What if a simple blood test could predict your risk of chronic disease years before the symptoms begin to occur? That’s the power of measuring the arachidonic acid (AA) to eicosapentaenoic acid (EPA) ratio in your blood.

What The AA/EPA Ratio Tells You

The AA/EPA ratio indicates the level of chronic low-level inflammation in every organ in your body. You can’t feel this type of inflammation, as it is below the perception of pain, which is why I call it silent pain. Its presence indicates some chronic disease is likely in your future. What types of chronic disease? How about obesity, type 2 diabetes, liver disease, kidney disease, autoimmune disease, neurological disease, and cancer. As I pointed out in The OmegaRx Zone more than 20 years ago, the higher the AA/EPA ratio in your blood, the more likely you are to develop one of those chronic diseases associated with increased silent pain, and the ideal AA/EPA ratio should be between 1.5 and 3 (1).

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The AA/EPA Ratio Is Rapidly Rising in Americans

Now a new study has shown that the average AA/EPA ratio in Americans participating in the NHANES study was greater than 40 (2). Unfortunately, that fact is buried in the Supplemental Facts section of that paper. In 2013, it was reported that the AA/EPA ratio in more than 3,000 members of the Framingham study who were similar to those in the new NHANES study was approximately 23 (3). This is more than a 70% increase. What caused such a radical increase in the AA/EPA ratio? The answer is simple: the increase in hyperinsulinemia.

Two Dietary Approaches That Work Together to Reduce The AA/EPA Ratio

What does this mean? If you want to live longer and better, then reducing hyperinsulinemia should be your number one task. The decrease in your AA/EPA ratio is the best blood marker of your success. The best way to reduce AA levels is to follow the Zone diet to reduce insulin levels that increase AA formation. The best way to increase EPA is to consume more omega-3 fatty acids in your diet. Ideally, do both simultaneously.

Increasing EPA is relatively easy using a daily supplement. For most people, a good starting dose would be about 1.6 grams of EPA per day. The average American consumes about 35 mg of EPA per day (4). This is about 45 times lower than my recommended daily intake for EPA. Since EPA is an essential nutrient, the lack of EPA in the diet may be the greatest deficiency facing our society.

Decreasing AA is a little more complicated, as you have to not only reduce the intake of linoleic acid but also slow its metabolic conversion into AA. This is critical because linoleic acid is the second most abundant fatty acid found in the blood (2) and the levels of hyperinsulinemia have been steadily increasing (5). This is confirmed by the continuing growth of obesity since 2013 (6). Thus, any increase in hyperinsulinemia in the body may accelerate the metabolism of linoleic acid into arachidonic acid (7). This may increase hyperinsulinemia (8).

Reducing the AA/EPA ratio is one of the blood markers that indicate successful use of Metabolic Engineering® to alter metabolic pathways by activating AMPK, the master regulator of your metabolism. Hyperinsulinemia is one of the primary inhibitors of AMPK activity (9).

Macronutrient Balance Matters More Than Calorie Restriction Alone

The best way to reduce hyperinsulinemia is calorie reduction. However, the balance of macronutrients in that level of calorie restriction may be even more important than the simple reduction of calorie intake. This was demonstrated in a 2022 study with type 2 diabetics (10).

In this six-month study, all food was prepared for the subjects, so no thinking was required. Both groups of type 2 diabetics had the same level of calorie restriction, but with a slightly different macronutrient composition. One group received the same macronutrient composition of the Zone diet, and the other group received a slightly higher level of carbohydrates and a lower level of protein, but the same level of fat. Both groups had similar levels of calorie restriction. Although the number of subjects (n=6) in both groups was small because of the expense of running such carefully controlled studies, the results are highly suggestive.

At the end of six months, all six of those following the diet with the macronutrient composition of the Zone diet had complete remission of their type 2 diabetes. In contrast, only one of the members of the other group with the same degree of calorie restriction had success.

This was not an isolated observation, as similar positive results were also seen in other earlier studies with pre-diabetic and non-diabetic obese subjects, suggesting a general response to a specific macronutrient composition (11, 12). Such results were predicted in my patent to reduce hyperinsulinemia issued in 2000 (13). It is pleasing to see them confirmed.

This is why combining adequate intake of EPA with following the Zone diet to activate AMPK becomes a powerful dietary approach to reduce hyperinsulinemia that is strongly associated with many chronic disease conditions.

How Long Does It Take?

How long will it take following Metabolic Engineering® to see a meaningful change in your AA/EPA ratio? About 30 days. How long do you keep following Metabolic Engineering® to reduce your likelihood of developing chronic disease and living longer? The rest of your life.

References

1. Sears B. The OmegaRx Zone. Regan Books. New York, NY (2002)

2. Powers CD, Sternberg MR, Mineva EM, Clifton CC, Leachman JR, Wambogo E, Pfeiffer CM. Over half of the United States population had an undesirably low omega-3 index based on erythrocyte membrane measurements: Results from the cross-sectional NHANES from August 2021 to August 2023. Curr Dev Nutr; 10:107715 (2026). doi: 10.1016/j.cdnut.2026.107715.

3. Harris WS, Pottala JV, Varvel SA, Borowski JJ, Ward JN, McConnell JP. Erythrocyte omega-3 fatty acids increase and linoleic acid decreases with age: observations from 160,000 patients. Prostaglandins Leukot Essent Fatty Acids, 88:257-63 (2013). doi: 10.1016/j.plefa.2012.12.004.

4. Froyen E, Maarafi Z. The consumption of omega-3 fatty acids in American adults. Current Developments in Nutrition 6, 902 (2022). doi.org/10.1093/cdn/nzac067.022.

5. Wu C, Ke Y, Nianogo RA. Trends in hyperinsulinemia and insulin resistance among nondiabetic US adults, NHANES, 1999-2018. J Clin Med. 14:3215 (2025). doi: 10.3390/jcm14093215.

6. Emmerich SD, Fryar CD, Stierman B, Ogden CL. Obesity and severe obesity prevalence in adults: United States, August 2021–August 2023. NCHS Data Brief, Number 508 September 2024 (2024)

7. Brenner RR. Nutrition and hormonal factors influencing desaturation of essential fatty acids. Progress in Lipid Research 20: 41-48 (1982)

8. Erion KA, Corkey BE. Hyperinsulinemia: A cause of obesity? Curr Obes Rep. 6: 178-186 (2017). doi: 10.1007/s13679-017-0261-z.

9. Valentine RJ, Coughlan KA, Ruderman NB, Saha AK. Insulin inhibits AMPK activity and phosphorylates AMPK Ser⁴⁸⁵/⁴⁹¹ through Akt in hepatocytes, myotubes and incubated rat skeletal muscle. Arch Biochem Biophys. 562:62-69 (2014). doi:10.1016/j.abb.2014.08.013.

10. Stentz FB, Lawson D, Tucker S, Christman J, Sands C. Decreased cardiovascular risk factors and inflammation with remission of type 2 diabetes in adults with obesity using a high protein diet: Randomized control trial. Obes Pillars. 4:100047 (2022). doi: 10.1016/j.obpill.2022.100047.

11. Stentz FB, Brewer A, Wan J, Garber C, Daniels B, Sands C, Kitabchi AE. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: Randomized control trial. BMJ Open Diabetes Res Care. 4(1):e000258 (2016). doi: 10.1136/bmjdrc-2016-000258.

12. Kitabchi AE, McDaniel KA, Wan JY, Tylavsky FA, Jacovino CA, Sands CW, Nyenwe EA, Stentz FB. Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial. Diabetes Care. 36:1919-1925 (2013). doi: 10.2337/dc12-1912.

13. Sears, B. Method of and nutritional and pharmaceutical compositions for reduction of hyperinsulinemia. U.S. Patent No. 6,140,304 (2000)

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