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

描述（由申请人提供）：1。这是一项R21建议，旨在进行一项临床试验，该试验将测试使用一种安全和微创的饮食干预措施，以增强对有毒多氯联苯（PCB）的清除，这些化合物的水平升高。为了进行这项研究，我们将在亚拉巴马的安尼斯顿招募受试者，该社区的相当一部分当地人口因受污染的商业废物而暴露于多氯联苯。目前，安尼斯顿的许多居民血液和脂肪组织中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，并可能面临更大的其他健康疾病的风险。由于以前的研究和诉讼，安尼斯顿居民已经意识到他们社区的环境PCB污染以及由此暴露导致的不良健康影响的相关风险。我们开创了一种方法，在饮食中添加少量不可吸收的脂肪，作为一种治疗工具，以安全的方式加速消除持久的亲脂性化合物，如PCB。我们的理论基础是，一旦PCB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中循环。在正常情况下，这些化合物从肠道被重吸收并返回血液，从而防止在粪便中排泄。在饮食中添加少量不可吸收的脂质提供了用于将污染物物理保留在肠腔内的基质，其然后允许污染物与脂质一起沿着排出。尽管任何一天的排泄量相对较小，但一年中的累积排泄量具有临床意义。Anniston人群提供了一个理想的人群，以有意义的方式评估这种干预措施，我们与当地社区团体结盟，协助招募受试者，并进行本研究所需的相对简单的饮食操作。我们将在已知多氯联苯水平升高的受试者中进行一项非吸收性脂肪的双盲、安慰剂对照研究。我们将测量这些受试者血液中多氯联苯含量的变化率。 公共卫生相关性： 我们将在亚拉巴马的安尼斯顿进行一项双盲、安慰剂对照的研究，研究对象是以前被证明体内多氯联苯负荷升高的受试者。我们将确定非吸收性膳食脂质通过阻断多氯联苯及其亲脂代谢物的肠肝循环来降低多氯联苯水平的功效。积极的结果将提供一种治疗选择，可能降低接触多氯联苯和其他持久性有机污染物的受试者的疾病风险。

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.