 100 mg和α-亚麻酸） 400毫克）或安慰剂以双盲方式治疗6个月。补充Omega-3导致除一个内在分量表（ P = 0.002）和外在化分量表（ P = 0.001）以外的所有其他人的显着组x时间交互作用，以及对call性情绪不稳性状（ P <0.05）和自恋（ P = 0.048）的交互作用注意。在6个月的治疗期结束时观察到了效果，并持续了6个月。163一项针对21例具有冲动攻击性的儿童（6至17岁）的随机，对照，交叉试验均未发现效果。与安慰剂（含10 mg标准鱼油的多酚橄榄油）相比，鱼油胶囊6周（每天4 g；每天EPA； 400 mg，DHA 2,000 mg）对侵略性的主要评价为一级（ P <0.05 ）。有趋势表明，鱼油会使行为评分恶化（ P = 0.056）。值得注意的是，研究中几乎40％（38.5％）的儿童在基线时表现出脂肪酸不足。167

尽管认为特定的亚人群更可能受益，包括围产期抑郁症，儿童/青少年抑郁症以及与双相情感障碍相关的抑郁症，但临床试验更支持在鱼油抑郁症治疗中占有一席之地。49，50，51指南已经发表了讨论鱼油和重度抑郁症（MDD）之间关系的文章。 《美国精神病医生协会治疗MDD患者的实践指南》讨论了omega-3脂肪酸的证据，并指出大多数数据都是辅助研究，并且受研究设计，剂量，持续时间和结果异质性的限制。需要更多数据。 136未提供有关成人MDD管理的加拿大情绪和焦虑治疗网络（CANMAT）临床指南（2016）建议将Omega-3脂肪酸作为轻度至中度MDD的二线单药治疗或辅助治疗（1级） ）和针对中重度疾病的二线辅助治疗（2级）.137 2015年Cochrane评估了成人中omega-3鱼油的MDD评估得出的结论是，EPA：DHA的联合剂量小于6.6 g /天，单独的EPA剂量未达到大于4 g /天，单一DHA剂量不大于2 g /天或EPA：DHA和其他n-3 PUFA不大于3.13 g /天，与安慰剂相比，在抑郁症状中的获益较小或中等具有统计意义，但不太可能具有临床意义。这是基于25个非常低质量的研究（N = 1,373）。一项将EPA与抗抑郁药进行比较的研究发现，EPA 1 g /天和氟西汀20 mg /天（n = 40）之间具有可比的疗效。17212周，双盲，随机，安慰剂对照的结果相似已记录MDD的35名韩国人正在试用。每天补充1,740 mg n-3 PUFA可以显着改善4个抑郁量表中的1个。 178对13项随机临床试验（N = 916）的系统评价和荟萃分析评估了补充鱼油对维持性血液透析的疗效。与安慰剂相比，补充鱼油可显着改善该患者人群的贝克抑郁量表得分，且研究之间无明显异质性。177为了解释先前荟萃分析中所经历的异质性，荟萃回归分析测试了EPA和DHA剂量，EPA的影响：DHA比率，抗抑郁药使用者百分比，基线MDD症状严重程度，研究持续时间，患者年龄，发表年份以及研究n-3 PUFA治疗MDD有效性的质量。对13项随机临床试验（N = 1,233）的荟萃分析发现，n-3 PUFA对MDD抑郁症状具有总体有益作用（ P = 0.006，随机效应模型）。荟萃回归测试显示，统计学上显着更好的结局与更高的EPA剂量，更高的抗抑郁药使用者百分比和更早的出版年份相关（分别为P = 0.009， P = 0.044， P = 0.04）。没有发现明显的出版偏见181。

尽管有证据表明痴呆症与饮食和血浆中的n-3脂肪酸含量低有关，但补充鱼油并未显示出可以逆转或预防痴呆症52或改善老年患者的生活质量53。

一项为期12个月的随机，双盲，安慰剂对照比较者试验（n = 39）在可能患有轻度阿尔茨海默病的患者中进行了检查（迷你精神状态检查[MMSE] 15-26；临床痴呆评分量表0.5-1），没有发现接受ALA（600 mg /天）加omega-3脂肪酸（DHA 675 mg /天，EPA 975 mg /天）联合治疗，omega-3单药治疗的患者中氧化应激指标（F2-异前列腺烷）水平的差异脂肪酸或安慰剂（含5％鱼油）。但是，在12个月内，联合疗法显着降低了认知和功能下降（分别为MMSE和日常的仪器活动）。152相比之下，一项为期16周，随机，双盲，安慰剂对照的试验随机分配了160名健康成年人鱼油3克（EPA 240毫克/ DHA 240毫克）加多种维生素，鱼油6克（EPA 480毫克/ DHA 480毫克）含或不含多种维生素，或安慰剂以确定鱼油对认知和心血管功能的影响。每个鱼油胶囊含鱼油1克（EPA和DHA分别为80毫克）和50单位的维生素E；应当指出，多种维生素还包含21种草药和其他天然产品以及益生菌。与安慰剂相比，所有治疗组中花生四烯酸（AA）/ EPA的比率均得到改善，从而证实了依从性。 EPA仅在6 g鱼油组中显着增加：不含复合维生素的情况下增加了57％，含复合维生素的情况下增加了96％。 16周时未观察到对任何认知功能评分的影响，例如信息处理速度，注意力和记忆力；然而，在6周时观察到短期记忆的治疗效果显着，安慰剂组的平均表现优于鱼油6 g组（ P <0.05）。另外，与鱼油3 g +多种维生素组相比，鱼油6 g组的主动脉脉压明显降低（ P <0.05）和基线水平（ P = 0.01）。与基线相比，该组的主动脉扩张压力也有所改善（ P = 0.01）。主动脉压力升高与脑血管损伤和认知障碍有关。没有严重不良事件的报道。176在接受LC-n3-FA（2,200 mg /天； EPA 1,320 mg + DHA 880 mg）的健康老年人（50至75岁）中，记忆力（但不是学习能力）显着改善）与接受安慰剂的受试者相比，进行了为期26周的比较，这是一项小型的随机，双盲，对照试验（n = 44）。测试对象定位内存（OLM）以及召回和识别性能。治疗后OLM的平均改善为13.2％，而安慰剂为3.5％（ P = 0.049）；在校正“饮食习惯变化”和“ ApoE-epsilon4等位基因”的协变量后，显着性成立（分别为P = 0.004和P = 0.007）。治疗组红细胞ω-3水平（EPA和DHA）显着升高（ P = 0.013），而安慰剂显着降低（ P = 0.032）；两组之间的差异也很显着（ P = 0.001）。在omega-3-index值的变化与回忆或学习分数之间未发现明显的线性关系。不良事件包括胃肠道症状，头痛和皮肤刺激。 187年，美国精神病协会（APA）指南治疗阿尔茨海默氏病和其他痴呆症的指南没有发现足够的确切新证据来改变2007年指南对包括鱼油在内的其他药物的建议.191

The American Academy of Neurology guideline on complementary and alternative medicine in multiple sclerosis (2014) advises that a low-fat diet supplemented with fish oil is probably ineffective for improving multiple sclerosis-related relapse, disability, magnetic resonance imaging lesions, or quality of life (moderate-quality evidence).162

Critical illness and surgical patients

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Randomized, controlled trials have been conducted in severely ill patients in intensive care units (ICUs) and among elective surgical patients comparing fish oil–enriched lipid emulsions with standard enteral formulations. Meta-analyses have been conducted that recognize the heterogenous nature of the study populations (including medical, surgical, and trauma related) and formulations used (ranging from EPA/DHA 1 to 6.6 g/L)54 and the difficulty in recruiting patients into trials.54, 55, 56, 57

Findings from these meta-analyses are in favor of supplemental fish oil in terms of reduced length of stay in hospital and in ICU, decreased ventilator time, decreased new organ failure, and decreased postoperative infections.54, 55, 56, 57, 58 Twenty-eight–day mortality was decreased in 1 meta-analysis of ICU patients54 but not in an analysis of major abdominal surgery. No serious adverse events were recorded in the included trials.56 Further clinical trials in patients with GI surgery, not included in the meta-analyses, have been conducted with similar positive results.59, 60, 61, 62

Cystic fibrosis

A pilot trial of intravenous fish oil emulsion in cystic fibrosis found no benefits and some potential deleterious effects.92 A systematic review and meta-analysis identified 4 randomized controlled trials that included 91 subjects that compared omega-3 fatty acid supplementation with placebo for effects on morbidity and mortality of patients with cystic fibrosis. EPA doses ranged from 200 mg to 3.2 g and study durations ranged from 6 weeks to 6 months. Only 1 small short-term study demonstrated clinical benefit (ie, lung function improvement, sputum volume reduction) and 2 longer-term studies reported increases in essential fatty acid content of white blood cell membranes and serum phospholipids; few adverse effects were reported. Evidence was lacking to draw any conclusions or recommendations that would impact clinical practice.154 A 2016 updated review included 4 randomized controlled trials (N = 91) published since 2013 that studied the effect of fish oil in children and adults with cystic fibrosis. Similar to the earlier review, sufficient data were not available to recommend routine use or draw firm conclusions for use in this patient population.183

Diabetes

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A Cochrane systematic review of patients with type 2 diabetes mellitus revealed that fish oil 3 to 18 g/day supplementation lowered triglycerides and had no statistically significant effect on glycemic control, total cholesterol, or HDL cholesterol. However, it did raise LDL cholesterol by 0.21 mmol/L (8.12 mg/kL), especially in patients with hypertriglyceridemia on doses higher than EPA 2 g.9 Further randomized controlled trials in overweight patients and in patients with type 2 diabetes do not demonstrate an effect of fish oils on insulin sensitivity or fasting blood glucose.63, 64 These findings are consistent with an Agency for Healthcare Research and Quality evidence report.65

As a component of medical nutrition therapy for patients with type 1 or type 2 diabetes, the American Diabetes Association (ADA) Standards of Care (2014) recommends an increase in foods containing n-3 fatty acids (EPA and DHA; from fatty fish), viscous fiber (eg, oats, legumes, citrus), and plant-based stanols/sterols based on beneficial effects observed on lipoprotein profiles, heart disease prevention, and overall positive health in patients with diabetes (moderate quality evidence). However, data do not support the use of n-3 fatty acids (EPA and DHA) for preventing or treating cardiovascular events (high-quality evidence). It was noted that in order to reduce risk of acute pancreatitis, patients with severe hypertriglyceridemia may benefit from immediate therapy with fish oil.160 Likewise, the ADA statement from 2015 recommends at least 2 servings per week of foods containing EPA and DHA, such as fatty fish (moderate-quality evidence). However, use of omega-3 supplements is still not supported in people with diabetes for prevention or treatment of cardiovascular events (high-quality evidence).168

Drug-resistant epilepsy

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Low-dose fish oil was associated with a significant 33.6% decrease in seizure frequency in 24 adults (average age, 33 years) with drug-resistant partial-onset or generalized tonic/clonic seizures compared with placebo (P = 0.02). Participants received 10 weeks of supplementation with low-dose (1,080 mg/day), high-dose (2,160 mg/day), and placebo in a randomized, 3-period crossover trial. A borderline significant 31% reduction was observed for low-dose fish oil compared with high-dose (P = 0.05).165

Dry eye disease

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In a double-blind, randomized, placebo-controlled trial (n = 27), fish oil supplementation (EPA 1,245 mg/day and DHA 540 mg/day) given for 12 weeks in combination with usual eye-drop dry eye treatment significantly improved subjective eye pain, break-up time of tear film, and rose bengal staining score compared with placebo.149 Similar results were documented in another double-blind, randomized, placebo-controlled trial in 456 adults with symptomatic computer vision syndrome in the northern part of the India subcontinent where a predominantly vegetarian diet provides unacceptable levels of omega-3 fatty acids. After 3 month's supplementation with omega-3 fatty acids (EPA 720 mg and DHA 480 mg) or placebo (olive oil), all primary and secondary outcome measures (dry eye score, tear production, tear film stability, and cellular morphology and goblet cell density) were significantly improved with omega-3 supplementation but not placebo. Six participants in the intervention group dropped out because of gastric intolerance to the fish oil supplements.180 The effect of omega-3 fatty acids on the neural architecture and immune response of the cornea was investigated in a small follow up pilot study conducted in 12 adults with moderate dry eye disease who had been part of a larger, double-blind, randomized, placebo-controlled trial. After 3 months of 1.5 g/day of omega-3 (1,000 mg EPA + 500 mg DHA) or olive oil (as placebo), the total corneal nerve branch and main fiber densities improved significantly ( P =0.004 and P =0.03, respectively) compared to placebo. Ocular symptom scores, absolute level of tear osmolarity, and tear osmolarity also improved significantly with treatment ( P =0.04, P =0.02, and P =0.04, respectively) compared to placebo.192 Similarly, dry eye symptoms, Meibomian gland score, tear film breakup time, and wetting outcomes were improved significantly with 6-month omega-3 fatty acid supplementation. In this particular double-blind, randomized, placebo-controlled trial (n=130), adults with dry eye symptoms who were also diagnosed with rosacea were eligible to participate. Omega-3 fatty acid supplementation was provided as EPA 720 mg plus DHA 480 mg daily for 6 months. A significant change in the slope of the regression plots indicated a direct treatment-related response to the omega-3 fatty acid dietary supplement. Gastric intolerance was the most common side effect reported in the treatment group that led to 8 patients (12%) dropping out in the omega-3 group.193

Gynecological

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Trials are limited, but suggest a role for fish oil in the management of dysmenorrhea. Reduced requirement for analgesia and reported reduction in pain have been found after 2 to 3 months of supplementation.93, 94, 95 A Cochrane systematic review and meta-analysis of dietary supplements for dysmenorrhea identified only low or very low quality studies with very small sample sizes. Very limited evidence of effectiveness was found for the treatment of primary dysmenorrhea with a fish oil 500 mg/day pearl capsule with or without vitamin B ₁ 100 mg/day compared to placebo or no treatment; these data suggested fish oil may not be as effective as vitamin B ₁ (1 randomized clinical trial, n = 120).182

A 2017 systematic review and meta-analysis of nutritional supplements and herbal medicines for polycystic ovary syndrome identified 3 studies that investigated omega-3 fish oils; however, data were summarized for only 2 (n=95). Incongruencies throughout this paper between reference numbers in the table of studies vs reference numbers in the text led to conflicting data, specifically for fish oil and study doses of EPA and DHA. Although the author declares that neither study reported on menstrual regulation, a meta-analysis of the data reported a significant treatment effect for omega-3s associated with reduced total cholesterol (−0.49 mmol, P <0.001) compared to placebo. Mixed findings were reported for several of the secondary outcomes, such as triglycerides, HDL, LDL, body mass index, fasting glucose, and insulin resistance.194

Hepatoprotective effects

A fish oil-based lipid emulsion is gaining popularity over conventional soybean oil-based parenteral nutrition because of its apparent ability to reduce the incidence of parenteral nutrition-associated liver disease or hepatobiliary dysfunction.96, 97, 98, 99

Clinical trials

A randomized controlled trial (n = 66) evaluated the hepatoprotective effect of omega-3 fish oil lipid emulsion versus standard parenteral nutrition (PN) in adult liver transplant patients diagnosed with end-stage liver disease or hepatic cellular carcinoma.142 Patients were randomized to either PN with standard 20% lipid emulsion or PUFA in which omega-3 fish oil emulsion (2 mL/kg/day) replaced part of the standard lipid emulsion. At 2 and 9 days after transplant, alanine aminotransferase and prothrombin time were significantly decreased ( P = 0.024 and P = 0.035, respectively) and on day 9, pathology revealed hepatocyte injury and inflammatory cell aggregation were markedly ameliorated in the PUFA group. Additionally, post-transplant hospital stay was significantly shorter in the PUFA group versus PN ( P = 0.041). Potential mechanisms for these effects include immunomodulation and down-regulation of inflammatory responses.142

Infant development

Dietary fat is fundamental for the growth and development of infants. DHA is an important component of structural lipids of cell membranes, and its perinatal availability has been related to visual acuity development, neurological development, behavior, and brain growth.66, 67 Accretion occurs primarily during the last trimester of pregnancy via the placenta and the infant's first year of life from breast milk and dietary sources.68, 69

临床资料

Evidence from systematic reviews provides little support for benefit of supplementation with long-chain PUFAs (LCPUFAs), such as DHA, to either term or preterm infants.68, 69, 153 Formula-fed infants have been shown to have less DHA than infants fed breast milk. Reduced neural function and visual acuity have been documented in preterm infants fed formula relative to those who were breast-fed. A review of LCPUFA supplementation studies demonstrated no benefit to visual or cognitive development in infants born at term receiving LCPUFA-supplemented formula.68 However, some evidence did show that omega-3 fatty acid supplementation of formula increases the early rate of visual maturation in preterm infants.69 Additionally, multivariate analysis revealed that risk of 'retinopathy of prematurity' was significantly decreased in very low birth weight (less than 1,500 g) preterm infants who received fish oil lipid emulsion in their total parenteral nutrition compared with those who did not, 5% vs 32.5%, respectively (odds ratio: 0.76; 95% confidence interval 0.06 to 0.911; P = 0.04).156

Malnourished infants, who may have poor fat absorption, appear to also absorb fish oil supplements well and use this source of fatty acid for more than an energy source.70

Although formula supplemented with omega-3 fatty acids increases DHA and EPA levels in healthy and malnourished infants, this may be at the expense of omega-6–derived fatty acids (eg, arachidonic acid). Because high levels of DHA and EPA appear to successfully compete for cyclooxygenase and other eicosanoid enzymes, formula-fed infants should be supplemented with omega-3 as well as omega-6 LCPUFAs if their fatty acid status is to be comparable with that of the breast-fed infant.66, 67, 71

炎症性肠病

动物资料

In animal models of inflammatory bowel disease, fish oil has been shown to exert a protective effect, which is considered to be via anti-inflammatory mechanisms.72

临床资料

Cochrane meta-analyses and systematic reviews of randomized controlled trials have been undertaken for the effect of omega-3 fatty acids in induction of remission in ulcerative colitis and for maintenance of remission of ulcerative colitis and Crohn disease.73, 74, 75 For induction of remission in ulcerative colitis, trials were of crossover and parallel design, and because of heterogeneity of outcomes and methodology, the data were not pooled. Of the 6 included studies, 1 small study showed benefit for induction within 3 months. The other trials showed benefit only for secondary outcome measures, and no recommendation can be made regarding the effect of fish oil supplementation.73 For maintenance of remission in ulcerative colitis74 and Crohn disease75 relapse rates were similar for omega-3 fatty acids and the control intervention. For Crohn disease, the meta-analysis included data from both of the large EPIC trials. The conclusion that omega-3 fatty acids have no effect on maintenance of remission is an update on previous meta-analyses.75 The Cochrane 2014 updated systematic review for Crohn disease concluded that omega-3s were probably ineffective for maintenance of remission based on the pooled analysis that had no significant heterogeneity. Interventions included both enteric-coated and gelatin capsules with EPA and DHA ranging from 1.2 to 3.3 g/day and 0.6 to 1.8 g/day, respectively, while placebo capsules contained corn oil, olive oil, or medium-chain triglyceride oil (ie, caprylic and capric acid).164

Lipid-lowering effects

动物资料

The relatively low risk of adverse events with the use of fish oils and widespread consumption of fish in the diet, along with evidence from numerous clinical studies, make data from animal studies in hyperlipidemia redundant.

临床资料

Several meta-analyses and systematic reviews of clinical trials in hyperlipidemia have been conducted.76, 77, 78, 79 Clinical reductions in triglycerides of −0.34 mmol/L (−30.12 mg/dL) (95% CI, −0.41 to −0.27 mmol/L [−36.32 to −23.91 mg/dL]) were found in a meta-analysis of 47 randomized, controlled trials (N = 16,511).76 In 2004, the FDA approved the use of a fish oil for reducing very high triglyceride levels (at least 500 mg/dL [5.65 mmol/L]) in adults as an adjunct to diet.78 The investigators of the effect of fish oil in maintenance of remission in Crohn disease (the EPIC trials) reported decreases in serum triglycerides in the study populations.75 A place in therapy is also suggested for fish oil in hypertriglyceridemia consequent to type 2 diabetes and chronic kidney disease and as add-on therapy with statins in cardiovascular disease.11, 76, 78, 79 Increases in LDL cholesterol as well as HDL have been observed, and may be clinically important.76, 78, 80 Other studies have noted changes in concentration and particle size of very low-density lipoproteins.79, 81

Comparative effectiveness of fish oil, gemfibrozil, fenofibrate, and atorvastatin on reducing triglyceride (TG) levels in routine clinical care of HIV-infected adults was evaluated via a large retrospective cohort (n = 493).143 Although new use of fish oil resulted in a 0.51 mmol/L reduction, fibrates were more effective producing a change of −0.75 mmol/L. Dosage information was only available for 14% of patients (61% received ≤2 g/day of fish oil, 2% ≥4 g/day). These results are smaller than those reported in previous trials and likely reflect doses used in clinical care per se versus controlled trials.143

There have been several guidelines published discussing the relationship between fish oils and hypertriglyceridemia. The American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis (2012) recommend that omega-3 fish oil is very effective in treating hypertriglyceridemia and may also be used as adjunctive therapy in lower doses.135 The 2013 American College of Cardiology (ACC)/ American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease (ASCVD) Risk in Adults states that if omega-3 fatty acids (eg, EPA and/or DHA) are used for the management of severe hypertriglyceridemia (500 mg/dL or more), it is reasonable to evaluate the patient for GI disturbances, skin changes, and bleeding.138 The Endocrine Society's clinical practice guideline on the management of hypertriglyceridemia (2012) states that the use of omega-3 fatty acids may be considered for treatment of triglyceride levels higher than 1,000 mg/dL. Due to variability in content amounts in over-the-counter preparations of omega-3, they suggest that nutritional labels should be studied to calculate the number of capsules required to obtain a dose of 3 to 5 g of n-3 fatty acids.139

Menopause

The Endocrine Society clinical practice guidelines for the treatment of symptoms of the menopause (2015) recommend counseling patients on the lack of consistent evidence for benefit of complementary medicine therapies, including fish oils, as an alternative nonhormonal therapy for vasomotor symptoms (weak recommendation; low quality evidence).188

肥胖

临床资料

A double-blind, randomized controlled trial found no significant difference in weight reduction, fat mass reduction, or inflammatory biomarkers with fish oil or placebo in parallel groups that followed a low energy diet for 12 weeks. However, significant correlations were identified in the fish oil group between leptin and weight change, fat mass, EPA, and DHA.144 Similar results were also found in another randomized, double-blind, placebo-controlled, parallel trial (N = 97) conducted in otherwise generally healthy overweight and obese women (body mass index, 27.5 to 40) on a 30% calorie-restricted diet for 10 weeks. Significant changes in waist-to-hip ratio were observed in the EPA 1,300 mg/day group (EPA + DHA 1,341 mg/day) but not in the alpha-lipoic acid (300 mg/day), ALA + EPA, or placebo groups; whereas a significant increase in weight lost was noted only in the ALA group. Total cholesterol was reduced significantly in all 4 groups; however, the EPA groups also experienced significant changes in LDL-cholesterol ( P < 0.05), beta-hydroxybutyrate ( P < 0.05), triglycerides ( P < 0.01), and diastolic blood pressure ( P < 0.05). Interestingly, the decline in leptin levels that accompanied the fat loss was significant in all groups except for the EPA group, in which the non-significant reduction in leptin was associated with a positive significant effect on resting metabolic rate (r = 0.42, P < 0.001).171

Renal effects

The ability of n-3 fatty acids to reduce eicosanoid production or action has led to the testing of dietary fish oil in patients with immunoglobulin A (IgA) nephropathy. In these patients, the initial immunological renal injury evokes cytokine and eicosanoid activity. Dietary fish oil has been tested in patients with several types of renal disease with varying results. Results in patients with IgA nephropathy are conflicting.100 The use of fish oil on lipoprotein-a in end-stage renal disease and among kidney transplant recipients has also been evaluated.101, 102

A systematic review and meta-analysis of 13 randomized clinical trials (N = 916) assessed the efficacy of fish oil supplementation on maintenance hemodialysis. Compared with placebo, supplementation with fish oil significantly improved arteriovenous graft thrombosis, cardiovascular events, depression scores, secondary hyperparathyroidism, C-reactive protein, and triglycerides without significant heterogeneity. No significant difference was found for lipids, some inflammatory biomarkers, or mortality. Dose subanalysis for less than 2 g/day and 2 g/day or more found no significant difference in these effects. Based on the studies reviewed, the authors suggested a dose of 1 to 2 g/day would be effective and well tolerated in this high-risk group; specific EPA or DHA was not noted. This suggestion was considered in line with the American Heart Association recommendation for patients at high cardiovascular risk (1 g/day with a dietary ratio of omega-6 to omega-3 of 4).177

Respiratory infections

临床资料

A 200 mL drink containing supplementation with fish oil (DHA 550 mg, EPA 550 mg), vitamin D ₃ 10 mcg, and whey protein 8 g twice daily for 16 weeks in young athletes did not provide a significant difference in the incidence, severity, or duration of upper respiratory tract infections; number of practitioner visits; or number of times medication was taken compared with placebo. However the total number of symptom days reported were significantly shorter with the intervention than placebo (1.72 ± 1.67 vs 2.79 ± 1.76; P < 0.05).179

Rheumatoid arthritis

EPA is a competitive substrate with arachidonic acid for the generation of less active eicosanoid metabolites (eg, leukotrienes) and acts to reduce inflammation.10 The most profound anti-inflammatory effects of n-3 fatty acids are on neutrophil function and mediator generation, providing a more likely benefit in neutrophilic inflammatory diseases, including arthritis.82

动物资料

The relatively low risk of adverse events with the use of fish oils and widespread consumption of fish in the diet, along with evidence from numerous clinical studies, make data from animal studies largely irrelevant.

临床资料

Inuit populations with a diet high in LCPUFAs (especially EPA and DHA from seal and fish oils), report a low incidence of rheumatoid arthritis.83 Meta-analyses of controlled trials have been conducted with equivocal findings.65, 83, 84 Issues raised by the analyses include confounding of results with the use of potentially active placebo oils (eg, corn and olive oil) and management of dropouts in the individual trials.83, 85 Reductions in patient-reported joint pain and morning stiffness and a reduced need for nonsteroidal anti-inflammatory drugs are potential benefits of fish oil therapy, while reduction in cardiovascular risk may also be a valuable attribute.83

A minimum daily dose of EPA/DHA 3 g appears to be necessary to reduce the release of leukotriene B4 from stimulated neutrophils and of interleukin-1 from monocytes, while dosages of more than 6 g/day do not appear to confer any additional benefit.48

In disease-modifying antirheumatic drug (DMARD)-naive adults with rheumatoid arthritis of less than 12-months onset, high-dose fish oil (5.5 g/day) significantly reduced failure of triple DMARD (methotrexate, sulfasalazine, hydroxychloroquine) therapy compared with control (0.4 g/day of fish oil) at 1 year follow up ( P = 0.002 unadjusted; P = 0.0006 adjusted). Time to first remission was also significantly less in the high-dose fish oil group ( P = 0.03 unadjusted; P = 0.04 adjusted).166

中风

动物资料

The relatively low risk of adverse events with the use of fish oils and widespread consumption of fish in the diet, along with evidence from numerous clinical studies, make data from animal studies in stroke largely irrelevant.

临床资料

Despite data from large trials being available (including the GISSI, JELIS, and EPIC-Norfolk trials), no consistent relationship between fish oil consumption and reduction in the risk of stroke has been established.34, 78, 86, 87 The etiology of the stroke may be of relevance, with omega-3 fatty acids considered to be more likely to demonstrate positive effects on stroke related to ischemic causes than hemorrhagic stroke because of platelet anti-aggregating properties.78, 86 A 2004 meta-analysis of prospective cohort studies found a higher incidence of stroke in people who never consumed fish or only consumed fish less than once per month versus a higher fish intake. A reduced risk for total stroke was found for intakes of fish at least once per week. Whole fish also contain the proteins taurine, arginine, and glutamine, which may be involved in cardiovascular function.78

A randomized, controlled trial evaluated the effect of daily fish oil supplementation 3 g for 12 weeks on quality of life outcomes in CT-confirmed ischemic stroke. No effect was found for all outcome measures, including serum triglycerides, total cholesterol, blood pressure, mood, and quality of life indicators.88

A 16-week randomized, double-blind, placebo-controlled trial randomly assigned 160 healthy adults to fish oil 3 g (EPA 240 mg/DHA 240 mg) plus a multivitamin, fish oil 6 g (EPA 480 mg/DHA 480 mg) with and without a multivitamin, or placebo to determine effects of fish oil on cognitive and cardiovascular function. Each fish oil capsule contained fish oil 1 g (80 mg each of EPA and DHA) plus 50 units of vitamin E; it should be noted that the multivitamin also contained 21 herbal and other natural products plus probiotics. The AA/EPA ratio improved in all treatment groups compared to placebo confirming compliance. EPA increased significantly only in the fish oil 6 g groups; by 57% without the multivitamin and by 96% with the multivitamin. The fish oil 6 g group experienced significantly lower aortic pulse pressure compared to the fish oil 3 g + multivitamin group ( P < 0.05) and to baseline ( P = 0.01); aortic augmentation pressure was also improved in this group compared to baseline ( P = 0.01). Higher aortic pressures are associated with cerebrovascular damage and cognitive impairment. No serious adverse events were reported.176

加药

The AHA recommends a minimum of 2 fatty fish meals per week.1, 34 Clinical trials suggest fish oil supplementation of omega-3 fatty acid 1 g/day in coronary heart disease, and where triglycerides are elevated, a minimum of omega-3 fatty acid 2 g/day up to a maximum of 4 g/day. Fish oil 1,000 mg approximates to omega-3 fatty acid 300 to 400 mg (EPA/DHA).34

Emulsified oral preparations have been developed to improve the taste over encapsulated fish oils and may increase digestion and absorption of the fatty acids via modifications in solubility.103 Encapsulated oils have been found to oxidize and become rancid over time and with processing method, which may have an effect on total EPA/DHA delivered.88, 104

怀孕/哺乳

Documented adverse effects have occurred in pregnancy and lactation. In 2004, the FDA recommended that pregnant women avoid certain fish due to the potential for mercury contamination; however, June 2014 draft revisions encourage pregnant women, those of child-bearing age, breastfeeding mothers, and young children to eat 2 or 3 servings (approximately 4 oz/serving) of low-mercury varieties of fish each week.169 The Food and Agriculture Organization of the United Nations and the World Health Organization recommend daily intake of omega-3 supplementation during pregnancy.170 Farmed salmon may have a greater potential for contamination than wild sources.78, 86, 104

Omega-3 fatty acids may prevent preterm birth via delayed induction of labor and cervical ripening through the inhibition of prostaglandin F2-alpha and E2 production, and by relaxation of the myometrium. A 2007 Cochrane meta-analysis found that mean gestation was 2.6 days longer (95% confidence interval [CI], 1.03 to 4.07) in women who took fish oil supplementation. No significant difference was found for the relative risk (RR) of birth before 37 weeks, while a significant decrease in the risk of birth before 34 weeks gestation was found (RR 0.69; 95% CI, 0.5 to 0.99).105 A 2015 meta-analysis of randomized clinical trials (N = 3,854) in women carrying singleton gestations without prior preterm birth, found no significant effect of omega-3 supplementation (total daily dose range, 650 to 3,000+ mg EPA + DHA; 200 to 500 mg DHA monotherapy) on rate of preterm birth before 37 weeks compared with controls. However, in a subgroup analysis in women who received EPA + DHA, mean birth weight was significantly higher (mean difference, 51.18 g). Additionally, perinatal death rate was lower in women receiving omega-3s before 21 weeks of gestation compared with controls.170

A study in which fish oil supplementation was taken after 22 weeks suggested an increase in oxidative stress in the plasma at week 30.106 Effects of fish oil on lipids and blood pressure do not appear to be sustained during pregnancy.107

While evidence indicates that the DHA and EPA composition of breast milk is affected by fish oil supplementation, there is little evidence in support of benefit to the infant.66, 67, 68, 69 Use of fish oil supplementation during pregnancy and breast-feeding to reduce the incidence of food allergy in infants has also been evaluated.19

互动互动

Agents with antiplatelet properties: Omega-3 fatty acids may enhance the antiplatelet effect of agents with antiplatelet properties. Monitor therapy.108, 109, 110, 111, 112, 113, 114

Anticoagulants: Omega-3 fatty acids may enhance the anticoagulant effect of anticoagulants. Monitor therapy.108, 111, 112, 113, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132

Ibrutinib: Omega-3 fatty acids may enhance the antiplatelet effect of Ibrutinib. Monitor therapy. International labeling: The ibrutinib Canadian product monograph recommends avoiding this combination.196, 197

不良反应

Fish oil at dosages of EPA/DHA 2 to 5.4 g/day has been well tolerated. In clinical trials, only mild GI-related adverse effects such as dyspepsia, diarrhea, and nausea were reported.30, 31, 56, 75 An increased risk of diarrhea was noted in a meta-analysis of trials conducted among patients with inflammatory bowel disease who were given enteric-coated, timed-release capsules.72

Prolonged bleeding time was noted during and after cardiac surgery in a 55-year-old man despite cessation of oral antiplatelet medications a week prior to surgery. Dramatic clinical improvement was noted immediately following transfusion of donor platelets. Follow up detailed inquiry revealed a 3-month history of supplementation with garlic-thyme (20 mg to 100 mg/day) and fish oils (EPA 675 mg + DHA 450 mg daily); both reported to potentially inhibit platelet aggregation.190

A safety study found similar adverse events for intervention (EPA 2 g/day for 12 weeks) and placebo groups. Increased body mass index and increased (but modest) bleeding time were reported.133

Although an increase in LDL cholesterol has been occasionally reported, evidence does not suggest that the risk is greater than the benefit related to increased fish oil consumption.76, 78

Fish oil supplementation should be used with caution in individuals who are allergic to seafood.

毒理学

综上所述

较常报道的副作用包括：消化不良和勃起。有关不良影响的完整列表，请参见下文。

对于消费者

适用于omega-3多不饱和脂肪酸：口服胶囊液体填充

需要立即就医的副作用

除了其所需的作用外，omega-3多不饱和脂肪酸还可能引起某些不良作用。尽管并非所有这些副作用都可能发生，但如果确实发生了，则可能需要医疗护理。

服用omega-3多不饱和脂肪酸时，如果出现以下任何副作用，请立即咨询医生：

发病率未知

• 牙龈出血
• 咳嗽
• 咳血
• 呼吸或吞咽困难
• 头晕
• 快速或不规则心跳
• 头痛
• 荨麻疹，瘙痒或皮疹
• 月经量增加或阴道流血
• 流鼻血
• 麻痹
• 伤口长期出血
• 眼睑或眼睛，面部，嘴唇或舌头周围浮肿或肿胀
• 红色或黑色，柏油样凳子
• 红色或深棕色尿液
• 出汗
• 胸闷
• 异常疲倦或虚弱

不需要立即就医的副作用

Omega-3多不饱和脂肪酸可能会出现一些副作用，通常不需要医疗。随着身体对药物的适应，这些副作用可能会在治疗期间消失。另外，您的医疗保健专业人员可能会告诉您一些预防或减少这些副作用的方法。

请咨询您的医疗保健专业人员，是否持续存在以下不良反应或令人讨厌，或者是否对这些副作用有任何疑问：

不常见

• 胃酸或酸
• 味道差，异常或不愉快（后味）
• ching
• 肿胀或饱满的感觉
• 口味改变
• 胃中多余的空气或气体
• 胃灼热
• 消化不良
• 胃部不适，不适或疼痛

发病率未知

• 腹泻
• 排便困难（凳子）
• 食欲不振
• 恶心或呕吐
• 气体通过
• 胃饱满

对于医疗保健专业人员

适用于omega-3多不饱和脂肪酸：口服胶囊，口服延迟释放胶囊，口服试剂盒，口服液，可咀嚼的口服片剂

胃肠道

常见（1％至10％）：勃起，消化不良，恶心，胃肠道疾病（包括腹胀，腹痛，便秘，腹泻，肠胃气胀，胃食管反流病，呕吐）

罕见（0.1％至1％）：胃肠道出血，肠胃炎

罕见（少于0.1％）：胃肠道疼痛

非常罕见（小于0.01％）：下消化道出血^[参考]

一般

最常见的不良事件是勃起，消化不良和味觉变态^[参考]

其他

常见（1％至10％）：感染，疼痛

罕见（0.1％至1％）：死亡^[参考]

皮肤科

普通（1％至10％）：皮疹

罕见（0.1％至1％）：特应性皮炎

罕见（少于0.1％）：荨麻疹，痤疮，皮疹瘙痒

未报告频率：瘙痒^[参考]

心血管的

罕见（0.1％至1％）：低血压^[参考]

肌肉骨骼

常见（1％至10％）：背痛^[Ref]

新陈代谢

罕见（0.1％至1％）：高血糖，痛风，高甘油三酸酯

非常罕见（小于0.01％）：血液乳酸脱氢酶增加^[参考]

神经系统

普通（1％至10％）：口味变态

罕见（0.1％至1％）：头晕，消化不良，头痛，多动^[参考]

呼吸道

罕见（0.1％至1％）：:光

非常罕见（小于0.01％）：鼻干

未报告频率：流感^[参考]

过敏症

稀有（小于0.1％）：超敏

上市后报告：过敏反应^[参考]

血液学

非常罕见（少于0.01％）：白细胞计数增加，

未报告频率：出血时间略有延长

上市后报告：出血性素质^[参考]

精神科

罕见（0.1％至1％）：抽动，发脾气，失眠^[Ref]

肝的

罕见（少于0.1％）：肝病（包括ALT升高，AST升高和转氨酶升高） ^[参考]

某些副作用可能没有报道。您可以将其报告给FDA。

成人高甘油三酯血症的常规剂量

1克仅处方产品：
每天口服4克；可以单剂量或分两次剂量给药。

评论：
-在开始治疗之前，仔细评估甘油三酸酯的水平，并确定其他可能的原因（例如糖尿病，甲状腺功能减退，药物治疗）并进行适当管理。
-在使用这种药物之前，患者应降低脂质饮食，并在使用这种药物期间继续饮食。
-胶囊应全部吞服；不要破碎，压碎，咀嚼或溶解胶囊。
-在临床试验中，药物与餐点同时使用。

肾脏剂量调整

数据不可用

肝剂量调整

数据不可用

预防措施

禁忌症：
-对任何成分过敏

有关其他预防措施，请参阅“警告”部分。

透析

数据不可用