Erythritol and xylitol differentially impact brain networks involved in appetite regulation in healthy volunteers.

BACKGROUND: There is a growing consensus that sugar consumption should be reduced and the naturally occurring, low-calorie sweeteners xylitol and erythritol are gaining popularity as substitutes, but their effect on brain circuitry regulating appetite is unknown. AIM: The study's objective was to examine the effects of the two sweeteners on cerebral blood flow (rCBF) and resting functional connectivity in brain networks involved in appetite regulation, and test whether these effects are related to gut hormone release. METHODS: The study was performed as a randomized, double-blind, placebo-controlled, cross-over trial. Twenty volunteers received intragastric (ig) loads of 50g xylitol, 75g erythritol, 75g glucose dissolved in 300mL tap water or 300mL tap water. Resting perfusion and blood oxygenation level-dependent data were acquired to assess rCBF and functional connectivity. Blood samples were collected for determination of CCK, PYY, insulin and glucose. RESULTS: We found: (i) xylitol, but not erythritol, increased rCBF in the hypothalamus, whereas glucose had the opposite effect; (ii) graph analysis of resting functional connectivity revealed a complex pattern of similarities and differences in brain network properties following xylitol, erythritol, and glucose; (iii) erythritol and xylitol induced a rise in CCK and PYY, (iv) erythritol had no and xylitol only minimal effects on glucose and insulin. CONCLUSION: Xylitol and erythritol have a unique combination of properties: no calories, virtually no effect on glucose and insulin while promoting the release of gut hormones, and impacting appetite-regulating neurocircuitry consisting of both similarities and differences with glucose.

Intranasal insulin administration decreases cerebral blood flow in cortico-limbic regions: A neuropharmacological imaging study in normal and overweight males.

AIM: To assess and compare the effects of 160 IU intranasal insulin (IN-INS) administration on regional cerebral blood flow (rCBF) in healthy male individuals with normal weight and overweight phenotypes. METHODS: Thirty young male participants (mean age 25.9 years) were recruited and stratified into two cohorts based on body mass index: normal weight (18.5-24.9 kg/m2 ) and overweight (25.0-29.9 kg/m2 ). On separate mornings participants received 160 IU of IN-INS using an intranasal protocol and intranasal placebo as part of a double-blind crossover design. Thirty minutes following administration rCBF data were collected using a magnetic resonance imaging method called pseudocontinuous arterial spin labelling. Blood samples were collected to assess insulin sensitivity and changes over time in peripheral glucose, insulin and C-peptide. RESULTS: Insulin sensitivity did not significantly differ between groups. Compared with placebo, IN-INS administration reduced rCBF in parts of the hippocampus, insula, putamen, parahippocampal gyrus and fusiform gyrus in the overweight group. No effect was seen in the normal weight group. Insula rCBF was greater in the overweight group versus normal weight only under placebo conditions. Peripheral glucose and insulin levels were not affected by IN-INS. C-peptide levels in the normal weight group decreased significantly over time following IN-INS administration but not placebo. CONCLUSION: Insulin-induced changes within key regions of the brain involved in gustation, memory and reward were observed in overweight healthy male individuals. Following placebo administration, differences in gustatory rCBF were observed between overweight and normal weight healthy individuals.