Combined Glucose and Thiamine Treatment for Sepsis

Sepsis is usually described as a dysregulated host response to infection associated with severe organ dysfunction and failure. In 2023 the author proposed that many aspects of sepsis suggested a physiological response and defence to infection that only became “dysregulated” if the infection was overwhelming or there was a deficiency of thiamine and/or intracellular glucose to provide ongoing fuel for the immune response and/or mitochondrial production of adenosine triphosphate (ATP).It was also proposed that during sepsis, the immune system received priority access to available glucose, prompting insulin resistance that minimised glucose utilisation by less essential tissues. Concurrently, mitochondrial ATP production via oxidative phosphorylation (OXPHOS) was deprioritised, with the immune system relying on anaerobic glycolysis for ATP generation. This suppression of OXPHOS was only a temporary measure; mitochondrial ATP production must be resumed for complete recovery. Persistent suppression culminated in critical ATP deficits and cell death.The 2023 paper also reviewed glucose, thiamine and insulin metabolism during sepsis and concluded that administering high-dose insulin alongside mild hyperglycaemia and intravenous thiamine—a pyruvate dehydrogenase kinase (PDK) inhibitor—might help restore physiological mitochondrial ATP production when administered during a crucial window in the sepsis process, potentially improving survival outcomes.The thrust of that hypothesis may have been validated by a recent experiment on sepsis in mice that found superior survival, albeit short-term, following treatment with combined glucose and thiamine compared to antibiotics.