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Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series
M C L Phillips1, J Leyden2, E J McManus1
1Department of Neurology, Waikato Hospital, Hamilton, New Zealand.
Background:
Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM.
Methods:
We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modified ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse effects were assessed.
Results:
Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. The mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). The most common adverse effects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. The metabolic strategy did not interfere with standard oncological treatments.
Conclusion:
This is the first study to observe the feasibility and safety of repeated, prolonged fasting combined with a modified ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse effects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: This study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. The study was registered on 4 December 2020.
Insights
This study shows that combining fasting and ketogenic diets is a safe and feasible metabolic strategy for glioblastoma patients. The approach helped patients maintain a potentially therapeutic glucose ketone index (GKI) for over five months.
Area of Science:
- Oncology
- Metabolic Medicine
- Nutritional Neuroscience
Background:
- Glioblastoma multiforme (GBM) presents unique metabolic vulnerabilities.
- Fasting and ketogenic diets can lower blood glucose and increase ketones, potentially impacting GBM.
- Combining these strategies may offer a synergistic approach to managing GBM via a therapeutic glucose ketone index (GKI).
Purpose of the Study:
- To assess the feasibility and safety of a combined metabolic strategy (fasting and ketogenic diet) in GBM patients.
- To determine if this strategy can sustain a potentially therapeutic GKI (<6).
- To evaluate the impact on standard oncological treatments.
Main Methods:
- A prospective case series involving 10 GBM patients.
- Patients underwent intermittent 5-7 day fasting every 1-2 months, combined with a modified ketogenic diet.
- Patients self-monitored blood glucose, ketone levels, and body weight; adverse effects were recorded.
Main Results:
- The combined metabolic strategy was maintained for a mean of 161 days.
- Patients spent 21% of the time fasting and 79% on the ketogenic diet.
- The mean GKI was 3.22, with a mean weight loss of 11.2%. Common side effects included fatigue and lightheadedness, and the strategy did not interfere with cancer treatments.
Conclusions:
- This is the first study demonstrating the feasibility and safety of repeated prolonged fasting with a ketogenic diet in GBM patients.
- The combined metabolic strategy was sustained for 5-6 months, maintaining a potentially therapeutic GKI.
- The intervention was well-tolerated, with mild adverse effects, and compatible with standard cancer therapies.
