Importancia de la colina durante el embarazo y lactancia. Una revisión sistemática / Importance of choline during pregnancy and lactation: A systematic review

El embarazo es uno de los momentos más importantes y difíciles por los que transcurre una mujer a lo largo de su vida. Supone un periodo de grandes necesidades de macro y micronutrientes para satisfacer las demandas del feto en desarrollo y evitar carencias, para así obtener el mejor resultado posible. Hoy en día, la mayoría de mujeres embarazadas o planeando estarlo conocen la importancia de obtener la cantidad requerida de ciertos tipos de nutrientes (proteínas, grasas, folato, etc.), así como evitar ciertos compuestos (alcohol, tabaco, fármacos, etc.) para evitar posibles complicaciones durante el embarazo. En los últimos años, con la mayor evidencia científica disponible, se ha ido demostrando como algunos de estos nutrientes podrían tener un papel más relevante del que se creía en el resultado óptimo del embarazo, siendo uno de estos nutrientes la colina. La suplementación con colina durante el embarazo ha demostrado ser un tratamiento no farmacológico capaz de mejorar cualidades tanto físicas (crecimiento) como mentales (memoria) del nuevo individuo. La colina se conoce como un nutriente esencial desde 1998 y varios estudios han demostrado su efectividad en modelos de roedores. La existencia de recientes publicaciones que versan sobre su aplicación en humanos hace necesaria la realización de una revisión sistemática. En esta revisión sistemática de la evidencia científica disponible desde el año 2012 hasta la actualidad que versa sobre la aplicación de un mayor consumo de colina mediante suplementación como tratamiento para mejorar los resultados del embarazo, su objetivo principal es determinar los efectos que puede tener en la cognición de los niños una intervención nutricional mediante suplementación de colina en madres embarazadas (AU)

Pregnancy is one of the most important and difficult moments that a woman goes through throughout her life. It is a period of great need for macro and micronutrients to meet the demands of the developing fetus and avoid deficiencies, in order to obtain the best possible result. Nowadays, most women who are pregnant or planning to become pregnant know the importance of getting the required amount of certain types of nutrients (proteins, fats, folate, etc.), as well as avoiding certain compounds (alcohol, tobacco, drugs, etc.) to avoid possible complications during pregnancy. In recent years, with the greatest scientific evidence available, it has been shown how some of these nutrients could have a more relevant role than previously believed in the optimal outcome of pregnancy. One of these nutrients being choline. Choline supplementation during pregnancy has been shown to be a non-pharmacological treatment capable of improving both physical (growth) and mental (memory) qualities of the new individual. Choline has been known as an essential nutrient since 1998 and several studies have shown its effectiveness in rodent models. The existence of recent publications that deal with its application in humans makes it necessary to carry out a systematic review. In this systematic review of the scientific evidence available from 2012 to the present that deals with the application of a higher intake of choline through supplementation as a treatment to improve pregnancy outcomes, its main objetive is to determine the effects that a nutritional intervention through choline supplementation in pregnant mothers can have on children's cognition (AU)

Effects of egg yolk choline intake on cognitive functions and plasma choline levels in healthy middle-aged and older Japanese: a randomized double-blinded placebo-controlled parallel-group study.

BACKGROUND: Choline, as a neurotransmitter acetylcholine precursor, is reportedly associated with cognitive function. Although there are several cohort and animal studies on choline-containing foods and cognitive function, only a few interventional studies were reported. Egg yolk is a rich source of different choline-containing chemical forms, such as phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and α-glycerophosphocholine (α-GPC). This study aimed to investigate the effect of consuming 300 mg of egg yolk choline per day on cognitive function of Japanese adults. METHODS: A 12-week, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 41 middle-aged and elderly males and females (43.9% female) aged ≥ 60 years and ≤ 80 years without dementia. Participants were randomly assigned to placebo and choline groups. The choline group received a supplement containing egg yolk choline (300 mg/day), and the placebo group received an egg yolk supplement free from choline for 12 weeks. Assessments of Cognitrax, Trail Making Tests (TMT) part A and B, the MOS 36-Item Short-Form Health Survey (SF-36), the Simplified Japanese Version of the WHO-Five Well-Being Index (WHO-5), and plasma choline levels were performed before and 6 and 12 weeks after supplement intake. In the present study, 19 subjects (9 in the placebo group and 10 in the choline group) were excluded due to the violation of the discontinuation criteria or participant compliance, and 41 subjects were analyzed. RESULTS: The change amount of verbal memory scores and verbal memory test-correct hit (delay) was significantly higher in the choline group than in the placebo group at baseline-6 and baseline-12 weeks. The plasma free choline level was significantly higher in the choline group compared with the placebo group at 6 weeks. Conversely, the choline group showed significantly lower Cognitrax processing speed scores, symbol digit coding testing correct responses, and SF-36 physical quality of life summary scores compared to the placebo group at 6 weeks. CONCLUSIONS: The results suggested that continued 300 mg/day intake of egg yolk choline improved verbal memory, which is a part of cognitive functions. To confirm the observed effects of egg yolk choline, more well-designed and large-scale studies are warranted. TRIAL REGISTRATION: Study protocols were pre-registered in the Clinical Trials Registration System (UMIN-CTR) (UMIN 000045050).

Associations of plasma betaine, plasma choline, choline intake, and MTHFR polymorphism (rs1801133) with anthropometric parameters of healthy adults are sex-dependent.

BACKGROUND: Choline and its metabolites apppear to have relationships with body mass index (BMI), body fat, and body weight, but the research results have proved inconsistent. We thus investigated the associations of plasma levels of trimethylamine N-oxide (TMAO), choline, and betaine with anthropometric measurements, including modulatory effects of genetics and diet. METHODS: The study was performed on a group of 421 adults, aged 20-40 years, who had been recruited in Poland. Plasma concentrations of choline, betaine, and TMAO were determined using reverse-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry. The following polymorphisms were genotyped using TaqMan probes: rs180113 (MTHFR), rs70991108 (DHFR), rs2236225 (MTHFD1), and rs7946 and rs12325817 (PEMT). We employed multivariate linear regression to examine the associations between anthropometric measurements, one-carbon metabolism metabolites, and genotypes. RESULTS: Higher plasma choline was associated with higher BMI (ß = 0.17; p < 0.01), body weight (ß = 0.11; p < 0.05), body fat mass (FM) (ß = 0.10; p < 0.05), and waist circumference (WC) (ß = 0.14; p < 0.01), whereas higher choline intake was associated with lower body FM (ß = -0.14; p < 0.01) and lower WC (ß = -0.12; p < 0.01). After stratification by sex, plasma betaine was found to be associated with lower BMI (ß = -0.20; p < 0.05) and body weight (ß = -0.16; p < 0.05) in men only, whereas choline intake was associated with lower body FM (ß = -0.19; p < 0.05) and waist-to-hip ratio (WHR) (ß = -0.19; p < 0.05) and MTHFR CC genotype was associated with WHR (ß = 0.15; p < 0.05) in women only. CONCLUSIONS: Higher plasma betaine and higher dietary choline are associated with lower FM and body weight, whereas higher plasma choline is positively associated with body weight status and adiposity. Moreover, these associations appear to be sex-specific.

Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms.

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (Lepob/ob). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics.

Optimal Dietary Intake Composition of Choline and Betaine Is Associated with Minimized Visceral Obesity-Related Hepatic Steatosis in a Case-Control Study.

Few studies on humans have comprehensively evaluated the intake composition of methyl-donor nutrients (MDNs: choline, betaine, and folate) in relation to visceral obesity (VOB)-related hepatic steatosis (HS), the hallmark of non-alcoholic fatty liver diseases. In this case-control study, we recruited 105 patients with HS and 104 without HS (controls). HS was diagnosed through ultrasound examination. VOB was measured using a whole-body analyzer. MDN intake was assessed using a validated quantitative food frequency questionnaire. After adjustment for multiple HS risk factors, total choline intake was the most significant dietary determinant of HS in patients with VOB (Beta: -0.41, p = 0.01). Low intake of choline (<6.9 mg/kg body weight), betaine (<3.1 mg/kg body weight), and folate (<8.8 µg/kg body weight) predicted increased odds ratios (ORs) of VOB-related HS (choline: OR: 22, 95% confidence interval [CI]: 6.5-80; betaine: OR: 14, 95% CI: 4.4-50; and folate: OR: 19, 95% CI: 5.2-74). Combined high intake of choline and betaine, but not folate, was associated with an 81% reduction in VOB-related HS (OR: 0.19, 95% CI: 0.05-0.69). Our data suggest that the optimal intake of choline and betaine can minimize the risk of VOB-related HS in a threshold-dependent manner.

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.

Do Micronutrient and Omega-3 Fatty Acid Supplements Affect Human Maternal Immunity during Pregnancy? A Scoping Review.

Maternal dietary micronutrients and omega-3 fatty acids support development of the fetal and neonatal immune system. Whether supplementation is similarly beneficial for the mother during gestation has received limited attention. A scoping review of human trials was conducted looking for evidence of biochemical, genomic, and clinical effects of supplementation on the maternal immune system. The authors explored the literature on PubMed, Cochrane Library, and Web of Science databases from 2010 to the present day using PRISMA-ScR methodology. Full-length human trials in English were searched for using general terms and vitamin A, B12, C, D, and E; choline; iodine; iron; selenium; zinc; and docosahexaenoic/eicosapentaenoic acid. Of 1391 unique articles, 36 were eligible for inclusion. Diverse biochemical and epigenomic effects of supplementation were identified that may influence innate and adaptive immunity. Possible clinical benefits were encountered in malaria, HIV infections, anemia, Type 1 diabetes mellitus, and preventing preterm delivery. Only limited publications were identified that directly explored maternal immunity in pregnancy and the effects of micronutrients. None provided a holistic perspective. It is concluded that supplementation may influence biochemical aspects of the maternal immune response and some clinical outcomes, but the evidence from this review is not sufficient to justify changes to current guidelines.

Prenatal choline supplementation improves child sustained attention: A 7-year follow-up of a randomized controlled feeding trial.

Numerous rodent studies demonstrate developmental programming of offspring cognition by maternal choline intake, with prenatal choline deprivation causing lasting adverse effects and supplemental choline producing lasting benefits. Few human studies have evaluated the effect of maternal choline supplementation on offspring cognition, with none following children to school age. Here, we report results from a controlled feeding study in which pregnant women were randomized to consume 480 mg choline/d (approximately the Adequate Intake [AI]) or 930 mg choline/d during the 3rd trimester. Sustained attention was assessed in the offspring at age 7 years (n = 20) using a signal detection task that showed benefits of maternal choline supplementation in a murine model. Children in the 930 mg/d group showed superior performance (vs. 480 mg/d group) on the primary endpoint (SAT score, p = .02) and a superior ability to maintain correct signal detections (hits) across the 12-min session (p = .02), indicative of improved sustained attention. This group difference in vigilance decrement varied by signal duration (p = .04). For the briefest (17 ms) signals, the 480 mg/d group showed a 22.9% decline in hits across the session compared to a 1.5% increase in hits for the 930 mg/d group (p = .04). The groups did not differ in vigilance decrement for 29 or 50 ms signals. This pattern suggests an enhanced ability to sustain perceptual amplification of a brief low-contrast visual signal by children in the 930 mg/d group. This inference of improved sustained attention by the 930 mg/d group is strengthened by the absence of group differences for false alarms, omissions, and off-task behaviors. This pattern of results indicates that maternal 3rd trimester consumption of the choline AI for pregnancy (vs. double the AI) produces offspring with a poorer ability to sustain attention-reinforcing concerns that, on average, choline consumption by pregnant women is approximately 70% of the AI.

Superior sensitivity of 18F-fluorocholine: PET localization in primary hyperparathyroidism.

BACKGROUND: Preoperative parathyroid imaging guides surgeons during parathyroidectomy. This study evaluates the clinical impact of 18F-fluorocholine positron emission tomography for preoperative parathyroid localization on patients with primary hyperparathyroidism. METHODS: Patients with primary hyperparathyroidism and indications for parathyroidectomy had simultaneous 18F-fluorocholine positron emission tomography imaging/magnetic resonance imaging. In patients who underwent subsequent parathyroidectomy, cure was based on lab values at least 6 months after surgery. Location-based sensitivity and specificity of 18F-fluorocholine positron emission tomography imaging was assessed using 3 anatomic locations (left neck, right neck, and mediastinum), with surgery as the gold standard. RESULTS: In 101 patients, 18F-fluorocholine positron emission tomography localized at least 1 candidate lesion in 93% of patients overall and in 91% of patients with previously negative imaging, leading to a change in preoperative strategy in 60% of patients. Of 76 patients who underwent parathyroidectomy, 58 (77%) had laboratory data at least 6 months postoperatively, with 55/58 patients (95%) demonstrating cure. 18F-fluorocholine positron emission tomography successfully guided curative surgery in 48/58 (83%) patients, compared with 20/57 (35%) based on ultrasound and 13/55 (24%) based on sestamibi. In a location-based analysis, sensitivity of 18F-fluorocholine positron emission tomography (88.9%) outperformed both ultrasound (37.1%) and sestamibi (27.5%), as well as ultrasound and sestamibi combined (47.8%). CONCLUSION: Long-term results in the first cohort in the United States to use 18F-fluorocholine positron emission tomography for parathyroid localization confirm its utility in a challenging cohort, with better sensitivity than ultrasound or sestamibi.

A cost-utility analysis of 18F-fluorocholine-positron emission tomography imaging for localizing primary hyperparathyroidism in the United States.

BACKGROUND: Primary hyperparathyroidism historically necessitated bilateral neck exploration to remove abnormal parathyroid tissue. Improved localization allows for focused parathyroidectomy with lower complication risks. Recently, positron emission tomography using radiolabeled 18F-fluorocholine demonstrated high accuracy in detecting these lesions, but its cost-effectiveness has not been studied in the United States. METHODS: A decision tree modeled patients who underwent parathyroidectomy for primary hyperparathyroidism using single preoperative localization modalities: (1) positron emission tomography using radiolabeled 18F-fluorocholine, (2) 4-dimensional computed tomography, (3) ultrasound, and (4) sestamibi single photon emission computed tomography (SPECT). All patients underwent either focused parathyroidectomy versus bilateral neck exploration, with associated cost ($) and clinical outcomes measured in quality-adjusted life-years gained. Model parameters were informed by literature review and Medicare costs. Incremental cost-utility ratios were calculated in US dollars/quality-adjusted life-years gained, with a willingness-to-pay threshold set at $100,000/quality-adjusted life-year. One-way, 2-way, and threshold sensitivity analyses were performed. RESULTS: Positron emission tomography using radiolabeled 18F-fluorocholine gained the most quality-adjusted life-years (23.9) and was the costliest ($2,096), with a total treatment cost of $11,245 or $470/quality-adjusted life-year gained. Sestamibi single photon emission computed tomography and ultrasound were dominated strategies. Compared with 4-dimentional computed tomography, the incremental cost-utility ratio for positron emission tomography using radiolabeled 18F-fluorocholine was $91,066/quality-adjusted life-year gained in our base case analysis, which was below the willingness-to-pay threshold. In 1-way sensitivity analysis, the incremental cost-utility ratio was sensitive to test accuracy, positron emission tomography using radiolabeled 18F-fluorocholine price, postoperative complication probabilities, proportion of bilateral neck exploration patients needing overnight hospitalization, and life expectancy. CONCLUSION: Our model elucidates scenarios in which positron emission tomography using radiolabeled 18F-fluorocholine can potentially be a cost-effective imaging option for primary hyperparathyroidism in the United States. Further investigation is needed to determine the maximal cost-effectiveness for positron emission tomography using radiolabeled 18F-fluorocholine in selected populations.

Prenatal Iron Deficiency and Choline Supplementation Interact to Epigenetically Regulate Jarid1b and Bdnf in the Rat Hippocampus into Adulthood.

Early-life iron deficiency (ID) causes long-term neurocognitive impairments and gene dysregulation that can be partially mitigated by prenatal choline supplementation. The long-term gene dysregulation is hypothesized to underlie cognitive dysfunction. However, mechanisms by which iron and choline mediate long-term gene dysregulation remain unknown. In the present study, using a well-established rat model of fetal-neonatal ID, we demonstrated that ID downregulated hippocampal expression of the gene encoding JmjC-ARID domain-containing protein 1B (JARID1B), an iron-dependent histone H3K4 demethylase, associated with a higher histone deacetylase 1 (HDAC1) enrichment and a lower enrichment of acetylated histone H3K9 (H3K9ac) and phosphorylated cAMP response element-binding protein (pCREB). Likewise, ID reduced transcriptional capacity of the gene encoding brain-derived neurotrophic factor (BDNF), a target of JARID1B, associated with repressive histone modifications such as lower H3K9ac and pCREB enrichments at the Bdnf promoters in the adult rat hippocampus. Prenatal choline supplementation did not prevent the ID-induced chromatin modifications at these loci but induced long-lasting repressive chromatin modifications in the iron-sufficient adult rats. Collectively, these findings demonstrated that the iron-dependent epigenetic mechanism mediated by JARID1B accounted for long-term Bdnf dysregulation by early-life ID. Choline supplementation utilized a separate mechanism to rescue the effect of ID on neural gene regulation. The negative epigenetic effects of choline supplementation in the iron-sufficient rat hippocampus necessitate additional investigations prior to its use as an adjunctive therapeutic agent.

Choline intake and associations with egg and dairy consumption among pregnant women attending a high-risk antenatal clinic in South Africa: the NuEMI study.

BACKGROUND: The importance of adequate choline intake during pregnancy has been well documented, but low intake is common. Total choline intake, main food sources of choline, as well as associations between choline intake and egg and dairy consumption were determined in a sample of pregnant women attending the high-risk antenatal clinic at a regional hospital in Bloemfontein, South Africa. METHODS: A cross-sectional study design was used. Trained fieldworkers collected dietary intake data using a validated quantified food frequency questionnaire (QFFQ), after which all food items were matched to foods in the USDA Database for the Choline Content of Common Foods (Release 2) to quantify choline intake. Logistic regression with backward selection (p < 0.05) was used to determine whether egg and dairy consumption were independently associated with a choline intake below the adequate intake (AI) level. RESULTS: The median daily intake of choline was 275 mg (interquartile range 185 mg - 387 mg) (N = 681). Most participants (84.7%) consumed less than the AI of 450 mg/day for choline. Meat and meat products, cereals, eggs and dairy contributed mostly to choline intake. Food items that contributed most to choline intake included full-cream milk, maize porridge, brown bread, deep-fried potatoes and deep-fried dough (vetkoek). A choline intake below the AI was significantly associated with lower egg and dairy intakes (p < 0.0001 and p = 0.0002 respectively). CONCLUSION: Most pregnant women in the current study had choline intakes below the AI. It is recommended that public health messaging targeted at pregnant women promote the consumption of foods that can significantly contribute to choline intake, such as eggs and dairy.

Krill-Oil-Dependent Increases in HS-Omega-3 Index, Plasma Choline and Antioxidant Capacity in Well-Conditioned Power Training Athletes.

There is evidence that both omega-3 polyunsaturated fatty acids (n-3 PUFAs) and choline can influence sports performance, but information establishing their combined effects when given in the form of krill oil during power training protocols is missing. The purpose of this study was therefore to characterize n-3 PUFA and choline profiles after a one-hour period of high-intensity physical workout after 12 weeks of supplementation. Thirty-five healthy power training athletes received either 2.5 g/day of Neptune krill oilTM (550 mg EPA/DHA and 150 mg choline) or olive oil (placebo) in a randomized double-blind design. After 12 weeks, only the krill oil group showed a significant HS-Omega-3 Index increase from 4.82 to 6.77% and a reduction in the ARA/EPA ratio (from 50.72 to 13.61%) (p < 0.001). The krill oil group showed significantly higher recovery of choline concentrations relative to the placebo group from the end of the first to the beginning of the second exercise test (p = 0.04) and an 8% decrease in total antioxidant capacity post-exercise versus 21% in the placebo group (p = 0.35). In conclusion, krill oil can be used as a nutritional strategy for increasing the HS-Omega-3 Index, recover choline concentrations and address oxidative stress after intense power trainings.

Habitual Choline Intakes across the Childbearing Years: A Review.

Choline is an important nutrient during the first 1000 days post conception due to its roles in brain function. An increasing number of studies have measured choline intakes at the population level. We collated the evidence focusing on habitual choline intakes in the preconceptual, pregnancy, and lactation life stages. We conducted a review including studies published from 2004 to 2021. Twenty-six relevant publications were identified. After excluding studies with a high choline intake (>400 mg/day; two studies) or low choline intake (<200 mg/day; one study), average choline intake in the remaining 23 studies ranged from 233 mg/day to 383 mg/day, even with the inclusion of choline from supplements. Intakes were not higher in studies among pregnant and lactating women compared with studies in nonpregnant women. To conclude, during the childbearing years and across the globe, habitual intakes of choline from foods alone and foods and supplements combined appear to be consistently lower than the estimated adequate intakes for this target group. Urgent measures are needed to (1) improve the quality of choline data in global food composition databases, (2) encourage the reporting of choline intakes in dietary surveys, (3) raise awareness about the role(s) of choline in foetal-maternal health, and (4) consider formally advocating the use of choline supplements in women planning a pregnancy, pregnant, or lactating.

The rumen microbiome inhibits methane formation through dietary choline supplementation.

Enteric fermentation from ruminants is a primary source of anthropogenic methane emission. This study aims to add another approach for methane mitigation by manipulation of the rumen microbiome. Effects of choline supplementation on methane formation were quantified in vitro using the Rumen Simulation Technique. Supplementing 200 mM of choline chloride or choline bicarbonate reduced methane emissions by 97-100% after 15 days. Associated with the reduction of methane formation, metabolomics analysis revealed high post-treatment concentrations of ethanol, which likely served as a major hydrogen sink. Metagenome sequencing showed that the methanogen community was almost entirely lost, and choline-utilizing bacteria that can produce either lactate, ethanol or formate as hydrogen sinks were enriched. The taxa most strongly associated with methane mitigation were Megasphaera elsdenii and Denitrobacterium detoxificans, both capable of consuming lactate, which is an intermediate product and hydrogen sink. Accordingly, choline metabolism promoted the capability of bacteria to utilize alternative hydrogen sinks leading to a decline of hydrogen as a substrate for methane formation. However, fermentation of fibre and total organic matter could not be fully maintained with choline supplementation, while amino acid deamination and ethanolamine catabolism produced excessive ammonia, which would reduce feed efficiency and adversely affect live animal performance.

Choline metabolome response to prenatal choline supplementation across pregnancy: A randomized controlled trial.

Pregnancy places a unique stress upon choline metabolism, requiring adaptations to support both maternal and fetal requirements. The impact of pregnancy and prenatal choline supplementation on choline and its metabolome in free-living, healthy adults is relatively uncharacterized. This study investigated the effect of prenatal choline supplementation on maternal and fetal biomarkers of choline metabolism among free-living pregnant persons consuming self-selected diets. Participants were randomized to supplemental choline (as choline chloride) intakes of 550 mg/d (500 mg/d d0-choline + 50 mg/d methyl-d9-choline; intervention) or 25 mg/d d9-choline (control) from gestational week (GW) 12-16 until Delivery. Fasting blood and 24-h urine samples were obtained at study Visit 1 (GW 12-16), Visit 2 (GW 20-24), and Visit 3 (GW 28-32). At Delivery, maternal and cord blood and placental tissue samples were collected. Participants randomized to 550 (vs. 25) mg supplemental choline/d achieved higher (p < .05) plasma concentrations of free choline, betaine, dimethylglycine, phosphatidylcholine (PC), and sphingomyelin at one or more study timepoint. Betaine was most responsive to prenatal choline supplementation with increases (p ≤ .001) in maternal plasma observed at Visit 2-Delivery (relative to Visit 1 and control), as well as in the placenta and cord plasma. Notably, greater plasma enrichments of d3-PC and LDL-C were observed in the intervention (vs. control) group, indicating enhanced PC synthesis through the de novo phosphatidylethanolamine N-methyltransferase pathway and lipid export. Overall, these data show that prenatal choline supplementation profoundly alters the choline metabolome, supporting pregnancy-related metabolic adaptations and revealing biomarkers for use in nutritional assessment and monitoring during pregnancy.

Pathobiological Relationship of Excessive Dietary Intake of Choline/L-Carnitine: A TMAO Precursor-Associated Aggravation in Heart Failure in Sarcopenic Patients.

The microecological environment of the gastrointestinal tract is altered if there is an imbalance between the gut microbiota phylases, resulting in a variety of diseases. Moreover, progressive age not only slows down physical activity but also reduces the fat metabolism pathway, which may lead to a reduction in the variety of bacterial strains and bacteroidetes' abundance, promoting firmicutes and proteobacteria growth. As a result, dysbiosis reduces physiological adaptability, boosts inflammatory markers, generates ROS, and induces the destruction of free radical macromolecules, leading to sarcopenia in older patients. Research conducted at various levels indicates that the microbiota of the gut is involved in pathogenesis and can be considered as the causative agent of several cardiovascular diseases. Local and systematic inflammatory reactions are caused in patients with heart failure, as ischemia and edema are caused by splanchnic hypoperfusion and enable both bacterial metabolites and bacteria translocation to enter from an intestinal barrier, which is already weakened, to the blood circulation. Multiple diseases, such as HF, include healthy microbe-derived metabolites. These key findings demonstrate that the gut microbiota modulates the host's metabolism, either specifically or indirectly, by generating multiple metabolites. Currently, the real procedures that are an analogy to the symptoms in cardiac pathologies, such as cardiac mass dysfunctions and modifications, are investigated at a minimum level in older patients. Thus, the purpose of this review is to summarize the existing knowledge about a particular diet, including trimethylamine, which usually seems to be effective for the improvement of cardiac and skeletal muscle, such as choline and L-carnitine, which may aggravate the HF process in sarcopenic patients.

Prenatal choline supplementation during mouse pregnancy has differential effects in alcohol-exposed fetal organs.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are preventable adverse outcomes consequent to prenatal alcohol exposure. Supplemental choline confers neuroprotection to the alcohol-exposed offspring, but its actions outside the brain are unclear. We previously reported that prenatal exposure of mice to 4.5 g/kg of alcohol decreased placental weight in females only, but decreased body weight and liver-to-body weight ratio and increased brain-to-body weight ratio in both sexes. Here we test the hypotheses that a lower alcohol dose will elicit similar outcomes, and that concurrent choline treatment will mitigate these outcomes. METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (3 g/kg; Alc) or maltodextrin (MD) from embryonic day (E) 8.5-17.5. Some also received a subcutaneous injection of 100 mg/kg choline chloride (Alc + Cho, MD + Cho). Outcomes were evaluated on E17.5. RESULTS: Alc dams had lower gestational weight gain than MD; this was normalized by choline. In males, Alc decreased placental weight whereas choline increased placental efficiency, and Alc + Cho (vs. MD) tended to further reduce placental weight and increase efficiency. Despite no significant alcohol effects on these measures, choline increased fetal body weight but not brain weight, thus reducing brain-to-body weight ratio in both sexes. This ratio was also lower in the Alc + Cho (vs. MD) fetuses. Alc reduced liver weight and the liver-to-body weight ratio; choline did not improve these. Placental weight and efficiency correlated with litter size, whereas placental efficiency correlated with fetal morphometric measurements. CONCLUSIONS: Choline prevents an alcohol-induced reduction in gestational weight gain and fetal body weight and corrects fetal brain sparing, consistent with clinical findings of improvements in alcohol-exposed children born to mothers receiving choline supplementation. Importantly, we show that choline enhances placental efficiency in the alcohol-exposed offspring but does not normalize fetal liver growth. Our findings support choline supplementation during pregnancy to mitigate the severity of FASD and emphasize the need to examine choline's actions in different organ systems.

Dietary Intake Adequacy and Food Sources of Nutrients Involved in the Methionine-Methylation Cycle in Women of Childbearing Age from the ANIBES Spanish Population.

Growing evidence confirms choline as a critical perinatal nutrient. However, intake levels of choline and betaine among the Spanish fertile population remain unknown. Given their role in one-carbon metabolism with potential epigenetic effects, the aim of the present study was to evaluate the dietary intakes, their adequacy to existing guidelines and the main food sources together with other micronutrients involved in the methylation-methionine cycle (vitamin B6, folates and vitamin B12) in women of childbearing age. The ANIBES study, a cross-sectional study of a representative sample of women of childbearing age (18-45 years, n = 641) resident in Spain, was used. The sample was divided into younger women (18-30 years, n = 251) and older women (31-45 years, n = 390). Dietary intake was assessed by a three-day dietary record by using a tablet device. Total median intakes for the total sample were 303.9 mg/d for choline; 122.6 mg/d for betaine; 1.3 mg/d for vitamin B6; 140.8 µg/d for folates, and 3.8 µg/d for vitamin B12. The older subgroup showed significantly higher choline (p < 0.05), betaine (p < 0.001) and folates (p < 0.05) intakes than younger women. Main food sources for the whole sample were meat and meat products for choline (28.3%), vitamin B6 (25.7%) and vitamin B12 (22.8%); cereals and derivatives (79.9%) for betaine; vegetables (20.0%) for folates. Overall intake adequacy was only observed for vitamin B12, with a very limited number of participants showing adequate intakes for all the other micronutrients. These results illustrate there is a relevant need to raise awareness about optimizing the status of the methionine cycle-related vitamins and cofactors in this potentially vulnerable population.

Maternal choline supplementation in a rat model of periconceptional alcohol exposure: Impacts on the fetus and placenta.

BACKGROUND: Maternal choline supplementation in rats can ameliorate specific neurological and behavioral abnormalities caused by alcohol exposure during pregnancy. We tested whether choline supplementation ameliorates fetal growth restriction and molecular changes in the placenta associated with periconceptional ethanol exposure (PCE) in the rat. METHODS: Sprague Dawley dams were given either 12.5% ethanol (PCE) or 0% ethanol (Con) in a liquid diet from 4 days prior to 4 days after conception. At day 5 of pregnancy, dams were either placed on a standard chow (1.6 g choline/kg chow) or an intermediate chow (2.6 g choline/kg chow). On day 10 of pregnancy, a subset of the intermediate dams were placed on a chow further supplemented with choline (7.2 g choline/kg chow), resulting in 6 groups. Fetuses and placentas were collected on day 20 of pregnancy for analysis. RESULTS: Choline supplementation resulted in increased fetal weight at late gestation, ameliorating the deficits due to PCE. This was most pronounced in litters on a standard chow during pregnancy. Choline also increased fetal liver weight and decreased fetal brain:liver ratio, independent of alcohol exposure. Placental weight was reduced as choline levels in the chow increased, particularly in female placentas. This resulted in a greater ratio of fetal:placental weight, suggesting increased placental efficiency. Global DNA methylation in the placenta was altered in a sex-specific manner by both PCE and choline. However, the increased glycogen deposition in female placentas, previously reported in this PCE model, was not prevented by choline supplementation. CONCLUSIONS: Our results suggest that choline has the potential to ameliorate fetal growth restriction associated with PCE and improve placental efficiency following prenatal alcohol exposure. Our study highlights the importance of maternal nutrition in moderating the severity of adverse fetal and placental outcomes that may arise from prenatal alcohol exposure around the time of conception.