Overview

EPA (eicosapentaenoic acid; 20:5(n-3)) and DHA (docosahexaenoic acid; 22:6(n-3))—are the key compounds when we talk about omega-3 fatty acids (FA). They're called “omega-3” from the location of the first double bond (non-saturation) sitting three carbons from the tail of their 20- or 22-carbon backbone. They are polyunsaturated fatty acids (PUFAs) and have been studied for decades for their physical and mental health benefits. They reduce cardiovascular risk–likely by reducing clotting–and have efficacy in mild-to-moderate depression, ADHD, and reduce symptoms of mild cognitive impairment. In the brain they 1) support neuroprotection and resolve inflammation, and 2) enhance membrane fluidity for better neuronal signaling. Unfortunately, 89% of US adults land in the “high-risk” zone for the Omega-3 Index, as measured by RBC values, with only 1% of adults in the “optimal” zone. This means Americans are not consuming nearly enough omega-3s to benefit from all they have to offer.

EPA is often referred to as anti-inflammatory but it would more accurately be called “inflammation-resolving.” It doesn’t block inflammation from starting, but once pro-inflammatory cytokines are raging, it helps dampen them and return your brain to baseline. Inflammation is a normal defense against infection and injury but can get out of control or keep going once the threat has passed. EPA (and eicosanoids/resolvins) stop the inflammatory process once the job is done. Why does this matter for attention? Chronic inflammation is linked to cognitive decline and depression and some theorize that inflammation causes or worsens inattention. Even better: EPA boosts attention with decent effect sizes of 0.3-0.9, varying by dose and subject group. In healthy adults, EPA >420mg/day improves executive function with an effect size of ~0.3. To fully dial down inflammation, target an intake of 1.3g EPA+DHA/day.

DHA is a building block for brain cells. It plays a different role than EPA by improving neuronal membrane fluidity–it represents 90% of brain omega-3s, 30-40% of FA in gray matter, and 10-20% total brain lipids. DHA’s bent shape prevents tight phospholipid packing, boosting flexibility within the cell surface. This enhanced fluidity supports ion channel and receptor function, synaptic vesicle release, and membrane-bound enzyme activity. DHA may also specifically support dopaminergic neurons–critical, since dopamine is the most important molecule for maintaining focus. Omega-3 deficiency decreases pre- and post-synaptic dopamine receptors (D2R) in the frontal cortex–undermining your brain’s attentional circuitry.

Omega-3s are generally safe and well-tolerated; the most common side effects are fishy burps or mild GI upset–these can be reduced by taking with fatty meals, which also improves absorption and makes the form of the omega-3 (FFA, TG, rTG, PL, or EE) virtually irrelevant. Above 3g/day they can increase bleeding time; talk to your doctor if you are on blood thinners. At >4g/day they can increase risk of atrial fibrillation. Intake up to 5g/d is considered safe by the European Food Safety Authority, though most stick to 500mg - 2,000mg of EPA + DHA daily. Don’t rely solely on pills: eat salmon, anchovies, sardines, and trout which are low in methylmercury but high in omega-3s. These fatty fish consumed twice weekly in 6oz servings adds an extra 3g EPA + DHA per meal and in combination with an omega-3 supplement of around 1,000mg per day should shift you from the high-risk to the optimal range of the Omega-3 Index within 3 months.

More in-depth mechanisms of action:
• Inflammation resolution and immune tone: EPA/DHA remodel inflammatory-cell membranes, shift eicosanoid profiles, and give rise to resolvins/protectins that help resolve inflammation. Effects include reduced leukocyte chemotaxis, adhesion-molecule expression, and cytokine signaling—factors linked to clearer cognition under stress load. 
• Neuronal membrane dynamics and neurotransmission: DHA-rich phospholipids support synaptic membranes, receptor function, and vesicle cycling; omega-3 status modulates dopaminergic systems implicated in attention, motivation, and mood. 
• Neural efficiency under cognitive load: In healthy adults, EPA-rich supplementation improved global accuracy/speed with a trend to lower prefrontal oxygenated hemoglobin during demanding tasks—consistent with improved processing efficiency.

Clinical studies supporting use (focus-relevant populations)

[Effect-size note: When variance data are incomplete, effect sizes are conservative estimates from reported outcomes. Across trials/meta-analyses below, expect small-to-moderate benefits (≈0.2–0.4) on attention/executive domains in non-demented populations.]

A) Healthy adults
Patan MJ, et al. Am J Clin Nutr. 2021;114(3):914–924.
• Population/design/duration: n=310 healthy adults (25–49 y); randomized, double-blind, parallel-group; 26 weeks.
• Ingredient/dose: EPA-rich oil 900 mg EPA + 360 mg DHA/day vs DHA-rich oil 900 mg DHA + 270 mg EPA/day vs olive-oil placebo.
• Endpoints: Computerized cognitive battery; near-infrared spectroscopy of prefrontal cortex.
• Results: EPA-rich oil improved global cognitive accuracy and speed vs placebo and vs DHA-rich oil; trend to reduced PFC oxy-Hb vs placebo.
• Estimated effect size: g ≈ 0.20–0.30 on global accuracy/speed.

B) Middle-aged/older adults without dementia
Suh SW, et al. BMC Med. 2024;22:109. (Systematic review and dose–response meta-analysis; 24 studies, n=9,660; 3–36 months.)
• Dose signal: Executive-function benefits rise within ~12 months and are most apparent with daily intake >500 mg total n-3, with up to ~420 mg/day EPA contributing; effects larger where baseline blood EPA+DHA is not very low.
• Estimated effect size: small overall; domain-specific gains in executive function. 

C) Immune/inflammatory function with cognitive relevance
Schmidt EB, et al. Arterioscler Thromb. 1991;11:429–435.
• Population/design/duration: Healthy males; dose-response supplementation for 6 weeks at 1.3 g, 4 g, or 9 g/day n-3.
• Endpoint: Neutrophil/monocyte chemotaxis.
• Results: Near-maximal inhibition around 1.3 g/day, supporting an anti-inflammatory exposure threshold relevant to cognitive performance under stress. 

D) Reviews
Shahidi F, Ambigaipalan P. Annu Rev Food Sci Technol. 2018;9:345–381.
• Broad review of sources, metabolism, bioavailability, and health effects across systems—including brain and cognition. 
Calder PC. Nutrients. 2010;2(3):355–374.
• Mechanistic review detailing how EPA/DHA alter inflammatory mediators and resolve inflammation, providing a biologic substrate for cognitive steadiness under load. 
Healy-Stoffel M, Levant B. CNS Neurol Disord Drug Targets. 2018;17(3):216–232.
• Review linking omega-3 status to dopamine-system function with implications for attention/motivation circuits. 

Safety
• Overall: Generally well tolerated in clinical trials; common mild effects include GI upset or fishy aftertaste. Taking with meals mitigates this.
• Hemostasis: At commonly used intakes (≈0.5–3 g/day EPA+DHA), studies show reduced leukocyte chemotaxis and other inflammatory signals without clinically meaningful bleeding risk in healthy users; individuals on anticoagulants or with bleeding disorders should consult a clinician. 
• Pregnancy/lactation: Omega-3s are critical nutrients; dosing and form should be discussed with a healthcare professional.
• Standard disclaimer: Educational information only -- not medical advice. Consult your clinician if you have an illnesses, take medications, are pregnant, or nursing.

References
• Shahidi F, Ambigaipalan P. Omega-3 Polyunsaturated Fatty Acids and Their Health Benefits. Annu Rev Food Sci Technol. 2018;9:345–381.
• Murphy RA, Devarshi PP, Ekimura S, Marshall K, Mitmesser SH. Long-chain omega-3 fatty acid serum concentrations across life stages in the USA: NHANES 2011–2012. BMJ Open. 2021;11:e043301. 
• Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients. 2010;2(3):355–374.
• Patan MJ, Kennedy DO, Husberg C, Hustvedt SO, Calder PC, et al. EPA-rich, but not DHA-rich, oil improves global cognitive function in healthy young adults: RCTs. Am J Clin Nutr. 2021;114(3):914–924.
• Suh SW, Lim E, Burm S-Y, et al. n-3 PUFAs and cognitive function in individuals without dementia: systematic review and dose–response meta-analysis. BMC Med. 2024;22:109. 
• Schmidt EB, Pedersen JO, Varming K, Ernst E, Jersild C, Grunnet N, Dyerberg J. n-3 fatty acids and leukocyte chemotaxis: dose-response in healthy males. Arterioscler Thromb. 1991;11:429–435. 
• Healy-Stoffel M, Levant B. n-3 (Omega-3) Fatty Acids: Effects on Brain Dopamine Systems. CNS Neurol Disord Drug Targets. 2018;17(3):216–232. 
• Nordøy A, et al. Absorption of EPA and DHA as ethyl esters and triglycerides by humans. Am J Clin Nutr. 1991;53:1185–1190.
• Lawson LD, Hughes BG. Absorption of EPA/DHA from fish-oil triacylglycerols or ethyl esters co-ingested with a high-fat meal. Biochem Biophys Res Commun. 1988;156(2):960–963.