Multisystem impact of altering acid load of ingested exogenous ketone supplements at rest in young healthy adults

Disruptions to acid-base are observed in extreme environments as well as respiratory and metabolic diseases. Exogenous ketone supplements (EKSs) have been proposed to mitigate these processes and provide therapeutic benefits by altering acid-base balance and metabolism, but direct comparison of various forms of EKS is lacking. Twenty healthy participants (M/F: 10/10; age: 20.6 ± 2.0 yr, height: 1.72 ± 0.08 m, body mass: 67.9 ± 10.2 kg) participated in a single-blind, randomized crossover design comparing ingestion of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (R-BD R-βHB) ketone monoester (KME), KME + sodium bicarbonate (KME + BIC), an R-βHB ketone salt (KS), and a flavor-matched placebo. Acid-base balance, blood R-βHB, glucose and lactate concentrations, blood gases, respiratory gas exchange, autonomic function, and cognitive performance were assessed at baseline and various timepoints for up to 120 min after ingestion. Compared with placebo (PLA), blood R-βHB concentrations were elevated in each EKS condition (∼2-4 mM; P < 0.01), and blood glucose concentrations were lower. Blood pH was lower in KME (-0.07 units), and higher in KS and KME + BIC (+0.05 units), compared with PLA (all P < 0.05). Heart rate was elevated, and autonomic function was altered in KME + BIC. There were no differences between conditions for blood gases, respiratory gas exchange, blood pressure, or cognitive performance. Exploratory analyses of between-sex differences demonstrated males and females responded similarly across all outcome measures. Altering the acid load of EKS modulated the response of blood R-βHB and glucose concentrations but had only modest effects on other outcome measures at rest in young healthy adults, with no differences observed between sexes.NEW & NOTEWORTHY Altering the acid load of ingested exogenous ketone supplements altered post-ingestion responses of circulating glucose and R-βHB concentrations, heart rate, and autonomic function, but did not alter blood gases, respiratory gas exchange, blood pressure, or cognitive performance at rest in young healthy adults.