Exogenous ketosis impacts neither performance nor muscle glycogen breakdown in prolonged endurance exercise

J Appl Physiol (1985). 2020 Jun 1;128(6):1643-1653. doi: 10.1152/japplphysiol.00092.2020. Epub 2020 May 14.


Available evidence indicates that ketone bodies inhibit glycolysis in contracting muscles. Therefore, we investigated whether acute exogenous ketosis by oral ketone ester (KE) intake early in a simulated cycling race can induce transient glycogen sparing by glycolytic inhibition, thereby increasing glycogen availability in the final phase of the event. In a randomized crossover design, 12 highly trained male cyclists completed a simulated cycling race (RACE), which consisted of 3-h intermittent cycling (IMT180'), a 15-min time trial (TT15'), and a maximal sprint (SPRINT). During RACE, subjects received 60 g carbohydrates/h combined with three boluses (25, 20, and 20 g) (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) or a control drink (CON) at 60 and 20 min before and at 30 min during RACE. KE intake transiently increased blood d-β-hydroxybutyrate to ~3 mM (range: 2.6-5.2 mM) during the first half of RACE (P < 0.001 vs. CON). Blood pH concomitantly decreased from approximately 7.42 to 7.36 (range: 7.29-7.40), whereas bicarbonate dropped from 26.0 to 21.6 mM (range: 20.1-23.7; both P < 0.001 vs. CON). Net muscle glycogen breakdown during IMT180' [KE: -78 ± 30 (SD); CON: -60 ± 22 mmol/kg wet wt; P = 0.08] and TT15' (KE: -9 ± 18; CON: -18 ± 18 mmol/kg wet wt; P = 0.35) was similar between KE and CON. Accordingly, mean power output during TT15' (KE: 273 ± 38; CON: 272 ± 37 W; P = 0.83) and time-to-exhaustion in the SPRINT (KE: 59 ± 16; CON: 58 ± 17 s; P = 0.66) were similar between conditions. In conclusion, KE intake during a simulated cycling race does not cause glycogen sparing, nor does it affect all-out performance in the final stage of a simulated race.NEW & NOTEWORTHY Exogenous ketosis produced by oral ketone ester ingestion during the early phase of prolonged endurance exercise and against the background of adequate carbohydrate intake neither causes muscle glycogen sparing nor improves performance in the final stage of the event. However, such exogenous ketosis may decrease buffering capacity in the approach of the final episode of the event. Furthermore, ketone ester intake during exercise may reduce appetite immediately after exercise.

Keywords: cycling performance; ketoacidosis; ketone ester; muscle glycogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose*
  • Dietary Carbohydrates
  • Exercise
  • Glycogen
  • Humans
  • Ketosis*
  • Male
  • Muscle, Skeletal
  • Muscles
  • Physical Endurance


  • Blood Glucose
  • Dietary Carbohydrates
  • Glycogen