4. Discussion
gastrointestinal distress
ADVERSE EFFECTS, SECONDARY
The purpose of the current investigation was to examine the tolerability and acceptability of a KME and KMES drink and their effects on circulating R-βHB and glucose concentrations in healthy young adults. Our hypothesis was that KME would raise circulating ketone concentrations to a greater magnitude and duration than KMES and PC. Both KME and KMES increased circulating R-βHB concentrations in a dose-dependent fashion with KME producing a more rapid rise than KMES at 15 min with similar responses by 30 min. Both total and incremental AUC for R-βHB concentrations were significantly higher for KME10 compared with KMES10 and PC. This supports part of our hypothesis, as KME raised circulating ketone concentrations to a greater magnitude than KMES and PC. However, duration was similar between KME and KMES, as concentrations decreased in a similar fashion and reached baseline by 120 min. Our secondary hypothesis was that KMES would have higher acceptability but lower tolerability compared with KME due to its unpleasant flavor and higher salt load. Supporting part of this hypothesis, acceptability was slightly lower for KME due to its more frequently reported aftertaste. However, reported adverse effects did not noticeably differ between exogenous ketone drinks.The dosage amounts in the present study were approximately 74.5 ± 14.8 mg/kg body weight (BW) for the 5 g doses and 149.1 ± 29.6 mg/kg BW for the 10 g doses when accounting for the weight of all participants. At a similar dosage to the highest concentration used in the present study, Stubbs and colleagues administered KME at 141 mg/kg body weight while fasting in healthy participants [A study by Veech and colleagues examined the effects of KME in healthy participants at a similar dose (140 mg/kg BW) [While we did not observe a statistically significant reduction in circulating glucose concentrations with the ketone drinks at either concentration, we found a negative correlation between R-βHB and glucose at 30 min for each condition except KME10. A similar effect was found in the study by Stubbs and colleagues, where both exogenous ketone drinks significantly decreased circulating glucose from 5.7 to 4.8 mM at one hour following administration [Although both exogenous ketone drinks had “unpleasant” flavor reported, the KME drink in the current study was slightly less acceptable than the KMES drink due to its more frequently reported aftertaste. To the best of our knowledge, previous studies have not characterized the flavor of exogenous ketone products. However, a limited number of studies have examined tolerability and noted mild adverse effects such as gastrointestinal distress [In the present study, participants were not required to alter their regular diet or exercise routine. As a result, the participants had diverse diet and exercise regimens. Future studies should aim to characterize the effects of meals, meal composition, and various forms of exercise on circulating concentrations of R-βHB. Understanding these effects will help define how exogenous ketones may affect consumers who are consuming ketone products on a regular basis. This study also applied what we determined was a more practical approach to dosing exogenous ketones, as drinks were provided in absolute amounts of total ketones as opposed to being dosed according to individual body mass. While there are disadvantages to this approach, namely that differences in body mass are likely to affect circulating concentrations, this strategy more realistically models how a consumer may purchase and utilize ketone products. Despite differences in body weight and sex within the study cohort, there were no significant differences in the magnitude of R-βHB observed. In fact, correlational analysis showed no significant associations between body weight or body weight normalized R-βHB concentrations at either dose for both exogenous ketones. Future studies are needed to determine if a relationship exists with higher doses of exogenous ketones.Additional studies are needed to investigate the acute, short-, and long-term effects of exogenous ketones, particularly as it relates to dosing, frequency of dosing, and duration of responses. It is possible that smaller, but more frequent, dosing not only can sustain higher concentrations but also can produce a scaffolding effect depending on when additional dosing occurs. Overall, single doses of the exogenous ketones used in this study increased circulating ketone concentrations rapidly and transiently. However, future studies that examine the effects of multiple doses of exogenous ketones are critical to establish the short- and long-term effects on circulating ketones to establish correlations between the magnitude and duration of circulating ketones on the outcomes desired. Circulating ketone concentrations reflect only a snapshot in time and do not fully appreciate absorption, uptake by central and peripheral tissues, and excretion, which are likely to play a significant role in the efficacy of certain outcomes desired.In the present study, KME increased R-βHB concentrations more rapidly than KMES, although peaks in R-βHB concentrations were similar for both. When consumed as repeated doses throughout the day, KME and KMES may achieve similarly sustained levels of R-βHB. Additionally, participants in the current study reported KMES as slightly more acceptable than KME.