Effect of dietary docosahexaenoic acid on desaturation and uptake in vivo of isotope‐labeled oleic, linoleic, and linolenic acids by male subjects

Abstract

The effect of dietary docosahexaenoic acid (22:6n-3, DHA) on the metabolism of oleic, linoleic, and linolenic acids was investigated in male subjects (n = 6) confined to a metabolic unit and fed diets containing 6.5 or <0.1 g/d of DHA for 90 d. At the end of the diet period, the subjects were fed a mixture of deuterated triglycerides containing 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. Blood samples were drawn at 0, 2, 4, 6, 8, 12, 24, 48, and 72 h. Methyl esters of plasma total lipids, triglycerides, phospholipids, and cholesterol esters were analyzed by gas chromatography-mass spectrometry. Chylomicron triglyceride results show that the deuterated fatty acids were equally well absorbed and diet did not influence absorption. Compared to the low-DHA diet (LO-DHA), clearance of the labeled fatty acids from chylomicron triglycerides was modestly higher for subjects fed the high DHA diet (HI-DHA). DHA supplementation significantly reduced the concentrations of most n-6[d2] and n-3[d4] long-chain fatty acid (LCFA) metabolites in plasma lipids. Accumulation of 20:5n-3[d4] and 22:6n-3[d4] was depressed by 76 and 88%, respectively. Accumulations of 20:3n-6[d2] and 20:4n-6[d2] were both decreased by 72%. No effect of diet was observed on acyltransferase selectivity or on uptake and clearance of 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. The results indicate that accumulation of n-3 LCFA metabolites synthesized from 18:3n-3 in typical U.S. diets would be reduced from about 120 to 30 mg/d by supplementation with 6.5 g/d of DHA. Accumulation of n-6 LCFA metabolites synthesized from 18:2n-6 in U.S. diets is estimated to be reduced from about 800 to 180 mg/d. This decrease is two to three times the amount of n-6 LCFA in a typical U.S. diet. These results support the hypothesis that health benefits associated with DHA supplementation are the combined result of reduced accretion of n-6 LCFA metabolites and an increase in n-3 LCFA levels in tissue lipids.

Metabolism and functional effects of plant-derived omega-3 fatty acids in humans

“…Several studies using ALA labelled with either 13 C or 2 H provide estimates for conversion rates to longer chain more unsaturated derivatives in humans [30,31,57,[108][109][110][111][112] (Table 5). Although the limitations of such studies have been discussed by Emken et al and by Burdge et al who suggest there are unresolved issues regarding tracer studies including; standardisation, quantification, and which lipid pool should be used as a measurement of fatty acid metabolism [113,114].…”

“…Emken et al investigated the effect of increased consumption of DHA. Subjects consumed either < 0.1 g/d DHA or supplemented their diet with 6.5 g/d of purified DHA for 90 days [108]. The group receiving supplemental DHA showed 76% lower EPA synthesis from ALA and 88% lower DHA synthesis.…”

Conversion of α-linolenic acid to longer-chain polyunsaturated fatty acids in human adults

“…While there are advantages in terms of safety, there are unresolved issues regarding standardisation of quantification of data (particularly how conversion between fatty acids should be estimated), kinetic modelling, variation between subjects including age and gender, the method of administration of the labelled fatty acid, the duration of the study, the extent to which the background diet is controlled and the use of measurements of labelled fatty acids in blood (including which lipid pool should be measured) as a marker of fatty acid metabolism within tissues [53]. Together these factors have resulted in considerable heterogeneity in the findings of studies of αLNA metabolism in humans using stable isotope tracers [21,23,25,27,32,[54][55][56][57]. This presents a considerable challenge to any attempt to reach a consensus view on αLNA metabolism in man.…”

Myristic acid increases Δ6-desaturase activity in cultured rat hepatocytes

“…While dietary PUFA are known to coordinately suppress the activity and expression of a wide variety of lipogenic enzymes including ∆6-desaturase [4][5][6][7][8][9], the effect of saturated fatty acids has been less explored. Moreover, most previous studies were performed in intact animals and employed complex mixtures of fatty acids under sufficient essential fatty acid supplementation, thereby making it difficult to discern the effects of specific saturated fatty acids on desaturase activities [10].…”