Human Studies Using Isotope Labeled Fatty Acids: Answered and Unanswered Questions

Human studies using deuterium-labeled fatty acids have answered many questions related to the metabolism and health effects of dietary fats. These studies also raised a number of unanswered questions and unresolved issues. For example, studies with cis and trans positional isomers dispelled concerns and allegations that the isomers in partially hydrogenated fats were poorly absorbed, accumulate in undesirable phospholipid acyl positions, mimic stearic acid and competed with oleic acid. Trans 18:1 isomers were metabolically intermediate between 16:0 and 18:0, so the unanswered question is why are the metabolic properties of trans fatty acids not consistent with their physiological effects? Results from H-2-18:0 studies address questions regarding stearic acid absorption and desaturation. Contrary to accepted dogma, stearic acid was well absorbed and less than 10% was desaturation to oleic acid. The still unanswered question is what is the metabolic basis for why 18:0 is less hypercholesterolemic than other saturated fatty acids? The question of whether humans convert 18:3n-3 to EPA and DHA was investigated by feeding male subjects a mixture of H-2-18:3n-3 and H-2-18:2n-6. The unequivocal answer was that 18:3n-3 is converted to EPA and DHA and the conversions for 18:3n-3 to 20:5n-3 and 18:2n-6 to 20:4n-6 were about equal. A major issue that remains unresolved is the wide variability between studies for the estimated conversion of 18:3n-3 to 20:5n-3 and 22:6n-3. The commercial availability of liquid oils hardened by interesterified with 18:0 has raised the question of whether fatty acids in the sn-2 and sn-1,3 TAG positions are metabolically equivalent. To answer this question, subjects were fed triglycerides containing H-2-16:0 and H-2-18:2n-6 at specific sn-1(3) and sn-2 acyl positions. The result was that dietary fatty acids at the sn-1(3) and sn-2 triacylglycerol positions are essentially metabolically equivalent.