THE ROLE OF DIETARY TRYPTOPHAN AND SEROTONIN IN HOT FLASHES AFTER BREAST CANCER

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的目的是通过使用公认的急性色氨酸耗竭范例来改变乳腺癌女性的中枢5-羟色胺神经传递，以提高我们对潮热病因的理解。色氨酸是5-羟色胺的前体。5-羟色胺可能与潮热有关。主要的假设是，饮食中色氨酸和5-羟色胺水平的变化与乳腺癌女性潮热有关，对色氨酸操纵的反应的变异性可以部分解释为5-羟色胺受体和转运体的遗传差异。受试者内，双盲、安慰剂对照、平衡、交叉设计。受试者将参加相隔一周的两个类似的10小时测试日。在一次测试中，他们将摄入一种浓缩的氨基酸饮料和封装的氨基酸(实验条件下，没有色氨酸)。在另一个测试日，女性将摄入一种烈性饮料(对照条件)。女性将在每一次测试前禁食8小时，接受连续抽血和客观潮热评估，并在第二天密切评估不良反应。如果数据支持我们的假设，我们将有强大的生理理由进行热潮热干预，包括增加色氨酸的饮食可获得性。这种饮食干预可以用来代替或补充SSRI，以消除潮热作为一种与乳腺癌治疗相关的频繁、严重和令人烦恼的疾病，从而改善对挽救生命的药物(如他莫昔芬)的依从性和整体生活质量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The study purpose is to improve our understanding of the etiology of hot flashes by using a well-established acute tryptophan depletion paradigm to alter central serotonin neurotransmission in women with breast cancer. The amino acid tryptophan is a precursor to serotonin. Serotonin may be involved in hot flashes. The main hypothesis is that alterations in dietary tryptophan and serotonin levels are involved in hot flashes in women with breast cancer and that variability in response to tryptophan manipulation can be partly explained by genetic variations in the serotonin receptors and transporters. A within subjects, double blind, placebo controlled, balanced, crossover design is proposed. Subjects will take part in two similar 10-hour test days scheduled one week apart. On one test day, they will ingest a concentrated amino acid drink and encapsulated amino acids (experimental condition, no tryptophan). On the other test day, women will ingest a ¿ strength drink (control condition). Women will fast for 8 hours prior to each test day, undergo serial blood sampling and objective hot flash assessment, and be closely assessed for adverse effects through to the following day. If data support our hypothesis, we will have strong physiological rationale to pursue a hot flash intervention involving increasing dietary availability of tryptophan. This dietary intervention might be used in lieu of, or in addition to, SSRI to eradicate hot flashes as a frequent, severe and bothersome breast cancer treatment related condition, thereby improving compliance with life-saving medications (e.g., tamoxifen) and overall quality of life.