Long-chain conversion of [13C]linoleic acid and α-linolenic acid in response to marked changes in their dietary intake in men

Nahed Hussein,Bruce A. Griffin,D. Joe Millward,Eric Ah-Sing,Paul Wilkinson,Clare Leach

doi:10.1194/jlr.m400225-jlr200

Abstract

We studied the long-chain conversion of [U-13C]alpha-linolenic acid (ALA) and linoleic acid (LA) and responses of erythrocyte phospholipid composition to variation in the dietary ratios of 18:3n-3 (ALA) and 18:2n-6 (LA) for 12 weeks in 38 moderately hyperlipidemic men. Diets were enriched with either flaxseed oil (FXO; 17 g/day ALA, n=21) or sunflower oil (SO; 17 g/day LA, n=17). The FXO diet induced increases in phospholipid ALA (>3-fold), 20:5n-3 [eicosapentaenoic acid (EPA), >2-fold], and 22:5n-3 [docosapentaenoic acid (DPA), 50%] but no change in 22:6n-3 [docosahexanoic acid (DHA)], LA, or 20:4n-6 [arachidonic acid (AA)]. The increases in EPA and DPA but not DHA were similar to those in subjects given the SO diet enriched with 3 g of EPA plus DHA from fish oil (n=19). The SO diet induced a small increase in LA but no change in AA. Long-chain conversion of [U-13C]ALA and [U-13C]LA, calculated from peak plasma 13C concentrations after simple modeling for tracer dilution in subsets from the FXO (n=6) and SO (n=5) diets, was similar but low for the two tracers (i.e., AA, 0.2%; EPA, 0.3%; and DPA, 0.02%) and varied directly with precursor concentrations and inversely with concentrations of fatty acids of the alternative series. [13C]DHA formation was very low (<0.01%) with no dietary influences.

Highlights

Experimental studies on the characteristics of the polyunsaturated fatty acid desaturase enzymes suggest that long-chain conversion of PUFA precursors is probably rate limited by the ⌬6-desaturase [10,11,12,13,14], with competition between the n-3, n-6, and n-9 substrates for the enzyme and relative affinities varying as n-3 Ͼ n-6 Ͼ n-9
Dietary compliance was excellent (Table 1), meeting the planned intakes of acid (LA) or [13C]␣-linolenic acid (ALA) (18.6 g/day in the flaxseed oil (FXO) diet, 0.9 g/day in the sunflower oil (SO) and fish oil supplementation (SOF) diets compared with 0.8 g/day at baseline), linoleic acid (LA) (24.8 g/day in the SO diet, 8.4 g/day in the FXO and SOF diets compared with 5.8 g/day at baseline), and longer chain n-3 (2.2 g/day eicosapentaenoic acid (EPA) and 1.4 g/day docosahexanoic acid (DHA) in the SOF diet, 0.8 g/day EPAϩDHA in the FA and SO diets compared with 0.7 g/day EPAϩDHA at baseline)
Our hypothesis in the work described here was that a marked change in the dietary LA/ALA ratio would change the relative rates of formation of n-6:n-3 long-chain polyunsaturated fatty acid (LCP) from their precursor fatty acids as measured by both 13C tracer studies and through compositional changes in erythrocyte fatty acid profiles

Summary

Introduction

Experimental studies on the characteristics of the polyunsaturated fatty acid desaturase enzymes suggest that long-chain conversion of PUFA precursors is probably rate limited by the ⌬6-desaturase [10,11,12,13,14], with competition between the n-3, n-6, and n-9 substrates for the enzyme and relative affinities varying as n-3 Ͼ n-6 Ͼ n-9 This suggests that in practice, the main influences on the elongation of ALA come from competition from linoleic acid (LA) and possibly trans fatty acids. We sought to evaluate the influence of a marked variation in the dietary ALA/LA ratios on their long-chain conversion in terms of a) their accumulation in phospholipids, with a comparison with preformed EPA and DHA from dietary fish oils, and b) the relative conversion rates of [U-13C]ALA and [U-13C]LA to their respective long-chain products In the latter studies, we took into account differential isotope dilution attributable to between-diet and between-series differences in ALA and LA pool sizes. The influence of these dietary changes on cardiovascular risk factors known to be responsive to fish oil supplements has been described elsewhere [31]

Methods

Results

Conclusion