Abstract Although medium-chain triglycerides (MCT) stimulate and carbohydrates inhibit ketone body synthesis, their quantitative interaction in humans is not well defined. This randomised, controlled, double-blind crossover study investigated how increasing glucose doses affects C8-MCT-induced ketone body synthesis after overnight fasting. Eleven healthy young woman (22. 5 ± 1. 9 years) received a constant dose of tricaprylin (99% C8; 0. 2 g/kg bodyweight) combined with increasing glucose doses (0. 2–0. 6 g/kg bodyweight). In additional interventions, both C8-MCT and glucose were increased in parallel. Plasma β-hydroxybutyrate (βHB), glucose, and insulin were measured for up to 300 min post-dose. Indirect calorimetry in a subset and side effects were monitored. C8-MCT significantly increased βHB concentrations at low and medium glucose doses compared with control, but not at highest glucose dose. When both substrates were increased equally (1: 1 ratio), ketone body synthesis increased. βHB was negative correlated with increasing glucose dosing at constant C8-MCT dosing, while parallel increases in both substrates showed a positive moderate correlation between βHB and C8-MCT doses. No dose-dependent side effects occurred. Overall, ketone body synthesis declines with rising glucose intake. It remains unclear whether a C8-MCT: glucose ratio of 1: 3 represents a metabolic cut-off or whether glucose intake becomes excessive due to linear effects. Trial registration This study was prospectively registered in the German Clinical Trials Register (DRKS ID DRKS00035373 https//www. bfarm. de/EN/BfArM/Tasks/GermanClinicalTrialsRegister/ₙode. html).
Frenser et al. (2026) studied this question.