Evaluate the therapeutic impact of ketogenic and other low-carbohydrate dietary interventions in glioblastoma.

Glioblastoma carries a poor prognosis despite multimodal therapy. Ketogenic diets may reduce tumor energy supply and influence tumor microenvironment through altered glucose and ketone metabolism. Clinical benefit remains uncertain.

A systematic search of PubMed, Scopus, and other databases (2000-2025) identified studies examining ketogenic or low-carbohydrate interventions in adult or pediatric glioblastoma. Eligible designs included randomized and single-arm trials, cohort and case series, case reports, and in vivo or in vitro studies. Two reviewers independently extracted data on study design, patient characteristics, dietary protocol, adherence, outcomes, metabolic markers, and safety. When feasible, pooled hazard or odds ratios (HR or OR) were calculated; otherwise, findings were summarized narratively.

Thirty-five studies met inclusion criteria (22 human, 13 pre-clinical). Human evidence included 150 patients, with three randomized trials providing the highest quality data. In recurrent disease, the pooled HR for overall survival with ketogenic therapy was 0.97 (95% CI 0.72-1.30), indicating no significant advantage. Non-randomized cohorts of newly diagnosed patients reported median progression-free survival of 9-13 months and overall survival of 20-32 months, with longer survival in those adhering to the diet for at least six months (HR = 0.6 for high- versus low-adherence groups). Quality of life was generally maintained, and adverse events were mild, often constipation or fatigue. Diets consistently lowered blood glucose and insulin while increasing ketone levels. Pre-clinical models demonstrated slowed tumor growth and synergy with radiotherapy (mean HR = 0.45 vs control). Heterogeneity of design limited quantitative pooling.                              

Ketogenic therapy appears feasible and safe as an adjunct to standard glioblastoma care, producing consistent metabolic changes and possible improvements in disease control for adherent patients. Current randomized evidence does not confirm a survival advantage. Larger standardized trials are needed to define efficacy, optimal duration, and responsive subgroups.