Selectively starving cancer cells through dietary manipulation: Methods and clinical implications

Future Oncology

Volumn 9, Issue 7, 2013, Pages 959-976

  Simone, Brittany A ^a   Champ, Colin E ^a   Rosenberg, Anne L ^a   Berger, Adam C ^a   Monti, Daniel A ^b   Dicker, Adam P ^a   Simone, Nicole L ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b THOMAS JEFFERSON UNIVERSITY HOSPITAL   (United States)

Author keywords

caloric restriction; cancer; diet; intermittent fasting; ketosis

Indexed keywords

ADIPONECTIN; INSULIN; LEPTIN; SOMATOMEDIN BINDING PROTEIN 1; SOMATOMEDIN BINDING PROTEIN 3; SOMATOMEDIN C;

CALORIC INTAKE; CALORIC RESTRICTION; CANCER CELL; CANCER INCIDENCE; CANCER LOCALIZATION; CANCER PATIENT; CANCER RISK; CANCER THERAPY; CARBOHYDRATE INTAKE; COMBINATION CHEMOTHERAPY; DEHYDRATION; DIET RESTRICTION; DIET SUPPLEMENTATION; DIET THERAPY; DIETARY COMPLIANCE; DISTANT METASTASIS; ELECTROLYTE DISTURBANCE; FATIGUE; HUMAN; INSULIN SENSITIVITY; KETOACIDOSIS; KETOGENIC DIET; LIFESTYLE MODIFICATION; LOW CARBOHYDRATE DIET; MACRONUTRIENT; MALNUTRITION; MEDITERRANEAN DIET; METABOLIC SYNDROME X; MITOCHONDRIAL RESPIRATION; MUSCLE ATROPHY; NONHUMAN; OBESITY; PRIMARY TUMOR; PRIORITY JOURNAL; PROTEIN INTAKE; REVIEW; TUMOR GROWTH; WEIGHT CHANGE; WEIGHT REDUCTION;

ANIMALS; CALORIC RESTRICTION; DIET, REDUCING; FASTING; HUMANS; KETOSIS; NEOPLASMS; OBESITY; PATIENT COMPLIANCE;

EID: 84880231512     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.13.31     Document Type: Review

References (119)

1. Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat. Rev. Cancer 4(8), 579-591 (2004).
2. Hursting SD, Slaga TJ, Fischer SM, Digiovanni J, Phang JM. Mechanism-based cancer prevention approaches: Targets, examples, and the use of transgenic mice. J. Natl Cancer Inst. 91(3), 215-225 (1999).
3. Fair AM, Montgomery K. Energy balance, physical activity, and cancer risk. Methods Mol. Biol. 472, 57-88 (2009).
4. Hursting SD, Berger NA. Energy balance, host-related factors, and cancer progression. J. Clin. Oncol. 28(26), 4058-4065 (2010).
5. Leroith D, Novosyadlyy R, Gallagher EJ, Lann D, Vijayakumar A, Yakar S. Obesity and Type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis; epidemiological and mechanistic evidence. Exp. Clin. Endocrinol. Diabetes 116(Suppl. 1), S4-S6 (2008).
6. Parekh N, Okada T, Lu-Yao GL. Obesity, insulin resistance, and cancer prognosis: Implications for practice for providing care among cancer survivors. J. Am. Diet. Assoc. 109(8), 1346-1353 (2009).
7. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 348(17), 1625-1638 (2003).
8. Wu AH, Yu MC, Tseng CC, Stanczyk FZ, Pike MC. Dietary patterns and breast cancer risk in Asian American women. Am. J. Clin. Nutr. 89(4), 1145-1154 (2009).
9. Mccarty MF. mTORC1 activity as a determinant of cancer risk - rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets. Med. Hypotheses 77(4), 642-648 (2011).
10. Tete S, Nicoletti M, Saggini A et al. Nutrition and cancer prevention. Int. J. Immunopathol. Pharmacol. 25(3), 573-581 (2012).
11. Speakman JR, Mitchell SE. Caloric restriction. Mol. Aspects Med. 32(3), 159-221 (2011).
12. Mattson MP, Wan R. Beneficial effects of intermittent fasting and caloric restriction on the cardiovascular and cerebrovascular systems. J. Nutr. Biochem. 16(3), 129-137 (2005).
13. Pallavi R, Giorgio M, Pelicci PG. Insights into the beneficial effect of caloric/dietary restriction for a healthy and prolonged life. Front. Physiol. 3, 318 (2012).
14. Merry BJ. Oxidative stress and mitochondrial function with aging - the effects of calorie restriction. Aging Cell 3(1), 7-12 (2004).
15. Rickman AD, Williamson DA, Martin CK et al. The CALERIE study: Design and methods of an innovative 25% caloric restriction intervention. Contemp. Clin. Trials 32(6), 874-881 (2011).
16. Tannenbaum A, Silverstone H. The influence of the degree of caloric restriction on the formation of skin tumors and hepatomas in mice. Cancer Res. 9(12), 724-727 (1949).
17. De Lorenzo MS, Baljinnyam E, Vatner DE, Abarzua P, Vatner SF, Rabson AB. Caloric restriction reduces growth of mammary tumors and metastases. Carcinogenesis 32(9), 1381-1387 (2011).
18. Michels KB, Ekbom A. Caloric restriction and incidence of breast cancer. JAMA 291(10), 1226-1230 (2004).
19. Suttie AW, Dinse GE, Nyska A, Moser GJ, Goldsworthy TL, Maronpot RR. An investigation of the effects of late-onset dietary restriction on prostate cancer development in the TRAMP mouse. Toxicol. Pathol. 33(3), 386-397 (2005).
20. Pollard M, Luckert PH, Snyder D. Prevention of prostate cancer and liver tumors in L-W rats by moderate dietary restriction. Cancer 64(3), 686-690 (1989).
21. Mukherjee P, El-Abbadi MM, Kasperzyk JL, Ranes MK, Seyfried TN. Dietary restriction reduces angiogenesis and growth in an orthotopic mouse brain tumour model. Br. J. Cancer 86(10), 1615-1621 (2002).
22. Pape-Ansorge KA, Grande JP, Christensen TA, Maihle NJ, Cleary MP. Effect of moderate caloric restriction and/or weight cycling on mammary tumor incidence and latency in MMTV-Neu female mice. Nutr. Cancer 44(2), 162-168 (2002).
23. Dirx MJ, Zeegers MP, Dagnelie PC, van den Bogaard T, van den Brandt PA. Energy restriction and the risk of spontaneous mammary tumors in mice: A meta-analysis. Int. J. Cancer 106(5), 766-770 (2003).
24. Chen RF, Good RA, Engelman RW et al. Suppression of mouse mammary tumor proviral DNA and protooncogene expression: Association with nutritional regulation of mammary tumor development. Proc. Natl Acad. Sci. USA 87(7), 2385-2389 (1990).
25. Engelman RW, Day NK, Chen RF et al. Calorie consumption level influences development of C3H/Ou breast adenocarcinoma with indifference to calorie source. Proc. Soc. Exp. Biol. Med. 193(1), 23-30 (1990).
26. Ershler WB, Berman E, Moore AL. Slower B16 melanoma growth but greater pulmonary colonization in calorie-restricted mice. J. Natl Cancer Inst. 76(1), 81-85 (1986).
27. Ong KR, Sims AH, Harvie M et al. Biomarkers of dietary energy restriction in women at increased risk of breast cancer. Cancer Prev. Res. (Phila.) 2(8), 720-731 (2009).
28. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat. Med. 23(7), 1111-1130 (2004).
29. Flowers MT, Ntambi JM. Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr. Opin. Lipidol. 19(3), 248-256 (2008).
30. Scaglia N, Igal RA. Stearoyl-CoA desaturase is involved in the control of proliferation, anchorage-independent growth, and survival in human transformed cells. J. Biol. Chem. 280(27), 25339-25349 (2005).
31. Tucci P Caloric restriction: Is mammalian life extension linked to p53? Aging (Albany NY) 4(8), 525-534 (2012).
32. Hursting SD, Perkins SN, Phang JM, Barrett JC. Diet and cancer prevention studies in p53-deficient mice. J. Nutr. 131(Suppl. 11), S3092-S3094 (2001).
33. Rochon J, Bales CW, Ravussin E et al. Design and conduct of the CALERIE study: Comprehensive assessment of the long-term effects of reducing intake of energy. J. Gerontol. A Biol. Sci. Med. Sci. 66(1), 97-108 (2011).
34. Sahingoz SA, Sanlier N. Compliance with Mediterranean Diet Quality Index (KIDMED) and nutrition knowledge levels in adolescents. A case study from Turkey. Appetite 57(1), 272-277 (2011).
35. Stevens VJ, Funk KL, Brantley PJ et al. Design and implementation of an interactive website to support long-term maintenance of weight loss. J. Med. Internet Res. 10(1), e1 (2008).
36. Schwarzfuchs D, Golan R, Shai I. Four-year follow-up after two-year dietary interventions. N. Engl. J. Med. 367(14), 1373-1374 (2012).
37. Mciver CM, Wycherley TP, Clifton PM. MTOR signaling and ubiquitin-proteosome gene expression in the preservation of fat free mass following high protein, calorie restricted weight loss. Nutr. Metab. (Lond.) 9(1), 83 (2012).
38. Morley JE, Chahla E, Alkaade S. Antiaging, longevity and calorie restriction. Curr. Opin. Clin. Nutr. Metab. Care 13(1), 40-45 (2010).
39. Kalaany NY, Sabatini DM. Tumours with PI3K activation are resistant to dietary restriction. Nature 458(7239), 725-731 (2009).
40. Acosta-Martinez M. PI3K: An attractive candidate for the central integration of metabolism and reproduction. Front. Endocrinol. (Lausanne) 2, 110 (2011).
41. Ray A, Nkhata KJ, Cleary MP. Effects of leptin on human breast cancer cell lines in relationship to estrogen receptor and HER2 status. Int. J. Oncol. 30(6), 1499-1509 (2007).
42. Calabrese EJ, Baldwin LA. Hormesis: A generalizable and unifying hypothesis. Crit. Rev. Toxicol. 31(4-5), 353-424 (2001).
43. Gredilla R, Barja G. Minireview: The role of oxidative stress in relation to caloric restriction and longevity. Endocrinology 146(9), 3713-3717 (2005).
44. Masoro EJ, Austad SN. The evolution of the antiaging action of dietary restriction: A hypothesis. J. Gerontol. A Biol. Sci. Med. Sci. 51(6), B387-391 (1996).
45. Wachsman JT. The beneficial effects of dietary restriction: Reduced oxidative damage and enhanced apoptosis. Mutat. Res. 350(1), 25-34 (1996).
46. Raffaghello L, Lee C, Safdie FM et al. Starvation-dependent differential stress resistance protects normal but not cancer cells against high-dose chemotherapy. Proc. Natl Acad. Sci. USA 105(24), 8215-8220 (2008).
47. Martin B, Mattson MP, Maudsley S. Caloric restriction and intermittent fasting: Two potential diets for successful brain aging. Ageing Res. Rev. 5(3), 332-353 (2006).
48. Buschemeyer WC 3rd, Klink JC, Mavropoulos JC et al. Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice. Prostate 70(10), 1037-1043 (2010).
49. Lee C, Raffaghello L, Brandhorst S et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapy. Sci. Transl. Med. 4(124), 124ra127 (2012).
50. Cleary MP, Grossmann ME. The manner in which calories are restricted impacts mammary tumor cancer prevention. J. Carcinog. 10, 21 (2011).
51. Bonorden MJ, Rogozina OP, Kluczny CM et al. Cross-sectional analysis of intermittent versus chronic caloric restriction in the TRAMP mouse. Prostate 69(3), 317-326 (2009).
52. Carlson AJ, Hoelzel F. Apparent prolongation of the life span of rats by intermittent fasting. J. Nutr. 31, 363-375 (1946).
53. Shao RP, Dao ML, Day NK, Good RA. Dietary manipulation of mammary tumor development in adult C3H/Bi mice. Proc. Soc. Exp. Biol. Med. 193(4), 313-317 (1990).
54. Lee C, Safdie FM, Raffaghello L et al. Reduced levels of IGF-I mediate differential protection of normal and cancer cells in response to fasting and improve chemotherapeutic index. Cancer Res. 70(4), 1564-1572 (2010).
55. Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: From model organisms to patients. Oncogene 30(30), 3305-3316 (2011).
56. Raffaghello L, Safdie F, Bianchi G, Dorff T, Fontana L, Longo VD. Fasting and differential chemotherapy protection in patients. Cell Cycle 9(22), 4474-4476 (2010).
57. Cleary MP, Jacobson MK, Phillips FC, Getzin SC, Grande JP, Maihle NJ. Weight-cycling decreases incidence and increases latency of mammary tumors to a greater extent than does chronic caloric restriction in mouse mammary tumor virus-transforming growth factor-alpha female mice. Cancer Epidemiol. Biomarkers Prev. 11(9), 836-843 (2002).
58. Muggeo M, Verlato G, Bonora E, Zoppini G, Corbellini M, De Marco R. Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: The Verona Diabetes Study. Circulation 96(6), 1750-1754 (1997).
59. Greenwood CE. Dietary carbohydrate, glucose regulation, and cognitive performance in elderly persons. Nutr. Rev. 61(5 Pt 2), S68-S74 (2003).
60. Froy O, Chapnik N, Miskin R. Effect of intermittent fasting on circadian rhythms in mice depends on feeding time. Mech. Ageing Dev. 130(3), 154-160 (2009).
61. Martin B, Pearson M, Kebejian L et al. Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess. Endocrinology 148(9), 4318-4333 (2007).
62. Groesbeck DK, Bluml RM, Kossoff EH. Long-term use of the ketogenic diet in the treatment of epilepsy. Dev. Med. Child. Neurol. 48(12), 978-981 (2006).
63. Hite AH, Berkowitz VG, Berkowitz K. Low-carbohydrate diet review: Shifting the paradigm. Nutr. Clin. Pract. 26(3), 300-308 (2011).
64. Warburg O. On the origin of cancer cells. Science 123(3191), 309-314 (1956).
65. Ahmad IM, Aykin-Burns N, Sim JE et al. Mitochondrial O2-and H2O2 mediate glucose deprivation-induced stress in human cancer cells. J. Biol. Chem. 280(6), 4254-4263 (2005).
66. Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 6(4), 280-293 (2007).
67. Dwarkanath BS, Zolzer F, Chandana S et al. Heterogeneity in 2-deoxy-d-glucose-induced modifications in energetics and radiation responses of human tumor cell lines. Int. J. Radiat. Oncol. Biol. Phys. 50(4), 1051-1061 (2001).
68. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem. J. 418(1), 29-37 (2009).
69. Simons AL, Fath MA, Mattson DM et al. Enhanced response of human head and neck cancer xenograft tumors to cisplatin combined with 2-deoxy-d-glucose correlates with increased 18F-FDG uptake as determined by PET imaging. Int. J. Radiat. Oncol. Biol. Phys. 69(4), 1222-1230 (2007).
70. Abdelwahab MG, Fenton KE, Preul MC et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS ONE 7(5), e36197 (2012).
71. Fine EJ, Segal-Isaacson CJ, Feinman RD et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: A pilot safety and feasibility dietary trial in 10 patients. Nutrition 28(10), 1028-1035 (2012).
72. Baserga R. The contradictions of the insulin-like growth factor 1 receptor. Oncogene 19(49), 5574-5581 (2000).
73. Shackelford DB, Shaw RJ. The LKB1-AMPK pathway: Metabolism and growth control in tumour suppression. Nat. Rev. Cancer 9(8), 563-575 (2009).
74. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66(21), 10269-10273 (2006).
75. Draznin B, Wang C, Adochio R, Leitner JW, Cornier MA. Effect of dietary macronutrient composition on AMPK and SIRT1 expression and activity in human skeletal muscle. Horm. Metab. Res. 44(09), 650-655 (2012).
76. Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic. Biol. Med. 51(2), 327-336 (2011).
77. Patel MS, Russell JJ, Gershman H. Ketone-body metabolism in glioma and neuroblastoma cells. Proc. Natl Acad. Sci. USA 78(11), 7214-7218 (1981).
78. Nebeling LC, Lerner E. Implementing a ketogenic diet based on medium-chain triglyceride oil in pediatric patients with cancer. J. Am. Diet. Assoc. 95(6), 693-697 (1995).
79. Phinney SD, Bistrian BR, Wolfe RR, Blackburn GL. The human metabolic response to chronic ketosis without caloric restriction: Physical and biochemical adaptation. Metabolism 32(8), 757-768 (1983).
80. Volek JS, Sharman MJ, Love DM et al. Body composition and hormonal responses to a carbohydrate-restricted diet. Metabolism 51(7), 864-870 (2002).
81. Nair KS, Welle SL, Halliday D, Campbell RG. Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. J. Clin. Invest. 82(1), 198-205 (1988).
82. Forsythe C, Phinney S, Fernandez M et al. Comparison of low fat and low carbohydrate diets on circulating fatty acid composition and markers of inflammation. Lipids 43(1), 65-77 (2008).
83. Champ CE, Volek JS, Siglin J, Jin L, Simone NL. Weight gain, metabolic syndrome, and breast cancer recurrence: Are dietary recommendations supported by the data? Int. J. Breast Cancer 2012, 506868 (2012).
84. Sampath A, Kossoff EH, Furth SL, Pyzik PL, Vining EP. Kidney stones and the ketogenic diet: Risk factors and prevention. J. Child Neurol. 22(4), 375-378 (2007).
85. Fine E, Segal-Isaacson C, Herzkopf S et al. A pilot safety-feasibility dietary trial targeting insulin inhibition in ten patients with advanced cancer. BMC Proc. 6(Suppl. 3), P60 (2012).
86. Champ CE, Baserga R, Mishra MV et al. Nutrient restriction and radiation therapy for cancer treatment: When less is more. Oncologist 18(1), 97-103 (2013).
87. Fuereder T, Jaeger-Lansky A, Hoeflmayer D et al. mTOR inhibition by everolimus counteracts VEGF induction by sunitinib and improves anti-tumor activity against gastric cancer in vivo. Cancer Lett. 296(2), 249-256 (2010).
88. Xue Q, Nagy JA, Manseau EJ, Phung TL, Dvorak HF, Benjamin LE. Rapamycin inhibition of the Akt/mTOR pathway blocks select stages of VEGF-A164-driven angiogenesis, in part by blocking s6 kinase. Arterioscler. Thromb. Vasc. Biol. 29(8), 1172-1178 (2009).
89. Faissner A, Heck N, Dobbertin A, Garwood J. DSD-1-proteoglycan/phosphacan and receptor protein tyrosine phosphatase-beta isoforms during development and regeneration of neural tissues. Adv. Exp. Med. Biol. 557, 25-53 (2006).
90. Wullschleger S, Loewith R, Hall MN. TOR signaling in growth and metabolism. Cell 124(3), 471-484 (2006).
91. Dang CV. Cancer cell metabolism: There is no ROS for the weary. Cancer Discov. 2(4), 304-307 (2012).
92. Sohal RS, Weindruch R. Oxidative stress, caloric restriction, and aging. Science 273(5271), 59-63 (1996).
93. Youngman LD, Park JY, Ames BN. Protein oxidation associated with aging is reduced by dietary restriction of protein or calories. Proc. Natl Acad. Sci. USA 89(19), 9112-9116 (1992).
94. Wenger JB, Chun SY, Dang DT, Luesch H, Dang LH. Combination therapy targeting cancer metabolism. Med. Hypotheses 76(2), 169-172 (2011).
95. Dang CV. Links between metabolism and cancer. Genes Dev. 26(9), 877-890 (2012).
96. Safdie F, Brandhorst S, Wei M et al. Fasting enhances the response of glioma to chemo-and radiotherapy. PLoS ONE 7(9), e44603 (2012).
97. Brown KA, Simpson ER. Obesity and breast cancer: Mechanisms and therapeutic implications. Front. Biosci. (Elite Ed.) 4, 2515-2524 (2012).
98. Kaaks R, Lundin E, Rinaldi S et al. Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden. Cancer Causes Control 13(4), 307-316 (2002).
99. Harvie M, Howell A. Energy restriction and the prevention of breast cancer. Proc. Nutr. Soc. 71(2), 263-275 (2012).
100. Escrich E, Solanas M, Moral R, Escrich R. Modulatory effects and molecular mechanisms of olive oil and other dietary lipids in breast cancer. Curr. Pharm. Des. 17(8), 813-830 (2011).
101. Escrich E, Moral R, Solanas M. Olive oil, an essential component of the Mediterranean diet, and breast cancer. Public Health Nutr. 14(12A), 2323-2332 (2011).
102. Cottet V, Touvier M, Fournier A et al. Postmenopausal breast cancer risk and dietary patterns in the E3N-EPIC prospective cohort study. Am. J. Epidemiol. 170(10), 1257-1267 (2009).
103. Buckland G, Agudo A, Lujan L et al. Adherence to a Mediterranean diet and risk of gastric adenocarcinoma within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study. Am. J. Clin. Nutr. 91(2), 381-390 (2010).
104. Jiao L, Mitrou PN, Reedy J et al. A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study. Arch. Intern. Med. 169(8), 764-770 (2009).
105. Fortes C, Mastroeni S, Melchi F et al. A protective effect of the Mediterranean diet for cutaneous melanoma. Int. J. Epidemiol. 37(5), 1018-1029 (2008).
106. Berrino F, Bellati C, Secreto G et al. Reducing bioavailable sex hormones through a comprehensive change in diet: The diet and androgens (DIANA) randomized trial. Cancer Epidemiol. Biomarkers Prev. 10(1), 25-33 (2001).
107. Villarini A, Pasanisi P, Traina A et al. Lifestyle and breast cancer recurrences: The DIANA-5 trial. Tumori 98(1), 1-18 (2012).
108. Orom UA, Lim MK, Savage JE et al. MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction. Cell Cycle 11(7), 1291-1295 (2012).
109. Bielohuby M, Sawitzky M, Stoehr BJ et al. Lack of dietary carbohydrates induces hepatic growth hormone (GH) resistance in rats. Endocrinology 152(5), 1948-1960 (2011).
110. Frystyk J, Delhanty PJ, Skjaerbaek C, Baxter RC. Changes in the circulating IGF system during short-term fasting and refeeding in rats. Am. J. Physiol. 277(2 Pt 1), E245-E252 (1999).
111. Shen XD, Hua WG, Chu WZ, Xu F, Wang YY, Chen HJ. [Physiological and biochemical effects of intermittent fasting combined with hunger-resistant food on mice]. Zhong Xi Yi Jie He Xue Bao 4(6), 589-592 (2006).
112. Huang P, Li S, Shao M et al. Calorie restriction and endurance exercise share potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance in mice. Nutr. Metab. (Lond.) 7, 59 (2010).
113. Al-Regaiey KA, Masternak MM, Bonkowski MS, Panici JA, Kopchick JJ, Bartke A. Effects of caloric restriction and growth hormone resistance on insulin-related intermediates in the skeletal muscle. J. Gerontol. A Biol. Sci. Med. Sci. 62(1), 18-26 (2007).
114. Garbow JR, Doherty JM, Schugar RC et al. Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet. Am. J. Physiol. Gastrointest. Liver Physiol. 300(6), G956-G967 (2011).
115. Bonkowski MS, Dominici FP, Arum O et al. Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity. PLoS ONE 4(2), e4567 (2009).
116. Foster GD, Wyatt HR, Hill JO et al. A randomized trial of a low-carbohydrate diet for obesity. N. Engl. J. Med. 348, 2082-2090 (2003).
117. Heijboer AC, Donga E, Voshol PJ et al. Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice. J. Lipid Res. 46(3), 582-588 (2005).
118. Escriva F, Gavete ML, Fermin Y et al. Effect of age and moderate food restriction on insulin sensitivity in Wistar rats: Role of adiposity. J. Endocrinol. 194(1), 131-141 (2007).
119. Longo VD, Finch CE Evolutionary medicine: From dwarf model systems to healthy centenarians? Science 299(5611), 1342-1346 (2003).