Metabolic and Epidemiologic Evaluation of Choline and Betaine Intake

胆碱和甜菜碱摄入量的代谢和流行病学评估

• 批准号: 7476484
• 负责人: EUNYOUNG CHO
• 金额: $ 8.75万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7476484
• 关键词: Address; Alcohols; Animals; Area; Betaine; Biological; Blood; Blood specimen; Carcinogens; Cereals; Choline; Choline Deficiency; Chronic Disease; Clinical Trials; Colorectal Adenoma; Colorectal Cancer; Complement; Condition; Consumption; DNA biosynthesis; DNA chemical synthesis; Daily; Data; Data Set; Databases; Development; Diet; Dietary Factors; End Point; Epidemiologic Studies; Evaluation; Fasting; Folate; Follow-Up Studies; Food; Food Supplements; Frequencies; General Population; Grant; Health; Health Professional; Homocysteine; Homocystine; Human; Individual; Intake; Knowledge; Lecithin; Malignant Neoplasms; Malignant neoplasm of liver; Measures; Membrane; Metabolic; Metabolism; Methionine; Methylation; Nurses' Health Study; Nutrient; Organ; Participant; Phospholipids; Physiological; Plasma; Population Study; Primary carcinoma of the liver cells; Prospective Studies; Questionnaires; Range; Research; Risk; Role; Simulate; Source; Sphingomyelins; Supplementation; Time; Woman; Work; adenoma; cancer risk; carcinogenesis; choline deficient diet; cost; experience; fortification; interest; male health; men; methyl group; size

DESCRIPTION (provided by applicant): Choline and betaine are nutrients involved in methyl-group metabolism, which is critical for DNA synthesis and methylation. Choline is also a precursor of membrane phospholipids, phosphatidylcholine and sphingomyelin. Animal studies have demonstrated that choline deficiency is a condition sufficient for the development of hepatocellular carcinoma in the absence of other carcinogens. A methyl-group-deficient diet with no choline and low methionine promotes chemically induced carcinogenesis in animals. Dietary factors related to methyl- group metabolism, including folate, alcohol, and methionine have been associated with cancers of several organs in human. However, the relation between choline and betaine intake and human cancers is unknown. Some animal studies have shown that repletion of choline following choline deficiency actually promote carcinogenesis. Thus, the association between choline and cancer may be more complicated and may involve other mechanisms other than methyl-group metabolism. Understanding the role of choline and betaine in human health has been hampered by lack of food composition data. Recently, we obtained choline and betaine composition data for foods measured by our food frequency questionnaire and found that higher choline and betaine intake was associated with lower fasting plasma homocysteine levels in women and men and higher choline intake was associated with an elevated risk of colorectal adenoma in women. In this proposed work, we would like to further expand our knowledge on the biological role of dietary choline and betaine in methyl-group metabolism and colonic carcinogenesis. First, using data from the Framingham Offspring Study, we propose to examine the relation between choline and betaine intake and plasma levels of postmethionine-loading homocysteine, an intermediate product in methyl-group metabolism and a potential indicator of body's methyl-group availability. Evaluation of postmethionine-loading levels rather than fasting levels of homocysteine will provide useful data, simulating biological conditions after a meal. We expect to include a total of 2,732 participants with diet and blood data. Second, we will examine choline and betaine intake in relation to the risks of colorectal adenoma and colorectal cancer in the Health Professionals Follow-up Study, a large prospective study of men. We expect to have 4,143 adenoma and 1,305 cancer cases. We will take advantage of existing high-quality and large size datasets. Because we attained experience and knowledge in choline research from our previous grant, we will be able to carry out the proposed work in an extremely time- and cost-effective manner. The findings from the proposed grant will complement our previous work on choline and betaine and enhance our understanding of the role of these nutrients in carcinogenesis in human as this area of research is largely unexplored.

描述（由申请人提供）： 胆碱和甜菜碱是参与甲基代谢的营养物质，甲基代谢对DNA合成和甲基化至关重要。胆碱也是膜磷脂、磷脂酰胆碱和鞘磷脂的前体。动物研究表明，胆碱缺乏是一个条件，足以发展为肝细胞癌，在没有其他致癌物质。不含胆碱和低蛋氨酸的甲基缺乏饮食促进动物化学诱导的致癌作用。与甲基代谢有关的膳食因素，包括叶酸、酒精和蛋氨酸，与人体多种器官的癌症有关。然而，胆碱和甜菜碱摄入量与人类癌症之间的关系尚不清楚。一些动物研究表明，胆碱缺乏后补充胆碱实际上会促进癌的发生。因此，胆碱和癌症之间的联系可能更加复杂，可能涉及甲基代谢以外的其他机制。由于缺乏食物成分数据，对胆碱和甜菜碱在人类健康中的作用的理解受到阻碍。最近，我们通过食物频率调查问卷获得了食物中胆碱和甜菜碱的组成数据，发现较高的胆碱和甜菜碱摄入量与女性和男性空腹血浆同型半胱氨酸水平较低相关，较高的胆碱摄入量与女性结直肠腺瘤风险升高相关。在这项拟议的工作中，我们希望进一步扩大我们的知识，在甲基代谢和结肠癌的生物学作用的饮食胆碱和甜菜碱。首先，使用的数据从Frachial后代的研究，我们建议检查胆碱和甜菜碱的摄入量和血浆水平的甲硫氨酸后加载同型半胱氨酸，在甲基代谢的中间产物和身体的甲基可用性的潜在指标之间的关系。评估蛋氨酸后负荷水平，而不是空腹水平的同型半胱氨酸将提供有用的数据，模拟饭后的生物条件。我们预计将包括2,732名有饮食和血液数据的参与者。其次，我们将在健康专业人员随访研究中检查胆碱和甜菜碱摄入量与结直肠腺瘤和结直肠癌风险的关系，这是一项针对男性的大型前瞻性研究。我们预计将有4,143例腺瘤和1,305例癌症病例。我们将利用现有的高质量和大规模数据集。因为我们从以前的资助中获得了胆碱研究的经验和知识，我们将能够以非常节省时间和成本的方式开展拟议的工作。拟议拨款的研究结果将补充我们以前在胆碱和甜菜碱方面的工作，并增强我们对这些营养素在人类致癌作用中的理解，因为这一研究领域在很大程度上尚未探索。