The Response of Choline and Folate Status to Controlled Levels of Choline Intake

胆碱和叶酸状态对胆碱摄入控制水平的反应

• 批准号: 6820578
• 负责人: MARIE A CAUDILL
• 金额: $ 21.1万
• 依托单位: CALIFORNIA STATE POLY U POMONA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6820578
• 关键词: DNA methylation; Mexican Americans; cardiovascular disorder; choline; dietary restriction; dietary supplements; dosage; folate; genetic polymorphism; genotype; health science research support; human subject; male; metabolism; methionine; miscellaneous oxidoreductase; neoplasm /cancer; nutrient intake activity; nutrient requirement; nutrition related tag; questionnaires; statistics /biometry; urinalysis

Choline, a dietary component, is a precursor for a variety of compounds including the methyl donor, betaine and is a possible determinant of chronic/developmental disease risk. The choline-adequate intake (AI) for men is 550 mg/d, about half the amount normally consumed in the diet. Choline requirements may be higher in persons with a common genetic variant in the folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR C677T). We propose to investigate the response of traditional and novel functional indices of choline and folate status to controlled choline [225, 550 (AI), 1100 (typical intake) and 2200 mg/d] and folate (400 mcg/d) intakes in young Mexican American men (18-45 y; n=56) grouped according to their MTHFR genotype with n=28 677 TT and n=28 of the more prevalent CC form. Further, we will employ a stable isotope tracer protocol to assess the fate of exogenous choline and the influence of MTHFR C->T genotype and levetof choline intake on that rate and extent of isotopic labeling of choline metabolites and other intermediates or products of one-carbon metabolism. A low choline diet (225 mg/d) will be consumed for 2 wk followed by randomization to supplemental choline or placebo for total choline intakes of 225 (7 TT and 7 CC); 550 (7 TT and 7 CC); 1100 (7 TT and 7 CC) and 2200 (7 CC and 7 TT) mg/d for 12wk. Throughout the study duration, the men will receive the 1998 folate RDA, 400 mcg/d as dietary folate equivalents and all other nutrients in adequate amounts. In addition, subjects (n=20) in the 550 and 2200 mg/d will consume 15% of their total choline intake as D13-choline from wk 12 to wk 14. The response of folate and choline nutritional status to vadous levels of controlled choline intake with constant folate intake will be assessed by several response variables (i.e, plasma folate, choline, betaine, homocysteine). Further, isotopic enrichment of choline metabolites or other one-carbon intermediates/products (i.e, choline, betaine, methionine and serine) will be measured in wk 14 plasma from subjects consuming the tracer.

胆碱是一种饮食成分，是多种化合物的前体，包括甲基捐献者，贝贝因，是慢性/发育疾病风险的决定因素。男性的胆碱剂量摄入量（AI）为550 mg/d，大约是饮食中通常消耗的一半。在叶酸代谢酶，甲基苯甲酸叶酸还原酶（MTHFR C677T）中，胆碱的需求可能更高。我们建议研究胆碱和叶酸状态对受控胆碱[225，550（AI），1100（典型摄入量）和2200 mg/d]和叶酸（400 mcg/d）摄入量的传统和新型功能指数和幼年的摄入量的响应。墨西哥裔美国人（18-45 y; n = 56）根据其MTHFR基因型进行分组，n = 28 677 tt和n = 28较普遍的CC形式。此外，我们将采用 稳定的同位素示踪剂方案，以评估外源性胆碱的命运以及MTHFR C-> T基因型和Levetof胆碱摄入对胆碱代谢产物的同位素标记以及一个碳代谢的其他中间体或产物的同位素标记的影响。 2周的胆碱饮食（225 mg/d）将消耗掉，然后随机分组以补充胆碱或安慰剂，总胆碱摄入量为225（7 tt和7 cc）； 550（7 tt和7 cc）; 1100（7 tt和7 cc）和2200（7 cc和7 tt）mg/d，12wk。在整个研究期间，男性将获得1998年的叶酸RDA，400 mcg/d作为饮食叶酸等效物，以及所有其他营养素。此外，从550和2200 mg/d中的受试者（n = 20）将消耗其总胆碱摄入量的15％，为D13-胆碱，从WK 12到WK 14。胆碱摄入量持续叶酸摄入量 将通过几个响应变量（即血浆叶酸，胆碱，甜菜碱，同型半胱氨酸）进行评估。此外，将在WK 14等离子体中测量食用示踪剂的受试者的WK 14血浆中测量胆碱代谢产物或其他单碳中间体/产品（即胆碱，甜菜碱，蛋氨酸和丝氨酸）的同位素富集。