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Early childhood is a period of rapid brain development, with increases in synapses rich in the omega-3 (ω-3) fatty acid, DHA (22:6ω-3) continuing well beyond infancy. Despite the importance of DHA to neural phospholipids, the requirement of dietary DHA for neurodevelopment remains unclear.The aim was to assess the dietary DHA and DHA status of young children, and determine the association with cognitive performance.This was a cross-sectional study of healthy children (5-6 y), some of whom were enrolled in a follow-up of a clinical trial (NCT00620672). Dietary intake data (Child DHA intakes were highly variable, with a stronger association between RBC DHA and DHA intake assessed by FFQ (rho = 0.383,Child RBC DHA but not dietary DHA was associated with multiple tests of cognitive performance. In addition, DHA intake was only moderately associated with RBC DHA, raising complex questions on the relation between diet, DHA transfer to membrane lipids, and neural function.

OBJECTIVES: Nutrients such as choline, betaine, folate, and vitamin B12 are required for proper growth and development, but little is known about these nutrients in children. Our objective was to determine intakes and biomarkers of these nutrients in school-aged children (5 to 6 years old). METHODS: A cross-sectional study of healthy children (n = 285) recruited from Vancouver, Canada were assessed. Dietary information was collected using three 24-hour recalls. Nutrient intakes were estimated using the Canadian Nutrient File and USDA database for choline; supplement use was collected by questionnaire. Plasma biomarkers were quantified by mass spectrometry and immunoassay. RESULTS: Daily dietary intakes were (mean ± SD) choline 250 ± 96 mg, betaine 88 ± 41 mg, folate 335 ± 126 µg DFE, and vitamin B12 3.78 ± 2.71 µg. Top food sources were dairy and eggs (42–57%) for choline and vitamin B12, and cereal and grains (41–60%) for betaine and folate. Only 40% of children met the choline adequate intake (AI) recommendation for North America (≥250 mg/d); 81.5% met the European AI (≥170 mg/d). Plasma free choline, betaine, and dimethylglycine concentrations were (mean ± SD) 8.62 ± 2.13 µmol/L, 45.3 ± 13.7 µmol/L, 3.34 ± 1.03 µmol/L, respectively. Dietary choline intake and plasma free choline were not related. However, dietary choline intake was positively associated with plasma dimethylglycine. Less than 5% of children had inadequate folate and vitamin B12 intakes. More than half of the children (59.4%) were consuming a supplement containing B-vitamins, but none included choline or betaine. Some children (5.26%) had total folic acid intakes above the North American upper limit (UL; >400 µg/d); 10.90% had intakes above the European UL (>300 µg/d). Vitamin B12 intake was positively associated with plasma total vitamin B12 (mean ± SD; 594 ± 158 pmol/L) in an adjusted model (sex, age, total energy intake, and supplement use; p

Altered total plasma n-6 and n-3 fatty acids are common in cystic fibrosis (CF). Whether alterations extend to plasma phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and are explained by diet is unclear. The present study was to describe the dietary intake of a large group of children with CF and to determine whether dietary fat composition explains differences in plasma PC and PE fatty acids between children with and without CF.Dietary intake was assessed using a food frequency questionnaire. Venous blood was collected. Plasma PC and PE were separately analyzed for fatty acids.Children with CF, n = 74, consumed more calories and fat (g/day and % energy), with significantly more saturates mainly from dairy foods and less polyunsaturates including linoleic acid (LA), arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) (% fat) than reference children, n = 71. A subset of children with CF, not differing in dietary intake from the larger group, had significantly lower LA and DHA, but higher EPA in plasma PC and had higher LA and lower ARA and DHA in plasma PE, compared to a subset of reference children. In both groups, LA intake and LA in plasma PC and PE were not associated. EPA and DHA intakes were positively associated with EPA and DHA, respectively, in plasma PC, but not PE, in reference children only.The fatty acid composition of plasma PC and PE is altered in CF. Fatty acid differences between children with and without CF are inconsistent between PC and PE and are not explained by dietary fat.

Choline is critical for infant development and mother&rsquo, s milk is the sole source of choline for fully breastfed infants until six months of age. Human milk choline consists to 85% of water-soluble forms of choline including free choline (FC), phosphocholine (PhosC), and glycerophosphocholine (GPC). Donor milk requires safe handling procedures such as cold storage and pasteurization. However, the stability of water-soluble forms of choline during these processes is not known. The objectives of this research were to determine the effect of storage and pasteurization on milk choline concentration, and the diurnal intra- and inter-individual variability of water-soluble choline forms. Milk samples were collected from healthy women who were fully breastfeeding a full-term, singleton infant &lt, 6 months. Milk total water-soluble forms of choline, PhosC, and GPC concentrations did not change during storage at room temperature for up to 4 h. Individual and total water-soluble forms of choline concentrations did not change after storage for 24 h in the refrigerator or for up to one week in the household freezer. Holder pasteurization decreased PhosC and GPC, and thereby total water-soluble choline form concentrations by &lt, 5%. We did not observe diurnal variations in PhosC and total water-soluble forms of choline concentrations, but significant differences in FC and GPC concentrations across five sampling time points throughout one day. In conclusion, these outcomes contribute new knowledge for the derivation of evidence-informed guidelines for the handling and storage of expressed human milk as well as the development of optimized milk collection and storage protocols for research studies.

Long-chain n-6 and n-3 PUFAs are important for growth and development. However, little is known about requirements and current dietary intakes of these fatty acids in toddlers.This study assessed dietary intakes of n-6 and n-3 PUFAs and determined the relation to circulating PUFAs in toddlers at ages 1 and 2 y.This is a secondary analysis of data from toddlers enrolled in a double-blind randomized controlled trial of arachidonic acid (ARA) and DHA supplementation between ages 1 and 2 y. Dietary intakes of fatty acids were estimated by 3-d food records, and fatty acid composition in plasma total phospholipids, red blood cell phosphatidylethanolamine (PE), and phosphatidylcholine (PC) were assessed by GC at baseline in all subjects (n = 110; mean age 1.12 y; 64% male) and in the control subjects at 2 y (n = 43).The dietary intakes of ARA, EPA, and DHA at age 1 y (baseline) were [mean (median)] 36.8 (30.0), 16.0 (0.00), and 31.1 (10.0) mg/d, respectively. Dietary intakes increased to 52.7 (45.0), 35.8 (0.00), and 64.8 (20.0) mg/d, respectively, at age 2 y (P 0.05). The predominant dietary source of EPA and DHA was fish/seafood; eggs were an important source of ARA and DHA. Dietary DHA intakes were positively associated with plasma PE and PC DHA (P 0.05). No relations between dietary ARA intakes and plasma PE and PC ARA (P 0.05) were observed.These findings suggest that most toddlers are not meeting the recommendation for dietary PUFA intakes and that higher dietary DHA intakes are reflected in plasma PE and PC DHA composition. Further work is required to investigate a biomarker for dietary ARA intake. This trial is registered at clinicaltrials.gov as NCT01263912.

Preterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes. A cohort of 60 preterm newborns (24–32 wk gestational age) was assessed using early and near-term magnetic resonance imaging (MRI) studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 mo corrected age was assessed using the Bayley Scales of Infant Development, 3rd edition. Adjusting for confounders, a 1% increase in postnatal docosahexaenoic acid (DHA) levels at early MRI was associated with 4.3-fold decreased odds of intraventricular hemorrhage, but was not associated with white matter injury or cerebellar haemorrhage. Higher DHA and lower linoleic acid (LA) levels at early MRI were associated with lower diffusivity in white matter tracts and corresponding improved developmental scores in follow-up. Higher DHA and lower LA levels in the first few weeks of life are associated with decreased intraventricular haemorrhage, improved microstructural brain development, and improved outcomes in preterm born children. Early and possibly antenatal interventions in high-risk pregnancies need to be studied for potential benefits in preterm developmental outcomes.

Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients for normal brain development. The principal dietary n-6 and n-3 PUFAs are linoleic acid (LA) and α-linolenic acid (ALA), respectively, We have previously shown that maternal dietary imbalance between these PUFAs, i.e., rich in LA and poor in ALA, affected brain development and increased anxiety-related behavior in the mouse offspring. Here we further addressed sex difference in anxiety-related behavior in the offspring exposed to maternal LA:ALA imbalance. We fed pregnant mice a LA excess/ALA deficient (LA(ex)/ALA(def)) diet, and raised their offspring on a well-balanced LA:ALA diet from an early lactation period. When the offspring were grown to adulthood, they were subjected to behavioral and biochemical analyses. We found that both male and female offspring exposed to the LA(ex)/ALA(def) diet showed increased anxiety-related behavior compared to those exposed to the control diet, which was differently observed between the sexes. The female offspring also exhibited hyperactivity by maternal intake of the LA(ex)/ALA(def) diet. On the other hand, abnormal depressive behavior was undetected in both sexes. We also found that the ratio of n-6 to n-3 PUFAs in the brain was unaffected regardless of maternal diet or offspring's sex. Since the n-6/n-3 ratio is known to influence emotional behavior, it is reasonable to assume that LA:ALA imbalance exposed during brain development is the key for causing enhanced anxiety in adulthood. The present study indicates that maternal dietary imbalance between LA and ALA increases offspring's anxiety-related behavior with a sex-dependent manner.

Vitamin D deficiency affects more that 1 billion people worldwide. Although thought to increase risk of bacterial infections, the importance of vitamin D on host defense against intestinal bacterial pathogens is currently unclear since injection of the active form of vitamin D, 1,25(OH)2D3, increased susceptibility to the enteric bacterial pathogen Citrobacter rodentium by suppressing key immune/inflammatory factors. To further characterize the role of vitamin D during bacteria-induced colitis, we fed weanling mice either vitamin D3-deficient or vitamin D3-sufficient diets for 5 wk and then challenged them with C. rodentium. Vitamin D3-deficient mice lost significantly more body weight, carried higher C. rodentium burdens, and developed worsened histological damage. Vitamin D3-deficient mice also suffered greater bacterial translocation to extra-intestinal tissues, including mesenteric lymph nodes, spleen, and liver. Intestinal tissues of infected vitamin D3-deficient mice displayed increased inflammatory cell infiltrates as well as significantly higher gene transcript levels of inflammatory mediators TNF-α, IL-1β, IL-6, TGF-β, IL-17A, and IL-17F as well as the antimicrobial peptide REG3γ. Notably, these exaggerated inflammatory responses accelerated the loss of commensal microbes and were associated with an impaired ability to detoxify bacterial lipopolysaccharide. Overall, these studies show that dietary-induced vitamin D deficiency exacerbates intestinal inflammatory responses to infection, also impairing host defense.

There are concerns around safety and tolerance of powder human milk fortifiers to optimize nutrition in preterm infants. The purpose of this study was to evaluate the tolerance and safety of a concentrated preterm formula (CPF) as a liquid human milk fortifier (HMF) for premature infants at increased risk of feeding intolerance. We prospectively enrolled preterm infants over an 18-month period, for whom a clinical decision had been made to add CPF to human milk due to concerns regarding tolerance of powder HMF. Data on feed tolerance, anthropometry, and serum biochemistry values were recorded. Serious adverse events, such as mortality, necrotizing enterocolitis (NEC), and sepsis, were monitored. A total of 29 babies received CPF fortified milk during the study period. The most common indication for starting CPF was previous intolerance to powder HMF. Feeding intolerance was noted in 4 infants on CPF. The growth velocity of infants was satisfactory (15.9 g/kg/day) after addition of CPF to feeds. The use of CPF as a fortifier in preterm babies considered at increased risk for feed intolerance seems well tolerated and facilitates adequate growth. Under close nutrition monitoring, this provides an additional option for human milk fortification in this challenging subgroup of preterm babies, especially in settings with limited human milk fortifier options.

Human milk contains nutritional, immunoprotective and developmental components that support optimal infant growth and development. The milk fat globule membrane (MFGM) is one unique component, comprised of a tri-layer of polar lipids, glycolipids, and proteins, that may be important for brain development. MFGM is not present in most infant formulas. We tested the effects of bovine MFGM supplementation on reflex development and on brain lipid and metabolite composition in rats using the “pup in a cup” model. From postnatal d5 to d18, rats received either formula supplemented with MFGM or a standard formula without MFGM; a group of mother-reared animals was used as reference/control condition. Body and brain weights did not differ between groups. MFGM supplementation reduced the gap in maturation age between mother-reared and standard formula-fed groups for the ear and eyelid twitch, negative geotaxis and cliff avoidance reflexes. Statistically significant differences in brain phospholipid and metabolite composition were found at d13 and/or d18 between mother-reared and standard formula-fed groups, including a higher phosphatidylcholine:phosphatidylethanolamine ratio, and higher phosphatidylserine, glycerol-3 phosphate, and glutamine in mother-reared compared to formula-fed pups. Adding MFGM to formula narrowed these differences. Our study demonstrates that addition of bovine MFGM to formula promotes reflex development and alters brain phospholipid and metabolite composition. Changes in brain lipid metabolism and their potential functional implications for neurodevelopment need to be further investigated in future studies.

ObjectiveWHO uses anthropometric classification scheme of childhood acute and chronic malnutrition based on low body mass index (BMI) (‘wasting’) and height for age (‘stunting’), respectively. The goal of this study was to describe a novel two-axis nutritional classification scheme to (1) characterise nutritional profiles in children undergoing abdominal surgery and (2) characterise relationships between preoperative nutritional status and postoperative morbidity.DesignThis was a retrospective observational cohort study.SettingThe setting was 50 hospitals caring for children in North America that participated in the American College of Surgeons National Surgical Quality Improvement Program Paediatric from 2011 to 2013.ParticipantsChildren >28 days who underwent major abdominal operations were identified.Interventions/main predictorThe cohort of children was divided into five nutritional profile groups based on both BMI and height for age Z-scores: (1) underweight/short, (2) underweight/tall, (3) overweight/short, (4) overweight/tall and (5) non-outliers (controls).Main outcome measuresMultiple variable logistic regressions were used to quantify the association between 30-day morbidity and nutritional profile groups while adjusting for procedure case mix, age and American Society of Anaesthesiologists class.ResultsA total of 39 520 cases distributed as follows: underweight/short (656, 2.2%); underweight/tall (252, 0.8%); overweight/short (733, 2.4%) and overweight/tall (1534, 5.1%). Regression analyses revealed increased adjusted odds of composite morbidity (35%) and reintervention events (75%) in the underweight/short group, while overweight/short patients had increased adjusted odds of composite morbidity and healthcare-associated infections (43%), and reintervention events (79%) compared with controls.ConclusionStratification of preoperative nutritional status using a scheme incorporating both BMI and height for age is feasible. Further research is needed to validate this nutritional risk classification scheme for other surgical procedures in children.

BackgroundThe naturally occurring α-tocopherol (α-T) stereoisomer, RRR-α-tocopherol (RRR-α-T), is known to be more bioactive than all-rac-α-tocopherol (all-rac-α-T), a synthetic racemic mixture of 8 stereoisomers. There is widespread use of all-rac-α-T in maternal supplements.ObjectiveThe aim of the study was to thoroughly describe the α-T stereoisomer profile of human milk.MethodsWe measured the α-T stereoisomer profile in milk from 2 cohorts of women: a cohort of 121 women who provided milk on days 30 and 60 of lactation (study 1) and a separate cohort of 51 women who provided milk on days 10, 21, 71, and 120 of lactation (study 2).ResultsRRR-α-T was the predominant stereoisomer (P < 0.0001) in all samples in both studies despite a large intrasubject range in total α-T (0.7–22 μg/mL). On average, RRR-α-T comprised 73–76% of total α-T, but average values for the synthetic stereoisomers were RRS, 8–14%; RSR, 6–8%; RSS, 5–6%; and the sum of 2S stereoisomers (Σ2S), 3–5%. Despite the predominance of RRR-α-T, the sum of the synthetic stereoisomers comprised as much as 48% of total α-T. We calculated the ratio of RRR to the sum of the synthetic 2R (RRS + RSR + RSS) stereoisomers (s2R) to assess the degree to which RRR is favored in milk. Consistent with discrimination among 2R stereoisomers in mammary tissue, RRR/s2R values ranged from 2.8 to 3.6, as opposed to the expected ratio of 0.33 if there was no discrimination. However, the RRR to s2R ratio did not correlate with milk α-T concentration, but both components of the ratio did.ConclusionsRRR-α-T is the predominant stereoisomer in human milk, concentrations of synthetic 2R stereoisomers were notable, and the relation between milk total α-T and stereoisomer profile is complex. Due to the wide range found in milk α-T stereoisomer profile, investigation into its impact on α-T status and functional outcomes in breastfed infants is warranted.

BACKGROUND Plasma concentrations of choline and its metabolites might serve as biomarkers for the health outcomes of several pathological states such as cardiovascular disease and cancer. However, information about the reliability of biomarkers of choline status is limited. We investigated biological variations in repeated measures of choline and metabolites in healthy adults to assess them as biomarkers. METHODS Blood samples were collected after an overnight fast at three-time points 12 days apart from 40 adults (mean age, 33 y; male, n = 21). A subset (n = 19; [male, n = 8]) provided one additional sample after a breakfast meal. Plasma free choline, betaine and dimethylglycine were measured using liquid chromatography-tandem mass spectrometry, and plasma phosphatidylcholine, sphingomyelin and lysophosphatidylcholine were measured using high-performance liquid chromatography. RESULTS The biological variations observed for choline and metabolites were ≤ 13% for adult fasting samples. This corresponded to intra-class correlations (ICC) that ranged from 0.593 to 0.770 for fasting values for choline and metabolites. A similar ICC range was also obtained between fasting and post-prandial states. Although most post-prandial concentrations of choline and metabolites were significantly higher (P

Choline has critical roles during periods of rapid growth and development, such as infancy. In human milk, choline is mostly present in water-soluble forms (free choline, phosphocholine, and glycerophosphocholine). It is thought that milk choline concentration is influenced by maternal choline intake, and the richest food sources for choline are of animal origin. Scarce information exists on milk choline from countries differing in animal-source food availability. In this secondary analysis of samples from previous trials, the concentrations of the water-soluble forms of choline were quantified by liquid chromatography-tandem mass spectrometry in mature milk samples collected from lactating women in Canada (n = 301) and in Cambodia (n = 67). None of the water-soluble forms of choline concentrations in milk differed between Canada and Cambodia. For all milk samples (n = 368), free choline, phosphocholine, glycerophosphocholine, and the sum of water-soluble forms of choline concentrations in milk were (mean (95%CI)) 151 (141, 160, 540 (519, 562), 411 (396, 427), and 1102 (1072, 1133) µmol/L, respectively. Theoretically, only 19% of infants would meet the current Adequate Intake (AI) for choline. Our findings suggest that the concentrations in milk of water-soluble forms of choline are similar in Canada and Cambodia, and that the concentration used to set the infant AI might be inaccurate.

Background Choline is an important nutrient during development. However, there are limited data on dietary choline intake and status in toddlers and the relation to neurodevelopmental outcomes. Objective This study assessed dietary choline intake and status in healthy toddlers at ages 1 and 2 y and determined the relation to neurodevelopmental outcomes. Methods This is a secondary analysis of data from healthy toddlers enrolled in a double-blind, randomized controlled trial of long-chain polyunsaturated fatty acid supplementation between ages 1 and 2 y. Dietary intakes of betaine and choline were estimated by 3-d food records; plasma free choline, betaine, and dimethylglycine were quantified by liquid chromatography-tandem mass spectrometry. Developmental outcomes were assessed at age 2 y with the use of the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III), Cognitive and Language composites, and the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI). Results The mean ± SD daily intake for total choline at age 1 y was 174 ± 56.2 mg/d and increased (P

BACKGROUND Vitamin D supplementation is recommended for breastfed infants. Maternal supplementation beginning in gestation is a potential alternative, but its efficacy in maintaining infant 25-hydroxyvitamin D [25(OH)D] concentration after birth is unknown. OBJECTIVES We determined the effect of 3 doses of maternal vitamin D supplementation beginning in gestation and continued in lactation on infant serum 25(OH)D and compared the prevalence of infant serum 25(OH)D cutoffs (>30, >40, >50, and >75 nmol/L) by dose at 8 wk of age. DESIGN Pregnant women (n = 226) were randomly allocated to receive 10, 25, or 50 μg vitamin D₃/d from 13 to 24 wk of gestation until 8 wk postpartum, with no infant supplementation. Mother and infant blood was collected at 8 wk postpartum. RESULTS At 8 wk postpartum, mean [nmol/L (95% CI)] infant 25(OH)D at 8 wk was higher in the 50-μg/d [75 (67, 83)] than in the 25-μg/d [52 (45, 58)] or 10-μg/d [45 (38, 52)] vitamin D groups (P 75 nmol/L compared with 44% in the 50-μg/d group (P 30 nmol/L. At 8 wk postpartum, mean maternal 25(OH)D concentration was higher in the 50-μg/d [88 (84, 91)] than in the 25-μg/d [78 (74, 81)] or 10-μg/d [69 (66, 73)] groups (P < 0.05). CONCLUSIONS Maternal supplementation beginning in gestation with 50 μg vitamin D₃/d protects 98% of unsupplemented breastfed infants against 25(OH)D deficiency (

Palmitic acid (16:0) is a saturated fatty acid present in the diet and synthesized endogenously. Although often considered to have adverse effects on chronic disease in adults, 16:0 is an essential component of membrane, secretory, and transport lipids, with crucial roles in protein palmitoylation and signal molecules. At birth, the term infant is 13-15% body fat, with 45-50% 16:0, much of which is derived from endogenous synthesis in the fetus. After birth, the infant accumulates adipose tissue at high rates, reaching 25% body weight as fat by 4-5 months age. Over this time, human milk provides 10% dietary energy as 16:0, but in unusual triglycerides with 16:0 on the glycerol center carbon. This paper reviews the synthesis and oxidation of 16:0 and possible reasons why the infant is endowed with large amounts of fat and 16:0. The marked deviations in tissues with displacement of 16:0 that can occur in infants fed vegetable oil formulas is introduced. Assuming fetal fatty acid synthesis and the unusual delivery of 16:0 in human milk evolved to afford survival advantage to the neonate, it is timely to question if 16:0 is an essential component of tissue lipids whereby both deficiency and excess are detrimental.

Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

The possibility that western diets poor in omega-3 and rich in omega-6 fatty acids contribute to the increasing burden of chronic diseases including neurological problems is becoming recognized. Modern, westernized diets provide 80 to 90% of polyunsaturated fatty acids as omega-6 linoleic acid (LA) and are depleted in omega-3 fatty acids, giving a distorted balance of LA to α-linoleic acid, and to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). LA intakes exceed Δ-6 desaturase needs for maximal activity. LA accumulates in blood and tissue lipids with increasing intake, and this exacerbates competition between LA and limited omega-3 fatty acids for metabolism and acylation into tissue lipids. Increasing EPA and DHA intake decreases tissue omega-6 fatty acids while also providing EPA and DHA. However, strategies for EPA and DHA supplementation do not address potential underlying problems of omega-6 and omega-3 fatty acid imbalance in the food supply.

Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94), p < 0.001) and girls (11.19 (4.69–17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.

Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition. Here we tested the effects of MFGM supplementation on intestinal development and the microbiome as well as its potential to protect against Clostridium difficile induced colitis. The pup-in-a-cup model was used to deliver either control or MFGM supplemented formula to rats from 5 to 15 days of age; with mother’s milk (MM) reared animals used as controls. While CTL formula yielded significant deficits in intestinal development as compared to MM littermates, addition of MFGM to formula restored intestinal growth, Paneth and goblet cell numbers, and tight junction protein patterns to that of MM pups. Moreover, the gut microbiota of MFGM and MM pups displayed greater similarities than CTL, and proved protective against C. difficile toxin induced inflammation. Our study thus demonstrates that addition of MFGM to formula promotes development of the intestinal epithelium and microbiome and protects against inflammation.

Low plasma sex hormone-binding globulin (SHBG) levels are a hallmark in chronic metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), which represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The functional link between altered SHBG production and NAFLD development and progression remains unclear. We investigated the effects of overexpressing human SHBG in 2 mouse models of NAFLD: a genetically induced double transgenic mouse and a diet-induced model. Remarkably, SHBG overexpression in both NAFLD models significantly reduced liver fat accumulation by reducing key lipogenic enzymes. These findings were corroborated by modulating SHBG expression and by adding exogenous SHBG in HepG2 cells, suggesting the cell autonomous nature of the mechanism. Mechanistically, exogenous SHBG treatment downregulated key lipogenic enzymes by reducing PPARγ messenger RNA and protein levels through activation of extracellular signal-regulated kinase-1/2 mitogen-activated protein kinase pathway. Taking together, we found that SHBG modulates hepatic lipogenesis. This is of importance because reduction of SHBG plasma levels in obese and type 2 diabetic subjects could be directly associated with NAFLD development through an increase in hepatic lipogenesis. Our results point to SHBG as a therapeutic target for preventing or arresting NAFLD development.

The science of lipid research continues to rapidly evolve and change. New knowledge enhances our understanding and perspectives on the role of lipids in health and nutrition. However, new knowledge also challenges currently held opinions. The following are the proceedings of the 2013 Canadian Nutrition Society Conference on the Advances in Dietary Fats and Nutrition. Content experts presented state-of-the-art information regarding our understanding of fish oil and plant-based n-3 polyunsaturated fatty acids, nutrigenomics, pediatrics, regulatory affairs, and trans fats. These important contributions aim to provide clarity on the latest advances and opinions regarding the role of different types of fats in health.

Background: Choline needs are increased in pregnancy. Choline can be used as a source of methyl for homocysteine remethylation to methionine, but choline synthesis requires methyls from methionine. Vitamin B-12 deficiency increases choline use for homocysteine methylation. Objectives: We investigated whether poor vitamin B-12 status occurs and contributes to low plasma choline and altered biomarkers of choline synthesis in pregnant women. With the use of a post hoc analysis, we addressed the association of maternal plasma vitamin B-12 status with postnatal growth rates in term infants. Design: Blood was analyzed for a prospective study of 264 and 220 pregnant women at 16 and 36 wk of gestation, respectively, and 88 nonpregnant women as a reference. Results: The proportion of women with a plasma total vitamin B-12 concentration ,148 pmol/L (deficient) or 148‐220 pmol/L (marginal) increased with pregnancy and pregnancy duration, which affected 3% and 9% of nonpregnant women, 10% and 21% of women at 16 wk of gestation, and 23% and 35% of women at 36 wk of gestation, respectively. Plasma free choline, betaine, and dimethylglycine were lower in women at 36 wk of gestation with a deficient or marginal compared with sufficient plasma total vitamin B-12 concentration (.220 pmol/L). Plasma total vitamin B-12 was positively associated with the increase in plasma free choline from midgestation to late gestation (P , 0.001). The postnatal growth rate to 9 mo was lower in infant boys of women classified as total vitamin B-12 deficient compared with sufficient. Conclusion: This study shows that maternal vitamin B-12 status is related to choline status in late gestation in a folate-replete population and may be a determinant of infant growth even in the absence of undernutrition. Am J Clin Nutr doi: 10.3945/ajcn.113.060269.

Fetal alcohol spectrum disorders result in long-lasting neurological deficits including decreases in synaptic plasticity and deficits in learning and memory. In this study we examined the effects of prenatal ethanol exposure on hippocampal synaptic plasticity in male and female Sprague-Dawley rats. Furthermore, we looked at the capacity for postnatal dietary intervention to rescue deficits in synaptic plasticity. Animals were fed an omega-3 enriched diet from birth until adulthood (PND55-70) and in vivo electrophysiology was performed by stimulating the medial perforant path input to the dentate gyrus and recording field excitatory post-synaptic potentials. LTP was induced by administering bursts of five 400 Hz pulses as a theta-patterned train of stimuli (200 ms inter-burst interval). Ethanol-exposed adult males, but not females, exhibited a significant reduction in LTP. This deficit in male animals was completely reversed with an omega-3 enriched diet. These results demonstrate that omega-3 fatty acids can have benefits following prenatal neuropathological insults and may be a viable option for alleviating some of the neurological deficits associated with FASD.

Human milk TAG contain 20–25% 16:0, with over 70% of the 16:0 at the TAG sn-2 position. The benefits of TAG sn-2 16:0 have been ascribed to reducing 16:0 excretion as insoluble fatty acid soaps. This study builds on knowledge that infants conserve milk TG sn-2 16:0 post-absorption. Comparison of plasma lipids from 120 day old infants fed formula containing 25–27% 16:0 with 29% 16:0 or 5% 16:0 at the TAG sn-2 position showed higher formula sn-2 16:0 led to lower 18:1n-9, but higher 18:2n-6 and 22:6n-3 in the infant plasma unesterified fatty acids, higher 18:0 in LDL TAG, and higher apo B and lower apo A-1. TAG-sn-2 16:0 may provide 16:0 in remnant particles for hepatic elongation to 18:0, needed for plasma and tissue phospholipids. We suggest attention to the plasma unesterified fatty acids as possible sources of fatty acids for membrane phospholipid synthesis.

Human milk provides the sole source of nutrition and immunological protection for neonates during the first weeks to months after birth. Triacylglycerols are one of the largest components of human milk and they provide fatty acids for energy and growth and development of the infant’s storage and membrane lipids. Fatty acids are one of the most variable components of human milk, with an undisputable, strong influence of maternal fatty acid nutrition, and smaller but potentially important contribution of maternal genetic variation. This review begins with the question of whether recent changes to the diet of modern women has shifted the composition of human milk essential n-6 and n-3 fatty acids, potentially resulting in failure to meet the needs of the young infant. This is followed by the emerging area of the link between lipid nutrition and genetic variability and its impact on human milk n-6 and n-3 fatty acids.

Background: Phosphatidylcholine (PC) produced via the S-adenosylmethionine–dependent phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway is enriched with docosahexaenoic acid (DHA). DHA plays a critical role in fetal development and is linked to health endpoints in adulthood. It is unknown whether choline, which can serve as a source of S-adenosylmethionine methyl groups, influences PC-DHA or the PC:PE ratio in pregnant and nonpregnant women. Objective: This study tested whether choline intake affects indicators of choline-related lipid metabolism, including erythrocyte and plasma PC-DHA and PC:PE ratios, in pregnant women in the third trimester and nonpregnant women. Design: Pregnant (n = 26) and nonpregnant (n =2 1) women consumed 480 or 930 mg choline/d and a daily DHA supplement for 12 wk. Blood was collected at baseline and at the midpoint and end of the study. PC-DHAwas analyzed as the proportion of total PC fatty acids. Results: Pregnant women had greater (P = 0.002) PC-DHA concentrations than did nonpregnant women at baseline. The proportion of erythrocyte and plasma PC-DHA increased (P # 0.002) in pregnant and nonpregnant women regardless of choline intake. However, in nonpregnant women, consumption of 930 mg choline/d led to greater (P , 0.001) erythrocyte PC-DHA and a more rapid increase (P , 0.001) in plasma PC-DHA. Lower (P = 0.001–0.024) erythrocyte and plasma PC:PE in pregnant women was not modified by choline intake. Conclusions: A higher choline intake may increase PEMT activity, resulting in greater PC-DHA enrichment of the PC molecule in nonpregnant women. Increased production of PC-DHA during pregnancy indicates elevated PEMT activity and a higher demand for methyl donors. This trial was registered at clinicaltrials.gov as NCT01127022. Am J Clin Nutr doi: 10.3945/ajcn.112.050211.

Purpose: Amounts and sources of trans fatty acids (TFA) and saturated fatty acids (SFA) were examined in the diets of children aged five to six years after changes in TFA in Canadian foods.Methods: Dietary intake was assessed for 100 Vancouver children, using three 24-hour recalls during parental interviews. Trans fatty acid and SFA intakes and food sources were determined for each child.Results: The TFA intake was 0.71 ± 0.31% of energy, and 12% of children consumed over 1% of energy from TFA. Saturated fatty acids intakes were 12.5 ± 3.39% of energy, and 81% of the children consumed more than 10% of energy from SFA. Monounsaturated and polyunsaturated fatty acid intakes were 12.0 ± 3.0% and 5.79 ± 2.16% of energy, respectively. Major sources of TFA were dairy products, fast foods, and bakery products. Major sources of SFA were dairy products, processed foods, fast food, and bakery products.Conclusions: The TFA intakes of children aged five to six years have decreased since 2004 to a 95th percentile intake of 1.28% of energy, but more than 80% of children consume over 10% of energy from SFA. Removing TFA from snacks and bakery products would decrease the highest TFA intakes to 1% of energy. This study suggests that increased efforts by industry or educational guidance for parents is required to enable selection of foods lower in TFA, and that greater emphasis is needed on SFA.

Background Human milk contains unique glycerophospholipids, including ethanolamine-containing plasmalogens (Pls-PEs) in the milk fat globule membrane, which have been implicated in infant brain development. Brain Pls-PEs accumulate postnatally and are enriched in long-chain polyunsaturated fatty acids (LC-PUFAs), particularly docosahexaenoic acid (DHA). Fatty acid (FA) composition of Pls-PEs in milk is poorly understood because of the analytical challenges in separating Pls-PEs from other phospholipids in the predominating presence of triacylglycerols. The variability of Pls-PE FAs and the potential role of maternal diet remain unknown. Objectives Our primary objectives were to establish improved methodology for extracting Pls-PEs from human milk, enabling FA analysis, and to compare FA composition between Pls-PEs and 2 major milk phospholipids, phosphatidylcholine and phosphatidylethanolamine. Our secondary objective was to explore associations between maternal DHA intake and DHA in milk phospholipids and variability in phospholipid-DHA within a woman. Methods Mature milk was collected from 25 women, with 4 providing 3 milk samples on 3 separate days. Lipids were extracted, and phospholipids were removed by solid phase extraction. Pls-PEs were separated by using normal-phase HPLC, recovered and analyzed for FAs by GLC. Diet was assessed by using a validated food-frequency questionnaire. Results Pls-PE concentration in human milk was significantly higher in LC-PUFAs than phosphatidylethanolamine and phosphatidylcholine, including arachidonic acid (AA) and DHA. The mean ± SD concentration of AAs in Pls-PEs was ∼2.5-fold higher than in phosphatidylethanolamine (10.5 ± 1.71 and 3.82 ± 0.92 g/100 g, respectively). DHA in Pls-PEs varied across women (0.95-6.51 g/100 g), likely independent of maternal DHA intake. Pls-PE DHA also varied within a woman across days (CV ranged from 9.8% to 28%). Conclusions Human milk provides the infant with LC-PUFAs from multiple lipid pools, including a source from Pls-PEs. The biological determinants of Pls-PE FAs and physiological relevance to the breastfed infant remain to be elucidated.

Several studies have investigated the potential health benefits, including those associated with neurological function, of then-3 fatty acid DHA. This has arisen in part because of the association between higher intakes of fish, which is a major dietary source of DHA, and reduced disease risk. In addition to DHA, fish also provides choline and vitamin D. The objective of the present study was to assess whether women in the first half of pregnancy with low fish intake also had low blood concentrations of vitamin D, choline and DHA. A total of 222 pregnant women at 16 weeks of gestation were examined for dietary intake, erythrocyte (phosphatidylethanolamine PE) DHA, plasma free choline and 25-hydroxyvitamin D (25(OH)D). Women who consumed ≤ 75 g fish/week (n56) compared to ≥ 150 g fish/week (n116) had lower dietary intake of DHA, total choline and vitamin D (Psd1·27), 6·83 (sd1·62) g/100 g total fatty acid, respectively,Psd1·65), 7·40 (sd2·05) μmol/l, respectively,P= 0·023) and 25(OH)D (50·3 (sd20·0), 62·5 (sd29·8) nmol/l, respectively,PPP

Levels of n-6, n-3, and medium-chain fatty acids (MCFA) in milk are highly variable. Higher carbohydrate intakes are associated with increased mammary gland MCFA synthesis, but the role of unsaturated fatty acids for milk MCFA secretion is unclear. This study addressed whether n-6 and n-3 fatty acids, which are known to inhibit hepatic fatty acid synthesis, influence MCFA in rat and human milk and the implications of varying MCFA, n-6, and n-3 fatty acids in rat milk for metabolic regulation in the neonatal liver. Rats were fed a low-fat diet or one of six higher-fat diets, varying in 16:0, 18:1n-9, 18:2n-6, 18:3n-3, and long-chain (LC) n-3 fatty acids. Higher maternal dietary 18:2n-6 or 18:3n-3 did not influence milk MCFA, but lower maternal plasma triglycerides, due to either a low-fat or a high-fat high-LC n-3 diet led to higher milk MCFA. MCFA levels were inversely associated with 18:1n-9, 18:2n-6, and 18:3n-3 in human milk, likely reflecting the association between dietary total fat and unsaturated fatty acids. High LC n-3 fatty acid in rat milk was associated with lower hepatic Pklr, Acly, Fasn, and Scd1 and higher Hmgcs2 in the milk-fed rat neonate, with no effect of milk 18:1n-9, 18:2n-6, or MCFA. These studies show that the dietary fatty acid composition does not impact MCFA secretion in milk, but the fatty acid composition of milk, particularly the LC n-3 fatty acid, is relevant to hepatic metabolic regulation in the milk-fed neonate.

Obesity due to nutrient excess leads to chronic pathologies including type 2 diabetes and cardiovascular disease. Related to nutrient excess, FoxO1 has a role in regulating fatty acid uptake and oxidation and triglyceride (TG) storage by mechanisms that are largely unresolved. We examined the mechanism behind palmitate (PA)-induced TG accumulation in cardiomyocytes. To mimic lipid excess, rat ventricular myocytes were incubated with albumin-bound PA (1 mM) or rats were administered Intralipid (20%). PA-treated cardiomyocytes showed a substantial increase in TG accumulation, accompanied by amplification of nuclear migration of phospho-p38 and FoxO1, iNOS induction, and translocation of CD36 to the plasma membrane. PA also increased Cdc42 protein and its tyrosine nitration, thereby rearranging the cytoskeleton and facilitating CD36 translocation. These effects were duplicated by TNF-α and reversed by the iNOS inhibitor 1400 W. PA increased the nuclear interaction between FoxO1 and NF-κB, reduced the nuclear presence of PGC-1α, and downregulated expression of oxidative phosphorylation proteins. In vivo a robust increase in cardiac TGs after Intralipid administration was also associated with augmentation of nuclear FoxO1 and iNOS expression. Impeding this FoxO1-iNOS-CD36 pathway could decrease cardiac lipid accumulation and oxidative/nitrosative stress and help ameliorate the cardiovascular complications associated with obesity and diabetes.

Human milk TG are a remarkable example of stereo-specific positioning of fatty acids with structures that are highly conserved and unusual. Not only does human milk contain high amounts of fat and 16:0, but ∼70% of the 16:0 is esterified at the TG stereo-specifically numbered (sn)-2 position, with preferential positioning of 18:1(n-9) and 18:2(n-6) at the TG sn-1,3 positions. The milk TG structures and digestive lipases combine to enable efficient digestion and absorption of 16:0 by conserving 16:0 in sn-2 monoacylglycerols, which are absorbed, reassembled, and secreted in plasma conserving the original milk TG configuration; these studies are reviewed in this article. The reason why the mammary gland invests in enzymes to provide the infant with 20–25% milk fatty acids as 16:0 rather than selecting against 16:0 is unknown, yet likely has a purpose given the mammary gland capacity for 10:0, 12:0, and 14:0 synthesis. Recent advances in the development-, tissue-, and species-specific activity of enzymes of TG synthesis and knowledge that dietary TG structures are maintained postabsorption suggest that the purpose of the milk TG structures is more sophisticated than simply avoiding 16:0 malabsorption. The overall aim is to expand consideration of fatty acids in the infant diet from a simple view of average fatty acid compositions to the complex lipids and molecular structures in which fatty acids are provided to tissues during early life and the biology through which the unique features of human milk enable the infant to grow and thrive on a high-fat, high-saturated-fat milk diet.

Understanding of the importance of dietary fatty acids has grown beyond a simple source of energy to complex roles in regulating gene expression and cell and intracellular communication. This is important because the metabolic and neuroendocrine environment of the fetus and infant plays a key role in guiding the set point of neural receptors that regulate energy homeostasis and expression of genes that control energy storage and oxidation. Early deviations in these pathways have the potential to lead to lasting adaptations, termed metabolic programming, which may combine to increase the risk of metabolic syndrome in later life. The quality of fatty acids in human diets has undergone major changes in the last 50 years, characterized by an increase in ω-6 and decrease in ω-3 fatty acids. Evidence is accumulating to support the concept that the maternal intake of ω-6 and ω-3 fatty acids in gestation and lactation, possibly involving both excess ω-6 and inadequate ω-3 fatty acids, can impact the developing infant tissue lipids and neuroendocrine and metabolic pathways relevant to metabolic programming. Further work is needed to understand the needs for different ω-6 and ω-3 fatty acids during fetal and infant life, and their roles with respect to development of energy homeostasis and metabolism.

Background: Apolipoprotein E (apoE) and cholesterol play a critical role in synapse and myelin maintenance and integrity and are thus appealing candidates in the pathogenesis of schizophrenia and bipolar disorder. To explore the role of these 2 molecules, we quantified cholesterol and apoE levels in prefrontal grey and white matter in patients with schizophrenia, bipolar disorder and healthy controls. Furthermore, we investigated the relations between apoE and cholesterol levels and the APOE genotype. Methods: We obtained dorsolateral prefrontal grey and white matter from the Stanley Medical Research Institute Brain Collection (schizophrenia n = 35, bipolar disorder n = 35 and controls n = 35). Cholesterol levels were quantified using high-pressure liquid chromatography, whereas apoE was measured by enzyme-linked immunosorbent assay. Results: We found no significant differences in cholesterol or apoE levels among the groups. ApoE levels were higher in grey matter than in white matter in all groups; conversely, levels of cholesterol were higher in white matter than in grey matter. We observed a significant inverse correlation between apoE and cholesterol levels in both grey and white matter. Furthermore, in grey matter, apoE levels were significantly higher in APOE ɛ2 carriers compared with APOE ɛ3 or APOE ɛ4 carriers, with cholesterol levels following the opposite trend. Limitations: Limitations of our study include our inability to control for potential confounding variables and the small numbers of APOE ɛ2 and ɛ4 carriers in each group. Conclusion: Although large amounts of cholesterol are present in white matter, apoE expression is limited. The APOE genotype may play a role in the regulation of both cholesterol and apoE levels in grey matter. The impact of APOE polymorphisms on lipid homeostasis in people with psychiatric disorders warrants further investigation.

d -3-Hydroxybutyrate (3OHB) is an alternative energy substrate for the brain during hypoglycemia, especially in infancy. Knowledge of the capacity and limits of 3OHB to compensate for cerebral glucose depletion during hypoglycemia in developing brain is important for its potential clinical use, but is scarce. We studied the effect of 3OHB treatment during insulin-induced hypoglycemia in 13-day-old rat pups. 3OHB treatment resulted in increased 3OHB plasma levels in hypoglycemic animals (3–4 mM vs. 0.5–1 mM untreated), and delayed the onset of clinical coma by 70 min and of burst-suppression coma by 90 min. 3OHB treated animals did not survive after resuscitation with glucose, compared to 80% survival of untreated hypoglycemic pups. Cleaved-caspase-3 immunohistochemistry and double labeling studies demonstrated a 20-fold increase of apoptotic mature oligodendrocytes in white matter of 3OHB treated animals. 3OHB treatment delays the onset of clinical and burst-suppression coma during hypoglycemia, but the prolonged duration of hypoglycemia is associated with increased mortality after resuscitation and cellular white matter injury.

The long-chain polyunsaturated n-6 and n-3 fatty acids are essential nutrients in membrane biogenesis and regulate gene expression via their eicosanoid metabolites. We investigated whether the n-6 and n-3 fatty acid supply as determined by maternal diet alters colonic phospholipid fatty acids, intestinal morphology, and epithelial barrier permeability during milk feeding with lasting effect on mucosal responsiveness to dinitrobenzene sulfonic acid (DNBS)-induced colitis in young adulthood. Female rats were fed diets with 20% energy from safflower oil (SO) or canola oil (CO), or 8% fish oil (FO) plus 2% SO (10% FO) or 18% FO plus 2% SO (20% FO) throughout gestation and lactation and offspring weaned to a standard diet at 21 days of age. At 15 days of age, pups in the 20% and 10% FO groups had lower 20:4n-6 and higher 20:5n-3 and 22:6n-3 in colon phospholipids ( P < 0.01), shorter crypts ( P < 0.05), and higher paracellular permeability than SO or CO groups. At 3 mo of age, male offspring in the FO groups showed lasting reduction of crypt depth and a heightened inflammatory response to DNBS. We demonstrate that early decreased colon 20:4n-6 with increased n-3 fatty acids impairs intestinal barrier development and sensitizes the colon response to inflammatory insults later in life.

Abnormal lipid profiles have been reported in the central nervous system (CNS) in individuals with schizophrenia, although the etiology of these changes remains to be elucidated. While treatment with second-generation antipsychotics has been associated with alterations in peripheral lipid levels and changes in erythrocyte membrane composition, the relationship between peripheral and CNS lipid levels is complex and the effect of antipsychotics on CNS lipid regulation is not yet understood. In this study we investigated whether sub-chronic administration of the second-generation antipsychotic clozapine and the first-generation antipsychotic haloperidol alters brain membrane lipid composition in male Sprague–Dawley rats. The relationship between brain membrane lipid composition and plasma cholesterol concentrations was also assessed. Our results indicate that brain lipid composition and plasma cholesterol concentrations are not altered following administration of antipsychotics. No correlation was observed between plasma and brain membrane cholesterol levels. Our findings suggest that observed alterations in brain lipid profiles in individuals with schizophrenia are not a consequence of treatment with antipsychotic medications.

Alterations in lipid metabolism may contribute to the pathology of hyperhomocysteinemia (HHcy). Our objective in this study was to test the hypothesis that HHcy is associated with changes in liver acyl CoA:cholesterol acyl transferase 2 (ACAT2) expression and cholesteryl esters (CE) in mice with HHcy. ACAT2 is encoded by Soat2 and functions to catalyze the esterification of cholesterol with acyl-CoA. Mice heterozygous for disruption of the cystathionine-beta-synthase gene (Cbs +/-) and C57BL/6 mice (Cbs +/+) were fed a control diet or a diet high in l-methionine (8.60 g/kg) and low in folic acid (0.20 mg/kg) to induce HHcy (HH diet). Lower Soat2 mRNA (P < 0.05) and ACAT protein (P < 0.001), higher total oleic acid [18:1(n-9)], and lower CE 18:1(n-9) was found in liver from Cbs +/- mice fed the HH diet, with higher plasma total homocysteine concentrations, than Cbs +/+ mice fed the control diet (35.01 +/- 5.6 vs. 2.21 +/- 0.6 mumol/L, respectively). In silico searches identified a CpG-rich region in the 5' portion of the Soat2 gene, which was differentially methylated (P < 0.05) in Cbs +/- mice fed the HH diet than in Cbs +/+ mice fed the control diet and was accompanied by higher (P < 0.05) B1 repeat element methylation, an indicator of global de novo methylation. These findings show altered methylation and expression of Soat2/ACAT2 in liver from mice with HHcy and suggest a role for changes in liver CE in the pathology of HHcy.

There is controversy whether children should have a dietary supply of preformed long-chain polyunsaturated n-3 fatty acids EPA and DHA. The aims of the workshop were to review evidence for a possible benefit of a preformed EPA and/or DHA supply, of data required to set desirable intakes for children aged 2–12 years, and of research priorities. The authors concluded that EPA and DHA intakes per kg body weight may often be low in 2- to 12-year-old children, relative to intakes per kg body weight of breast-fed infants and adult intakes, but reliable data are scarce. Little information is available that increasing dietary intakes of EPA or DHA in children has benefits to physical or mental function or other health endpoints. Studies addressing EPA and DHA intakes and tissue status among groups of children with different dietary habits, and measures of relevant development and health endpoints, are needed for developing potential advice on desirable intakes of EPA and/or DHA in children. At this time it appears prudent to advise that dietary intakes in childhood are consistent with future eating patterns supporting adult health, such as prevention of metabolic disorders and CVD, supporting immune function, and reproductive health. In conclusion, the available information relating dietary EPA and DHA intakes in children aged 2–12 years to growth, development and health is insufficient to derive dietary intake recommendations for EPA and DHA. Adequately designed studies addressing dietary intakes, measures of status and relevant functional or health effects across this age group are needed.

BACKGROUND: Arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids are important in membrane glycerophospholipids. Higher maternal blood ARA, EPA, and DHA concentrations in gestation are associated with higher maternal-to-fetal transfer of ARA, EPA, and DHA, respectively, which emphasizes the importance of maternal fatty acid status in gestation. As in the brain, red blood cell (RBC) ethanolamine phosphoglycerides (EPGs) are high in plasmalogen, ARA, and DHA. OBJECTIVE: We determined the relation between dietary n-6 (omega-6) and n-3 (omega-3) fatty acid intakes and n-6 and n-3 fatty acids in RBC EPGs and phosphatidylcholine in near-term pregnant women. DESIGN: The subjects were 105 healthy Canadian pregnant (36 wk gestation) women. Fatty acid intakes were estimated by food-frequency questionnaire, and fasting venous blood samples were collected. RESULTS: DHA and EPA intakes were positively associated with RBC EPG and phosphatidylcholine concentrations of DHA (rho = 0.309 and 0.369, respectively; P < 0.001) and EPA (rho = 0.391 and 0.228, respectively; P < 0.001) and inversely associated with RBC EPG 22:4n-6 and 22:5n-6 (P < 0.001). In RBCs, concentrations of linoleic acid (LA, 18:2n-6) were inversely associated with DHA, EPA, and ARA, respectively, in EPGs (r = -0.432, P < 0.01; r = -0.201, P < 0.04; and r = -0.303, P < 0.01) and phosphatidylcholine (r = -0.460, -0.490, and -0.604; P < 0.01 for all). CONCLUSIONS: Membrane fatty acids are influenced by the amount and balance of fatty acid substrates. Our results suggest the competitive interaction of LA with ARA, EPA, and DHA, with no evidence that higher LA increases ARA. Biochemical indicators to suggest that DHA is limiting are present in our population. This trial was registered at clinicaltrials.gov as NCT00620672.

Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes ( n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean ± SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 ± 0.2 vs. 10.2 ± 1.9 ng·ml−1·90 min−1, P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated ( r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 ± 1.9 vs. 8.6 ± 1.2 ng·ml−1·90 min−1, P = 0.005). In a second group of subjects ( n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 ± 0.5 vs. 4.5 ± 0.6 μg/ml, P = 0.029) and cholinesterase activity (705 ± 33 vs. 1,013 ± 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process. Desacyl ghrelin increases in gestational diabetes, possibly reflecting resistance to the inhibitory effect of insulin on ghrelin secretion.