A dieta cetogênica pode auxiliar no tratamento do câncer? Uma análise crítica
DOI:
https://doi.org/10.47320/rasbran.2020.1467Resumo
Existe um crescente interesse na eficácia terapêutica da dieta cetogênica, dada a hipótese de que a restrição de carboidratos (CHO) favoreceria uma menor atividade de células tumorais. Mesmo assim, tais dietas continuam sendo um tema controverso na área de oncologia. Assim, este trabalho tem como objetivo sumarizar os estudos que já investigaram os potenciais efeitos terapêuticos da dieta cetogênica no tratamento do Câncer em pacientes humanos. Foi realizada uma revisão narrativa da literatura, nas bases de dados Literatura Latino- Americana e do Caribe (LILACS), Scientific Electronic Library Online (SciELO), Sistema Online de Busca e Análise de Literatura Médica (MEDLINE) e base Centro Latino Americano e do Caribe de Informação em Ciências da Saúde (BIREME). As seguintes palavras-chaves foram utilizadas isoladamente ou em associação: câncer, nutrição, restrição de carboidrato, células cancerígenas, e dieta cetogênica. Artigos publicados entre 2010 e 2018 e nos idiomas Inglês e Português foram selecionados. Nenhum estudo clínico randomizado foi encontrado. Ao longo dos estudos revisados, os quais se incluíam em sua maioria desenhos quasiexperimentais e estudos de caso, 221 pacientes foram selecionados. Resultados mistos foram observados, tanto apoiando quanto refutando a eficácia terapêutica da dieta cetogênica no tratamento de pacientes com câncer. Importantemente, apenas 92 (42%) desses pacientes foram submetidos à dieta cetogênica, dos quais somente 41% tiveram boa aderência à dieta. Estudos clínicos randomizados, investigando grandes segmentos de pacientes por longos períodos, com metodologias e protocolos dietéticos comparáveis, ainda são necessários antes que tal dieta possa ser recomendada como tratamento complementar do Câncer.
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Referências
Young VR. Energy metabolism and requirements in the cancer patient. Cancer Res. 1977; 37(7):2336-47.
ABC do câncer: abordagens básicas para o controle do câncer [internet]. Rio de Janeiro: INCA - Instituto Nacional de Câncer; [cited 2011]. Available from https://www.inca.gov.br/publicacoes/livros/abc-do-cancer-abordagens-basicas-para-o-controle-do-cancer.
Orenstein AJ. Freedom of Negro Races from Cancer. Br Med J. 1923; 2:342. DOI: https://doi.org/10.1136/bmj.2.3269.342-c
Brown GM, Cronk LB, Boag TJ. The occurrence of cancer in an Eskimo. Cancer. 1952; 5(1):142-3. DOI: https://doi.org/10.1002/1097-0142(195201)5:1<142::AID-CNCR2820050119>3.0.CO;2-Q
Cordain L, Miller JB, Eaton SB, Mann N. Macronutrient estimations in hunter-gatherer diets. Am J Clin Nutr. 2000; 72(6):1589-92. DOI: https://doi.org/10.1093/ajcn/72.6.1589
Thomas DT, Erdman KA, Burke LM. American College of Sports Medicine Joint Position Statement. Nutrition and Athletic Performance. Med Sci Sports Exerc. 2016; 48(3):543-68. DOI: https://doi.org/10.1249/MSS.0000000000000852
Carrera-Bastos P, Fontes-Villalba M, O’Keefe JH, Lindeberg S, Cordain L. The western diet and lifestyle and diseases of civilization. Res Rep Clin Card. 2011; 2:15-35. DOI: https://doi.org/10.2147/RRCC.S16919
Kohl HW 3rd, Craig CL, Lambert EV, Inoue S, Alkandari JR, Leetongin G, et al. The pandemic of physical inactivity: global action for public health. Lancet. 2012; 380(9839):294-305. DOI: https://doi.org/10.1016/S0140-6736(12)60898-8
Warburg, O. Uber den Stoffwechsel der Tumoren. Berlin: Springer; 1926. Translated: The metabolism of tumors. London: Arnold Constable; 1930.
Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324(5930):1029–33. DOI: https://doi.org/10.1126/science.1160809
Lambert DW, Wood IS, Ellis A, Shirazi-Beechey SP. Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. Br J Cancer. 2002;86(8):1262-9. DOI: https://doi.org/10.1038/sj.bjc.6600264
Mathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 2001;276(46):43407-12. DOI: https://doi.org/10.1074/jbc.M108181200
Moreno-Sanchez R, Rodríguez-Enríquez S, Marín-Hernandez A, Saavedra E. Energy metabolism in tumor cells. FEBS J. 2007;274(6):1393-418. DOI: https://doi.org/10.1111/j.1742-4658.2007.05686.x
Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11(2):85-95. DOI: https://doi.org/10.1038/nrc2981
Brouns F. Overweight and diabetes prevention: is a low-carbohydrate-high-fat diet recommendable? Eur J Nutr. 2018;57(4):1301-12.
Allen BG, Bhatia SK, Anderson CM, Gilmore JM, Sibenaller ZA, Mapuskar KA, et al. Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism. Redox Biol. 2014;2:963-70. DOI: https://doi.org/10.1016/j.redox.2014.08.002
Morscher RJ, Aminzadeh-Gohari S, Feichtinger RG, Mayr JA, Lang R, Neureiter D, et al. Inhibition of Neuroblastoma Tumor Growth by Ketogenic Diet and/or Calorie Restriction in a CD1-Nu Mouse Model. PLoS One. 2015;10(6):e0129802. DOI: https://doi.org/10.1371/journal.pone.0129802
Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol. 2012;3:59. DOI: https://doi.org/10.3389/fphar.2012.00059
Martin K, Jackson CF, Levy RG, Cooper PN. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2016;2:CD001903. DOI: https://doi.org/10.1002/14651858.CD001903.pub3
Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report. Nutr. Metab. (Lond.) 2010; 7:33. DOI: https://doi.org/10.1186/1743-7075-7-33
Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutr Metab (Lond). 2011; 8(1):54. DOI: https://doi.org/10.1186/1743-7075-8-54
Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano MC, Tomuta N, et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition. 2012; 28(10):1028–35. DOI: https://doi.org/10.1016/j.nut.2012.05.001
Schroeder U, Himpe B, Pries R, Vonthein R, Nitsch S, Wollenberg B. Decline of lactate in tumor tissue after ketogenic diet: In vivo microdialysis study in patients with head and neck cancer. Nutr Cancer. 2013; 65(6):843-9 DOI: https://doi.org/10.1080/01635581.2013.804579
Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ, et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol. 2014; 117(1):125–31. DOI: https://doi.org/10.1007/s11060-014-1362-0
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. DOI: https://doi.org/10.3892/ijo.2014.2382
Schwartz K, Chang HT, Nikolai M, Pernicone J, Rhee S, Olson K, et al. 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: https://doi.org/10.1186/s40170-015-0129-1
Branca JJV, Pacini S, Ruggiero M. Effects of pre-surgical vitamin D supplementation and ketogenic diet in a patient with recurrent breast cancer. Anticancer Res. 2015; 35(10):5525–32.
Jansen N, Walach H. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice. Oncol Lett. 2016; 11(1):584-92. DOI: https://doi.org/10.3892/ol.2015.3923
Klement RJ, Sweeney RA. Impact of a ketogenic diet intervention during radiotherapy on body composition: I. Initial clinical experience with six prospectively studied patients. BMC Res Notes. 2016; 9:143. DOI: https://doi.org/10.1186/s13104-016-1959-9
Tan-Shalaby JL, Carrick J, Edinger K, Genovese D, Liman AD, Passero VA, et al. Modified Atkins diet in advanced malignancies—final results of a safety and feasibility trial within the Veterans Affairs Pittsburgh Healthcare System. Nutr Metab (Lond). 2016; 13:52. DOI: https://doi.org/10.1186/s12986-016-0113-y
Wanka C, Steinbach JP, Rieger J. Tp53-induced glycolysis and apoptosis regulator (TIGAR) protects glioma cells from starvation-induced cell death by up-regulating respiration an dimproving cellular redox homeostasis. J Biol Chem. 2012; 287:33436–46. DOI: https://doi.org/10.1074/jbc.M112.384578
de Souza RJ, Swain JF, Appel LJ, Sacks FM. Alternatives for macronutrient intake and chronic disease: A comparison of the OmniHeart diets with popular diets and with dietary recommendations. Am J Clin Nutr. 2008; 88(1):1-11. DOI: https://doi.org/10.1093/ajcn/88.1.1
Johnstone AM, Horgan GW, Murison SD, Bremner DM, Lobley GE. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr. 2008; 87(1):44-55. DOI: https://doi.org/10.1093/ajcn/87.1.44
Boden G, Sargrad K, Homko C, Mozzoli M, Stein TP. Effect of a low carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med. 2005; 142(6):403-11. DOI: https://doi.org/10.7326/0003-4819-142-6-200503150-00006
Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gómez AL, Scheett TP, et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal weight men. J Nutr. 2002; 132(7):1879-1885. DOI: https://doi.org/10.1093/jn/132.7.1879
Brouns F. Overweight and diabetes prevention: is a low-carbohydrate-high-fat diet recommendable? Eur J Nutr. 2018; 57(4):1301-12. DOI: https://doi.org/10.1007/s00394-018-1636-y
Henderson CB, Filloux FM, Alder SC, Lyon JL, Caplin DA. Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis. J Child Neurol. 2006; 21(3):193–8. DOI: https://doi.org/10.2310/7010.2006.00044
Klein P, Tyrlikova I, Mathews GC. Dietary treatment in adults with refractory epilepsy: a review. Neurology. 2014; 83(21):1978–85. DOI: https://doi.org/10.1212/WNL.0000000000001004
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