Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment

Hae-Yun Chung, Yoo Kyoung Park, Hae-Yun Chung, Yoo Kyoung Park

Abstract

Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

Keywords: High-fat diet; Ketogenic diet; Ketosis; Neoplasms.

Conflict of interest statement

CONFLICTS OF INTEREST No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1
Flowchart of study search and selection.

References

    1. Demark-Wahnefried W, Morey MC, Sloane R, Snyder DC, Cohen HJ. Promoting healthy lifestyles in older cancer survivors to improve health and preserve function. J Am Geriatr Soc 2009;57 Suppl 2:S262–4.10.1111/j.1532-5415.2009.02507.x
    1. Kushi LH, Kwan ML, Lee MM, Ambrosone CB. Lifestyle factors and survival in women with breast cancer. J Nutr 2007;137: 236S–42S.
    1. Patterson RE, Cadmus LA, Emond JA, Pierce JP. Physical activity, diet, adiposity and female breast cancer prognosis: a review of the epidemiologic literature. Maturitas 2010;66:5–15.10.1016/j.maturitas.2010.01.004
    1. Imoberdorf R, Rühlin M, Ballmer PE. Cancer and nutrition: a paradigma shift. Laryngorhinootologie 2017;96:514–8.
    1. Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med 2017;9:eaai8700.10.1126/scitranslmed.aai8700
    1. Champ CE, Baserga R, Mishra MV, Jin L, Sotgia F, Lisanti MP, et al. Nutrient restriction and radiation therapy for cancer treatment: when less is more. Oncologist 2013;18:97–103.10.1634/theoncologist.2012-0164
    1. Bonkowski MS, Dominici FP, Arum O, Rocha JS, Al Regaiey KA, Westbrook R, et al. Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity. PLoS One 2009;4:e4567.10.1371/journal.pone.0004567
    1. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029–33.10.1126/science.1160809
    1. Huebner J, Marienfeld S, Abbenhardt C, Ulrich C, Muenstedt K, Micke O, et al. Counseling patients on cancer diets: a review of the literature and recommendations for clinical practice. Anti-cancer Res 2014;34:39–48.
    1. Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. . [updated March 2011].
    1. Fearon KC, Borland W, Preston T, Tisdale MJ, Shenkin A, Calman KC. Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. Am J Clin Nutr 1988;47:42–8.
    1. Rossi-Fanelli F, Franchi F, Mulieri M, Cangiano C, Cascino A, Ceci F, et al. Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients. Clin Nutr 1991;10:228–32.10.1016/0261-5614(91)90043-C
    1. Breitkreutz R, Tesdal K, Jentschura D, Haas O, Leweling H, Holm E. Effects of a high-fat diet on body composition in cancer patients receiving chemotherapy: a randomized controlled study. Wien Klin Wochenschr 2005;117:685–92.10.1007/s00508-005-0455-3
    1. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kämmerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutr Metab (Lond) 2011;8:54.10.1186/1743-7075-8-54
    1. 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;28:1028–35.10.1016/j.nut.2012.05.001
    1. 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;65:843–9.10.1080/01635581.2013.804579
    1. 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;44:1843–52.10.3892/ijo.2014.2382
    1. 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;11:584–92.
    1. 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;9:143.10.1186/s13104-016-1959-9
    1. 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;13:52.10.1186/s12986-016-0113-y
    1. Maurer GD, Brucker DP, Bähr 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;11:315.10.1186/1471-2407-11-315
    1. Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 2003;89: 1375–82.10.1038/sj.bjc.6601269
    1. Stafford P, Abdelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab (Lond) 2010;7:74.10.1186/1743-7075-7-74
    1. Freedland SJ, Mavropoulos J, Wang A, Darshan M, Demark-Wahnefried W, Aronson WJ, et al. Carbohydrate restriction, prostate cancer growth, and the insulin-like growth factor axis. Prostate 2008;68:11–9.10.1002/pros.20683
    1. Masko EM, Thomas JA, 2nd, Antonelli JA, Lloyd JC, Phillips TE, Poulton SH, et al. Low-carbohydrate diets and prostate cancer: how low is “low enough”? Cancer Prev Res (Phila) 2010;3:1124–31.10.1158/1940-6207.CAPR-10-0071
    1. Mavropoulos JC, Buschemeyer WC, 3rd, Tewari AK, Rokhfeld D, Pollak M, Zhao Y, et al. The effects of varying dietary carbohydrate and fat content on survival in a murine LNCaP prostate cancer xenograft model. Cancer Prev Res (Phila) 2009;2:557–65.10.1158/1940-6207.CAPR-08-0188
    1. Beck SA, Tisdale MJ. Nitrogen excretion in cancer cachexia and its modification by a high fat diet in mice. Cancer Res 1989;49:3800–4.
    1. Otto C, Kaemmerer U, Illert B, Muehling B, Pfetzer N, Wittig R, et al. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides. BMC Cancer 2008;8:122.10.1186/1471-2407-8-122
    1. Lee C, Raffaghello L, Brandhorst S, Safdie FM, Bianchi G, Martin-Montalvo A, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci Transl Med 2012;4:124ra27.10.1126/scitranslmed.3003293
    1. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report. Nutr Metab (Lond) 2010;7:33.10.1186/1743-7075-7-33
    1. McNally MA, Pyzik PL, Rubenstein JE, Hamdy RF, Kossoff EH. Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. Pediatrics 2009;124:e300–4.10.1542/peds.2009-0217
    1. Yancy WS, Jr, Olsen MK, Guyton JR, Bakst RP, Westman EC. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004;140:769–77.10.7326/0003-4819-140-10-200405180-00006

Source: PubMed

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