Effect of Fish Oil Supplementation on the n-3 Fatty Acid Content of Red Blood Cell Membranes in Preterm Infants

Abstract

ABSTRACT. Very low birth weight infants demonstrate significant reductions in red blood cell membrane docosahexaenoic acid (DHA, 22:6n-3) following delivery unless fed human milk. The purpose of the present study was to determine if a dietary source of DHA (MaxEPA, R. P. Scherer Corporation, Troy, MI) could prevent the decline in red blood cell phospholipid DHA in very low birth weight infants whose enteral feeding consisted of a preterm formula without DHA. Longitudinal data were obtained on membrane phospholipid DHA in both unsupplemented and MaxEPA-supplemented infants by a combination of thinlayer and gas chromatography. These infants (n = 39) ranged in age from 10 to 53 days at enrollment (0 time). At enrollment, phospholipid DHA and arachidonic acid (20:4n-6) were inversely correlated with age in days. During the study, mean red blood cell phospholipid DHA declined without supplementary DHA as determined by biweekly measurement, but infants supplemented with MaxEPA maintained the same weight percent of phospholipid (phosphatidylethanolanine, phosphatidylcholine, and phosphatidylserine) DHA as at enrollment. and retinal membranes (3). Dietary manipulations which limit accumulation of DHA to 25-50% of controls in these membranes were associated with a 33% reduction in discrimination learning in rats (4), significant reductions in electroretinogram a-wave amplitudes (5), and a 25% loss of visual acuity in the rhesus monkey (5, 6). Furthermore, changes in electroretinograms observed after early deprivation persist following subsequent biochemical normalization of retinal membrane DHA in both species (5,7). Accumulation of DHA in the central nervous system begins at about the 26th wk of gestation in the human fetus (8) with the weight percent of phospholipid DHA approaching adult levels by term (9). Studies in developing rats suggest that differences in red blood cell phospholipid DHA are indicative of qualitative differences in accumulation in the central nervous system. Studies done in very low birth weight preterm infants showed that red blood cell PE DHA was high at birth, but the weight percent declined in the period before infants were nourished completely by orogastric feedings (1). Subsequently, an additional decline in PE DHA occurred in infants fed formula, whereas DHA increased in infants fed mother's milk (I).Infant formula contains linolenic acid (1 8:3n-3) a precursor of DHA. Linoleic (18:2n-6) and linolenic acid are not interconvertible and compete for elongation and desaturation by the same enzyme system. Thus conversion of 20:3n-6 to 20:4n-6 and 20:4n-3 to 20:5n-3 is catalyzed by A5-desaturase and the elongation products of 20:4n-6 and 20:5n-3 (22:4n-6 and 22:5n-3, respectively) are converted to 22:5n-6 and 22:6n-3 by A4-desaturase.Humans appear to have low A4-desaturase activity as indicated by the following observations: 1) diets enriched in 18:3n-3 increase phospholipid 20:5n-3 the A5-desaturase product, but not 22:6n-3, its A4-desaturase product (10); 2) red blood cell membrane phospholipid...

Long-Term Feeding of Formulas High in Linolenic Acid and Marine Oil to Very Low Birth Weight Infants: Phospholipid Fatty Acids

“…VLBW infants may also be at risk for inadequate accumulation of this fatty acid during development, not because of n-3-deficient diets, but because they miss the period of greatest intrauterine accretion (10)(11)(12) and frequently receive diets without DHA after birth (13)(14)(15). RBC DHA declines over time in VLBW infants, and the decline is diminished by human milk feeding (16), bolus administration of marine oil (17), and formulas containing ultrasonically dispersed marine oil (1 8). All of these feeding trials (1 6-18) were of short duration (4-8 wk).…”

“…Short-term study (study 1). The objectives of this study were I ) to compare the acute effects of commercially prepared formulas containing two levels of marine oil on several 20-to 22-carbon n-6 and n-3 fatty acids in preterm infants and 2 ) to make this comparison with formulas containing 3.0% LLA (1.5% energy) instead of 0.6 to 2.0% LLA (approximately 0.3-1 .O% energy) as fed previously (16)(17)(18). Accordingly, infants were fed one of three preterm formulas varying only in their quantity of eicosapentaenoate (EPA, 20:5n-3) and docosahexaenoate (DHA, 22:6n-3) for a period of 4 wk: Formula A did not contain marine oil and was free of EPA and DHA; formula B contained 0.3% EPA and 0.2% DHA from marine oil; and formula C contained 0.7% EPA and 0.4% DHA from marine oil ( Table 2).…”

“…The second study, the extended feeding trial, was designed to provide data about the long-term effects of feeding 0.3% EPA and 0.2% DHA from marine oil on RBC and plasma phospholipid DHA and EPA of VLBW infants. Additionally, we were interested in the qualitative and quantitative effects of extended marine oil feeding on phospholipid AA in these infants: Short-term feeding trials with marine oil supplementation (17,18) have not consistently shown effects on phospholipid AA, but EPA and DHA in marine oil are known to reduce AA in membrane phospholipids. Extended marine oil feeding, coupled with the known declines in AA that occur after premature birth (I 6), could result in clinically significant declines in AA.…”

Selective changes to phosphatidylcholine and phosphatidylethanolamine molecular species in the developing fetal guinea pig liver and plasma

“…One possible interpretation of postnatal changes in the human liver phospholipid molecular species [13] and plasma fatty acid [14][15][16] compositions, in addition to the effects of commencement of oral feeding, is changes to the specificity of fetal hepatic phospholipid biosynthesis. If so, it will then be important to determine the mechanism which regulates developmental changes to hepatic phospholipid metabolism and the effect of variations in this process between individuals on tissue maturation and subsequent function.…”

“…The analysis of liver collected from human infants who were either stillborn or died between 3 and 24 weeks of birth showed a signficant increase in hepatic sn-2 18:2n-6 molecular species during early postnatal life [13]. A decline in plasma 22:6n-3 and arachidonic acid (20:4n-6) has also been reported during the first six weeks after birth in human infants [13][14][15][16]. Such changes to liver and plasma fatty acid composition have been largely attributed to the major nutritional adaptation from placental to milk feeding and consequently the role of any developmental process independent of nutrition has not been established.…”