Developing a biomarker panel to assess choline nutritional status

胆碱是一种重要和必需的营养物质，但目前还没有有效的生物标志物来评估胆碱的营养状况，可以在临床或公共卫生实践中实际应用。胆碱是一种必需的营养素，具有足够的摄入量(AI)和美国医学研究所食品与营养委员会设定的可耐受上限(UL)水平和建议的每日摄入量(RDI)。鉴于健康的胆碱摄入量范围狭窄，鉴于建立了维持健康的胆碱RDI，考虑到美国饮食摄入量的3倍差异，考虑到常见基因变异对胆碱需求的影响，以及由于血浆胆碱浓度不能充分反映状况，我们建议开发和验证一组实验室测试，以评估人类的胆碱状态。从更大的一组测量中，我们将确定与使用同位素稀释测量胆碱池大小最相关的生物标志物测量。健康志愿者(男性60人，绝经前女性60人，绝经后女性60人)，作为门诊患者，每天摄入100%的胆碱(550毫克/天)，连续2周，然后转换为50%的建议胆碱摄入量2周，然后转换为25%的建议胆碱摄入量2周，然后转换为10%的建议胆碱摄入量(55毫克胆碱)2周。最后，所有受试者将被安排100%胆碱饮食，为期2周的胆碱补充。在每个节食期的最后3天，受试者将摄入去氢胆碱。我们将收集血浆和尿样进行代谢分析(先前研究中确定的可能预测胆碱状态的生物标志物小分子)、同位素稀释估计胆碱池大小，并将对肝脏进行瞬时弹性成像以评估肝脏脂肪。这些研究将被用来确定用于计算胆碱状态分数的最佳生物标志物集合，该分数与使用同位素稀释法评估的胆碱池大小很好地相关。最后，胆碱和叶酸代谢基因中的SNP与低胆碱饮食导致器官功能障碍的风险增加有关。我们将通过确定携带这些SNPs的人在任何给定的胆碱饮食摄入量中是否比没有这些SNPs的人有更低的胆碱池大小/更差的胆碱状态评分来测试我们的胆碱状况评分。

Choline is an important and essential nutrient, but there are no good validated biomarkers for assessing choline nutritional status that can be practically applied in clinical or public health practice. Choline is a required nutrient with Adequate Intake (AI) and a Tolerable Upper Limit (UL) levels set by the U.S. Institute of Medicine's Food and Nutrition Board and a Recommended Daily Intake (RDI). Given the narrow range for healthy intake of choline, given the establishment of a RDI of choline to maintain health, given the 3-fold variation in dietary intake in the US, given the effects of common genetic variants on requirements for choline and because plasma choline concentrations do not adequately reflect status, we propose that a panel of laboratory tests be developed and validated that assess choline status in humans. From a larger set of measures, we will identify the biomarker measures that best correlate with measurements of choline pool size using isotope dilution. Healthy volunteers (n=60 males, 60 premenopausal females and 60 postmenopausal females), as outpatients, will consume meals containing 100% of the recommended intake of choline (550 mg choline/day) for 2 weeks, they will then be switched to a diet containing 50% of the recommended intake of choline for 2 weeks, then switched to a diet containing 25% of the recommended intake of choline for 2 weeks, and then switched to a diet containing 10% of the recommended intake of choline (55 mg choline) for 2 weeks. Finally, all subjects will be placed on the 100% choline diet for 2 weeks of choline repletion. On the last 3 days of each diet period, subjects will consume deuterated choline. Plasma and urine samples will be collected for metabolomic assays (biomarker small molecules identified in a previous study as likely to predict choline status), isotopic dilution estimation of choline pool size and we will perform transient elastography of liver to assess liver fat. These studies will be used to determine the optimal set of biomarkers to use in calculating a choline status score that correlates well with choline pool size assessed using isotope dilution. Finally, SNPs in genes of choline and folate metabolism have been associated with increased risk for developing organ dysfunction on a low choline diet. We will test our choline status score by determining whether people with these SNPs have a lower choline pool size/worse choline status score for any given choline dietary intake than do people without these SNPs.