The impact of lactic acid and medium chain triglyceride on blood glucose, lactate and diurnal motor activity: A re-examination of a treatment of major depression using lactic acid

Abstract While investigating the effect of alternative energy substrates on extracellular brain glucose or lactate, Beland-Millar (2017) noted a reduction of physical activity after intraperitoneal administration of lactate and ketone bodies. These observations were similar to an older study that examined the impact of drinking a sodium lactate/lactic acid solution before sleep in hospitalized patients with major depression. Patients and control participants self-reported drowsiness, early sleep onset and better overall sleep after consumption. Some patients showed improved mood after several days of treatment. We re-evaluated the effects of the solution used (0.59 g/kg) as well as several smaller doses (0.47, 0.35, 0.24 and 0.12 g/kg) on blood lactate and glucose in CD-1 mice and on sleep onset associated activity reduction. Because of adverse effects with the lactate/lactic acid solution, we also examined the effects of a medium chain triglyceride (MCT) solution (10, 5, 2.5, and 1 ml/kg) on blood lactate and glucose. Oral gavage administration of lactic acid/lactate produced adverse effects particularly for the largest doses. However consumption of 10 and 5 ml/kg volumes of MCT oils significantly increased blood lactate concentration to levels comparable to Lowenbach's solution without piloerection indicative of adverse effects. To evaluate pre-sleep activity reduction produced by lactate, mice were intraperitoneally administered diluted sodium lactate (2.0 g/kg, 1.0 g/kg, 0.5 g/kg, 0.25 g/kg, or saline) for 6 days, 120 min before their sleep period and their running activity was measured. Larger lactate doses reduced pre-sleep running each day up to 60 min post injection. Smaller doses reduced running after a single treatment only. These results suggest that the modulation of blood lactate levels may be useful in treating sleep onset problems associated with depression.