This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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