The consumption of n-3 PUFAs is associated with multiple health benefits, but the extent of the benefit differs based on whether a-linolenic acid (ALA), docosahexaenoic acid (DHA), or eicosapentaenoic acid (EPA) are consumed.  Oxygenated derivates of PUFAs, or oxylipins, are formed from multiple enzymatic reactions, and oxylipins have multiple biological activities related to inflammation and immune function, for example.  There are a variety of factors that can influence the production of oxylipins, such as sex and age, metabolism and their concentrations.  In order to explore these determinants further, Gabbs and colleagues conducted a study using ALA and DHA-rich supplements to determine the effect of time course and sex on plasma oxylipin concentrations.  Results from their study are published in the March 2021 issue of The Journal of Nutrition.

Subjects for this work were enrolled in a randomized, double-blind crossover trial and included 6 males and 6 nonpregnant, nonlactating females.  They were provided capsules containing approximately 4 g/d of either ALA or DHA.  The treatments were administered during > 6-wk wash-in and wash-out phases.  Plasma concentrations of PUFA and oxylipins were determined on days 0, 1, 3, 7, 14, and 28.

Even though ALA supplementation led to elevated plasma ALA concentrations, it did not affect the levels of ALA oxylipins after 28 days.  In contrast, DHA supplements led to an increase in both plasma DHA and DHA oxylipins.  Time course and sex difference patterns in plasma EPA and EPA oxylipins were similar with DHA supplementation. 

Upcoming ASN Webinar: Research Designs to Account for Diversity and Inclusiveness and Impact Food Guidance Policy

March 11, 2022, 12:30 – 2:00 PM EST

This webinar focuses on the consideration of diversity and inclusion when conducting research to inform and implement food and nutrition guidance policy. This webinar is part of the CASP Nutrition Policy Webinar series, designed to help ASN members better understand the interface between research and nutrition policy.

Register Today!

Of the DHA oxylipins measured, nine reached a plateau in the females, but only 4 reached a plateau in the male subjects.  Some of the oxylipins elevated by DHA administration did not reflect the precursor PUFA consumed.  These observations led the authors to conclude that with similar doses of DHA and ALA, DHA has a greater impact on n-3 and n-6 oxylipins, and that the changes were greater and occurred earlier in the supplementation time frame in female subjects.

In a commentary on this article, Calder suggests the substrate-product relationships must be impacted by subtleties created by PUFA handling and metabolism occurring in males and females.  These could include the roles of sex differences in diet, body size and composition, physical activity and sex hormone status, all of which Calder suggests deserve further examination. 


Gabbs M, Zahradka P, Taylor CG, Aukema HM.  Time course and sex effects of a-linolenic acid-rich and DHA-rich supplements on human plasma oxylipins:  A randomized double-blind crossover trial. The Journal of Nutrition, Volume 151, Issue 3, March 2021, Pages 513–522,

Calder PC. Sex differences in the plasma accumulation of oxylipins in response to supplemental n-3 fatty acids. The Journal of Nutrition, Volume 151, Issue 3, March 2021, Pages 462–464,