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

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 本研究的目的是通过使用一个成熟的急性色氨酸耗竭范例来改变乳腺癌妇女的中枢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5-羟色胺水平的改变与乳腺癌妇女的潮热有关，色氨酸操纵反应的变异性可以部分解释为5-羟色胺受体和转运蛋白的遗传变异。拟定了受试者内、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小时测试日，时间间隔为一周。在一个测试日，他们将摄入浓缩氨基酸饮料和胶囊化氨基酸（实验条件，无色氨酸）。在另一个测试日，女性将摄入一种强度饮料（对照条件）。女性将在每个测试日之前禁食8小时，进行连续血液采样和客观潮热评估，并密切评估不良反应直至第二天。如果数据支持我们的假设，我们将有很强的生理学依据来进行涉及增加色氨酸膳食可用性的潮热干预。这种饮食干预可以代替SSRI或与SSRI一起使用，以根除作为频繁、严重和令人烦恼的乳腺癌治疗相关病症的潮热，从而改善对挽救生命药物的依从性（例如，他莫昔芬）和总体生活质量。

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.