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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的目的是通过建立一个成熟的急性色氨酸耗竭模式来改变乳腺癌妇女的中枢血清素神经传递，从而提高我们对潮热病因的理解。色氨酸是血清素的前体。血清素可能与潮热有关。主要的假设是饮食中色氨酸和血清素水平的改变与乳腺癌女性的潮热有关，而对色氨酸控制的反应的变异性可以部分地用血清素受体和转运体的遗传变异来解释。提出了一种受试者内、双盲、安慰剂对照、平衡、交叉设计。受试者将参加两个相似的10小时测试，间隔一周。在一天的测试中，他们将摄入浓缩氨基酸饮料和胶囊氨基酸（实验条件，不含色氨酸）。在另一个测试日，女性将摄入一杯+浓度的饮料（对照条件）。女性将在每个测试日之前禁食8小时，进行连续的血液采样和客观的潮热评估，并密切评估直到第二天的不良反应。如果数据支持我们的假设，我们将有强大的生理基础来追求热潮热干预，包括增加饮食中色氨酸的可用性。这种饮食干预可以代替或补充SSRI来根除潮热，这是一种常见的、严重的、令人烦恼的乳腺癌治疗相关疾病，从而提高对救命药物（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.