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.