Compound-specific isotope analysis reveals no retroconversion of DHA to EPA but substantial conversion of EPA to DHA following supplementation: a randomized control trial

Background: It has long been believed that DHA supplementation increases plasma EPA via the retroconversion pathway in mammals. However, in rodents this increase in EPA is likely due to a slower metabolism of EPA, but this has never been tested directly in humans. Objective: The aim of this study was to use the natural variations in C-13:C-12 ratio (carbon-13 isotopic abundance [delta C-13]) of n-3 PUFA supplements to assess n-3 PUFA metabolism following DHA or EPA supplementation in humans. Methods: Participants (aged 21.6 +/- 2.2 y) were randomly assigned into 1 of 3 supplement groups for 12 wk: 1) olive oil control, 2) similar to 3 g/d DHA, or 3) similar to 3 g/d EPA. Blood was collected before and after the supplementation period, and concentrations and d13C of plasma n-3 PUFA were determined. Results: DHA supplementation increased (P < 0.05) plasma EPA concentrations by 130% but did not affect plasma delta C-13-EPA (-31.0 +/- 0.30 to -30.8 +/- 0.19, milliUrey +/- SEM, P > 0.05). In addition, EPA supplementation did not change plasma DHA concentrations (P > 0.05) but did increase plasma delta C-13-DHA (-27.9 +/- 0.2 to -25.6 +/- 0.1, P < 0.05) toward delta C-13-EPA of the supplement (-23.5 +/- 0.22). EPA supplementation increased plasma concentrations of EPA and docosapentaenoic acid (DPAn-3) by 880% and 200%, respectively, and increased plasma delta C-13-EPA (-31.5 +/- 0.2 to -25.7 +/- 0.2) and delta C-13-DPAn-3 (-28.9 +/- 0.3 to -25.0 +/- 0.1) toward delta C-13-EPA of the supplement. Conclusions: In this study, we show that the increase in plasma EPA following DHA supplementation in humans does not occur via retroconversion, but instead from a slowed metabolism and/or accumulation of plasma EPA. Furthermore, substantial amounts of supplemental EPA can be converted into DHA. [delta C-13] of n-3 PUFA in humans is a powerful and underutilized tool that can track dietary n-3 PUFA and elucidate complex metabolic questions.