title: Incorporation and washout of orally administered n-3 fatty acid ethyl esters in different plasma lipid fractions.
abstract: The aim of the present study was to quantify the incorporation of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into plasma lipids after oral administration of n-3 fatty acid ethyl esters, since little is known about the rate and pattern of incorporation into plasma lipid fractions. In addition, we aimed to obtain preliminary information regarding EPA half-life, which is needed to establish an optimal dosing schedule. Five healthy volunteers 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 (TAG) 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 showed 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 not increase at all. Remarkably, incorporation of DHA into TAG was even higher 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 and a half-life of several days in the second phase. In conclusion, EPA ethyl esters are rapidly incorporated into plasma lipids, especially into PL. The relatively long half-life of EPA in plasma would permit a dosing schedule with intervals of > or = 12 h in supplementation studies.
authors.affiliation: Institute of Internal Medicine II, Erasmus University of Rotterdam, The Netherlands.
authors.forename: S D
authors.initials: SD
authors.lastname: Zuijdgeest-van Leeuwen
authors.forename: P C
authors.initials: PC
authors.lastname: Dagnelie
authors.forename: T
authors.initials: T
authors.lastname: Rietveld
authors.forename: J W
authors.initials: JW
authors.lastname: van den Berg
authors.forename: J H
authors.initials: JH
authors.lastname: Wilson
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002788:Cholesterol Esters / Q000737:chemistry; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
chemical_list: D002788:Cholesterol Esters; D010743:Phospholipids; D014280:Triglycerides; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid