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Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters.

ABSTRACT: Background:Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols. Methods:Thirteen recreational male distance runners (24.8?±?9.6 years, 72.5?±?8.3 kg, VO2max 60.1?±?5.4 ml/kg/min) participated in this randomized, double-blind, crossover design study. The first two sessions consisted of a 5-km running time trial familiarization and a VO2max test. During subsequent trials, subjects were randomly assigned to one (KS1: 22.1 g) or two (KS2: 44.2 g) doses of beta-hydroxybutyrate (?HB) and medium chain triglycerides (MCTs) or flavor matched placebo (PLA). Blood R-?HB, glucose, and lactate concentrations were measured at baseline (0-min), post-supplement (30 and 60 min), post-exercise (+?0 min, +?15 min). Time, heart rate (HR), rating of perceived exertion (RPE), affect, respiratory exchange ratio, oxygen consumption (VO2), carbon dioxide production, and ventilation were measured during exercise. Cognitive performance was evaluated prior to and post-exercise. Results:KS significantly increased R-?HB, with more potent and prolonged elevations in KS2, illustrating an administrative and dosing effect. R-?HB was significantly decreased in KS1 compared to KS2 illustrating a dosing and exercise interaction effect. Blood glucose elevated post-exercise but was unchanged across groups. Blood lactate significantly increased post-exercise but was augmented by KS administration. Gaseous exchange, respiration, HR, affect, RPE, and exercise performance was unaltered with KS administration. However, clear responders and none-responders were indicated. KS2 significantly augmented cognitive function in pre-exercise conditions, while exercise increased cognitive performance for KS1 and PLA to pre-exercise KS2 levels. Conclusion:Novel ?HB?+?MCT formulation had a dosing effect on R-?HB and cognitive performance, an administrative response on blood lactate, while not influencing gaseous exchange, respiration, HR, affect, RPE, and exercise performance.

SUBMITTER: Prins PJ

PROVIDER: S-EPMC7523040 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters.

Prins Philip J PJ D'Agostino Dominic P DP Rogers Christopher Q CQ Ault Dana L DL Welton Gary L GL Jones Dalton W DW Henson Samuel R SR Rothfuss Tyler J TJ Aiken Kylie G KG Hose Jantzen L JL England Emilia L EL Atwell Adam D AD Buxton Jeffrey D JD Koutnik Andrew P AP

Nutrition & metabolism 20200929

<h4>Background</h4>Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to their multifaceted physiological and signaling properties but limiting our understanding is the isolated analyses of individual types and dose/dosing protocols.<h4>Methods</h4>Thirteen recreational male distance runners (24.8 ± 9.6 years, 72.5 ± 8.3 kg, VO<sub>2max</sub> 60.1 ± 5.4 ml/kg/min) participated in this randomized, double-blind, crossover design study. The ...[more]

PMID: 33005207

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Project description:Exogenous ketone ester and ketone ester mixed with ketone free acid formulations are rapidly entering the commercial marketspace. Short-term animal and human studies using these products suggest significant potential for primary or secondary prevention of a number of chronic disease conditions. However, a number of questions need to be addressed by the field for optimal use in humans, including variable responses among available exogenous ketones at different dosages; frequency of dosing; and their tolerability, acceptability, and efficacy in long-term clinical trials. The purpose of the current investigation was to examine the tolerability, acceptability, and circulating R-beta-hydroxybutyrate (R-βHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-βHB compared with placebo control (PC). Fourteen healthy young adults (age: 21 ± 2 years, weight: 69.7 ± 14.2 kg, percent fat: 28.1 ± 9.3%) completed each of the five study conditions: placebo control (PC), 5 g KME (KME5), 10 g KME (KME10), 5 g (KMES5), and 10 g KMES (KMES10) in a randomized crossover fashion. Circulating concentrations of R-βHB were measured at baseline (time 0) following an 8-12 h overnight fast and again at 15, 30, 60, and 120 min following drink ingestion. Participants also reported acceptability and tolerability during each condition. Concentrations of R-βHB rose to 2.4 ± 0.1 mM for KME10 after 15 min, whereas KMES10 similarly peaked (2.1 ± 0.1 mM) but at 30 min. KME5 and KMES5 achieved similar peak R-βHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-βHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-βHB and glucose at the 30 min time point for each condition except KME10 and PC. Tolerability was similar among KME and KMES, although decreases in appetite were more frequently reported for KMES. Acceptability was slightly higher for KMES due to the more frequently reported aftertaste for KME. The results of this pilot investigation illustrate that the KME and KMES products used increase circulating R-βHB concentrations to a similar extent and time course in a dose-dependent fashion with slight differences in tolerability and acceptability. Future studies are needed to examine variable doses, frequency, and timing of exogenous ketone administration for individuals seeking to consume ketone products for health- or sport performance-related purposes.

Project description:BackgroundInterest in therapeutic applications of exogenous ketones has grown significantly, spanning patients with heart failure to endurance athletes. Exogenous ketones engender significant effects on cardiac function in heart failure and provide an ergogenic benefit in athletes. The aim of this study was to assess the effects of exogenous ketones on cardiac function in healthy participants.MethodsIn a single-arm intervention study, 20 fasting, healthy participants underwent comprehensive echocardiography (two-dimensional, Doppler, and strain) before and 30 min after weight-based oral ketone ester administration. The relationship between changes in log-transformed biomarker levels and change in absolute global longitudinal strain (GLS) was assessed using linear regression.ResultsThe mean age was 30 ± 7 years, 50% were women, 45% were nonwhite, and the average body mass index was 24.3 ± 3.1 kg/m2. Ketone ingestion acutely elevated β-hydroxybutyrate levels from a median of 0.13 mmol/L (interquartile range, 0.10-0.37 mmol/L) to 3.23 mmol/L (interquartile range, 2.40-4.97 mmol/L) (P < .001). After ketone ester consumption, systolic blood pressure, heart rate, biventricular function, left ventricular GLS, and left atrial (LA) strain all augmented, while systemic vascular resistance decreased. Displayed as mean change, increases in ejection fraction (3.1%; 95% CI, 2.0%-4.2%; P < .001), GLS (2.0%; 95% CI, 1.4%-2.7%; P < .001), right ventricular S' (1.1 cm/sec; 95% CI, 0.4-1.8 cm/sec; P = .004), LA reservoir strain (7%; 95% CI, 3%-12%; P = .005), and LA contractile strain (4%; 2%-6%; P = .001) were observed. During robustly achieved ketosis, change in GLS was inversely associated with change in nonesterified fatty acids (P = .019).ConclusionsIn a single-arm study, systolic blood pressure, heart rate, biventricular function, and LV and LA strain acutely augmented after ketone ester ingestion in healthy, fasting participants, similar to several effects observed in the failing heart. These data may provide supporting data for the ergogenic benefits observed in athletes and may become increasingly relevant with exogenous ketone consumption across a variety of cardiovascular and noncardiovascular applications.

Project description:Salinity, a severe worldwide issue, compromises the economic production of medicinal plants including mints and causes drug-yield decline. γ-Aminobutyric acid (GABA) is a tolerance-inducing signaling bio-molecule in various plant physiological processes. Pineapple mint (Mentha suaveolens Ehrh.) is a valuable medicinal herb with an exhilarating scent of citrus fruit. Piperitenone oxide is the major bioactive constituent of its essential oil, having significant demand by pharmaceutical industries. Nonetheless, modeling and optimizing the effective concentration of GABA remain within twin foci of interest. Therefore, a two factor-five level (NaCl 0-150 mM and GABA 0-2.4 mM) central composite design was conducted to model and optimize drug yield and physiological responses of M. suaveolens. Based on the design of experiments (DoE) approach, different linear, quadratic, cubic, and quartic models were assigned to the response variables. Change trends of shoot and root dry weights followed a simple linear model, whereas sophisticated models (i.e., multiple polynomial regression) were fitted to the other traits. NaCl stress inevitably reduced root and shoot dry weight, piperitenone oxide content, relative water content, pigments content, and maximum quantum yield of PSII. However, content of malondialdehyde (MDA) and total flavonoid, and DPPH radical scavenging activity were increased under salinity. Under severe NaCl stress (150 mM), the essential oil content (0.53%) was increased three times in comparison with control (0.18%). Optimization analysis demonstrated that the highest amount of essential oil (0.6%) and piperitenone oxide (81%) as a drug yield-determining component would be achievable by application of 0.1-0.2 mM GABA under 100 mM NaCl. The highest dry weight of root and shoot was predicted to be achieved at 2.4 mM GABA. Overall, extremely severe NaCl stress (i.e., more than 100 mM) in which a sharp drop in yield components value was observed seemed to be out of M. suaveolens salinity tolerance range. Hence, it is rationale to compensate the decrease of drug yield by foliar application of a dilute GABA solution (i.e., 0.1-0.2 mM) under 100 mM NaCl stress or lower levels.

Project description:AimsRecent evidence has demonstrated that ketone bodies, particularly β-hydroxybutyrate (BHB), are beneficial to the failing heart due to their potential as an alternative energy substrate as well as their anti-inflammatory and anti-oxidative properties. Exogenous supplementation of ketones also helps prevent heart failure (HF) development in rodent models, but whether ketones can be used to treat HF remains unexplored. Herein, we investigated whether chronic supplementation of ketones is beneficial for the heart in a mouse model of established HF.Methods and resultsTo elevate circulating ketone levels, we utilized (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate [ketone ester (KE)]. C57Bl/6N male mice were subjected to transverse aortic constriction (TAC) surgery. After developing HF, mice were treated with either 20% KE or vehicle via drinking water for 2 weeks. In another cohort, mice 3-4 weeks post-TAC received acute intravenous infusions of BHB or saline for 1 h and their cardiac function was measured. 20% KE significantly elevated blood BHB in mice (P < 0.01) without inducing ketoacidosis or altering other metabolic parameters. Mice with overt HF (30-45% ejection fraction) treated with 20% KE displayed significantly elevated circulating ketone levels compared with vehicle-treated mice (P < 0.05). The significant cardiac dysfunction in mice with HF continued to worsen after 2 weeks of vehicle treatment, whereas this decline was absent in KE-treated mice (mean difference 4.7% ejection fraction; P < 0.01). KE treatment also alleviated TAC-induced cardiomyocyte hypertrophy (P < 0.05) and reduced the TAC-induced elevated cardiac periostin (P < 0.05), a marker of activated fibroblasts. Cardiac fibrosis was also significantly reduced with KE treatment in TAC mice (P < 0.01). In another cohort, acute BHB infusion significantly increased the cardiac output of mice with HF (P < 0.05), providing further support that ketone therapy can be used to treat HF.ConclusionsWe show that chronic treatment of exogenous ketones is of benefit to the failing heart and that chronic ketone elevation may be a therapeutic option for HF. Further investigations to elucidate the underlying mechanism(s) are warranted.

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Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters.

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Dose response of a novel exogenous ketone supplement on physiological, perceptual and performance parameters.

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