Fasting-Mimicking Diet Inhibits Autophagy and Synergizes with Chemotherapy to Promote T-Cell-Dependent Leukemia-Free Survival

Researchers gave mice a 3-day Fasting Mimicking Diet (FMD) once a week, alone and with the chemotherapy drug vincristine, in a BCR-ABL B acute lymphoblastic leukemia model. Mice were fed either a high-fat diet or a standard diet. The authors measured survival, ran RNA sequencing and protein assays on autophagy markers, substituted the autophagy inhibitor chloroquine for the diet, inhibited the autophagy genes ULK1 and ATG9a in cell experiments, and gave anti-CD8 antibodies in a further group.

The authors reported that the diet cycles increased the efficacy of vincristine and improved survival in high-fat-diet-fed mice, and that in standard-diet-fed mice the combination promoted cancer-free survival. They reported a vincristine-dependent decrease in several autophagy markers that was greater under the fasting and diet conditions, and that chloroquine could substitute for the diet in combination with vincristine. In cell experiments, inhibiting ULK1 and ATG9a increased vincristine's toxicity. They reported that anti-CD8 antibodies reversed the survival effect, which they read as pointing to a central role for the immune system.

These findings come from mouse leukemia models and from cells in culture, not from people, and this is not a study of Prolon. The survival effects occurred only in combination with a chemotherapy drug, so the contribution of the diet on its own is not separated out. None of these outcomes was measured in patients in this paper.