Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1.

IMPACT STATEMENT: This review will provide a summary of recent advances in choline transport research and highlight important novel areas of focus in the field.

Higher dietary choline intake is associated with lower risk of nonalcoholic fatty liver in normal-weight Chinese women.

BACKGROUND: Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population. OBJECTIVE: We examined the association between choline intake and nonalcoholic fatty liver. METHODS: Participants included 56,195 Chinese women and men, 40-75 y of age, with no or negligible alcohol consumption and with no history of hepatitis, cardiovascular disease, or cancer. All participants reported undergoing liver ultrasonography. Fatty liver was defined by self-report of a physician diagnosis. Habitual dietary intakes were assessed via validated food-frequency questionnaires. RESULTS: The average total choline intakes were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men. Major food sources were eggs, soy foods, red meat, fish, and vegetables. A higher choline intake was associated with lower risk of fatty liver; after adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01). The inverse association was attenuated after further adjustment for history of metabolic disease and, in particular, BMI. The corresponding ORs (95% CIs) were 0.88 (0.75, 1.03) in women (P-trend = 0.05) and 0.85 (0.68, 1.06) in men (P-trend = 0.09). Stratified analyses suggested a potential effect modification by obesity status in women; the OR (95% CI) across extreme quintiles was 0.72 (0.57, 0.91) in normal-weight women vs. 1.05 (0.84, 1.31) in overweight or obese women (P-trend = 0.007 vs. 0.99, P-interaction < 0.0001). CONCLUSION: Higher dietary choline intake may be associated with lower risk of nonalcoholic fatty liver only in normal-weight Chinese women.

Choline supply of preterm infants: assessment of dietary intake and pathophysiological considerations.

BACKGROUND: Choline forms the head group of phosphatidylcholines, comprising 40-50 % of cellular membranes and 70-95 % of phospholipids in surfactant, bile, and lipoproteins. Moreover, choline serves as the precursor of acetylcholine and is important for brain differentiation and function. While accepted as essential for fetal and neonatal development, its role in preterm infant nutrition has not yet gained much attention. METHODS: The adequate intake of choline of preterm infants was estimated from international recommendations for infants, children, and adults. Choline intake relative to other nutrients was determined retrospectively in all inborn infants below 1,000 g (extremely low birth weight) or below 28 weeks gestational age, admitted to our department in 2006 and 2007 (N = 93). RESULTS: Estimation of adequate intake showed that children with 290 g body weight need more choline than those with 1,200 g (31.4 and 25.2 mg/kg/day, respectively). Day-by-day variability was high for all nutrient intakes including choline. In contrast to the continuous intrauterine choline delivery, median supply reached a plateau at d11 (21.7 mg/kg/day; 25th/75th percentile: 19.6; 23.9). Individual choline supply at d0-d1 and d2-d3 was <10 mg/kg/day in 100 and 69 % of infants, respectively. Furthermore, intakes <10 mg/kg/day were frequently observed beyond day 11. Median adequate intakes (27.4 mg/kg/day at 735 g body weight) were achieved in <2 %. CONCLUSIONS: Nutritional intake of choline in this cohort of preterm infants was frequently less than the estimated adequate intake, with particular shortage until postnatal d10. Because choline is important for brain development, future studies are needed to investigate the effects of adequate nutritional choline intake on long-term neurodevelopment in VLBW infants.

Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction.

When dietary choline is restricted, most men and postmenopausal women develop multiorgan dysfunction marked by hepatic steatosis (choline deficiency syndrome (CDS)). However, a significant subset of premenopausal women is protected from CDS. Because hepatic PEMT (phosphatidylethanolamine N-methyltransferase) catalyzes de novo biosynthesis of choline and this gene is under estrogenic control, we hypothesized that there are SNPs in PEMT that disrupt the hormonal regulation of PEMT and thereby put women at risk for CDS. In this study, we performed transcript-specific gene expression analysis, which revealed that estrogen regulates PEMT in an isoform-specific fashion. Locus-wide SNP analysis identified a risk-associated haplotype that was selectively associated with loss of hormonal activation. Chromatin immunoprecipitation, analyzed by locus-wide microarray studies, comprehensively identified regions of estrogen receptor binding in PEMT. The polymorphism (rs12325817) most highly linked with the development of CDS (p < 0.00006) was located within 1 kb of the critical estrogen response element. The risk allele failed to bind either the estrogen receptor or the pioneer factor FOXA1. These data demonstrate that allele-specific ablation of estrogen receptor-DNA interaction in the PEMT locus prevents hormone-inducible PEMT expression, conferring risk of CDS in women.

Choline: an essential nutrient for public health.

Choline was officially recognized as an essential nutrient by the Institute of Medicine (IOM) in 1998. There is significant variation in the dietary requirement for choline that can be explained by common genetic polymorphisms. Because of its wide-ranging roles in human metabolism, from cell structure to neurotransmitter synthesis, choline-deficiency is now thought to have an impact on diseases such as liver disease, atherosclerosis, and, possibly, neurological disorders. Choline is found in a wide variety of foods. Eggs and meats are rich sources of choline in the North American diet, providing up to 430 milligrams per 100 grams. Mean choline intakes for older children, men, women, and pregnant women are far below the adequate intake level established by the IOM. Given the importance of choline in a wide range of critical functions in the human body, coupled with less-than-optimal intakes among the population, dietary guidance should be developed to encourage the intake of choline-rich foods.

Choline: are our university students eating enough?

Choline is an essential nutrient; dietary deficiency of choline is associated with impaired liver function, elevated blood concentrations of alanine aminotransferase, creatinine phosphokinase and homocysteine. There is also depletion of acetylcholine concentration in the brain, leading to deficit in memory function. The authors examined the dietary intake of choline in groups of students at the Mona Campus of the University of the West Indies. Sixty-two medical students (first and second years) and biochemistry students (final year) were recruited They were asked to (including amounts) record all foods and drinks consumed for three days (two weekdays and one weekend day). The sheets were collected and the amount of choline and betaine (a metabolite of choline) consumed were calculated Dietary intake of folate was also evaluated. The analysis revealed that 86.2% of the females and 90.9% of the males reported diets that delivered less daily choline than the adequate intake quoted by the Institute of Medicine of the National Academy of Sciences, USA (425-550 mg/day). The betaine consumption ranged between 25 to 620 mg/day (no adequate intake documented) and the folate consumed was more than the recommended daily allowance of folate (180-200 microg/day). The dietary intake of choline in the majority of students is below adequate intake. Although folate also serves similar functions to choline, it is unlikely that it can substitute for choline in all physiological aspects and therefore the implications of low dietary choline need further investigation.

Choline: are our university students eating enough? / La Colina: ¿la Ingieren nuestros estudiantes universitarios en cantidades suficientes?

Choline is an essential nutrient; dietary deficiency of choline is associated with impaired liver function, elevated blood concentrations of alanine aminotransferase, creatinine phosphokinase and homocysteine. There is also depletion of acetylcholine concentration in the brain, leading to deficit in memory function. The authors examined the dietary intake of choline in groups of students at the Mona Campus of the University of the West Indies. Sixty-two medical students (first and second years) and biochemistry students (final year) were recruited They were asked to (including amounts) record all foods and drinks consumed for three days (two weekdays and one weekend day). The sheets were collected and the amount of choline and betaine (a metabolite of choline) consumed were calculated Dietary intake of folate was also evaluated. The analysis revealed that 86.2of the females and 90.9of the males reported diets that delivered less daily choline than the adequate intake quoted by the Institute of Medicine of the National Academy of Sciences, USA (425-550 mg/day). The betaine consumption ranged between 25 to 620 mg/day (no adequate intake documented) and the folate consumed was more than the recommended daily allowance of folate (180-200 microg/day). The dietary intake of choline in the majority of students is below adequate intake. Although folate also serves similar functions to choline, it is unlikely that it can substitute for choline in all physiological aspects and therefore the implications of low dietary choline need further investigation.

La colina es un nutriente esencial. La deficiencia dietética de colina está asociada con el deterioro de la función hepática, así como con elevadas concentraciones en sangre de alanina-aminotrans-ferasa, creatinina-fosfoquinasa y homocisteína. Asimismo, se produce un agotamiento de la concentración de acetilcolina en el cerebro, lo cual conduce a un déficit en la función de la memoria. Los autores examinaron la ingestión dietética de colina en grupos de estudiantes del campus de Mona de la Universidad de West Indies. Se reclutaron sesenta y dos estudiantes de ciencias médicas (de primer y segundo año) y bioquímica (FAltimo año). Se les pidió que tomaran notas (incluyendo cantidades) de todos los alimentos y bebidas consumidos en tres días (dos días de entre semana y un día de fin de semana). Se recogieron las anotaciones y se calculó el consumo de colina y betaína (un metabolito de la colina). Se evaluó la ingestión de folato. El análisis reveló que el 86.2% de las mujeres y el 90.9% de los hombres, reportaron dietas cuyo suministro de colina por día se hallaba por debajo del consumo adecuado indicado por el Instituto de Medicina de la Academia Nacional de Ciencias de Estados Unidos (425–550 mg/día). El consumo de betaína osciló de 25 a 620 mg/día (no existe documentación sobre el consumo adecuado), en tanto que el folato consumido estuvo por encima de la ingestión diaria de folato recomendada (180 – 200 ug/día). El consumo dietético de colina de la mayoría de los estudiantes está por debajo del consumo adecuado.

Choline may be an essential nutrient in malnourished patients with cirrhosis.

Elemental diets designed for nutritional support in protein-calorie malnutrition are often deficient in choline, a nonessential nutrient. Previously, malnourished patients on these diets were found to be at risk of developing plasma choline deficiency. We have now estimated the prevalence of this deficiency by determining fasting plasma levels of choline among cirrhotic and noncirrhotic malnourished male subjects maintained on regular hospital mixed food or elemental parenteral and enteral formulas. Plasma choline concentrations (microM, average +/- SD) were as follows: (i) mixed foods, 11.3 +/- 4.3 for cirrhotic (n = 22) and 9.3 +/- 2.4 for noncirrhotic (n = 12) patients; (ii) parenteral formula, 5.3 +/- 1.6 for cirrhotic (n = 5) and 8.6 +/- 5.2 for noncirrhotic (n = 16) subjects; and (iii) enteral formula, 6.1 +/- 1.2 for cirrhotic (n = 5) and 11.7 +/- 1.9 for noncirrhotic (n = 4) subjects. The level for healthy normal subjects eating mixed foods was 12.0 +/- 2.2. The prevalence of plasma choline deficiency, i.e., plasma levels greater than or equal to 2 SD below the normal average, was as follows: parenteral formula, all cirrhotic and 10 of 16 noncirrhotic subjects; enteral formula, all cirrhotic and none of the noncirrhotic subjects. The reversibility of choline deficiency was examined in a longitudinal study of three phases involving 10 patients--5 with alcoholic cirrhosis (all on enteral formula); 5 noncirrhotic (1 on enteral and 4 on parenteral formula). During phase 1 (3-day equilibration period; ad libitum regular hospital diet), plasma choline levels were within the normal range for all subjects. During phase 2 (2 wk, choline depletion phase, elemental formulas), choline levels were subnormal in all cirrhotic subjects (5.1 +/- 2.0 microM) on enteral formula and all noncirrhotic patients on parenteral formula (5.9 +/- 1.3 microM). During phase 3 (2 wk, choline repletion phase, elemental formula + 6 g choline/day), the levels normalized in all patients (cirrhotic 11.4 +/- 3.1 microM and noncirrhotic 11.9 +/- 3.2 microM). Analyses of abdominal computed tomographic scans and plasma liver chemistries in the cirrhotic subjects during the three phases suggested a correlation between plasma choline deficiency and hepatic steatosis and abnormal liver enzyme levels in some patients. Therefore, choline may be an essential nutrient in malnourished cirrhotic patients and its deficiency may be associated with adverse hepatic effects.