3-Hydroxybutyrate administration elevates plasma parathyroid hormone in a pilot human randomized, controlled, cross over trial

Abstract

Content: Ketone bodies, in particular 3-hydroxybutyrate (3OHB), are known to possess important energetic and signaling capacities. There is a growing block of evidence, that ketogenic dieting (KD), fasting, and sodium glucose transporter 2 inhibitor (SGLT2i) treatment are associated with hyperparathyroidism and negative bone health.

Objective: We aimed to study the effect of exogenous 3OHB administration on bone metabolism, specifically the effect on parathyroid hormone (PTH) and calcium/phosphate homeostasis.

Design: A randomized, controlled, cross over study with two arms: i) saline infusion and ii) 3OHB infusion.

Setting: The study was conducted at Aarhus University Hospital.

Participants: We examined eight healthy human subjects aged 50-70 years.

Intervention: Continuous intravenous DL-3OHB-NaCl infusion or 0.9% NaCl was administered for 390 min.

Main outcome measures: The study was designed to test the impact of 3OHB on PTH, calcium-phosphate, C-terminal Telopeptide (CTX), and Procollagen I N-terminal Propeptide (PINP). The study was a post hoc study.

Results: The PTH concentration increased by 25% with a concomitant drop in phosphate of 30% in the 3OHB group. 3OHB infusion increased concentrations of CTX by 5%, without changes in PINP and albumin corrected calcium concentrations.

Conclusion: In conclusion, 3OHB administration increases PTH concentration and markers of bone resorption. These findings suggest a possible negative effect on bone health, which needs to be determined in future studies.

Trial registration: ClinicalTrials.gov NCT02814474.

Keywords: 3-Hydroxybutyrate; Bone; C-terminal telopeptide (CTX); Calcium; Parathyroid hormone; Phosphate.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.