Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans.

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-ßHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-ßHB 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-ßHB 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-ßHB 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-ßHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-ßHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-ßHB 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-ßHB 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.

Acute beetroot juice supplementation improves exercise tolerance and cycling efficiency in adults with obesity.

BACKGROUND: Exercise training improves health outcomes in individuals with obesity (IO); however, it remains challenging for IO to adhere to exercise. Thus, it is critical to identify novel strategies that improve exercise tolerance (ET) and adherence in IO. Beetroot juice (BRJ), high in inorganic dietary nitrate, consistently improves exercise performance in athletes, individuals with cardiopulmonary diseases, and nonobese lean individuals. These improvements may be explained by reduced oxygen uptake (VO2 ) during exercise, enhanced blood flow, and greater mitochondrial efficiency. To date, we are aware of no studies that have compared the effects of BRJ, sodium nitrate (NaNO3), and nitrate-depleted BRJ (PLA) for improving ET and cardiometabolic health in IO. PURPOSE: Determine if BRJ improves ET, exercise efficiency (EE), and cardiometabolic health in IO and identify possible mechanisms of action. METHODS: Vascular hemodynamic, submaximal- and maximal-exercise VO2 , and time to exhaustion (TTE) were assessed in 16 participants 2.5 hr following consumption of: 1) BRJ, 2) NaNO3 , 3) PLA, or 4) CON. RESULTS: A significant treatment effect was observed for submaximal exercise VO2 (p = .003), and TTE (p < .001). Post hoc analyses revealed lower VO2 during submaximal exercise in BRJ compared to PLA (p = .009) NaNO3 (p = .042) and CON (0.009), equating to an average improvement of ~ 7% with BRJ. TTE was greater for BRJ compared to other treatment arms, PLA (p = .008), NaNO3 (p = .038), and CON (p=<0.001), equating to ~ 15% improvement with BRJ. No significant changes were observed for other outcomes. CONCLUSIONS: Consumption of BRJ improved EE during submaximal exercise by 7%, and TTE by 15% compared to other conditions. These results suggest that BRJ may improve EE and exercise tolerance in IO.

Increased vitamin D is associated with decline of naïve, but accumulation of effector, CD8 T cells during early aging.

Given the protective roles of 25-hydroxyvitamin D (25[OH]D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, intensive repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the highest levels of the vitamin D receptor compared with other major immune cells. The effects of vitamin D on CD8 T cells during aging, however, remain unclear. This study determined the relationship between vitamin D levels and CD8 T-cell status in 34 healthy female subjects (all >60 years old). The CD8 T cell phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D serum groups (≤30 ng/ml) had higher percentages of CD28+CD95-CD8+ (naïve) T cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast, subjects with high levels of 25(OH)D had very low percentages of naïve CD8 T cells but very high percentages of effector CD8 T cells. There was a significant inverse correlation between 25(OH)D levels and the frequency of naïve CD8 T cells. The results show that higher levels of vitamin D are correlated with decreased frequencies of naïve CD8 T cells during early aging, suggesting that higher levels of 25(OH)D accelerate CD8 T-cell senescence. These results warrant the further evaluation of the effects of vitamin D supplementation in immune aging.