Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans

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. Subjects received a 1-g oral dose of an isotope tracer of  -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  -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. (Author's Abstract)
This research attempts to develop an accurate model of  -linolenic acid metabolism in humans based on direct data obtained from an isotope tracer. A goal of the mathematical analysis used was to determine the quantitative contributions of each of the dietary fatty acids to the maintenance of long-chain n-3 PUFA homeostasis in plasma. Data obtained indicated that a high rate of flow of 18:3n-3 exiting the biosynthetic pathway may restrict the rate of long-chain PUFA biosynthesis. In this study, only about 0.2% of plasma 18:3n-3 was used in the biosynthesis of 20:5n-3. In contrast, it has been reported that adult humans consuming vegetable oils enriched with  -linolenic acid (flax seed oil) had marked increases in plasma 20:5n-3 as well as increased amounts in the phospholipid fraction of neutrophils but no increases in DHA.  There is much controversy and differing results regarding the conversion of 18:3n-3 to long-chain n-3 PUFA. Gender and diet effects play a role as does individual genetic differences in enzyme activity. Further research is needed to address these discrepancies. (Editor's comments)