Abstract
A physiological compartmental model of α-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects. Subjects received a 1-g oral dose of an isotope tracer of α-linolenate (d5-18:3n-3 ethyl ester) while subsisting on a rigorously controlled beef-based diet. By utilizing the Windows Simulation and Analysis Modeling program, kinetic parameters were determined for each subject. Half-lives and mean transit times of the n-3 fatty acids in the plasma were also determined. The model predicted plasma values for the n-3 fatty acids in good accordance with the measured steady state concentrations and also predicted dietary linolenic acid intake for each subject in accordance with values determined by lipid analysis of the diet. Only about 0.2% of the plasma 18:3n-3 was destined for synthesis of 20:5n-3, approximately 63% of the plasma 20:5n-3 was accessible for production of 22:5n-3, and 37% of 22:5n-3 was available for synthesis of 22:6n-3. The inefficiency of the conversion of 18:3n-3 to 20:5n-3 indicates that the biosynthesis of long-chain n-3 PUFA from α-linolenic acid is limited in healthy individuals. In contrast, the much greater rate of transfer of mass from the plasma 20:5n-3 compartment to 22:5n-3 suggests that dietary eicosapentaenoic acid may be well utilized in the biosynthesis of 22:6n-3 in humans. —Pawlosky, R. J., J. R. Hibbeln, J. A. Novotny, and N. Salem, Jr. Physiological compartmental analysis of α-linolenic acid metabolism in adult humans.
Highlights
A physiological compartmental model of ␣-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects
Three sets of information should be evaluated: 1) dietary fatty acid intake from each individual collected over a specified time, 2) kinetic parameters that describe the flux of the distinct biosynthetic intermediates from each subject, and 3) accurate determinations of the masses of endogenous fatty acids in the precursor pools that are available for biosynthesis
This study was carried out to describe the in vivo metabolism of n-3 fatty acids, using isotope tracer methodology to determine plasma steady state fatty acid masses in healthy humans subsisting on a controlled beef-based diet
Summary
A physiological compartmental model of ␣-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects. An accurate model of ␣-linolenic acid metabolism in humans based on direct data obtained from an isotope tracer would be valuable in assessing the contribution of biosynthesis in the maintenance of long-chain n-3 PUFA in the body. Several human studies have been carried out by using stable isotope-based approaches to determine the conversion of essential fatty acids to long-chain PUFA [19,20,21,22,23,24], little quantitative information exists that utilizes compartmental modeling to assess metabolism of 18:3n-3 in humans [25]. Three sets of information should be evaluated: 1) dietary fatty acid intake from each individual collected over a specified time, 2) kinetic parameters (isotopic tracer data) that describe the flux of the distinct biosynthetic intermediates from each subject, and 3) accurate determinations of the masses of endogenous fatty acids in the precursor pools that are available for biosynthesis
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