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Exogenous ketone monoesters can raise blood β-OHB and lower glucose without other nutritional modifications or invasive procedures. However, unpleasant taste and potential gastrointestinal discomfort may make adherence to supplementation challenging. Two novel ketone supplements promise an improved consumer experience but differ in their chemical properties; it is currently unknown how these affect blood β-OHB and blood glucose compared to the ketone monoester. In a double-blind randomized cross-over pilot study, N=12 healthy individuals (29 ± 5 years, BMI = 25 ± 4 kg/m2, 42% female) participated in three experimental trials with a different ketone supplement providing 10 grams of active ingredient in each; (i) the monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, (ii) D-β-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood β-OHB and glucose were measured via finger prick capillary blood samples at baseline and across 240 minutes post-supplementation. Supplement acceptability, hunger, and gastrointestinal distress were assessed via questionnaires. β-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak β-OHB (p < 0.001) differed between conditions with highest values seen in the ketone monoester condition. Blood glucose was reduced after consumption of each supplement, with no differences in total and incremental area under the curve across supplements. Supplement acceptability was greatest for D-β-hydroxybutyric acid with R-1,3-butanediol, with no effect on hunger or evidence of gastrointestinal distress across all supplements. All ketone supplements tested raised β-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements. [ABSTRACT FROM AUTHOR]

In the workplace, people are often sedentary for prolonged time and do not regularly engage in physical activity—two factors independently linked to premature morbidity and mortality. This study aimed to determine the receptivity of incorporating practical stair-climbing "exercise snacks" (Snacks; three isolated bouts of ascending 53–60 stairs performed sporadically throughout the day) into workplace settings compared to more traditional high-intensity interval training (HIIT; performed as three bouts of 53-60 stairs within a structured HIIT workout) and to explore if these exercise strategies could influence sedentary and physical activity behaviour. Fourteen participants (12 women; Mage = 38.9 ± 10.2 years) completed two supervised exercise trials (Snacks and HIIT) followed by 1 week participating in either form of exercise in their workplace. Ratings of perceived exertion (RPE), affective valence, enjoyment, and self-efficacy were measured at the supervised exercise sessions. During the follow-up period, sedentary behaviour and physical activity were measured with an accelerometer. Affective valence was more positive (p = 0.03; η2p = 0.21) and there was a lower rise in RPE (p = 0.01; η2p = 0.29) during Snacks than HIIT. Post-exercise enjoyment of, and self-efficacy towards, Snacks and HIIT were high and similar (ps > 0.05). After the supervised trials, 10/14 of the participants preferred Snacks and 4/14 preferred HIIT (p = 0.18). On days when participants chose to perform either exercise modality, the average number of sit-to-stands in a 24 h period was increased (48.3 ± 8.7 to 52.8 ± 7.8; p = 0.03; Hedge's g = 0.73) and moderate-to-vigorous physical activity tended to increase (21.9 ± 18.2 to 38.1 ± 22.1 min; p = 0.06; Hedge's g = 0.60) compared to days when they chose not to exercise. Stair-climbing exercise snacks may be an attractive approach to implement in the workplace setting and has potential to positively impact sedentary behaviour and physical activity metrics. [ABSTRACT FROM AUTHOR]

Acute ingestion of the exogenous ketone monoester supplement [(R)-3-hydroxybutyl-(R)-3-hydroxybutyrate] lowers blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, it is unknown how acute or repeated ingestion of exogenous ketones affects blood glucose control in individuals with type 2 diabetes (T2D). We conducted two randomized, counterbalanced, double-blind, placebo-controlled crossover trials to determine if 1) acute exogenous ketone monoester (0.3 g/kg body mass; N = 18) or 2) 14-day thrice daily premeal exogenous ketone monoester (15 g; N = 15) supplementation could lower blood glucose in individuals living with T2D. A single dose of the ketone monoester supplement elevated blood β-OHB to ×2 mM. There were no differences in the primary outcomes of plasma glucose concentration (acutely) or serum fructosamine (glycemic control across 14 days) between conditions. Ketone monoester ingestion acutely increased insulin and lowered nonesterified fatty acid concentrations; plasma metabolomics confirmed a reduction in multiple free fatty acids species and select gluconeogenic amino acids. In contrast, no changes were observed in fasting metabolic outcomes following 14 days of supplementation. In the context of these randomized controlled trials, acute or repeated ketone monoester ingestion in adults with T2D did not lower blood glucose when consumed acutely in a fasted state and did not improve glycemic control following thrice daily premeal ingestion across 14 days. Future studies exploring the mechanistic basis for the (lack of) glucose-lowering effect of exogenous ketone supplementation in T2D and other populations are warranted. NEW & NOTEWORTHY: Exogenous ketone supplements can acutely lower blood glucose, suggesting therapeutic potential in individuals with impaired glucose metabolism. However, the effect of exogenous ketones on glucose metabolism in adults with type 2 diabetes has not been investigated in a controlled setting. In adults with type 2 diabetes, ketone monoester ingestion did not lower blood glucose acutely in a fasted state and did not improve glycemic control across thrice daily premeal ingestion across 14 days. [ABSTRACT FROM AUTHOR]

High-intensity interval training (HIIT) has garnered attention in recent years as a time-efficient exercise option for improving cardiovascular and metabolic health. New research demonstrates that HIIT may be particularly effective for improving postprandial hyperglycemia in individuals with, or at risk for, type 2 diabetes (T2D). These findings have clinical relevance because elevated postprandial hyperglycemia is a significant risk factor for cardiovascular morbidity and mortality. This article summarizes the latest evidence demonstrating that HIIT can improve postprandial glucose control to highlight the potential application of HIIT in the prevention and management of T2D and associated cardiovascular complications.

New Findings: What is the topic of this review?The integrative physiological response to exogenous ketone supplementation.What advances does it highlight?The physiological effects and therapeutic potential of exogenous ketones on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. Also highlighted are current challenges and future directions of the field. Exogenous oral ketone supplements, primarily in form of ketone salts or esters, have emerged as a useful research tool for manipulating metabolism with potential therapeutic application targeting various aspects of several common chronic diseases. Recent literature has investigated the effects of exogenously induced ketosis on metabolic health, cardiovascular function, cognitive processing, and modulation of inflammatory pathways and immune function. This narrative review provides an overview of the integrative physiological effects of exogenous ketone supplementation and highlights current challenges and future research directions. Much of the existing research on therapeutic applications – particularly mechanistic studies – has involved pre‐clinical rodent and/or cellular models, requiring further validation in human clinical studies. Existing human studies report that exogenous ketones can lower blood glucose and improve some aspects of cognitive function, highlighting the potential therapeutic application of exogenous ketones for type 2 diabetes and neurological diseases. There is also support for the ability of exogenous ketosis to improve cardiac metabolism in rodent models of heart failure with supporting human studies emerging; long‐terms effects of exogenous ketone supplementation on the human cardiovascular system and lipid profiles are needed. An important avenue for future work is provided by research accelerating technologies that enable continuous ketone monitoring and/or the development of more palatable ketone mixtures that optimize plasma ketone kinetics to enable sustained ketosis. Lastly, research exploring the physiological interactions between exogenous ketones and varying metabolic states (e.g., exercise, fasting, metabolic disease) should yield important insights that can be used to maximize the health benefits of exogenous ketosis. [ABSTRACT FROM AUTHOR]