Arachidonic acid supply and metabolism in human infants born at full term

Infants need arachidonic acid (AA; C20:4n-6) for eicosanoid synthesis and deposition in growing tissues, including brain. Human milk supplies performed AA in amounts considered to meet accretion in membrane-rich tissues, but vegetable oil-based infant formulas do not contain AA. We studied two groups of ten healthy infants, each fed human milk or formula, and analyzed plasma lipid composition. Percentage contributions of AA to plasma phospholipids were stable over two months after birth in breast-fed infants, but infants fed formula developed significantly (P<0.05) lower levels at the ages of two weeks (formula 6.9% vs. breast 9.4%, w/w), one month (6.2 vs. 9.1%), and two months (5.7 vs 8.4%). In a second trial, we randomized infants to receive (from birth to age four months) formula without or with both AA and docosahexaenoic acid (DHA; C22:6n-3) at levels typical for mature human milk. Infants fed conventional formula showed a continuous decrease of phospholipid AA over time, whereas feeding of formula supplemented with AA and DHA led to significantly higher AA levels, similar to those in breast-fed infants (two months: supplemented 9.6% vs. unsupplemented 7.1%; four months; 8.7 vs. 6.6%). In order to estimate infantile capacity for endogenous synthesis of AA, we fed four term neonates with newly diagnosed phenylketonuria (mean age 18 d) a formula with all fat contributed by corn oil, which has a higher natural¹³C-enrichment than European human milk or formula. Analysis of¹³C-enrichment in plasma fatty acids over four days allowed us to estimate infantile AA synthesis. We found an increased¹³C-value in plasma AA of all infants, which indicates that term neonates can synthesize AA. However, with a simplified isotope balance equation, we estimate that endogenous synthesis contributed only about 23% of total plasma arachidonic acid by day four. We conclude that full-term infants fed formula may require a dietary supply of some preformed AA if the biochemical status of breast-fed infants is to be achieved. Based on a presentations at the AOCS Annual Meeting & Expo in San Antonio, Texas, May 7‐11, 1995.     

First Trimester Urine and Serum Metabolomics for Prediction of Preeclampsia and Gestational Hypertension: A Prospective Screening Study

Hypertensive disorders of pregnancy, including preeclampsia, are major contributors to maternal morbidity. The goal of this study was to evaluate the potential of metabolomics to predict preeclampsia and gestational hypertension from urine and serum samples in early pregnancy, and elucidate the metabolic changes related to the diseases. Metabolic profiles were obtained by nuclear magnetic resonance spectroscopy of serum and urine samples from 599 women at medium to high risk of preeclampsia (nulliparous or previous preeclampsia/gestational hypertension). Preeclampsia developed in 26 (4.3%) and gestational hypertension in 21 (3.5%) women. Multivariate analyses of the metabolic profiles were performed to establish prediction models for the hypertensive disorders individually and combined. Urinary metabolomic profiles predicted preeclampsia and gestational hypertension at 51.3% and 40% sensitivity, respectively, at 10% false positive rate, with hippurate as the most important metabolite for the prediction. Serum metabolomic profiles predicted preeclampsia and gestational hypertension at 15% and 33% sensitivity, respectively, with increased lipid levels and an atherogenic lipid profile as most important for the prediction. Combining maternal characteristics with the urinary hippurate/creatinine level improved the prediction rates of preeclampsia in a logistic regression model. The study indicates a potential future role of clinical importance for metabolomic analysis of urine in prediction of preeclampsia.     

Effect of medium-chain triglycerides on calbindin-D9k expression in the intestine

These studies determined the effect of the saturated fat source in infant formula on the expression of calbindin-D9k (CaBP-9k). Piglets were fed from birth to 8 d with milk or formula containing saturated fatty acids as medium-chain triglycerides (MCT), coconut oil, palm oil (Palm 1), or synthesized triglycerides with 16∶0 directed to thesn-2 position (Palm 2). Levels of intestinal CaBP-9k mRNA were significantly (P<0.01) higher in piglets fed formula with MCT than in piglets fed the other formula or milk; and higher in piglets fed the Palm-1 than in piglets fed Palm-2 formula. This is the first evidence that MCT alter piglet intestinal CaBP-9k mRNA.     

Influence of Fatty Acid Profile of Total Parenteral Nutrition Emulsions on the Fatty Acid Composition of Different Tissues of Piglets

Total parenteral nutrition (TPN) studies in human babies of very-low-birth-weight suggest that the lipid emulsions currently available are not optimum for neonatal nutrition. Since fatty acid metabolism in human and pigs is very similar, the present study examines how lipid emulsions used in clinical TPN (i.e. ClinOleic, Intralipid, Lipofundin or Omegaven), with different fatty acid compositions, administered to neonatal piglets for 7 days, influenced their tissue fatty acid composition as compared to those enterally fed with a sow milk replacer. A positive linear relationship was found between the proportion of all individual fatty acids in the lipid emulsions or in the milk replacer versus those in plasma, skeletal muscle, subcutaneous fat, liver, heart, pancreas, stomach or intestine total lipids or in brain phospholipids, the latter showing the lowest correlation coefficient. With the exception of brain, the proportion of either oleic acid or alpha-linolenic acid in the individual tissues was correlated with those present in the corresponding lipid emulsion or milk replacer, whereas the proportion of linoleic acid correlated significantly with all the tissues studied. With the exception of brain phospholipids, both eicosapentaenoic and docosahexaenoic acids were higher in the tissues of piglets receiving Omegaven than in all other groups. In conclusion, with the exception of the brain, fatty acid composition of plasma and different tissues in piglets are strongly influenced by the fatty acid profile of TPN emulsions. Fatty acid composition of brain phospholipids are, however, much less influenced by dietary composition, indicating an active and efficient metabolism that ensures its appropriate composition at this key stage of development.     

Dietary phospholipid alters biliary lipid composition in formula-fed piglets

Plasma cholesterol, arachidonic acid (AA, 20∶4n−6), and docosahexaenoic acid (DHA, 22∶6n−3) are higher in breast-fed infants than in infants fed formula without cholesterol, AA, or DHA. This study investigated differences in plasma, hepatic, and bile lipids and phospholipid fatty acids, and expression of hepatic proteins involved in sterol metabolism that result from feeding formula with cholesterol with egg phospholipid to provide AA and DHA. For this study, three groups of piglets were evaluated: piglets fed formula with 0.65 mmol/L cholesterol, the same formula with 0.8% AA and 0.2% DHA from egg phospholipid, and piglets fed sow milk. Piglets fed the formula with phospholipid AA and DHA had higher plasma high density lipoprotein, but not apoprotein (apo) B cholesterol or triglyceride; higher bile acid and phospholipid concentrations in bile; and higher liver and bile phospholipid AA and DHA than piglets fed formula without AA and DHA (P<0.05). Hydroxy methylglutaryl (HMG)-CoA reductase and 7-α-hydroxylase, the rate-limiting enzymes of cholesterol and bile acid synthesis, respectively, and low density lipoprotein receptor mRNA levels were not different between piglets fed formula without and with phospholipid AA and DHA, but HMG-CoA reductase and 7α-hydroxylase mRNA were higher, and plasma apo B containing lipoprotein cholesterol was lower in all piglets fed formula than in piglets fed milk. These studies show that supplementing formula with AA and DHA from egg phospholipid alters bile metabolism by increasing the bile AA and DHA, and bile acid and phospholipid.     

Nervonic acid in red blood cell sphingomyelin in premature infants: An index of myelin maturation?

The present study addresses the question whether nervonic acid (24∶1n−9) accumulation in sphingomyelin (SM) of red blood cells (RBC) could yield information on cerebrum maturation in premature infants. The study included 28 premature eutrophic infants of 31.5 wk gestational age. Eleven were fed with human milk, nine with a regulator formula and eight with an α-linolenate-enriched formula. The fatty acid composition of the SM fraction was determined by gas-liquid chromatography on a 50-m fused silica capillary column. At 32 wk gestational age, the main fatty acids in SM were 16∶0, 18∶0, 20∶0, 22∶0, 24∶0 and 24∶1n−9. After five weeks of feeding, at week 37 of postconceptional age, the most striking variation was a rise in 24∶1n−9, from 9.9±0.7 to 12.8±0.9 (P<0.02), regardless of regimen in all three feeding groups. The rise in 24∶1n−9 after birth in premature eutrophic infants is the beginning of a trend toward the higher levels in 24∶1n−9 observed in mature newborns and older infants. The 24∶1n−9 level in SM of RBC from premature infants may reflect 24∶1n−9 levels in SM of brain and could thus reflect brain maturity.     

Addition of long-chain polyunsaturated fatty acids to formula for very low birth weight infants

Thirty-four premature infants who were appropriate for gestational age and weighing less than 1500 g at birth were fed “preemie” SMA-24 formula, “preemie” SMA-24 formula manufactured to contain C₂₀ and C₂₂ ω6 and ω3 fatty acids (LCPE-SMA), or expressed milk (EBM). Blood samples were drawn from a small arm vein during the first week of life and after 28 days of feeding. The fatty acid content of plasma phospholipids was determined. Infants fed SMA-24 had a high content of 18∶2ω6 in plasma phospholipids. Feeding LCPE-SMA normalized plasma phospholipid levels of C₂₀ and C₂₂ ω6 and ω3 fatty acids to be similar to levels of C₂₀ and C₂₂ ω6 and ω3 fatty acids found in infants fed EBM, and significantly higher than characteristic levels for infants fed SMA-24. Feeding LCPE-SMA or EBM results in a balanced incorporation of C₂₀ and C₂₂ ω6 and ω3 fatty acids into phospholipids derived from the liver or perhaps the small intestine. Based on a paper presented at the Symposium on Milk Lipids held at the 1990 AOCS Annual Meeting, Baltimore, MD, April 1990.     

Dietary saturated,monounsaturated, n−6 and n−3 fatty acids,and cholesterol influence platelet fatty acids in the exclusively formula-fed piglet

Platelet lipid composition is important to normal platelet morphology and function, and is influenced by dietary fatty acids and cholesterol. The fatty acid composition and cholesterol content of infant formulas differs from those of human milk, but the possible effects on platelet lipids in young infants is not known. This was studied in piglets fed from birth to 18 d of age with one of eight formulas differing in saturated fatty acid chain length, or content of 18∶1, 20∶5n−3 plus 22∶6n−3, or cholesterol. A reference group of piglets fed sow milk was also studied. Sow milk has a fatty acid composition and cholesterol content similar to that of human milk. Piglets fed formulas high in 18∶1 (34.9–40.8% wt fatty acids) and low in 16.0 (≤6.5% wt fatty acids) had lower platelet counts and greater platelet size than piglets fed sow milk (40.4% 18∶1, 30.7% 16∶0). Piglets fed formulas high in 16∶0 (27–29.6%) and 18∶1 (40–40.6%), or low in both 16∶0 (5.9–6.1%) and 18∶1 (10.8–11.2%), had similar platelet counts and size to piglets fed sow milk. Platelet phospholipid % 20∶4n−6 was lower in all the groups of piglets fed formula than in the group fed sow milk. Addition of fish oil with 20∶5n−3 plus 22∶6n−3 to the formula further decreased platelet phospholipid 20∶4n−6. Addition of cholesterol to the formula increased the platelet phospholipid % 20∶4n−6 and platelet volume.     

Influence of dietary long-chain PUFA on premature baboon lung FA and dipalmitoyl PC composition

One of the major survival challenges of premature birth is production of lung surfactant. The lipid component of surfactant, dipalmitoyl PC (DPPC), increases in concentration in the period before normal term birth via a net shift in FA composition away from unsaturates. We investigated the influence of dietary DHA and arachidonic acid (AA) on lung FA composition and DPPC concentration in term and preterm baboons. Pregnant animals/neonates were randomized to one of four groups: breast-fed (B), term formula-fed (T⁻), preterm formulafed (P⁻), and preterm fed formula supplemented with DHA-AA (P⁺). Breast milk contained 0.68%wt DHA and the P⁺ group formula contained 0.61%wt DHA. In the preterm groups (P⁻ and P⁺), pregnant females received a course of antenatal corticosteroids. At the adjusted age of 4 wk, neonate lung tissue was harvested, and FA composition and DPPC were analyzed. Palmitate was ∼28%wt of lung total FA and no significant differences were found among the four treatment groups. In contrast, DPPC in the B group lung tissue was significantly greater than DPPC in the unsupplemented groups, but not compared with the P⁺ group. The B and P⁺ groups were not significantly different in DHA and AA, but were different compared with the unsupplemented (T, P⁻) groups. These results indicate that LCP supplementation increases lung DHA and AA, without compromising overall lung 16∶0 or DPPC. The shift in FA composition toward greater unsaturation in the groups consuming LCP supported improved surfactant lipid concentration in preterm neonate lungs.     

The nutritive value of Brazilian soy products tested in malnourished children

The nutritive value of a soya milk and soya protein isolate available in Brazil was tested in formulas fed to 30 malnourished children during a period of 25 days. The chemical composition of all formulas was similar, including their energy and protein content. The protein (1.5 g/100 ml) was supplied by either cow's milk, unfortified soy milk, unfortified soy protein isolate, and methionine-enriched soy milk or methionine-enriched soy isolate. Methionine was added at the level of 1.5 g/100 g of protein. The trials included clinical, biochemical and nitrogen balance studies, and results indicated that these soy products formulas did not have the same nutritive value of cow's milk. However, the nutritional quality of soy milk was improved by methionine supplementation, but the soy protein isolate was not affected by the addition of the same amino acid. Average nitrogen retention as percent of intake ranged from 31.8 to 34.7 in the children fed cow's milk. Those that received soy milk retained 10.5 to 15.3%, and when methionine was added the average retention increased from 17.2 to 24.8%. When the isolated soy protein was fed, the average retention values were 14.7 to 16.5% without methionine, and 11.0% when the methionine-supplemented formula was used. Factors that could influence the results and the importance of the subject are discussed.     

In Utero Exposure to Δ9-Tetrahydrocannabinol Leads to Postnatal Catch-Up Growth and Dysmetabolism in the Adult Rat Liver

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9-tetrahydrocannabinol (Δ9-THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9-THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9-THC i.p. from embryonic day (E) 6.5 through E22. Exposure to Δ9-THC decreased the liver to body weight ratio at birth, followed by catch-up growth by three weeks of age. At six months, Δ9-THC-exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interestingly, decreases in miR-203a-3p and miR-29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9-THC-exposed offspring. Collectively, these findings indicate that prenatal Δ9-THC exposure results in long-term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms.     

Diet and the fatty acids in the plasma of lambs during the first eight days after birth

This study reports the plasma lipid changes in lambs receiving either ewes' milk or a reconstituted low fat milk powder during the first eight days after birth. The liveweight gains of the lambs on the artificial diet was less than half that observed in the lambs on the natural diet. The plasma lipid levels in the lambs on the natural diet increased considerably after birth due to large increases in the concentrations of the cholesteryl ester, triglyceride and phospholipid fractions. For the lambs on the artificial diet these fractions remained similar to those observed at birth. In both groups unesterified fatty acid fractions decreased after birth. The main difference between the two groups of lambs was the large increase in C₁₈ polyunsaturated fatty acids observed after birth in the lambs on the natural diet. The triene-tetraene ratio of the fatty acids in the lambs on the natural diet decreased from 1.0 at birth to 0.08 after eight days whereas in the lambs on the artificial diet the ratio increased to 2.9. These composition changes are discussed in relationship to the metabolism of essential fatty acids in monogastric animals.     

Essentiality of dietary ω3 fatty acids for premature infants: Plasma and red blood cell fatty acid composition

Pre-term infants, that are not breast-fed, are deprived of vital intrauterine fat accretion during late pregnancy and must rely on formula to obtain fatty acids essential for normal development, particularly of the visual system. Preterm infants (30 wk postconception) receiving human milk were compared to infants given one of the following formulae: Formula A was a commercial preterm formula with predominantly 18∶2ω6 (24.2%) and low (0.5%) 18∶3ω3; Formula B was based on soy oil and contained similar 18∶2ω6 levels (20%) and high 18∶3ω3 (2.7%); Formula C was also a soy oil-based formula (20% 18∶2, 1.4% 18∶3) but was supplemented with marine oil to provide ω3 long-chain polyunsaturated fatty acids (LCP) at a level (docosahexaenoic acid, DHA, 0.35%) equivalent to human milk. At entry (10 days of age), the fatty acid composition of plasma and red blood cell (RBC) membrane lipids of the formula groups were identical. By 36 wk postconception, the DHA content in lipids of group A was significantly reduced compared to that in the human milk and marine oil formula groups. Omega-3 LCP results were further amplified by 57 wk with compensatory increases in 22∶5ω6 in both plasma and RBC lipids. Provision of 2.7% α-linolenic acid in formula group B was sufficient to maintain 22∶6ω3 levels equivalent to those in human milk-fed infants at 36 wk but not at 57 wk. Effects on the production of thiobarbituric acid reactive substances and fragility of RBC attributable to the marine oil supplementation were negligible. The results support the essentiality of ω3 fatty acids for preterm infants to obtain fatty acid profiles comparable to infants receiving human milk. Formula for preterm infants should be supplemented with ω3 fatty acids including LCP. Based on a paper presented at the Symposium on Milk Lipids held at the AOCS Annual Meeting, Baltimore, MD, April 1990.     

Postnatal Catch-Up Growth Programs Telomere Dynamics and Glucose Intolerance in Low Birth Weight Mice

Low birth weight and rapid postnatal weight gain are independent predictors of obesity and diabetes in adult life, yet the molecular events involved in this process remain unknown. In inbred and outbred mice, this study examines natural intrauterine growth restriction (IUGR) in relation to body weight, telomere length (TL), glucose tolerance, and growth factor gene (Igf1, Igf2, Insr, Igf1r, and Igf2r) mRNA expression levels in the brain, liver, and muscle at 2- and 10 days of age and then at 3- and 9 months of age. At birth, ~15% of the animals showed IUGR, but by 3 and 9 months, half of these animals had regained the same weight as controls without IUGR (recuperated group). At 10 days, there was no difference in TL between animals undergoing IUGR and controls. However, by 3 and 9 months of age, the recuperated animals had shorter TL than the control and IUGR-non recuperated animals and also showed glucose intolerance. Further, compared to controls, Igf1 and Igf2 growth factor mRNA expression was lower in Day 2-IUGR mice, while Igf2r and Insr mRNA expression was higher in D10-IUGR animals. Moreover, at 3 months of age, only in the recuperated group were brain and liver Igf1, Igf2, Insr, and Igf2r expression levels higher than in the control and IUGR-non-recuperated groups. These data indicate that catch-up growth but not IUGR per se affects TL and glucose tolerance, and suggest a role in this latter process of insulin/insulin-like growth signaling pathway gene expression during early development.     

Possible essentiality of docosahexaenoic acid in Japanese monkey neonates: Occurrence in colostrum and low biosynthetic capacity in neonate brains

The importance of mother's milk as a source of docosahexaenoic acid (DHA) in Japanese monkey neonates was investigated. The DHA content in monkey colostrum total lipids was 2.2%, similar to or slightly higher than in humans. A comparison of the biosynthetic capacity of brain microsomes from monkeys of different age (up to 10 years) showed that chain elongation/desaturation of linolenic acid and eicosapentaenoic acid in neonates was significantly less pronounced than in adults. In particular, the formation of DHA, which is the product of Δ4 desaturase, was negligible. These results suggest that milk is an important source of DHA in Japanese monkey neonates.     

Fasting and postprandial lipid response to the consumption of modified milk fats by guinea pigs

The objective of the present study was to investigate the effect of three modified milk fats with different melting profiles on fasting and postprandial lipid responses and on fecal fat content in guinea pigs. We hypothesized that the consumption of modified milk fat with a high m.p. results in reduced fasting and postprandial lipid responses compared with that of modified milk fat fractions with lower m.p. To test this hypothesis, male Hartley guinea pigs were fed isoenergetic diets containing 110 g of fat/kg, either from one of the three modified milk fats with high (HMF), medium (MMF), or low melting profiles (LMF), or from one of the two reference fats as whole mil fat (MF) or a fat blend similar to that of nonhydrogenated soft margarine (MA) for 28 d. Food intake (P<0.05) and body weight gain (P<0.05) were reduced in the animals fed the HMF diet compared with the other groups. In the fasting state, plasma LDL cholesterol was highest in animals fed the LMF diet, intermediary in those fed the MMF and MF diets, and lowest in those fed the HMF and MA diets (P<0.05). Postprandially, the areas under the 0- to 3-h curves for the changes in plasma TG were lower in the HMF group than in the MA- and LMF-fed guinea pigs (P<0.05). The fecal fat content was higher (P<0.05) in the HMF group compared to the other milk fat groups. The present results suggest that modified milk fats can impact food intake, body weight gain, fasting cholesterolemia, and postprandial triglyceridemia, and these changes may be attributed to an altered fat absorption.     

Lutein-fortified infant formula fed to healthy term infants: evaluation of growth effects and safety

Background/Objectives  

Breast milk contains lutein derived from the mother's diet. This carotenoid is currently not added to infant formula, which has a small and variable lutein content from innate ingredients. This study was conducted to compare the growth of infants fed lutein-fortified infant formula with that of infants fed infant formula without lutein fortification.     

Possibility of Breast Cancer Prevention: Use of Soy Isoflavones and Fermented Soy Beverage Produced Using Probiotics

The various beneficial effects of soybeans, which are rich in phytochemicals, have received much attention because of increasing health awareness. Soy milk that has been fermented using lactic acid bacteria has been used to prepare cheese-like products, tofu (bean-curd), and yogurt-type products. However, the distinct odor of soybeans has limited the acceptance of such foods, particularly in Western countries. In Japan, while tofu and soy milk have long been habitually consumed, the development of novel, palatable food products has not been easy. The unpleasant odor of soy milk and the absorption efficiency for isoflavones can be improved using a recently developed fermented soy milk beverage. Cancer has been the leading cause of death, and breast cancer is the most common malignancy among women. The most common type of breast cancer is estrogen-dependent, and the anti-estrogenic effects of isoflavones are known. The present review focuses on the characteristics of soy milk fermented using probiotics, an epidemiological study examining the incidence of breast cancer and soy isoflavone consumption, and a non-clinical study examining breast cancer prevention using fermented soy milk beverage.     

The combined effects of dietary proteins and fish oil on cholesterol metabolism in rats of different ages

Male Sprague-Dawley rats at the ages of four weeks and nine months were fed purified diets containing 20% proteins either as casein (CAS), milk whey protein (WHY), or soybean protein (SOY) with 5% sardine oil for four weeks. The hypocholesterolemic effect of SOY was not statistically evident as compared to milk proteins at both ages, although serum cholesterol tended to be low in the SOY groups. A significant agedependent increase in serum cholesterol was observed in all dietary groups. Liver cholesterol concentrations were comparable in young rats, whereas in adults they were significantly lower in the SOY than in the CAS or WHY groups. At both ages, the activity of liver 3-hydroxy-3-methylglutaryl coenzyme A reductase tended to be higher in the SOY than in the other groups. Fecal steroid excretion was significantly higher in rats fed SOY than those fed either CAS or WHY, especially in adult rats. Significant age- and dietary protein-effects were observed in fatty acid profiles of liver microsomal phospholipids. Thus, the effects of dietary proteins on various lipid parameters were essentially maintained even when fish oil served as the source of dietary fat.     

Docosahexaenoic acid in developing brain and retina of piglets fed high or low α-linolenate formula with and without fish oil

Docosahexaenoic acid (22∶6n−3) can be synthesized in the liver and/or brain from α-linolenic acid (18∶3n−3) and is required in large amounts in structural membranes of developing brain and retina. The adequacy and efficacy of formulas containing 18∶3n−3 and/or fish oil in providing 22∶6n−3 for deposition was investigated in piglets fed formula from birth to 15 days. The test formulas contained high (HL) or low (LL) 18∶3n−3 (3.9 or 0.7% of the total formula fatty acids, respectively), or low 18∶3n−3 plus fish oil (LL+FO) to provide C₂₀ and C₂₂ n−3 polyunsaturated fatty acids (0.8% of total fatty acids). Fatty acid analyses of synaptic plasma membrane and retina ethanolamine phospholipids (EPL), which are especially enriched in 22∶6n−3, were compared to those of 15-day-old piglets fed sow milk (SM). Feeding LL resulted in lower 22∶6n−3 in synaptic plasma membrane. Fatty acid levels in HL and LL+FO piglets were equivalent to SM, with the exception of lower 22∶5n−3 in the synaptic plasma membrane of LL+FO and in the retina of HL and LL+FO-fed piglets. Levels of 22∶4n−6 were also lower in the retina of the LL+FO group. The results suggest formula 18∶3n−3 is at least 24% as effective as C₂₀ and C₂₂ n−3 fatty acids as a source of membrane 22∶6n−3. This study shows dietary 18∶3n−3, as the only n−3 fatty acid, can support deposition of comparable percentage of 22∶6n−3 to natural milk. Fish oil also supported tissue levels of 22∶6n−3 similar to natural milk; however, lower 22∶4n−6 may indicate possible inhibitory effects on n−6 metabolism. Recipient of the 1967 Science and Engineering Scholarship, Natural Sciences & Engineering Research Council of Canada.