PURPOSE: Physical endurance is limited by muscle carbohydrate stores (glycogen)1. Glycogen depletion dramatically reduces external work2. Ketone bodies (D-β-hydroxybutyrate and acetoacetate) are natural 4-carbon molecules synthesised in the fasted liver. Animal studies show that ketones increase glycogen synthesis in the presence of carbohydrate3,4. The study hypothesis is that ketone supplementation augments replenishment of glycogen stores in man, beyond that achieved by optimum carbohydrate provision alone. METHODS: 12 well-trained British Forces servicemen underwent a validated interval protocol to deplete muscle glycogen. They were randomised to control drink + intravenous carbohydrate (Cont-CHO), ketone drink + intravenous carbohydrate (Ket-CHO) or control drink + intravenous saline (Cont-saline) in a randomised, blinded, crossover study. Carbohydrate was delivered by standardised 2-hour 10mM glucose – hyperglcaemic clamp. Glycogen was measured in muscle biopsies (pre and post feeding). RESULTS: Ketone supplementation achieved a D-β-hydroxybutyrate of 5.3(±0.48) vs. 0.4(±0.1) mmol/L with Cont-CHO condition. There was an associated 33% increase in whole body glucose disposal 125.8(±4.2) vs. 94.7(±3.2) g, for Ket-CHO vs Cont-CHO (p<0.001). Muscle glycogen increased significantly 246(±32.4) vs 164(±12.5) mmol glycosyl units/kg dry weight of muscle (p=0.017) and insulin levels doubled: 31.1(±5.7) vs 16.4(±2.7) mU/L (p<0.01) for Ket-CHO vs Cont-CHO. CONCLUSIONS: There is increased glucose uptake and higher muscle glycogen deposition following ketone supplementation in man, beyond levels achievable by ‘gold-standard’ high-dose intravenous glucose infusion alone. The additional novel finding of a doubling of endogenous insulin has significant implications for the augmentation of exercise recovery and anabolic metabolism.