Metabolic Therapy in Glioblastoma-Mapping the Evidence for Ketogenic Diet as an Adjunctive Strategy

Background/Objectives: Glioblastoma multiforme (GB) is an extremely aggressive tumor of the central nervous system, characterized by rapid growth, high invasiveness, and significant resistance to treatment. A growing body of data indicates that metabolic reprogramming of GB cells may be a therapeutic target, and that the ketogenic diet (KD)-by limiting glucose and inducing ketosis-may modulate tumor metabolism. The aim of this review was to provide a synthetic presentation of the current state of knowledge regarding the use of KD as an adjunctive therapy in the treatment of GB, with a particular focus on the mechanisms of action, safety, feasibility and results of clinical trials. Methods: The review was conducted in accordance with the Joanna Briggs Institute methodology and the PRISMA-ScR guidelines. A systematic search of PubMed, Scopus, EBSCO, Web of Science, Google Scholar, and Cochrane Library (1-10 April 2026) included studies on the use of KD in patients with GB. Full-text observational studies, randomised trials and reviews were included in the analysis. Data extraction was carried out according to the Population-Concept-Context (PCC) model. Results: Of the 26 publications identified, 12 met the inclusion criteria. Preclinical data consistently indicate that KD may reduce glycolysis, lower insulin and IGF-1 levels, increase oxidative stress in cancer cells, and modulate the inflammatory microenvironment. Clinical trials confirm the safety and feasibility of KD, as well as the ability to maintain stable ketosis. Preliminary data suggest potential metabolic benefits and improved quality of life, however, clinical efficacy remains inconclusive due to small trials, heterogeneous dietary protocols, and a lack of randomized trials. The variety of interventions used (classic KD; MCT-KD-Medium-chain triglyceride KD; KD-IF-KD and intermittent fasting) makes it difficult to compare the results. Conclusions: The KD represents a promising, low-toxic strategy to support the treatment of GB, based on biological basis. Available data indicate its safety and feasibility, but there is insufficient evidence to recommend its routine use in clinical practice. Large, multicenter, randomized trials with standardized dietary protocols and objective monitoring of metabolic parameters are needed to unambiguously assess the impact of KD on disease survival and progression.