A short-term ketogenic diet combined with short-term fasting before chemotherapy in treating patients with acute leukaemia: a randomised controlled trial.

The isocaloric KD (Section 10 and Appendix A for detailed description) will consist of 90% energy from fat, 5-7% from protein, and 3-5% from carbohydrate. The ketogenic diet intervention will be administered 3 times per day (breakfast, lunch, and dinner) beginning 2-6 days before scheduled chemotherapy. The number of days prior to chemotherapy is variable because the start of chemotherapy depends on whether the patient has been admitted, has a central line in place, has completed all required pre-chemotherapy testing, and is clear of any infections or secondary conditions that delay chemotherapy. Generally, most patients will consume the ketogenic diet for 4-5 days. A minimum of 48 h is generally necessary to enter ketosis. The subject will fast, that is eat and drink nothing except water for 16 hours before scheduled chemotherapy. The ketogenic diet will then be continued 3 times per day during chemotherapy (7 days for the first cycle and, optionally,5 days for subsequent cycles). The total duration of the dietary intervention is 9-15 days for the first cycle of treatment and up to 10 days for subsequent cycles. For participants 60 years of age and younger, a further 2-4 cycles of therapy will be administered, and for those over 60, a further 1-2 cycles will be administered. Each cycle of treatment is administered at a frequency of approximately 28 days. In patients deemed unfit for intensive chemotherapy, treatment will be venetoclax and azacytidine, consisting of continuous oral venetoclax combined with a 7-day course of daily subcutaneous azacytidine repeated every 28 days until disease progression or unacceptable toxicity. The usual treatment for ALL patients is hyper-CVAD, with part A receiving 4 days chemotherapy and Part B, 3 days, during which the KD will be given. Administration of the KD will be adjusted for other ALL regimens. Upon randomisation to the intervention group, the study team will notify the dietetics department to start the patient in the ketogenic diet for the induction chemotherapy cycle. The hospital will administer the ketogenic diet that consist of a fixed menu including several different breakfast meals (e.g. scrambled eggs and bacon, avocado, and Hollandaise sauce) and several lunch/dinner meals (e.g. Keto mashed potato, poached fish and hollandaise sauce, avocado pulp). To increase meal variety and compliance, the study team will provide additional keto snacks to the patient (roasted nuts, keto chocolate, etc.), approved by the dietician. A list of approved keto snacks and recipes will be provided to the patient and their relatives in case they wish to bring food from home that is compliant with the intervention diet. The list and recipes will comply with the Food Safety protocols established by the hospital dietetics department. If food intake is insufficient or inadequate, the hospital dietician will offer 200 ml Ketocal drinks as a supplement. Each meal will supply a 4:1 ratio of fat: protein/CHO. The meals and snacks will be eaten ad-libitum and will provide approximately 2000 calories per day for female and 2500 calories per day for male participants. Participants dietary preferences will be considered, with the possibility to exclude certain meals and substitute them for the patient’s preference within the keto menu.