Lactate infusion increases brain energy content during euglycemia but not hypoglycemia in healthy men

A special characteristic of the brain is the usage of lactate as alternative fuel instead of glucose to preserve its energy homeostasis. This physiological function is valid for sufficient cerebral glucose supply, as well as presumably during hypoglycemia, given that exogenous lactate infusion suppresses hormonal counterregulation. However, it is not yet clarified whether this effect is mediated by the use of lactate as an alternative cerebral energy substrate or any other mechanism. We hypothesized that under conditions of limited access to glucose (ie, during experimental hypoglycemia) lactate infusion would prevent hypoglycemia‐induced neuroenergetic deficits in a neuroprotective way. In a randomized, double‐blind, crossover study, lactate vs placebo infusion was compared during hyperinsulinemic‐hypoglycemic clamps in 16 healthy young men. We measured the cerebral high‐energy phosphate content — ie, adenosine triphosphate (ATP), phosphocreatine (PCr) and inorganic phosphate (Pi) levels — by 31 P‐magnetic resonance spectroscopy as well as the neuroendocrine stress response. During euglycemia, lactate infusion increased ATP/Pi as well as PCr/Pi ratios compared with baseline values and placebo infusion. During hypoglycemia, there were no differences between the lactate and the placebo condition in both ratios. Hormonal counterregulation was significantly diminished upon lactate infusion. Our data demonstrate an elevated cerebral high‐energy phosphate content upon lactate infusion during euglycemia, whereas there was no such effect during experimental hypoglycemia. Nevertheless, lactate infusion suppressed hypoglycemic hormonal counterregulation. Lactate thus adds to cerebral energy provision during euglycemia and may contribute to an increase in ATP reserves, which in turn protects the brain against neuroglucopenia under recurrent hypopglycemic conditions, eg, in diabetic patients.