College of Medicine, China Medical University, Taichung, Taiwan; Department of Psychiatry & Mind-Body Interface Laboratory (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; WinShine Clinics in Specialty of Psychiatry, Kaohsiung, Taiwan; Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan; Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung City, Taiwan.
Adv Nutr. 2023 Nov;14(6):1326-1336. doi: 10.1016/j.advnut.2023.08.003. Epub 2023 Aug 9.
There is no comprehensive review of the evidence to support omega-3 polyunsaturated fatty acids (PUFAs) as a relatively safe and tolerable intervention. This study aimed to provide a meta-analytic and comprehensive review on the adverse effects of all kinds of ω-3 PUFA supplementation reported in randomized controlled trials (RCTs) in human subjects. A systematic review of RCTs published between 1987 and 2023 was carried out based on searches of 8 electronic databases. All RCTs that compared the adverse effects of ω-3 PUFAs containing eicosapentaenoic acid, docosahexaenoic acid, or both compared with controls (a placebo or a standard treatment) were included. The primary outcome was the adverse effects related to ω-3 PUFA prescription. A total of 90 RCTs showed that the ω-3 PUFA group, when compared with the placebo, had significantly higher odds of occurrence of diarrhea (odds ratio [OR] = 1.257, P = 0.010), dysgeusia (OR = 3.478, P < 0.001), and bleeding tendency (OR = 1.260, P = 0.025) but lower rates of back pain (OR = 0.727, P < 0.001). The subgroup analysis showed that the prescription ω-3 PUFA products (RxOME3FAs) had higher ω-3 PUFA dosages than generic ω-3 PUFAs (OME3FAs) (3056.38 ± 1113.28 mg/d compared with 2315.92 ± 1725.61 mg/d), and studies on RxOME3FAs performed more standard assessments than OME3FAs on adverse effects (63% compared with 36%). There was no report of definite ω-3 PUFA-related serious adverse events. The subjects taking ω-3 PUFAs were at higher odds of experiencing adverse effects; hence, comprehensive assessments of the adverse effects may help to detect minor/subtle adverse effects associated with ω-3 PUFAs. This study was registered at PROSPERO as CRD42023401169.
目前尚无综合评估证据表明ω-3 多不饱和脂肪酸（PUFAs）是一种相对安全且耐受良好的干预措施。本研究旨在对所有类型的ω-3 PUFA 补充剂在人体随机对照试验（RCT）中报告的不良反应进行荟萃分析和综合评估。根据对 8 个电子数据库的检索，开展了一项关于 1987 年至 2023 年期间发表的 RCT 的系统综述。所有将 ω-3 PUFAs（含二十碳五烯酸、二十二碳六烯酸或两者）与对照（安慰剂或标准治疗）进行比较的 RCT 均纳入研究。主要结局为与 ω-3 PUFA 处方相关的不良反应。共 90 项 RCT 表明，与安慰剂相比，ω-3 PUFA 组腹泻（比值比 [OR] = 1.257，P = 0.010）、味觉障碍（OR = 3.478，P < 0.001）和出血倾向（OR = 1.260，P = 0.025）的发生风险更高，但背痛（OR = 0.727，P < 0.001）的发生率更低。亚组分析显示，处方 ω-3 PUFA 产品（RxOME3FAs）的 ω-3 PUFA 剂量高于通用 ω-3 PUFAs（OME3FAs）（3056.38 ± 1113.28 mg/d 比 2315.92 ± 1725.61 mg/d），且 RxOME3FAs 研究对不良反应的评估比 OME3FAs 更标准（63%比 36%）。没有报告与 ω-3 PUFA 相关的明确严重不良事件。服用 ω-3 PUFAs 的受试者出现不良反应的风险更高；因此，全面评估不良反应有助于发现与 ω-3 PUFAs 相关的轻微/隐匿性不良反应。本研究已在 PROSPERO 注册，注册号为 CRD42023401169。
