Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

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#humans #randomized-controlled-trials-as-topic #fatty-acids-omega-3 #eicosapentaenoic-acid #fatty-acids-unsaturated

Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Chang et al., 2023 | Adv Nutr | Meta Analysis

Citation

Chang Jane Pei-Chen, Tseng Ping-Tao, ... Su Kuan-Pin. Safety of Supplementation of Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Adv Nutr. 2023-Nov;14(6):1326-1336. doi:10.1016/j.advnut.2023.08.003

Abstract

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.

Key Findings

This study was registered at PROSPERO as CRD42023401169.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 90
Age Range See abstract
Condition See abstract

MeSH Terms

  • Humans
  • Randomized Controlled Trials as Topic
  • Fatty Acids, Omega-3
  • Eicosapentaenoic Acid
  • Fatty Acids, Unsaturated
  • Dietary Supplements

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Meta-Analysis, Systematic Review, Journal Article, Research Support, Non-U.S. Gov't
  • Vertical: omega-3

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09