Effects of the Ketogenic Diet in the Treatment of Gliomas: A Systematic Review

Beatriz Sargaço, Patrícia Almeida Oliveira, Maria Luz Antunes, Ana Catarina Moreira, Beatriz Sargaço, Patrícia Almeida Oliveira, Maria Luz Antunes, Ana Catarina Moreira

Abstract

The ketogenic diet (KD) is a restrictive therapeutic diet, distinguished by being hyperlipidic, normoproteic, and hypoglucidic. This diet simulates biochemical changes related to fasting periods to achieve systemic ketosis. The metabolic particularities of glioma tumors motivated the rise in investigations and nutritional strategies, such as KD, to modulate the glycemic response as a treatment. This systematic review followed the PRISMA recommendations and was published in PROSPERO, with the identification CRD42021264173. The databases used were EMBASE, PubMed/Medline, Scopus, and Web of Science, and the studies were analyzed using the web-based application Rayyan. To analyze the risk of bias, Cochrane RevMan 5 software was used. For the analysis and treatment of statistical data, Microsoft® Excel® was used. A total of nine original articles were included. Data on survival, symptomology, and quality of life were collected. Mean overall survival was 15.9 months. Constipation and fatigue were the most reported symptoms. In 44.4% of the studies, an improvement in the quality of life was found. The KD is supported by most published studies as an effective therapy in the treatment of malignant gliomas due to its positive effects on patient survival. It was not possible to conclude the effectiveness of KD on quality of life.

Keywords: glioblastoma; glioma; ketogenic diet; survival.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow chart—study selection procedure.
Figure 2
Figure 2
Symptomatology associated with KD therapy in glioma patients.
Figure 3
Figure 3
Perception of quality of life in glioma patients undergoing KD.
Figure 4
Figure 4
Risk of bias summary—risk of bias analysis for each included study [8,10,15,16,17,27,28,29,30].

References

    1. Artzi M., Liberman G., Vaisman N., Bokstein F., Vitinshtein F., Aizenstein O., Ben Bashat D. Changes in cerebral metabolism during ketogenic diet in patients with primary brain tumors: 1H-MRS study. J. Neuro-Oncol. 2017;132:267–275. doi: 10.1007/s11060-016-2364-x.
    1. 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:e433–e438. doi: 10.3747/co.26.4889.
    1. Poff A., Koutnik A.P., Egan K.M., Sahebjam S., D’Agostino D., Kumar N.B. Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma. Semin. Cancer Biol. 2019;56:135–148. doi: 10.1016/j.semcancer.2017.12.011.
    1. Schwartz K.A., Noel M., Nikolai M., Chang H.T. Investigating the ketogenic diet as treatment for primary aggressive brain cancer: Challenges and lessons learned. Front. Nutr. 2018;5:11. doi: 10.3389/fnut.2018.00011.
    1. Foppiani A., De Amicis R., Lessa C., Leone A., Ravella S., Ciusani E., Silvani A., Zuccoli G., Battezazati A., Lamperti E., et al. Isocaloric Ketogenic Diet in Adults with High-Grade Gliomas: A Prospective Metabolic Study. Nutr. Cancer. 2021;73:1004–1014. doi: 10.1080/01635581.2020.1779759.
    1. Vasconelos C., Rola M. Dieta Cetogénica—Abordagem Nutricional. Rev. Nutrícias. 2014;22:16–19.
    1. Van der Louw E., van den Hurk D., Neal E., Leiendecker B., Fitzsimmon G., Dority L., Thompson L., Marchio M., Dudzinska M., Dressler A., et al. Ketogenic diet guidelines for infants with refractory epilepsy. Eur. J. Paediatr. Neurol. 2016;20:798–809. doi: 10.1016/j.ejpn.2016.07.009.
    1. Rieger J., Bähr O., Maurer G.D., Hattingen E., Franz K., Brucker D., Walenta S., Kammerer U., Coy J.F., Waller M., et al. ERGO: A pilot study of ketogenic diet in recurrent glioblastoma. Int. J. Oncol. 2014;45:1843–1852. doi: 10.3892/ijo.2014.2382.
    1. Vidali S., Aminzadeh S., Lambert B., Rutherford T., Sperl W., Kofler B., Feichtinger R.G. Mitochondria: The ketogenic diet—A metabolism-based therapy. Int. J. Biochem. Cell Biol. 2015;63:55–59. doi: 10.1016/j.biocel.2015.01.022.
    1. Van der Louw E.J.T.M., Reddingius R.E., Olieman J.F., Neuteboom R.F., Catsman-Berrevoets C.E. Ketogenic diet treatment in recurrent diffuse intrinsic pontine glioma in children: A safety and feasibility study. Pediatric Blood Cancer. 2019;66:e27561. doi: 10.1002/pbc.27561.
    1. Woolf E.C., Scheck A.C. The ketogenic diet for the treatment of malignant glioma. J. Lipid Res. 2015;56:5–10. doi: 10.1194/jlr.R046797.
    1. Morris A.A.M. Cerebral ketone body metabolism. J. Inherit. Metab. Dis. 2005;28:109–121. doi: 10.1007/s10545-005-5518-0.
    1. Ebrahimpour-Koujan S., Shayanfar M., Benisi-Kohansal S., Mohammad-Shirazi M., Sharifi G., Esmaillzadeh A. Adherence to low carbohydrate diet in relation to glioma: A case-control study. Clin. Nutr. 2019;38:2690–2695. doi: 10.1016/j.clnu.2018.11.023.
    1. Perry A., Wesseling P. Histologic classification of gliomas. Handb. Clin. Neurol. 2016;134:71–95.
    1. Van der Louw E.J.T.M., Olieman J.F., van den Bemt P.M., Bromberg J.E., Oomen-de Hoop E., Neuteboom R.F., Catsman-Berrevoets C.E., Vincent A.J. Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: A feasibility and safety study. Ther. Adv. Med. Oncol. 2019;11:1758835919853958N. doi: 10.1177/1758835919853958.
    1. Champ C.E., Palmer J.D., Volek J.S., Werner-Wasik M., Andrews D.W., Evans J.J., Glass J., Kim L., Shi W. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J. Neuro-Oncol. 2014;117:125–131. doi: 10.1007/s11060-014-1362-0.
    1. Martin-McGill K.J., Marson A.G., Smith C.T., Jenkinson M.D. The modified ketogenic diet in adults with glioblastoma: An evaluation of feasibility and deliverability within the national health service. Nutr. Cancer. 2018;70:643–649. doi: 10.1080/01635581.2018.1460677.
    1. Woolf E.C., Syed N., Scheck A.C. Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: Novel approaches to adjuvant brain tumor therapy. Front. Mol. Neurosci. 2016;9:122. doi: 10.3389/fnmol.2016.00122.
    1. Winter S.F., Loebel F., Dietrich J. Role of ketogenic metabolic therapy in malignant glioma: A systematic review. Crit. Rev. Oncol. Hematol. 2017;112:41–58. doi: 10.1016/j.critrevonc.2017.02.016.
    1. Wen P.Y., Kesari S. Malignant Gliomas in Adults. 2008. [(accessed on 8 May 2021)]. Available online: .
    1. Louis D.N., Ohgaki H., Wiestler O.D., Cavenee W.K., Burger P.C., Jouvet A., Scheithauer W., Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109. doi: 10.1007/s00401-007-0243-4.
    1. Strowd R.E., Grossman S.A. The role of glucose modulation and dietary supplementation in patients with central nervous system tumors. Curr. Treat. Options Oncol. 2015;16:36. doi: 10.1007/s11864-015-0356-2.
    1. Moher D., Tetzlaff J., Altman D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009;6:332–336. doi: 10.1371/journal.pmed.1000097.
    1. Guidance Notes for Registering a Systematic Review Protocol with PROSPERO. 2016. [(accessed on 8 May 2021)]. Available online: .
    1. Ouzzani M., Hammady H., Fedorowicz Z., Elmagarmid A. Rayyan—A web and mobile app for systematic reviews. Syst. Rev. 2016;5:210. doi: 10.1186/s13643-016-0384-4.
    1. Review Manager (RevMan) The Cochrane Collaboration; London, UK: 2020. Version 5.4.1.
    1. Perez A., van der Louw E., Nathan J., El-Ayadi M., Golay H., Korff C., Ansari M., Catsman-Berrevoets C., von Bueren A.O. Ketogenic diet treatment in diffuse intrinsic pontine glioma in children: Retrospective analysis of feasibility, safety, and survival data. Cancer Rep. 2021;4:e1383. doi: 10.1002/cnr2.1383.
    1. Panhans C.M., Gresham G., Amaral J.L., Hu J. Exploring the feasibility and effects of a ketogenic diet in patients with CNS malignancies: A retrospective case series. Front. Neurosci. 2020;14:390.
    1. Klein P., Tyrlikova I., Zuccoli G., Tyrlik A., Maroon J.C. Treatment of glioblastoma multiforme with “classic” 4:1 ketogenic diet total meal replacement. Cancer Metabol. 2020;8:682243. doi: 10.1186/s40170-020-00230-9.
    1. Martin-McGill K.J., Marson A.G., Tudur Smith C., Young B., Mills S.J., Cherry M.G., Jenkinson M.D. Ketogenic diets as an adjuvant therapy for glioblastoma (KEATING): A randomized, mixed methods, feasibility study. J. Neuro-Oncol. 2020;147:213–227. doi: 10.1007/s11060-020-03417-8.
    1. Schwartz K., Chang H.T., Nikolai M., Pernicone J., Rhee S., Olson K., Kurniali P.C., Hord N.G., Noel M. 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. Cancer Metab. 2015;3:3. doi: 10.1186/s40170-015-0129-1.
    1. Zuccoli G., Marcello N., Pisanello A., Servadei F., Vaccaro S., Mukherjee P., Seyfried T.N. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case report. Nutr. Metab. 2010;7:33. doi: 10.1186/1743-7075-7-33.
    1. Noorlag L., de Vos F.Y., Kok A., Broekman M.L., Seute T., Robe P.A., Snijders T.J. Treatment of malignant gliomas with ketogenic or caloric restricted diets: A systematic review of preclinical and early clinical studies. Clin. Nutr. 2019;38:1986–1994. doi: 10.1016/j.clnu.2018.10.024.
    1. Mosek A., Natour H., Neufeld M.Y., Shiff Y., Vaisman N. Ketogenic diet treatment in adults with refractory epilepsy: A prospective pilot study. Seizure. 2009;18:30–33. doi: 10.1016/j.seizure.2008.06.001.
    1. Kossoff E., Wang H.S. Dietary therapies for epilepsy. Biomed. J. 2013;36:2–8. doi: 10.4103/2319-4170.107152.
    1. Bergqvist A.G.C. Long-term monitoring of the ketogenic diet: Do’s and don’ts. Epilepsy Res. 2012;100:261–266. doi: 10.1016/j.eplepsyres.2011.05.020.
    1. Sampaio L.P.d. Ketogenic diet for epilepsy treatment. Arq. Neuro-Psiquiatr. 2016;74:842–848. doi: 10.1590/0004-282X20160116.
    1. Martin-McGill K.J., Srikandarajah N., Marson A.G., Smith C.T., Jenkinson M.D. The role of ketogenic diets in the therapeutic management of adult and paediatric gliomas: A systematic review. CNS Oncol. 2018;7:CNS17. doi: 10.2217/cns-2017-0030.

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