It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.Polyunsaturated acids of the n-6 series are essential for proper growth and development (1). This may be supplied as linoleic acid (18:2n6), although arachidonic acid (20:4n6) may also be required (2). Recent evidence derived from non-human primates suggests that n-3 fatty acids are also essential for optimal neural development (3). In human infants, decreases in the level of plasma and erythrocyte membrane docosahexaenoate (22:6n3) are associated with poorer retinal development (4) and lower visual acuity as measured behaviorally by forced choice preferential looking testing and electrophysiologically using pattern reversal visual evoked potential methodology (5). Cognitive scores at 12 months are also lower in infants fed docosahexaenoate-deficient formula (6). This neural n-3 deficiency syndrome has been the subject of several recent reviews (7-10). Carlson et al. (11) have suggested that adequate 20:4n6 is also necessary for optimal growth and cognition. Birch et al. (5) found that a diet high in the n-3 precursor linolenate (18:3n3) was not able to support optimal visual function and that the supply of preformed 22:6n3 appeared necessary in premature infants (5).The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.These studies underline the importance of understanding the metabolism of the 18-carbon essential fatty acids to their elongated and desaturated forms in vivo, particularly of 20:4n6 and 22:6n3. However, not only is there a complete lack of information concerning essential fatty acid metabolism in early human development but there is also a paucity of information in adults and in other primates. In vitro experiments have included the demonstration of A6 desaturation of 14C-labeled 18:2n6 or 18:3n3 and the A5 desaturation of 20:3n6 in liver microsomes from human infants (12) In this study, the ability of human infants to elongate and desaturate essential fatty acids in vivo has been...
The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.
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