Using diet in conjunction with conventional cancer care is often to support weight management (gain or loss), or to improve side effects of chemotherapy (constipation or diarrhea) or to prevent recurrence (we have specific evidence for certain diets to reduce recurrence depending on your cancer type).
Rarely do we see a diet that has been shown to impact the progression of cancer itself, and improve important markers such as overall survival. Brain cancers such as Glioblastoma Multiforme illustrate major differences in cancer cell metabolism when compared to regular cells, which points to possible uses of therapeutic diets to change disease progression.
GBM cells have multiple unique metabolism points, in that they require more than average glucose in order to produce energy (they are less efficient at producing fuel than regular cells), and they are less able to use alternate fuel sources such as ketone bodies. By contrast, healthy brain cells have a more adaptable metabolism.
Using a very low glucose diet (ketogenic, very low carbohydrate or calorically restricted) has been examined specifically for GBM, and in laboratory settings we can see alterations in tumor progression, and see tumor cells ‘struggle’ in these low glucose environments. Isolated tumors in labs seem to have reduced blood flow (good thing), and produce less growth-factors (very good thing) when exposed to low glucose, which can be mimicked in patients by following a ketogenic diet (1).
Ketogenic diets have been studied in treatment resistant epilepsy in children with good success. Going into ketosis (body derives fuel from protein and fat instead of glucose), decreases the availability of glucose for brain cells and tumor cells, and given GBM’s heavy reliance on available glucose, this diet shuts off the main fuel source for these tumor types. Even supplementing a normal diet with ketone bodies has shown to improve outcomes in GBM, meaning that both the reduction in glucose, and the increase in ketone bodies are having a positive impact on tumor progression.
When we track GBM patients over time, we know that patients who are pre-diabetic at diagnosis, or who become diabetic or insulin resistant through their treatment (often caused by chronic prednisone use) survive between 4-8 months shorter than patients with healthy blood sugar balance (2). Also, when patients are treated for blood sugar (with drugs such as Metformin) they tend to fair better, and live longer than patients who’s blood sugar problems go untreated.
Applying a ketogenic diet under medical supervision has become one of the most successful diet interventions for cancer, and for GBM, we have specific research to suggest better outcomes only when combined with conventional care. Patients who use ketogenic diets, or ketogenic plus caloric restriction show improved progression free survival, overall survival, and improved quality of life measures such as insomnia (a very common problem) and depression (3–5). A ketogenic diet alone unfortunately shows no impact on survival, and only when combined with other treatments do we see improvement in GBM.
Therapeutic diets in cancer should be prescribed and tracked by a medical professional to ensure that nutrient requirements are being met, and that the diet fits the need of the individual patient. Many chemotherapy drugs will change a patient’s needs, and may necessitate additional treatment options for this diet to be successful. In our office, ketogenic diets are used in combination with nutraceuticals which have evidence for GBM such as melatonin (6,7) and IV Vitamin C (8).
- Oppermann H, Ding Y, Sharma J, Berndt Paetz M, Meixensberger J, Gaunitz F, et al. Metabolic response of glioblastoma cells associated with glucose withdrawal and pyruvate substitution as revealed by GC-MS. Nutr Metab. 2016;13:70.
- Mayer A, Vaupel P, Struss H-G, Giese A, Stockinger M, Schmidberger H. Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme. Strahlenther Onkol Organ Dtsch Rontgengesellschaft Al. 2014 Oct;190(10):933–8.
- Rieger J, Bähr O, Maurer GD, Hattingen E, Franz K, Brucker D, et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol. 2014 Jun;44(6):1843–52.
- Varshneya K, Carico C, Ortega A, Patil CG. The Efficacy of Ketogenic Diet and Associated Hypoglycemia as an Adjuvant Therapy for High-Grade Gliomas: A Review of the Literature. Cureus. 2015 Feb;7(2):e251.
- Woolf EC, Scheck AC. The ketogenic diet for the treatment of malignant glioma. J Lipid Res. 2015 Jan;56(1):5–10.
- Lissoni P, Giani L, Zerbini S, Trabattoni P, Rovelli F. Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms. Nat Immun. 1998;16(1):27–33.
- Lissoni P, Meregalli S, Nosetto L, Barni S, Tancini G, Fossati V, et al. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology. 1996 Feb;53(1):43–6.
- Herst PM, Broadley KWR, Harper JL, McConnell MJ. Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest. Free Radic Biol Med. 2012 Apr 15;52(8):1486–93.