Restricting carbohydrates to fight head and neck cancer—is this realistic?

References

1. 1.↵
   2. Wood RM,
   3. Lander VL,
   4. Mosby EL,
   5. Hiatt WR.

   Nutrition and the head and neck cancer patient. Oral Surg Oral Med Oral Pathol 1989;68:391–395.

   OpenUrlCrossRefPubMed
2. 2.↵
   2. Donaldson SS,
   3. Lenon RA.

   Alterations of Nutritional Status: Impact of Chemotherapy and Radiation Therapy. Cancer 1979;43:2036–2052.

   OpenUrlCrossRefPubMedWeb of Science
3. 3.↵
   2. Bassett MR,
   3. Dobie RA.

   Patterns of Nutritional Deficiency in Head and Neck Cancer. Otolaryngol Head Neck Surg 1983;91:119–125.

   OpenUrlCrossRefPubMed
4. 4.↵
   2. Alshadwi A,
   3. Nadershah M,
   4. Carlson ER,
   5. Young LS,
   6. Burke PA,
   7. Daley BJ.

   Nutritional Considerations for Head and Neck Cancer Patients: A Review of the Literature. J Oral Maxillofac Surg 2013;71:1853–1860.

   OpenUrlCrossRefPubMed
5. 5.↵
   2. Champ CE,
   3. Mishra MV,
   4. Showalter TN,
   5. Ohri N,
   6. Dicker AP,
   7. Simone NL.

   Dietary recommendations during and after cancer treatment: consistently inconsistent? Nutr Cancer 2013;65:430–439.

   OpenUrlCrossRefPubMed
6. 6.↵
   2. Zhu XP,
   3. Zhu LL,
   4. Zhou Q.

   Prescribing practice and evaluation of appropriateness of enteral nutrition in a university teaching hospital. Ther Clin Risk Manag 2013;9:37–43.

   OpenUrl
7. 7.↵
   2. Fietkau R,
   3. Lewitzki V,
   4. Kuhnt T,
   5. Hölscher T,
   6. Hess CF,
   7. Berger B, et al.

   A Disease-Specific Enteral Nutrition Formula Improves Nutritional Status and Functional Performance in Patients With Head and Neck and Esophageal Cancer Undergoing Chemoradiotherapy: Results of a Randomized, Controlled, Multicenter Trial. Cancer 2013;119:3343–3353.

   OpenUrlPubMed
8. 8.↵
   2. Richtsmeier WJ,
   3. Dauchy R,
   4. Sauer LA.

   In Vivo Nutrient Uptake by Head and Neck Cancers. Cancer Res 1987;47:5230–5233.

   OpenUrlAbstract/FREE Full Text
9. 9.↵
   2. Sandulache VC,
   3. Ow TJ,
   4. Pickering CR,
   5. Frederick MJ,
   6. Zhou G,
   7. Fokt I, et al.

   Glucose, Not Glutamine, Is the Dominant Energy Source Required for Proliferation and Survival of Head and Neck Squamous Carcinoma Cells. Cancer 2011;117:2926–2938.

   OpenUrlCrossRefPubMedWeb of Science
10. 10.↵
    2. Seyfried TN,
    3. Shelton LM.

    Cancer as a metabolic disease. Nutr Metab (Lond) 2010;7:7.

    OpenUrlCrossRefPubMed
11. 11.↵
    2. Seyfried TN,
    3. Flores RE,
    4. Poff AM,
    5. D’Agostino DP.

    Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis 2014;35:515–527.

    OpenUrlCrossRefPubMedWeb of Science
12. 12.↵
    2. Klement RJ,
    3. Kämmerer U.

    Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab (Lond) 2011;8:75.

    OpenUrlCrossRefPubMed
13. 13.↵
    2. Holm E,
    3. Kämmerer U.

    Lipids and Carbohydrates in Nutritional Concepts for Tumor Patients. Aktuel Ernährungsmed 2011;36:286–298.

    OpenUrl
14. 14.↵
    2. Klement RJ,
    3. Champ CE.

    Calories, carbohydrates, and cancer therapy with radiation: exploiting the five R’s through dietary manipulation. Cancer Metastasis Rev 2014;33:217–229.

    OpenUrlCrossRefPubMed
15. 15.↵
    2. Minami S.

    Versuche an überlebendem Carcinomgewebe. Biochem Zeitschr 1923;142:334–350.

    OpenUrl
16. 16.
    2. Warburg O,
    3. Posener K,
    4. Negelein E.

    Über den Stoffwechsel der Carcinomzelle. Biochem Zeitschr 1924;152:309–343.

    OpenUrlWeb of Science
17. 17.
    2. Warburg O.

    Über den Stoffwechsel der Carcinomzelle. Klin Wochenschr 1925;4:534–536.

    OpenUrlCrossRef
18. 18.
    2. Warburg O,
    3. Wind F,
    4. Negelein E.

    Über den Stoffwechsel von Tumoren im Körper. Klin Wochenschr 1926;5:829–832.

    OpenUrlCrossRef
19. 19.↵
    2. Warburg O,
    3. Wind F,
    4. Negelein E.

    The Metabolism of Tumors in the Body. J Gen Physiol 1927;8:519–530.

    OpenUrlFREE Full Text
20. 20.↵
    2. Agarwal V,
    3. Branstetter BF 4th.,
    4. Johnson JT.

    Indications for PET/CT in the Head and Neck. Otolaryngol Clin North Am 2008;41:23–49.

    OpenUrlCrossRefPubMedWeb of Science
21. 21.↵
    2. Subramaniam RM,
    3. Truong M,
    4. Peller P,
    5. Sakai O,
    6. Mercier G.

    Fluorodeoxyglucose-positron-emission tomography imaging of head and neck squamous cell cancer. AJNR Am J Neuroradiol 2010;31:598–604.

    OpenUrlAbstract/FREE Full Text
22. 22.↵
    2. Allal AS,
    3. Dulguerov P,
    4. Allaoua M,
    5. Haenggeli CA,
    6. El-Ghazi el A,
    7. Lehmann W, et al.

    Standardized Uptake Value of 2-[(18)F] Fluoro-2-Deoxy-D-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy. J Clin Oncol 2002;20:1398–1404.

    OpenUrlAbstract/FREE Full Text
23. 23.
    2. Allal AS,
    3. Slosman DO,
    4. Kebdani T,
    5. Allaoua M,
    6. Lehmann W,
    7. Dulguerov P.

    Prediction of Outcome in Head-And-Neck Cancer Patients Using the Standardized Uptake Value of 2-[(18)F]Fluoro-2-Deoxy-D-Glucose. Int J Radiat Oncol Biol Phys 2004;59:1295–1300.

    OpenUrlCrossRefPubMedWeb of Science
24. 24.
    2. Torizuka T,
    3. Tanizaki Y,
    4. Kanno T,
    5. Futatsubashi M,
    6. Naitou K,
    7. Ueda Y, et al.

    Prognostic Prognostic value of 18F-FDG PET in patients with head and neck squamous cell cancer. AJR Am J Roentgenol 2009;192:W156–W160.

    OpenUrlCrossRefPubMedWeb of Science
25. 25.↵
    2. Suzuki H,
    3. Kato K,
    4. Fujimoto Y,
    5. Itoh Y,
    6. Hiramatsu M,
    7. Naganawa S, et al.

    Prognostic value of (18)F-fluorodeoxyglucose uptake before treatment for pharyngeal cancer. Ann Nucl Med 2014;28:356–362.

    OpenUrlCrossRefPubMed
26. 26.↵
    2. Chan SC,
    3. Chang JT,
    4. Lin CY,
    5. Ng SH,
    6. Wang HM,
    7. Liao CT, et al.

    Clinical utility of 18 F-FDG PET parameters in patients with advanced nasopharyngeal carcinoma: predictive role for different survival endpoints and impact on prognostic stratification. Nucl Med Commun 2011;32:989–996.

    OpenUrlCrossRefPubMed
27. 27.↵
    2. Kubicek GJ,
    3. Champ C,
    4. Fogh S,
    5. Wang F,
    6. Reddy E,
    7. Intenzo C, et al.

    FDG-PET staging and importance of lymph node SUV in head and neck cancer. Head Neck Oncol 2010;2:19.

    OpenUrlCrossRefPubMed
28. 28.↵
    2. Langen KJ,
    3. Braun U,
    4. Rota Kops E,
    5. Herzog H,
    6. Kuwert T,
    7. Nebeling B, et al.

    The Influence of Plasma Glucose Levels on Uptake in Bronchial Carcinomas. J Nucl Med 1993;34:355–359.

    OpenUrlAbstract/FREE Full Text
29. 29.↵
    2. Greven KM,
    3. Williams DW 3rd.,
    4. McGuirt WF Sr.,
    5. Harkness BA,
    6. D’Agostino RB  Jr.,
    7. Keyes JW  Jr., et al.

    Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer. Head Neck 2001;23:942–946.

    OpenUrlCrossRefPubMedWeb of Science
30. 30.↵
    2. Koukourakis MI,
    3. Giatromanolaki A,
    4. Winter S,
    5. Leek R,
    6. Sivridis E,
    7. Harris AL.

    Lactate dehydrogenase 5 expression in squamous cell head and neck cancer relates to prognosis following radical or postoperative radiotherapy. Oncology 2009;77:285–292.

    OpenUrlCrossRefPubMedWeb of Science
31. 31.↵
    2. Walenta S,
    3. Mueller-Klieser WF.

    Lactate: Mirror and Motor of Lactate: mirror and motor of tumor malignancy. Semin Radiat Oncol 2004;14:267–274.

    OpenUrlCrossRefPubMedWeb of Science
32. 32.↵
    2. Serganova I,
    3. Rizwan A,
    4. Ni X,
    5. Thakur SB,
    6. Vider J,
    7. Russell J, et al.

    Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype. Clin Cancer Res 2011;17:6250–6261.

    OpenUrlAbstract/FREE Full Text
33. 33.↵
    2. Walenta S,
    3. Salameh A,
    4. Lyng H,
    5. Evensen JF,
    6. Mitze M,
    7. Rofstad EK, et al.

    Correlation of High Lactate Levels in Head and Neck Tumors with Incidence of Metastasis. Am J Pathol 1997;150:409–415.

    OpenUrlPubMedWeb of Science
34. 34.↵
    2. Brizel DM,
    3. Schroeder T,
    4. Scher RL,
    5. Walenta S,
    6. Clough RW,
    7. Dewhirst MW, et al.

    Elevated Tumor Lactate Concentrations Predict for an Increased Risk of Metastases in Head-And-Neck Cancer. Int J Radiat Oncol Biol Phys 2001;51:349–353.

    OpenUrlCrossRefPubMedWeb of Science
35. 35.↵
    2. Sun A,
    3. Johansson S,
    4. Turesson I,
    5. Dasu A,
    6. Sörensen J.

    Imaging tumor perfusion and oxidative metabolism in patients with head-and-neck-cancer using 1- [11C]-acetate PET during radiotherapy: preliminary results. Int J Radiat Oncol Biol Phys 2012;82:554–560.

    OpenUrlPubMed
36. 36.↵
    2. Semenza GL.

    HIF-1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010;20:51–56.

    OpenUrlCrossRefPubMedWeb of Science
37. 37.↵
    2. Hirschhaeuser F,
    3. Sattler UGA,
    4. Mueller-Klieser W.

    Lactate: a metabolic key player in cancer. Cancer Res 2011;71:6921–6925.

    OpenUrlAbstract/FREE Full Text
38. 38.↵
    2. Husain Z,
    3. Huang Y,
    4. Seth P,
    5. Sukhatme VP.

    Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol 2013;191:1486–1495.

    OpenUrlAbstract/FREE Full Text
39. 39.↵
    2. Sonveaux P,
    3. Végran F,
    4. Schroeder T,
    5. Wergin MC,
    6. Verrax J,
    7. Rabbani ZN, et al.

    Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. J Clin Invest 2008;118:3930–3942.

    OpenUrlCrossRefPubMedWeb of Science
40. 40.↵
    2. Otto C,
    3. Klingelhöffer C,
    4. Biggemann L,
    5. Melkus G,
    6. Mörchel P,
    7. Jürgens C, et al.

    Analysis of the Metabolism of Ketone Bodies and Lactate by Gastrointestinal Tumor Cells in vitro. Aktuel Ernährungsmed 2014;39:51–59.

    OpenUrl
41. 41.↵
    2. Curry JM,
    3. Tuluc M,
    4. Whitaker-Menezes D,
    5. Ames JA,
    6. Anantharaman A,
    7. Butera A, et al.

    Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer. Cell Cycle 2013;12:1371–1384.

    OpenUrlCrossRefPubMed
42. 42.↵
    2. Boidot R,
    3. Végran F,
    4. Meulle A,
    5. Le Breton A,
    6. Dessy C,
    7. Sonveaux P, et al.

    Regulation of Monocarboxylate Transporter MCT1 Expression by p53 Mediates Inward and Outward Lactate Fluxes in Tumors. Cancer Res 2012;72:939–948.

    OpenUrlAbstract/FREE Full Text
43. 43.↵
    2. Doherty JR,
    3. Cleveland JL.

    Targeting lactate metabolism for cancer therapeutics. J Clin Invest 2013;123:3685–3692.

    OpenUrlCrossRefPubMedWeb of Science
44. 44.↵
    2. Leemans CR,
    3. Braakhuis BJM,
    4. Brakenhoff RH.

    The molecular biology of head and neck cancer. Nat Rev Cancer 2011;11:9–22.

    OpenUrlCrossRefPubMedWeb of Science
45. 45.↵
    2. Suh Y,
    3. Amelio I,
    4. Guerrero Urbano T,
    5. Tavassoli M.

    Clinical update on cancer: molecular oncology of head and neck cancer. Cell Death Dis 2014;5:e1018.
46. 46.↵
    2. Liang Y,
    3. Liu J,
    4. Feng Z.

    The regulation of cellular metabolism by tumor suppressor p53. Cell Biosci 2013;3:9.

    OpenUrlCrossRefPubMed
47. 47.↵
    2. Lee P,
    3. Vousden KH,
    4. Cheung EC.

    TIGAR, TIGAR, burning bright. Cancer Metab 2014;2:1.

    OpenUrl
48. 48.↵
    2. Landor SK,
    3. Mutvei AP,
    4. Mamaeva V,
    5. Jin S,
    6. Busk M,
    7. Borra R, et al.

    Hypo- and hyperactivated Notch signaling induce a glycolytic switch through distinct mechanisms. Proc Natl Acad Sci 2011;108:18814–18819.

    OpenUrlAbstract/FREE Full Text
49. 49.↵
    2. Garcia-Cao I,
    3. Song MS,
    4. Hobbs RM,
    5. Laurent G,
    6. Giorgi C,
    7. de Boer VC, et al.

    Systemic elevation of PTEN induces a tumor suppressive metabolic state. Cell 2012;149:49–62.

    OpenUrlCrossRefPubMedWeb of Science
50. 50.↵
    2. Robey RB,
    3. Hay N.

    Is Akt the “Warburg kinase”?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol 2009;19:25–31.

    OpenUrlCrossRefPubMedWeb of Science
51. 51.↵
    2. Yang D,
    3. Wang M-T,
    4. Tang Y,
    5. Chen Y,
    6. Jiang H,
    7. Jones TT, et al.

    Impairment of mitochondrial respiration in mouse fibroblasts by oncogenic H-RAS(Q61L). Cancer Biol Ther 2010;9:122–133.

    OpenUrlCrossRefPubMedWeb of Science
52. 52.
    2. DeBerardinis RJ,
    3. Lum JJ,
    4. Hatzivassiliou G,
    5. Thompson CB.

    The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation. Cell Metab 2008;7:11–20.

    OpenUrlCrossRefPubMedWeb of Science
53. 53.↵
    2. Chen C,
    3. Pore N,
    4. Behrooz A,
    5. Ismail-Beigi F,
    6. Maity A.

    Regulation of glut1 mRNA by hypoxia-inducible factor-1. Interaction between H-ras and hypoxia. J Biol Chem 2001;276:9519–9525.

    OpenUrlAbstract/FREE Full Text
54. 54.↵
    2. Gerhäuser C.

    Cancer cell metabolism, epigenetics and the potential influence of dietary components – A perspective. Biomed Res 2012;23.
55. 55.↵
    2. Gasche JA,
    3. Goel A.

    Epigenetic mechanisms in oral carcinogenesis. Future Oncol 2012;8:1407–1425.

    OpenUrlCrossRefPubMed
56. 56.↵
    2. Yeh KT,
    3. Chang JG,
    4. Lin TH,
    5. Wang YF,
    6. Tien N,
    7. Chang JY, et al.

    Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer. Oncol Rep 2003;10:659–663.

    OpenUrlPubMedWeb of Science
57. 57.↵
    2. Gerald D,
    3. Berra E,
    4. Frapart YM,
    5. Chan DA,
    6. Giaccia AJ,
    7. Mansuy D, et al.

    JunD Reduces Tumor Angiogenesis by Protecting Cells from Oxidative Stress. Cell 2004;118:781–794.

    OpenUrlCrossRefPubMedWeb of Science
58. 58.↵
    2. Meijer TWH,
    3. Kaanders JHAM,
    4. Span PN,
    5. Bussink J.

    Targeting Hypoxia, HIF-1, and Tumor Glucose Metabolism to Improve Radiotherapy Efficacy. Clin Cancer Res 2012;18:5585–5594.

    OpenUrlAbstract/FREE Full Text
59. 59.↵
    2. Quennet V,
    3. Yaromina A,
    4. Zips D,
    5. Rosner A,
    6. Walenta S,
    7. Baumann M, et al.

    Tumor lactate content predicts for response to fractionated irradiation of human squamous cell carcinomas in nude mice. Radiother Oncol 2006;81:130–135.

    OpenUrlCrossRefPubMed
60. 60.↵
    2. Sattler UGA,
    3. Meyer SS,
    4. Quennet V,
    5. Hoerner C,
    6. Knoerzer H,
    7. Fabian C, et al.

    Glycolytic metabolism and tumour response to fractionated irradiation. Radiother Oncol 2010;94:102–109.

    OpenUrlCrossRefPubMed
61. 61.↵
    2. Spitz DR,
    3. Sim JE,
    4. Ridnour LA,
    5. Galoforo SS,
    6. Lee YJ.

    Glucose Deprivation-Induced Oxidative Stress in Human Tumor Cells. A Fundamental Defect in Metabolism? Ann N Y Acad Sci 2000;899:349–362.

    OpenUrlCrossRefPubMedWeb of Science
62. 62.
    2. Ahmad IM,
    3. Aykin-Burns N,
    4. Sim JE,
    5. Walsh SA,
    6. Higashikubo R,
    7. Buettner GR, et al.

    Mitochondrial O2- and H2O2 Mediate Glucose Deprivation-induced Stress in Human Cancer Cells. J Biol Chem 2005;280:4254–4263.

    OpenUrlAbstract/FREE Full Text
63. 63.↵
    2. Aykin-Burns N,
    3. Ahmad IM,
    4. Zhu Y,
    5. Oberley LW,
    6. Spitz DR.

    Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 2009;418:29–37.

    OpenUrlAbstract/FREE Full Text
64. 64.↵
    2. Graham NA,
    3. Tahmasian M,
    4. Kohli B,
    5. Komisopoulou E,
    6. Zhu M,
    7. Vivanco I.

    Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Mol Syst Biol 2012;8:589.

    OpenUrlAbstract/FREE Full Text
65. 65.↵
    2. Sun W,
    3. Liu Y,
    4. Glazer CA,
    5. Shao C,
    6. Bhan S,
    7. Demokan S, et al.

    TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res 2010;16:857–866.

    OpenUrlAbstract/FREE Full Text
66. 66.↵
    2. Völker H-U,
    3. Scheich M,
    4. Schmausser B,
    5. Kämmerer U,
    6. Eck M.

    Overexpression of transketolase TKTL1 is associated with shorter survival in laryngeal squamous cell carcinomas. Eur Arch Otorhinolaryngol 2007;264:1431–1436.

    OpenUrlCrossRefPubMed
67. 67.↵
    2. Grimm M,
    3. Schmitt S,
    4. Teriete P,
    5. Biegner T,
    6. Stenzl A,
    7. Hennenlotter J, et al.

    A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells. BMC Cancer 2013;13:569.

    OpenUrlCrossRefPubMed
68. 68.↵
    2. Zhou S,
    3. Kachhap S,
    4. Sun W,
    5. Wu G,
    6. Chuang A,
    7. Poeta L, et al.

    Frequency and phenotypic implications of mitochondrial DNA mutations in human squamous cell cancers of the head and neck. Proc Natl Acad Sci 2007;104:7540–7545.

    OpenUrlAbstract/FREE Full Text
69. 69.↵
    2. Lai CH,
    3. Huang SF,
    4. Liao CT,
    5. Chen IH,
    6. Wang HM,
    7. Hsieh LL.

    Clinical Significance in Oral Cavity Squamous Cell Carcinoma of Pathogenic Somatic Mitochondrial Mutations. PLoS One 2013;8:e65578.
70. 70.↵
    2. Wallace DC,
    3. Fan W,
    4. Procaccio V.

    Mitochondrial energetics and therapeutics. Annu Rev Pathol 2010;5:297–348.

    OpenUrlCrossRefPubMedWeb of Science
71. 71.↵
    2. Singh KK,
    3. Kulawiec M,
    4. Still I,
    5. Desouki MM,
    6. Geradts J,
    7. Matsui S-I.

    Inter-genomic cross talk between mitochondria and the nucleus plays an important role in tumorigenesis. Gene 2005;354:140–146.

    OpenUrlCrossRefPubMedWeb of Science
72. 72.↵
    2. Allen BG,
    3. Bhatia SK,
    4. Buatti JM,
    5. Brandt KE,
    6. Lindholm KE,
    7. Button AM, et al.

    Ketogenic Diets Enhance Oxidative Stress and Radio- Chemo-Therapy Responses in Lung Cancer Xenografts. Clin Cancer Res 2013;19:3905–3913.

    OpenUrlAbstract/FREE Full Text
73. 73.↵
    2. Sun W,
    3. Zhou S,
    4. Chang SS,
    5. McFate T,
    6. Verma A,
    7. Califano JA.

    Mitochondrial mutations contribute to HIF1alpha accumulation via increased reactive oxygen species and up-regulated pyruvate dehydrogenease kinase 2 in head and neck squamous cell carcinoma. Clin Cancer Res 2009;15:476–484.

    OpenUrlAbstract/FREE Full Text
74. 74.↵
    2. Challen C,
    3. Brown H,
    4. Cai C,
    5. Betts G,
    6. Paterson I,
    7. Sloan P, et al.

    Mitochondrial DNA mutations in head and neck cancer are infrequent and lack prognostic utility. Brit J Cancer 2011;104:1319–1324.

    OpenUrlPubMed
75. 75.↵
    2. Warburg O.

    On the Origin of Cancer Cells. Science 1956;123:309–314.

    OpenUrlFREE Full Text
76. 76.↵
    2. King A,
    3. Selak MA,
    4. Gottlieb E.

    Succinate dehydrogenase and fumarate hydratase: linking mitochondrial dysfunction and cancer. Oncogene 2006;25:4675–4682.

    OpenUrlCrossRefPubMedWeb of Science
77. 77.↵
    2. Demetrakopoulos GE,
    3. Linn B,
    4. Amos H.

    Rapid loss of ATP by tumor cells deprived of glucose: contrast to normal cells. Biochem Biophys Res Commun 1978;82:787–794.

    OpenUrlCrossRefPubMed
78. 78.
    2. Shim H,
    3. Chun YS,
    4. Lewis BC,
    5. Dang CV.

    A unique glucose-dependent apoptotic pathway induced by c-Myc. Proc Natl Acad Sci 1998;95:1511–1516.

    OpenUrlAbstract/FREE Full Text
79. 79.
    2. Li Y,
    3. Liu L,
    4. Tollefsbol TO.

    Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. FASEB J 2010;24:1442–1453.

    OpenUrlCrossRefPubMedWeb of Science
80. 80.
    2. Priebe A,
    3. Tan L,
    4. Wahl H,
    5. Kueck A,
    6. He G,
    7. Kwok R, et al.

    Glucose deprivation activates AMPK and induces cell death through modulation of Akt in ovarian cancer cells. Gynecol Oncol 2011;122:389–395.

    OpenUrlCrossRefPubMed
81. 81.↵
    2. Mathews EH,
    3. Stander BA,
    4. Joubert AM,
    5. Liebenberg L.

    Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations. Nutrition 2014;30:218–227.

    OpenUrl
82. 82.↵
    2. Demetrius LA,
    3. Coy JF,
    4. Tuszynski JA.

    Cancer proliferation and therapy: the Warburg effect and quantum metabolism. Theor Biol Med Model 2010;7:2.

    OpenUrlCrossRefPubMed
83. 83.↵
    2. Davies P,
    3. Demetrius LA,
    4. Tuszynski JA.

    Implications of quantum metabolism and natural selection for the origin of cancer cells and tumor progression Implications of quantum metabolism and natural selection. AIP Adv 2012;2:11101.

    OpenUrlPubMed
84. 84.↵
    2. Champ CE,
    3. Baserga R,
    4. Mishra MV,
    5. Jin L,
    6. Sotgia F,
    7. Lisanti MP, et al.

    Nutrient restriction and radiation therapy for cancer treatment: when less is more. Oncologist. 2013;18:97–103.

    OpenUrlAbstract/FREE Full Text
85. 85.↵
    2. Simone BA,
    3. Champ CE,
    4. Rosenberg AL,
    5. Berger AC,
    6. Monti DA,
    7. Dicker AP, et al.

    Selectively starving cancer cells through dietary manipulation: methods and clinical implications. Future Oncol 2013;9:959–976.

    OpenUrlCrossRefPubMedWeb of Science
86. 86.↵
    2. Klement RJ.

    Calorie or Carbohydrate Restriction? The Ketogenic Diet as Another Option for Supportive Cancer Treatment. Oncologist 2013;18:1056.

    OpenUrlFREE Full Text
87. 87.↵
    2. Marchut E,
    3. Gumińska M,
    4. Kedryna T.

    The inhibitory effect of various fatty acids on aerobic glycolysis in Ehrlich ascites tumour cells. Acta Biochim Pol 1986;33:7–16.

    OpenUrlPubMed
88. 88.↵
    2. Nebeling LC,
    3. Miraldi F,
    4. Shurin SB,
    5. Lerner E.

    Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995;14:202–208.

    OpenUrlCrossRefPubMedWeb of Science
89. 89.↵
    2. Zuccoli G,
    3. Marcello N,
    4. Pisanello A,
    5. Servadei F,
    6. Vaccaro S,
    7. 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.

    OpenUrlCrossRefPubMed
90. 90.↵
    2. Fine EJ,
    3. Segal-isaacson CJ,
    4. Feinman RD,
    5. Herszkopf S,
    6. Romano MC,
    7. 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;28:1028–1035.

    OpenUrlCrossRefPubMedWeb of Science
91. 91.↵
    2. Schroeder U,
    3. Himpe B,
    4. Pries R,
    5. Vonthein R,
    6. Nitsch S,
    7. 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;65:843–849.

    OpenUrl
92. 92.↵
    2. Cahill GF  Jr.,
    3. Veech RL.

    Ketoacids? Good medicine? Trans Am Clin Climatol Assoc 2003;114:149–61; discussion 162-3.

    OpenUrlPubMed
93. 93.↵
    2. Tisdale MJ,
    3. Brennan RA.

    Loss of acetoacetate coenzyme A transferase activity in tumours of peripheral tissues. Brit J Cancer 1983;47:293–297.

    OpenUrlCrossRefPubMedWeb of Science
94. 94.
    2. Skinner R,
    3. Trujillo A,
    4. Ma X,
    5. Beierle EA.

    Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 2009;44:212–216.

    OpenUrlCrossRefPubMed
95. 95.
    2. Maurer GD,
    3. Brucker DP,
    4. Bähr O,
    5. Harter PN,
    6. Hattingen E,
    7. 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.

    OpenUrlCrossRefPubMed
96. 96.↵
    2. Chang HT,
    3. Olson LK,
    4. Schwartz KA.

    Ketolytic and glycolytic enzymatic expression profiles in malignant gliomas: implication for ketogenic diet therapy. Nutr Metab (Lond) 2013;10:47.

    OpenUrlCrossRefPubMed
97. 97.↵
    2. Manning BD,
    3. Cantley LC.

    AKT/PKB Signaling: Navigating Downstream. Cell 2007;129:1261–1274.

    OpenUrlCrossRefPubMedWeb of Science
98. 98.↵
    2. Limesand KH,
    3. Chibly AM,
    4. Fribley A.

    Impact of targeting insulin-like growth factor signaling in head and neck cancers. Growth Horm IGF Res 2013;23:135–140.

    OpenUrlCrossRefPubMed
99. 99.↵
    2. Pollak M.

    The insulin and insulin-like grwoth factor receptor family in neoplasia: an update. Nat Rev Cancer 2012;12:159–169.

    OpenUrlCrossRefPubMedWeb of Science
100. 100.↵
     2. Pollak M.

     Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer 2008;8:915–928.

     OpenUrlCrossRefPubMedWeb of Science
101. 101.↵
     2. Iyengar NM,
     3. Kochhar A,
     4. Morris PG,
     5. Morris LG,
     6. Zhou XK,
     7. Ghossein RA, et al.

     Impact of Obesity on the Survival of Patients With Early-Stage Squamous Cell Carcinoma of the Oral Tongue. Cancer 2014;120:983–991.

     OpenUrlCrossRefPubMed
102. 102.↵
     2. Hardie DG,
     3. Alessi DR.

     LKB1 and AMPK and the cancer-metabolism link – ten years after. BMC Biol 2013;11:36.

     OpenUrlCrossRefPubMed
103. 103.↵
     2. Porporato PE,
     3. Dhup S,
     4. Dadhich RK,
     5. Copetti T,
     6. Sonveaux P.

     Anticancer targets in the glycolytic metabolism of tumors : a compehensive review. Front Pharmacol 2011;2:49.

     OpenUrlCrossRefPubMed
104. 104.↵
     2. Curry NL,
     3. Mino-Kenudson M,
     4. Oliver TG,
     5. Yilmaz OH,
     6. Yilmaz VO,
     7. Moon JY, et al.

     Pten-Null Tumors Cohabiting the Same Lung Display Differential AKT Activation and Sensitivity to Dietary Restriction. Cancer Discov 2013;3:908–921.

     OpenUrlAbstract/FREE Full Text
105. 105.↵
     2. Stafford P,
     3. Abdelwahab MG.
     4. Kim do Y,
     5. Preul MC,
     6. Rho JM,
     7. 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.

     OpenUrlCrossRefPubMed
106. 106.↵
     2. Scheck AC,
     3. Abdelwahab MG,
     4. Fenton KE,
     5. Stafford P.

     The ketogenic diet for the treatment of glioma: insights from genetic profiling. Epilepsy Res 2012;100:327–337.

     OpenUrlCrossRefPubMed
107. 107.↵
     2. Shimazu T,
     3. Hirschey MD,
     4. Newman J,
     5. He W,
     6. Shirakawa K,
     7. Le Moan N, et al.

     Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 2013;339:211–214.

     OpenUrlAbstract/FREE Full Text
108. 108.↵
     2. Newman JC,
     3. Verdin E.

     Ketone bodies as signaling metabolites. Trends Endocrinol Metab 2014;25:42–52.

     OpenUrlCrossRefPubMed
109. 109.↵
     2. Giudice FS,
     3. Pinto DSJ,
     4. Nör JE,
     5. Squarize CH,
     6. Castilho RM.

     Inhibition of Histone Deacetylase Impacts Cancer Stem Cells and Induces Epithelial-Mesenchyme Transition of Head and Neck Cancer. PLoS One 2013;8:e58672.
110. 110.↵
     2. Chang CC,
     3. Lin BR,
     4. Chen ST,
     5. Hsieh TH,
     6. Li YJ,
     7. Kuo MY.

     HDAC2 promotes cell migration/invasion abilities through HIF-1a stabilization in human oral squamous cell carcinoma. J Oral Pathol Med 2011;40:567–575.

     OpenUrlCrossRefPubMed
111. 111.↵
     2. Ujpál M,
     3. Matos O,
     4. Bíbok G,
     5. Somogyi A,
     6. Szabó G,
     7. Suba Z.

     Diabetes and Oral Tumors in Hungary. Diabetes Care 2004;27:770–774.

     OpenUrlAbstract/FREE Full Text
112. 112.↵
     2. Shanmugam N,
     3. Reddy MA,
     4. Guha M,
     5. Natarajan R.

     High Glucose–Induced Expression of Proinflammatory Cytokine and Chemokine Genes in Monocytic Cells. Diabetes 2003;52:1256–1264.

     OpenUrlAbstract/FREE Full Text
113. 113.↵
     2. Wen Y,
     3. Gu J,
     4. Li SL,
     5. Reddy MA,
     6. Natarajan R,
     7. Nadler JL.

     Elevated Glucose and Diabetes Promote Interleukin-12 Cytokine Gene Expression in Mouse Macrophages. Endocrinology 2006;147:2518–2525.

     OpenUrlCrossRefPubMedWeb of Science
114. 114.↵
     2. Freund E.

     Zur Diagnose des Carcinoms. Wiener Medizinische Blätter 1885;9.
115. 115.↵
     2. Maestu I,
     3. Pastor M,
     4. Aparicio J,
     5. Oltra A,
     6. Herranz C,
     7. Montalar J, et al.

     Pretreatment prognostic factors for survival in small-cell lung cancer: A new prognostic index and validation of three known prognostic indices on 341 patients. Ann Oncol 1997;8:547–553.

     OpenUrlCrossRefPubMedWeb of Science
116. 116.
     2. Weiser MA,
     3. Cabanillas ME,
     4. Konopleva M,
     5. Thomas DA,
     6. Pierce SA,
     7. Escalante CP, et al.

     Relation between the duration of remission and hyperglycemia during induction chemotherapy for acute lymphocytic leukemia with a hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate-cytarabine regimen. Cancer 2004;100:1179–1185.

     OpenUrlCrossRefPubMedWeb of Science
117. 117.
     2. McGirt MJ,
     3. Chaichana KL,
     4. Gathinji M,
     5. Attenello F,
     6. Than K,
     7. Ruiz AJ, et al.

     Persistent outpatient hyperglycemia is independently associated with decreased survival after primary resection of malignant brain astrocytomas. Neurosurgery 2008;63:286–291.

     OpenUrlCrossRefPubMed
118. 118.
     2. Derr RL,
     3. Ye X,
     4. Islas MU,
     5. Desideri S,
     6. Saudek CD,
     7. Grossman SA.

     Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol 2009;27:1082–1086.

     OpenUrlAbstract/FREE Full Text
119. 119.
     2. Lamkin DM,
     3. Spitz DR,
     4. Shahzad MM,
     5. Zimmerman B,
     6. Lenihan DJ,
     7. Degeest K, et al.

     Glucose as a Prognostic Factor in Ovarian Carcinoma. Cancer 2009;115:1021–1027.

     OpenUrlCrossRefPubMed
120. 120.
     2. Erickson K,
     3. Patterson RE,
     4. Flatt SW,
     5. Natarajan L,
     6. Parker BA,
     7. Heath DD, et al.

     Clinically Defined Type 2 Diabetes Mellitus and Prognosis in Early-Stage Breast Cancer. J Clin Oncol 2011;29:54–60.

     OpenUrlAbstract/FREE Full Text
121. 121.
     2. Villarreal-Garza C,
     3. Shaw-Dulin R,
     4. Lara-Medina F,
     5. Bacon L,
     6. Rivera D,
     7. Urzua L, et al.

     Impact of diabetes and hyperglycemia on survival in advanced breast cancer patients. Exp Diabetes Res 2012;2012:732027.

     OpenUrlCrossRefPubMed
122. 122.↵
     2. Minicozzi P,
     3. Berrino F,
     4. Sebastiani F,
     5. Falcini F,
     6. Vattiato R,
     7. Cioccoloni F, et al.

     High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease. Eur J Cancer 2013;49:3881–3888.

     OpenUrlCrossRefPubMed
123. 123.↵
     2. Rabinovitch R,
     3. Grant B,
     4. Berkey BA,
     5. Raben D,
     6. Ang KK,
     7. Fu KK, et al.

     Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: a secondary analysis of RTOG trial 90-03. Head Neck 2006;28:287–296.

     OpenUrlCrossRefPubMedWeb of Science
124. 124.↵
     2. Muñoz IP,
     3. Plaza FC.

     Head and Neck Cancer: Multidisciplinary Approach is a must, Including Radiation Oncologist and Anaesthesiologist. Surgery Curr Res 2014;4:157.

     OpenUrl
125. 125.↵
     2. Raffaghello L,
     3. Lee C,
     4. Safdie FM,
     5. Wei M,
     6. Madia F,
     7. Bianchi G, et al.

     Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci 2008;105:8215–8220.

     OpenUrlAbstract/FREE Full Text
126. 126.
     2. Safdie F,
     3. Brandhorst S,
     4. Wei M,
     5. Wang W,
     6. Lee C,
     7. Hwang S, et al.

     Fasting enhances the response of glioma to chemo- and radiotherapy. PLoS One 2012;7:e44603.
127. 127.
     2. Lee C,
     3. Raffaghello L,
     4. Brandhorst S,
     5. Safdie FM,
     6. Bianchi G,
     7. 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.

     OpenUrlAbstract/FREE Full Text
128. 128.↵
     2. Saleh AD,
     3. Simone BA,
     4. Savage J,
     5. Sano Y,
     6. Jin L,
     7. Champ C, et al.

     Caloric restriction augments radiation efficacy in breast cancer. Cell Cycle 2013;12:1955–1963.

     OpenUrlCrossRefPubMed
129. 129.↵
     2. Cantó C,
     3. Auwerx J.

     Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+? Pharmacol Rev 2012;64:166–187.

     OpenUrlCrossRefPubMed
130. 130.↵
     2. Veech RL.

     The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids 2004;70:309–319.

     OpenUrlCrossRefPubMedWeb of Science
131. 131.↵
     2. Lin Z,
     3. Fang D.

     The Roles of SIRT1 in Cancer. Genes Cancer 2013;4:97–104.

     OpenUrl
132. 132.↵
     2. Yu XM,
     3. Liu Y,
     4. Jin T,
     5. Liu J,
     6. Wang J,
     7. Ma C, et al.

     The Expression of SIRT1 and DBC1 in Laryngeal and Hypopharyngeal Carcinomas. PLoS One 2013;8:e66975.
133. 133.↵
     2. Ming M,
     3. Shea CR,
     4. Guo X,
     5. Li X,
     6. Soltani K,
     7. Han W, et al.

     Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C. Proc Natl Acad Sci U S A 2010;107:22623–8.

     OpenUrlAbstract/FREE Full Text
134. 134.↵
     2. Magee BA,
     3. Potezny N,
     4. Rofe AM,
     5. Conyers RA.

     The inhibition of malignant cell growth by ketone bodies. Aust J Exp Biol Med Sci 1979;57:529–539.

     OpenUrlCrossRefPubMed
135. 135.↵
     2. Fine EJ,
     3. Miller A,
     4. Quadros E V,
     5. Sequeira JM,
     6. Feinman RD.

     Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2. Cancer Cell Int 2009;9:14.

     OpenUrlPubMed
136. 136.↵
     2. Rieger J,
     3. Bähr O,
     4. Maurer GD,
     5. Hattingen E,
     6. Franz K,
     7. Brucker D, et al.

     ERGO: A pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol 2014;44:1843–1852.

     OpenUrlPubMed
137. 137.↵
     2. Rossi-Fanelli F,
     3. Franchi F,
     4. Mulieri M,
     5. Cangiano C,
     6. Cascino A,
     7. Ceci F, et al.

     Effect of energy substrate manipulation on tumor cell proliferation in parenterally fed cancer patients. Clin Nutr 1991;10:228–232.

     OpenUrlPubMed
138. 138.↵
     2. Mukherjee P,
     3. Sotnikov AV,
     4. Mangian HJ,
     5. Zhou J,
     6. Visek WJ,
     7. Clinton SK.

     Energy Intake and Prostate Tumor Growth, Angiogenesis, and Vascular Endothelial Growth Factor Expression. J Natl Cancer Inst 1999;91:512–523.

     OpenUrlCrossRefPubMedWeb of Science
139. 139.
     2. Mukherjee P,
     3. Abate LE,
     4. Seyfried TN.

     Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors Antiangiogenic and Proapoptotic Effects of Dietary Restriction on Experimental Mouse and Human Brain Tumors. Clin Cancer Res 2004;10:5622–5629.

     OpenUrlAbstract/FREE Full Text
140. 140.↵
     2. Urits I,
     3. Mukherjee P,
     4. Meidenbauer J,
     5. Seyfried TN.

     Dietary restriction promotes vessel maturation in a mouse astrocytoma. J Oncol 2012;2012:264039.

     OpenUrlPubMed
141. 141.↵
     2. Woolf EC,
     3. Scheck AC.

     The Ketogenic Diet for the Treatment of Malignant Glioma. J Lipid Res 2014. [Epub ahead of print].
142. 142.↵
     2. Christopoulos A,
     3. Ahn SM,
     4. Klein JD,
     5. Kim S.

     Biology of Vascular Endothelial Grwoth Factor and its Receptors in Head And Neck Cancer: Beyond Angiogenesis. Head Neck 2011;33:1220–1229.

     OpenUrlCrossRefPubMed
143. 143.↵
     2. Poff AM,
     3. Ari C,
     4. Seyfried TN,
     5. Agostino DPD.

     The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer. PLoS One 2013;8:e65522.
144. 144.↵
     2. D’Agostino DP,
     3. Pilla R,
     4. Held HE,
     5. Landon CS,
     6. Puchowicz M,
     7. Brunengraber H, et al.

     Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats. Am J Physiol Regul Integr Comp Physiol 2013;304:R829–R836.

     OpenUrlCrossRefPubMedWeb of Science
145. 145.↵
     2. Johns N,
     3. Stephens NA,
     4. Fearon KCH.

     Muscle wasting in cancer. Int J Biochem Cell Biol 2013;45:2215–2229.

     OpenUrlCrossRefPubMed
146. 146.↵
     2. Selberg O,
     3. Selberg D.

     Norms and correlates of bioimpedance phase angle in healthy human subjects, hospitalized patients, and patients with liver cirrhosis. Eur J Appl Physiol 2002;86:509–516.

     OpenUrlCrossRefPubMedWeb of Science
147. 147.↵
     2. Toso S,
     3. Piccoli A,
     4. Gusella M,
     5. Menon D,
     6. Bononi A,
     7. Crepaldi G, et al.

     Altered Tissue Electric Properties in Lung Cancer Patients as Detected by Bioelectric Impedance Vector Analysis. Nutrition 2000;16:120–124.

     OpenUrlCrossRefPubMedWeb of Science
148. 148.
     2. Gupta D,
     3. Lammersfeld CA,
     4. Burrows JL,
     5. Dahlk SL,
     6. Vashi PG,
     7. Grutsch JF, et al.

     Bioelectrical impedance phase angle in clinical practice: implications for prognosis in advanced colorectal cancer. Am J Clin Nutr 2004;80:1634–1638.

     OpenUrlAbstract/FREE Full Text
149. 149.↵
     2. Gupta D,
     3. Lammersfeld CA,
     4. Vashi PG,
     5. King J,
     6. Dahlk SL,
     7. Grutsch JF, et al.

     Bioelectrical impedance phase angle as a prognostic indicator in breast cancer. BMC Cancer 2008;8:249.

     OpenUrlCrossRefPubMed
150. 150.↵
     2. De Luis DA,
     3. Aller R,
     4. Izaola O,
     5. Terroba M,
     6. Cabezas G,
     7. Cuellar L.

     Tissue electric properties in head and neck cancer patients. Ann Nutr Metab 2006;50:7–10.

     OpenUrlCrossRefPubMed
151. 151.↵
     2. McCall JL,
     3. Tuckey JA,
     4. Parry BR.

     Serum tumour necrosis factor alpha and insulin resistance in gastrointestinal cancer. Br J Surg 1992;79:1361–1363.

     OpenUrlCrossRefPubMedWeb of Science
152. 152.
     2. Noguchi Y,
     3. Yoshikawa T,
     4. Marat D,
     5. Doi C,
     6. Makino T,
     7. Fukuzawa K, et al.

     Insulin Resistance in Cancer Patients Is Associated with Enhanced Tumor Necrosis Factor-alpha Expression in Skeletal Muscle. Biochem Biophys Res Commun 1998;253:887–892.

     OpenUrlCrossRefPubMedWeb of Science
153. 153.
     2. Makino T,
     3. Noguchi Y,
     4. Yoshikawa T,
     5. Doi C,
     6. Nomura K.

     Circulating interleukin 6 concentrations and insulin resistance in patients with cancer. Br J Surg 1998;85:1658–1662.

     OpenUrlCrossRefPubMedWeb of Science
154. 154.↵
     2. Yoshikawa T,
     3. Noguchi Y,
     4. Doi C,
     5. Makino T,
     6. Nomura K.

     Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure. Nutrition 2001;17:590–593.

     OpenUrlCrossRefPubMedWeb of Science
155. 155.↵
     2. Marks PA,
     3. Bishop JS.

     The glucose metabolism of patients with malignant disease and of normal subjects as studied by means of an intravenous glucose tolerance test. J Clin Invest 1957;36:254–264.

     OpenUrlPubMedWeb of Science
156. 156.↵
     2. Lundholm K,
     3. Hoim G,
     4. Scherstén T.

     Insulin Resistance in Patients with Cancer. Cancer Res 1978;38:4665–4670.

     OpenUrlAbstract/FREE Full Text
157. 157.↵
     2. Norton JA,
     3. Maher M,
     4. Wesley R,
     5. White D,
     6. Brennan MF.

     Glucose lntolerance in Sarcoma Patients. Cancer 1984;54:3022–3027.

     OpenUrlCrossRefPubMedWeb of Science
158. 158.↵
     2. Hansell DT,
     3. Davies JWL,
     4. Burns HJG,
     5. Shenkin A.

     The Oxidation of Body Fuel in Cancer Patients. Ann Surg 1986;204:637–642.

     OpenUrlPubMedWeb of Science
159. 159.↵
     2. Gambardella A,
     3. Paolisso G,
     4. D’Amore A,
     5. Granato M,
     6. Verza M,
     7. Varricchio M.

     Different Contribution of Substrates Oxidation to Insulin Resistance in Malnourished Elderly Patients with Cancer. Cancer 1993;72:3106–3113.

     OpenUrlCrossRefPubMed
160. 160.↵
     2. Körber J,
     3. Pricelius S,
     4. Heidrich M,
     5. Müller MJ.

     Increased lipid utilization in weight losing and weight stable cancer patients with normal body weight. Eur J Clin Nutr 1999;53:740–745.

     OpenUrlCrossRefPubMed
161. 161.↵
     2. Breitkreutz R,
     3. Tesdal K,
     4. Jentschura D,
     5. Haas O,
     6. Leweling H,
     7. Holm E.

     Effects of a high-fat diet on body composition in cancer patients receiving chemotherapy: a randomized controlled study. Wien Klin Wochenschr 2005;117:685–692.

     OpenUrlPubMed
162. 162.↵
     2. Fearon KC,
     3. Borland W,
     4. Preston T,
     5. Tisdale MJ,
     6. Shenkin A,
     7. Calman KC.

     Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. Am J Clin Nutr 1988;47:42–48.

     OpenUrlAbstract/FREE Full Text
163. 163.↵
     2. Rich AJ,
     3. Wright PD.

     Ketosis and nitrogen excretion in undernourished surgical patients. JPEN J Parenter Enteral Nutr 1979;3:350–354.

     OpenUrlCrossRefPubMed
164. 164.↵
     2. Buse MG,
     3. Biggers JF,
     4. Friderici KH,
     5. Buse JF.

     Oxidation of branched chain amino acids by isolated hearts and diaphragms of the rat. The effect of fatty acids, glucose, and pyruvate respiration. J Biol Chem 1972;247:8085–8096.

     OpenUrlAbstract/FREE Full Text
165. 165.↵
     2. Palaiologos G,
     3. Felig P.

     Effects of ketone bodies on amino acid metabolism in isolated rat diaphragm. Biochem J 1976;154:709–716.

     OpenUrlAbstract/FREE Full Text
166. 166.↵
     2. Klement RJ,
     3. Frobel T,
     4. Albers T,
     5. Fikenzer S,
     6. Prinzhausen J,
     7. Kämmerer U.

     A pilot case study on the impact of a self-prescribed ketogenic diet on biochemical parameters and running performance in healthy and physically active individuals. Nutr Med 2013;1:10.

     OpenUrl
167. 167.↵
     2. Volek JS,
     3. Sharman MJ,
     4. Love DM,
     5. Avery NG,
     6. Gómez AL,
     7. Scheett TP, et al.

     Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism 2002;51:864–870.

     OpenUrlCrossRefPubMedWeb of Science
168. 168.↵
     2. Paoli A,
     3. Grimaldi K,
     4. D’Agostino D,
     5. Cenci L,
     6. Moro T,
     7. Bianco A, et al.

     Ketogenic diet does not affect strength performance in elite artistic gymnasts. J Int Soc Sports Nutr 2012;9:34.

     OpenUrlCrossRefPubMed
169. 169.↵
     2. Jager-Wittenaar H,
     3. Dijkstra PU,
     4. Vissink A,
     5. Langendijk JA,
     6. van derLaan BFAM,
     7. Pruim J, et al.

     Changes in Nutritional Status and Dietary Intake During and After Head And Neck Cancer Treatment. Head Neck 2011;33:863–870.

     OpenUrlCrossRefPubMed
170. 170.↵
     2. Aapro M,
     3. Arends J,
     4. Bozzetti F,
     5. Fearon K,
     6. Grunberg SM,
     7. Herrstedt J, et al.

     Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force. Ann Oncol 2014;25:1492–1499.

     OpenUrlCrossRefPubMedWeb of Science
171. 171.↵
     2. Huebner J,
     3. Marienfeld S,
     4. Abbenhardt C,
     5. Ulrich C,
     6. Muenstedt K,
     7. Micke O, et al.

     Counseling Patients on Cancer Diets: A Review of the Literature and Recommendations for Clinical Practice. Anticancer Res 2014;34:39–48.

     OpenUrlAbstract/FREE Full Text
172. 172.↵
     2. Arends J,
     3. Bodoky G,
     4. Bozzetti F,
     5. Fearon K,
     6. Muscaritoli M,
     7. Selga G, et al.

     ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Clin Nutr 2006;25:245–259.

     OpenUrlCrossRefPubMedWeb of Science
173. 173.↵
     2. Manninen AH.

     High-Protein Weight Loss Diets and Purported Adverse Effects: Where is the Evidence? J Int Soc Sport Nutr 2004;1:45.

     OpenUrl
174. 174.
     2. Manninen AH.

     Metabolic effects of the very-low-carbohydrate diets: misunderstood “villains” of human metabolism. J Int Soc Sports Nutr 2004;1:7–11.

     OpenUrlCrossRefPubMed
175. 175.↵
     2. Manninen A.

     High-Protein Diets: Putting Rumors to Rest. J Am Coll Cardiol 2004;44:1526.

     OpenUrlFREE Full Text
176. 176.↵
     2. Schmidt M,
     3. Pfetzer N,
     4. Schwab M,
     5. Strauss I,
     6. 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.

     OpenUrlCrossRefPubMed
177. 177.↵
     2. Fearon K,
     3. Strasser F,
     4. Anker SD,
     5. Bosaeus I,
     6. Bruera E,
     7. Fainsinger RL, et al.

     Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011;12:489–495.

     OpenUrlCrossRefPubMedWeb of Science
178. 178.↵
     2. Langius JA,
     3. Zandbergen MC,
     4. Eerenstein SE,
     5. van Tulder MW,
     6. Leemans CR,
     7. Kramer MH, et al.

     Effect of nutritional interventions on nutritional status, quality of life and mortality in patients with head and neck cancer receiving (chemo) radiotherapy : a systematic review. Clin Nutr 2013;32:671–678.

     OpenUrlCrossRefPubMed
179. 179.↵
     2. Hashim SA,
     3. Vanltallie TB.

     Ketone Body Therapy: From ketogenic diet to oral administration of ketone ester. J Lipid Res 2014;55:1818–1826.

     OpenUrlAbstract/FREE Full Text
180. 180.↵
     2. Lucà-Moretti M.

     Comparative study of the administration of anabolic amino acids. Confirms the discovery of the Master Amino Acid Pattern. An R Acad Nac Med (Madr) 1998;115:397–413; discussion 413-416.

     OpenUrlPubMed
181. 181.↵
     2. Lønbro S,
     3. Dalgas U,
     4. Primdahl H,
     5. Johansen J,
     6. Nielsen JL,
     7. Overgaard J, et al.

     Lean body mass and muscle function in head and neck cancer patients and healthy individuals – results from the DAHANCA 25 study. Acta Oncol 2013;52:1543–1551.

     OpenUrlCrossRefPubMed