By roughly day two of a fasting-mimicking diet, the body switches to a ketogenic mode burning visceral fat, the brain uses beta-hydroxybutyrate, and organs including the liver, heart, immune system, and oligodendrocytes shrink.
"the fasting-mimicking diet really by day two of the diet—and only by day two or so of the diet—the system starts switching to a ketogenic mode. You start burning visceral fat as your major source of energy, your brain starts moving from burning sugar to burning ketone bodies, you know, beta-hydroxybutyrate. So, as I said, everything starts shrinking: the immune system starts shrinking, the liver, the heart, even the oligodendrocytes, as we've shown in our multiple sclerosis paper." (said at 0:40:20)
The speaker describes physiological and cellular responses to a fasting-mimicking diet (FMD) developed in research by Valter Longo and colleagues. Preclinical and clinical studies confirm that prolonged fasting or multi-day FMD cycles induce a shift to ketogenesis, raising circulating beta-hydroxybutyrate, utilizing fat stores, and reducing circulating white blood cells. In animal models, fasting cycles cause reversible decreases in the mass of various organs (such as liver and spleen) through cell shrinkage and autophagy/apoptosis, followed by stem-cell-mediated regeneration during refeeding. In their multiple sclerosis model (Choi et al., 2016), FMD induced apoptosis of autoimmune T cells and stimulated oligodendrocyte precursor cell regeneration and remyelination. However, translating transient cellular depletion and organ mass fluctuations observed in rodent models into broad statements that human organs and oligodendrocytes 'shrink' requires qualification, as direct evidence for organ shrinkage and oligodendrocyte dynamics derives primarily from preclinical animal models.
- context: A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Scler… (Cell reports 2016)
"Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355)." (abstract, results, passage verified)
pubmedfull study (doi) - context: Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseas… (Molecular and cellular endocrinology 2017)
"Recent studies indicate that both the type and levels of nutrients can influence the generation, survival and function of lymphocytes and therefore can affect several autoimmune diseases. Here, we review the dysregulation of lymphocytes during autoimmunity and aging, the mechanisms associated with loss of immune function, and how fasting mimicking diets and other dietary interventions affect autoimmunity and immunosenescence." (abstract, passage verified)
pubmedfull study (doi)