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Episode 38 : Episode 38 [CODE #7] The Ketone HYPE Miracle Fuel or Marketing Gimmick? 🧪
💬 Got a question or feedback? Write us at: [email protected]
☕ Buy a Gel Caf for Lactate to support the work: ko-fi.com/lactate
Summary:
From a $10 million DARPA military project to the "jet fuel" of the professional peloton, exogenous ketones promise a dual-fuel state previously impossible in human evolution; achieving nutritional ketosis (>0.5 mM) while maintaining full glycogen stores. The physiology is rigorous but double-edged: while ketone esters increase thermodynamic efficiency (higher P/O ratio) and spare muscle glycogen by entering the Krebs Cycle directly as Acetyl-CoA, they simultaneously inhibit the Pyruvate Dehydrogenase Complex (PDH), effectively braking glycolysis and capping high-intensity anaerobic power. For training, this dictates a strict protocol: avoid usage during criteriums, VO₂max intervals, or stochastic racing where sprint power is required; instead, utilize esters immediately post-exercise to upregulate mTOR and accelerate glycogen resynthesis, or reserve them for steady-state ultra-endurance efforts exceeding six hours where intensity remains sub-threshold. The nuance lies in the formulation hierarchy, as common salts often fail to reach therapeutic levels (>2 mM) and carry massive sodium loads, while the gold-standard monoesters risk severe gastrointestinal distress, famously rumored to have impacted Tom Dumoulin’s 2017 Giro d'Italia.
Keywords: exogenous ketones, ketone esters, dual fuel, glycogen sparing, pdh inhibition, recovery, mtor, darpa, ultra-endurance, metabolic flexibility
🎙️ Lactate, the podcast that deciphers science to improve your performance.
Key references :
Cox, P. J., et al. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.07.010
Leckey, J. J., et al. (2017). Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Frontiers in Physiology. https://doi.org/10.3389/fphys.2017.00806
Poffé, C., et al. (2019). Exogenous Ketosis Impacts Training Overload and Recovery. American Journal of Physiology-Cell Physiology. https://doi.org/10.1152/ajpcell.00098.2019
NIH. (2025). The Effect of Exogenous Ketone Bodies on Cognition: A Systematic Review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12458514/
Veech, R. (2003). Development of Ketone Ester Diets. NIH Grant Z01-AA000112-01. https://grantome.com/grant/NIH/Z01-AA000112-01
Voices generated by artificial intelligence from the scientific report produced by the Lactate team.
By LACTATEEpisode 38 : Episode 38 [CODE #7] The Ketone HYPE Miracle Fuel or Marketing Gimmick? 🧪
💬 Got a question or feedback? Write us at: [email protected]
☕ Buy a Gel Caf for Lactate to support the work: ko-fi.com/lactate
Summary:
From a $10 million DARPA military project to the "jet fuel" of the professional peloton, exogenous ketones promise a dual-fuel state previously impossible in human evolution; achieving nutritional ketosis (>0.5 mM) while maintaining full glycogen stores. The physiology is rigorous but double-edged: while ketone esters increase thermodynamic efficiency (higher P/O ratio) and spare muscle glycogen by entering the Krebs Cycle directly as Acetyl-CoA, they simultaneously inhibit the Pyruvate Dehydrogenase Complex (PDH), effectively braking glycolysis and capping high-intensity anaerobic power. For training, this dictates a strict protocol: avoid usage during criteriums, VO₂max intervals, or stochastic racing where sprint power is required; instead, utilize esters immediately post-exercise to upregulate mTOR and accelerate glycogen resynthesis, or reserve them for steady-state ultra-endurance efforts exceeding six hours where intensity remains sub-threshold. The nuance lies in the formulation hierarchy, as common salts often fail to reach therapeutic levels (>2 mM) and carry massive sodium loads, while the gold-standard monoesters risk severe gastrointestinal distress, famously rumored to have impacted Tom Dumoulin’s 2017 Giro d'Italia.
Keywords: exogenous ketones, ketone esters, dual fuel, glycogen sparing, pdh inhibition, recovery, mtor, darpa, ultra-endurance, metabolic flexibility
🎙️ Lactate, the podcast that deciphers science to improve your performance.
Key references :
Cox, P. J., et al. (2016). Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.07.010
Leckey, J. J., et al. (2017). Ketone Diester Ingestion Impairs Time-Trial Performance in Professional Cyclists. Frontiers in Physiology. https://doi.org/10.3389/fphys.2017.00806
Poffé, C., et al. (2019). Exogenous Ketosis Impacts Training Overload and Recovery. American Journal of Physiology-Cell Physiology. https://doi.org/10.1152/ajpcell.00098.2019
NIH. (2025). The Effect of Exogenous Ketone Bodies on Cognition: A Systematic Review. https://pmc.ncbi.nlm.nih.gov/articles/PMC12458514/
Veech, R. (2003). Development of Ketone Ester Diets. NIH Grant Z01-AA000112-01. https://grantome.com/grant/NIH/Z01-AA000112-01
Voices generated by artificial intelligence from the scientific report produced by the Lactate team.