Arachidonic Acid/EPA Ratio
The AA/EPA ratio compares arachidonic acid (the primary pro-inflammatory omega-6) to eicosapentaenoic acid (the primary anti-inflammatory omega-3). These fatty acids directly compete to produce either inflammatory or anti-inflammatory signaling molecules. The ratio between them predicts your body’s inflammatory tendency with remarkable precision.
While the broader omega-6/omega-3 ratio captures the overall balance between these fatty acid families, the AA/EPA ratio zooms in on the two most biologically active players: arachidonic acid (AA) from the omega-6 family and eicosapentaenoic acid (EPA) from the omega-3 family. These two fatty acids are the primary substrates for producing eicosanoids — the powerful signaling molecules that control inflammation, blood clotting, and immune responses.
Arachidonic acid is the precursor to pro-inflammatory eicosanoids: prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and leukotriene B4 (LTB4). These molecules promote inflammation, constrict blood vessels, aggregate platelets, and recruit immune cells. They’re essential for acute inflammatory responses — fighting infection, healing wounds — but become harmful when chronically elevated.
EPA produces competing eicosanoids: prostaglandin E3 (PGE3), thromboxane A3 (TXA3), and leukotriene B5 (LTB5). These are far less inflammatory — or even anti-inflammatory — compared to their AA-derived counterparts. EPA also gives rise to resolvins, specialized mediators that actively resolve inflammation and promote tissue healing.
Here’s the critical point: AA and EPA compete for the same enzymes (cyclooxygenase, lipoxygenase). When AA predominates, the inflammatory mediators dominate. When EPA is abundant, it “crowds out” AA, shifting the balance toward resolution. The AA/EPA ratio directly reflects which side is winning this molecular competition in your cells.
Key Benefits of Testing
The AA/EPA ratio provides a precise, focused assessment of inflammatory potential that broader omega ratios don’t capture. It measures the direct competition between the most relevant fatty acids — the ones actually being converted to signaling molecules — rather than including fatty acids with less direct inflammatory impact.
Japanese researchers have particularly championed this marker, given Japan’s historically high fish consumption and researchers’ interest in understanding why cardiovascular disease rates differ between Japan and Western countries. Studies have shown that Japanese populations with AA/EPA ratios around 1.0-1.5 have significantly lower cardiovascular event rates than Western populations with ratios of 10-15 or higher.
For cardiovascular risk assessment, the AA/EPA ratio adds information beyond traditional markers. Someone with “good” cholesterol numbers might still have high inflammatory potential indicated by an elevated AA/EPA ratio — a hidden risk factor worth knowing about.
For those managing inflammatory conditions — cardiovascular disease, rheumatoid arthritis, inflammatory bowel disease, psoriasis — the AA/EPA ratio provides a specific target for dietary intervention. Unlike vague advice to “eat more fish,” a high AA/EPA ratio with a specific numeric target gives concrete direction and a way to measure progress.
For monitoring dietary changes or supplementation, the AA/EPA ratio shows with precision whether your intervention is working at the cellular level. You might increase fish intake or start EPA supplements and want to know: is it actually shifting my inflammatory balance? Testing provides the answer.
What Does the AA/EPA Ratio Measure?
The AA/EPA ratio is calculated by dividing the concentration or percentage of arachidonic acid by the concentration or percentage of EPA in blood. A ratio of 5:1 means you have five times as much AA as EPA; a ratio of 1:1 means equal amounts.
Arachidonic Acid (AA, 20:4n-6)
A 20-carbon omega-6 fatty acid with four double bonds. AA is either consumed directly from animal foods (meat, poultry, eggs) or synthesized from linoleic acid (the main dietary omega-6 from vegetable oils). It’s a major component of cell membranes and the primary substrate for pro-inflammatory eicosanoid production.
AA isn’t inherently “bad” — it’s essential for normal physiology, including immune function, blood clotting, and brain development. Problems arise when AA dramatically exceeds EPA, shifting eicosanoid production toward chronic inflammation.
Eicosapentaenoic Acid (EPA, 20:5n-3)
A 20-carbon omega-3 fatty acid with five double bonds. EPA comes primarily from fatty fish and fish/algae oil supplements. It competes directly with AA for the same enzymes, producing less inflammatory or anti-inflammatory eicosanoids and specialized pro-resolving mediators (resolvins).
EPA is particularly associated with cardiovascular benefits and anti-inflammatory effects. The REDUCE-IT trial showed that high-dose EPA (icosapent ethyl) reduced cardiovascular events in high-risk patients, independent of triglyceride effects.
Sample Types
Red blood cell (RBC) membrane: Reflects longer-term fatty acid status (preceding 2-3 months). Most stable and clinically meaningful for assessing chronic inflammatory potential.
Plasma/serum: Reflects more recent intake. More variable but can show short-term changes.
Whole blood: Combination approach. Some testing platforms use finger-stick dried blood spots for convenience.
Interpretation Framework
Lower AA/EPA ratios are better, indicating more EPA relative to AA and a more favorable inflammatory balance:
Very high ratio (>15): Typical of standard Western diets with high omega-6 and minimal fish/omega-3. Strongly pro-inflammatory cellular environment.
High ratio (10-15): Still significantly elevated. Dietary modification recommended.
Moderate ratio (5-10): Some fish consumption or omega-3 supplementation likely, but room for improvement.
Low ratio (2-5): Reasonable balance. Regular fish consumption and/or supplementation.
Optimal ratio (1-2): Excellent anti-inflammatory balance. Typical of populations with high fish intake (Japanese, Inuit).
Very low ratio (<1): Very high EPA relative to AA. Seen with high-dose EPA supplementation or very high fish intake.
Why the AA/EPA Ratio Matters
The Eicosanoid Balance
Eicosanoids are hormone-like molecules produced locally in tissues with profound effects on inflammation, blood clotting, blood pressure, and immune responses. They’re synthesized on-demand from membrane fatty acids when cells are activated.
The cyclooxygenase (COX) and lipoxygenase (LOX) enzymes that produce eicosanoids don’t distinguish between AA and EPA — they process whichever is available. When cells have more AA in their membranes, they produce more AA-derived inflammatory mediators. When EPA is abundant, it competitively inhibits AA conversion and produces its own less inflammatory products.
This isn’t just theory — it’s measurable. Studies show that EPA supplementation reduces urinary markers of AA-derived prostaglandins and increases EPA-derived metabolites. The AA/EPA ratio in blood directly predicts this eicosanoid shift.
Silent Inflammation
Dr. Barry Sears popularized the concept of “silent inflammation” — chronic, low-grade inflammation that doesn’t cause obvious symptoms but accelerates aging, cardiovascular disease, and other chronic conditions. The AA/EPA ratio, in his framework, is the key metric for detecting this silent process.
Unlike acute inflammation (redness, swelling, pain), silent inflammation operates below the threshold of perception. You feel fine, but your cells are in a chronically pro-inflammatory state. Traditional markers like hs-CRP capture some of this, but the AA/EPA ratio provides a complementary and perhaps more specific view of the fatty acid-driven component.
Japanese Evidence
Japanese researchers have extensively studied the AA/EPA ratio, motivated by observations that Japanese populations have much lower cardiovascular disease rates than Western populations despite similar (or higher) smoking rates and blood pressure.
Key findings from Japanese research:
JELIS trial: Adding EPA to statin therapy reduced cardiovascular events by 19% in Japanese patients. Notably, participants had average AA/EPA ratios around 1.4 — far lower than typical Western values — yet still benefited from additional EPA.
Population studies: Coastal Japanese communities with traditional high-fish diets have AA/EPA ratios around 1.0-1.5, compared to 10-15+ in inland populations eating Western-style diets. Cardiovascular risk tracks with this ratio.
Mechanistic studies: Japanese research has linked higher AA/EPA ratios to more unstable atherosclerotic plaques, increased cardiovascular events after stent placement, and poorer outcomes in heart failure.
Beyond Cardiovascular Disease
The AA/EPA ratio is relevant to any condition where inflammation plays a role:
Autoimmune conditions: Rheumatoid arthritis, lupus, inflammatory bowel disease may benefit from shifting toward lower AA/EPA ratios.
Mental health: Some research links elevated AA/EPA ratios to depression and anxiety. EPA supplementation has shown benefit in depression trials.
Metabolic health: Inflammation contributes to insulin resistance and metabolic syndrome. The AA/EPA ratio reflects this inflammatory component.
What Can Affect Your AA/EPA Ratio?
Factors That Increase the Ratio (More AA Relative to EPA)
High omega-6 vegetable oil consumption: Soybean, corn, sunflower, safflower oils provide linoleic acid, which converts to arachidonic acid. This is the primary dietary driver of high AA in Western diets.
Low fish intake: Without marine omega-3 sources, EPA remains low while AA accumulates from omega-6-rich diets.
High meat consumption: Red meat, poultry, and eggs contain preformed AA. Combined with low fish intake, this elevates the ratio.
Processed and fast foods: Typically prepared with omega-6-rich oils and lacking omega-3 content.
Factors That Decrease the Ratio (More EPA Relative to AA)
Fatty fish consumption: The most effective strategy. Salmon, mackerel, sardines, herring, anchovies are rich in EPA. Regular consumption (2-3 times weekly or more) substantially lowers the ratio.
Fish oil supplements: Concentrated EPA (and DHA). Particularly effective are EPA-concentrated formulations or high-dose regimens.
Algae-based EPA supplements: Vegan source of EPA for those avoiding fish products.
Reducing omega-6 oil consumption: Cooking with olive oil, avocado oil, or butter instead of soybean/corn oil reduces AA precursor intake.
Grass-fed animal products: Contain somewhat less AA and more omega-3 than grain-fed counterparts.
Genetic Factors
FADS1/FADS2 variants: Genetic polymorphisms in fatty acid desaturase genes affect conversion of linoleic acid to AA and ALA to EPA. Some individuals are “hyperconverters” who produce more AA from dietary omega-6; others are “hypoconverters.” This genetic variation influences individual responses to dietary changes.
Understanding Your Results
Interpreting Your AA/EPA Ratio
Context matters — consider your ratio alongside symptoms, other inflammatory markers, and cardiovascular risk factors:
Ratio >15: Strongly pro-inflammatory. Typical of standard Western diet with high vegetable oil consumption and minimal fish. Significant dietary modification recommended — substantial increase in fatty fish and/or EPA supplementation, plus reduction in omega-6-rich oils.
Ratio 10-15: Elevated inflammatory potential. Moderate dietary changes — more fish, less vegetable oil, consider supplementation — can meaningfully improve the ratio.
Ratio 5-10: Moderate. Shows some attention to fatty acid balance but room for improvement. Adding consistent fish consumption or supplementation should achieve further reduction.
Ratio 2-5: Good. Reflects regular fish intake and/or supplementation with attention to omega-6 intake. Maintaining current patterns is reasonable; some may aim for further optimization.
Ratio 1-2: Excellent. Typical of high fish consumers or consistent EPA supplementation. This range is associated with lowest cardiovascular risk in population studies.
Ratio <1: Very high EPA relative to AA. Seen with aggressive supplementation. Generally safe, though some practitioners prefer ratios not go below 0.5 to ensure adequate AA for normal physiology.
Using Results to Guide Change
Establish baseline: Know where you’re starting from.
Set a target: For most people, moving toward a ratio of 1.5-3 represents a reasonable goal that balances anti-inflammatory benefits with practicality.
Implement changes: Increase fatty fish to 3+ servings weekly, add EPA-rich fish oil if needed (1-2 grams EPA daily for meaningful ratio change), and reduce vegetable oil consumption.
Retest in 3-4 months: RBC fatty acids take months to fully reflect changes. Retesting shows whether your intervention achieved the target.
Combining with Other Markers
The AA/EPA ratio is most informative when combined with:
Omega-3 Index: Confirms absolute EPA+DHA status, not just ratio.
hs-CRP: Directly measures inflammation. AA/EPA ratio predicts inflammatory potential; CRP shows current inflammatory state.
Lipid panel: Triglycerides respond to omega-3 intake; complete cardiovascular picture includes both.
Health Connections
Cardiovascular Disease
Atherosclerosis: Elevated AA/EPA ratio is associated with more unstable arterial plaques — the type prone to rupture and cause heart attacks.
Post-stent outcomes: Japanese studies show higher AA/EPA ratios predict more cardiovascular events after coronary stenting.
Heart failure: Higher AA/EPA ratios are associated with worse outcomes in heart failure patients.
Inflammatory Conditions
Rheumatoid arthritis: Optimizing the AA/EPA ratio may reduce inflammation and medication requirements.
Inflammatory bowel disease: The fatty acid balance affects intestinal inflammation and may complement standard therapy.
Mental Health
Depression: Elevated AA/EPA ratios are associated with depression in some studies. EPA supplementation has antidepressant effects, potentially mediated by shifting this ratio.
Metabolic Health
Insulin resistance: Inflammation contributes to insulin resistance. Optimizing the AA/EPA ratio addresses the fatty acid component of metabolic inflammation.
Why Regular Testing Matters
Baseline testing reveals your current inflammatory potential and guides intervention intensity. Follow-up testing (3-4 months after changes) confirms whether dietary modifications or supplementation achieved the target.
Regular periodic testing may be valuable for:
Cardiovascular risk optimization: The AA/EPA ratio adds inflammatory risk information beyond traditional lipid markers.
Managing inflammatory conditions: Monitoring whether dietary intervention maintains optimal fatty acid balance as part of comprehensive treatment.
Supplement verification: Confirming that EPA supplementation is actually shifting the ratio as intended. Individual absorption varies.
Those with depression: Tracking whether omega-3 intervention is optimizing the ratio as part of mental health management.
Related Biomarkers Often Tested Together
Omega-3 Index — EPA + DHA percentage. Confirms absolute omega-3 status alongside the ratio.
Omega-6/Omega-3 Ratio — Broader ratio including all omega-6 and omega-3 fatty acids.
Arachidonic Acid — Individual AA level, the numerator of the ratio.
hs-CRP — Direct inflammation measurement. Complements the AA/EPA ratio’s assessment of inflammatory potential.
Lipid Panel — Traditional cardiovascular markers. Complete assessment includes both lipids and fatty acid status.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Most practitioners suggest targeting a ratio between 1.5 and 3.0 — the range seen in populations with high fish consumption and low cardiovascular disease rates. Achieving ratios below 5 represents significant improvement from typical Western values (10-15+). The optimal ratio may vary by individual circumstances and health goals.
The omega-6/omega-3 ratio includes all fatty acids in both families (linoleic acid, ALA, etc.). The AA/EPA ratio focuses specifically on the two fatty acids that directly compete to produce inflammatory mediators. It’s more precise for assessing inflammatory potential because AA and EPA are the actual substrates for eicosanoid production, while other fatty acids have less direct inflammatory impact.
Theoretically, extremely low ratios (well below 1.0) could mean insufficient AA for normal physiological functions — AA is needed for immune function, wound healing, and brain development. However, this is rarely a practical concern. Most people trying to improve their ratio are nowhere near this territory. Ratios of 1.0-2.0 provide excellent anti-inflammatory balance while maintaining adequate AA.
To meaningfully reduce a high AA/EPA ratio, most people need 1-2 grams of EPA daily from fish and/or supplements, combined with reduced omega-6 intake. Higher doses may be needed for very elevated ratios or aggressive optimization goals. The actual dose requirement varies individually — testing shows your personal response.
Traditional Japanese diets include fish at almost every meal — far more than typical Western consumption. This provides abundant EPA while relatively lower vegetable oil consumption limits AA. The result is AA/EPA ratios of 1.0-2.0, compared to 10-15+ in typical Western populations. This dietary difference is believed to contribute to Japan’s lower cardiovascular disease rates.
References
Key Sources:
- Yokoyama M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-1098. https://doi.org/10.1016/S0140-6736(07)60527-3
- Ninomiya T, et al. Association between ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cardiovascular disease. J Atheroscler Thromb. 2013;20(4):378-385. https://doi.org/10.5551/jat.15263
- Sears B. The Zone. Regan Books; 1995.
- Calder PC. Eicosanoids. Essays Biochem. 2020;64(3):423-441. https://doi.org/10.1042/EBC20190083
- Serhan CN. Pro-resolving lipid mediators are leads for resolution physiology. Nature. 2014;510(7503):92-101. https://doi.org/10.1038/nature13479
