This peer-reviewed study published in Nutrients demonstrates the therapeutic efficacy of D-Pinitol as a multi-target disease modifier in a humanized 5×FAD mouse model of Alzheimer’s disease. Chronic oral administration of D-Pinitol significantly improved cognitive performance, reduced amyloid-β plaque burden, decreased tau hyperphosphorylation, and restored brain insulin signaling through activation of the PI3K/Akt pathway.
Beyond central nervous system effects, the study reveals a systemic mechanism of action. D-Pinitol normalized key metabolic hormones, reduced pro-inflammatory markers, strengthened intestinal barrier integrity, and modulated gut microbiota composition, leading to reduced endotoxemia and neuroinflammation. These findings position D-Pinitol as a unique nutraceutical candidate addressing the multifactorial nature of neurodegeneration through coordinated metabolic, endocrine, and gut–brain axis regulation.