Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients.

BACKGROUND & AIMS: Obesity and low muscle mass are associated with worse outcomes of colorectal cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in rectal cancer patients undergoing radiotherapy. METHODS: Patients with non-metastasized rectal cancer were allocated to either the KD (N = 24) or the SD (N = 25) group during radiotherapy. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Pathologic response in patients undergoing neoadjuvant treatment was evaluated at the time of surgery. RESULTS: A total of 18 KD and 23 SD patients completed the study and were eligible for analysis. The SD group experienced no noteworthy changes in any body composition parameter. In contrast, patients in the KD group lost significant amounts of body weight and fat mass, averaging 0.5 and 0.65 kg/week (p < 0.0001). There was a rapid loss of intracellular water consistent with initial intramuscular glycogen and water depletion, but skeletal muscle tissue was conserved. Pathological tumor responses were somewhat greater in the KD group, with a larger mean Dworak regression grade (p = 0.072) and larger percentage of near-complete (yT0N0 or yT1N1) responses (43 versus 15%, p = 0.116) that almost reached statistical significance in intention-to-treat analysis (50% versus 14%, p = 0.018). CONCLUSIONS: In rectal cancer patients undergoing curative radiotherapy, a KD significantly reduced body weight and fat mass while preserving skeletal muscle mass. We could demonstrate a trend for KDs contributing synergistically to pathological tumor response, a finding in line with preclinical data that warrants future confirmation in larger studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.