Exogenous ketosis can improve psychocognitive functioning during exercise as well as stimulate postexercise muscular recovery. Therefore, we hypothesized that ketone ester (KE) supplementation can counteract the decline in psychocognitive functioning during ultra-endurance exercise and stimulate muscular recovery. Eighteen recreational runners participated in a full 100 km trail run (RUN, = 8), or ran to premature exhaustion (80 km: = 6; 60 km: = 4). Before (25 g), during (25 g·h), and after (5 × 25 g in 24 h) RUN they received ketone ester ()-3-hydroxybutyl ()-3-hydroxybutyrate (KE, = 9) supplements or a noncaloric placebo (CON, = 9). Blood samples and muscle biopsies were taken, and mental alertness was assessed by a psychocognitive test battery at different times before, during, and up to 36 h after RUN. Compared with CON (<0.3 mM), in KE blood d-β-hydroxybutyrate concentration was consistently elevated to ∼2-3 mM during RUN. In CON, RUN increased visual reaction times from 353 ± 53 to 419 ± 54 ms, and movement execution times from 174 ± 47 to 245 ± 64 ms. But this effect was fully negated by KE ( < 0.05). Plasma dopamine concentrations doubled in KE during RUN but remained stable in CON, resulting in higher concentrations after RUN in KE (4.1 ± 1.7 nM) than in CON (2.4 ± 0.8 nM, = 0.048). KE also inhibited muscular infiltration of macrophages and suppressed AMPK phosphorylation status until 36-h postexercise ( < 0.05 KE vs. CON). In conclusion, KE increases circulating dopamine concentration and improves mental alertness, as well as improves postexercise muscular inflammation in ultra-endurance exercise. Oral ketone ester ingestion elevates circulating dopamine concentration during ultra-endurance exercise. This is associated with improved mental alertness. Furthermore, ketone ester intake inhibits postexercise skeletal muscle macrophage infiltration, and counteracts the increase in AMPK phosphorylation after exercise, which indicates improved muscular energy status.
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