Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation

Authors: CHANG, WAN-CHI - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SO, JISUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LAMON-FAVA, STEFANIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/22/2021
Publication Date: 8/11/2021
Citation: Chang, W., So, J., Lamon-Fava, S. 2021. Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation. Scientific Reports. 11:16324. https://doi.org/10.1038/s41598-021-95590-7.
DOI: https://doi.org/10.1038/s41598-021-95590-7

Interpretive Summary: The rate of obesity is increasing at an alarming rate in the U.S. and globally. Obesity affects the whole body metabolism resulting in insulin resistance and an increased risk of diabetes and cardiovascular disease (CVD). Fish and fish oil, containing a mixture of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may reduce the risk of CVD. However, the effect of EPA and DHA on metabolism is not known. We assessed the effect of supplementation with 3 grams/day of EPA versus 3 grams/day DHA on different measures of metabolism in 21 men and women with obesity. We found that both EPA and DHA improved serum levels of compounds involved in the metabolism of carbohydrates, fats, and proteins, but that DHA had a stronger effect then EPA.

Technical Abstract: The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cell function and metabolism, but the differential effects of EPA and DHA are not known. In a randomized, controlled, double-blind, crossover study, we assessed the effects of 10-week supplementation with EPA-only and DHA-only (3 g/d), relative to a 4-week lead-in phase of high oleic acid sunflower oil (3 g/day, defined as baseline), on fasting serum metabolites in 21 subjects (9 men and 12 post-menopausal women) with chronic inflammation and some characteristics of metabolic syndrome. Relative to baseline, EPA significantly lowered the tricarboxylic acid (TCA) cycle intermediates fumarate and a-ketoglutarate and increased glucuronate, UDP-glucuronate, and non-esterified DHA. DHA significantly lowered the TCA cycle intermediates pyruvate, citrate, isocitrate, fumarate, a-ketoglutarate, and malate, and increased succinate and glucuronate. Pathway analysis showed that both EPA and DHA significantly affected the TCA cycle, the interconversion of pentose and glucuronate, and alanine, and aspartate and glutamate pathways (FDR<0.05) and that DHA had a significantly greater effect on the TCA cycle than EPA. Our results indicate that EPA and DHA exhibit both common and differential effects on cell metabolism in subjects with chronic inflammation and some key aspects of metabolic syndrome.