Brain energy metabolism has been found to be disturbed in migraine. A mitochondrial defect may reduce the threshold for migraine attacks both increasing neuronal excitability and leading migrainous brain to a hyper-responsiveness to triggering stimuli. Riboflavin, a major co-factor in oxidative metabolism, may overcome this impairment. RCT studies in adult confirmed that riboflavin is safe and probably effective in migraine prophylaxis, based on level B evidence. Improving brain energy metabolism may reduce the susceptibility to migraine when brain energy demand increases due to both physiological and biopsychological factors.