Resistance Exercise and Creatine in Colorectal Cancer

Colorectal cancer is the third most commonly diagnosed cancer in the world. Sarcopenia, defined as a loss of skeletal muscle mass and function, is highly prevalent in colorectal cancer, with rates of up to 60% reported. Sarcopenia etiology in cancer is multifactorial, with aging and inactivity compounded by treatment toxicities, malnutrition, tumor burden, and high-grade inflammation. Consequently, it's unlikely that unimodal interventions will be sufficient to overcome the burden of sarcopenia in this population. Creatine monohydrate is a naturally occurring compound in the body that plays a critical role in energy provision during exercise.4 Creatine is the most widely studied nutritional supplement to date, with well over 1,000 studies establishing its safety and effectiveness in men, women and older adults, in addition to other clinical populations. There is strong and consistent evidence that creatine supplementation can enhance the positive adaptations to resistance training in older adults and clinical populations. Therefore, there is strong potential for the application of creatine and resistance training to offset the decline in muscle mass and function after cancer treatment. The purpose of the proposed study is to examine the feasibility and acceptability of creatine supplementation combined with resistance exercise, compared to resistance exercise alone in individuals treated for colorectal cancer who are sarcopenic. We propose a randomized controlled pilot trial, examining the effects of 10-week multimodal resistance exercise and creatine supplementation (EXSUPP) (n=20) relative to resistance exercise alone (EXPLA) (n=20) in individuals treated for colorectal cancer who have sarcopenia. The specific aims of this project are to 1) determine the feasibility and acceptability of the intervention in colorectal cancer patients? diagnosed with sarcopenia after cancer treatment, 2) compare the effects of an exercise and creatine supplementation intervention (EXSUPP) to exercise alone (EXPLA) on body composition, muscle strength, physical function, and quality of life and 3) explore muscle molecular-level adaptations, i.e., mitochondrial health and protein turnover, in response to the interventions. This project will be one of the first to combine exercise with creatine, specifically targeting sarcopenia in individuals previously treated for colorectal cancer. This project is directly in line with the priority research initiative from the NCI Cancer MoonshotSM to "minimize Cancer Treatment's Debilitating Side Effects." Our trial is innovative in addressing one of the most important health problems for individuals treated for colorectal cancer in that it will be the first to 1) examine the feasibility and acceptability of a multimodal exercise and nutritional intervention relative to exercise alone in individuals treated for colorectal cancer who are sarcopenic and 2) explore the molecular mechanisms underpinning the response to exercise and nutritional interventions.