Ketogenic Diet and Brain Health: Cerebrovascular Mechanisms, Neuroprotection, and Translational Implications

Background: Ketogenic dietary therapies (KDTs), characterized by substantial carbohydrate restriction and increased dietary fat intake, were originally developed for the treatment of drug-resistant epilepsy but have recently attracted broader scientific interest. In the context of population aging and the increasing prevalence of cognitive impairment and dementia, their potential relevance for brain health has received growing attention. Experimental and emerging clinical evidence suggests that ketogenic metabolism may influence biological processes involved in brain aging, including cerebrovascular regulation, neuroinflammatory signaling, and cerebral energy metabolism. Objective: This narrative review aims to synthesize current evidence on the relationship between ketogenic dietary therapies and brain health, with particular emphasis on cerebrovascular mechanisms, neuroinflammatory pathways, and neuroprotective processes relevant to aging. The review also briefly introduces the Semmelweis Study as an example of a translational research framework for evaluating nutrition-related interventions in real-world preventive settings. Methods: A narrative literature review was conducted using structured searches of major scientific databases to identify experimental and human studies investigating ketogenic dietary interventions, cerebrovascular mechanisms, and neuroprotective outcomes. Publications related to the Semmelweis Study were included solely to illustrate implementation-oriented research approaches and not as evidence supporting dietary efficacy. Results: Available evidence indicates that ketogenic dietary interventions may modulate several biological pathways relevant to brain health, including cerebral energy metabolism, mitochondrial function, oxidative stress regulation, and inflammatory signaling. However, the current evidence base is dominated by preclinical studies and short-term human investigations, and direct evidence linking ketogenic dietary therapies to long-term cerebrovascular or cognitive outcomes remains limited. Conclusions: Ketogenic dietary therapies represent metabolically distinct dietary strategies with potential relevance for cerebrovascular and neuroprotective mechanisms. Nevertheless, human evidence remains heterogeneous and insufficient to support broad clinical recommendations. Future research should prioritize well-designed long-term human studies with clearly defined metabolic, cerebrovascular, and cognitive endpoints. Translational research frameworks may facilitate the evaluation of feasibility, safety, and implementation of ketogenic interventions in aging populations.