Ketone monoester reduces blood glucose, exogenous CHO oxidation, and oxidation efficiency in trained male cyclists when fed 120 g/h of CHO during exercise.

We examined the effects of ketone monoester (KME) and carbohydrate (CHO) coingestion on exogenous CHO oxidation (via U-13C-enriched glucose-fructose drinks), metabolomic responses, and exercise capacity. In a randomized crossover design (after 36 h of CHO loading and pre-exercise meal of 12 and 2 g·kg-1, respectively), eight trained male cyclists (V̇o2max; 66 ± 7 mL·kg-1·min-1) ingested 0 g·h-1 (PLA), 120 g·h-1 CHO (CHO), or 120 g·h-1 CHO + 75-g ketone monoester (CHO + KME) during 3 h of cycling at power outputs corresponding to 95% of lactate threshold (LT) followed by exercise to exhaustion at 150% LT. Mean blood glucose concentrations during exercise were different between all pairwise comparisons (P < 0.05) such that CHO > CHO + KME > PLA (4.9 ± 0.3, 4.4 ± 0.2, 3.7 ± 0.4 mmol·L-1, respectively). Mean exogenous CHO oxidation (1.35 ± 0.15 vs. 1.50 ± 0.16 g·min-1, P < 0.01) and oxidation efficiency was lower in CHO + KME (67 ± 7%) compared with CHO (75 ± 6%, P < 0.01). Exercise capacity was greater (P < 0.05) in CHO (349 ± 189 s) and CHO + KME (319 ± 225 s) compared with PLA (75 ± 105 s), though no differences were evident between CHO and CHO + KME (P > 0.05). Ketone monoester ingestion increased abundance of metabolites associated with carbohydrate metabolism (glucaric acid) and protein turnover (3-methylhistidine). We conclude that ketone monoester ingestion does not enhance exercise capacity and reduces blood glucose concentrations, exogenous CHO oxidation, and oxidation efficiency when compared with CHO alone.NEW & NOTEWORTHY To promote exercise performance, endurance athletes frequently consume CHO during exercise at ingestion rates of 90-120 g·h-1. Here, we report for the first time that coingestion of a ketone monoester before and during prolonged cycling reduces blood glucose concentrations, exogenous CHO oxidation, and oxidation efficiency compared with CHO alone (120 g·h-1; 1:0.8 ratio of maltodextrin and fructose). Ketone monoester ingestion also increased plasma abundance of metabolites associated with carbohydrate metabolism (glucaric acid) and protein turnover (3-methylhistidine).