Ketone ester supplementation blunts overreaching symptoms during endurance training overload

J Physiol. 2019 Jun;597(12):3009-3027. doi: 10.1113/JP277831. Epub 2019 May 22.


Key points: Overload training is required for sustained performance gain in athletes (functional overreaching). However, excess overload may result in a catabolic state which causes performance decrements for weeks (non-functional overreaching) up to months (overtraining). Blood ketone bodies can attenuate training- or fasting-induced catabolic events. Therefore, we investigated whether increasing blood ketone levels by oral ketone ester (KE) intake can protect against endurance training-induced overreaching. We show for the first time that KE intake following exercise markedly blunts the development of physiological symptoms indicating overreaching, and at the same time significantly enhances endurance exercise performance. We provide preliminary data to indicate that growth differentiation factor 15 (GDF15) may be a relevant hormonal marker to diagnose the development of overtraining. Collectively, our data indicate that ketone ester intake is a potent nutritional strategy to prevent the development of non-functional overreaching and to stimulate endurance exercise performance.

Abstract: It is well known that elevated blood ketones attenuate net muscle protein breakdown, as well as negate catabolic events, during energy deficit. Therefore, we hypothesized that oral ketones can blunt endurance training-induced overreaching. Fit male subjects participated in two daily training sessions (3 weeks, 6 days/week) while receiving either a ketone ester (KE, n = 9) or a control drink (CON, n = 9) following each session. Sustainable training load in week 3 as well as power output in the final 30 min of a 2-h standardized endurance session were 15% higher in KE than in CON (both P < 0.05). KE inhibited the training-induced increase in nocturnal adrenaline (P < 0.01) and noradrenaline (P < 0.01) excretion, as well as blunted the decrease in resting (CON: -6 ± 2 bpm; KE: +2 ± 3 bpm, P < 0.05), submaximal (CON: -15 ± 3 bpm; KE: -7 ± 2 bpm, P < 0.05) and maximal (CON: -17 ± 2 bpm; KE: -10 ± 2 bpm, P < 0.01) heart rate. Energy balance during the training period spontaneously turned negative in CON (-2135 kJ/day), but not in KE (+198 kJ/day). The training consistently increased growth differentiation factor 15 (GDF15), but ∼2-fold more in CON than in KE (P < 0.05). In addition, delta GDF15 correlated with the training-induced drop in maximal heart rate (r = 0.60, P < 0.001) and decrease in osteocalcin (r = 0.61, P < 0.01). Other measurements such as blood ACTH, cortisol, IL-6, leptin, ghrelin and lymphocyte count, and muscle glycogen content did not differentiate KE from CON. In conclusion, KE during strenuous endurance training attenuates the development of overreaching. We also identify GDF15 as a possible marker of overtraining.

Keywords: GDF15; exercise recovery; ketone; overreaching and overtraining.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Beverages
  • Bicycling
  • Biomarkers / blood
  • Double-Blind Method
  • Endurance Training*
  • Esters / pharmacology*
  • Growth Differentiation Factor 15 / blood
  • Humans
  • Ketones / pharmacology*
  • Ketones / urine
  • Male
  • Young Adult


  • Biomarkers
  • Esters
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Ketones