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

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.

Automated summary

This study examined the impact of exogenous 3OHB administration on bone metabolism, specifically on PTH, calcium/phosphate homeostasis, and bone turnover markers. It was found that 3OHB infusion led to an increase in PTH concentration, a decrease in phosphate levels, and an increase in markers of bone resorption. These findings suggest a potential negative effect of 3OHB on bone health, which warrants further investigation in future studies.