14-Day Ketone Supplementation Lowers Glucose and Improves Vascular Function in Obesity: A Randomized Crossover Trial

• Published in: The journal of clinical endocrinology and metabolism Vol. 106; no. 4; pp. e1738 - e1754
• Main Authors: Walsh, Jeremy J, Neudorf, Helena, Little, Jonathan P
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.04.2021
• Subjects: 3-Hydroxybutyric Acid - administration & dosage; Adult; Aged; Blood glucose; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood Glucose Self-Monitoring; Blood Pressure - drug effects; Blood sugar monitoring; Body mass index; Cardiovascular diseases; Cardiovascular Physiological Phenomena - drug effects; Cardiovascular System - drug effects; Caspase-1; Cell activation; Clinical s; Cross-Over Studies; Dextrose; Dietary Supplements; Double-Blind Method; Ethylenediaminetetraacetic acid; Female; Glucose; Glucose monitoring; Hemodynamics - drug effects; Humans; Hyperglycemia; Hyperglycemia - blood; Hyperglycemia - physiopathology; Hyperglycemia - prevention & control; Inflammation; Ketones; Ketones - administration & dosage; Lipopolysaccharides; Male; Middle Aged; Monocytes; Obesity; Obesity - blood; Obesity - diet therapy; Obesity - physiopathology; Placebos; Postprandial Period; Risk factors; Supplements; Time Factors; Vasodilation - drug effects; β-hydroxybutyrate; flow-mediated dilation; NLRP3 inflammasome; glucose-lowering; inflammation; postprandial glucose
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgaa925

Abstract Context Postprandial hyperglycemia increases systemic inflammation and is a risk factor for cardiovascular disease. A ketone monoester (KME) drink containing β-hydroxybutyrate (β-OHB) rapidly lowers plasma glucose, which may be a strategy protecting against postprandial hyperglycemia. Objective We hypothesized that KME would attenuate 2-hour postprandial glucose, lower systemic inflammation, and improve vascular function in adults with obesity. Methods In a randomized crossover design, 14 participants with obesity (age = 56 ± 12 years; body mass index = 32.8 ± 7.7 kg/m2) consumed KME (12 g β-OHB) or placebo 15 minutes prior to each meal for 14 days with all meals provided and matched between conditions. Postprandial glycemia was assessed by continuous glucose monitoring. Vascular function and inflammation were assessed before and after treatment periods. Results Postprandial glucose was 8.0% lower in KME versus placebo (g = 0.735; P = 0.011) and 24-hour average glucose reduced by 7.8% (g = 0.686; P = 0.0001). Brachial artery flow-mediated dilation increased from 6.2  ±  1.5% to 8.9 ± 3.3% in KME (g = 1.05; P = 0.0004) with no changes in placebo (condition × time interaction, P = 0.004). There were no changes in plasma cytokines; however, lipopolysaccharide-stimulated monocyte caspase-1 activation was lower following KME supplementation versus placebo (stimulation × condition × time interaction; P = 0.004). The KME supplement was well tolerated by participants and adherence to the supplementation regimen was very high. Conclusions In adults with obesity, 14 days of premeal KME supplementation improves glucose control, enhances vascular function, and may reduce cellular inflammation. KME supplementation may be a viable, nonpharmacological approach to improving and protecting vascular health in people with heightened cardiometabolic risk.