Trujillo-Gonzalez Isis, Horita David A, Stegall Julie, Coble Rachel, Paules Evan M, Lulla Anju A, Baah Emmanuel, Bottiglieri Teodoro, Sha Wei, Kohlmeier Martin, Friday Walter B, Zeisel Steven H
Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC 28081, USA.
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
medRxiv. 2025 Jul 16:2025.07.15.25331567. doi: 10.1101/2025.07.15.25331567.
Choline is an essential nutrient, and insufficient intake negatively affects organs such as the liver, brain, and muscles. In the United States, average choline intake remains below the Adequate Intake (AI) (550 mg/day men, 425 mg/day women). Although conventional dietary assessment tools can identify people who are eating diets low in choline, no metabolite biomarkers have been proven to reliably assess choline intake.
We tested whether plasma concentrations of choline and its metabolites could determine dietary choline intake. We also assessed whether liver elastography (Fibroscan) could detect diet-induced changes in liver fat.
In a double-blind, randomized, crossover feeding study, participants adhered to 3 distinct dietary patterns for 2-wk intervals, delivering approximately 100%, 50%, and 25% of the choline AI. On Day 12 of each dietary arm, in addition to the food supplied, subjects consumed a single bolus of 2.2 mmol trimethyl-d-choline. Plasma concentrations of choline, betaine and phosphatidylcholine (PtdCho) were measured using mass spectrometry. Targeted assays quantified choline, betaine, phosphatidylcholine and total homocysteine concentrations. Liver fat content was evaluated non-invasively using Fibroscan.
Plasma concentrations of d-choline, betaine, and their isotopic enrichment ratio (IER) varied with dietary intake (q<0.0001), and PtdCho IER also differed significantly (q=0.001). In targeted analysis, choline and betaine concentrations were highly responsive to dietary choline intake, while PtdCho and tHcy were not. Receiver Operator Characteristic (ROC) analysis showed strong accuracy using plasma choline (AUC=0.81) and betaine (AUC=0.80), with improved accuracy when combined (AUC= 0.83). Fibroscan identified a subset of participants with increased liver fat in response to the 25% AI vs. 100% AI choline diet, though patterns varied among individuals.
Plasma choline and betaine concentrations are robust biomarkers of dietary choline intake under controlled feeding. These findings support targeted metabolite profiling to improve choline intake assessment and reveal induvial variability in liver response to low choline intake.
胆碱是一种必需营养素，摄入不足会对肝脏、大脑和肌肉等器官产生负面影响。在美国，胆碱的平均摄入量仍低于适宜摄入量（AI）（男性为550毫克/天，女性为425毫克/天）。尽管传统的膳食评估工具可以识别出胆碱摄入量低的人群，但尚未有代谢物生物标志物被证明能可靠地评估胆碱摄入量。
我们测试了血浆中胆碱及其代谢物的浓度是否能确定膳食胆碱摄入量。我们还评估了肝脏弹性成像（Fibroscan）是否能检测出饮食引起的肝脏脂肪变化。
在一项双盲、随机、交叉喂养研究中，参与者以2周为间隔遵循3种不同的饮食模式，分别提供约100%、50%和25%的胆碱AI。在每种饮食阶段的第12天，除了提供的食物外，受试者还一次性服用2.2毫摩尔的三甲基-d-胆碱。使用质谱法测量血浆中胆碱、甜菜碱和磷脂酰胆碱（PtdCho）的浓度。靶向分析定量了胆碱、甜菜碱、磷脂酰胆碱和总同型半胱氨酸的浓度。使用Fibroscan对肝脏脂肪含量进行无创评估。
d-胆碱、甜菜碱的血浆浓度及其同位素富集率（IER）随饮食摄入量而变化（q<0.0001），PtdCho IER也有显著差异（q=0.001）。在靶向分析中，胆碱和甜菜碱浓度对膳食胆碱摄入量高度敏感，而PtdCho和总同型半胱氨酸则不然。受试者工作特征（ROC）分析显示，血浆胆碱（AUC=0.81）和甜菜碱（AUC=0.80）的准确性很高，两者结合时准确性更高（AUC=0.83）。Fibroscan识别出一部分参与者，他们在摄入25%AI胆碱饮食与100%AI胆碱饮食相比时肝脏脂肪增加，不过个体之间的模式有所不同。
在控制喂养条件下，血浆胆碱和甜菜碱浓度是膳食胆碱摄入量的可靠生物标志物。这些发现支持靶向代谢物分析以改善胆碱摄入量评估，并揭示个体对低胆碱摄入的肝脏反应差异。
