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: 7119054
• 负责人: MARIE A CAUDILL
• 金额: $ 25.59万
• 依托单位: CALIFORNIA STATE POLY U POMONA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7119054
• 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.

胆碱是一种膳食成分，是多种化合物的前体，包括甲基供体甜菜碱，并且是慢性/发育疾病风险的可能决定因素。男子的胆碱适当摄入量为550毫克/天，约为饮食中正常摄入量的一半。叶酸代谢酶亚甲基四氢叶酸还原酶（MTHFR C677 T）具有常见遗传变异的人对胆碱的需求可能更高。我们建议研究胆碱和叶酸状态的传统和新功能指标对控制胆碱的反应[225，550（AI），1100（典型摄入量）和2200 mg/d]和叶酸（400微克/天）的摄入量在年轻的墨西哥裔美国男性（18-45岁; n=56）分组，根据他们的MTHFR基因型与n=28 677 TT和n=28更普遍的CC形式。此外，我们将采用 稳定同位素示踪方案来评估外源性胆碱命运以及MTHFR C->T基因型和胆碱摄入水平对胆碱代谢物和其它一碳代谢中间体或产物的同位素标记的速率和程度的影响。低胆碱饮食（225 mg/d）将持续2周，然后随机分配至补充胆碱或安慰剂组，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，持续12周。在整个研究期间，男性将接受1998年叶酸RDA，400 mcg/d作为膳食叶酸当量和足量的所有其他营养素。此外，550和2200 mg/d组受试者（n=20）从第12周至第14周将消耗其总胆碱摄入量的15%作为D13-胆碱。叶酸和胆碱营养状况对不同水平的控制性胆碱摄入和恒定叶酸摄入的反应 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）来评估。此外，将在来自消耗示踪剂的受试者的第14周血浆中测量胆碱代谢物或其他一碳中间体/产物（即胆碱、甜菜碱、甲硫氨酸和丝氨酸）的同位素富集。