Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions

The aim of the present study was to quantify the incorporation of eicosapen taenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known a bout the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-lif e, which is needed to establish an optimal dosing schedule. Five healthy vo lunteers ingested two 8.5 g doses of n-3 fatty acid ethyl esters daily for 7 d, supplying 6.0 g EPA/d and 5.3 g DHA/d. The fatty acid compositions of plasma phospholipids (PL), cholesteryl esters (CE) and triacylglycerols (TA G) were determined during supplementation and during a washout period of 7 d. Half-lives of EPA and DHA were calculated. The proportion of EPA in PL s howed a 15-fold increase after 7 d (P < 0.001), while DHA showed a smaller increase (P < 0.01). In CE, EPA also increased (P < 0.05), while DHA did no t increase at all. Remarkably, incorporation of DHA into TAG was even highe r than that of EPA. Half-life of EPA in PL ranged from 1.63 to 2.31 d (mean 1.97 (sE 0.15) d), whereas mean half-life of EPA in CE was 3.27 (sE 0.56) d. In three subjects, washout of EPA and DHA from TAG seemed to follow a bi -exponential pattern, with a short half-life (<1 d) in the initial phase an d a half-life of several days in the second phase. In conclusion, EPA ethyl eaters are rapidly incorporated into plasma lipids, especially into FL. Th e relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of greater than or equal to 12 h in supplementation studies .