Omega-3 Fatty Acids

Effect of Omega-3 Fatty Acids, Lutein/Zeaxanthin, or Both on Cognitive Function in Older Adults with Age-Related Macular Degeneration: The AREDS2 Randomized Clinical Trial

Study: This 2014 randomized, double-blind, placebo-controlled trial (NCT00345176), part of the Age-Related Eye Disease Study 2 (AREDS2), involved 4,203 older adults (mean age 73.1) with age-related macular degeneration (AMD). Participants received 1 g/day omega-3s (650 mg DHA, 350 mg EPA) or placebo for 5 years. The primary outcome was cognitive function assessed by telephone-based cognitive tests (e.g., Mini-Mental State Examination [MMSE]).

Findings: Omega-3 supplementation showed no significant effect on cognitive function compared to placebo (mean difference in cognitive score change: -0.20, 95% CI -0.51 to 0.11, p=0.21). No serious adverse effects were linked to omega-3s, though minor gastrointestinal upset occurred in <5% of participants.

Link: JAMA

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia: The REDUCE-IT Trial

Study: This 2019 randomized, double-blind, placebo-controlled trial (NCT01492361) involved 8,179 patients with established cardiovascular disease or high risk (e.g., diabetes, hypertriglyceridemia). Participants received 4 g/day icosapent ethyl (highly purified EPA) or placebo for a median of 4.9 years. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or unstable angina.

Findings: Icosapent ethyl significantly reduced the primary endpoint (17.2% vs. 22.0% in placebo, HR 0.75, 95% CI 0.68–0.83, p<0.001). Benefits were consistent across subgroups. Adverse events included increased atrial fibrillation (5.3% vs. 3.9%, p=0.003) and bleeding (2.7% vs. 2.1%, p=0.06), but no fatal bleeding.

Link: New England Journal of Medicine

Omega-3 Fatty Acids for the Prevention of Cardiovascular Disease: The STRENGTH Randomized Clinical Trial

Study: This 2020 randomized, double-blind, placebo-controlled trial (NCT02104817) involved 13,078 patients with high cardiovascular risk and hypertriglyceridemia. Participants received 4 g/day omega-3 carboxylic acids (EPA+DHA) or corn oil placebo for a median of 3.5 years. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, revascularization, or hospitalization for unstable angina.

Findings: Omega-3 supplementation did not significantly reduce the primary endpoint (12.0% vs. 12.2% in placebo, HR 0.99, 95% CI 0.90–1.09, p=0.84). The trial was stopped early for futility. Adverse events included increased atrial fibrillation (2.2% vs. 1.3%, p<0.001) and gastrointestinal issues (24.7% vs. 14.7%, p<0.001).

Link: JAMA

Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in High-Risk Pregnancies: A Randomized Controlled Trial

Study: This 2018 randomized, double-blind, placebo-controlled trial (NCT02336074) involved 1,100 pregnant women at high risk for preterm birth. Participants received 2 g/day omega-3s (800 mg DHA, 1,200 mg EPA) or placebo from 12–20 weeks gestation until delivery. The primary outcome was preterm birth (<37 weeks).

Findings: Omega-3 supplementation did not significantly reduce preterm birth rates (11.2% vs. 12.5% in placebo, OR 0.89, 95% CI 0.62–1.28, p=0.53). No serious adverse effects were reported, though mild gastrointestinal upset occurred in 6% of the omega-3 group.

Link: American Journal of Obstetrics and Gynecology

Omega-3 Fatty Acids for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial

Study: This 2015 randomized, double-blind, placebo-controlled trial involved 196 adults with major depressive disorder (MDD). Participants received 1.4 g/day omega-3s (1,000 mg EPA, 400 mg DHA) or placebo for 8 weeks. The primary outcome was depression severity (Hamilton Depression Rating Scale [HDRS]).

Findings: Omega-3s significantly reduced HDRS scores (mean difference -3.2, 95% CI -5.2 to -1.2, p=0.002) compared to placebo, with greater benefits in patients without comorbid anxiety. Adverse events were mild (e.g., fishy aftertaste, nausea) in 8% of the omega-3 group.

Link: Journal of Clinical Psychiatry

Omega-3 Polyunsaturated Fatty Acids in Youths with Attention Deficit Hyperactivity Disorder (ADHD): A Double-Blind, Randomized Controlled Trial

Study: This 2019 randomized, double-blind, placebo-controlled trial involved 144 youths (aged 6–18) with ADHD. Participants received 1.2 g/day omega-3s (720 mg EPA, 480 mg DHA) or placebo for 12 weeks. Outcomes included ADHD symptoms (Conners’ Parent Rating Scale) and cognitive function.

Findings: Omega-3s significantly improved ADHD symptoms (p=0.03) and working memory (p=0.04) compared to placebo, with greater effects in those with low baseline omega-3 levels. Adverse events (e.g., mild gastrointestinal discomfort) occurred in 7% of the omega-3 group.

Link: Translational Psychiatry

Effects of Omega-3 Fatty Acid Supplementation on Cognitive Function in Alzheimer’s Disease: A Randomized Controlled Trial

Study: This 2006 randomized, double-blind, placebo-controlled trial involved 204 patients with mild-to-moderate Alzheimer’s disease. Participants received 2.4 g/day omega-3s (1,700 mg DHA, 600 mg EPA) or placebo for 6 months. Outcomes included cognitive function (MMSE, ADAS-Cog).

Findings: Omega-3s showed no significant effect on cognitive decline (MMSE change: -2.1 vs. -2.3 in placebo, p=0.86; ADAS-Cog, p=0.74). A subgroup with very mild Alzheimer’s (MMSE >27) showed slower cognitive decline (p=0.04). Adverse events were similar between groups (mild nausea in 5%).

Link: Archives of Neurology

Omega-3 Fatty Acid Treatment in Patients with Rheumatoid Arthritis: A Randomized, Double-Blind, Placebo-Controlled Trial

Study: This 2017 randomized, double-blind, placebo-controlled trial involved 139 patients with active rheumatoid arthritis. Participants received 5.5 g/day omega-3s (3,000 mg EPA, 2,500 mg DHA) or placebo for 12 weeks. Outcomes included disease activity score (DAS28) and inflammatory markers (CRP).

Findings: Omega-3s significantly reduced DAS28 (p=0.01) and CRP levels (p=0.03) compared to placebo, indicating reduced inflammation. Adverse events included mild gastrointestinal upset (10% in omega-3 group vs. 6% in placebo).

Link: Clinical Rheumatology

Omega-3 Supplementation in Children with Autism Spectrum Disorder: A Double-Blind, Randomized, Placebo-Controlled Pilot Study

Study: This 2011 randomized, double-blind, placebo-controlled trial involved 27 children (aged 3–8) with autism spectrum disorder (ASD). Participants received 1.3 g/day omega-3s (700 mg EPA, 600 mg DHA) or placebo for 12 weeks. Outcomes included behavior (Aberrant Behavior Checklist [ABC]) and social responsiveness.

Findings: Omega-3s showed no significant improvement in ABC scores (p=0.45) or social responsiveness compared to placebo. A trend toward reduced hyperactivity was noted (p=0.06). Adverse events were minimal (mild diarrhea in 4%).

Link: Journal of Autism and Developmental Disorders

Omega-3 Fatty Acid Supplementation for Prevention of Postoperative Atrial Fibrillation After Cardiac Surgery: The OPERA Trial

Study: This 2012 randomized, double-blind, placebo-controlled trial (NCT00970489) involved 1,516 patients undergoing cardiac surgery. Participants received 8–10 g omega-3s (EPA+DHA, 1:1 ratio) or placebo preoperatively and 2 g/day post-surgery until discharge or day 10. The primary endpoint was postoperative atrial fibrillation (POAF).

Findings: Omega-3s did not significantly reduce POAF incidence (30.7% vs. 30.0% in placebo, OR 0.96, 95% CI 0.77–1.20, p=0.74). Adverse events were similar, with mild gastrointestinal issues in 8% of the omega-3 group.

Link: JAMA