Phosphatidylcholine supplementation in pregnant women consuming moderate-choline diets does not enhance infant cognitive function: a randomized, double-blind, placebo-controlled trial.

Background: Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development.

Objective: The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring.

Design: In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum.

Development and implementation of the guiding stars nutrition guidance program.

PURPOSE . To describe the collaborative process between a grocery retailer and a panel of nutrition experts used to develop a nutrition guidance system (Guiding Stars) that evaluates the nutrient profile of all edible products in the supermarket, and to report the results of the food and beverage ratings. DESIGN .

Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans.

Background: Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed that mice that lack functional PEMT have dramatically reduced concentrations of docosahexaenoic acid (DHA; 22:6n-3) in plasma and of liver phosphatidylcholine (PtdCho)-a phospholipid formed by PEMT.

Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency.

Background & Aims: Nonalcoholic fatty liver disease affects up to 30% of the US population, but the mechanisms underlying this condition are incompletely understood. We investigated how diet standardization and choline deficiency influence the composition of the microbial community in the human gastrointestinal tract and the development of fatty liver under conditions of choline deficiency.

Methods: We performed a 2-month inpatient study of 15 female subjects who were placed on well-controlled diets in which choline levels were manipulated.

Dietary choline requirements of women: effects of estrogen and genetic variation.

Background: Choline is obtained from the diet and from the biosynthesis of phosphatidylcholine. Phosphatidylcholine is catalyzed by the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT), which is induced by estrogen. Because they have lower estrogen concentrations, postmenopausal women are more susceptible to the risk of organ dysfunction in response to a low-choline diet.

Choline intake and genetic polymorphisms influence choline metabolite concentrations in human breast milk and plasma.

Background: Choline is essential for infant nutrition, and breast milk is a rich source of this nutrient. Common single nucleotide polymorphisms (SNPs) change dietary requirements for choline intake.

Objective: The aim of this study was to determine whether total choline intake and/or SNPs influence concentrations of choline and its metabolites in human breast milk and plasma.

Metabolomic profiling can predict which humans will develop liver dysfunction when deprived of dietary choline.

Choline is an essential nutrient, and deficiency causes liver and muscle dysfunction. Common genetic variations alter the risk of developing organ dysfunction when choline deficient, probably by causing metabolic inefficiencies that should be detectable even while ingesting a normal choline-adequate diet. We determined whether metabolomic profiling of plasma at baseline could predict whether humans will develop liver dysfunction when deprived of dietary choline.

Guiding stars: the effect of a nutrition navigation program on consumer purchases at the supermarket.

Background: To improve diet quality and overall population health, the need to develop nutritional rating systems that are comprehensive in scope and easy for the consumer to understand and use at the point-of-purchase has emerged.

Objective: Our aim was to examine the effect of a comprehensive storewide supermarket point-of-purchase nutrition navigation intervention by using a shelf-label 3-tiered star icon on consumer food and beverage choices and their associated nutritional quality.

Design: By using a natural experiment design, purchasing data from 2006 to 2008 were obtained from a Northeast supermarket chain with 168 stores located in northern New England and New York and examined at preimplementation and at 1- and 2-y follow-up periods.

Dose response effects of dermally applied diethanolamine on neurogenesis in fetal mouse hippocampus and potential exposure of humans.

Diethanolamine (DEA) is a common ingredient of personal care products. Dermal administration of DEA diminishes hepatic stores of the essential nutrient choline and alters brain development. We previously reported that 80 mg/kg/day of DEA during pregnancy in mice reduced neurogenesis and increased apoptosis in the fetal hippocampus.

Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women: a phase I clinical trial.

Objective: A phase I double-blind clinical trial was conducted to evaluate the effects of a high oral dose of soy isoflavones administered daily for 84 days to healthy postmenopausal women. Principal outcome measures included DNA damage, apoptosis, and changes indicative of estrogenic stimulation.

Design: After eligibility and equol-producer status were determined, stratified randomization was used to assign women to the isoflavone (active) or placebo group.

Lymphocyte gene expression in subjects fed a low-choline diet differs between those who develop organ dysfunction and those who do not.

Background: Some humans fed a low-choline diet develop hepatosteatosis, liver and muscle damage, and lymphocyte apoptosis. The risk of developing such organ dysfunction is increased by the presence of single-nucleotide polymorphisms (SNPs) in genes involved in folate and choline metabolism.

Objective: We investigated whether these changes that occur in the expression of many genes when humans are fed a low-choline diet differ between subjects who develop organ dysfunction and those who do not.

Sex and menopausal status influence human dietary requirements for the nutrient choline.

Background: Although humans require dietary choline for methyl donation, membrane function, and neurotransmission, choline can also be derived from the de novo synthesis of phosphatidylcholine, which is up-regulated by estrogen. A recommended Adequate Intake (AI) exists for choline; however, an Estimated Average Requirement has not been set because of a lack of sufficient human data.

Objective: The objective of the study was to evaluate the dietary requirements for choline in healthy men and women and to investigate the clinical sequelae of choline deficiency.

Dietary isoflavones differentially induce gene expression changes in lymphocytes from postmenopausal women who form equol as compared with those who do not.

Human and animal studies suggest that dietary soy isoflavones reduce cancer risk, ameliorate postmenopausal syndrome and decrease bone resorption in postmenopausal women. The capacity to form the metabolite equol from daidzein is suggested as an important modulator of response to isoflavones; this capacity depends on gut colonization with appropriate bacteria. We administered a dietary supplement containing high-dose purified soy isoflavones (genistein, 558 mg/day; daidzein, 296 mg/day; and glycitein, 44 mg/day) to 30 postmenopausal women for 84 days and collected peripheral lymphocytes at timed intervals.

Choline deficiency increases lymphocyte apoptosis and DNA damage in humans.

Background: Whereas deficiency of the essential nutrient choline is associated with DNA damage and apoptosis in cell and rodent models, it has not been shown in humans.

Objective: The objective was to ascertain whether lymphocytes from choline-deficient humans had greater DNA damage and apoptosis than did those from choline-sufficient humans.

Design: Fifty-one men and women aged 18-70 y were fed a diet containing the recommended adequate intake of choline (control) for 10 d.

Common genetic polymorphisms affect the human requirement for the nutrient choline.

Humans eating diets deficient in the essential nutrient choline can develop organ dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs) in genes involved in choline metabolism influence the dietary requirement of this nutrient. Fifty-seven humans were fed a low choline diet until they developed organ dysfunction or for up to 42 days.

Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans.

Choline is a required nutrient, and some humans deplete quickly when fed a low-choline diet, whereas others do not. Endogenous choline synthesis can spare some of the dietary requirement and requires one-carbon groups derived from folate metabolism. We examined whether major genetic variants of folate metabolism modify susceptibility of humans to choline deficiency.

Polymorphism of the PEMT gene and susceptibility to nonalcoholic fatty liver disease (NAFLD).

Phosphatidylethanolamine N-methyltransferase (PEMT) catalyzes phosphatidylcholine synthesis. PEMT knockout mice have fatty livers, and it is possible that, in humans, nonalcoholic fatty liver disease (NAFLD) might be associated with PEMT gene polymorphisms. DNA samples from 59 humans without fatty liver and from 28 humans with NAFLD were genotyped for a single nucleotide polymorphism in exon 8 of PEMT, which leads to a V175M substitution.

Ad libitum choline intake in healthy individuals meets or exceeds the proposed adequate intake level.

Choline is an essential nutrient for humans that is used to synthesize membrane phospholipids and the neurotransmitter acetylcholine. Betaine, a metabolite of choline, functions as a methyl-group donor in the conversion of homocysteine to methionine, and is important for renal function. Accurate analysis of choline intake was previously not possible because the choline content of most foods was not known.

Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load.

Background: Elevated concentrations of homocysteine in blood may be an independent risk factor for the development of atherosclerosis. Elevated homocysteine concentrations can be caused by decreased methylation of homocysteine to form methionine, as occurs in folate deficiency. A parallel pathway exists for methylation of homocysteine, in which choline, by way of betaine, is the methyl donor.

Choline- and betaine-defined diets for use in clinical research and for the management of trimethylaminuria.

This article describes the development of a series of choline- and betaine-controlled diets that were served to research subjects as part of an ongoing study of diet requirements in humans. These diets were developed based on the analysis of choline and betaine in individual foods. The calculated diets were compared with analyses of all foods combined into a single sample for each day.

Clinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasia.

A phase I clinical trial was conducted to determine the safety, pharmacokinetic parameters, and efficacy of orally administered isoflavones (genistein and daidzein, potential cancer chemotherapeutic agents) over a 3-mo period in men with prostate neoplasia. Twenty men, ages 40 and above, with stage B, C, or D adenocarcinoma of the prostate were treated with a multiple-dose regimen of a soy isoflavone formulation (delivering approximately 300 or 600 mg/day genistein and half this much daidzein) for 84 days. The delivered dose of isoflavones was more than 10-fold higher than that typically taken by prostate cancer patients.

Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts.

Background: Choline is a required nutrient, and humans deprived of choline develop liver damage.

Objective: This study examined the effect of choline deficiency on muscle cells and the release of creatine phosphokinase (CPK) as a sequela of that deficiency.

Design: Four men were fed diets containing adequate and deficient amounts of choline, and serum was collected at intervals for measurement of CPK.

Lack of significant genotoxicity of purified soy isoflavones (genistein, daidzein, and glycitein) in 20 patients with prostate cancer.

Background: Genistein may be useful in the prevention or treatment of prostate cancer; however, it causes genetic damage in cultured human cells.

Objective: The objective was to assess the potential genotoxicity of a purified soy unconjugated isoflavone mixture in men with prostate cancer.

Design: Twenty patients with prostate cancer were treated with 300 mg genistein/d for 28 d and then with 600 mg/d for another 56 d.

Wnt-3A enhances bone morphogenetic protein-2-mediated chondrogenesis of murine C3H10T1/2 mesenchymal cells.

We have recently reported the chondrogenic effect of bone morphogenetic protein-2 (BMP-2) in high density cultures of the mouse multipotent mesenchymal C3H10T1/2 cell line and have shown the functional requirement of the cell-cell adhesion molecule N-cadherin in BMP-2-induced chondrogenesis in vitro (Denker, A. E., Nicoll, S.

Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis.

Members of both the Wnt and bone morphogenetic protein (BMP) families of signaling molecules have been implicated in the regulation of cartilage development. A key component of the Wnt signaling pathway is the cytosolic protein, beta-catenin. We have recently shown that the chondrogenic activity of BMP-2 in vitro involves the action of the cell-cell adhesion protein, N-cadherin, which functionally complexes with beta-catenin.