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

Abstract

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. The aim of this study was to use the natural variations in 13C:12C ratio (carbon-13 isotopic abundance[δ13C]) of n-3 PUFA supplements to assess n-3 PUFA metabolism following DHA or EPA supplementation in humans. Participants (aged 21.6±2.2 y) were randomly assigned into 1 of 3 supplement groups for 12 wk: 1) olive oil control, 2) ∼3 g/d DHA, or 3) ∼3 g/d EPA. Blood was collected before and after the supplementation period, and concentrations and δ13C of plasma n-3 PUFA were determined. DHA supplementation increased (P<0.05) plasma EPA concentrations by 130% but did not affect plasma δ13C-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 δ13C-DHA (-27.9±0.2 to -25.6±0.1, P<0.05) toward δ13C-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 δ13C-EPA (-31.5±0.2 to -25.7±0.2) and δ13C-DPAn-3 (-28.9±0.3 to -25.0±0.1) toward δ13C-EPA of the supplement. 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. δ13C of n-3 PUFA in humans is a powerful and underutilized tool that can track dietary n-3 PUFA and elucidate complex metabolic questions. This trial was registered at clinicaltrials.gov as NCT03378232.