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Ketogenic Diet for Malignant Gliomas: a Review

  • Nutrition and the Brain (J Nasser, Section Editor)
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Abstract

Purpose of Review

In this review, we examine the postulated mechanisms of therapeutic effect of ketogenic diets in the treatment of gliomas, review the completed clinical trials, and discuss further directions in this field.

Recent Findings

Cancers including gliomas are characterized by derangements in cellular metabolism. In vitro and animal studies have revealed that dietary interventions to reduce glucose and glycolytic pathways in gliomas may have a therapeutic effect. Early trials in patients with malignant gliomas have shown feasibility, but are not robust enough yet to demonstrate clinical applicability.

Summary

Therapies for malignant gliomas of the brain are increasingly using a multi-targeted approach. The use of ketogenic diets and its variants may offer a unique and promising anti-glioma treatment by exploiting metabolic alterations seen in cancers including gliomas seen at the cellular level, which may work in concert with other therapies.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96.

    Article  CAS  PubMed  Google Scholar 

  2. Bush NA, Chang SM, Berger MS. Current and future strategies for treatment of glioma. Neurosurg Rev. 2017;40(1):1–14.

    Article  PubMed  Google Scholar 

  3. Fine HA, Dear KB, Loeffler JS, Black PM, Canellos GP. Meta-analysis of radiation therapy with and without adjuvant chemotherapy for malignant gliomas in adults. Cancer. 1993;71(8):2585–97.

    Article  CAS  PubMed  Google Scholar 

  4. Stupp R, Taillibert S, Kanner AA, Kesari S, Steinberg DM, Toms SA, et al. Maintenance therapy with tumor-treating fields plus temozolomide vs temozolomide alone for glioblastoma: a randomized clinical trial. JAMA. 2015;314(23):2535–43.

    Article  CAS  PubMed  Google Scholar 

  5. McGranahan T, Therkelsen KE, Ahmad S, Nagpal S. Current state of immunotherapy for treatment of glioblastoma. Curr Treat Options in Oncol. 2019;20(3):24.

    Article  Google Scholar 

  6. Kamran N, Alghamri MS, Nunez FJ, Shah D, Asad AS, Candolfi M, et al. Current state and future prospects of immunotherapy for glioma. Immunotherapy. 2018;10(4):317–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol. 1927;8(6):519–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    Article  CAS  PubMed  Google Scholar 

  9. Bough KJ, Rho JM. Anticonvulsant mechanisms of the ketogenic diet. Epilepsia. 2007;48(1):43–58.

    Article  CAS  PubMed  Google Scholar 

  10. Arora N, Mehta TR. Role of the ketogenic diet in acute neurological diseases. Clin Neurol Neurosurg. 2020;192:105727.

    Article  PubMed  Google Scholar 

  11. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008;7(6):500–6.

    Article  PubMed  Google Scholar 

  12. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, et al. A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy. Epilepsia. 2009;50(5):1109–17.

    Article  PubMed  Google Scholar 

  13. Sharma S, Sankhyan N, Gulati S, Agarwala A. Use of the modified Atkins diet for treatment of refractory childhood epilepsy: a randomized controlled trial. Epilepsia. 2013;54(3):481–6.

    Article  CAS  PubMed  Google Scholar 

  14. Muzykewicz DA, Lyczkowski DA, Memon N, Conant KD, Pfeifer HH, Thiele EA. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia. 2009;50(5):1118–26.

    Article  CAS  PubMed  Google Scholar 

  15. Maurer GD, Brucker DP, Bahr O, Harter PN, Hattingen E, Walenta S, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer. 2011;11:315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Seyfried TN, Shelton L, Arismendi-Morillo G, Kalamian M, Elsakka A, Maroon J, et al. Provocative question: should ketogenic metabolic therapy become the standard of care for glioblastoma? Neurochem Res. 2019;44(10):2392–404.

    Article  CAS  PubMed  Google Scholar 

  17. Li Y, Lupo JM, Parvataneni R, Lamborn KR, Cha S, Chang SM, et al. Survival analysis in patients with newly diagnosed glioblastoma using pre- and postradiotherapy MR spectroscopic imaging. Neuro-Oncol. 2013;15(5):607–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yang L, Venneti S, Nagrath D. Glutaminolysis: a hallmark of cancer metabolism. Annu Rev Biomed Eng. 2017;19:163–94.

    Article  CAS  PubMed  Google Scholar 

  19. Barami K, Lyon L, Conell C. Type 2 diabetes mellitus and glioblastoma multiforme-assessing risk and survival: results of a large retrospective study and systematic review of the literature. World Neurosurg. 2017;106:300–7.

    Article  PubMed  Google Scholar 

  20. Cancer Genome Atlas Research N, Brat DJ, Verhaak RG, Aldape KD, Yung WK, Salama SR, et al. Comprehensive, integrative genomic analysis of diffuse lower-grade gliomas. N Engl J Med. 2015;372(26):2481–98.

    Article  Google Scholar 

  21. Yan H, Parsons DW, Jin G, McLendon R, Rasheed BA, Yuan W, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med. 2009;360(8):765–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Rathmell JC, Fox CJ, Plas DR, Hammerman PS, Cinalli RM, Thompson CB. Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival. Mol Cell Biol. 2003;23(20):7315–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab (Lond). 2007;4:5.

    Article  Google Scholar 

  24. De Feyter HM, Behar KL, Rao JU, Madden-Hennessey K, Ip KL, Hyder F, et al. A ketogenic diet increases transport and oxidation of ketone bodies in RG2 and 9L gliomas without affecting tumor growth. Neuro-Oncol. 2016;18(8):1079–87.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Flavahan WA, Wu Q, Hitomi M, Rahim N, Kim Y, Sloan AE, et al. Brain tumor initiating cells adapt to restricted nutrition through preferential glucose uptake. Nat Neurosci. 2013;16(10):1373–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lv M, Zhu X, Wang H, Wang F, Guan W. Roles of caloric restriction, ketogenic diet and intermittent fasting during initiation, progression and metastasis of cancer in animal models: a systematic review and meta-analysis. PLoS One. 2014;9(12):e115147.

    Article  PubMed  PubMed Central  Google Scholar 

  27. . Klement RJ, Champ CE, Otto C, Kammerer U. Anti-tumor effects of ketogenic diets in mice: a meta-analysis. PLoS One. 2016;11(5):e0155050 A meta-analysis examining animal model studies that employed KD evaluating for effect on tumor growth.

    Article  PubMed  PubMed Central  Google Scholar 

  28. . Noorlag L, De Vos FY, Kok A, Broekman MLD, Seute T, Robe PA, et al. Treatment of malignant gliomas with ketogenic or caloric restricted diets: a systematic review of preclinical and early clinical studies. Clin Nutr. 2019;38(5):1986–94 A thorough review and compilation of pre-clinical and early clinical studies investigating KD or calorie restricted diets for treatment of malignant gliomas.

    Article  CAS  PubMed  Google Scholar 

  29. Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P, et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS One. 2012;7(5):e36197.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Rieger J, Bahr 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;44(6):1843–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Klement RJ, Brehm N, Sweeney RA. Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes. Med Oncol. 2020;37(2):14.

    Article  CAS  PubMed  Google Scholar 

  32. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr. 1995;14(2):202–8.

    Article  CAS  PubMed  Google Scholar 

  33. Martin-McGill KJ, Srikandarajah N, Marson AG, Tudur Smith C, Jenkinson MD. The role of ketogenic diets in the therapeutic management of adult and paediatric gliomas: a systematic review. CNS Oncol. 2018;7(2):CNS17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Woodhouse C, Ward T, Gaskill-Shipley M, Chaudhary R. Feasibility of a modified Atkins diet in glioma patients during radiation and its effect on radiation sensitization. Curr Oncol. 2019;26(4):e433–e8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. van der Louw E, Olieman JF, van den Bemt P, Bromberg JEC, Oomen-de Hoop E, Neuteboom RF, et al. Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. Ther Adv Med Oncol. 2019;11:1758835919853958.

    PubMed  PubMed Central  Google Scholar 

  36. Martin-McGill KJ, Marson AG, Tudur Smith C, Young B, Mills SJ, Cherry MG, et al. Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): a randomized, mixed methods, feasibility study. J Neurooncol. 2020;147(1):213–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Ye F, Li XJ, Jiang WL, Sun HB, Liu J. Efficacy of and patient compliance with a ketogenic diet in adults with intractable epilepsy: a meta-analysis. J Clin Neurol. 2015;11(1):26–31.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurosurgery, Global Neurosciences Institute, 3100 Princeton Pike Ste D, Lawrenceville, NJ, 08648, USA

    Jonathan G. Thomas & Erol Veznedaroglu

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  1. Jonathan G. Thomas
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Correspondence to Jonathan G. Thomas.

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As this was a review paper, no human or animal research was conducted by the authors.

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Thomas, J.G., Veznedaroglu, E. Ketogenic Diet for Malignant Gliomas: a Review. Curr Nutr Rep 9, 258–263 (2020). https://doi.org/10.1007/s13668-020-00332-2

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