Our open-labelled, non-randomised cross-over trial is published. We studied the effects of short-term ketosis-suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). (66 days in total with a 6 month qualifying lead in) Results: Adherence to each phase was confirmed with daily capillary BHB tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 mmol/L). Ketosis suppression significantly increased: 👉Insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) mmol/L (p = 0.0002) 👉IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045) 👉Glucose, 1.17-fold from 4.36 (± 0.53) to 5.12 mmol/L (± 0.59, P2; p = 0.0088) 👉Respiratory quotient, 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427) 👉PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428). 👉VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift. 👉Sustained ketosis showed no adverse health effects and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women. Conclusions: Evolutionary evidence suggests that ancestral populations were predominantly adapted to patterns of intermittent and time-restricted feeding, as opposed to continuous nutritional intake, rich in farinaceous and sucrose carbohydrates that stimulate bolus insulin secretion. The escalating prevalence of T2DM, obesity, CVD, AD, and cancer observed in populations adhering to multiple substantial carbohydrate-dominated meals in developed nations is a testament to this. Individuals maintaining long-standing habitual NK, when subjected to 21 days of consuming carbohydrate to suppress ketosis, followed with restricting carbohydrate, reverted to an evolutionary ketotic state within one day, indicate metabolic flexibility and health. The negative changes in biomarkers associated with chronic diseases and ageing, which occur from a one-time excursion in a 1-year period of 21 consecutive days of suppressing ketosis, are rapidly restored after restoring the baseline dietary lifestyle of carbohydrate restriction which does not overstimulate insulin demand and secretion. Our data show that long-standing NK appears to provide major health benefits in the maintenance of euglycaemia, with low insulin and IGF-1, the triad of markers most strongly associated with chronic diseases and biological ageing. NK serves as a reliable surrogate marker for these parameters to understand an individual’s metabolic phenotype, and therefore risk. This study was conducted to establish a detailed metabolic phenotype biomarker profile in a long-standing healthy ketosis cohort, providing a NK control group for other studies to establish metabolic phenotypes in people with cancer, CVD, AD, T2DM, and ageing, and to assess treatment efficacy using KMT in gaining better health. Sustained NK may mitigate hyperinsulinemia without impairing metabolic flexibility and carbohydrate tolerance in metabolically healthy individuals. Maintaining low insulin requirement and IGF-1 levels through endogenous NK may offer lower chronic disease risk, resulting in benefits to both lifespan and healthspan. mdpi.com/1422-0067/24/2… Awesome co-authors: @Yvoni_Kyr @_kurtisedwards @_LucyPetagine @tnseyfried @TommyDeeMD @ascarbs @jacomesandra @AdrianSotoMota @kenbrookler @valennutrition @NovaesVanusa @Brads_science
