3-Hydroxybutyrate administration elevates plasma parathyroid hormone in a pilot human randomized, controlled, cross over trial
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Updated: Oct 22, 2025
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Published on: July 14, 2023
Mads Svart1, Lars Christian Gormsen2, Rasmus Espersen3
1Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus N, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus N, Denmark.
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.
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