Benefits of Dietary Nitrate in Cognitive Decline Associated With Type 2 Diabetes: Pathways and Therapeutic Potential

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycaemia, which are associated with a high risk of developing several complications, including cognitive dysfunction. Cognitive decline is particularly prevalent in T2DM, encompassing deficits in memory, executive function and information processing speed, which ultimately impact quality of life. The molecular mechanistic and cellular pathways linking T2DM and cognitive dysfunction are complex and multifactorial, involving hyperglycaemia-induced oxidative distress, chronic inflammation, vascular dysfunction and impaired insulin signalling in the brain. METHODS: In this review, we examine how these interconnected pathways compromise key neuronal and vascular processes essential to maintaining brain proper functioning. Moreover, we explore how emerging evidence suggests that dietary nitrate, found abundantly in vegetables like beetroot and spinach, may offer innovative therapeutic benefits for individuals with T2DM. Finally, we discuss pre-clinical and clinical evidence, addressing challenges specific to T2DM populations that may influence the outcomes of nitrate interventions and highlighting future perspectives for leveraging dietary nitrate as a therapeutic innovative strategy to improve cognitive health in T2DM. RESULTS: Emerging evidence suggests that once ingested, dietary nitrate may act as a bioprecursor of nitric oxide (˙NO), playing a pivotal role in promoting glucose homeostasis, mitigating oxidative distress and inflammation and improving vascular function, mechanisms that collectively counteract the drivers of cognitive decline in T2DM. CONCLUSIONS: Dietary nitrate represents a promising nutritional strategy to target mechanisms underlying T2DM-associated cognitive dysfunction. Nevertheless, further studies are required to clarify its therapeutic efficacy, optimal intervention protocols and long-term impact on cognitive health in T2DM.