An insight into the importance of B vitamins and melatonin in the prevention of diabetes through modulation of the brain energy metabolism- a comprehensive review

Energy metabolism is the biochemical pathway of converting macronutrients (carbohydrates, protein, and fat) to cellular energy for the maintenance of cell homeostasis. The brain is an organ that consumes unproportional energy compared to its size. Glucose (glycogen, in storage form of glucose) is the principal source of brain energy. Impairment in brain energy metabolism results in neuronal loss and subsequent neurodegenerative diseases including AD, PD, amyotrophic lateral sclerosis, Huntington’s disease, etc. However, metabolic disorders such as chronic hyperglycemia, and insulin resistance are also linked with neuronal activity. Dysregulation in neuronal transmission is associated with oxidative stress and brain insulin resistance. Diabetes mellitus jeopardizes brain function through various mechanisms including glucose toxicity, BBB damage, neuroinflammation, and gliosis. B vitamins as antioxidants and neuroprotective agents, can improve brain glucose metabolism. Melatonin is a potent free radical scavenger and it can also modulate cellular cytokine levels and prevent insulin resistance. The neuroprotective and antihyperglycemic effects of melatonin improve the brain's antioxidant defense system, decrease brain NOS activity, and prevent glucose toxicity. Hence this review suggests a therapeutic use of a combination of melatonin and B vitamins to improve brain functioning disrupted by diabetes.