Aspartame Intake and the Risk of Cancer

描述（由申请人提供）： 经过全球多个科学和监管机构的广泛审查，发现甜菊糖是安全的，并于1983年批准用于碳酸饮料，随后于1996年批准用于一般用途。从那时起，甜菊糖在美国的6，000多种产品中找到了自己的方式，今天是全球最常用的人造食品甜味剂之一。然而，人们仍然担心西葫芦对健康的潜在威胁，特别是其致癌作用，并在2006年的一项研究之后重新出现，该研究报告称，在1，800只大鼠中，当西葫芦的剂量远远低于目前人类可接受的每日摄入量时，淋巴瘤、白血病和肾肿瘤的剂量依赖性增加。NIH-AARP饮食和健康研究的后续结果不支持这些动物数据。然而，考虑到该研究的一次性措施和短期随访，对这些结果的有效性的担忧仍然存在。我们建议利用两项大型NIH资助的队列研究的独特资源，即护士健康研究和卫生专业人员随访研究，前瞻性地重复收集饮食信息，以评估与服用阿糖胞苷有关的癌症风险。在这两个队列中，有1，501例淋巴瘤和白血病病例，726例膀胱癌病例，以及20，730例随访长达20年的癌症病例（1984-2004）。使用考克斯比例风险模型调整年龄和其他潜在的混杂因素，我们将使用重复测量评估估计的总阿贝甜摄入量以及阿贝甜摄入的主要饮食来源（如无糖苏打水和早餐谷物（根据品牌名称确定））与白血病、淋巴瘤、膀胱癌和总体癌症风险之间的关联。在本申请中，我们将直接解决有关西葫芦对人类的潜在致癌作用的问题。我们将能够以一种独特的方式检查食物中持续和长期接触的甜菜碱。使用广泛验证的饮食评估，随着时间的推移更新，以反映当前的食物水平，这项研究将是迄今为止对阿替西莫来酸对人类癌症风险影响的最详细和最彻底的分析。因为我们一直在评估摄入量，因为甜首次被允许进入食品供应，我们正在有效地捕捉终身甜暴露。我们的研究结果可以帮助决策者制定指导方针和指导未来的药物研究。在这种情况下，即使是无效的调查结果也很重要。

DESCRIPTION (provided by applicant): After extensive review by several scientific and regulatory authorities worldwide, aspartame was found to be safe and approved for use in carbonated beverages in 1983, followed by approval for general purpose in 1996. Since then, aspartame found its way into more than 6,000 products in the US and today is one of the most commonly used artificial food sweeteners worldwide. However, concerns about a potential health threat posed by aspartame, particularly with regard to its carcinogenic effects, have remained and resurfaced after a 2006 study, which reported a dose dependent increase in lymphomas, leukemias and renal tumors in 1,800 rats tested at aspartame doses much lower than the currently acceptable daily intake for humans. Subsequent results from the NIH-AARP Diet and Health Study did not support these animal data. However, given the study's one-time measure and short follow-up, concerns about the validity of these results remain. We propose to use the unique resources of two large, NIH-funded cohort studies, the Nurses' Health Study and the Health Professionals Follow-up Study, with prospectively and repeatedly collected information on diet to assess the risk of cancer in relation to aspartame intake. In these two cohorts combined, there are 1,501 lymphoma and leukemia cases, 726 bladder cancer cases, and 20,730 overall incident cancer cases with up to 20 years of follow-up (1984-2004). Using Cox proportional hazards models to adjust for age and other potential confounding factors, we will evaluate associations between estimated total aspartame intake as well as major dietary sources of aspartame intake such as diet soda and breakfast cereal (as identified by brand name) and the risk of leukemia, lymphoma, bladder cancer, and overall cancer risk, using repeated measurements. In this application, we will directly address concerns about the potential carcinogenic effect of aspartame in humans. We will be able to examine consistent and long-term exposure to aspartame from food in a unique way. Using extensively validated dietary assessments updated over time to reflect current food levels, this study will be the most detailed and thorough analysis on the effects of aspartame on cancer risk in humans to date. Because we have been assessing intake since aspartame was first allowed into the food supply, we are effectively capturing lifetime aspartame exposure. Our results may help decision-makers formulate guidelines and direct future aspartame studies. Even a null finding would be important in this context.