The disordering effects of docosahexaenoic acid (DHA) on membrane lipid fluidity may counter the stabilising effects of eicosapentaenoic acid (EPA) and explain the discordant clinical outcomes seen with different omega-3 fatty acid (n3-FA) formulations in studies such as REDUCE-IT and STRENGTH.
In a comparative study of n3-FA effects on membrane lipid dynamics and width in large unilamellar vesicles, DHA alone increased bulk lipid fluidity as indicated by a dose-dependent reduction in apparent rotational correlation time (ARCT); at 10 mol%, there was a ~20% (p<0.05) reduction from ~19 to ~16 nsec compared to control (untreated membranes).
In contrast, EPA had no significant disordering effect except when combined at equimolar levels; the EPA/DHA combination showed a reduction in ARCT to ~18 nsec at 10 mol% that was different from EPA alone (p<0.05). Consistent with these findings, small angle x-ray scattering (SAXS) analysis showed DHA containing membranes had a reduced width compared to EPA by 5% or 3 Å (p<0.05) due to increased trans-gauche isomerisations in the phospholipid acyl chains.
The researchers concluded that EPA maintained membrane fluidity while DHA increased fluidity and thus reduced membrane width due to its additional carbons and double bond. The EPA/DHA combination increased membrane fluidity compared to control and EPA alone.
Reference
Sheratt SCR, Shrivastav S, Libby P et al. Eicosapentaenoic Acid and Docosahexaenoic Acid Have Competing Effects on Membrane Lipid Dynamics Due to Differences in Structure. Presented at American Heart Association Scientific Sessions 2023 (11-13 November, Philadelphia, USA). AT.APS.P1 – Lipid Metabolism in Cardiovascular and Metabolic Disease. Sa1008
