T. Sasayama, K. Tanaka, H. Nagashima, M. Takahashi, M. Yamanishi, M. Kuroda, S. Tabuchi, K. Hagihara, S. Yamanishi, Y. Ikeuchi, Y. Fujita, H. Iwahashi, S. Hotta, M. Matsunaga, S. Sanada, Y. Muragaki, et al. (2026). Ketogenic diet therapy for high-grade gliomas combined with standard treatment using an angiogenesis inhibitor: An exploratory pilot study on feasibility. Neuro-oncology advances, 8(1), vdaf264. https://doi.org/10.1093/noajnl/vdaf264

PubMed 41727338

[Abstract]
BACKGROUND: Altered tumor metabolism has renewed interest in ketogenic strategies, despite limited clinical evidence in glioma. Whereas the ketogenic diet (KD) alone elevates intratumoral amino acids, bevacizumab (BEV) co-administration suppresses these metabolites and curtails tumor growth, pointing to a synergistic therapeutic potential.

METHODS: We conducted a clinical pilot study to evaluate the combination of KD and standard therapy, combining BEV, in patients with malignant glioma. A standardized modified ketogenic diet (mKD) regimen was implemented: carbohydrate intake was restricted to 10 g/day in the first week, 20 g/day in the following 2 months, and ≤30 g/day thereafter. MCT oil was administered at ≥50 mL/day, and ketone formula supplements were provided as needed. The primary endpoint was to assess safety and feasibility.

RESULTS: 10 patients were enrolled. The duration of mKD ranged from 63 to 1,954 days, with a median of 185 days. All patients showed a rapid increase in serum ketone levels and achieved therapeutically adequate glucose-ketone index values. All participants met the predefined safety criteria, and no severe adverse events were reported. One patient discontinued the diet owing to moderate abdominal pain. The objective response rate was 50%, and notably, one patient remained on mKD for more than 5 years without tumor recurrence. The median progression-free survival from mKD initiation was 9.5 months, and the median overall survival was 31 months.

CONCLUSIONS: The combination of mKD and standard therapy with BEV was safe and feasible in patients with malignant glioma. Larger clinical trials are needed to determine its anti-tumor efficacy and clinical benefit.