Background: Lowered cerebral energy status relates to increased calorie consumption and obesity in humans. Transcranial direct current stimulation (tDCS), in turn, reduces food intake and systemic blood glucose levels. We hypothesized that this may be due to an increase in cerebral high energy phosphate content.
Methods: In a randomized sham-controlled crossover design, 14 healthy male volunteers of normal-weight were tested under daily anodal tDCS vs. sham for 8 days. Cerebral energy metabolism, i.e., adenosine triphosphate (ATP), phosphocreatine (PCr) levels, and respective ratios to inorganic phosphate (Pi), was assessed by 31phosphorous magnetic resonance spectroscopy. We further determined parameters of systemic glucose metabolism and the hypothalamic-pituitary-adrenal (HPA) axis, as well as food intake.
Results: On day 1, we found interaction effects between tDCS and sham in high energy phosphate to Pi ratios (P < 0.01 for both) due to higher PCr/Pi (P < 0.039) and predominantly higher ATP/Pi (P < 0.029) after tDCS compared with sham. Also after 8 days of daily stimulation, analogous interaction effects were found (P ≤0.013, for both). On average, blood glucose levels were lower on day 1 and day 8 after tDCS compared with sham (P < 0.034 for both), without any differences in insulin and c-peptide concentrations, or HPA-axis activity. Moreover, we found a significant negative correlation between carbohydrate intake and ATP/Pi ratios immediately before eating (r= 0.558; P= 0.047).
Conclusions: As hypothesized, our data demonstrate that tDCS enhances cerebral high energy phosphate content, reduces food intake, and lowers blood glucose concentrations independent of insulin, c-peptide or HPA-axis regulation. These findings suggest that an increase in high energy phosphate levels may underlie the reducing effects of tDCS on blood glucose and food intake.