Related Experiment Video
Updated: Jul 17, 2026

Using a Combination of Indirect Calorimetry, Infrared Thermography, and Blood Glucose Levels to Measure Brown Adipose Tissue Thermogenesis in Humans
Published on: June 2, 2023
Ketosis elevates plasma concentrations of D-β-hydroxybutyryl-phenylalanine (BHB-Phe) in humans
Mette Glavind Bülow Pedersen1,2, Emaan Ghias3, Maj Bangshaab4
1Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N, 8200, Denmark. metteglavind@clin.au.dk.
Introduction:
β-hydroxybutyrate (BHB), produced during ketosis, can conjugate with amino acids forming BHB-amino acids. D-BHB-phenylalanine (D-BHB-Phe) is the most abundant BHB-amino acid and has been shown to reduce appetite and induce weight loss in mice, but its function and regulation in humans remain unclear. The objective of this study was to determine whether D-BHB-Phe concentrations vary across different degrees and forms of ketosis in humans.
Methods:
Plasma D-BHB-Phe was measured in samples from four clinical cross-over trials (i) after 21 days on a ketogenic diet (n = 10), (ii) after oral consumption of 30 g ketone salt (KS) and 30 g ketone ester (KE) (n = 14), (iii) after oral KE at doses of 10, 20 and 40 g (n = 10) and (iv) after oral versus intravenous KS administration (n = 8).
Results:
After 21 days of ketogenic dieting, plasma D-BHB-Phe became detectable (median 2.1 nmol/L; range 0.9-19.9), compared with near-undetectable concentrations during the standard diet (median 0; range 0-0.9; p = 0.005). Oral KS and KE increased D-BHB-Phe compared with placebo (intervention x time, p < 0.001). D-BHB-Phe rose dose-dependently after 10 g, 20 g, and 40 g of KE (intervention x time, p < 0.001). Oral KS induced higher peak concentrations of D-BHB-Phe (15.6 ± 6.4 nmol/L) compared with iso-ketotic intravenous KS infusion, which elicited only a modest peak (1.5 ± 0.3 nmol/L; intervention x time, p < 0.001). A positive association between the D-BHB and D-BHB-Phe concentration was observed in pooled analyses but was not consistent across cohorts.
Conclusion:
D-BHB-Phe is inducible by ketosis in humans. Our findings suggest involvement of the splanchnic bed in its production and support further exploration of D-BHB-Phe's role in appetite regulation and metabolic health.
Clinical Trial Registrations:
NCT05012748, NCT03935841, NCT05263401, NCT05581043.
More Related Videos
06:57Determining Basal Energy Expenditure and the Capacity of Thermogenic Adipocytes to Expend Energy in Obese Mice
Published on: November 11, 2021
05:42Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements
Published on: January 7, 2019
Related Concept Videos
Diabetic Ketoacidosis ll: Pathophysiology
Diabetic Ketoacidosis l: Introduction
Inborn Errors of Metabolism
Hyperglycemia
Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
Metabolic States of the Body: Fasting and Starvation