Background: Chemotherapy targets rapidly proliferating cells- damaging both malignant and healthy cells. Chemotherapy-induced cellular damage to healthy tissue causes its notorious acute and chronic side effects. Preclinical data show that a ketotic state inhibits the insulin/IGF-1/mTOR pathway and induces cellular repair pathways, thereby protecting healthy cells. We hypothesise that, in humans, metabolic ketosis will provide chemo-protection to healthy cells by upregulating DNA repair and inhibiting cellular senescence, while sensitising cancer cells to chemotherapy by depriving them of their main energy source, glucose.
Aim: To analyse the effects of a ketogenic diet alongside chemotherapy on healthy and leukemic cells in acute leukemia patients.
Methods: Changes in markers of DNA repair, cellular senescence and proliferation were analysed using flow cytometry in healthy and cancer cells from patients pre-, during, and post-chemotherapy treatment.
Results: Preliminary data at 24 and 48 hrs of chemotherapy showed increased y-H2AX expression in leukemic cells in subjects receiving a ketogenic diet (n = 3) compared to the control diet (n = 4). Furthermore, non-leukaemic T-cells from ketogenic subjects’ post-chemotherapy showed a decrease in the cellular senescence markers p16, p21 and SA β-galactosidase compared to control subjects. ATM, 53BP1 and p53 were minimally altered in both study arms.
Conclusion: Preliminary data show that a ketogenic diet increases chemotherapy-induced DNA damage in leukaemic cells during chemotherapy, while it decreases cellular senescence markers in healthy lymphocytes post-treatment, highlighting the potential dual role of this diet as a first-line adjuvant and chemo-protective therapy.