Research

EPA (Eicosapentaenoic Acid)

129 peer-reviewed studies curated from PubMed and Semantic Scholar.

14
Meta-analyses
5
Systematic reviews
95
RCTs
15
Other studies
Meta-analyses (11%)
Systematic reviews (4%)
RCTs (74%)
Observational (1%)

Studies

Sorted by quality and recency

2026·FASEB journal : official publication of the Federation of American Societies for Experimental Biology·Zhenxing Li, Bing Zhang

Effects of Omega-3 Supplementation on Inflammation and Recovery in Sports: A Meta-Analysis.

Meta-analysisInflammation Recovery

Meta-analysis of 41 RCTs on EPA and DHA supplementation, showing significant reductions in markers of inflammation and muscle injury, such as interleukin-6 and creatine kinase. Doses of 2g/day or more for at least 6 weeks were most effective, particularly in recreational athletes.

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2025·Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer·Hanlin Lu, Zhihua Zhang, Fengxia Liu

Comparison of EPA and DHA&EPA on body weight, BMI, and lean body mass in cancer patients: a network meta-analysis.

Meta-analysisn = 1,892Nutrition Physique

Network meta-analysis of 26 RCTs involving 1892 cancer patients comparing EPA alone vs. DHA&EPA combined supplementation. DHA&EPA showed significant improvements in body weight and BMI, but no significant effects on lean body mass. Confidence in evidence was moderate to high for body weight and BMI, and moderate for lean body mass.

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2025·Acta cardiologica·John P Sheppard, Suvasini Lakshmanan, Leonard Palatnic, et al

Effects of purified eicosapentaenoic acid versus mixed eicosapentaenoic/docosahexaenoic acid pharmacotherapies on coronary plaque volume: network meta-analysis of prospective coronary imaging trials.

Meta-analysisn = 860Heart Health

Network meta-analysis of 10 trials with 860 patients comparing the effects of EPA versus EPA/DHA on coronary plaque volume. EPA, when combined with statins, significantly reduced coronary plaque volumes, whereas EPA/DHA did not show a consistent benefit.

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2024·Journal of the American Heart Association·Mustafa Javaid, Kadhim Kadhim, Bilal Bawamia, et al

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Meta-analysisn = 120,643Heart Health

Systematic review and meta-analysis of 11 RCTs with 120,643 patients assessing bleeding risk associated with omega-3 PUFAs. No overall increased bleeding risk was found, but high-dose purified EPA showed a modest increase in bleeding risk.

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2024·Food & function·Siqi Luo, Hongmei Hou, Yongjin Wang, et al

Effects of omega-3, omega-6, and total dietary polyunsaturated fatty acid supplementation in patients with atherosclerotic cardiovascular disease: a systematic review and meta-analysis.

Meta-analysisn = 40,861Heart Health Longevity

This systematic review and meta-analysis included 21 publications from 17 studies with 40,861 participants, examining the effects of omega-3, omega-6, and total PUFA intake on mortality and cardiovascular events in ASCVD patients. Omega-3 intake was associated with reduced all-cause mortality, CVD mortality, and CVD events, while omega-6 and total PUFA showed no significant effects.

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2024·Circulation·Katsumi Miyauchi, Hiroshi Iwata, Yuji Nishizaki, et al

Randomized Trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy-Statin and Eicosapentaenoic Acid (RESPECT-EPA).

RCTn = 3,884Heart Health

This randomized trial evaluated the efficacy of icosapent ethyl (EPA) in patients with coronary artery disease and low EPA/AA ratio on statin treatment. Over 5 years, the primary endpoint of cardiovascular events was numerically lower in the EPA group but did not reach statistical significance. The secondary endpoint of coronary events was significantly lower in the EPA group, though new-onset atrial fibrillation was higher.

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2023·Prostaglandins, leukotrienes, and essential fatty acids·Christos F Kelaiditis, E Leigh Gibson, Simon C Dyall

Effects of long-chain omega-3 polyunsaturated fatty acids on reducing anxiety and/or depression in adults; A systematic review and meta-analysis of randomised controlled trials.

Meta-analysisn = 1,426Mood

Systematic review and meta-analysis of 10 RCTs with 1426 participants assessing the efficacy of EPA, DHA, and DPAn-3 in reducing anxiety and depression severity. Significant reduction in depression severity was found with EPA-enriched interventions at specific doses, but mixed findings and publication bias were noted.

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2023·Prostaglandins, leukotrienes, and essential fatty acids·H Fuller, A D Race, H Fenton, et al

Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial.

RCTn = 401

This study measured plasma and rectal mucosal oxylipins in participants of the seAFOod trial, who received aspirin and EPA, alone and in combination, for 12 months. The study confirmed that prolonged treatment with EPA is associated with increased plasma 18-HEPE concentrations, which correlate with rectal mucosal levels, but do not predict polyp prevention efficacy.

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2023·Journal of Clinical Ophthalmology and Research·M. Patil, Ravindra Banakar, B. Manjunath, et al

An open-label randomized clinical trial to evaluate the efficacy and tolerability of flax seed nutritional supplementation in comparison with omega-3 fatty acid capsule in mild dry eye disease

RCTn = 268

Open-label randomized clinical trial comparing flax seed supplementation to omega-3 fatty acid capsules in 268 subjects with mild dry eye disease over 3 months. Both treatments improved Schirmer test and TBUT scores, with no significant difference between groups in OSDI scores. Flax seed is a cost-effective alternative for dry eye treatment.

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2023·Atherosclerosis·Essa Hariri, Abdul Aziz Asbeutah, Abdulaziz Malik, et al

Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.

RCTn = 242Heart Health -

Secondary analysis of a randomized trial with 242 patients with coronary artery disease on statin therapy, comparing 1.86g EPA and 1.5g DHA daily to control over 30 months. Both groups showed significant progression in coronary artery calcium scores, with no significant difference between them, despite a reduction in triglyceride levels with EPA and DHA.

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2022·Journal of cardiology·Yujiro Yokoyama, Toshiki Kuno, Sae X Morita, et al

Eicosapentaenoic Acid for Cardiovascular Events Reduction- Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Meta-analysisn = 141,009Heart Health

Systematic review and network meta-analysis of 17 RCTs with 141,009 patients comparing omega-3 fatty acid supplementation (EPA, EPA+DHA) to various placebo oils for cardiovascular outcomes. EPA reduced rates of cardiovascular death, myocardial infarction, and stroke compared to mineral oil but not other oils or controls. Combined EPA+DHA reduced cardiovascular death risk compared to controls.

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2022·Progress in lipid research·Bo Yang, Ping-Tao Tseng, Xiang Hu, et al

Comparative efficacy of omega-3 polyunsaturated fatty acids on major cardiovascular events: A network meta-analysis of randomized controlled trials.

Meta-analysisn = 88,359Heart Health

Network meta-analysis of 39 RCTs with 88,359 participants assessing the efficacy of omega-3 PUFAs on major cardiovascular events. Pure EPA was found to be the best option for secondary prevention, while no efficacy was observed for primary prevention.

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2022·Journal of internal medicine·Peder L Myhre, Are A Kalstad, Sjur H Tveit, et al

Changes in eicosapentaenoic acid and docosahexaenoic acid and risk of cardiovascular events and atrial fibrillation: A secondary analysis of the OMEMI trial.

RCTn = 881Heart Health

Secondary analysis of the OMEMI trial assessing changes in EPA and DHA serum concentrations during n-3 PUFA supplementation in elderly patients post-AMI. Greater increases in EPA were associated with lower risk of major adverse cardiovascular events but higher risk of new-onset atrial fibrillation.

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2022·Nutrition reviews·Rena I Kosti, Maria I Kasdagli, Andreas Kyrozis, et al

Fish intake, n-3 fatty acid body status, and risk of cognitive decline: a systematic review and a dose-response meta-analysis of observational and experimental studies.

Meta-analysisBrain Health

Systematic review and meta-analysis evaluating the association between fish intake, EPA/DHA supplementation, and cognitive decline. Fish intake of up to 2 portions per week was associated with reduced risk of dementia and Alzheimer's Disease. EPA and DHA positively impacted executive functions but not overall cognitive performance.

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2021·Mechanisms of ageing and development·Mariangela Rondanelli, Simone Perna, Antonella Riva, et al

Effects of n-3 EPA and DHA supplementation on fat free mass and physical performance in elderly. A systematic review and meta-analysis of randomized clinical trial.

Meta-analysisn = 2,220Physical Performance Physique

Systematic review and meta-analysis of 14 RCTs with 2220 participants on n-3 EPA and DHA supplementation in the elderly. Supplementation decreased Time Up and Go test time but showed no significant effects on other physical performance indicators. Fat free mass showed a non-significant improvement trend.

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2018·Journal of psychiatric research·Muhammad Abdullah, Benjamin Jowett, Paula Jane Whittaker, et al

The effectiveness of omega-3 supplementation in reducing ADHD associated symptoms in children as measured by the Conners' rating scales: A systematic review of randomized controlled trials.

Systematic reviewn = 926Brain Health -

Systematic review of randomized controlled trials examining the effectiveness of omega-3 supplementation in reducing ADHD symptoms in children and adolescents. The review included seven trials with a total of 926 participants. Overall, there was a slightly greater reduction in Conners' rating scale score in the experiment group, but findings were not statistically significant.

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2014·Nephrology (Carlton, Vic.)·Thida M Myint, Gopi K Rangan, Angela C Webster

Treatments to slow progression of autosomal dominant polycystic kidney disease: systematic review and meta-analysis of randomized trials.

Meta-analysisn = 2,262

Meta-analysis of randomized trials assessing interventions for autosomal dominant polycystic kidney disease (ADPKD). Eicosapentaenoic acid was studied in a single trial and did not alter the progression of total kidney volume or renal dysfunction. Somatostatin analogues and vasopressin receptor antagonists showed some efficacy in attenuating TKV increase.

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2007·Lancet (London, England)·Mitsuhiro Yokoyama, Hideki Origasa, Masunori Matsuzaki, et al

Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.

RCTn = 18,645Heart Health

RCT of 18,645 hypercholesterolaemic patients in Japan comparing 1800 mg of EPA daily with statin to statin only over a mean follow-up of 4.6 years. EPA group showed a 19% relative reduction in major coronary events compared to controls, with significant reductions in unstable angina and non-fatal coronary events.

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2000·The Cochrane database of systematic reviews·C B Joy, R Mumby-Croft, L A Joy

Polyunsaturated fatty acid (fish or evening primrose oil) for schizophrenia.

Systematic reviewn = 204Mental Clarity

Systematic review of polyunsaturated fatty acid supplementation in schizophrenia treatment. Four trials (n=204) suggest a positive effect of eicosapentaenoic acid (EPA) on mental state outcomes, though data is limited. EPA may help avoid standard antipsychotic drugs in some cases, while primrose oil showed no clear effects.

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2024·Journal of clinical lipidology·Maral Amangurbanova, Ralph Daher, Abdul Aziz Asbeutah, et al

Higher epicardial adipose tissue volume is associated with higher coronary fatty plaque volume and is regulated by waist circumference but not EPA+DHA supplementation.

RCTn = 139Heart Health -

RCT of 139 CAD patients on statins, randomized to 3.36 g EPA+DHA daily or control for 30 months. EPA+DHA supplementation reduced triglycerides by 6.7% but did not affect epicardial adipose tissue volume (EATV), which was regulated by waist circumference. EATV was associated with higher coronary fatty plaque volume.

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2024·Nutrients·Bodo Speckmann, Tanja Wagner, Paul M Jordan, et al

SynbioticDSM 32963 and n-3 PUFA Salt Composition Elevates Pro-Resolving Lipid Mediator Levels in Healthy Subjects: A Randomized Controlled Study.

RCTn = 72Inflammation

RCT with 72 healthy participants comparing SynΩ3 (EPA and DHA lysine salts with Bacillus megaterium) to placebo and fish oil. SynΩ3 significantly increased circulating SPM precursor levels, suggesting potential benefits for inflammation resolution.

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2024·Brain, behavior, and immunity·Hsueh-Fang Wang, Wen-Chun Liu, Halliru Zailani, et al

A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine.

RCTn = 70Brain Health Womens Health Mood

A 12-week randomized, double-blind, placebo-controlled trial evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine prevention in 70 individuals. The EPA group showed significant reductions in monthly migraine days, headache severity, and improvements in disability, anxiety, depression, and quality of life compared to placebo. The study suggests high-dose EPA as a potential prophylactic for episodic migraine management.

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2024·Frontiers in pharmacology·Agian Jeffilano Barinda, Harri Hardi, Melva Louisa, et al

Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress.

Systematic reviewLongevity

Systematic review of animal studies and clinical trial registries analyzing the repurposing potential of cardiometabolic drugs to increase lifespan. Metformin, acarbose, and aspirin are the most studied in animal trials, with omega-3 fatty acid and metformin showing potential in clinical trials for targeting aging.

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2024·The Journal of nutrition·Ge Sun, Harriett Fuller, Hayley Fenton, et al

The Relationship Between Dietary and Supplemental omega-3 Highly Unsaturated Fatty Acid Intake, Blood and Tissue omega-3 Highly Unsaturated Fatty Acid Concentrations, and Colorectal Polyp Recurrence: A Secondary Analysis of the seAFOod Polyp Prevention Trial.

RCT

Secondary analysis of the seAFOod trial investigating the relationship between omega-3 HUFA intake and colorectal polyp outcomes. The study found that individuals with a higher change in EPA concentration had a lower polyp detection rate and reduced polyp number, suggesting a protective effect of EPA on colorectal polyp recurrence.

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2023·Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology·Stefania Lamon-Fava, Minying Liu, Boadie W Dunlop, et al

Clinical response to EPA supplementation in patients with major depressive disorder is associated with higher plasma concentrations of pro-resolving lipid mediators.

RCTn = 61Mood Inflammation

A 12-week randomized trial with 61 patients with major depressive disorder tested EPA supplementation at 1, 2, and 4 g/d against placebo. The 4 g/d EPA group showed higher response rates in depression symptom reduction and greater increases in pro-resolving lipid mediators, suggesting a positive effect on mood and inflammation.

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2023·PloS one·Scott T Minton, Anthony L Almada, Joseph L Evans, et al

Comparative membrane incorporation of omega-3 fish oil triglyceride preparations differing by degree of re-esterification: A sixteen-week randomized intervention trial.

RCTn = 60

This 128-day double-blind, parallel-design study randomized 60 young, healthy subjects into two groups to compare the blood lipidomic response to two rTG fish oil supplements differing by degree of re-esterification. The Ultimate Omega group showed significantly greater erythrocyte PLFA profiles and serum PLFA ratios compared to the MEG-3 group, suggesting the percentage of rTG in fish oil preparations may influence lipidomic pharmacodynamics.

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2022·European archives of psychiatry and clinical neuroscience·Sara Carucci, Roberta Romaniello, Giovanni Demuru, et al

Omega-3/6 supplementation for mild to moderate inattentive ADHD: a randomised, double-blind, placebo-controlled efficacy study in Italian children.

RCTn = 160Focus -

RCT evaluating the efficacy of Omega-3/6 supplementation in Italian children with inattentive ADHD. No significant superiority of Omega-3/6 over placebo was observed on the primary outcome of ADHD-RS-inattention score after 6 months. A mild, non-clinically significant improvement was noted on the ADHD-RS-total score.

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2022·Journal of the American Heart Association·Kevin C Maki, Harold E Bays, Christie M Ballantyne, et al

A Head-to-Head Comparison of a Free Fatty Acid Formulation of Omega-3 Pentaenoic Acids Versus Icosapent Ethyl in Adults With Hypertriglyceridemia: The ENHANCE-IT Study.

RCTn = 100Heart Health Inflammation

This open-label, randomized, 2-way crossover trial compared the pharmacodynamic responses and plasma omega-3 levels of EPA+DPA-FFA and EPA-EE in 100 hypertriglyceridemic subjects. EPA+DPA-FFA significantly increased plasma EPA, DPA, and total omega-3 levels more than EPA-EE and reduced triglycerides and high-sensitivity C-reactive protein without increasing LDL cholesterol.

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2022·The Journal of clinical psychiatry·David Mischoulon, Boadie W Dunlop, Becky Kinkead, et al

Omega-3 Fatty Acids for Major Depressive Disorder With High Inflammation: A Randomized Dose-Finding Clinical Trial.

RCTn = 61Mood Inflammation

This randomized clinical trial compared the effects of three doses of eicosapentaenoic acid (EPA) versus placebo on inflammatory biomarkers and depressive symptoms in 61 unmedicated adults with major depressive disorder and high inflammation. EPA 4 g/d showed a medium effect size for response rates versus placebo, potentially alleviating MDD in overweight individuals with elevated inflammatory markers.

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2022·Food & function·Xinwen Ding, Yinfei Xu, Pan Nie, et al

Changes in the serum metabolomic profiles of subjects with NAFLD in response to n-3 PUFAs and phytosterol ester: a double-blind randomized controlled trial.

RCTNutrition

Double-blind RCT investigating the effects of co-supplementation with n-3 PUFAs and phytosterol ester on serum metabolomic profiles in subjects with NAFLD. The study found that the combination was more effective at improving metabolic disorders and ameliorating hepatic steatosis than either supplement alone.

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2021·Pharmacia·Mahmoud S. Abu-Samak, L. Hasoun, Abeer Barham, et al

The supplementary effects of omega-3 fatty acid alone and in a combination with vitamin D3 on serum leptin levels: A randomized clinical trial on men and women with vitamin D deficiency

RCTn = 146

This RCT assessed the effects of omega-3 fatty acids (n-3FA), vitamin D3 (VD3), and their combination on serum leptin levels in 146 participants with vitamin D deficiency. The n-3FA group showed a significant increase in serum leptin and triglyceride levels. The combination therapy significantly increased serum 25OHD and triglyceride levels, with an insignificant increase in serum leptin.

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2020·Journal of pediatric endocrinology & metabolism : JPEM·Mardia Guadalupe López-Alarcón, Víctor Saúl Vital-Reyes, Francisco Iván Hernández-Hernández, et al

The role of LCPUFA-ω3 on the obesity-associated hyperandrogenemia of pubertal girls: secondary analysis of a randomized clinical trial.

RCTn = 117Hormone Health

Secondary analysis of a randomized clinical trial examining the effect of LCPUFA-ω3 supplementation on hyperandrogenemia in pubertal girls with obesity. The study found that EPA supplementation increased adiponectin and SHBG levels while decreasing free testosterone, suggesting a preventive role of EPA on hyperandrogenemia risk.

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2020·Prostaglandins, leukotrienes, and essential fatty acids·Stefania Lamon-Fava, Jisun So, David Mischoulon, et al

Dose- and time-dependent increase in circulating anti-inflammatory and pro-resolving lipid mediators following eicosapentaenoic acid supplementation in patients with major depressive disorder and chronic inflammation.

RCTn = 61Inflammation

A 12-week randomized trial with 61 MDD patients assessed the effects of EPA supplementation on plasma concentrations of EPA metabolites and SPMs. EPA supplementation increased plasma EPA and EPA-derived metabolites dose-dependently, with significant increases in 18-HEPE and RvE2-3 levels, and a reduction in plasma arachidonic acid.

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2020·Journal of cardiology·Shigemasa Tani, Tsukasa Yagi, Rei Matsuo, et al

Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study.

RCTn = 60Heart Health

This pilot 6-month randomized study investigated the effects of eicosapentaenoic acid (EPA) on lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease. The EPA group showed significant decreases in medium, small, and very small LDL particles, and increases in large and very large HDL particles, suggesting potential anti-atherosclerotic effects.

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2018·Lancet (London, England)·Mark A Hull, Kirsty Sprange, Trish Hepburn, et al

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial.

RCTn = 709

This multicentre, randomised, double-blind, placebo-controlled trial tested the efficacy of eicosapentaenoic acid (EPA) and aspirin, alone and in combination, for the prevention of colorectal adenomas in individuals with sporadic colorectal neoplasia. The study found no significant effect of EPA or aspirin on adenoma detection rate compared to placebo. EPA and aspirin were well tolerated, though gastrointestinal adverse events were higher in the EPA group.

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2018·Journal of clinical lipidology·Abdulhamied Alfaddagh, Tarec K Elajami, Mohamad Saleh, et al

The effect of eicosapentaenoic and docosahexaenoic acids on physical function, exercise, and joint replacement in patients with coronary artery disease: A secondary analysis of a randomized clinical trial.

RCTn = 291Physical Performance Joint Bone Health

Secondary analysis of an RCT with 291 CAD patients comparing Lovaza (EPA and DHA) supplementation to control over 1 year. The Lovaza group showed improved physical function, increased exercise, and reduced joint replacement compared to controls.

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2017·Journal of human nutrition and dietetics : the official journal of the British Dietetic Association·S AbuMweis, S Jew, R Tayyem, et al

Eicosapentaenoic acid and docosahexaenoic acid containing supplements modulate risk factors for cardiovascular disease: a meta-analysis of randomised placebo-control human clinical trials.

Meta-analysisHeart Health Inflammation

Meta-analysis of 171 clinical trials examining the effects of EPA and DHA supplements on cardiovascular risk factors. The analysis found significant reductions in triglycerides, blood pressure, heart rate, and C-reactive protein, with increases in both LDL and HDL cholesterol.

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2016·International journal of cardiology·Kazumasa Nosaka, Toru Miyoshi, Mutsumi Iwamoto, et al

Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study.

RCTn = 241Heart Health

RCT of 241 patients with acute coronary syndrome comparing pitavastatin with or without 1800mg/day of EPA initiated within 24h after PCI. The EPA group had a lower incidence of cardiovascular events and death from cardiovascular causes compared to the control group.

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2015·Drug design, development and therapy·Bruno Amato, Rita Compagna, Maurizio Amato, et al

Aterofisiol(®) in carotid plaque evolution.

RCTn = 214Heart Health

RCT evaluating the effects of Aterofisiol, a supplement containing omega-3, vitamins K2, B6, B12, OPC, and resveratrol, on atherosclerotic plaque composition and neurological symptoms in patients with carotid stenosis. Aterofisiol reduced lipid content in plaques and adverse neurological events compared to placebo.

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2015·Nutricion hospitalaria·Dalila Pinto de Souza Fernandes, Fabiane Aparecida Canaan Rezende, Gabriele Pereira Rocha, et al

EFFECT OF EICOSAPENTAENOIC ACID AND DOCOSAHEXAENOIC ACID SUPPLEMENTATIONS TO CONTROL COGNITIVE DECLINE IN DEMENTIA AND ALZHEIMER'S DISEASE: A SYSTEMATIC REVIEW.

Systematic reviewBrain Health

Systematic review of randomized clinical trials on EPA and DHA supplementation in elderly with dementia or Alzheimer's disease. EPA and/or DHA did not affect cognitive test scores overall, but improved verbal fluency and attention in patients with very mild dementia or APOEε4 negative genotype. No effect on cognitive decline in advanced AD patients.

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2014·American journal of hypertension·Paige E Miller, Mary Van Elswyk, Dominik D Alexander

Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials.

Meta-analysisn = 70Heart Health

Meta-analysis of 70 RCTs examining the effect of EPA and DHA on blood pressure. EPA+DHA provision reduced systolic and diastolic blood pressure, with the strongest effects observed in untreated hypertensive subjects.

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2012·The British journal of nutrition·Elizabeth A Miles, Philip C Calder

Influence of marine n-3 polyunsaturated fatty acids on immune function and a systematic review of their effects on clinical outcomes in rheumatoid arthritis.

Systematic reviewJoint Bone Health Inflammation Immunity

Systematic review of 23 studies examining the effects of marine n-3 PUFAs on rheumatoid arthritis. Evidence suggests a modest benefit on joint swelling, pain, morning stiffness, and disease activity, with reduced use of non-steroidal anti-inflammatory drugs.

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2025·The Journal of nutrition·Neha Balakrishnan, Saame Raza Shaikh, Caroline E Childs, et al

Effects of EPA+DHA and Corn Oil Supplementation on PUFA Concentrations across Plasma Lipid Pools and on Downstream Oxylipins: Exploratory Results from a Randomized Controlled Trial in Healthy Humans.

RCTn = 21Inflammation

Exploratory analysis from a double-blind, placebo-controlled trial with 21 participants, examining the effects of EPA+DHA supplementation on plasma lipid pools and oxylipins. EPA+DHA increased anti-inflammatory oxylipins and decreased proinflammatory oxylipins, with significant changes in lipid pool concentrations compared to corn oil supplementation.

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2024·Clinical nutrition (Edinburgh, Scotland)·Mariëlle P K J Engelen, Sunday Y Simbo, Laura E Ruebush, et al

Functional and metabolic effects of omega-3 polyunsaturated fatty acid supplementation and the role of β-hydroxy-β-methylbutyrate addition in chronic obstructive pulmonary disease: A randomized clinical trial.

RCTn = 46Inflammation Physique

RCT of 46 COPD patients comparing EPA/DHA supplementation with and without HMB to placebo over 10 weeks. EPA/DHA increased lean soft tissue, while HMB+EPA/DHA reduced fat mass and increased protein breakdown, suggesting enhanced protein turnover. Inflammatory cytokines were reduced in the HMB+EPA/DHA group.

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2024·Journal of the American Nutrition Association·Yosuke Tsuchiya, Hisashi Ueda, Takashi Shimizu, et al

Eicosapentaenoic Acid and Medium-Chain Triacylglycerol Structured Lipid Supplementation Improves Muscular Endurance Exercise Performance and Reduces Muscle Fatigue in Young Healthy Male.

RCTn = 20Physical Performance Recovery

This 8-week, placebo-controlled, randomized, double-blind trial studied the effects of EPA/MCT supplementation on muscle endurance and fatigue in 20 healthy young men. The EPA/MCT group showed improved muscle endurance performance and reduced muscle fatigue compared to the placebo group.

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2023·BMC nephrology·Wen-Ching Yang, Hui-Min Hsieh, Jun-Peng Chen, et al

Effects of a low-protein nutritional formula with dietary counseling in older adults with chronic kidney disease stages 3-5: a randomized controlled trial.

RCTn = 47Physical Performance Nutrition

RCT of 47 older adults with CKD stages 3-5 comparing low-protein diet plus a 6% low-protein formula (LPF) to low-protein diet alone. The intervention group showed significant improvements in hand grip strength and gait speed, and higher intake of EPA, DHA, and various micronutrients.

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2023·BMC Oral Health·Mirella Stańdo-Retecka, Paweł Piątek, M. Namiecińska, et al

Clinical and microbiological outcomes of subgingival instrumentation supplemented with high-dose omega-3 polyunsaturated fatty acids in periodontal treatment – a randomized clinical trial

RCTn = 40Inflammation

This randomized clinical trial evaluated the impact of omega-3 PUFA supplementation combined with scaling and root planing in patients with periodontitis. The test group showed significant short-term improvements in clinical attachment level, bleeding on probing, and microbiological outcomes compared to the control group. However, after 6 months, only lower bleeding on probing rates remained significant.

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2023·Medicine and science in sports and exercise·Jeffery L Heileson, Dillon R Harris, Sara Tomek, et al

Long-Chain Omega-3 Fatty Acid Supplementation and Exercise-Induced Muscle Damage: EPA or DHA?

RCTn = 30Recovery Physical Performance

RCT of 30 males comparing 4 g/day EPA + DHA, EPA, DHA, and placebo over 7 weeks on recovery from exercise-induced muscle damage. EPA and DHA improved leg press performance and reduced muscle soreness compared to placebo. EPA + DHA did not clearly enhance recovery compared to individual components.

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2023·Nutrients·Katsunori Tsuji, Yosuke Tsuchiya, Kaori Yokoi, et al

Eicosapentaenoic Acid and Medium-Chain Triacylglycerol Structured Lipids Improve Endurance Performance.

RCTn = 19Physical Performance

This 8-week randomized double-blind placebo-controlled study involved 19 healthy men to examine the effects of structured lipids containing EPA and MCTs on cardiorespiratory endurance. The STG group showed significant improvements in time to exhaustion and time to reach the anaerobic threshold compared to the PM group.

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2023·Atherosclerosis·Jisun So, Dayong Wu, Albert K Tai, et al

Monocyte transcriptomic profile following EPA and DHA supplementation in men and women with low-grade chronic inflammation.

RCTn = 16Inflammation Heart Health

RCT with 16 subjects (8 men and 8 women) aged 50-75 with low-grade chronic inflammation, comparing 3g/d EPA, 3g/d DHA, and placebo. EPA and DHA repressed genes involved in protein turnover and mitochondrial energy metabolism in both sexes. EPA resulted in lower expression of inflammatory genes in men and lower ER stress response genes in women compared to DHA.

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2022·BMC Rheumatology·L. Stamp, R. Grainger, C. Frampton, et al

Effect of omega-three supplementation on serum urate and gout flares in people with gout; a pilot randomized trial

RCTn = 40Inflammation

A 6-month pilot randomized trial in 40 people with gout assessed the effect of 6.2 g omega-3 fish oil daily on serum urate, weight, and BMI. No significant difference was found in serum urate or BMI changes between groups. However, higher omega-three concentrations correlated with fewer gout flares, suggesting potential prophylactic benefits.

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2022·Prostaglandins, leukotrienes, and essential fatty acids·Ruxandra D Rotarescu, Kimia Rezaei, David M Mutch, et al

Increases in plasma n-3 tetracosapentaenoic acid and tetracosahexaenoic acid following 12 weeks of EPA, but not DHA, supplementation in women and men.

RCTn = 24

This secondary analysis of a double-blind randomized control trial assessed changes in plasma levels of omega-3 tetracosapentaenoic acid (TPAn-3) and tetracosahexaenoic acid (THA) in women and men following 12 weeks of supplementation with 3g/day EPA, DHA, or olive oil. EPA supplementation significantly increased plasma TPAn-3 and THA levels, with women showing higher concentrations than men. DHA supplementation had no effect.

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2022·Journal of clinical lipidology·Jisun So, Bela F Asztalos, Katalin Horvath, et al

Ethyl EPA and ethyl DHA cause similar and differential changes in plasma lipid concentrations and lipid metabolism in subjects with low-grade chronic inflammation.

RCTn = 21Heart Health

Randomized, double-blind, crossover study of 10-week supplementation with 3 g/d pure EPA and DHA in 21 older men and postmenopausal women with low-grade chronic inflammation. Both EPA and DHA lowered plasma TG concentrations, but only DHA increased LDL-C concentrations. EPA lowered CETP, while DHA lowered LCAT activity, with sex-specific variations observed.

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2021·Atherosclerosis·Anthony D Pisaniello, Peter J Psaltis, Peta M King, et al

Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects.

RCTn = 40Heart Health Inflammation

A double-blind RCT and cell-culture study with 40 healthy volunteers supplemented with EPA, DHA, fish oil, or placebo for 30 days. EPA reduced markers of vascular inflammation, such as CCL2 and VCAM1, and showed inverse correlations with these markers, suggesting cardiovascular benefits.

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2021·Molecular psychiatry·Alessandra Borsini, Anna Nicolaou, Dolores Camacho-Muñoz, et al

Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.

RCTn = 22Inflammation Brain Health Mood

The study investigated the effects of EPA and DHA on inflammation, neurogenesis, and depression. In vitro and clinical investigations showed that EPA and DHA metabolites prevented cytokine-induced reduction in neurogenesis and apoptosis. In a clinical trial with 22 patients with Major Depressive Disorder, treatment with EPA or DHA increased specific lipid metabolites and correlated with less severe depressive symptoms.

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2021·Journal of diabetes investigation·Yumie Takeshita, Chisato Teramura, Kyoko Kamoshita, et al

Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ-specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes.

RCTn = 20

RCT examining the effect of eicosapentaenoic acid (EPA) on serum selenoprotein P levels and organ-specific insulin sensitivity in 20 humans with dyslipidemia and type 2 diabetes. Serum SeP levels were unchanged, but EPA treatment enhanced %FFA and was correlated with changes in hepatic and skeletal muscle insulin sensitivity.

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2020·Nutrients·Mirella Stańdo, Paweł Piątek, M. Namiecińska, et al

Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial

RCTn = 30Inflammation

RCT evaluating the effect of omega-3 PUFA supplementation (EPA and DHA) in patients with stage III and IV periodontitis. The test group showed significant reductions in bleeding on probing and improvements in clinical attachment loss compared to the control group. Pro-inflammatory cytokines were lower, and anti-inflammatory IL-10 was higher in the test group.

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2020·Atherosclerosis·Jisun So, Dayong Wu, Alice H Lichtenstein, et al

EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study.

RCTn = 21Inflammation

Randomized, double-blind, crossover study comparing the effects of EPA and DHA supplementation on monocyte inflammatory response in 21 subjects with chronic inflammation. EPA and DHA differentially modulated cytokine expression and plasma PUFA SPM lipidome, with DHA showing a broader effect in attenuating pro-inflammatory cytokines.

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2020·Physiological reports·Takuma Morishima, Yosuke Tsuchiya, Hisashi Ueda, et al

Muscular endurance and muscle metabolic responses to 8 weeks of omega-3 polyunsaturated fatty acids supplementation.

RCTn = 19Physical Performance -

RCT of 19 healthy men testing 8 weeks of EPA and DHA supplementation on muscular endurance. The study found no significant differences in maximal repetitions, muscle oxygen availability, MVC, or blood lactate between the fish oil and placebo groups.

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2020·Prostaglandins, leukotrienes, and essential fatty acids·Koen Manusama, Michiel Balvers, Marlies Diepeveen-de Bruin, et al

In vitro dissolution behaviour and absorption in humans of a novel mixed l-lysine salt formulation of EPA and DHA.

RCTn = 8

This study investigated the in vitro dissolution and human absorption of a novel l-lysine salt formulation of EPA and DHA (Lys-FFA) compared to an oil-based ethyl-ester (EE) supplement. The Lys-FFA formulation showed rapid absorption and significantly higher bioavailability of EPA and DHA in human volunteers compared to the EE formulation.

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2019·European journal of nutrition·Kiki P van der Burg, Lachlan Cribb, Joseph Firth, et al

EPA and DHA as markers of nutraceutical treatment response in major depressive disorder.

RCTn = 158Mood

Post hoc analysis of an 8-week RCT with 158 participants investigating a nutraceutical combination including Omega-3 (EPA 1g/DHA 656mg) for Major Depressive Disorder. EPA and DHA levels in red cell membranes increased and correlated with a decrease in depressive symptoms. Higher baseline omega-6 levels also correlated with depression reduction.

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2019·The Journal of clinical psychiatry·Robert M Carney, Kenneth E Freedland, Eugene H Rubin, et al

A Randomized Placebo-Controlled Trial of Omega-3 and Sertraline in Depressed Patients With or at Risk for Coronary Heart Disease.

RCTn = 144Mood -

RCT of 144 patients with major depressive disorder and CHD or CHD risk factors, comparing sertraline with EPA to sertraline with placebo. After 10 weeks, no significant differences were found in depressive symptoms between the groups.

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2019·Molecular nutrition & food research·Quan Zhou, Zheqing Zhang, Ping Wang, et al

EPA+DHA, but not ALA, Improved Lipids and Inflammation Status in Hypercholesterolemic Adults: A Randomized, Double-Blind, Placebo-Controlled Trial.

RCTn = 123Heart Health Inflammation

A randomized, double-blind, placebo-controlled trial comparing the effects of EPA+DHA versus ALA on lipid profiles and inflammatory status in hypercholesterolemic adults. EPA+DHA supplementation led to significant decreases in triglycerides and IL-6 production, while ALA did not increase EPA/DHA composition in PBMCs.

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2019·Translational psychiatry·Jane Pei-Chen Chang, Kuan-Pin Su, Valeria Mondelli, et al

High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels.

RCTn = 92Focus Mental Clarity Mood

A 12-week, double-blind, placebo-controlled trial with 92 children and adolescents with ADHD examined the effects of high-dose eicosapentaenoic acid (EPA) on cognitive function. The EPA group showed improvements in focused attention and vigilance, particularly in those with low baseline EPA levels. However, those with high baseline EPA levels showed less improvement in impulsivity and other ADHD symptoms.

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2019·Clinical rheumatology·Marijana Tomic-Smiljanic, Dragan Vasiljevic, Aleksandra Lucic-Tomic, et al

Influence of different supplementation on platelet aggregation in patients with rheumatoid arthritis.

RCTn = 60Heart Health Inflammation

RCT involving 60 rheumatoid arthritis patients assessing the influence of omega-3 PUFA supplementation on platelet aggregation. Patients using concentrated fish oil showed a significant reduction in platelet aggregation compared to those without supplementation.

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2019·Schizophrenia research·D. Robinson, J. Gallego, M. John, et al

A potential role for adjunctive omega-3 polyunsaturated fatty acids for depression and anxiety symptoms in recent onset psychosis: Results from a 16 week randomized placebo-controlled trial for participants concurrently treated with risperidone.

RCTn = 50Mood Stress

RCT of omega-3 supplementation (EPA 740 mg and DHA 400 mg daily) as an adjunctive treatment for recent onset psychosis in participants aged 15-40 years. The study found a trend level treatment effect favoring omega-3 on the Brief Psychiatric Rating Scale, with significant improvements in depression-anxiety symptoms among those not receiving lorazepam. Omega-3 treatment was associated with fewer adverse events compared to placebo.

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2019·The British journal of nutrition·Annette L West, Elizabeth A Miles, Karen A Lillycrop, et al

Postprandial incorporation of EPA and DHA from transgenic Camelina sativa oil into blood lipids is equivalent to that from fish oil in healthy humans.

RCTNutrition -

Double-blind, postprandial cross-over trial comparing incorporation of EPA and DHA from transgenic Camelina sativa seed oil (CSO) and commercial blended fish oil (BFO) into blood lipids in healthy adults. No significant differences were found between the oils in terms of EPA and DHA incorporation into plasma lipids or other measured parameters.

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2018·BMC cancer·Marie-Hélène Guertin, Karine Robitaille, Jean-François Pelletier, et al

Effects of concentrated long-chain omega-3 polyunsaturated fatty acid supplementation before radical prostatectomy on prostate cancer proliferation, inflammation, and quality of life: study protocol for a phase IIb, randomized, double-blind, placebo-controlled trial.

RCTn = 130Inflammation Mens Health

This phase IIb randomized, double-blind, placebo-controlled trial evaluates the effects of MAG-EPA supplementation on prostate cancer proliferation, inflammation, and quality of life in 130 men undergoing radical prostatectomy. The study aims to assess changes in prostate cancer cell proliferation, inflammatory mediators, and psychosocial functioning over a year.

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2018·Epilepsy & behavior : E&B·Fatma A S Ibrahim, Kebreab Ghebremeskel, Manar E Abdel-Rahman, et al

The differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on seizure frequency in patients with drug-resistant epilepsy - A randomized, double-blind, placebo-controlled trial.

RCTn = 99Brain Health

A randomized, double-blind, placebo-controlled trial investigated the effects of EPA and DHA on seizure frequency in 99 patients with drug-resistant epilepsy. Both EPA and DHA groups showed a significant reduction in seizure frequency compared to placebo, with a 42% and 39% reduction in seizure incidence rate ratio, respectively. Both treatment groups also had more seizure-free days compared to placebo.

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2018·The Journal of nutrition·Annette L West, Grete Mørk Kindberg, Svein Olaf Hustvedt, et al

A Novel Self-Micro-Emulsifying Delivery System Enhances Enrichment of Eicosapentaenoic Acid and Docosahexaenoic Acid after Single and Repeated Dosing in Healthy Adults in a Randomized Trial.

RCTn = 80Nutrition

RCT comparing a self-micro-emulsifying delivery system (SMEDS) of EPA and DHA ethyl esters with standard ethyl esters in 80 healthy adults. SMEDS resulted in higher concentrations of EPA and DHA in plasma, mononuclear cells, and RBCs after single and repeated dosing, enhancing delivery of omega-3 fatty acids.

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2018·Clinical nutrition ESPEN·S. Keshavarz, S. Mostafavi, S. Akhondzadeh, et al

Omega-3 supplementation effects on body weight and depression among dieter women with co-morbidity of depression and obesity compared with the placebo: A randomized clinical trial.

RCTn = 65Mood Physique

RCT of 65 women with depression and obesity comparing omega-3 supplementation to placebo over 12 weeks. Omega-3 significantly reduced depression and body weight compared to placebo, though it did not prevent weight regain after stopping supplementation.

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2017·Journal of cardiology·Tetsu Watanabe, Kaoru Ando, Hyuma Daidoji, et al

A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.

RCTn = 193Heart Health

RCT of 193 CHD patients comparing high-dose pitavastatin (PTV) alone to PTV with eicosapentaenoic acid (EPA) for 6-8 months. The PTV/EPA group showed greater reduction in total atheroma volume and lipid volume, particularly in stable angina pectoris patients. EPA addition improved EPA/AA ratio and reinforced plaque stabilization.

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2017·Frontiers in Pharmacology·J. Bradbury, S. Myers, B. Meyer, et al

Chronic Psychological Stress Was Not Ameliorated by Omega-3 Eicosapentaenoic Acid (EPA)

RCTn = 90Stress -

A randomized double-blind, placebo-controlled trial tested the effect of 2.2 g/day EPA supplementation on chronic psychological stress in 90 adults. The study found no significant effect of EPA on perceived stress levels after 12 weeks.

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2016·Journal of affective disorders·Yutaka J Matsuoka, Kei Hamazaki, Daisuke Nishi, et al

Change in blood levels of eicosapentaenoic acid and posttraumatic stress symptom: A secondary analysis of data from a placebo-controlled trial of omega3 supplements.

RCTn = 110Mental Clarity

Secondary analysis of a placebo-controlled trial examining the association between changes in blood levels of eicosapentaenoic acid (EPA) and PTSD symptoms in 110 participants with severe physical injury. Increased erythrocyte levels of EPA were associated with lower severity of PTSD symptoms in the omega3 supplements arm.

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2016·Food & Nutrition Research·Mohammed S. Ellulu, H. Khaza’ai, I. Patimah, et al

Effect of long chain omega-3 polyunsaturated fatty acids on inflammation and metabolic markers in hypertensive and/or diabetic obese adults: a randomized controlled trial

RCTn = 64Inflammation Heart Health

RCT of 64 hypertensive and/or diabetic obese adults assessing the effects of LC ω-3 PUFAs on inflammatory markers. Treatment with eicosapentaenoic acid and docosahexaenoic acid significantly reduced hs-CRP, FBG, and TG levels, but did not achieve clinical significance compared to the control group.

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2015·Molecular psychiatry·M. Rapaport, A. Nierenberg, Pamela J. Schettler, et al

Inflammation as a Predictive Biomarker for Response to Omega-3 Fatty Acids in Major Depressive Disorder: A Proof of Concept Study

RCTn = 155Mood Inflammation

This study investigated whether inflammatory biomarkers moderate the clinical response to omega-3 fatty acids in subjects with major depressive disorder. Subjects were randomized to EPA-enriched, DHA-enriched, or placebo treatments. Results showed that subjects with high inflammation improved more on EPA than placebo or DHA, with EPA-placebo separation increasing with more markers of high inflammation.

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2015·Prostaglandins, leukotrienes, and essential fatty acids·K C Maki, J G Geohas, M R Dicklin, et al

Safety and lipid-altering efficacy of a new omega-3 fatty acid and antioxidant-containing medical food in men and women with elevated triacylglycerols.

RCTn = 102Heart Health

This randomized, double-blind, placebo-controlled trial investigated the effects of a medical food containing eicosapentaenoic acid, astaxanthin, and gamma/delta tocotrienols on lipid profiles in 102 subjects with elevated triacylglycerols. PDL-0101 significantly reduced median triacylglycerols compared to placebo after eight weeks, demonstrating its efficacy in managing elevated TAG.

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2015·Clinical nutrition (Edinburgh, Scotland)·Alireza Soleimani, Mohsen Taghizadeh, Fereshteh Bahmani, et al

Metabolic response to omega-3 fatty acid supplementation in patients with diabetic nephropathy: A randomized, double-blind, placebo-controlled trial.

RCTn = 60Inflammation -Nutrition

This randomized, double-blind, placebo-controlled trial evaluated the effects of omega-3 fatty acid supplementation from flaxseed oil on insulin resistance, lipid concentrations, and biomarkers of inflammation and oxidative stress in 60 patients with diabetic nephropathy. Omega-3 supplementation significantly improved insulin sensitivity and reduced serum triglycerides and VLDL-cholesterol, but had no significant effect on inflammation and oxidative stress markers.

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2015·Clinical nutrition (Edinburgh, Scotland)·Monize Aydar Nogueira, Claudia Pinto Oliveira, Venâncio Avancini Ferreira Alves, et al

Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial.

RCTn = 50Inflammation

RCT evaluating the effects of omega-3 PUFA supplementation from flaxseed and fish oils in 50 patients with NASH. The study found that omega-3 supplementation significantly impacted plasma lipid profiles and was associated with improved liver histology.

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2015·Atherosclerosis·Fumiyoshi Tsunoda, Stefania Lamon-Fava, Bela F Asztalos, et al

Effects of oral eicosapentaenoic acid versus docosahexaenoic acid on human peripheral blood mononuclear cell gene expression.

RCTn = 50Inflammation Heart Health

RCT comparing the effects of six-week supplementation with olive oil, EPA, or DHA on gene expression in peripheral blood mononuclear cells. EPA significantly affected gene expression in pathways related to interferon signaling and other processes, suggesting potential benefits for CVD risk reduction.

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2013·American journal of obstetrics and gynecology·Ellen L Mozurkewich, Chelsea M Clinton, Julie L Chilimigras, et al

The Mothers, Omega-3, and Mental Health Study: a double-blind, randomized controlled trial.

RCTn = 126Mood -

RCT of 126 pregnant women at risk for depression comparing EPA-rich fish oil, DHA-rich fish oil, and soy oil placebo. No differences in depressive symptoms were found between groups, though serum DHA concentrations were inversely related to BDI scores in late pregnancy.

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2013·Translational psychiatry·H Bentsen, K Osnes, H Refsum, et al

A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.

RCTn = 99Mental Clarity

A randomized placebo-controlled trial examined the effects of ethyl-eicosapentaenoate (EPA) and vitamins E+C on schizophrenia patients. EPA and vitamins separately increased drop-out rates and impaired psychotic symptoms in low PUFA patients, but combined they did not differ from placebo. In high PUFA patients, no significant effects were observed.

PubMedRead on PubMed
2012·European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology·Hassan Mozaffari-Khosravi, Mojtaba Yassini-Ardakani, Mohsen Karamati, et al

Eicosapentaenoic acid versus docosahexaenoic acid in mild-to-moderate depression: a randomized, double-blind, placebo-controlled trial.

RCTn = 81Mood

RCT comparing the efficacy of EPA versus DHA as adjuvants to maintenance medication treatments for mild-to-moderate depression in 81 outpatients. EPA showed a significantly lower mean HDRS score at study endpoint compared to DHA and placebo, suggesting greater efficacy of EPA as an adjunctive treatment.

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2012·Clinical nutrition (Edinburgh, Scotland)·Christine Dawczynski, Karen A Massey, Christina Ness, et al

Randomized placebo-controlled intervention with n-3 LC-PUFA-supplemented yoghurt: effects on circulating eicosanoids and cardiovascular risk factors.

RCTn = 53Heart Health Inflammation

RCT with 53 mildly hypertriacylglycerolemic subjects consuming control or n-3 LC-PUFA-enriched yoghurt for 10 weeks. The 3 g n-3 LC-PUFA group showed increased plasma and RBC n-3 LC-PUFA levels, improved cardiovascular risk factors, and reduced inflammatory mediators.

PubMedRead on PubMed
2011·Brain, behavior, and immunity·Janice K Kiecolt-Glaser, Martha A Belury, Rebecca Andridge, et al

Omega-3 supplementation lowers inflammation and anxiety in medical students: a randomized controlled trial.

RCTn = 68Inflammation Stress

This 12-week RCT compared omega-3 supplementation with placebo in 68 medical students. Omega-3 supplementation led to a 14% decrease in IL-6 production and a 20% reduction in anxiety symptoms, suggesting potential benefits for reducing inflammation and anxiety.

PubMedRead on PubMed
2011·The British journal of nutrition·Natalie Sinn, Catherine M Milte, Steven J Street, et al

Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial.

RCTn = 50Mood Brain Health

A 6-month double-blind RCT investigated the effects of EPA and DHA supplementation on depressive symptoms, quality of life, and cognition in 50 older adults with mild cognitive impairment. EPA and DHA improved Geriatric Depression Scale scores compared to linoleic acid, with DHA also improving verbal fluency. Increased DHA and EPA intake was associated with mental health benefits.

PubMedRead on PubMed
2010·Atherosclerosis·Abbie L Cawood, Ren Ding, Frances L Napper, et al

Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability.

RCTn = 121Heart Health Inflammation

RCT of 121 patients awaiting carotid endarterectomy, randomized to consume control or n-3 PUFA ethyl ester capsules. Higher EPA content in plaques was associated with reduced foam cells, T cells, inflammation, and increased stability.

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2009·The Journal of clinical psychiatry·David Mischoulon, George I Papakostas, Christina M Dording, et al

A double-blind, randomized controlled trial of ethyl-eicosapentaenoate for major depressive disorder.

RCTn = 57Mood

A double-blind, randomized controlled trial of 57 adults with major depressive disorder comparing 1 g/d of eicosapentaenoic acid (EPA) to placebo for 8 weeks. EPA showed a decrease in HDRS-17 scores, but the advantage over placebo did not reach statistical significance, possibly due to small sample size and low completer rates.

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2008·The American journal of clinical nutrition·Nachum Vaisman, Nehemia Kaysar, Yahalomit Zaruk-Adasha, et al

Correlation between changes in blood fatty acid composition and visual sustained attention performance in children with inattention: effect of dietary n-3 fatty acids containing phospholipids.

RCTn = 83Focus

RCT investigating the effects of EPA and DHA conjugated to phospholipids or triacylglycerol on blood fatty acid composition and visual sustained attention in children with inattention. The PL-n-3 group showed significant improvements in TOVA scores and changes in blood fatty acid profiles compared to placebo.

PubMedRead on PubMed
2006·The Cochrane database of systematic reviews·C B Joy, R Mumby-Croft, L A Joy

Polyunsaturated fatty acid supplementation for schizophrenia.

Meta-analysisn = 30

Meta-analysis reviewing the effects of polyunsaturated fatty acids, particularly omega-3, for schizophrenia. Small trials suggest omega-3 may reduce the need for neuroleptics and improve mental state, but results are inconclusive. The review highlights the need for larger, well-designed studies.

PubMedRead on PubMed
2004·European journal of clinical nutrition·P H J Remans, J K Sont, L W Wagenaar, et al

Nutrient supplementation with polyunsaturated fatty acids and micronutrients in rheumatoid arthritis: clinical and biochemical effects.

RCTn = 66Inflammation -

Double-blind, placebo-controlled RCT in 66 RA patients testing nutrient supplementation with EPA, DHA, GLA, and micronutrients. No significant clinical benefit was observed in tender joint count or other clinical parameters, though plasma concentrations of EPA, DHA, and vitamin E increased.

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2003·Cardiovascular research·Faisel Khan, Khalid Elherik, Caroline Bolton-Smith, et al

The effects of dietary fatty acid supplementation on endothelial function and vascular tone in healthy subjects.

RCTn = 173Heart Health

Double-blind, randomized, placebo-controlled study of 173 healthy volunteers evaluating the effects of various oil supplements on vascular tone and endothelial function. Tuna fish oil supplementation significantly improved acetylcholine responses, indicating a beneficial effect on endothelial function.

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2003·The American journal of clinical nutrition·Yvonne E Finnegan, Anne M Minihane, Elizabeth C Leigh-Firbank, et al

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects.

RCTn = 150Heart Health

This placebo-controlled, parallel study compared the effects of increased dietary intakes of ALA and EPA+DHA on atherogenic risk factors in 150 moderately hyperlipidemic subjects. The study found no significant differences in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure between n-3 PUFA interventions and the n-6 PUFA control. However, fasting triacylglycerols decreased significantly with EPA+DHA compared to ALA, and LDL oxidation susceptibility was higher with EPA+DHA.

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2001·The American journal of clinical nutrition·F Thies, G Nebe-von-Caron, J R Powell, et al

Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged >55 y.

RCT

RCT examining the effect of dietary supplementation with various polyunsaturated fatty acids on NK cell activity in healthy subjects aged 55-75. Only fish oil, specifically eicosapentaenoic acid (EPA), significantly reduced NK cell activity, with effects reversing 4 weeks after stopping supplementation.

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2018·Diabetes & metabolic syndrome·Mohammad Hassan Golzari, Mohammad Hassan Javanbakht, Ehsan Ghaedi, et al

Effect of Eicosapentaenoic acid (EPA) supplementation on cardiovascular markers in patients with type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

RCTn = 36Heart Health

A randomized, double-blind, placebo-controlled trial in 36 patients with type 2 diabetes mellitus assessed the effect of 2g/day EPA supplementation for 8 weeks. EPA significantly reduced methionine and cysteine levels and the atherogenic index of plasma, suggesting beneficial effects on cardiovascular markers.

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2018·Lipids in Health and Disease·E. Sarkkinen, M. Savolainen, J. Taurio, et al

Prospective, randomized, double-blinded, placebo-controlled study on safety and tolerability of the krill powder product in overweight subjects with moderately elevated blood pressure

RCTn = 35

Randomized, double-blinded, placebo-controlled study on the safety and tolerability of krill powder in 35 overweight subjects with mildly or moderately elevated blood pressure. The study found no significant changes in blood pressure or lipid values, and krill powder was deemed safe with a low risk of adverse events.

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2018·Lipids in health and disease·Essi S Sarkkinen, Markku J Savolainen, Jyrki Taurio, et al

Prospective, randomized, double-blinded, placebo-controlled study on safety and tolerability of the krill powder product in overweight subjects with moderately elevated blood pressure.

RCTn = 35

RCT with 35 overweight subjects with elevated blood pressure testing safety and tolerability of krill powder. No serious adverse events were reported, and no significant changes were observed in blood pressure or lipid values. Krill powder was found to be safe in therapeutic doses.

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2017·Nutrition Journal·P. S. Silva, M. Mediano, G. M. S. Silva, et al

Omega-3 supplementation on inflammatory markers in patients with chronic Chagas cardiomyopathy: a randomized clinical study

RCTn = 42Inflammation Heart Health

This randomized clinical study investigated the effects of omega-3 PUFAs supplementation on inflammatory markers and lipid profile in patients with chronic Chagas cardiomyopathy. The omega-3 group showed greater improvements in serum triglycerides and IL-10 levels compared to the placebo group after 8 weeks.

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2017·Photodermatology, photoimmunology & photomedicine·Nancy L Morse, Anna-Jean Reid, Marc St-Onge

An open-label clinical trial assessing the efficacy and safety of Bend Skincare Anti-Aging Formula on minimal erythema dose in skin.

RCTn = 28Skin Hair Health

Open-label clinical trial assessing the efficacy and safety of Bend Skincare Anti-Aging Formula on minimal erythema dose in skin. The formula, containing EPA, DHA, GLA, lutein, zeaxanthin, and vitamin D3, significantly improved tolerance to UV exposure, increasing MED at 4 and 8 weeks compared with baseline. Treatment was well tolerated with no adverse events.

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2017·Clinical pharmacology in drug development·Yoshinori Noda, Catarina Nilsson, Hitoshi Shimada, et al

Safety, Tolerability, and Pharmacokinetics of Single and Multiple Oral Doses of an Omega-3-Carboxylic Acid Formulation in Healthy Male Japanese Subjects: A Phase 1 Single-Blind, Randomized, Placebo-Controlled Trial.

RCTn = 24

Phase 1 single-blind, randomized, placebo-controlled trial investigating the safety, tolerability, and pharmacokinetics of OM3-CA (omega-3-carboxylic acids) in healthy male Japanese subjects. OM3-CA was well tolerated, with adverse events including alanine aminotransferase increase and diarrhea. Pharmacokinetic profiles of EPA and DHA were comparable between Japanese and white subjects.

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