Quantitation of Human Whole-Body Synthesis-Secretion Rates of DHA and EPA from Circulating Unesterified α-Linolenic Acid at Steady State

摘要

The rate at which dietary α-linolenate (ALA) is desaturated and elongated to its longer chain n-3 PUFA in humans is not agreed upon. In this study, we applied a methodology developed in rodents to investigate whole body, presumably hepatic, synthesis-secretion rates of esterified n-3 PUFA from circulating unesterified ALA in two healthy overweight women after ten weeks of low linoleate diet exposure. During continuous iv infusion of d5-ALA, 17 arterial blood samples were collected from each subject at −10, 0, 10, 20, 40, 60, 80, 100, 120, 150, 180, 210 min, and at 4, 5, 6, 7, and 8 h after beginning infusion. Plasma esterified d5-n-3 PUFA concentrations were plotted against infusion time and fit to a sigmoidal curve using nonlinear regression. These curves were used to estimate kinetic parameters using a kinetic analysis developed in rodents. Calculated synthesis-secretion rates of esterified eicosapentaenoate (EPA), n-3 docosapentaenoate, docosahexaenoic acid (DHA), tetracosapentaenate, and tetracosahexaenoate from circulating unesterified ALA were 2.1 and 2.7; 1.7 and 5.3; 0.47 and 0.27; 0.30 and 0.30; 0.32 and 0.27 mg/day for subjects S01 and S02, respectively. This study provides new estimates of whole body synthesis-secretion rates of esterified longer chain n-3 PUFA from circulating unesterified ALA in human subjects. This method now can be extended to study factors that regulate human whole-body PUFA synthesis-secretion in health and disease.