[Ketogenic diet: a new nutritional strategy for cancer therapy?]

Le régime cétogène : une stratégie alimentaire efficace en complément des traitements contre le cancer ?

Publisher: La Société de biologie Country of Publication: France NLM ID: 101544020 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2105-0686 (Electronic) Linking ISSN: 21050678 NLM ISO Abbreviation: Biol Aujourdhui Subsets: MEDLINE

Original Publication: Paris : La Société de biologie

Diet, Ketogenic* ; Neoplasms*/diet therapy; Humans

Cancer is a disease that can appear in several tissues and that kills more than 150 000 people in France every year. Cancer cells have mutations in their genome that lead to changes in their metabolism, compared to healthy cells. They use mostly glycolysis as their energy source, but not fatty acid oxidation. Currently, treatments used against cancer are nonspecific and have many side effects. Thus it appears increasingly important to find new strategies against cancer cells progression while protecting surrounding healthy cells and decreasing side effects. Ketogenic diet, which is a low-sugar high-fat diet, could be an interesting candidate as it alters the energy machinery of the cell and keeps away its primary energy source (glucose). This diet is largely used to treat refractory epilepsy and begins to be studied in oncology as well. This article describes the scientific evidence of the beneficial effects of the ketogenic diet and aims at showing how this complementary treatment could be useful against several cancers.
(© Société de Biologie, 2020.)

Abdelwahab, M.G., Fenton, K.E., Preul, M.C., Rho, J.M., Lynch, A., Stafford, P., Scheck, A.C. (2012). The Ketogenic Diet Is an Effective Adjuvant to Radiation Therapy for the Treatment of Malignant Glioma. PLOS ONE, 7, e36197.
Adekola, K., Rosen, S.T., Shanmugam, M. (2012). Glucose transporters in cancer metabolism. Curr Opin Oncol, 24, 650-654.
Allen, B.G., Bhatia, S.K., Anderson, C.M., Eichenberger-Gilmore, J.M., Sibenaller, Z.A., Mapuskar, K.A., Schoenfeld, J.D., Buatti, J.M., Spitz, D.R., Fath, M.A. (2014). Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol, 2, 963-970.
Baskar, R., Dai, J., Wenlong, N., Yeo, R., Yeoh, K.-W. (2014). Biological response of cancer cells to radiation treatment. Front Mol Biosci, 1, 24.
Bauchet, L., Rigau, V., Mathieu-Daudé, H., Figarella-Branger, D., Hugues, D., Palusseau, L., Bauchet, F., Fabbro, M., Campello, C., Capelle, L., Durand, A., Trétarre, B., Didier Frappaz, D., Henin, D., Menei, P., Honnorat, J., Segnarbieux, F. (2007). French brain tumor data bank: methodology and first results on 10 000 cases. J Neurooncol, 84, 189-199.
Bergqvist, A.G.C. (2012). Long-term monitoring of the ketogenic diet: Do’s and Don’ts. Epilepsy Res, 100, 261-266.
Blackadar, C.B. (2016). Historical review of the causes of cancer. World J Clin Oncol, 7, 54-86.
Boison, D. (2017). New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol, 30, 187-192.
Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R.L., Torre, L.A., Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68, 394-424.
Chung, H.-Y., Park, Y.K. (2017). Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment. J Cancer Prev, 22, 127-134.
Clegg, M.E. (2010). Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance. Int J Food Sci Nut, 61, 653-679.
Collège des Enseignants de Nutrition, Nutrition – Enseignement intégré, Elsevier Masson, 2014. ISBN 978-2-294-73852-4.
Cozzo, A.J., Fuller, A.M., Makowski, L. (2017). Contribution of Adipose Tissue to Development of Cancer. Compr Physiol, 8, 237-282.
Defossez, G., Le Guyader-Peyrou, S., Uhry, Z., Grosclaude, P., Colonna, M., Dantony, E., Delafosse, P., Molinié, F., Woronoff, A.S., Bouvier, A.M., Uhry, Z. (2019). Estimations nationales de l’incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018. Étude à partir des registres des cancers du réseau Francim, Vol. 1, Tumeurs solides, 167 p.
Deng, T., Lyon, C.J., Bergin, S., Caligiuri, M.A., Hsueh, W.A. (2016). Obesity, Inflammation, and Cancer. Ann Rev Pathol, 11, 421-449.
Dieudonné-Rahm, N., De Micheli, R., Hottinger, A. (2016). Prise en charge palliative des glioblastomes. Rev Med Suisse, 12, 853-856.
Erickson, N., Boscheri, A., Linke, B., Huebner, J. (2017). Systematic review: isocaloric ketogenic dietary regimes for cancer patients. Med Oncol, 34, 72.
Faes, S., Dormond, O. (2015). PI3K and AKT: Unfaithful Partners in Cancer. Int J Mol Sci, 16, 21138-21152.
Gupta, L., Khandelwal, D., Kalra, S., Gupta, P., Dutta, D., Aggarwal, S. (2017). Ketogenic diet in endocrine disorders: Current perspectives. J Postgrad Med, 63, 242-251.
Hanahan, D., Weinberg, R.A. (2011). Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674.
Hopkins, B.D., Pauli, C., Du, X., Wang, D.G., Li, X., Wu, D., Amadiume, S.C., Goncalves, M.D., Hodakoski, C., Lundquist, M.R., Bareja, R., Ma, Y., Harris, E.M., Sboner, A., Beltran, H., Rubin, M.A., Mukherjee, S., Cantley, L.C. (2018). Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature, 560, 499-503.
Hsu, P.P., Sabatini, D.M. (2008). Cancer Cell Metabolism: Warburg and Beyond. Cell, 134, 703-707.
Khodabakhshi, A., Akbari, M.E., Mirzaei, H.R., Mehrad-Majd, H., Kalamian, M., Davoodi, S.H. (2020). Feasibility, Safety, and Beneficial Effects of MCT-Based Ketogenic Diet for Breast Cancer Treatment: A Randomized Controlled Trial Study. Nutr Cancer, 72, 627-634.
Klement, R.J., Brehm, N., Sweeney, R.A. (2020). Ketogenic diets in medical oncology: a systematic review with focus on clinical outcomes. Med Oncol, 37, 14.
Kosinski, C., Jornayvaz, F.R. (2017). Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies. Nutrients, 9, 517.
Malthièry, Y., Savagner, F. (2006). Métabolisme énergétique de la cellule cancéreuse : exemple des tumeurs endocrines riches en mitochondries. Ann Endocrinol, 67, 205-213.
Matoba, S., Kang, J.-G., Patino, W.D., Wragg, A., Boehm, M., Gavrilova, O., Hurley, P.J., Bunz, F., Hwang, P.M. (2006). p53 Regulates Mitochondrial Respiration. Science, 312, 1650-1653.
Meyer-Rogge, S., Meyer-Rogge, K. (2012). Biochimie métabolique. De Boeck. ISBN 978-2-8041-7147-6.
Pereira de Brito Sampaio, L. (2016). Ketogenic diet for epilepsy treatment. Arq Neuropsiquiatr, 74, 842-848.
Ramanathan, A., Wang, C., Schreiber, S.L. (2005). Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Proc Natl Acad Sci USA, 102, 5992-5997.
Rieger, J., Bähr, O., Maurer, G.D., Hattingen, E., Franz, K., Brucker, D., Walenta, S., Kämmerer, U., Coy, J.F., Weller, M., Steinbach, J.P. (2014). ERGO: A pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol, 44, 1843-1852.
Rouzbahani, F., Shirkhoda, M., Memari, F., Dana, H., Chalbatani, G., Mahmoodzadeh, H., Samarghandi, N., Gharagozlou, E., Hadloo, M., Maleki, A., Sadeghian E., Nia, E., Nia, N., Hadjilooei, F., Rezaeian, O., Meghdadi, S., Miri, S., Jafari, F., Rayzan, E., Marmari, V. (2018). Immunotherapy a New Hope for Cancer Treatment: A Review. Pak J Biol Sci, 21, 135-150.
Saloustros, E., Mavroudis, D. (2013). Hormonotherapy: Present and future in er+ breast cancer. Forum Clin Oncol, 4, 32-43.
San-Millán, I., Brooks, G.A. (2017). Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect. Carcinogenesis, 38, 119-133.
Sarosiek, T. (2017). [Systemic treatment of early breast cancer– Current state of knowledge after the conference St Gallen 2017]. Pol Merkur Lekarski, 43, 232-236.
Schönfeld, P., Wojtczak, L. (2016). Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res, 57, 943-954.
Shimizu, K., Saito, H., Sumi, K., Sakamoto, Y., Tachi, Y., Iida, K. (2018). Short-term and long-term ketogenic diet therapy and the addition of exercise have differential impacts on metabolic gene expression in the mouse energy-consuming organs heart and skeletal muscle. Nutr Res, 60, 77-86.
Sumithran, P., Proietto, J. (2008). Ketogenic diets for weight loss: A review of their principles, safety and efficacy. Obes Res Clin Pract, 2, I-II.
Świderska, E., Strycharz, J., Wróblewski, A., Szemraj, J., Drzewoski, J., Śliwińska, A. (2018). Role of PI3K/AKT Pathway in Insulin-Mediated Glucose Uptake. Blood Glucose Levels. IntechOpen. ISBN 978-1-78985-526-5.
Van der Louw, E.J.T.M., Olieman, J.F., van den Bemt, P.M.L.A., Bromberg, J.E.C., Oomen-de Hoop, E., Neuteboom, R.F., Catsman-Berrevoets, C.E., Vincent, A.J.P.E. (2019). Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study. Ther Adv Med Oncol, 11, 1758835919853958.
Warburg, O. (1956). On the Origin of Cancer Cells. Science, 123, 309-314.
Weber, D.D., Aminzadeh-Gohari, S., Tulipan, J., Catalano, L., Feichtinger, R.G., Kofler, B. (2019). Ketogenic diet in the treatment of cancer – Where do we stand? Mol Metab, 33, 102-121.
Yang, J., Nie, J., Ma, X., Wei, Y., Peng, Y., Wei, X. (2019). Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer, 18, 26.

Keywords: Warburg effect; cancer therapy; effet Warburg; ketogenic diet; mitochondria; mitochondrie; oxidative metabolism; phosphorylation oxydative; régime cétogène; thérapie anticancéreuse
Local Abstract: [Publisher, French] Le régime cétogène : une stratégie alimentaire efficace en complément des traitements contre le cancer ? [Publisher, French] Le cancer est une pathologie qui touche tout type de tissu et qui tue chaque année en France plus de 150 000 personnes. Les cellules cancéreuses présentent des modifications dans leur métabolisme par rapport aux cellules saines, puisqu’elles tirent leur énergie très majoritairement de la glycolyse anaérobie et non de la phosphorylation oxydative mitochondriale : on parle de l’effet Warburg. À l’heure actuelle, les traitements les plus utilisés pour soigner le cancer en routine sont des traitements dits non spécifiques qui présentent de nombreux effets secondaires, altérant la vie des patients. Il semble de plus en plus crucial de trouver de nouvelles stratégies pour lutter contre la progression des cellules cancéreuses. Le régime cétogène, pauvre en sucres et riche en lipides, est un candidat intéressant, puisqu’il affaiblit la machinerie énergétique de la cellule cancéreuse. Ce régime est déjà utilisé dans le cadre de la prise en charge de l’épilepsie réfractaire aux traitements classiques, et commence à être étudié en cancérologie également. Cet article, qui fait le point sur les preuves scientifiques des effets bénéfiques du régime cétogène, souligne son intérêt thérapeutique potentiel comme traitement complémentaire pour lutter contre certains cancers.

Date Created: 20201228 Date Completed: 20211006 Latest Revision: 20220419

20231215

10.1051/jbio/2020014

33357370