The Effect of Novel Exogenous Ketone Supplements on Blood Beta-Hydroxybutyrate and Glucose.

Exogenous ketone monoesters can raise blood ß-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 ß-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-ß-hydroxybutyric acid with R-1,3-butanediol, and (iii) R-1,3-butanediol. Blood ß-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. ß-OHB was elevated compared to baseline in all conditions. Total and incremental area under the curve (p < 0.05) and peak ß-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-ß-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 ß-OHB with highest values seen after ketone monoester ingestion. Blood glucose was lowered similarly across the assessed time frame with all three supplements.

Effects of Exogenous Ketone Supplementation on Blood Glucose: A Systematic Review and Meta-analysis.

Recently developed ketone (monoester or salt) supplements acutely elevate blood ß-hydroxybutyrate (BHB) exogenously without prolonged periods of fasting or carbohydrate restriction. Previous (small-scale) studies have found a blood glucose-lowering effect of exogenous ketones. This study aimed to systematically review available evidence and conduct meta-analyses of studies reporting on exogenous ketones and blood glucose. We searched 6 electronic databases on 13 December 2021 for randomized and nonrandomized trials of any length that reported on the use of exogenous ketones. We calculated raw mean differences (MDs) in blood BHB and glucose in 2 main analyses: 1) after compared with before acute ingestion of exogenous ketones and 2) following acute ingestion of exogenous ketones compared with a comparator supplement. We pooled effect sizes using random-effects models and performed prespecified subgroup analyses to examine the effect of potential explanatory factors, including study population, exercise, blood BHB, and supplement type, dosing, and timing. Risk of bias was examined using Cochrane's risk-of-bias tools. Studies that could not be meta-analyzed were summarized narratively. Forty-three trials including 586 participants are summarized in this review. Following ingestion, exogenous ketones increased blood BHB (MD = 1.73 mM; 95% CI: 1.26, 2.21 mM; P < 0.001) and decreased mean blood glucose (MD = -0.54 mM; 95% CI: -0.68, -0.40 mM; P < 0.001). Similarly, when compared with placebo, blood BHB increased (MD = 1.98 mM; 95% CI: 1.52, 2.45 mM; P < 0.001) and blood glucose decreased (MD = -0.47 mM; 95% CI: -0.57, -0.36 mM; P < 0.001). Across both analyses, significantly greater effects were seen with ketone monoesters compared with salts (P < 0.001). The available evidence indicates that acute ingestion of exogenous ketones leads to increased blood BHB and decreased blood glucose. Limited evidence on prolonged ketone supplementation was found.

L-Arginine Improves Endurance to High-Intensity Interval Exercises in Overweight Men.

The effects of acute consumption of L-Arginine (L-Arg) in healthy young individuals are not clearly defined, and no studies on the effects of L-Arg in individuals with abnormal body mass index undertaking strenuous exercise exist. Thus, we examined whether supplementation with L-Arg diminishes cardiopulmonary exercise testing responses, such as ventilation (VE), VE/VCO2, oxygen uptake (VO2), and heart rate, in response to an acute session of high-intensity interval exercise (HIIE) in overweight men. A double-blind, randomized crossover design was used to study 30 overweight men (age, 26.5 ± 2.2 years; body weight, 88.2 ± 5.3 kilogram; body mass index, 28.0 ± 1.4 kg/m2). Participants first completed a ramped-treadmill exercise protocol to determine VO2max velocity (vVO2max), after which they participated in two sessions of HIIE. Participants were randomly assigned to receive either 6 g of L-Arg or placebo supplements. The HIIE treadmill running protocol consisted of 12 trials, including exercise at 100% of vVO2max for 1 min interspersed with recovery intervals of 40% of vVO2max for 2 min. Measurements of VO2 (ml·kg-1·min-1), VE (L/min), heart rate (beat per min), and VE/VCO2 were obtained. Supplementation with L-Arg significantly decreased all cardiorespiratory responses during HIIE (placebo+HIIE vs. L-Arg+HIIE for each measurement: VE [80.9 ± 4.3 L/min vs. 74.6 ± 3.5 L/min, p < .05, ES = 1.61], VE/VCO2 [26.4 ± 1.3 vs. 24.4 ± 1.0, p < .05, ES = 1.8], VO2 [26.4 ± 0.8 ml·kg-1·min-1 vs. 24.4 ± 0.9 ml·kg-1·min-1, p < .05, ES = 2.2], and heart rate [159.7 ± 6.3 beats/min vs. 155.0 ± 3.7 beats/min, p < .05, d = 0.89]). The authors conclude consuming L-Arg before HIIE can alleviate the excessive physiological strain resulting from HIIE and help to increase exercise tolerance in participants with a higher body mass index who may need to exercise on a regular basis for extended periods to improve their health.

Acute L-Arginine supplementation does not affect red blood cell aggregation and deformability during high intensity interval exercise in healthy men.

BACKGROUND: L-Arginine, the precursor of NO might be involved in improving the cardiovascular disorders via regulation of functional properties of erythrocytes. OBJECTIVE: This study investigated the effects of L-Arginine supplementation on responses of red blood cell (RBC) properties to high intensity interval exercise (HIIE). METHODS: Ten overweight healthy men participated voluntarily in the study and performed two HIIE trials with and without L-Arginine in two separate weeks. The HIIE protocol included 12 intervals of 3-min encompassed 1-min running at 100% of vVO2max and 2-min active recovery at 40% of vVO2max. Three blood samples were taken before and after supplementation, and immediately after exercise; and were used to measure red blood cell properties. RESULTS: The HIIE protocol increased hematocrit, hemoglobin and lactate significantly (P < 0.05), but had no significant effect on RBC aggregation, RBC deformability, and fibrinogen concentration. When data were compared for two trials no significant differences between the responses of RBC properties to two HIIE protocols were detected (P > 0.05), whereas the increases in lactate concentration following HIIE was significantly lower in L-Arginine than placebo trial (P < 0.05). CONCLUSIONS: It is concluded that L-Arginine consumption prior to HIIE does not lead to any improvement in RBC properties during HIIE in overweight healthy men.