TABLE 1.
Summary of the human studies assessing the effects of ketone supplements on exercise performance, cognition during or after exertion, or postexercise recovery
| Study (reference) | Participants | Acute/chronic1 | Supplementation | Control intervention | Exercise | Main results (ketones vs. control) |
|---|---|---|---|---|---|---|
| Cox et al. (3)2 | 8 endurance athletes | Acute | Ketone ester (573 mg/kg body weight) and dextrose before exercise, under fasting conditions | Taste- and color-matched CHO drink | 1-h steady-state workload at 75% of Wmax followed by a 30-min TT | ↑ Performance;↑ plasma D-βHB,↓ FFA, glucose, and lactate during exercise |
| Dearlove et al. (10) | 12 trained participants | Acute | Ketone ester [330 mg/kg body weight of (R)-3-hydroxybutyrate (R)-1,3-butanediol] before exercise, under fasting conditions | Noncaloric drink (bitter-flavored water) | Incremental cycle test to exhaustion | ↔ Performance;↑ plasma D-βHB after exercise;↑ workload at OBLA;↓ plasma glucose and lactate during exercise |
| Evans et al. (21) | 19 trained cyclists | Acute | Ketone salts (380 mg/kg body weight) 60 and 15 min before exercise, under fasting conditions | Water | Incremental cycle exercise up to 80% of VO2peak | ↑ Plasma D-βHB;↓ glucose before and during exercise;no changes in indirect markers of performance |
| Evans and Egan (11) | 11 male team sport athletes | Acute | Ketone ester [750 mg/kg body weight of R-βHB (R)1,3-butanediol] and CHO before exercise, under fasting conditions | Taste-matched CHO solution | Loughborough intermittent shuttle test [5 × 15 min of intermittent activity followed by shuttle run to exhaustion (lasting ∼4 min)] | ↔ Performance;↑ plasma D-βHB;↓ plasma glucose and lactate during exercise;↑ cognition |
| Evans et al. (12) | 8 endurance-trained runners | Acute | Ketone ester (573 mg/kg body weight) and CHO before and during exercise, under fed conditions | Taste-matched CHO solution | 1 h of submaximal exercise [∼65% of VO2max) followed by a 10-km running TT (∼40 min)] | ↔ Performance;↑ plasma D-βHB during exercise;↔ cognition |
| Faull et al. (13) | 12 trained participants | Acute | Ketone ester [330 mg/kg body weight of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] before exercise, under fasting conditions | Noncaloric drink (bitter-flavored water) | Incremental cycle test to exhaustion | ↔ Performance;↑ plasma D-βHB before exercise |
| Holdsworth et al. (22) | 12 well-trained male athletes | Acute | Ketone ester [0.573 mL/kg body weight of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] under fasting conditions after a glycogen-depleting exercise protocol | Noncaloric drink with sweeteners and citrus flavoring | Intermittent exercise alternating 2-min intervals at 90% and 50% PPO; workload was decreased progressively by 10% PPO as fatigue appeared, until exhaustion (60% PPO) | ↑ Plasma D-βHB after exercise;↑ glucose uptake and endogenous insulin concentration;↑ muscle glycogen content |
| James and Kjerulf Greer (23) | 10 non–aerobically trained participants | Acute | 11,700 mg of ketone salts taken together with decarbonated, noncaffeinated diet cola before exercise after a fast ≥4 h | Decarbonated, noncaffeinated diet cola | Two 6-min stages of the Bruce protocol | ↔ Performance;↑ plasma D-βHB concentration before and after exercise |
| Leckey et al. (19) | 11 male internationally competitive cyclists | Acute | Ketone ester (250 mg/kg body weight of 1,3-butanediol acetoacetate diester) 30 min and immediately before exercise, under fed conditions | Viscosity- and color-matched drink with bitter flavor | 31-km TT on a cycling ergometer (∼50-min duration) | ↓ Performance;↓ plasma FFAs, glucose and lactate;↑ plasma acetoacetate and D-βHB during exercise |
| O'Malley et al. (20) | 10 healthy, recreationally active males | Acute | Ketone salts (300 mg/kg body weight) with lemon juice and stevia 30 min before exercise, under fasting conditions | Lemon juice and stevia | Steady-state exercise at 30%, 60%, and 90% of VT followed by a 150-kJ cyclingTT (∼11-min duration) | ↓ Performance;↑ D-βHB and total fat oxidation during exercise;↓ plasma glucose and total CHO oxidation during exercise |
| Poffé et al. (24) | 18 physically active males | Chronic | Ketone ester [25 g of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] after each exercise session and 30 min presleep during an intensive 3-wk training program, provided along with a 500-mL high-dose protein-carbohydrate drink following exercise | Isocaloric bitter drink containing16.4 g pure medium-chain triglycerides, provided along with a 500-mL high-dose protein-CHO drink following exercise | 3 wk of exercise training that aimed at inducing functional overreaching (2 sessions/d, 6 d/wk) | ↑ Plasma D-βHB 30 min postexercise↑ training workload in week 3;↑ TT performance;↔ body composition;↓ markers of overreaching (e.g., plasma GDF15 concentrations, urinary catecholamine excretion, and heart rate decrease) |
| Poffé et al. (14) | 12 highly trained male cyclists | Acute | Ketone ester [65 g of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] provided in 3 boluses ingested 60 and 20 min before exercise, and at minute 30 during the exercise protocol; supplement was provided under fed conditions and subjects ingested CHO before and during exercise (60 g/h) | Viscosity- and taste-matched supplement (with less caloric content than the ketone supplement); subjects ingested CHO before and during exercise | Simulated cycling race consisting of 3 h of submaximal intermittent cycling followed by a 15-min TT and an all-out sprint | ↔ Performance;↑ plasma and urine D-βHB;↓ plasma glucose following ketone ingestion;↓ FFAs during exercise;↔ plasma lactate;↓ blood pH and bicarbonate concentration during submaximal exercise;↔ muscle glycogen and intramyocellular triglyceride content and breakdown |
| Poffé et al. (25) | 9 well-trained male cyclists | Acute | Ketone ester [65 g of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] provided in 3 boluses | Viscosity- and taste-matched supplement; subjects ingested CHO before and during exercise (60 g/h) | Simulated cycling race consisting of 3 h of submaximal intermittent cycling followed by a 15-min | ↑ TT performance (only when provided with bicarbonate);↔ sprint performance;↑ plasma and urine D-βHB; |
| ingested 60 and 20 min before exercise, and at minute 30 during the exercise protocol; supplement was provided under fed conditions and subjects ingested CHO before and during exercise (60 g/h); the ketone ester supplement was provided with and without bicarbonate (300 mg/kg) | TT and an all-out sprint | ↔ blood glucose and lactate;↓ blood pH and bicarbonate concentration, but prevented with bicarbonate | ||||
| Rodger et al. (15) | 12 highly trained male cyclists | Acute | Ketone salts (11,700 mg) with sugar-free lemonade 20 min before and during exercise, after a fast ≥2.5 h | Taste-matched placebo diluted in sugar-free lemonade | Submaximal cycling (80% VT2) for 90 min followed by a 4-min TT | ↔ Performance;↑ plasma D-βHB and RER during exercise |
| Scott et al. (16) | 11 male runners | Acute | Ketone ester (500 mg/kg body weight of 1,3-butanediol) and CHO, under fasting conditions75% was taken before submaximal exercise, and 25% before the TT | Caloric-matched CHO drink | 60 min of submaximal running (75% VO2max) followed by a 5-km running TT (∼21-min duration) | ↔ Performance;↑ plasma D-βHB;↓ lactate during exercise |
| Shaw et al. (17) | 9 trained male cyclists | Acute | Ketone ester (350 mg/kg body weight of 1,3-butanediol) with an orange-flavored drink 30 min before exercise and again 60 min during submaximal exercise, after a fast ≥4 h | Orange-flavored drink | 85 min of submaximal exercise (85% of VT2) followed by a 7-kJ/kg TT (∼29 min) | ↔ Performance;↑ plasma D-βHB after exercise |
| Vandoorne et al. (26) | 8 healthy trained males | Acute | Ketone ester [0.5 g/kg body weight of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate] immediately after a glycogen-depleting exercise protocol and 0.25 g/kg/h thereafter for 5 h; the supplement was provided in the fed state and along with a CHO/protein recovery drink | Isocaloric supplement of long-chain triglycerides that was similar in taste and appearance, provided along with the same recovery drink as in the experimental condition | Unilateral knee extensions at the highest power output possible for 5 min, 9 series of 30 extensions at 30%1RM, and 5 series of 6 extensions at 70%1RM | ↑ Plasma D-βHB;↓ plasma glucose;↔ plasma insulin;↑ mTORC1 activation (higher phosphorylation status ofS6K1 and 4EBP1);↓ AMPK activation;↔ glycogen resynthesis |
| Waldman et al. (18) | 15 healthy, recreationally active males | Acute | Ketone salts (11,380 mg of D-ßHB) 30 min before exercise, under fed conditions | Caloric-matched drink with similar taste and smell | Four 15-s cycling sprints | ↔ Performance;↑ plasma D-βHB after exercise;↔ cognition |
Note: for simplicity purposes, only the main results related to performance and to significant changes in physiological changes are shown. AMPK, AMP-activated protein kinase; CHO, carbohydrate; D-βHB, D-β-hydroxybutyrate; FFA, free fatty acid; GDF15, growth differentiation factor 15; mTOR1, mammalian target or rapamycin; OBLA, onset of blood lactate accumulation; PPO, peak power output; RER, respiratory exchange ratio; RPE, rating of perceived exertion; S6K1 (ribosomal protein S6 kinase β1, also known as p70S6 kinase); TT, time trial; VO2max, maximal oxygen uptake; VO2peak, peak oxygen uptake; VT, ventilatory threshold; VT2, second ventilatory threshold; Wmax, maximal power output; 1RM, 1 repetition maximum; 4EBP1, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1; ↑, increase; ↔, no change; ↓, decrease.
1
“acute” refers to supplementation before or during an acute exercise bout only, whereas “chronic” refers to repeated supplementation over days.
2
The study by Cox et al. included several experiments, but only the one reporting performance measures is shown in the table.