Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients

Nutrition

Volumn 28, Issue 10, 2012, Pages 1028-1035

  Fine, Eugene J ^a   Segal Isaacson, C J ^a   Feinman, Richard D ^b   Herszkopf, Silvia ^c   Romano, Maria C ^c   Tomuta, Norica ^a   Bontempo, Amanda F ^c   Negassa, Abdissa ^a   Sparano, Joseph A ^d  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b SUNY DOWNSTATE MEDICAL CENTER   (United States)

^c ALBERT EINSTEIN CANCER CENTER   (United States)

^d MONTEFIORE MEDICAL CENTER   (United States)

Author keywords

Calorie restriction; Cancer metabolism; Carbohydrate restriction; Diet; Insulin inhibition; Ketosis; Therapy; Warburg effect

Indexed keywords

3 HYDROXYBUTYRIC ACID; ELECTROLYTE; INSULIN; SOMATOMEDIN B; SOMATOMEDIN C;

ADULT; ADVANCED CANCER; AGED; ARTICLE; BODY MASS; BODY WEIGHT; BREAST CANCER; CALORIC INTAKE; CALORIC RESTRICTION; CANCER REGRESSION; CLINICAL ARTICLE; CLINICAL TRIAL; COLORECTAL CANCER; CORRELATION ANALYSIS; DISEASE ASSOCIATION; DISEASE COURSE; ELECTROLYTE BLOOD LEVEL; ESOPHAGUS CANCER; FEASIBILITY STUDY; FEMALE; FOOD COMPOSITION; FOOD INTAKE; GLYCOLYSIS; HUMAN; INSULIN BLOOD LEVEL; KETOACIDOSIS; LOW CARBOHYDRATE DIET; LUNG CANCER; MALE; OVARY CANCER; PATIENT COMPLIANCE; PATIENT MONITORING; PATIENT SAFETY; PILOT STUDY; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; UTERINE TUBE CARCINOMA; WEIGHT REDUCTION;

AGED; DIET, CARBOHYDRATE-RESTRICTED; DIETARY CARBOHYDRATES; DISEASE PROGRESSION; ENERGY INTAKE; FEASIBILITY STUDIES; FEMALE; GLYCOLYSIS; HUMANS; INSULIN; KETOSIS; MALE; MIDDLE AGED; NEOPLASMS; PILOT PROJECTS; WEIGHT LOSS;

EID: 84865427329     PISSN: 08999007     EISSN: 18731244     Source Type: Journal    
DOI: 10.1016/j.nut.2012.05.001     Document Type: Article

References (96)

1. Warburg O. On the origin of cancer cells. Science 1956, 123:309-314.
2. Gillies R.J., Robey I., Gatenby R.A. Causes and consequences of increased glucose metabolism of cancers. J Nucl Med 2008, 49(suppl 2):24S-42S.
3. Vander Heiden M.G., Cantley L.C., Thompson C.B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033.
4. Hoskin P.J., Sibtain A., Daley F.M., Wilson G.D. GLUT1 and CAIX as intrinsic markers of hypoxia in bladder cancer: relationship with vascularity and proliferation as predictors of outcome of ARCON. Br J Cancer 2003, 89:1290-1297.
5. Lambert D.W., Wood I.S., Ellis A., Shirazi-Beechey S.P. Molecular changes in the expression of human colonic nutrient transporters during the transition from normality to malignancy. Br J Cancer 2002, 86:1262-1269.
6. Yamamoto T., Seino Y., Fukumoto H., Koh G., Yano H., Inagaki N., et al. Over-expression of facilitative glucose transporter genes in human cancer. Biochem Biophys Res Commun 1990, 170:223-230.
7. Mathupala S.P., Ko Y.H., Pedersen P.L. Hexokinase-2 bound to mitochondria: cancer's stygian link to the "Warburg effect" and a pivotal target for effective therapy. Semin Cancer Biol 2009, 19:17-24.
8. Mathupala S.P., Rempel A., Pedersen P.L. 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, 276:43407-43412.
9. Abdel-Nabi H., Doerr R.J., Lamonica D.M., Cronin V.R., Galantowicz P.J., Carbone G.M., et al. Staging of primary colorectal carcinomas with fluorine-18 fluorodeoxyglucose whole-body PET: correlation with histopathologic and CT findings. Radiology 1998, 206:755-760.
10. Bang S., Chung H.W., Park S.W., Chung J.B., Yun M., Lee J.D., et al. The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer. J Clin Gastroenterol 2006, 40:923-929.
11. Findlay M., Young H., Cunningham D., Iveson A., Cronin B., Hickish T., et al. Noninvasive monitoring of tumor metabolism using fluorodeoxyglucose and positron emission tomography in colorectal cancer liver metastases: correlation with tumor response to fluorouracil. J Clin Oncol 1996, 14:700-708.
12. Vansteenkiste J.F., Stroobants S.G., De Leyn P.R., Dupont P.J., Verbeken E.K. Potential use of FDG-PET scan after induction chemotherapy in surgically staged IIIa-N2 non-small-cell lung cancer: a prospective pilot study. The Leuven Lung Cancer Group. Ann Oncol 1998, 9:1193-1198.
13. Weber W.A., Wieder H. Monitoring chemotherapy and radiotherapy of solid tumors. Eur J Nucl Med Mol Imaging 2006, 33(suppl 1):27-37.
14. Gunter M.J., Hoover D.R., Yu H., Wassertheil-Smoller S., Manson J.E., Li J., et al. A prospective evaluation of insulin and insulin-like growth factor-I as risk factors for endometrial cancer. Cancer Epidemiol Biomarkers Prev 2008, 17:921-929.
15. Gunter M.J., Hoover D.R., Yu H., Wassertheil-Smoller S., Rohan T.E., Manson J.E., et al. Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res 2008, 68:329-337.
16. Lann D., LeRoith D. The role of endocrine insulin-like growth factor-I and insulin in breast cancer. J Mammary Gland Biol Neoplasia 2008, 13:371-379.
17. Albanes D., Weinstein S.J., Wright M.E., Mannisto S., Limburg P.J., Snyder K., et al. Serum insulin, glucose, indices of insulin resistance, and risk of prostate cancer. J Natl Cancer Inst 2009, 101:1272-1279.
18. Fine E., Segal-Isaacson C., Feinman R., Sparano J. Carbohydrate restriction in patients with advanced cancer: a protocol to assess safety and feasibility with an accompanying hypothesis. Community Oncol 2008, 5:22-26.
19. Fine E.J., Miller A., Quadros E.V., Sequeira J.M., Feinman R.D. Acetoacetate reduces growth and ATP concentration in cancer cell lines which over-express uncoupling protein 2. Cancer Cell Int 2009, 9:14.
20. Kalaany N.Y., Sabatini D.M. Tumours with PI3K activation are resistant to dietary restriction. Nature 2009, 458:725-731.
21. Sengupta S., Peterson T.R., Laplante M., Oh S., Sabatini D.M. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 2010, 468:1100-1104.
22. Shackelford D.B., Shaw R.J. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression. Nat Rev Cancer 2009, 9:563-575.
23. Fung A.S., Wu L., Tannock I.F. Concurrent and sequential administration of chemotherapy and the mammalian target of rapamycin inhibitor temsirolimus in human cancer cells and xenografts. Clin Cancer Res 2009, 15:5389-5395.
24. Yao J.C., Lombard-Bohas C., Baudin E., Kvols L.K., Rougier P., Ruszniewski P., et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 2010, 28:69-76.
25. Zeng Q., Yang Z., Gao Y.J., Yuan H., Cui K., Shi Y., et al. Treating triple-negative breast cancer by a combination of rapamycin and cyclophosphamide: an in vivo bioluminescence imaging study. Eur J Cancer 2010, 46:1132-1143.
26. David-Pfeuty T., Legraverend M., Ludwig O., Grierson D.S. Targeting the cell cycle and the PI3K pathway: a possible universal strategy to reactivate innate tumor suppressor programmes in cancer cells. Int J Oncol 2010, 36:873-881.
27. Lopez-Fauqued M., Gil R., Grueso J., Hernandez-Losa J., Pujol A., Moline T., et al. The dual PI3K/mTOR inhibitor PI-103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. Int J Cancer 2010, 126:1549-1561.
28. Cantrell L.A., Zhou C., Mendivil A., Malloy K.M., Gehrig P.A., Bae-Jump V.L. Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy. Gynecol Oncol 2009, 116:92-98.
29. Garcia-Garcia C., Fumarola C., Navaratnam N., Carling D., Lopez-Rivas A. AMPK-independent down-regulation of cFLIP and sensitization to TRAIL-induced apoptosis by AMPK activators. Biochem Pharmacol 2010, 79:853-863.
30. Hsu Y.C., Meng X., Ou L., Ip M.M. Activation of the AMP-activated protein kinase-p38 MAP kinase pathway mediates apoptosis induced by conjugated linoleic acid in p53-mutant mouse mammary tumor cells. Cell Signal 2010, 22:590-599.
31. Lin J.N., Lin V.C., Rau K.M., Shieh P.C., Kuo D.H., Shieh J.C., et al. Resveratrol modulates tumor cell proliferation and protein translation via SIRT1-dependent AMPK activation. J Agric Food Chem 2010, 58:1584-1592.
32. Luo Z., Zang M., Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol 2010, 6:457-470.
33. Koh M.Y., Spivak-Kroizman T.R., Powis G. Inhibiting the hypoxia response for cancer therapy: the new kid on the block. Clin Cancer Res 2009, 15:5945-5946.
34. Leeman-Neill R.J., Wheeler S.E., Singh S.V., Thomas S.M., Seethala R.R., Neill D.B., et al. Guggulsterone enhances head and neck cancer therapies via inhibition of signal transducer and activator of transcription-3. Carcinogenesis 2009, 30:1848-1856.
35. Sun X., Jiang H., Jiang X., Tan H., Meng Q., Sun B., et al. Antisense hypoxia-inducible factor-1alpha augments transcatheter arterial embolization in the treatment of hepatocellular carcinomas in rats. Hum Gene Ther 2009, 20:314-324.
36. Fantin V.R., St-Pierre J., Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell 2006, 9:425-434.
37. Geschwind J.F., Ko Y.H., Torbenson M.S., Magee C., Pedersen P.L. Novel therapy for liver cancer: direct intraarterial injection of a potent inhibitor of ATP production. Cancer Res 2002, 62:3909-3913.
38. Pedersen P.L. The cancer cell's "power plants" as promising therapeutic targets: an overview. J Bioenerg Biomembr 2007, 39:1-12.
39. Edefonti V., Decarli A., La Vecchia C., Bosetti C., Randi G., Franceschi S., et al. Nutrient dietary patterns and the risk of breast and ovarian cancers. Int J Cancer 2008, 122:609-613.
40. Marsh J., Mukherjee P., Seyfried T.N. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet. Nutr Metab (Lond) 2008, 5:33.
41. Mukherjee P., Mulrooney T.J., Marsh J., Blair D., Chiles T.C., Seyfried T.N. Differential effects of energy stress on AMPK phosphorylation and apoptosis in experimental brain tumor and normal brain. Mol Cancer 2008, 7:37.
42. Zhu Z., Jiang W., McGinley J.N., Thompson H.J. 2-Deoxyglucose as an energy restriction mimetic agent: effects on mammary carcinogenesis and on mammary tumor cell growth in vitro. Cancer Res 2005, 65:7023-7030.
43. Kuhajda F.P., Jenner K., Wood F.D., Hennigar R.A., Jacobs L.B., Dick J.D., et al. Fatty acid synthesis: a potential selective target for antineoplastic therapy. Proc Natl Acad Sci U S A 1994, 91:6379-6383.
44. Lu S., Archer M.C. Fatty acid synthase is a potential molecular target for the chemoprevention of breast cancer. Carcinogenesis 2005, 26:153-157.
45. Zhou W., Simpson P.J., McFadden J.M., Townsend C.A., Medghalchi S.M., Vadlamudi A., et al. Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res 2003, 63:7330-7337.
46. Hernandez T.L., Sutherland J.P., Wolfe P., Allian-Sauer M., Capell W.H., Talley N.D., et al. Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. Am J Clin Nutr 2010, 91:578-585.
47. Hwalla N., Shaker L., Torbay N., Azar S.T., Habbal Z., Adra N. Postprandial glycemic and insulinemic responses to high-carbohydrate vs high-protein meals in obese normoglycemic subjects with varied insulin sensitivity. Nutri Res 2005, 25:535-548.
48. Nuttall F.Q., Gannon M.C., Saeed A., Jordan K., Hoover H. The metabolic response of subjects with type 2 diabetes to a high-protein, weight-maintenance diet. J Clin Endocrinol Metab 2003, 88:3577-3583.
49. Gannon M.C., Nuttall F.Q. Effect of a high-protein, low-carbohydrate diet on blood glucose control in people with type 2 diabetes. Diabetes 2004, 53:2375-2382.
50. Cifuentes M., García M.A., Arrabal P.M., Martínez F., Yañez M.J., Jara N., et al. Insulin regulates GLUT1-mediated glucose transport in MG-63 human osteosarcoma cells. J Cell Physiol 2011, 226:1425-1432.
51. Demetrakopoulos G.E., Brennan M.F. Tumoricidal potential of nutritional manipulations. Cancer Res 1982, 42(2 suppl):756s-765s.
52. Fearon K.C., Borland W., Preston T., Tisdale M.J., Shenkin A., Calman K.C. Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. Am J Clin Nutr 1988, 47:42-48.
53. Magee B.A., Potezny N., Rofe A.M., Conyers R.A. The inhibition of malignant cell growth by ketone bodies. Aust J Exp Biol Med Sci 1979, 57:529-539.
54. Mavropoulos J.C., Isaacs W.B., Pizzo S.V., Freedland S.J. Is there a role for a low-carbohydrate ketogenic diet in the management of prostate cancer?. Urology 2006, 68:15-18.
55. Nebeling L.C., Miraldi F., Shurin S.B., 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.
56. Tisdale M.J., Brennan R.A., Fearon K.C. Reduction of weight loss and tumour size in a cachexia model by a high fat diet. Br J Cancer 1987, 56:39-43.
57. Seyfried T.N., Mukherjee P. Targeting energy metabolism in brain cancer: review and hypothesis. Nutr Metab (Lond) 2005, 2:30.
58. Moulton C.J., Valentine R.J., Layman D.K., Devkota S., Singletary K.W., Wallig M.A., et al. A high protein moderate carbohydrate diet fed at discrete meals reduces early progression of N-methyl-N-nitrosourea-induced breast tumorigenesis in rats. Nutr Metab (Lond) 2010, 7:1.
59. Seyfried T.N., Sanderson T.M., El-Abbadi M.M., McGowan R., Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 2003, 89:1375-1382.
60. 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.
61. Ho V.W., Leung K., Hsu A., Luk B., Lai J., Shen S.Y., et al. A low carbohydrate, high protein diet slows tumor growth and prevents cancer initiation. Cancer Res 2011, 71:4484-4493.
62. Sharman M.J., Kraemer W.J., Love D.M., Avery N.G., Gomez A.L., Scheett T.P., et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr 2002, 132:1879-1885.
63. Yancy W.S., Foy M., Chalecki A.M., Vernon M.C., Westman E.C. A low-carbohydrate, ketogenic diet to treat type 2 diabetes. Nutr Metab (Lond) 2005, 2:34.
64. Samaha F.F., Iqbal N., Seshadri P., Chicano K.L., Daily D.A., McGrory J., et al. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med 2003, 348:2074-2081.
65. Foster G.D., Wyatt H.R., Hill J.O., Makris A.P., Rosenbaum D.L., Brill C., et al. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med 2010, 153:147-157.
66. Nielsen J.V., Joensson E. Low-carbohydrate diet in type 2 diabetes. Stable improvement of bodyweight and glycemic control during 22 months follow-up. Nutr Metab (Lond) 2006, 3:22.
67. Sharman M.J., Volek J.S. Weight loss leads to reductions in inflammatory biomarkers after a very-low-carbohydrate diet and a low-fat diet in overweight men. Clin Sci (Lond) 2004, 107:365-369.
68. Volek J.S., Sharman M.J., Gomez A.L., DiPasquale C., Roti M., Pumerantz A., et al. Comparison of a very low-carbohydrate and low-fat diet on fasting lipids, LDL subclasses, insulin resistance, and postprandial lipemic responses in overweight women. J Am Coll Nutr 2004, 23:177-184.
69. 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, 8:54.
70. Fine E., Segal-Isaacson C., Sparano J., Herszkopf S., Feinman R. The RECHARGE Trial (Reduced Carbohydrates in Resistant Aggressive Tumors). FDG-PET to monitor metastatic cancer in very low carbohydrate diet. A study to assess feasibility. J Nucl Med 2008, 49. 370P-c.
71. Harris J.A., Benedict F.G. A biometric study of basal metabolism in man. Publication 279 1919, Carnegie Institute of Washington, Washington, DC, p 279.
72. Young H., Baum R., Cremerius U., Herholz K., Hoekstra O., Lammertsma A.A., et al. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer 1999, 35:1773-1782.
73. Jana S., Zhang T., Milstein D.M., Isasi C.R., Blaufox M.D. FDG-PET and CT characterization of adrenal lesions in cancer patients. Eur J Nucl Med Mol Imaging 2006, 33:29-35.
74. Nahmias C., Wahl L.M. Reproducibility of standardized uptake value measurements determined by 18F-FDG PET in malignant tumors. J Nucl Med 2008, 49:1804-1808.
75. Efron B., Tibshirani R.J. An introduction to the bootstrap 1993, Chapman & Hill, San Francisco.
76. Cockcroft D., Gault M. Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16:31-41.
77. 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).7:33.
78. Carde P., Koscielny S., Franklin J., Axdorph U., Raemaekers J., Diehl V., et al. Early response to chemotherapy: a surrogate for final outcome of Hodgkin's disease patients that should influence initial treatment length and intensity?. Ann Oncol 2002, 13(suppl 1):86-91.
79. Romer W., Hanauske A.R., Ziegler S., Thodtmann R., Weber W., Fuchs C., et al. Positron emission tomography in non-Hodgkin's lymphoma: assessment of chemotherapy with fluorodeoxyglucose. Blood 1998, 91:4464-4471.
80. Spaepen K., Stroobants S., Dupont P., Vandenberghe P., Thomas J., de Groot T., et al. Early restaging positron emission tomography with (18)F-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 2002, 13:1356-1363.
81. Atkins R.C. Dr. Atkins' new diet revolution 2002, Avon Books, New York.
82. Seyfried B.T., Kiebish M., Marsh J., Mukherjee P. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet. J Cancer Res Ther 2009, 5(suppl 1):S7-S15.
83. Beck S.A., Tisdale M.J. Effect of insulin on weight loss and tumour growth in a cachexia model. Br J Cancer 1989, 59:677-681.
84. Adam-Perrot A., Clifton P., Brouns F. Low-carbohydrate diets: nutritional and physiological aspects. Obes Rev 2006, 7:49-58.
85. Johnstone A.M., Horgan G.W., Murison S.D., Bremner D.M., Lobley G.E. 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.
86. Hursting S.D., Smith S.M., Lashinger L.M., Harvey A.E., Perkins S.N. Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research. Carcinogenesis 2010, 31:83-89.
87. Longo V.D., Fontana L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci 2010, 31:89-98.
88. Bonorden M.J., Rogozina O.P., Kluczny C.M., Grossmann M.E., Grambsch P.L., Grande J.P., et al. Intermittent calorie restriction delays prostate tumor detection and increases survival time in TRAMP mice. Nutr Cancer 2009, 61:265-275.
89. Johnson J.B., John S., Laub D.R. Pretreatment with alternate day modified fast will permit higher dose and frequency of cancer chemotherapy and better cure rates. Med Hypotheses 2009, 72:381-382.
90. Shelton L.M., Huysentruyt L.C., Mukherjee P., Seyfried T.N. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse. ASN Neuro 2010, 2:e00038.
91. Azar G.J.B.L. Similarities of carbohydrate deficiency and fasting. Arch Intern Med 1962, 112:92-97.
92. Klein S., Wolfe R.R. Carbohydrate restriction regulates the adaptive response to fasting. Am J Physiol Endocrinol Metabl 1992, 262(5 Pt 1):E631-E636.
93. Raffaghello L., Lee C., Safdie F.M., Wei M., Madia F., Bianchi G., et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc Natl Acad Sci U S A 2008, 105:8215-8220.
94. Safdie FM DT, Quinn D, Fontana L, Wei M, Lee C, Cohen P, and LongoVD. Fasting and cancer treatment in humans: a case series report. Aging 2009;1:1-20.
95. Gunter M.J., Hoover D.R., Yu H., Wassertheil-Smoller S., Rohan T.E., Manson J.E., et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst 2009, 101:48-60.
96. Harber M.P., Schenk S., Barkan A.L., Horowitz J.F. Effects of dietary carbohydrate restriction with high protein intake on protein metabolism and the somatotropic axis. J Clin Endocrinol Metab 2005, 90:5175-5181.