The origin of betaine in mouse oocytes and preimplantation embryos†.

Betaine has important roles in preimplantation mouse embryos, including as an organic osmolyte that functions in cell volume regulation in the early preimplantation stages and as a donor to the methyl pool in blastocysts. The origin of betaine in oocytes and embryos was largely unknown. Here, we found that betaine was present from the earliest stage of growing oocytes.

Genetic admixture predictors of fetal alcohol spectrum disorders (FASD) in the South African Cape Coloured population.

Ancestrally admixed populations are underrepresented in genetic studies of complex diseases, which are still dominated by European-descent populations. This is relevant not only from a representation standpoint but also because of admixed populations' unique features, including being enriched for rare variants, for which effect sizes are disproportionately larger than common polymorphisms. Furthermore, results from these populations may be generalizable to other populations.

A Narrative Review on Maternal Choline Intake and Liver Function of the Fetus and the Infant; Implications for Research, Policy, and Practice.

Dietary choline is needed to maintain normal health, including normal liver function in adults. Fatty liver induced by a choline-deficient diet has been consistently observed in human and animal studies. The effect of insufficient choline intake on hepatic fat accumulation is specific and reversible when choline is added to the diet.

Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes.

Background: Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood.

Valuing the Diversity of Research Methods to Advance Nutrition Science.

The ASN Board of Directors appointed the Nutrition Research Task Force to develop a report on scientific methods used in nutrition science to advance discovery, interpretation, and application of knowledge in the field. The genesis of this report was growing concern about the tone of discourse among nutrition professionals and the implications of acrimony on the productive study and translation of nutrition science. Too often, honest differences of opinion are cast as conflicts instead of areas of needed collaboration.

Effects of a Novel High-Quality Protein Infant Formula on Energetic Efficiency and Tolerance: A Randomized Trial.

Objectives: Protein overfeeding in infants can have negative effects, such as diabetes and childhood obesity; key to reducing protein intake from formula is improving protein quality. The impact of a new infant formula [study formula (SF)] containing alpha-lactalbumin, lactoferrin, partially hydrolyzed whey, and whole milk on growth and tolerance compared to a commercial formula (CF) and a human milk reference arm was evaluated.

Methods: This randomized, double-blind trial included healthy, singleton, term infants, enrollment age ≤14 days.

Targeting Treatments to Health Disparities.

These initial data suggest that with prenatal vitamins and choline supplements, we might decrease one risk factor associated with poorer health outcomes disproportionally affecting Black families, ie, preterm birth. Dissemination of this research fulfills the principle of Justice in the Belmont Report, to ensure that participants from different racial, ethnic and socioeconomic groups receive benefits from research directed to their specific problems.

Polymorphisms in SLC44A1 are associated with cognitive improvement in children diagnosed with fetal alcohol spectrum disorder: an exploratory study of oral choline supplementation.

Background: The essential nutrient choline provides one-carbon units for metabolite synthesis and epigenetic regulation in tissues including brain. Dietary choline intake is often inadequate, and higher intakes are associated with improved cognitive function.

Objective: Choline supplements confer cognitive improvement for those diagnosed with fetal alcohol spectrum disorder (FASD), a common set of neurodevelopmental impairments; however, the effect sizes have been modest.

Two methods for assessment of choline status in a randomized crossover study with varying dietary choline intake in people: isotope dilution MS of plasma and in vivo single-voxel magnetic resonance spectroscopy of liver.

Background: Choline deficiency has numerous negative health consequences; although the preponderance of the US population consumes less than the recommended Adequate Intake (AI), clinical assessment of choline status is difficult. Further, several pathways involved in primary metabolism of choline are estrogen-sensitive and the AI for premenopausal women is lower than that for men.

Objectives: We sought to determine whether in vivo magnetic resonance spectroscopy (MRS) of liver and/or isotope-dilution MS of plasma could identify biomarkers reflective of choline intake (preregistered primary outcomes 1 and 2, secondary outcome 1).

Prenatal choline, cannabis, and infection, and their association with offspring development of attention and social problems through 4 years of age.

Background: Prenatal choline is a key nutrient, like folic acid and vitamin D, for fetal brain development and subsequent mental function. We sought to determine whether effects of higher maternal plasma choline concentrations on childhood attention and social problems, found in an initial clinical trial of choline supplementation, are observed in a second cohort.

Methods: Of 183 mothers enrolled from an urban safety net hospital clinic, 162 complied with gestational assessments and brought their newborns for study at 1 month of age; 83 continued assessments through 4 years of age.

Black American Maternal Prenatal Choline, Offspring Gestational Age at Birth, and Developmental Predisposition to Mental Illness.

Black Americans have increased risk for schizophrenia and other mental illnesses with prenatal origins. Prenatal choline promotes infant brain development and behavioral outcomes, but choline has not been specifically assessed in Black Americans. Pregnant women (N = 183, N = 25 Black Americans) enrolled in a study of prenatal stressors and interactions with prenatal choline.

The Association of Dietary Choline and Betaine With the Risk of Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study.

Objective: To examine the association between dietary intake of choline and betaine and the risk of type 2 diabetes.

Research Design And Methods: Among 13,440 Atherosclerosis Risk in Communities (ARIC) study participants, the prospective longitudinal association between dietary choline and betaine intake and the risk of type 2 diabetes was assessed using interval-censored Cox proportional hazards and logistic regression models adjusted for baseline potential confounding variables.

Results: Among 13,440 participants (55% women, mean age 54 [SD 7.

Four-year follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder.

Background: Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial.

Precision (Personalized) Nutrition: Understanding Metabolic Heterogeneity.

People differ in their requirements for and responses to nutrients and bioactive molecules in the diet. Many inputs contribute to metabolic heterogeneity (including variations in genetics, epigenetics, microbiome, lifestyle, diet intake, and environmental exposure). Precision nutrition is not about developing unique prescriptions for individual people but rather about stratifying people into different subgroups of the population on the basis of biomarkers of the above-listed sources of metabolic variation and then using this stratification to better estimate the different subgroups' dietary requirements, thereby enabling better dietary recommendations and interventions.

Protein Intake at Twice the RDA in Older Men Increases Circulatory Concentrations of the Microbiome Metabolite Trimethylamine-N-Oxide (TMAO).

Higher dietary protein intake is increasingly recommended for the elderly; however, high protein diets have also been linked to increased cardiovascular disease (CVD) risk. Trimethylamine-N-oxide (TMAO) is a bacterial metabolite derived from choline and carnitine abundant from animal protein-rich foods. TMAO may be a novel biomarker for heightened CVD risk.

Perspective: Dietary Biomarkers of Intake and Exposure-Exploration with Omics Approaches.

While conventional nutrition research has yielded biomarkers such as doubly labeled water for energy metabolism and 24-h urinary nitrogen for protein intake, a critical need exists for additional, equally robust biomarkers that allow for objective assessment of specific food intake and dietary exposure. Recent advances in high-throughput MS combined with improved metabolomics techniques and bioinformatic tools provide new opportunities for dietary biomarker development. In September 2018, the NIH organized a 2-d workshop to engage nutrition and omics researchers and explore the potential of multiomics approaches in nutritional biomarker research.

Choline: The Neurocognitive Essential Nutrient of Interest to Obstetricians and Gynecologists.

Choline is an essential nutrient for proper liver, muscle, and brain functions as well as for lipid metabolism and cellular membrane composition and repair. Humans can produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway; however, most individuals must consume this vitamin through the diet to prevent deficiency. An individual's dietary requirement for choline is dependent on common genetic variants in genes required for choline, folate, and one-carbon metabolism.

Low availability of choline disrupts development and function of the retina.

Adequate supply of choline, an essential nutrient, is necessary to support proper brain development. Whether prenatal choline availability plays a role in development of the visual system is currently unknown. In this study, we addressed the role of choline supply for the development and later function of the retina in a mouse model.

A Conceptual Framework for Studying and Investing in Precision Nutrition.

Nutrients and food-derived bioactive molecules must transit complex metabolic pathways, and these pathways vary between people. Metabolic heterogeneity is caused by genetic variation, epigenetic variation, differences in microbiome composition and function, lifestyle differences and by variation in environmental exposures. This review discusses a number of these sources of metabolic heterogeneity and presents some of the research investments that will be needed to make applications of precision nutrition practical.

Choline: The Underconsumed and Underappreciated Essential Nutrient.

Choline has been recognized as an essential nutrient by the Food and Nutrition Board of the National Academies of Medicine since 1998. Its metabolites have structural, metabolic, and regulatory roles within the body. Humans can endogenously produce small amounts of choline via the hepatic phosphatidylethanolamine -methyltransferase pathway.

Dietary choline and betaine intakes and risk of total and lethal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study.

Purpose: Two prior cohort studies suggested that choline, but not betaine intake, is associated with an increased risk of advanced prostate cancer (PCa). Given that evidence remains limited, we evaluated whether intakes of choline and derivative betaine are associated with total and lethal PCa risk and PCa death in men with PCa.

Methods: We included 6,528 men (24.

Betaine-homocysteine -methyltransferase deficiency causes increased susceptibility to noise-induced hearing loss associated with plasma hyperhomocysteinemia.

Betaine-homocysteine -methyltransferases (BHMTs) are methionine cycle enzymes that remethylate homocysteine; hence, their malfunction leads to hyperhomocysteinemia. Epidemiologic and experimental studies have revealed a correlation between hyperhomocysteinemia and hearing loss. Here, we have studied the expression of methionine cycle genes in the mouse cochlea and the impact of knocking out the gene in the auditory receptor.

MicroRNA-129-5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex.

Choline availability modulates neurogenesis and cerebral cortex development through the regulation of neural progenitor cell (NPC) proliferative and differentiation capacity. In this study, we demonstrated that cortical NPC self-renewal is controlled by choline via the expression of a microRNA (miR-129-5p), whose role in the developing brain has not been examined, and which, in turn, inhibits synthesis of the epidermal growth factor receptor (EGFR) protein. Specifically, we found that low choline (LC) availability led to the upregulation of miR-129-5p expression in cortical NPCs in vitro and in vivo, causing the downregulation of EGFR and thereby disrupting NPC self-renewal and cortical neurogenesis.