Metabolic and Neuroenergetic Effects of Intranasal Vitamin C Application in the Human Brain

<b>Background</b>: Compared with normal weight, obese individuals display a variety of deviant measures in neuroenergetic status, food intake behavior, glucose metabolism, and circulating vitamin C levels. A chronically lowered neuroenergetic content is associated with increased food intake and disturbed glucose metabolism in obesity. In turn, a vitamin C deficiency found in obesity may be connected to these disturbances. Therefore, we investigated the effects of vitamin C application in the human brain. <b>Methods:</b> We intranasally applied vitamin C (80 mg ascorbic acid/day) vs. placebo for 8 consecutive days in 15 normal weight (BMI 20-25 kg/m²) and 15 obese (BMI > 30 kg/m²) men. The neuroenergetic content of adenosine triphosphate (ATP) and phosphocreatine (PCr) was assessed by ³¹phosphorous magnetic resonance spectroscopy, a non-invasive real-time technique to measure high-energy phosphate compounds in living tissues. Peripheral vitamin C, glucose, and insulin concentrations were measured, and spontaneous food intake was quantified by the standardized buffet test. <b>Results:</b> In the obese group, vitamin C application acutely suppressed the physiological insulin response on the first experimental day (<i>p</i> = 0.003). The following eight days of intranasal vitamin C led to higher serum vitamin C concentrations as compared to placebo (<i>p</i> = 0.011), compensated for the missing food intake-induced serum vitamin C rise (<i>p</i> ≤ 0.002), and attenuated a PCr decline (<i>p</i> = 0.008) in this group. Correlation analyses revealed a general link between serum vitamin C concentrations and the neuroenergetic state in both groups (<i>p</i> ≤ 0.033). Food intake was not influenced. <b>Conclusions:</b> Intranasal vitamin C application acutely improves insulin sensitivity, compensates for a vitamin C deficiency, and may act in a neuroprotective way in obese men. It could therefore be a future candidate as an adjuvant therapeutic option in obesity treatment.