Research Appraisalother

Effect of glucose on medium chain triglyceride induced ketosis in healthy adults in a randomized, double-blind, controlled study

Scientific reportsFrenser, Marius, Fobker, Manfred, Feuerborn, Renata Antonina et al.9 Apr 2026DOI

Clinical Snapshot

70CEBM
Evidence: Weakother

PICO Framework

P — PopulationEleven healthy young women aged 22.5 ± 1.9 years
I — InterventionTricaprylin (C8-MCT, 0.2 g/kg bodyweight) combined with increasing glucose doses (0.2-0.6 g/kg bodyweight)
C — ComparatorControl condition and varying glucose:MCT ratios including 1:1 parallel increases
O — OutcomesPlasma β-hydroxybutyrate (βHB), glucose, and insulin concentrations measured up to 300 minutes post-dose

Bottom Line

This small crossover study demonstrates that glucose intake dose-dependently inhibits MCT-induced ketosis in healthy young women. While the double-blind design strengthens internal validity, the tiny sample size (n=11) and narrow population severely limit generalisability. The finding that ketone production ceases at higher glucose doses (1:3 MCT:glucose ratio) provides mechanistic insights but lacks clinical relevance for most patient populations. The study contributes to understanding metabolic interactions but offers limited practical guidance for clinical practice. Larger, more diverse studies are needed before these findings can inform therapeutic recommendations.

Evidence: Weak

Key Findings

  • P Value: Significance reported but specific values not provided

  • Effect Size: Negative correlation between βHB and increasing glucose at constant C8-MCT; positive moderate correlation with parallel substrate increases

  • Primary Outcome: Plasma β-hydroxybutyrate concentrations significantly increased with C8-MCT at low and medium glucose doses but not at highest glucose dose

  • Nnt Or Sensitivity: C8-MCT:glucose ratio of 1:3 may represent metabolic threshold

  • Confidence Interval: Not reported in abstract

Clinical Application

Requires precise dosing calculations and metabolic monitoring, limiting practical implementation MCT supplements available through TGA-approved channels; relevant for sports nutrition and ketogenic diet counselling but limited clinical applications Limited to healthy young adults, particularly women, seeking nutritional ketosis

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 ).

References

  1. 1.Frenser, M., Fobker, M., Feuerborn, R. A., Marquardt, T., & Fischer, T. (2026). Effect of glucose on medium chain triglyceride induced ketosis in healthy adults in a randomized, double-blind, controlled study. Scientific Reports. https://doi.org/10.1152/japplphysiol.00053.2024
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