Omega-3 / Fish Oil
Research reviewed: Up until 03/2026
Omega-3 / Fish Oil (EPA & DHA (Eicosapentaenoic acid & Docosahexaenoic acid)) is a dietary supplement with 18 published peer-reviewed studies involving 113,286 participants, researched for Cardiovascular Health, Inflammation & Joint Health, Depression & Mental Health and 2 more areas.
Evidence at a Glance
Strength is scored by study design, sample size, study type, and outcomes
Cardiovascular Health
ModerateInflammation & Joint Health
ModerateDepression & Mental Health
ModerateCognitive Health
WeakTriglyceride Reduction
ModerateResearch Visualised
Visual breakdown of the clinical data.
Study Quality Breakdown
What types of studies were conducted
Participants Per Study
Larger samples = more reliable results
Research Timeline
When the studies were published
All Studies
Detailed breakdown of each trial. Click to expand.
Cardiovascular Health
To determine whether icosapent ethyl (highly purified EPA) reduces cardiovascular events in statin-treated patients with elevated triglycerides.
Study Type
Phase 3b, multicenter, randomised, double-blind, placebo-controlled trial (REDUCE-IT)
Purpose
To determine whether icosapent ethyl (highly purified EPA) reduces cardiovascular events in statin-treated patients with elevated triglycerides.
Dose
4 g/day of icosapent ethyl (pure EPA ethyl ester), taken as 2 g twice daily
Participants
8,179 patients aged 45+ with established cardiovascular disease, or 50+ with diabetes plus additional risk factors
Duration
Median follow-up of 4.9 years
Results
The study found a significant 25% relative risk reduction in the primary composite endpoint of major cardiovascular events. The primary endpoint occurred in 17.2% of the EPA group versus 22.0% in the placebo group. Cardiovascular death was reduced by 20%. Total ischaemic events were reduced by 30%. A small increase in atrial fibrillation hospitalisation was observed (3.1% vs 2.1%). This is considered the landmark trial for high-dose EPA in cardiovascular prevention.
How They Measured It
Composite primary endpoint: cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularisation, or unstable angina requiring hospitalisation.
To test whether EPA added to statin therapy reduces major coronary events in hypercholesterolaemic patients in Japan.
Study Type
Prospective, randomised, open-label, blinded endpoint analysis (JELIS)
Purpose
To test whether EPA added to statin therapy reduces major coronary events in hypercholesterolaemic patients in Japan.
Dose
1,800 mg/day of purified EPA added to low-dose statin therapy (pravastatin 10 mg or simvastatin 5 mg)
Participants
18,645 patients with total cholesterol ≥6.5 mmol/L, mean age 61, 69% female
Duration
Mean follow-up of 4.6 years
Results
The study found a significant 19% relative reduction in major coronary events (2.8% in the EPA group versus 3.5% in the control group). The benefit was primarily driven by a reduction in unstable angina. Notably, the benefit was not explained by cholesterol lowering alone, suggesting EPA has additional cardioprotective mechanisms beyond lipid effects. Patients in the secondary prevention subgroup gained the most benefit.
How They Measured It
Primary endpoint: major coronary events including sudden cardiac death, fatal and non-fatal MI, unstable angina, and coronary revascularisation.
To test whether omega-3 fatty acids and/or vitamin E reduce mortality and cardiovascular events in patients who recently survived a heart attack.
Study Type
Randomised, open-label trial with 2×2 factorial design (GISSI-Prevenzione)
Purpose
To test whether omega-3 fatty acids and/or vitamin E reduce mortality and cardiovascular events in patients who recently survived a heart attack.
Dose
1 g/day of omega-3 PUFA (approximately 850 mg EPA+DHA as ethyl esters)
Participants
11,324 patients surviving recent myocardial infarction
Duration
3.5 years
Results
Omega-3 supplementation was associated with a 15% reduction in the composite primary endpoint, a 21% reduction in total mortality, a 30% reduction in cardiovascular mortality, and a striking 45% reduction in sudden cardiac death. Vitamin E showed no significant benefit. Researchers estimated 5.7 lives saved per 1,000 patients treated per year. This was one of the first large trials establishing omega-3 benefits post-heart attack.
How They Measured It
Composite of death, nonfatal MI, and nonfatal stroke.
To test whether daily omega-3 fatty acids reduce the risk of cancer and cardiovascular disease in the general population (primary prevention).
Study Type
Nationwide, randomised, double-blind, placebo-controlled, 2×2 factorial trial (VITAL)
Purpose
To test whether daily omega-3 fatty acids reduce the risk of cancer and cardiovascular disease in the general population (primary prevention).
Dose
1 g/day of marine omega-3 (460 mg EPA + 380 mg DHA as fish oil)
Participants
25,871 US adults (men ≥50 and women ≥55), including 5,106 African Americans
Duration
Median 5.3 years
Results
No significant reduction in the primary endpoint of major cardiovascular events overall. However, notable secondary findings included a 28% reduction in heart attack risk and a 50% reduction in fatal heart attacks. People with low baseline fish intake saw a 19% reduction in major cardiovascular events. African American participants showed a particularly strong reduction in heart attack risk. No benefit was found for cancer prevention.
How They Measured It
Co-primary endpoints: major cardiovascular events (MI, stroke, CV death) and invasive cancer of any type.
To test whether omega-3 PUFA reduces mortality and morbidity in patients with chronic heart failure.
Study Type
Randomised, double-blind, placebo-controlled trial (GISSI-HF)
Purpose
To test whether omega-3 PUFA reduces mortality and morbidity in patients with chronic heart failure.
Dose
1 g/day of n-3 PUFA (EPA+DHA)
Participants
6,975 patients with NYHA class II-IV heart failure
Duration
Median follow-up of 3.9 years
Results
The study found a significant 9% reduction in all-cause mortality and an 8% reduction in the composite of mortality plus cardiovascular hospitalisation. In per-protocol analysis of patients who consistently took the supplement, the reduction in all-cause death was 14%. A small but significant improvement in left ventricular ejection fraction was also observed. The benefits were modest but consistent.
How They Measured It
Co-primary endpoints: time to death from any cause, and time to death or admission to hospital for cardiovascular reasons.
To determine whether a combined EPA+DHA formulation reduces cardiovascular events in high-risk statin-treated patients with hypertriglyceridaemia.
Study Type
Double-blind, randomised, multicenter, placebo-controlled trial (STRENGTH)
Purpose
To determine whether a combined EPA+DHA formulation reduces cardiovascular events in high-risk statin-treated patients with hypertriglyceridaemia.
Dose
4 g/day of omega-3 carboxylic acids (EPA + DHA combined), corn oil as comparator
Participants
13,078 statin-treated patients at high cardiovascular risk, mean age 62.5, 35% women, 70% with diabetes
Duration
Stopped early for futility; median follow-up approximately 3.5 years
Results
No cardiovascular benefit was found. The primary composite endpoint occurred in 12.0% of the omega-3 group versus 12.2% of the placebo group. The trial was stopped early for futility. Higher rates of gastrointestinal adverse events and atrial fibrillation were observed with the active treatment. This is an important contrast with REDUCE-IT: STRENGTH used mixed EPA+DHA while REDUCE-IT used pure EPA, suggesting DHA may counteract some of EPA's cardiovascular benefits.
How They Measured It
Composite of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularisation, or hospitalised unstable angina.
Inflammation & Joint Health
To determine if high-dose fish oil allows rheumatoid arthritis patients to discontinue NSAIDs without disease flare, and to assess clinical and immune effects.
Study Type
Double-blind, placebo-controlled, prospective randomised controlled trial
Purpose
To determine if high-dose fish oil allows rheumatoid arthritis patients to discontinue NSAIDs without disease flare, and to assess clinical and immune effects.
Dose
130 mg/kg/day of omega-3 fatty acids (approximately 3.5-5 g/day EPA+DHA from fish oil concentrate: 44% EPA, 24% DHA). Corn oil capsules as placebo.
Participants
66 patients with definite or classic rheumatoid arthritis
Duration
26-30 weeks (18-22 weeks on diclofenac + supplements, then 8 weeks after NSAID discontinuation)
Results
Researchers observed significant decreases in tender joints, morning stiffness (reduced by 67.7 minutes), physician and patient global assessments, and physician pain evaluation in the fish oil group. These improvements persisted 8 weeks after stopping NSAIDs. The inflammatory marker IL-1-beta was also significantly reduced. No improvements were seen in the corn oil placebo group. This suggests high-dose fish oil may reduce the need for anti-inflammatory medication in RA.
How They Measured It
Tender joint count, morning stiffness duration, physician and patient global assessments, physician pain evaluation, IL-1-beta levels.
To evaluate whether omega-3 PUFAs reduce the need for NSAID use in rheumatoid arthritis patients.
Study Type
Systematic review and meta-analysis of randomised controlled trials
Purpose
To evaluate whether omega-3 PUFAs reduce the need for NSAID use in rheumatoid arthritis patients.
Dose
Studies used doses >2.7 g/day of omega-3 for >3 months
Participants
10 RCTs involving 183 RA patients on omega-3 and 187 on placebo
Duration
All included trials >3 months
Results
The meta-analysis found that omega-3 clearly and significantly reduced NSAID consumption in RA patients, with no heterogeneity between studies. The researchers concluded that omega-3 at doses above 2.7 g/day for more than 3 months significantly reduces the need for anti-inflammatory medication in rheumatoid arthritis.
How They Measured It
Standardised mean difference in NSAID consumption across pooled RCTs.
To evaluate the effect of omega-3 fatty acids as adjunctive therapy in patients with active rheumatoid arthritis already receiving disease-modifying drugs.
Study Type
Double-blind, randomised, placebo-controlled trial
Purpose
To evaluate the effect of omega-3 fatty acids as adjunctive therapy in patients with active rheumatoid arthritis already receiving disease-modifying drugs.
Dose
Approximately 3 g/day EPA+DHA
Participants
60 patients (49 females, 11 males) with active rheumatoid arthritis
Duration
12 weeks
Results
76% of patients receiving omega-3 reported satisfaction with their treatment compared to only 37.5% in the placebo group. Improvements in disease activity measures were observed. The study supports the use of omega-3 as an additional therapy alongside standard RA medications.
How They Measured It
Disease activity measures and patient satisfaction ratings.
Depression & Mental Health
To test whether omega-3 supplementation improves symptoms in patients with major depressive disorder, as an add-on to usual treatment.
Study Type
Double-blind, placebo-controlled randomised controlled trial
Purpose
To test whether omega-3 supplementation improves symptoms in patients with major depressive disorder, as an add-on to usual treatment.
Dose
9.6 g/day of omega-3 PUFAs (EPA+DHA combined)
Participants
28 outpatients aged 18-60 with DSM-IV major depressive disorder
Duration
8 weeks
Results
Participants taking omega-3 had significantly greater improvements in depression scores compared to placebo. Significant differences appeared as early as week 4 and continued through weeks 6 and 8. The rate of depression score reduction was significantly faster in the omega-3 group. The treatment was well tolerated with no significant side effects.
How They Measured It
Hamilton Rating Scale for Depression (HRSD) scores at baseline and weeks 4, 6, and 8.
To estimate the overall efficacy of omega-3 PUFAs (EPA and DHA) for depression and identify the optimal formulations.
Study Type
Systematic review and meta-analysis of 26 double-blind randomised controlled trials
Purpose
To estimate the overall efficacy of omega-3 PUFAs (EPA and DHA) for depression and identify the optimal formulations.
Dose
Varied across studies; key finding was EPA at doses ≤1 g/day in formulations with ≥60% EPA was most effective
Participants
26 double-blind RCTs including 2,160 participants with depression
Duration
Varied across included trials
Results
The meta-analysis found an overall beneficial effect of omega-3 on depression. Crucially, formulations with pure EPA or predominantly EPA (≥60% of total omega-3) were the ones that showed significant benefit. DHA-only formulations showed no significant antidepressant effect. The optimal dose appears to be EPA at 1 g/day or less. This suggests the antidepressant effect of fish oil is driven specifically by EPA, not DHA.
How They Measured It
Standardised mean difference in depression outcome measures across pooled RCTs.
To test whether omega-3 supplementation prevents late-life depression in the general adult population.
Study Type
Randomised, double-blind, placebo-controlled trial (VITAL-DEP, ancillary to VITAL)
Purpose
To test whether omega-3 supplementation prevents late-life depression in the general adult population.
Dose
1 g/day of fish oil (465 mg EPA + 375 mg DHA)
Participants
18,353 adults, mean age 67.5 years, 49.2% women; 16,657 at risk of incident depression and 1,696 at risk of recurrent depression
Duration
Median 5.3 years
Results
Omega-3 showed no benefit for preventing depression or improving mood in the general population. A slight, nominally significant increased risk of depression was observed in the omega-3 group, though no meaningful differences in mood scores over follow-up were found. The study concluded that omega-3 supplements should not be used solely to prevent depression in adults who are not already depressed.
How They Measured It
Incident and recurrent depression diagnoses, mood scores (PHQ-8).
Cognitive Health
To evaluate whether omega-3 supplementation slows cognitive decline in patients with mild to moderate Alzheimer's disease.
Study Type
Randomised, double-blind, placebo-controlled trial (OmegAD Study)
Purpose
To evaluate whether omega-3 supplementation slows cognitive decline in patients with mild to moderate Alzheimer's disease.
Dose
1,720 mg DHA + 600 mg EPA per day. Placebo: 4,000 mg corn oil.
Participants
204 patients with mild to moderate Alzheimer's disease; 174 completed the study
Duration
6 months double-blind phase, followed by 6 months open-label omega-3 for both groups
Results
No significant cognitive benefit was found in the overall group on any measure at 6 or 12 months. However, a pre-specified subgroup of 32 patients with very mild cognitive impairment (MMSE >27) showed a significantly slower rate of cognitive decline with omega-3. In this subgroup, placebo patients declined by 2.6 MMSE points versus only 0.5 points with omega-3 over 6 months. This suggests omega-3 may only help if started very early before significant cognitive decline has occurred.
How They Measured It
ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale), MMSE (Mini-Mental State Examination), CDR (Clinical Dementia Rating).
To determine if DHA supplementation slows cognitive and functional decline in patients with mild to moderate Alzheimer's disease.
Study Type
Randomised, double-blind, placebo-controlled trial (ADCS-DHA Trial)
Purpose
To determine if DHA supplementation slows cognitive and functional decline in patients with mild to moderate Alzheimer's disease.
Dose
2 g/day of algal-derived DHA
Participants
402 patients with mild-to-moderate Alzheimer's disease at 51 US sites
Duration
18 months
Results
DHA supplementation did not slow cognitive decline, functional decline, or brain atrophy on any primary or secondary outcome measure. However, in a subgroup analysis, patients who did not carry the APOE-e4 gene (a genetic risk factor for Alzheimer's) showed significantly slower cognitive decline with DHA treatment. This suggests that genetic factors may influence whether someone responds to omega-3 for brain health.
How They Measured It
Rate of change on ADAS-cog, CDR sum of boxes, activities of daily living, brain volume on MRI.
To test whether DHA supplementation improves cognitive function in healthy older adults with age-related cognitive decline (not dementia).
Study Type
Randomised, double-blind, placebo-controlled trial (MIDAS - Memory Improvement with DHA Study)
Purpose
To test whether DHA supplementation improves cognitive function in healthy older adults with age-related cognitive decline (not dementia).
Dose
900 mg/day of algal DHA
Participants
485 healthy subjects aged ≥55 with mild memory complaints (MMSE >26)
Duration
24 weeks (6 months)
Results
Participants taking DHA made significantly fewer errors on visual and spatial memory tests and showed improved immediate and delayed verbal recognition memory compared to placebo. Blood DHA levels doubled and were directly correlated with the degree of cognitive improvement. The researchers described the benefit as equivalent to having the learning and memory skills of someone approximately 3 years younger. DHA was well tolerated.
How They Measured It
CANTAB Paired Associate Learning test (visuospatial memory), Verbal Recognition Memory test.
Triglyceride Reduction
To evaluate the efficacy and safety of icosapent ethyl (pure EPA) for lowering triglycerides in patients with very high levels (≥500 mg/dL).
Study Type
Multicenter, randomised, double-blind, placebo-controlled Phase III trial (MARINE Trial)
Purpose
To evaluate the efficacy and safety of icosapent ethyl (pure EPA) for lowering triglycerides in patients with very high levels (≥500 mg/dL).
Dose
Icosapent ethyl 4 g/day or 2 g/day versus placebo
Participants
229 patients with very high triglycerides (≥500 and ≤2,000 mg/dL)
Duration
12 weeks
Results
At the 4 g/day dose, triglycerides were reduced by 33.1% compared to placebo. Non-HDL cholesterol was reduced by 15.7%, and total cholesterol by 14.9%. Plasma EPA levels increased by over 500%. Importantly, unlike other omega-3 products, LDL cholesterol did not increase. The treatment also reduced various harmful lipoprotein particles.
How They Measured It
Percentage change in fasting triglycerides, non-HDL-C, total cholesterol, LDL-C, and other lipid markers from baseline.
To evaluate icosapent ethyl in statin-treated patients with persistent high triglycerides (200-499 mg/dL) despite having controlled LDL cholesterol.
Study Type
Randomised, double-blind, placebo-controlled Phase III trial (ANCHOR Trial)
Purpose
To evaluate icosapent ethyl in statin-treated patients with persistent high triglycerides (200-499 mg/dL) despite having controlled LDL cholesterol.
Dose
Icosapent ethyl 4 g/day or 2 g/day versus placebo
Participants
702 statin-treated patients; 73% with diabetes, 39% women
Duration
12 weeks
Results
At 4 g/day, triglycerides were reduced by 21.5%, non-HDL cholesterol by 13.6%, and VLDL cholesterol by 24.4%. The inflammatory marker hsCRP was reduced by 22%, and oxidised LDL (a marker of harmful cholesterol) was reduced by 13.3%. Plasma EPA levels increased by 637%. No increase in LDL cholesterol was observed. Safety profile was similar to placebo.
How They Measured It
Percentage change in triglycerides, non-HDL-C, VLDL-C, hsCRP, oxidised LDL, ApoB, and other biomarkers.
To evaluate the efficacy and safety of omega-3 free fatty acids at multiple doses for lowering triglycerides in patients with severe hypertriglyceridaemia.
Study Type
Randomised, double-blind, placebo-controlled, dose-ranging trial (EVOLVE Trial)
Purpose
To evaluate the efficacy and safety of omega-3 free fatty acids at multiple doses for lowering triglycerides in patients with severe hypertriglyceridaemia.
Dose
2 g/day, 3 g/day, or 4 g/day of omega-3 carboxylic acids (EPA+DHA) versus olive oil placebo
Participants
Patients with very high triglycerides (≥500 mg/dL)
Duration
12 weeks
Results
Triglyceride reduction was dose-dependent: 2 g/day reduced triglycerides by 25.9%, 3 g/day by 25.5%, and 4 g/day by 30.9%, compared to only 4.3% decline with placebo. All three doses were significantly better than placebo. The results suggest a near-maximal triglyceride-lowering effect is achieved at 4 g/day.
How They Measured It
Percentage change in triglycerides from baseline at multiple dose levels.
Frequently Asked Questions
Common questions about Omega-3 / Fish Oil research
There are currently 18 peer-reviewed studies on Omega-3 / Fish Oil (EPA & DHA (Eicosapentaenoic acid & Docosahexaenoic acid)), involving 113,286 total participants. Research covers Cardiovascular Health, Inflammation & Joint Health, Depression & Mental Health and 2 more areas. The overall evidence strength is rated as Strong.
The evidence is currently rated as "Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (16 human studies), and reported outcomes.
Omega-3 / Fish Oil has been researched for: Cardiovascular Health, Inflammation & Joint Health, Depression & Mental Health, Cognitive Health, Triglyceride Reduction. Each area has its own body of evidence which you can explore in the study breakdowns above.
Yes, 16 out of 18 studies are human trials. Human trials carry more weight in our evidence scoring system.
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