Efficiency of conversion of α-linolenic acid to long chain n-3 fatty acids in man

Abstract

Alpha-linolenic acid (18:3n-3) is the major n-3 (omega 3) fatty acid in the human diet. It is derived mainly from terrestrial plant consumption and it has long been thought that its major biochemical role is as the principal precursor for long chain polyunsaturated fatty acids, of which eicosapentaenoic (20:5n-3) and docosahexaenoic acid (22:6n-3) are the most prevalent. For infants, n-3 long chain polyunsaturated fatty acids are required for rapid growth of neural tissue in the perinatal period and a nutritional supply is particularly important for development of premature infants. For adults, n-3 long chain polyunsaturated fatty acid supplementation is implicated in improving a wide range of clinical pathologies involving cardiac, kidney, and neural tissues. Studies generally agree that whole body conversion of 18:3n-3 to 22:6n-3 is below 5% in humans, and depends on the concentration of n-6 fatty acids and long chain polyunsaturated fatty acids in the diet. Complete oxidation of dietary 18:3n-3 to CO2 accounts for about 25% of 18:3n-3 in the first 24 h, reaching 60% by 7 days. Much of the remaining 18:3n-3 serves as a source of acetate for synthesis of saturates and monounsaturates, with very little stored as 18:3n-3. In term and preterm infants, studies show wide variability in the plasma kinetics of 13C n-3 long chain polyunsaturated fatty acids after 13C-18:3n-3 dosing, suggesting wide variability among human infants in the development of biosynthetic capability to convert 18:3n-3 to 22:6n3. Tracer studies show that humans of all ages can perform the conversion of 18:3n-3 to 22:6n3. Further studies are required to establish quantitatively the partitioning of dietary 18:3n-3 among metabolic pathways and the influence of other dietary components and of physiological states on these processes.

Fatty acid composition of wild anthropoid primate milks

“…The levels of 22:6n-3 in captive-living anthropoid populations were significantly higher than those of their wild-living superfamily counterparts. Data from humans (Brenna, 2005;Francois et al, 2003) and baboons (Greiner et al, 1997;Su et al, 2005) also support the hypothesis that 22:6n-3 levels in milk increase with an increased source of preformed 22:6n-3.…”

“…18:2n-6 is the precursor for all omega-6 (n-6) PUFA, including arachidonic acid (AA, and 18:3n-3 is the precursor for all omega-3 (n-3) PUFA including docosahexaenoic acid (DHA,. Biosynthesis of LCPUFA from PUFA precursors will depend on both the quantity of 18:2n-6 and 18:3n-3 in the diet (Jensen et al, 1995;Carlson, 1999;Brenna, 2005), the ratio of n-3 to n-6 PUFA in the diet (Huang and Brenna, 2001;Brenna, 2005) and the ability to convert n-3 and n-6 PUFA into their longer chain metabolites (Agostoni et al, 2001;Carlson, 2001;Brenna, 2005). Variation in conversion efficiency among species may produce different LCPUFA milk fatty acid composition despite similar dietary intakes of n-3 and n-6 PUFA precursors.…”

Dietary PUFA and cancer

“…The conversion from C 18 : 3n-3 (α-linolenic acid) to C 20 : 5n-3 has been demonstrated to range between 8 and 20 %, while conversion from C 18 : 3n-3 to C 22 : 6n-3 is even lower, i.e. 0·5-9 % (49)(50)(51) . The interaction between certain PUFA types and families, such as C 20 : 5n-3 and C 20 : 3n-6, can determine the effect produced on cell survival and neoplastic development.…”

Should animal fats be back on the table? A critical review of the human health effects of animal fat

“…2. The human metabolism has a trivial ability to increase DHA given extra a-linolenic acid in the diet (Bézard et al 1994;Brenna 2002;Burdge and Calder 2005;Harper et al 2006), although levels of DHA in the serum of self-reported vegans is higher than expected, which if accurate suggests regulation of DHA levels and enhanced endogenous synthesis of DHA in the absence of dietary intake (Welch et al 2010). The starting ratio of shorter-chain n-6 to n-3 PUFA in the diet largely determines the ratio of longer-chain PUFA that are synthesised, and the ratio stored in tissues or cholesteryl-esters is Table 2.…”