Feature Paper: Suppressed Ketosis, Hypoketonaemia, Raises GKI and Liver Markers in Lean Women - Cover of the MDPI Livers, Volume 5, Issue 3 (September 2025)

Cover Story: The KetoSAge human trial examined ten lean, healthy, pre-menopausal women who were habitually in ketosis (~3.9 years). Participants suppressed ketosis-inducing hypoketonaemia for 21 days via a higher carbohydrate intake, aligned with standard healthy eating guidelines, before returning to euketonaemia. Hypoketonaemia resulted in significant increases in ALT (~1.9-fold), GGT (1.3-fold), ALT/AST (1.30-fold), GKI (22.23-fold), and HOMA-IR (2.13-fold). These metabolic disturbances reversed when euketonaemia was re-established. Our findings highlight that even short periods of hypoketonaemia can induce hepatic stress, insulin resistance, and subclinical hyperinsulinaemia, emphasising liver enzymes and GKI as sensitive biomarkers of metabolic shifts associated with chronic diseases, with euketonaemia resulting in levels associated with optimal health.