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Effects of beef- and fish-based diets on the kinetics of n-3 fatty acid metabolism in human subjects^1,2

¹ From the Food Composition Laboratory, Beltsville Human Nutrition Research Center, US Department of Agriculture, Beltsville, MD (RJP); the Laboratory of Membrane Biochemistry and Biophysics (JRH, YL, and NS) and the Laboratory of Clinical Studies (PR and NS), National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD; and the Nutrition Department, National Institutes of Health Clinical Center, Bethesda, MD (SG and GLB).

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 (d₅) 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 d₅-18:3n-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 d₅-22:6n-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-3Am J Clin Nutr 2003;77:–72.

Key Words: Fatty acid kinetics • -linolenic acid • n-3 fatty acids • docosahexaenoic acid • compartmental model • isotope tracer • fish diet

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