Abstract
The predominant use of glucose anaerobically by cancer cells (Warburg effect) may
be the most important characteristic the majority of these cells have in common and,
therefore, a potential metabolic pathway to be targeted during cancer treatment. Because
this effect relates to fuel oxidation, dietary manipulation has been hypothesized
as an important strategy during cancer treatment. As such, the concept of a ketogenic
diet (KD) in cancer emerged as a metabolic therapy (ie, targeting cancer cell metabolism)
rather than a dietary approach. The therapeutic mechanisms of action of this high-fat,
moderate-to-low protein, and very-low-carbohydrate diet may potentially influence
cancer treatment and prognosis. Considering the lack of a dietetics-focused narrative
review on this topic, we compiled the evidence related to the use of this diet in
humans with diverse cancer types and stages, also focusing on the nutrition and health
perspective. The use of KD in cancer shows potentially promising, but inconsistent,
results. The limited number of studies and differences in study design and characteristics
contribute to overall poor quality evidence, limiting the ability to draw evidence-based
conclusions. However, the potential positive influences a KD may have on cancer treatment
justify the need for well-designed clinical trials to better elucidate the mechanisms
by which this dietary approach affects nutritional status, cancer prognosis, and overall
health. The role of registered dietitian nutritionists is demonstrated to be crucial
in planning and implementing KD protocols in oncology research settings, while also
ensuring patients’ adherence and optimal nutritional status.
Keywords
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References
- The metabolism of tumors in the body.J Gen Physiol. 1927; 8: 519-530
- The Warburg effect: How does it benefit cancer cells?.Trends Biochem Sci. 2016; 41: 211-218
- Role of multifaceted regulators in cancer glucose metabolism and their clinical significance.Oncotarget. 2016; 7: 31572-31585
- Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose.Eur J Nuc Med. 1996; 23: 1641-1674
- Substrate balances across colonic carcinomas in humans.Cancer Res. 1995; 55: 1373-1378
- Is there a role for carbohydrate restriction in the treatment and prevention of cancer?.Nutr Metab (Lond). 2011; 8: 75
- Fasting as a method for treating epilepsy.Med Rec. 1921; 99: 1037-1039
- The effects of ketonemia on course of epilepsy.Mayo Clin Proc. 1921; 2: 307-308
- Similarities of carbohydrate deficiency and fasting.Arch Intern Med. 1963; 112: 333-337
- Carbohydrate restriction regulates the adaptive response to fasting.Am J Physiol. 1992; 262: E631-E636
- Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism.Redox Biol. 2014; 2C: 963-970
- 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: e115147
- Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients.Nutrition. 2012; 28: 1028-1035
- ERGO: A pilot study of ketogenic diet in recurrent glioblastoma.Int J Oncol. 2014; 44: 1843-1852
- 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: 1-11
- Beyond weight loss: A review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets.Eur J Clin Nutr. 2013; 67: 789-796
- Nutrition and Your Health: Dietary Guidelines for Americans 2015-2020. US Government Printing Office, Washington, DC2015
- Ketogenic diet and other dietary treatments for epilepsy.Cochrane Database Syst Rev. 2016; 2: CD001903
- The ketogenic diet as a treatment paradigm for diverse neurological disorders.Front Pharmacol. 2012; 3: 59
- 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: 44-55
- Ketosis and appetite-mediating nutrients and hormones after weight loss.Eur J Clin Nutr. 2013; 67: 759-764
- Protein-induced satiety: Effects and mechanisms of different proteins.Physiol Behav. 2008; 94: 300-307
- Fuel metabolism in starvation.Annu Rev Nutr. 2006; 26: 1-22
- Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet.Am J Clin Nutr. 2009; 90: 519-526
- Nonequilibrium thermodynamics and energy efficiency in weight loss diets.Theor Biol Med Model. 2007; 4: 1-13
- Ketogenic diet and phytoextracts. Comparison of the efficacy of Mediterranean, zone and tisanoreica diet on some health risk factors.Agro FOOD Industry Hi Tech. 2010; 21: 24-29
- Medium term effects of a ketogenic diet and a Mediterranean diet on resting energy expenditure and respiratory ratio.BMC Proc. 2012; 6: 1-2
- Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast.Diabetes. 1976; 25: 494-504
- 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: 403-411
- Long term effects of ketogenic diet in obese subjects with high cholesterol level.Mol Cell Biochem. 2006; 286: 1-9
- Effects of diet composition and ketosis on glycemia during very-low-energy-diet therapy in obese patients with non-insulin-dependent diabetes mellitus.Am J Clin Nutr. 1996; 63: 110-115
- The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: A pilot study.Nutr Metab. 2005; 2: 35
- Effects of twenty days of the ketogenic diet on metabolic and respiratory parameters in healthy subjects.Lung. 2015; 193: 939-945
- A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women.J Clin Endocrinol Metab. 2003; 88: 1617-1623
- Weight loss with a low-carbohydrate, mediterranean, or low-fat diet.N Engl J Med. 2008; 359: 229-241
- A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.J Nutr. 2002; 132: 1879-1885
- Modification of lipoproteins by very low-carbohydrate diets.J Nutr. 2005; 135: 1339-1342
- Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet.Lipids. 2009; 44: 297-309
- Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme.J Neurooncol. 2014; 117: 125-131
- Cancer cachexia: Influence of systemic ketosis on substrate levels and nitrogen metabolism.Am J Clin Nutr. 1988; 47: 42-48
- Decline of lactate in tumor tissue after ketogenic diet: In vivo microdialysis study in patients with head and neck cancer.Nutr Cancer. 2013; 65: 843-849
- Effect of energy substrate manipulation on tumour cell proliferation in parenterally fed cancer patients.Clin Nutr. 1991; 10: 228-232
- Effects of a high-fat diet on body composition in cancer patients receiving chemotherapy: A randomized controlled study.Wien Klin Wochenschr. 2005; 117: 685-692
- Total nutritional manipulation in humans: Report of a cancer patient.Clin Nutr. 1996; 15: 207-209
- Effects of pre-surgical vitamin D supplementation and ketogenic diet in a patient with recurrent breast cancer.Anticancer Res. 2015; 35: 5525-5532
- Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case report.Nutr Metab (Lond). 2010; 7: 33
- 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
- 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
- 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: 584-592
- 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
- Comparison of survival between cerebellar and supratentorial glioblastoma patients: Surveillance, epidemiology, and end results (SEER) analysis.Neurosurgery. 2013; 73 (discussion 246; quiz 246): 240-246
- Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.N Engl J Med. 2005; 352: 987-996
- Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: Implication for ketogenic diet therapy.Nutr Metab (Lond). 2013; 10: 47
- Does nutrition support stimulate tumor growth in humans?.Nutr Clin Pract. 2011; 26: 174-180
- [11C] Acetoacetate utilization by breast and prostate tumors: A PET and biodistribution study in mice.Mol Imaging Biol. 2008; 10: 217-223
- Very low-carbohydrate and low-fat diets affect fasting lipids and postprandial lipemia differently in overweight men.J Nutr. 2004; 134: 880-885
- Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: A meta-analysis of randomised controlled trials.Br J Nutr. 2013; 110: 1178-1187
- Fasting lipoprotein and postprandial triacylglycerol responses to a low-carbohydrate diet supplemented with n-3 fatty acids.J Am Coll Nutr. 2000; 19: 383-391
- Nutritional support of the oncology patient.Crit Rev Oncol Hematol. 2013; 87: 172-200
- A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care.Appl Physiol Nutr Metab. 2008; 33: 997-1006
- Body composition assessment in nutrition research: Value of BIA technology.Eur J Clin Nutr. 2013; 67: S71-S78
- Bioelectrical impedance analysis-part II: Utilization in clinical practice.Clin Nutr. 2004; 23: 1430-1453
- Glycogen storage: Illusions of easy weight loss, excessive weight regain, and distortions in estimates of body composition.Am J Clin Nutr. 1992; 56: 292S-293S
- Variation in total body water with muscle glycogen changes in man.Acta Phys Scand. 1970; 80: 11-18
- Low-carb diets, fasting and euphoria: Is there a link between ketosis and gamma-hydroxybutyrate (GHB)?.Med Hypotheses. 2007; 68: 268-271
- Ketogenic diets: From cancer to mitochondrial diseases and beyond.Eur J Clin Invest. 2016; 46: 285-298
- Mitochondria: The ketogenic diet—A metabolism-based therapy.Int J Biochem Cell Biol. 2015; 63: 55-59
- Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet.Pediatrics. 2009; 124: e300-e304
- The alkalizer citrate reduces serum uric acid levels and improves renal function in hyperuricemic patients treated with the xanthine oxidase inhibitor allopurinol.Endocr Res. 2010; 35: 145-154
- American Gastroenterological Association technical review on constipation.Gastroenterology. 2013; 144: 218-238
- Calories, carbohydrates, and cancer therapy with radiation: Exploiting the five R's through dietary manipulation.Cancer Metastasis Rev. 2014; 33: 217-229
- Sarcopenia and cachexia in the era of obesity: Clinical and nutritional impact.Proc Nutr Soc. 2016; 75: 188-198
- Energy expenditure and body composition changes after an isocaloric ketogenic diet in overweight and obese men.Am J Clin Nutr. 2016; 104: 324-333
- Lean tissue imaging: A new era for nutritional assessment and intervention.JPEN. J Parenteral Enteral Nutr. 2014; 38: 940-953
- Cancer cachexia in the age of obesity: Skeletal muscle depletion is a powerful prognostic factor, independent of body mass index.J Clin Oncol. 2013; 31: 1539-1547
- Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: A population-based study.Lancet Oncol. 2008; 9: 629-635
- The ketogenic diet: A practical guide for caregivers.J Am Diet Assoc. 1998; 98: 316-321
- Optimal clinical management of children receiving the ketogenic diet: Recommendations of the International Ketogenic Diet Study Group.Epilepsia. 2009; 50: 304-317
- Development and evaluation of a ketogenic diet program.J Am Diet Assoc. 1999; 99: 1554-1558
- Ketogenic dietary therapies in adults with epilepsy: A practical guide.Pract Neurol. 2016; 16: 208-214
- Functionalities and input methods for recording food intake: a systematic review.Int J Med Inform. 2013; 82: 653-664
- Smartphone applications for promoting healthy diet and nutrition: A literature review.Jacobs J Food Nutr. 2015; 2: 021
- New technology in dietary assessment: A review of digital methods in improving food record accuracy.Proc Nutr Soc. 2013; 72: 70-76
- Dietary fiber and body weight.Nutrition. 2005; 21: 411-418
- Nutrition and physical activity guidelines for cancer survivors.CA Cancer J Clin. 2012; 62: 243-274
- Urinary excretion of beta-hydroxybutyrate and acetoacetate during experimental ketosis.Q J Exper Physiol Cognate Med Sci. 1968; 53: 181-193
- Carbohydrate restriction in patients with advanced cancer: A protocol to assess safety and feasibility with an accompanying hypothesis.Comm Oncol. 2008; 5: 22-26
Biography
C. L. P. Oliveira is a doctoral degree student, Nutrition and Metabolism, Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Biography
C. M. Prado is a registered dietitian, an assistant professor, and CAIP Chair in Nutrition, Food, and Health, Department of Agricultural, Food, and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.
Biography
S. Mattingly is a postdoctoral fellow, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Biography
M. B. Sawyer is an associate professor, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Biography
R. Schirrmacher is an associate professor, Department of Oncology, Medical Isotope Cyclotron Facility, University of Alberta, Edmonton, Alberta, Canada.
Biography
E. J. Fine is a clinical professor, Department of Radiology (Nuclear Medicine), Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY.
Article info
Publication history
Published online: March 30, 2017
Accepted:
February 2,
2017
Received:
June 29,
2016
Footnotes
STATEMENT OF POTENTIAL CONFLICT OF INTEREST No potential conflict of interest was reported by the authors.
FUNDING/SUPPORT None to report.
Identification
Copyright
© 2018 by the Academy of Nutrition and Dietetics.
