Ketone ester supplementation blunts overreaching symptoms during endurance training overload

Abstract

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.

Figure 1. Overview of the training programme

HIIT, high‐intensity interval training: 30 s all‐out sprints interspersed by 4.5 min active recovery intervals (50 W). The number of sprints was increased from 4 in week 1, to 5 in week 2, and 6 in week 3. IMT, intermittent endurance sessions. Week 1 and 2: 5 × 6 min with 8 min recovery. Week 3: 5 × 8 min with 6 min recovery, ET, constant‐load endurance training sessions. EPT_120min, 120 min endurance performance test. Training intensities for IMT and ET are expressed as a percentage of the mean power output effected during the 30 min time‐trial (TT_30min) in the pre‐test.

Figure 2. Effect of ketone ester supplementation on blood d‐βHB concentrations and urinary ketone excretion

Data are mean ± SEM for fasted morning blood d‐βHB concentration (A) and nocturnal urinary ketone excretion (B) before (Pre) and at the end of weeks 1 (Week 1), 2 (Week 2) and 3 (Week 3) of the training period, and after 3 (Day +3) and 7 (Day +7) recovery days after training. During the training period the subjects received either control (○, n = 9) or ketone ester supplements (●, n = 9) immediately after each training session. C, blood d‐βHB concentrations before (Pre‐ex), and immediately (Post‐ex) and 30 min after (30’ post‐ex) the IMT sessions on days 6, 13 and 20. ^* P < 0.05 KE vs. CON at time points indicated; ^# P < 0.05 vs. PRE for both KE and CON; ^§ P < 0.05 vs. pre‐ex for the indicated group.

Figure 3. Effect of ketone ester supplementation on training workload

A, individual data points together with means ± SEM representing total work output per week. B, means ± SEM for work output per training session in subjects receiving either control (○/bars, n = 9) or ketone ester (●/bars, n = 9) supplements. The subjects performed 28 training sessions over a 3‐week training period. ^* P < 0.05 KE vs. CON at time points indicated; ^# P < 0.05 vs. PRE for both KE and CON.

Figure 4. Effect of ketone ester supplementation on exercise performance

Data are means ± SEM. A and B, mean power output during the 30 min simulated time‐trial (TT_30min) (A) and in a 90 s all‐out cycling bout (90S) (B) before (Pre) and at the end of weeks 1 (Week 1), 2 (Week 2) and 3 (Week 3) of the training period, and after 3 (Day +3) and 7 (Day +7) days of recovery. C, mean power output in the final half an hour of a 120 min endurance performance test (EPT_120min) on day 18 of the training period. Subjects received either control (○/open bars, n = 9) or ketone ester (●/filled bars, n = 9) during each training session. ^* P < 0.05 KE vs. CON; ^# P < 0.05 vs. PRE for both KE and CON; ^§ P < 0.05 vs. PRE for indicated group.

Figure 5. Effect of ketone ester supplementation on heart rate

Data are means ± SEM and represent changes in resting (HR_Rest), submaximal (HR_Submax) and maximal (HR_Max) heart rate before (Pre), and at the end of weeks 1 (Week 1), 2 (Week 2) and 3 (Week 3) of the training period, and after 3 (Day +3) and 7 (Day +7) recovery days. Subjects received either control (○, n = 9) or ketone ester supplements (●, n = 9) following each training session. ^* P < 0.05 KE vs. CON; ^# P < 0.05 vs. PRE for both KE and CON; ^§ P < 0.05 vs. PRE for indicated group.

Figure 6. Effect of ketone ester supplementation on urinary catecholamine excretion

Data are means ± SEM for urinary (A) adrenaline and (B) noradrenaline excretion before (Pre) and at the end of weeks 1 (Week 1), 2 (Week 2) and 3 (Week 3) of the training period, and after 3 (Day +3) and 7 (Day +7) days of recovery after training. Subjects received either control (○, n = 9) or ketone ester supplements (●, n = 9) following each training session. ^* P < 0.05 KE vs. CON; ^# P < 0.05 vs. PRE for both KE and CON; ^§ P < 0.05 vs. PRE for indicated group.

Figure 7. Effect of ketone ester supplementation on ‘appetite’ hormones involved in energy balance regulation

Data are means ± SEM and represent changes in (A) GDF15 and (B) leptin concentration before (Pre), after 1 (Week 1), 2 (Week 2) and 3 (Week 3) weeks of training and following 3 (Day +3) and 7 (Day +7) days of recovery. Subjects received either control (○, n = 9) or ketone ester supplements (●, n = 9) during the training period. ^* P < 0.05 KE vs. CON; ^# P < 0.05 vs. PRE for both KE and CON; ^§ P < 0.05 vs. PRE for indicated group.

Figure 8. Relationship between GDF15 and maximal heart rate

Correlation analyses showing a strong negative correlation between alterations in maximal heart rate (∆HR_max) and both (A) absolute and (B) delta GDF15 during the training period. Individual data points represent changes after 1 (Week 1), 2 (Week 2) and and 3 (Week 3) weeks of training, compared to pre‐test values.