Oral Communications 32P C01 Oral ketone body supplementation accelerates and enhances glycogen synthesis in human skeletal muscle following exhaustive exercise

PURPOSE: Physical endurance is limited by muscle carbohydrate stores (glyco-gen) 1. Glycogen depletion dramatically reduces external work 2. Ketone bodies (D-β-hydroxybutyrate and acetoacetate) are natural 4-carbon molecules synthe-sised in the fasted liver. Animal studies show that ketones increase glycogen synthesis in the presence of carbohydrate 3,4. 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. A study of the glycogen metabolism during exercise in man. Effect of acetoacetate on glucose metabolism in the soleus and extensor digitorum longus muscles of the rat. Nonglucose substrates increase glycogen synthesis in vivo in dog heart. Where applicable, the authors confirm that the experiments described here conform with the Physiological Society ethical requirements. Oxygen insufficiency (hypoxia) is a condition prevalent amongst a range of diseased populations. Furthering our understanding of hypoxic acclimation and of potential methods to alleviate hypoxic stress is thus highly clinically relevant. A controversial aspect of acclimation is skeletal muscle metabolic remodelling, a process that may be aided by nitrate supplementation. Mechanisms of nitrate action have been shown to involve interaction with a master regulator of fat metabolism, peroxisome prolif-erator-activated receptor alpha (PPARα) [1]. In this study, the potential for nitrate to aid hypoxic acclimatisation in skeletal muscle (soleus) and the role of PPARα in this Oral Communications 34P process were investigated. Wild type (WT) …