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Glycodeoxycholic Acid Inhibits Primary Bile Acid Synthesis With Minor Effects on Glucose and Lipid Homeostasis in
Emma C E Meessen1, Soumia Majait2, Ümran Ay3,4
1Department of Endocrinology and Metabolism, Amsterdam University Medical Centres-Location AMC, University of Amsterdam, 1105 AZ, Amsterdam, The Netherlands.
The Journal of Clinical Endocrinology and Metabolism
|June 12, 2024
Summary
Oral glycine-conjugated deoxycholic acid (GDCA) supplementation elevated fibroblast growth factor 19 (FGF19) and inhibited bile acid synthesis but had minimal impact on metabolism in healthy men.
Area of Science:
- Metabolic research
- Endocrinology
- Gastroenterology
Background:
- Bile acids regulate lipid, glucose, and energy metabolism via specific receptors.
- Short-term bile acid use may increase GLP-1 and energy expenditure.
- Prolonged supplementation, like chenodeoxycholic acid for gallstones, can cause adverse effects.
Purpose of the Study:
- To assess the safety and metabolic effects of oral glycine-conjugated deoxycholic acid (GDCA) in healthy men.
- To evaluate GDCA's impact on bile acid synthesis and metabolic parameters over 30 days.
- To compare regular and slow-release GDCA capsule formulations.
Main Methods:
- A proof-of-concept study involving 20 healthy lean men.
- Administration of GDCA at 10 mg/kg/day for 30 days.
- Use of regular and slow-release capsules to mimic physiological bile acid release.
Main Results:
- GDCA increased postprandial total bile acids and FGF19, suppressed primary bile acids, and reduced hepatic bile acid synthesis.
- Minimal effects observed on lipid, glucose, and energy metabolism indices.
- No serious adverse events; mild liver transaminase increases and gastrointestinal issues were reported.
Conclusions:
- GDCA administration elevates FGF19 and inhibits primary bile acid synthesis, suggesting therapeutic potential.
- Expanding the bile acid pool with GDCA did not significantly impact energy metabolism in healthy individuals.
- Further research is needed to explore GDCA's therapeutic applications and long-term safety profile.
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