Valenzuela Tallón, Pedro LuisSantalla Hernández, AlfredoBrea Alejo, LidiaBustos, AsunciónOzcoidi, Laureano M.Castellote Bellés, LauraFerrer Costa, RoserVillarreal Salazar, MónicaBarranco Gil, DavidLucía Mulas, AlejandroEt al.2025-01-122024Valenzuela, P. L., Santalla, A., Alejo, L. B., Bustos, A., Ozcoidi, L. M., Castellote-Bellés, L., Ferrer-Costa, R., Villarreal-Salazar, M., Morán, M., Barranco-Gil, D., Pinós, T., & Lucia, A. (2024). Acute ketone supplementation in the absence of muscle glycogen utilization: Insights from McArdle disease. Clinical Nutrition, 43(3), 692-700. https://doi.org/10.1016/j.clnu.2024.01.0260261-56141532-1983http://hdl.handle.net/11268/13459Background & aims: Ketone supplementation is gaining popularity. Yet, its effects on exercise performance when muscle glycogen cannot be used remain to be determined. McArdle disease can provide insight into this question, as these patients are unable to obtain energy from muscle glycogen, presenting a severely impaired physical capacity. We therefore aimed to assess the effects of acute ketone supplementation in the absence of muscle glycogen utilization (McArdle disease). Methods: In a randomized cross-over design, patients with an inherited block in muscle glycogen breakdown( i.e.,McArdle disease,n¼8) and healthycontrols (n¼7) underwent a submaximal (constant-load) test that was followed by a maximal ramp test, after the ingestion of a placebo or an exogenous ketone ester supplement (30 g of D-beta hydroxybutyrate/D 1,3 butanediol monoester). Patientswere also assessed after carbohydrate (75 g) ingestion, which is currently considered best clinical practice in McArdle disease. Results: Ketone supplementation induced ketosis in all participants (blood [ketones] ¼ 3.7 ± 0.9 mM) and modified somegas-exchange responses (notably increasing respiratory exchange ratio, especially in patients). Patients showed an impaired exercise capacity ( 65 % peak power output (PPO) compared to controls, p < 0.001) and ketone supplementation resulted in a further impairment ( 11.6 % vs. placebo, p¼ 0.001),with no effects in controls (p ¼ 0.268). In patients, carbohydrate supplementation resulted in a higher PPO compared to ketones (þ21.5 %,p¼0.001) anda similar responsewas observed vs.placebo (þ12.6 %,p¼0.057). Conclusions: In individuals who cannot utilize muscle glycogen but have a preserved ability to oxidize blood-borne glucose and fat (McArdle disease), acute ketone supplementation impairs exercise capacity, whereas carbohydrate ingestion exerts the opposite, beneficial effect.engSuplementos dietéticosEnfermedad del almacenamiento de glucógenojournal article10.1016/j.clnu.2024.01.026restricted accessNutriciónEfectos fisiológicosMetabolismoGoal 3: Ensure healthy lives and promote well-being for all at all ages