Novel, Noninvasive Biomarker of Fruit & Vegetable Intake

水果/蔬菜和慢性疾病的流行病学研究一直受到缺乏非侵入性客观生物标记物的限制，这些生物标记物反映了饮食摄入量/对干预措施的饮食依从性。血液中类胡萝卜素的浓度被认为是水果和蔬菜摄入量的最佳生物标记物，但需要静脉穿刺术，对于大型队列研究和干预试验来说，成本高得令人望而却步。类胡萝卜素在包括皮肤在内的许多人体组织中都有发现，皮肤中类胡萝卜素的浓度(来自皮肤活检)已被证明是强烈的 与血浆中相同类胡萝卜素的浓度显著相关(例如，β-胡萝卜素，r=0.75)。我们建议采用现有的拉曼光谱技术来评估体内人体组织的类胡萝卜素状态，作为水果和蔬菜摄入量的生物标记物。更具体地说，我们建议(I)改进我们现有的仪器，例如拥有一种坚固耐用的便携式设备，用于在活体内快速评估人体皮肤的类胡萝卜素状态。一旦我们的原型仪器被适当地改进，我们然后建议(Ii)评估重复性， 通过一次和一段时间的拉曼光谱估计的皮肤类胡萝卜素水平的受试者内变异性和受试者间变异性。在完成这个目标后，我们的最终目标是(Iii)确定拉曼光谱评估的类胡萝卜素状态与其他衡量类胡萝卜素状态的指标(包括水果/蔬菜的饮食摄入量)与特定的类胡萝卜素、血浆类胡萝卜素浓度和皮肤活检组织中的类胡萝卜素浓度之间的相关性。这项前景看好的技术目前正在开发/改进中，用于评估 人类视网膜组织中的类胡萝卜素(国家眼科研究所)；目前的提议将极大地扩大这种非侵入性技术在癌症流行病学和预防研究中的潜在用途。拉曼光谱技术作为一种突破性的方法在大规模人群中快速筛选类胡萝卜素水平具有巨大的潜力，开发和验证是将该技术应用于人类种群研究和监测的关键。

Epidemiologic studies of fruits/vegetables and chronic disease have been limited by the lack of non-invasive objective biomarkers of dietary intake/dietary adherence to interventions. Blood concentrations of carotenoids are considered the best biological markers of fruit and vegetable intake, but require venipuncture and are prohibitively expensive for large cohort studies and intervention trials. Carotenoids are found in many human tissues including skin, and skin concentrations of carotenoids (from dermal biopsies) have been shown to be strongly and significantly correlated with plasma concentrations of the same carotenoids (e.g., beta-carotene, r=0.75). We propose to adapt an existing technology, Raman spectroscopy, for the assessment of the carotenoid status of human tissues in vivo as a biomarker of fruit and vegetable intake. More specifically, we propose to (i) refine our current instrument such as to have a rugged, portable device for rapidly assessing carotenoid status ill human skin in vivo. Once our protype instrument is appropriately refined, we then propose to (ii) evaluate the reproducibility, intra-subject variability, and inter-subject variability in dermal cartenoid levels as estimated by Raman spectroscopy at one time and over time. Upon completion of this aim, our final aim is to (iii) determine the correlation between carotenoid status as assessed by Raman spectroscopy and other measures of carotenoid status including dietary intake of fruits/vegetables and specific carotenoids, plasma carotenoid concentrations and carotenioid concentrations in dermal biopsies. This promising technology is currently being developed/refined for the assessment of carotenoids in human retinal tissue (National Eye Institute); the current proposal would greatly broaden the potential use of this noninvasive technology for cancer epidemiology and prevention studies. Raman spectroscopic technology has tremendous potential as a breakthrough method for rapid screening of carotenoid levels in large populations, and development and validation are critically required to move this technology into human population research and surveillance.