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.
