Treatment of glioma patients with ketogenic diets: report of two cases treated with an IRB-approved energy-restricted ketogenic diet protocol and review of the literature

Abstract

BackgroundBased on the hypothesis that cancer cells may not be able to metabolize ketones as efficiently as normal brain cells, the ketogenic diet (KD) has been proposed as a complementary or alternative therapy for treatment of malignant gliomas.Case presentationWe report here our experience in treating two glioma patients with an IRB-approved energy-restricted ketogenic diet (ERKD) protocol as monotherapy and review the literature on KD therapy for human glioma patients. An ERKD protocol was used in this pilot clinical study. In addition to the two patients who enrolled in this study, we also reviewed findings from 30 other patients, including 5 patients from case reports, 19 patients from a clinical trial reported by Rieger and 6 patients described by Champ. A total of 32 glioma patients have been treated using several different KD protocols as adjunctive/complementary therapy. The two patients who enrolled in our ERKD pilot study were monitored with twice daily measurements of blood glucose and ketones and daily weights. However, both patients showed tumor progression while on the ERKD therapy. Immunohistochemistry reactions showed that their tumors had tissue expression of at least one of the two critical mitochondrial ketolytic enzymes (succinyl CoA: 3-oxoacid CoA transferase, beta-3-hydroxybutyrate dehydrogenase 1). The other 30 glioma patients in the literature were treated with several different KD protocols with varying responses. Prolonged remissions ranging from more than 5 years to 4 months were reported in the case reports. Only one of these patients was treated using KD as monotherapy. The best responses reported in the more recent patient series were stable disease for approximately 6 weeks. No major side effects due to KD have been reported in any of these patients.ConclusionsWe conclude that 1. KD is safe and without major side effects; 2. ketosis can be induced using customary foods; 3. treatment with KD may be effective in controlling the progression of some gliomas; and 4. further studies are needed to determine factors that influence the effectiveness of KD, whether as a monotherapy, or as adjunctive or supplemental therapy in treating glioma patients.Trial registrationClinicalTrials.gov# NCT01535911

Efficacy of a ketogenic diet with concomitant intranasal perillyl alcohol as a novel strategy for the therapy of recurrent glioblastoma

“…It was consistently reported that patients undergoing the KD presented with reduced blood glucose levels and beneficial therapeutic responses, including the transient disappearance of the brain tumor tissue (29)(30)(31). Thus, these case reports, along with numerous anecdotal observations, presented encouraging signs of metabolic reprogramming by the KD, along with the increased efficacy of standard of care treatment for malignant glioma (23,29).…”

“…It has been postulated that a ketogenic diet, i.e., a diet consisting of high fat, low carbohydrates and adequate protein, may be useful in the treatment of brain tumors (25)(26)(27)(28)(29)(30)(31). The present study was conducted to assess the therapeutic efficacy and safety of a KD concomitant with intranasal perillyl alcohol as a novel therapeutic strategy for recurrent GBM.…”

Systematic Review of the Use of Ketones in the Management of Acute and Chronic Neurological Disorders

“…Poor compliance was associated with the KD due to poor palatability [34,36]. Henderson et al reported a higher rate of diarrhoea in the ketogenic diet group compared to the placebo group however this was not discussed in the other studies [27].…”

“…Schwartz et al investigated whether the oral KD could alter glioma progression in two adult male patients with Glioblastoma Multiforme (GBM) [34]. Both patients had advanced posterior GBM and had already received surgery, radiotherapy and chemotherapy.…”

“…There was insufficient power to draw conclusions on neurological outcomes with either group. 10 Schwartz et al, [34] Case studies with literature review Adult patients with GBM…”