Choline Supplementation Research Articles

Effect of Dietary Choline Chloride Supplementation on Growth Performance and Carcass Characteristics of Broiler Chickens Reared to 32 Days of Age

Research on the impact of supplementing additional dietary choline to modern, large-frame broiler chickens is limited, and current choline recommendations are outdated. The objective of this study was to determine the effect of additional dietary choline chloride supplementation on growth performance and carcass characteristics of modern broilers reared to 32 days of age. Corn and soybean meal-based diets were formulated to contain an additional 0, 400, 800, 1200, 1600, or 2000 mg of choline chloride per kg of feed above the choline present in the basal diet ingredients. As-hatched Ross 708 × Yield Plus broiler chicks (n = 2160; 30 birds per pen; 44 ± 0.2 g initial BW) were randomly allotted to the experimental diets, reared for 31 days, and processed at day 32. Growth performance, carcass yield, and breast myopathy incidence were not impacted by supplemental choline. However, abdominal fat pad weight tended to diminish with increasing dietary choline, and drumstick yield was reduced in birds fed over 800 mg per kg of feed. These results indicate feeding additional choline does not impact growth performance but may result in changes in carcass characteristics of modern, high-yielding broilers reared for 32 days.

Effects of Supplementation with Rumen-Protected Choline and Methionine on Metabolic Profile and Some Reproductive Parameters in Dairy Cattle During Transition Period

This study conducted to determine effect of the rumen-protected choline and methionine supplementation to peripartum dairy cattle on metabolic profile, metabolic disorders and some reproductive parameters. For this, 3-6 year-old, multiparous, healthy and pregnant 32 high-yield Holstein dairy cows were divided into 4 different groups during trial as: a control (CON) group with no supplementation to the ration; a 75 gr/day rumen-protected choline chloride (CHOL) supplemented group, 42 gr/ day methionine (MET) supplemented group, 75 gr/ day choline chloride and 42 gr/ day methionine (MET + CHOL) supplemented group were during three weeks before and after parturation. Blood samples were taken at wk -3, calving, wk 3 and wk 10 and were analyzed. Health problems and reproductive data were recorded during treatment. Statistically significant differences were detected in non-esterified fatty acids (NEFA), insulin like growth factor-1 (IGF-1), glucose, total protein, albumin, direct bilirubin, total cholesterol and very low density lipoproteins (VLDL). Results of this study suggested that rumen-protected choline and methionine supplementation to the rations of dairy cattle affected some metabolic profile parameters. The statistical differences in metabolic profile tests did not affect metabolic diseases and reproductive parameters.

Choline Supplementation Does Not Promote Atherosclerosis in CETP-Expressing Male Apolipoprotein E Knockout Mice

Dietary trimethylamines, such as choline, metabolized by intestinal microbiota to trimethylamine are absorbed by the gut and oxidized to trimethylamine N-oxide (TMAO). The objective of this study was to determine the effect of choline supplementation on atherosclerosis progression in Apoe−/− mice expressing human cholesterol ester transfer protein (hCETP) using the same diets as in previously reported studies. Mice expressing hCETP, after transfection with AAV2/8-hCETP, were fed an 18% protein diet with either 0.09% (standard chow), 0.5% or 1% choline for 16 weeks. Control mice not transfected with hCETP were fed 1% choline. Dietary choline supplementation increased plasma TMAO levels at 8 and 16 weeks. When atherosclerotic lesions were measured in the thoracic aorta and aortic root, there were no differences between any of the treatment groups in the amount of plaque development at either site. Throughout the study, no significant changes in plasma lipids or major classes of lipoproteins were observed in hCETP-expressing mice. Plasma-oxidized low density lipoprotein, myeloperoxidase and high density lipoprotein inflammatory index were measured at 16 weeks, with no significant changes in any of these inflammatory markers between the four treatment groups. Despite increasing plasma TMAO levels, dietary choline supplementation in Apoe−/− mice expressing hCETP did not promote atherosclerosis.

Impairment of transcription factor Gcr1p binding motif perturbs OPI3 transcription in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the transcription factor GCR1 plays a vital role in carbohydrate metabolism and in the current study we tried to elucidate its role in lipid metabolism. In silico analysis revealed the upstream activation sequence (UAS) in the promoter region of OPI3 possessed six conserved recognition sequences for Gcr1p and the ChIP assay confirmed the binding of Gcr1p on the OPI3 promoter region. The real-time quantitative polymerase chain reaction and promoter-reporter activity revealed a substantial reduction in OPI3 expression and was supported with decreased phosphatidylcholine (PC) level that is rescued with exogenous choline supplementation in gcr1∆ cells. Simultaneously, there was an increase in triacylglycerol level, accompanied with increased number and size of lipid droplets in gcr1∆ cells. The expression of pT1, pT2 truncations in opi3∆ cells revealed the -1 to -500 bp in the promoter region is essential for the activation of OPI3 transcription. The mutation specifically at UASCT box (-265) in the OPI3 promoter region displayed a reduction in the PC level and the additional mutation at UASINO (-165) further reduced the PC level. Collectively, our data suggest that the GCR1 transcription factor also regulates the OPI3 expression and has an impact on lipid homeostasis.

Increasing doses of biocholine on apparent digestibility, ruminal fermentation, and performance in dairy cows

Biocholine is an herbal feed additive considered a natural alternative to synthetic choline, with relatively low rumen degradability composed of cellulose and choline conjugates, namely phosphatidylcholine. Rumen-protected choline has been largely evaluated during the peripartum period, but few studies evaluated the effects of choline supplementation after the transition period. The objective of this study was to determine the effects of increasing doses of biocholine on feed intake, feed particle sorting, total apparent digestibility, ruminal fermentation, milk yield and composition, purine derivative excretion, and nitrogen balance. Twenty-four Holstein cows (163 ± 98 days in milk, 27.6 ± 7.14 kg/d milk yield), 4 of which were ruminally cannulated, were enrolled to this study. Cows were blocked according to milk yield, days in milk, and presence of ruminal cannulas, then all cows were randomly assigned to a treatment sequence in a replicated 4 × 4 Latin square experiment design. The experimental treatments were a control (CON) diet, and biocholine (BC; Biocholine FC®, Nutriquest Technofeed Nutrição Animal Ltda., Campinas, Brazil) fed at 7, 14, and 21 g/d. Cows were allowed 14 d of adaptation to treatments and the last 7 days of each period were used for sampling. The forage to concentrate ratio of the basal diet was 48:52 (on a dry matter basis) with corn silage as the single forage source, and diet was provided in the form of total mixed ration. No treatment effects were detected on feed intake, but BC quadratically affected (P = 0.010) sorting for feed particles >19 mm and linearly increased (P = 0.037) ether extract digestibility (840, 834, 843, and 853 g/kg for cows fed BC at 0, 7, 14, and 21 g/d, respectively). Biocholine supplementation tended to quadratically decrease ruminal pH (6.17, 6.04, 6.11, and 6.11 for cows fed BC at 0, 7, 14, and 21 g/d, respectively) but had no effect on concentrations of total volatile fatty acids and NH3-N. Biocholine had a positive quadratic effect (P ≤ 0.042) on milk yield (29.5, 30.5, 30.0, and 29.8 kg/d for cows fed BC at 0, 7, 14, and 21 g/d, respectively) and feed efficiency (1.20, 1.25, 1.21, and 1.21 kg milk/kg DM intake for cows fed BC at 0, 7, 14, and 21 g/d, respectively). Biocholine tended to quadratically affect (P = 0.058) N excretion through milk (157, 162, 160, and 159 g/d for cows fed BC at 0, 7, 14, and 21 g/d, respectively). There was no evidence for treatment effects on purine derivatives excretion. In conclusion, feeding BC may improve milk yield and feed efficiency of dairy cows. Predicted maxima response in milk yield and feed efficiency were observed at 10 g/d of BC.

Choline diet improves serum lipid parameters and alters egg composition in breeder ducks.

BackgroundCholine is an important nutrient, playing key roles in numerous metabolic pathways relevant to animal health.ObjectivesThe objective of this study was to evaluate the effect of dietary choline on the lipid parameters, cardiovascular health (CVH), and levels of egg trimethylamine (TMA) and cholesterol in breeder ducks during the late laying period.MethodsA total of 60 Jingjiang ducks were randomly separated into six replicates of 10 ducks each. After peak production until 65 weeks of age, the birds were fed a control basal diet. The same ducks served as the control group until 65 weeks of age, when the same ducks served as the choline‐supplemented group, after 15 days of dietary choline supplementation at 2955 mg/kg choline above and over the basal diet initially provided. The 15 days of choline supplementation included an initial 5‐day acclimatisation period.ResultsDietary choline supplementation increased serum TMA (p < 0.01), high‐density lipoprotein cholesterol, very low‐density lipoprotein, and triglyceride levels in older breeder ducks. However, it did not change the levels of trimethylamine N‐oxide but decreased the atherosclerosis index compared with those of the control group (p < 0.01). Moreover, it increased (p < 0.01) the egg yolk TMA levels but did not change the concentrations of cholesterol in egg yolk.ConclusionsDietary choline supplementation had a beneficial effect on lipid parameters and CVH in older breeder ducks, although it increased the serum and egg yolk TMA levels.

The acute dose and baseline amplitude-dependent effects of CDP-choline on deviance detection (MMN) in chronic schizophrenia: A pilot study.

The detection of deviant auditory features is empirically supported as impaired in schizophrenia and has been shown to associate with functional outcome. Modulated by glutamate neurotransmission, this sensory process has also been shown to relate to the α7 nicotinic acetylcholine receptor (nAChR) system, a prioritized molecular target for the development of novel cognition targeted pharmacological treatments. This pilot study assessed the acute effects of CDP-Choline, a choline supplement with α7 nAChR agonist properties, on the mismatch negativity (MMN), an event-related potential index of the detection of an acoustic change, in a sample of individuals diagnosed with chronic schizophrenia. Utilizing a randomized, placebo-controlled, double-blind design, the dose-dependent (500 mg, 1,000 mg, 2,000 mg), baseline amplitude-dependent (low vs. high), and deviant feature-dependent effects of CDP-Choline on the MMN were examined. CDP-choline's effects interacted with dosage, deviance feature, and baseline amplitude with low baseline amplitude patients demonstrating enhanced MMNs, and high baseline amplitude patients demonstrating suppressed MMNs in response to CDP-Choline. These findings offer tentative support for the involvement of the α7 nAChR system in auditory MMN abnormalities in schizophrenia and supports further research assessing the effects of long-term treatment with CDP-Choline in the personalized treatment of auditory deviance processing impairments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dietary choline in gonadectomized kittens improved food intake and body composition but not satiety, serum lipids, or energy expenditure.

Gonadectomy is a major risk factor for feline obesity. The lipotropic effects of choline have demonstrated benefits for growth and carcass composition in livestock. The consumption of supplemental choline on body weight (BW), body composition, lipid metabolism, energy expenditure (EE), and serum satiety hormones were evaluated in 15 gonadectomized male kittens. Kittens were offered a base diet formulated for growth (3310mg choline/kg dry matter [DM]) to daily energy requirements (DER) over an 11-week acclimation. Post-gonadectomy, kittens were assigned to a base diet (CONTROL, n = 7) or choline group (base diet with additional choline at 300mg/kg BW0.75 as a top dress) (CHOLINE, n = 8). For 12-weeks post-neuter, kittens were offered three times their DER over three meals to mimic ad libitum feeding. At week -1 and 12, body composition was assessed using dual energy x-ray absorptiometry (DXA), 24-hour indirect calorimetry was performed for EE and respiratory quotients (RQ), and fasted serum samples were analyzed for lipid compounds and satiety hormones. Daily food intake (FI) and weekly BW were measured. Data was analyzed as a repeated measures of variance (ANCOVA) using the GLIMMIX procedure with time and group as fixed effects. CHOLINE had lower mean daily FI and lower rates of BW accretion (P<0.05) in contrast to CONTROL. All absolute body composition data increased over time for both groups, with lower increases in total tissue mass (P = 0.031) and fat mass (P = 0.005) in CHOLINE. Serum satiety hormones and lipid compounds did not differ (P>0.05) between groups, but both groups experienced a decrease in low-density lipoproteins and increase in high-density lipoproteins (P<0.05). Primary substrate utilization showed lipid use when fasted and use of protein or mixed macronutrients in the fed state. Fed state EE decreased post-gonadectomy (P = 0.004), however, CHOLINE did not affect total EE or RQ. These results suggest that supplemental dietary choline reduces FI, BW, and fat mass and may help to reduce the propensity of weight gain and subsequent obesity in gonadectomized feline populations.

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome.

We previously demonstrated that intake of three eggs/d for 4 weeks increased plasma choline and decreased inflammation in subjects with metabolic syndrome (MetS). The purpose of the current study was to further explore the effects of phosphatidylcholine (PC) provided by eggs versus a choline bitartrate (CB) supplement on the gut microbiota, trimethylamine N-oxide (TMAO) formation, and plasma carotenoids lutein and zeaxanthin in MetS. This randomized, controlled crossover clinical trial included 23 subjects with MetS. Following a washout period of 2 weeks without consuming any choline-containing foods, subjects were randomly allocated to consume either three eggs/d or a CB supplement for 4 weeks (both diets had a choline equivalent of 400 mg/day). DNA was extracted from stool samples to sequence the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and the α-diversity of the community were determined using QIIME software. Plasma TMAO, methionine, betaine, and dimethylglycine (DMG) were quantified by stable isotope dilution liquid chromatography with tandem mass spectrometry. Plasma carotenoids, lutein, and zeaxanthin were measured using reversed-phase high-performance liquid chromatography. There were significant increases in plasma lutein and zeaxanthin after egg intake compared to the baseline or intake of CB supplement (p < 0.01). In contrast, TMAO was not different between treatments compared to the baseline (p > 0.05). Additionally, while diet intervention had no effects on microbiota diversity measures or relative taxa abundances, a correlation between bacterial biodiversity and HDL was observed. Following egg intake, the observed increases in plasma lutein and zeaxanthin may suggest additional protection against oxidative stress, a common condition in MetS.

Effects of choline chloride on the ruminal microbiome at 2 dietary neutral detergent fiber concentrations in continuous culture

Our objective was to evaluate the effects of unprotected choline chloride (Cho) on the ruminal microbiome at 2 dietary neutral detergent fiber (NDF) concentrations. We hypothesized that the effects of Cho on ruminal bacterial populations would depend on NDF. Eight dual-flow continuous-culture fermentors were arranged in a duplicated 4 × 4 Latin square as a 2 × 2 factorial with the following treatments: (1) 30% NDF-control (30% NDF diet, no supplemental choline); (2) 30% NDF-Cho (30% NDF diet plus 1.9 g of choline ion per kg of dry matter); (3) 40% NDF-control (40% NDF diet, no supplemental choline); and (4) 40% NDF-Cho (40% NDF diet plus 1.9 g of choline ion per kg of dry matter). We did 4 fermentation periods of 10 d each and used the last 3 d for collection of samples of solid and liquid digesta effluents for DNA extraction. Overall, 32 solid and 32 liquid samples were analyzed by amplification of the V4 variable region of bacterial 16S rRNA. Data were analyzed with R (R Project for Statistical Computing) and SAS (SAS Institute Inc.) to determine effects of Cho, NDF, and NDF × Cho on taxa relative abundance. The correlation of propionate molar proportion with taxa relative abundance was also analyzed. At the phylum level, relative abundance of Firmicutes in the liquid fraction tended to be greater when Cho was supplemented with a 30% NDF diet. At the order level, Cho increased Coriobacteriales in solid fraction and decreased Fibrobacterales in liquid fraction. Moreover, Cho decreased abundance of Clostridiales and increased Selenomonadales in the solid fraction, only with the 30% NDF diet. For genera, lower abundance of Pseudobutyrivibrio resulted from Cho in solid and liquid fractions. Greater abundance of Succinivibrio in solid and Selenomonas and Selenomonas 1 in liquid resulted from Cho with the 30% NDF diet. Propionate molar proportion was positively correlated with relative abundance of order Selenomonadales in solid and liquid fractions, and with genus Succinivibrio in solid and genera Selenomonas and Selenomonas 1 in liquid. Our results indicate that Cho primarily decreases abundance of bacteria involved in fiber degradation and increases abundance of bacteria mainly involved in nonstructural carbohydrate degradation and synthesis of propionate, particularly when a diet with 30% NDF is provided.

Pregnancy-induced alterations of 1-carbon metabolism and significance for maternal nutrition requirements.

The pregnancy-induced alterations in 1-carbon (1C) metabolism, effects of advancing gestation on maternal plasma concentrations of methyl nutrients, and potential implications for maternal dietary intake and infant clinical outcomes are summarized in this narrative review. 1C metabolism encompasses a series of pathways where 1C units are transferred among nutrients such as B vitamins, choline, and amino acids (the methyl nutrients). Use of isotopic tracers and measuring methyl nutrients in maternal plasma and infant cord blood has advanced the understanding of 1C flux in pregnancy and kinetics of maternal-placental-fetal transfer. Methyl nutrients are supplied from maternal plasma to the placenta and fetus to support growth and 1C metabolism in these compartments. A literature review was completed in MEDLINE and Google Scholar using search terms related to 1C metabolism, methyl nutrients, and nutrition requirements in pregnancy. English-language articles were reviewed in which 1C metabolism in pregnancy, maternal-placental-fetal transfer of methyl nutrients, and determinants of maternal plasma concentrations of methyl nutrients among healthy pregnant women were assessed. Adaptations in 1C metabolism occur throughout a healthy pregnancy to support this unique period of accelerated growth. Studies report similar temporal changes in plasma concentrations of many methyl nutrients, including B vitamins, choline, betaine, methionine, and cysteine, among healthy pregnant women from diverse geographic regions. Other key findings discussed in this review include an apparent high degree of B vitamin transfer to the placenta and fetus, influence of choline supplementation on 1C flux and possible benefit of supplementation for infant cognitive development, and that glycine may be conditionally essential in pregnancy. Understanding the flux of 1C metabolism in pregnancy and methyl nutrient transfer from maternal plasma is needed to establish appropriate plasma references ranges and, ultimately, dietary recommendations that aim to prevent deficiency and associated adverse health outcomes for mother and baby.

Choline Supplementation Partially Restores Dendrite Structural Complexity in Developing Iron-Deficient Mouse Hippocampal Neurons

BackgroundFetal-neonatal iron deficiency causes learning/memory deficits that persist after iron repletion. Simplified hippocampal neuron dendrite structure is a key mechanism underlying these long-term impairments. Early life choline supplementation, with postnatal iron repletion, improves learning/memory performance in formerly iron-deficient (ID) rats. ObjectivesTo understand how choline improves iron deficiency–induced hippocampal dysfunction, we hypothesized that direct choline supplementation of ID hippocampal neurons may restore cellular energy production and dendrite structure. MethodsEmbryonic mouse hippocampal neuron cultures were made ID with 9 μM deferoxamine beginning at 3 d in vitro (DIV). At 11 DIV, iron repletion (i.e., deferoxamine removal) was performed on a subset of ID cultures. These neuron cultures and iron-sufficient (IS) control cultures were treated with 30 μM choline (or vehicle) between 11 and 18 DIV. At 18 DIV, the independent and combined effects of iron and choline treatments (2-factor ANOVA) on neuronal dendrite numbers, lengths, and overall complexity and mitochondrial respiration and glycolysis were analyzed. ResultsCholine treatment of ID neurons (ID + Cho) significantly increased overall dendrite complexity (150, 160, 180, and 210 μm from the soma) compared with untreated ID neurons to a level of complexitythat was no longer significantly different from IS neurons. The average and total length of primary dendrites in ID + Cho neurons were significantly increased by ∼15% compared with ID neurons, indicating choline stimulation of dendrite growth. Measures of mitochondrial respiration, glycolysis, and ATP production rates were not significantly altered in ID + Cho neurons compared with ID neurons, remaining significantly reduced compared with IS neurons. Iron repletion significantly improved mitochondrial respiration, ATP production rates, overall dendrite complexity (100–180 μm from the soma), and dendrite and branch lengths compared with untreated ID neurons. ConclusionsBecause choline partially restores dendrite structure in ID neurons without iron repletion, it may have therapeutic potential when iron treatment is not possible or advisable. Choline's mechanism in ID neurons requires further investigation.

The impact of micronutrient supplementation in alcohol-exposed pregnancies on reaction time responses of preschoolers in Ukraine.

The potential of micronutrients to ameliorate the impact of prenatal alcohol exposure (PAE) on attentional regulation skills was explored in a randomized clinical trial conducted in Ukraine. Women who differed in prenatal alcohol use were recruited during pregnancy and assigned to one of three groups [No study-provided supplements, Multivitamin/Mineral Supplement (MVM), or MVM plus Choline]. Their offspring were seen in the preschool period and a reaction time task was administered. Participants were asked to press a response button as quickly as possible as 30 stimuli from the same category (animals) were presented consecutively and then followed by six stimuli from a novel category (vehicles). Number correct, mean latency of the response over trials, and variability in the latency were analyzed separately by sex. During the initial animal trials, boys whose mothers received MVM during pregnancy had more correct responses and reduced response latency compared to boys whose mothers had no MVM treatment. During vehicle trials, maternal choline supplementation was associated with increased response speed in males without a PAE history. Females receiving supplements did not show the same benefits from micronutrient supplementation and were more adversely impacted by prenatal alcohol exposure. Relationships between maternal levels of choline, betaine, and dimethylglycine (DMG) and task performance were also assessed. Although no effects were found for choline after adjusting for multiple comparisons, lower baseline DMG level was associated with greater accuracy and shorter latency of responses in the initial animal trials and shorter latency in the vehicle trials in female preschoolers. Level of betaine in Trimester 3 was associated with reduced variability in the latency of male responses during the animal trials. Maternal micronutrient supplementation in pregnancy appears to improve preschool reaction time performance, but the effects varied as a function of sex and PAE exposure status.

Protective role of Dietary Choline and Docosahexaenoic acid or Environmental enrichment in attenuating high fat diet-induced arterial wall changes in obese rats

Childhood obesity increases body mass index and long term metabolic disturbances. The present study is designed to analyze postnatal obesity-induced changes in body mass index and common carotid artery wall thickness and the role of dietary choline and DHA or environmental enrichment in mitigating these changes. Four groups of male rat pups (n=8/group) were assigned as Normal control (NC), Obese (OB) fed high-fat diet, Obesity-induced supplemented choline and DHA (OB+CHO+DHA) with 5mmol/kg/day of choline and 150 mg/ day of DHA, Obesity-induced environmental enrichment (OB+EE) exposed to environmental enrichment for 90 days. Body mass index was calculated after 90 days. Subsequently, rats were euthanized to excise common carotid artery. 5µ thick sections were processed for haematoxylin and eosin and Verhoff –Vangeison stains. Mean body weight, body mass index, thickness of tunica intima, media and percentage of collagen fibers in artery were significantly higher in OB group (p&lt; 0.01, &lt;0.001,&lt; 0.01, &lt; 0.001, &lt; 0.05) as compared to the same in NC rats respectively. These changes were significantly (p&lt;0.01, &lt; 0.05) attenuated in OB+CHO+DHA and OB+EE groups compared to OB rats. Increased body mass index in early ages is an indicator for atherosclerosis. Supplementation of dietary choline and DHA or environmental enrichment exposure attenuates these changes from an early young age.

A Preliminary Study of Clinical Practice and Prenatal Nutrition in Rural Kansas.

IntroductionThe primary purpose of this study was to determine if new recommendations for prenatal supplements of docosahexaenoic acid (DHA) and choline have been implemented into care by physicians who care for pregnant women in rural Kansas communities. Both nutrients are inadequate in the diet of most pregnant women in the U.S., and not all prenatal supplements provide DHA and choline.MethodsA cross sectional web-based survey was developed and provided by the University of Kansas Medical Center (KUMC) students to 44 rural Kansas clinics believed to have physicians who provide obstetrical care. Questions about DHA and choline were embedded in a larger survey focused on prenatal care. A total of 29 surveys were returned, however, only 21 were completed by physicians who provided obstetrical care.ResultsDHA (3/21) and choline (0/21) rarely were singled out for recommendation in contrast to folic acid (16/21) and iron (14/21). Participants stated that most women sought prenatal care during the first trimester of their pregnancy and indicated that they recommended prenatal vitamins at the first visit. Eleven gave patients a prescription for prenatal vitamins. The remaining patients either chose traditional over the counter prenatal vitamin capsules or less traditional chewable (gummy) vitamins, which provided lower concentrations of nutrients. Common barriers to nutritional counseling were limited resources and time constraints. Clinicians assessed their confidence and ability to provide nutritional counseling as moderate and competent, respectively.ConclusionsNew nutritional recommendations for DHA and choline have not been implemented into standard of care in rural Kansas.

Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder.

Fetal alcohol spectrum disorder (FASD) is common and represents a significant public health burden, yet very few interventions have been tested in FASD. Cognitive deficits are core features of FASD, ranging from broad intellectual impairment to selective problems in attention, executive functioning, memory, visual–perceptual/motor skills, social cognition, and academics. One potential intervention for the cognitive impairments associated with FASD is the essential nutrient choline, which is known to have numerous direct effects on brain and cognition in both typical and atypical development. We provide a summary of the literature supporting the use of choline as a neurodevelopmental intervention in those affected by prenatal alcohol. We first discuss how alcohol interferes with normal brain development. We then provide a comprehensive overview of the nutrient choline and discuss its role in typical brain development and its application in the optimization of brain development following early insult. Next, we review the preclinical literature that provides evidence of choline’s potential as an intervention following alcohol exposure. Then, we review a handful of existing human studies of choline supplementation in FASD. Lastly, we conclude with a review of practical considerations in choline supplementation, including dose, formulation, and feasibility in children.

Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner.

Maternal methyl donor supplementation during pregnancy has demonstrated lasting influence on offspring DNA methylation. However, it is unknown whether an adverse postnatal environment, such as high-fat (HF) feeding, overrides the influence of prenatal methyl donor supplementation on offspring epigenome. In this study, we examined whether maternal supplementation of choline (CS), a methyl donor, interacts with prenatal and postnatal HF feeding to alter global and site-specific DNA methylation in offspring. We fed wild-type C57BL/6J mouse dams a HF diet with or without CS throughout gestation. After weaning, the offspring were exposed to HF feeding for 6 weeks resembling a continued obesogenic environment. Our results suggest that maternal CS under the HF condition (HFCS) increased global DNA methylation and DNA methyltransferase 1 (Dnmt1) expression in both fetal liver and brain. However, during the postnatal period, HFCS offspring demonstrated lower global DNA methylation and Dnmt1 expression was unaltered in both the liver and visceral adipose tissue. Site-specific DNA methylation analysis during both fetal and postnatal periods demonstrated that HFCS offspring had higher methylation of CpGs in the promoter of Srebf1, a key mediator of de novo lipogenesis. In conclusion, the influence of maternal CS on offspring DNA methylation is specific to HF feeding status during prenatal and postnatal periods. Without continued CS during the postnatal period, global DNA methylation enhanced by prenatal CS in the offspring was overridden by postnatal HF feeding.

Prenatal Folate and Choline Levels and Brain and Cognitive Development in Children: A Critical Narrative Review.

Women’s nutritional status during pregnancy can have long-term effects on children’s brains and cognitive development. Folate and choline are methyl-donor nutrients and are important for closure of the neural tube during fetal development. They have also been associated with brain and cognitive development in children. Animal studies have observed that prenatal folate and choline supplementation is associated with better cognitive outcomes in offspring and that these nutrients may have interactive effects on brain development. Although some human studies have reported associations between maternal folate and choline levels and child cognitive outcomes, results are not consistent, and no human studies have investigated the potential interactive effects of folate and choline. This lack of consistency could be due to differences in the methods used to assess folate and choline levels, the gestational trimester at which they were measured, and lack of consideration of potential confounding variables. This narrative review discusses and critically reviews current research examining the associations between maternal levels of folate and choline during pregnancy and brain and cognitive development in children. Directions for future research that will increase our understanding of the effects of these nutrients on children’s neurodevelopment are discussed.

Nutritional support and prophylaxis of azithromycin for pregnant women to improve birth outcomes in peri-urban slums of Karachi, Pakistan\u2014a protocol of multi-arm assessor-blinded randomized controlled trial (Mumta PW trial)

BackgroundMaternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan.MethodsThe trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. All pregnant women (PW), if identified between > 8 and < 19 weeks of gestation based on ultrasound, will be offered routine antenatal care (ANC) counseling and voluntary participation in the trial after written informed consent. A total number of 1836 PW will be enrolled with informed consent and randomly allocated to one of the four arms receiving: (1) ANC counseling only (control group), (2) ANC counseling plus BEP supplement (intervention arm 1), (3) ANC counseling plus BEP supplement plus 2 doses azithromycin (intervention arm 2), or (4) ANC counseling plus BEP supplement plus daily single dose of nicotinamide and choline (intervention arm 3).Trial registrationClinicalTrials.govNCT04012177. Registered on July 9, 2019.

Choline supplementation influences ovarian follicular development.

Female infertility is a health issue for both humans and animals and despite developments in medical interventions, there are still some conditions that cannot be treated successfully. It is important to explore other potential therapies or remedies that could improve reproductive health. Choline is an over-the-counter supplement and essential nutrient that has many health benefits. It has been suggested to be beneficial in various aspects of fertility, including fetal development and endocrine disorders like polycystic ovarian syndrome (PCOS). However, choline's impact on ovarian function has not been explored. To study the effects of choline on ovarian development, 36 female Yorkshire × Landrace pigs were fed the following four supplemented diets between 90 and 186 days of age: (1) Control (corn and soybean meal-based diet that met estimated nutrient requirements, n = 9); (2) Choline (additional 500 mg choline per 1 kg of control diet, n = 8); (3) Omega-3 (additional 5556 mg Omega-3 per 1 kg control diet by introducing fish oil); (4) Choline + Omega-3 (500 mg choline + 5556 mg Omega-3 per 1 kg control diet). Pigs fed the choline-supplemented diet were compared to the control group and those fed diets supplemented with Omega-3 as fertility-promoting agent. It was found that the number of corpus luteum per ovary in the Choline (16.25 ± 2.88), Omega-3 (10.78 ± 1.71) and Choline + Omega-3 (14.89 ± 2.97) groups were all higher in comparison to that of the control group (5.56 ± 1.72, p < 0.05). The percentage of antral follicles in the Choline + Omega-3 group were higher compared to the control group (p < 0.05). To elucidate the potential molecular mechanism of choline on these improved ovarian phenotypes, the expression of a group of genes that are involved in ovarian development, including cytochrome P450 family 11 subfamily A member 1 (CYP11A1), follicle stimulating hormone receptor (FHSR) and luteinizing hormone receptor (LHR), was analyzed using RT-qPCR. The expression of both LHR and CYP11A1 was significantly upregulated in the choline-supplemented group (p < 0.05), while there are no differences in FSHR expression among all the groups. Additionally, the expression of miR-21, -378, -574, previously found to be important in ovarian function, were examined. Our data showed that miR-574 was upregulated in the Choline group while miR-378 was upregulated in the Choline + Omega-3 group in comparison to the control group (p < 0.05). Further, serum metabolite analysis showed that 1-(5Z, 8Z, 11Z, 14Z, 17Z-eicosapentaenoyl)-sn-glycero-3-phosphocholine, a form of phosphatidylcholine metabolite, was significantly increased in all the treatment groups (p < 0.05), while testosterone was significantly increased in both Omega-3 and Choline + Omega-3 groups (p < 0.05) and tended to be reduced in the choline-supplemented group (p = 0.08) compared to the control group. Our study demonstrated choline's influence on ovarian function in vivo, and offered insights into the mechanisms behind its positive effect on ovarian development phenotype.