Ketosis Suppression and Ageing (KetoSAge): Suppression of ketosis negatively affects multiple biomarkers associated with chronic diseases and ageing

Metabolic dysfunctions are among the best documented hallmarks of ageing. Ageing is typically understood in its chronological context, as the length of time that has passed since a person’s birth, whereas biological age is the measure of functional age, often measured in terms of physical and mental performance, as well as morbidities that decrease quality of life and youth-span. Cardiovascular disease, Alzheimer’s disease, cancer, type 2 diabetes mellitus, metabolic-dysfunction-associated steatosis liver disease, and fragility fractures are diseases of hyperinsulinaemia that reduce life and healthspan. Hyperinsulinaemia pathologies present with increases in loss of function at all levels, from: the cellular, tissue, organ and ultimately systemic. Sustained ketosis with euglycaemia is a measurable metabolic phenotype to indicate absence of hyperinsulinaemia. This thesis investigates the metabolic phenotype of long-term sustained ketosis (euketonaemia) in healthy females with no prior metabolic diseases. Assessing their baseline biochemical profile (metabolic phenotype) and changes in biomarkers associated with ageing and age associated diseases after suppressing ketosis (SuK) for 21 days, followed by a further investigation after removing the intervention of suppressing ketosis, with the participants reverting back to their habitual lifestyle of being in a state of ketosis for 21 days, to further ascertain if the changes seen after the ketosis suppression phase, were likely due to the intervention. Over 50 biomarkers were tested, suppression of ketosis was found to negatively affect a host of markers most strongly associated with ageing and declining metabolic health. Strategies that can prevent and/or reduce hyperinsulinaemia may therefore improve cellular and vascular health, leading to decreased risk of developing chronic diseases that reduce quality of life, healthspan and lifespan.