Intervention to Reduce Body Burden of PCBs in Residents of Anniston Alabama

描述(由申请人提供)：1.简介这是一项R21提案，旨在进行一项临床试验，测试使用一种安全和微创的饮食干预措施，以加强有毒多氯联苯(PCB)从这些化合物水平升高的个人中的清除。为了进行这项研究，我们将在阿拉巴马州的安尼斯顿招募受试者，在这个社区，由于受污染的商业废物，当地人口中有相当一部分人暴露在多氯联苯中。安尼斯顿的许多居民目前血液和脂肪组织的多氯联苯水平明显升高。此外，这些人的2型糖尿病患病率增加了几倍，并有可能面临更大的其他健康疾病风险。由于之前的研究和诉讼，Anniston居民已经意识到他们社区的环境多氯联苯污染以及这种暴露导致的不利健康影响的相关风险。我们已经开创了一种方法，将少量不可吸收的脂肪添加到饮食中，作为一种治疗工具，以安全的方式加速消除持久性亲脂化合物，如多氯联苯。我们的理论基础是，一旦多氯联苯和其他有机氯污染物进入人体，它们就会在包括小肠在内的几个器官之间循环。在正常情况下，这些化合物从肠道重新吸收并返回血液，从而防止从粪便中排出。在饮食中添加少量不可吸收的脂肪提供了一个基质，用于物理地将污染物保留在肠腔内，然后允许污染物与脂肪一起排泄。虽然任何一天的排泄量都相对较小，但一年中的累积排泄量在临床上是有意义的。安尼斯顿人口提供了一个理想的人群来以有意义的方式评估这一干预措施，我们已经与当地社区团体结盟，以协助招募受试者并进行本研究所需的相对简单的饮食控制。我们将对已知多氯联苯水平升高的受试者中的一种不可吸收脂肪进行双盲、安慰剂对照研究。我们将测量这些受试者血液中多氯联苯水平的变化率。 公共卫生相关性： 项目简介我们将在阿拉巴马州的安尼斯顿进行一项双盲、安慰剂对照研究，研究对象是以前被证明体内多氯联苯负荷增加的人。我们将通过阻断多氯联苯及其亲脂代谢产物的肠-肝循环来确定非可吸收膳食脂质在降低多氯联苯水平方面的有效性。积极的结果将为可能降低暴露于多氯联苯和其他持久性有机污染物的受试者的疾病风险提供一种治疗选择。

DESCRIPTION (provided by applicant): 1. Introduction This is an R21 proposal to conduct a clinical trial which will test the use of a safe and minimally invasive dietary intervention to enhance the removal of toxic polychlorinated biphenyls (PCBs) from individuals with elevated levels of these compounds. To conduct this study, we will enroll subjects in Anniston, Alabama, a community in which a significant portion of the local population has been exposed to PCBs as a result of contaminated commercial waste. Many of the residents of Anniston currently have markedly elevated blood and adipose tissue PCB levels. In addition, these individuals have a several-fold increased prevalence of type-2 diabetes and are potentially at greater risk of other health disorders. Due to previous research and litigation, Anniston residents are already aware of environmental PCB contamination in their community and the associated risk for adverse health effects resulting from this exposure. We have pioneered a method for adding a small amount of non-absorbable fat to the diet for use as a therapeutic tool which hastens the elimination of persistent lipophilic compounds, such as PCBs, in a safe manner. Our rationale is based on the fact that once PCBs and other organochlorine pollutants enter the body, they circulate among several organs including the small intestine. Under normal circumstances, these compounds are reabsorbed from the intestine and returned to the blood, and are thus prevented from being excreted in the feces. The addition of a small amount of non-absorbable lipid in the diet provides a matrix for physically retaining the pollutants within the intestinal lumen, which then allows the pollutants to be excreted along with the lipid. Although the excretion on any given day is relatively small, the cumulative excretion over the course of a year becomes clinically significant. The Anniston population provides an ideal population to assess this intervention in a meaningful way, and we have allied with a local community group to assist in the recruitment of subjects and to carry out the relatively simple dietary manipulations required for this study. We will carry out a double-blind, placebo controlled study of a non-absorbable fat in subjects known to have elevated levels of PCBs. We will measure the rate of change of the blood levels of PCBs in these subjects. PUBLIC HEALTH RELEVANCE: Project Narrative We will carry out a double-blind, placebo controlled study in Anniston, Alabama in subjects previously shown to have elevated body burdens of PCBs. We will determine the efficacy of non-absorbable dietary lipid in reducing PCB levels by interrupting enterohepatic circulation of PCBs and their lipophilic metabolites. A positive outcome will offer a treatment option for the potential reduction of the risk of disease in subjects exposed to PCBs and other persistent organic pollutants.