BACKGROUND: We have found that a ketogenic diet (KD) during the course of radiotherapy (RT) was feasible and led to a preservation or favorable changes of body composition. Based on these observations and theoretical considerations, we initiated a study to investigate the impact of a KD or a ketogenic breakfast intervention in patients undergoing RT. METHODS: All patients presenting for curative RT with age between 18 and 75, body mass index between 18 and 34 kg/m and a histologically confirmed cancer of the breast, colorectum or head and neck region are considered for inclusion. Exclusion criteria are Karnofsky index <70, pregnancy, metallic body parts that interfere with bioimpedance analysis (BIA), type I diabetes, known enzyme defects that contradict a KD and renal insufficiency. Randomization is achieved by all consecutive patients first entering the control group and then an intervention group 1 until both groups contain 15 breast, 15 colorectal and 5 head and neck cancer patients. Intervention group 1 will receive each radiotherapy fraction after an overnight fast and subsequently ingest a ketogenic breakfast consisting of (i) 50-250 ml of a medium-chain triglyceride drink (betaquick, vitaflo, Bad Homburg, Germany) plus (ii) 5-15 g amino acids (MAP, dr. reinwald healthcare gmbh+co kg, Schwarzenbruck, Germany). If willing to undertake a complete KD for the duration of RT, patients are entered into intervention group 2. Intervention group 2 does not have to fast prior to RT fractions but will be supplemented with MAP analogous to intervention group 1. The control group will not receive dietary advice to follow a KD or reduce carbohydrate intake. The objective is twofold: (i) to test whether the ketogenic interventions are feasibly, as measured by the number of dropouts; (ii) to see whether intervention groups 1 and 2 attain a better preservation of BIA phase angle than the control group. ENDPOINTS: Primary endpoints are the feasibility of the interventions (measured through dropout rates), and changes in body weight and composition (measured through BIA). Secondary endpoints are changes in quality of life (EORTC questionnaires) and blood parameters as well as the occurrence and grade of toxicities and grade of regression after surgery in case of colorectal carcinomas.