Low skeletal muscle mass and function, is prevalent in up to 60% of colorectal cancer patients. This condition arises from a combination of factors such as aging, inactivity, treatment side effects, malnutrition, tumor burden, and inflammation. Given this complexity, singular interventions may not be sufficient to address low muscle mass in this group.

Creatine monohydrate, a compound vital for energy during exercise, has been extensively researched and proven safe and effective across various demographics, including older adults and clinical populations. Studies show that creatine enhances benefits from resistance training, indicating potential to counter muscle mass and function decline post-cancer treatment.

This study aims to assess the feasibilty of combining creatine supplementation with resistance training versus resistance training alone in colorectal cancer survivors treated with chemotherapy. A randomized controlled pilot trial will compare a 10-week program of resistance exercise plus creatine (EXSUPP) with resistance exercise alone (EXPLA), each with 20 participants.

Colorectal cancer is the third most commonly diagnosed cancer in the world. Low muscle mass 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 low muscle mass 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. 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 individuals with colorectal cancer 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."

Inclusion Criteria:

• Individuals ≥12 months post treatment with chemotherapy for colorectal cancer
• >18 years

Exclusion Criteria:

1. are receiving active treatment for their cancer;
2. had a musculoskeletal, cardiovascular, neurological, or psychological condition that precluded participation in RET;
3. had been participating in structured RET two or more times per week for the past 6 months
4. are currently taking supplements containing creatine for 4 weeks prior to the start of the RCT, or
5. are receiving medications that might alter body composition (metformin, corticosteroids etc.).