Glucose effects on the brain in the healthy and unhealthy individuals: metabolic and cognitive aspects

Introduction: Glucose serves as the brain’s primary energy substrate and plays a critical role in maintaining cognitive function. Even slight fluctuations in glucose levels can influence attention, learning, and emotional regulation. Materials and Methods: The authors organised a screening of PubMed and Google Scholar reference databases on relevant articles from 1995 till 2025 to perform a systematic review. Results: Glucose metabolism and its regulation in the brain: The brain consumes a significant portion of the body’s glucose, especially in cortical and subcortical regions involved in cognitive processing. Glucose regulation is mediated by neuroglia, particularly astrocytes, which are essential for energy transfer and utilization. Neurobehavioral and neuroimaging markers: Neuroimaging studies using fMRI and PET reveal distinct patterns of activation in the brain ’ s reward system when comparing glucose and fructose consumption. Glucose more strongly activates the hypothalamus and regions related to satiety and appetite regulation, whereas fructose is associated with a reduced sense of fullness. Effects of sweet substances on cognitive function: Comparisons between glucose and non-caloric sweeteners (e.g., sucralose) highlight differences in the engagement of dopaminergic pathways and reward anticipation mechanisms. Glucose demonstrates a more stable effect on short-term memory and attention. Role of incretins and calorie awareness: Gut hormones such as GLP-1 are involved in satiety signaling and influence activity in limbic structures. Additionally, cognitive awareness of caloric content and food composition can modulate neural responses, underscoring the importance of cognitive factors in regulating eating behavior. Conclusion: Understanding the differences in perception and processing of glucose, fructose, and non-caloric sweeteners is crucial for developing dietary strategies and interventions for metabolic and neuropsychiatric disorders. Further research into neuroenergetics and individual variability in nutrient responses may support more precise and personalized approaches in medicine.