Specialized Nutritional Support Improves Muscle Function and Maintains Physical Activity Without Affecting Chemotherapy Efficacy in a Colorectal Cancer Mouse Model

Abstract Objectives Skeletal muscle wasting and fatigue are commonly observed in cancer patients receiving chemotherapy and are associated with reduced treatment outcome and quality of life. Nutritional support may mitigate these side effects, but potential interference with chemotherapy efficacy could be of concern. Here, we investigated the effects of a ω-3-PUFA (EPA and DHA), leucine-enriched, high protein (100% whey), additional vitamin D and prebiotic fibers “Specific Nutritional Composition” (SNC) and chemotherapy on state-of-the-art tumor organoid models and muscle cells and studied muscle function, physical activity, systemic inflammation, and chemotherapy efficacy in a mouse model of aggressive colorectal cancer (CRC). Methods Chemotherapy treatment consisted of oxaliplatin and 5-fluorouracil. Tumor formation (caliper) and physical activity (infrared camera's) were assessed over time, while tumor-bearing mice received a diet with or without SNC. Ex vivo muscle performance was determined by myography, muscle fatty acid composition by gas-chromatography, and plasma cytokine levels by Luminex xMAP technology. Patient-derived CRC-organoids and C2C12-myotubes were used to determine whether SNC affects chemotherapy-sensitivity in vitro. Results SNC increased the muscle contraction capacity of chemotherapy-treated tumor-bearing mice (P < 0.05), and enriched ω-3 fatty acid composition in muscle without affecting treatment efficacy (P < 0.0001) compared to control tumor-bearing mice. Mice receiving SNC maintained physical activity after chemotherapy and showed decreased systemic inflammation and splenomegaly. Therapeutic response of CRC-organoids was unaffected by SNC nutrients, while C2C12 cell viability and protein synthesis significantly improved. Conclusions The results show that specialized nutritional support can be used to maintain muscle function and levels of physical activity during chemotherapy without increasing tumor viability. Therefore, nutritional strategies have potential value in promoting cancer and chemotherapy tolerance. Funding Sources This research is part of the SCOPE project (Specialized nutrition to improve outcomes of COlorectal cancer PatiEnts) and is supported by the Province of Utrecht, The Netherlands.