Effects of grape seed flour supplementation in perioperatetive colorectal cancer patients with cachexia on weight and muscle loss attenuation: a double-blind randomized controlled trial

• Grant number: 19/19988-2
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Daniela Caetano Gonçalves
• Grantee: Daniela Caetano Gonçalves
• Host Institution: Instituto de Saúde e Sociedade (ISS). Universidade Federal de São Paulo (UNIFESP). Campus Baixada Santista. Santos , SP, Brazil
• City of the host institution: Santos
• Associated researchers: Gabriela Salim Ferreira de Castro ; Geovana Silva Fogaça Leite ; Luciana Pellegrini Pisani ; Marilia Cerqueira Leite Seelaender

Abstract

Cancer cachexia is a multifactorial syndrome characterized by involuntary and progressive loss of lean mass, in the presence or not of fat loss, accompanied by anorexia, neuroendocrine changes and inflammation. The syndrome, very common in solid tumors of the gastrointestinal tract, decreases patient's quality of life and survival time, has a high prevalence in the late stages of cancer and is responsible for the direct death of 20% of cancer patients. Negative protein balance and muscle tissue degradation are associated with the inflammatory condition inherent to cachexia, leading to muscle failure, which is recognized as secondary sarcopenia. Until then, no drug can cure cachexia and its reversal is not possible only by the energy-protein adequacy. Oxidative stress, resulting from the imbalance between free radical production and the body's antioxidant capacity, is present in the muscle that is degrading in cachexia and indicates its direct role in the activation of different proteolytic pathways, such as ubiquitin-proteasome and autophagy. In this sense, the present project investigates possible therapeutic effects of supplementation of Chardonnay grape seed flour, rich in antioxidant polyphenols, in the attenuation or prevention of muscle loss related to cancer-associated cachexia during a perioperative colorectal surgery period of 42-day. Two distinct groups, stratified by gender and ethnicity, will be randomly allocated in: intervention group (grape seed flour) or placebo (corn starch). The following analyzes will be performed to verify the efficacy of the intervention: reduction in the percentage of weight loss, body composition, fatigue, strength, quality of life, nutritional assessment, biochemical assessment (blood glucose, CRP, proinflammatory cytokines), gene expression and protein metabolism markers in muscle cells (atrogin-1, MuRF-1, calpain, pAkt), biological markers of oxidative stress, microbiota analysis. Adverse events will be collected to discuss the possibility of harms due to supplementation. Statistical analysis will be performed by ANCOVA, covariated for age, Body Mass Index (BMI), Surgical Apgar Score and Charlson Comorbidity Index. Results will be represented as mean and standard deviation, being considered significant when p is inferior than 0.05. (AU)