Validating Multiple Stable Isotope Measures of Diet in the NPAAS Feeding Study

描述(由申请人提供)：这项建议解决了营养流行病学研究的一个关键障碍：可用于评估饮食与健康之间关系的客观生物标记物数量很少。由于饮食与疾病的关系可能很微妙，很难用自我报告的方法来建立，因此迫切需要开发和验证更客观的饮食生物标记物，用于研究。这项拟议的研究将根据碳、氮和硫的稳定同位素比率来评估一套甜味剂、肉类和鱼类摄入量的饮食生物标记物。碳同位素比率是甜味剂摄入量的候选生物标志物，因为它在玉米和甘蔗中含量很高，而玉米和甘蔗是美国饮食中甜味剂的主要来源。氮同位素比率是肉类摄入量的候选生物标记物，因为相对于植物，动物的氮同位素比率较高。硫同位素比率是鱼类摄入量的一个候选生物标记物，因为相对于陆地食物，海洋食品的含量更高。然而，这些措施尚未在适当的框架中得到验证，这阻碍了它们被用作营养流行病学的工具。在这里，我们测试两种方法来验证感兴趣的食物的同位素测量：第一，通过使用饮食的多同位素模型来增加特异性，第二，通过测量与这些食物密切相关的特定氨基酸的稳定同位素比率。我们使用NPAAS喂养研究的血清样本来测试这些方法，这是一项为期两周的受控喂养研究，对象是华盛顿州西雅图的150名年龄在60-80岁的女性。NPAAS喂养研究分别将每个参与者的受控饮食与她通常的摄入量进行匹配，以保持与STUY人群相似的摄入量分布，并达到生物标记物验证所需的控制水平。具体目标1将测试基于血清碳、氮和硫稳定同位素比率的单同位素或多同位素模型是否可以在NPAAS喂养研究中提供甜味剂、鱼和肉类摄入量的有效和具体测量。具体目标2将测试特定血清氨基酸的碳同位素比率是否可以替代类似或改进的有效性和特异性的多同位素模型。所有稳定的同位素比率将使用连续流动同位素比率质谱仪进行测量。这项建议是朝着验证饮食的多个稳定同位素生物标记物作为客观饮食评估的新工具迈出的第一步。使用来自NPAAS喂养研究的样本提供了一个有效且具有成本效益的机会来批判性地评估和提炼这些标记物，以便在流行病学研究中更广泛地使用。

DESCRIPTION (provided by applicant): This proposal addresses a key barrier to research in nutritional epidemiology: the small number of objective biomarkers available for assessing relationships between diet and health. Because diet-disease associations may be subtle and are difficult to establish using self-reported methods, there is a pressing need to develop and validate more objective dietary biomarkers for use in research. The proposed study will evaluate a set of dietary biomarkers for sweetener, meat and fish intake based on the stable isotope ratios of carbon, nitrogen and sulfur. The carbon isotope ratio is a candidate biomarker of sweetener intake because it is high in corn and sugar cane, the major sources of dietary sweeteners in the US. The nitrogen isotope ratio is a candidate biomarker of meat intake, because it is elevated in animals relative to plants. The sulfur isotope ratio is a candidate biomarker of fish intake, because marine foods are elevated relative to terrestrial foods. However, these measures have not yet been validated in an appropriate framework, which has prevented their adoption as tools for nutritional epidemiology. Here we test two approaches to validating isotopic measures for foods of interest: first, by using multi- isotopic models of diet o increase specificity, and second, by measuring the stable isotope ratios of specific amino acids that are closely linked to those foods. We test these approaches using serum specimens from the NPAAS Feeding Study, a 2-week controlled feeding study of 150 women ages 60-80 in Seattle, WA. The NPAAS Feeding Study individually matches each participant's controlled diet to her usual intake, in order to maintain intake distributions that are similar to those of the stuy population and achieve the level of control needed for biomarker validation. Specific Aim 1 will test whether single or multi-isotopic models based on serum carbon, nitrogen, and sulfur stable isotope ratios can provide valid and specific measures of sweetener, fish and meat intake in the NPAAS Feeding Study. Specific Aim 2 will test whether the carbon isotope ratio of specific serum amino acids can provide alternatives to multi-isotopic models of similar or improved validity and specificity. All stable isotope ratios will be measured using continuous-flow isotope ratio mass spectrometry. This proposal is a first step toward validating multiple stable isotope biomarkers of diet as new tools for objective dietary assessment. Using samples from the NPAAS Feeding Study provides an efficient and cost-effective opportunity to critically assess and refine these markers for more general use in epidemiologic research.