Effects of beef-and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects

Background: The quantity and type of dietary polyunsaturated fatty acids (PUFAs) can alter essential fatty acid metabolism in humans. Diets rich in 20- and 22-carbon PUFAs may inhibit desaturase expression or activity and decrease the synthesis of long-chain unsaturated fatty acids. Objective: It was theorized that the fat content of a fish-based diet would inhibit the kinetics of the in vivo metabolism of n-3 fatty acids compared with a beef-based diet. Design: A compartmental model was used to determine the coefficients of the kinetic rate constants from the plasma concentration time curves of pentadeuterated (d(5)) 18:3n-3, 20:5n-3, 22:5n-3, and 22:6n-3 of 10 subjects who subsisted on 3 diets with different long-chain PUFA contents. For 3 wk, subjects reported their food intake from their usual diets and then consumed a beef-based diet for 3 wk and then a fish-based diet for an additional 3 wk. Subjects consumed 1 g d(5)-18:3n-3 ethyl ester at weeks 3, 6, and 9. Blood was drawn over 168 h and the plasma analyzed for fatty acids. The coefficients of the kinetic constants of n-3 fatty acid metabolism and the percentage utilization of the substrates were determined. Results: Across all diets, < 1% of plasma 18:3n-3 was utilized for long-chain PUFA synthesis. There was a 70% reduction in the value of the rate constant coefficient that regulated transfer of the isotope from the 22:5n-3 compartment to 22:6n-3 when the fish-based diet was compared with the beef-based diet. The turnover rate of plasma d(5)-22:6n-3 also decreased. Conclusions: The primary effect of a fish-based diet on the kinetics of n-3 metabolism involves processes that inhibit the synthesis of 22:6n-3 from 22:5n-3. These processes may involve a system of feedback control mechanisms responsive to the plasma concentration of 22:6n-3