Increases in plasma n-3 tetracosapentaenoic acid and tetracosahexaenoic acid following 12 weeks of EPA, but not DHA, supplementation in women and men

Dietary feeding and stable isotope studies in rodents support that the 24-carbon omega-3 polyunsaturated fatty acids, tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA), are immediate precursors to docosahexaenoic acid (DHA, 22:6n-3). In this study, we assessed for the first time, changes in TPAn-3 or THA levels following omega-3 PUFA supplementation in humans, providing insight into human omega-3 PUFA metabolism. In this secondary analysis of a double-blind randomized control trial, women and men (19 – 30 years, n = 10 – 14 per sex, per diet) were supplemented with 3 g/day EPA, DHA, or olive oil control for 12 weeks. Plasma TPAn-3 and THA concentrations were determined by gas chromatography-mass spectrometry to determine changes following supplementation in a sex-specific manner (sex x time). EPA supplementation significantly increased (p < 0.0001) plasma TPAn-3 by 215% (1.3 ± 0.1 – 4.1 ± 0.7, nmol/mL ± SEM) and THA by 112% (1.7 ± 0.2 – 3.6 ± 0.5, nmol/mL ± SEM). Furthermore, women had 111% and 99% higher plasma TPAn-3 and THA in the EPA supplemented group compared to men (p < 0.0001). There were no significant effects of time on plasma TPAn-3 or THA concentrations in the DHA supplemented or olive oil supplemented groups. In conclusion, EPA, but not DHA, supplementation in humans increased plasma TPAn-3 and THA levels, suggesting that THA accumulates prior to conversion to DHA in the n-3 PUFA synthesis pathway. Furthermore, women generally exhibit higher plasma TPAn-3 and THA concentrations compared with men, suggesting that women have a greater ability to accumulate 24-carbon n-3 PUFA in plasma via EPA and DPAn-3 elongation, which may explain the known higher DHA levels in women.

Summary: In this secondary analysis of a double-blind randomized control trial, we assessed changes in omega-3 (n-3) tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA) plasma levels in women and men (19 – 30 years, n = 10 – 14 per sex, per diet) following 12-weeks of n-3 PUFA supplementation (3 g/day EPA, DHA or olive oil). Women had higher plasma TPAn-3 in all supplementation groups and higher THA levels in the EPA and olive oil groups (p < 0.0001) compared to men. EPA supplementation increased (p < 0.0001) plasma TPAn-3 by 215% (1.3 ± 0.1 – 4.1 ± 0.7, nmol/mL ± SEM) and THA by 112% (1.7 ± 0.2 – 3.6 ± 0.5, nmol/mL ± SEM), but DHA supplementation had no effect. For the first time in humans, we show that plasma TPAn-3 and THA levels are higher in women and increased with EPA, but not DHA supplementation, suggesting an accumulation of THA prior to conversion to DHA in the n-3 PUFA synthesis pathway.