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

胆碱是一种饮食成分，是包括甲基供体甜菜碱在内的各种化合物的前体，可能是慢性/发育性疾病风险的决定因素。男性的胆碱摄入量(AI)为550毫克/天，约为正常饮食摄入量的一半。在叶酸代谢酶亚甲基四氢叶酸还原酶(MTHFR C677T)中有常见基因变异的人对胆碱的需求可能更高。我们建议调查传统的和新的胆碱和叶酸状态功能指标对受控胆碱[225,550(AI)，1100(典型摄入量)和2200 mg/d]和叶酸(400 mcg/d)摄入量的响应。墨西哥裔美国青年男性(18-45岁；n=56)按MTHFR基因分组，n=28 677 TT，n=28流行的CC类型。此外，我们将聘请一名 稳定的同位素示踪方案，评估外源性胆碱的去向，以及MTHFR、C&GT；T基因型和胆碱摄入水平对胆碱代谢物和其他一碳代谢中间体或产品同位素标记的速度和程度的影响。低胆碱饮食(225 mg/d)摄入2wk，然后随机补充胆碱或安慰剂，总胆碱摄入量为225(7tt和7tc)；550(7tt和7cc)；1100(7tt和7cc)和2200(7tc和7tt)mg/d，共12wk。在整个研究过程中，这些男性将摄入1998年的叶酸RDA，每天400微克作为膳食叶酸当量，以及适量的所有其他营养素。此外，每天摄入550毫克和2200毫克的受试者(n=20)在第12周至第14周期间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控制胆碱摄入量和恒定叶酸摄入量的反应 将通过几个反应变量(即，血浆叶酸、胆碱、甜菜碱、同型半胱氨酸)进行评估。此外，将在服用示踪剂的受试者的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、蛋氨酸和丝氨酸)的同位素浓缩。

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.