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

描述（由申请人提供）：该提案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志物数量很少。由于饮食与疾病的关联可能很微妙，并且很难使用自我报告的方法来确定，因此迫切需要开发和验证更客观的饮食生物标志物以用于研究。拟议的研究将根据碳、氮和硫的稳定同位素比率评估一组甜味剂、肉类和鱼类摄入量的饮食生物标志物。碳同位素比率是甜味剂摄入量的候选生物标志物，因为它在美国膳食甜味剂的主要来源玉米和甘蔗中含量很高。氮同位素比率是肉类摄入量的候选生物标志物，因为它在动物中相对于植物中较高。硫同位素比率是鱼类摄入量的候选生物标志物，因为海洋食物相对于陆地食物而言较高。然而，这些措施尚未在适当的框架中得到验证，这阻碍了它们被采用作为营养流行病学的工具。 在这里，我们测试了两种验证感兴趣食物的同位素测量的方法：首先，通过使用饮食的多同位素模型来增加特异性，其次，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。我们使用来自 NPAAS 喂养研究的血清样本来测试这些方法，该研究是一项针对华盛顿州西雅图 150 名 60-80 岁女性的为期 2 周的对照喂养研究。 NPAAS 喂养研究将每个参与者的受控饮食与其平时的摄入量单独匹配，以维持与研究人群相似的摄入量分布，并达到生物标志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一或多同位素模型是否可以在 NPAAS 喂养研究中提供甜味剂、鱼和肉摄入量的有效且具体的测量。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为具有相似或改进的有效性和特异性的多同位素模型提供替代方案。所有稳定同位素比率将使用连续流同位素比率质谱法进行测量。 该提案是验证饮食的多种稳定同位素生物标志物作为客观饮食评估新工具的第一步。使用 NPAAS 喂养研究的样本提供了一个高效且具有成本效益的机会来严格评估和完善这些标志物，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.