• TANUDEEP DATTA Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.
  • MOHAMMAD AZAMTHULLA Department of Pharmacology, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bengaluru, Karnataka, India.


At present, various complications such as diabetes, cardiovascular diseases, cancer, and neurological disorders have become treatable, almost completely, but the drugs used for the treatment may cause some severe side effects such as hypoglycemia, kidney complications, diarrhea, anemia, rashes, dyskinesia, insomnia, hypotension, confusion, hallucinations, compulsive behavior, and neurological complications. Some treatments cause defects in whole organ systems including damage to the immune system, lungs, heart, nerve endings, and reproductive organs. Many treatment approaches are using non-pharmacological techniques for treating diseases, without synthetic drugs. One such technique is fasting, a process where starvation conditions are imitated voluntarily. Intermittent fasting is done in ratios of fasting and food intake, where a person deprives himself of food for 16 h and food intake is followed for the rest of 8 h. Alternate day fasting includes alternate days of food intake and fasting. Time-restricted feeding is done by allowing food consumption only during the metabolically active phase of the day. Fasting mimicking diet is done by reducing food intake to very small levels which mimics the conditions of fasting. Reported beneficial effects of fasting have been found in diseases such as cancer, blood pressure disorders, autoimmune diseases, fibrosis, inflammation, insulin sensitivity, and oxidative stress.

Keywords: Time-restricted feeding, Fasting mimicking diet, Caloric restriction, Dietary restriction


1. Cerqueira FM, da Cunha FM, Da Silva CC, Chausse B, Romano RL, Garcia CC, et al. Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance. Free Radic Biol Med 2011;51:1454-60.
2. Thomas JA, Poulton S, Phillips T, Jessica C. Effect of intermittent fasting on prostate cancer and prostate cancer: Can eliminating carbohydrates. J Urol 2009;181:53.
3. Dorighello GG, Rovani JC, Luhman CJ, Paim BA, Raposo HF, Vercesi AE, et al. Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice. Br J Nutr 2014;111:979-86.
4. di Biase S, Longo VD. Fasting-induced differential stress sensitization in cancer treatment. Mol Cell Oncol 2016;3:e1117701.
5. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab 2014;19:418-30.
6. Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell based regeneration and reverse immunosuppression. Cell Stem Cell 2014;14:810-23.
7. Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, et al. Intermittent calorie restriction enhances epithelial-mesenchymal transition through the alteration of energy metabolism in a mouse tumor model. Int J Oncol 2018;52:413-23.
8. Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, et al. A diet mimicking fasting promotes regeneration and reduces autoimmunity and multiple sclerosis symptoms. Cell Rep 2016;15:2136-46.
9. Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider N. Effects of intermittent feeding upon body weight and lifespan in inbred mice: Interaction of genotype and age. Mech Ageing Dev 1990;55:69-87.
10. Liu B, Page AJ, Hutchison AT, Wittert GA, Heilbronn LK. Intermittent fasting increases energy expenditure and promotes adipose tissue browning in mice. Nutrition 2019;66:38-43.
11. Camelo L, de Marinho TS, Águila MB, Souza-Mello V, Barbosa-da-Silva S. Intermittent fasting exerts beneficial metabolic effects on blood pressure and cardiac structure by modulating local renin-angiotensin system in the heart of mice fed high-fat or high-fructose diets. Nutr Res 2019;63:51-62.
12. Hoddy KK, Kroeger CM, Trepanowski JF, Barnosky A, Bhutani S, Varady KA. Meal timing during alternate day fasting: Impact on body weight and cardiovascular disease risk in obese adults. Obesity 2014;22:2524-31.
13. Trepanowski JF, Kroeger CM, Barnosky A, Klempel MC, Bhutani S, Hoddy KK, et al. Effect of alternate-day fasting on weight loss, weight maintenance, and cardioprotection among metabolically healthy obese adults: A randomized clinical trial. JAMA Intern Med 2017;177:930-8.
14. Klempel MC, Kroeger CM, Varady KA. Alternate day fasting (ADF) with a high-fat diet produces similar weight loss and cardio-protection as ADF with a low-fat diet. Metabolism 2013;62:137-43.
15. Catenacci VA, Pan Z, Ostendorf D, Brannon S, Gozansky WS, Mattson MP, et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity 2016;24:1874-83.
16. Castello L, Froio T, Maina M, Cavallini G, Biasi F, Leonarduzzi G, et al. Alternate-day fasting protects the rat heart against age-induced inflammation and fibrosis by inhibiting oxidative damage and NF-kB activation. Free Radic Biol Med 2010;48:47-54.
17. Joslin PM, Bell RK, Swoap SJ. Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance. J Anim Physiol Anim Nutr 2017;101:1036-45.
18. Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity 2013;21:1370-9.
19. Alhamdan BA, Garcia-Alvarez A, Alzahrnai AH, Karanxha J, Stretchberry DR, Contrera KJ, et al. Alternate-day versus daily energy restriction diets: Which is more effective for weight loss? A systematic review and meta-analysis. Obes Sci Pract 2016;2:293-302.
20. Greenhill C. Benefits of Time-restricted Feeding. Nat Rev Endocrinol 2018;14:626.
21. Upadhyay A, Anjum B, Godbole NM, Rajak S, Shukla P, Tiwari S, et al. Time-restricted feeding reduces high-fat diet associated placental inflammation and limits adverse effects on fetal organ development. Biochem Biophys Res Commun 2019;514:415-21.
22. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 2012;15:848-60.
23. Sundaram S, Yan L. Time-restricted feeding reduces adiposity in mice fed a high-fat diet. Nutr Res 2016;36:603-11.
24. Chaix A, Zarrinpar A, Miu P, Panda S. Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 2014;20:991-1005.
25. Adamovich Y, Rousso-Noori L, Zwighaft Z, Neufeld-Cohen A, Golik M, Kraut-Cohen J, et al. Circadian clocks and feeding time regulate the oscillations and levels of hepatic triglycerides. Cell Metab 2014;19:319-30.
26. Feng D, Liu T, Sun Z, Bugge A, Mullican SE, Alenghat T, et al. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science 2011;331:1315-9.
27. Chaix A, Lin T, Le HD, Chang MW, Panda S. Time-restricted feeding prevents obesity and metabolic syndrome in mice lacking a circadian clock. Cell Metab 2019;29:303-19.
28. Wang H, van Spyk E, Liu Q, Geyfman M, Salmans ML, Kumar V, et al. Time-restricted feeding shifts the skin circadian clock and alters UVB-induced DNA damage. Cell Rep 2017;20:1061-72.
29. Woodie LN, Luo Y, Wayne MJ, Graff EC, Ahmed B, O’Neill AM, et al. Restricted feeding for 9 h in the active period partially abrogates the detrimental metabolic effects of a Western diet with liquid sugar consumption in mice. Metabolism 2018;82:1-13.
30. Sutton EF, Beyl R, Early KS, Cefalu WT, Ravussin E, Peterson CM. Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress even without weight loss in men with prediabetes. Cell Metab 2018;27:1212-21.
31. Gasmi M, Sellami M, Denham J, Padulo J, Kuvacic G, Selmi W, et al. Time-restricted feeding influences immune responses without compromising muscle performance in older men. Nutrition 2018;51-52:29-37.
32. Mukherjee P, Abate LE, Seyfried TN. Antiangiogenic and proapoptotic effects of dietary restriction on experimental mouse and human brain tumors. Clin Cancer Res 2004;10:5622-9.
33. Finch CE. Energy balance, inflammation, and aging. In: The Biology of Human Longevity. Berlin: Elsevier; 2007. p. 175-232.
34. Daynes RA, Pugh TD, Ershler WB. Dietary restriction from middle age attenuates age-associated lymphoma development and interleukin 6 dysregulation in C57BL/6 mice. Cancer Res 1994;54:3054-61.
35. Mehendale HM. Role of tissue repair and death proteins in liver injury. In: Drug-Induced Liver Disease. Amsterdam, Netherlands: Elsevier Inc.; 2013. p. 195-213.
36. Barclay JL, Shostak A, Leliavski A, Tsang AH, Jöhren O, Müller-Fielitz H, et al. High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in cry-deficient mice. Am J Physiol Endocrinol Metab 2013;304:E1053-63.
37. Dunn SE, Kari FW, French J, Leininger JR, Travlos G, Wilson R, et al. Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53- deficient mice. Cancer Res 1997;57:4667-72.
38. Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, et al. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A 2003;100:6216-20.
39. Weinruch R, Walford RL. Dietary restriction in mice beginning at 1 year of age: Effect on life-span and spontaneous cancer incidence. Science 2012;215:1415-8.
40. Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging in mice by dietary restriction: Longevity, cancer, immunity and lifetime energy intake. J Nutr 1986;116:641-54.
41. Wei M, Brandhorst S, Shelehchi M, Mirzaei H, Cheng CW, Budniak J, et al. Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and cardiovascular disease. Sci Transl Med 2017;9:8700.
42. Rangan P, Choi I, Wei M, Navarrete G, Guen E, Brandhorst S, et al. Fasting-mimicking diet modulates microbiota and promotes intestinal regeneration to reduce inflammatory bowel disease pathology. Cell Rep 2019;26:2704-19.
43. Choi IY, Lee C, Longo VD. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Mol Cell Endocrinol 2017;455:4-12.
44. Cheng CW, Villani V, Buono R, Wei M, Kumar S, Yilmaz OH, et al. Fasting-mimicking diet promotes ngn3-driven ?-cell regeneration to reverse diabetes. Cell 2017;168:775-88.
45. van Landeghem L, Blue RE, Dehmer JJ, Henning SJ, Helmrath MA, Lund PK. Localized intestinal radiation and liquid diet enhance survival and permit evaluation of long-term intestinal responses to high dose radiation in mice. PLoS One 2012;7:e51310.
46. Shelton LM, Huysentruyt LC, Mukherjee P, Seyfried TN. Calorie restriction as an anti-invasive therapy for malignant brain cancer in the VM mouse. ASN Neuro 2010;2:171-7.
47. Walford RL, Mock D, Verdery R, MacCallum T. Calorie restriction in biosphere 2: Alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Gerontol A Biol Sci Med Sci 2002;57:B211-24.
48. Russell WR, Gratz SW, Duncan SH, Holtrop G, Ince J, Scobbie L, et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr 2011;93:1062-72.
49. Fontana L, Klein S, Holloszy JO. Long-term low-protein, low-calorie diet and endurance exercise modulate metabolic factors associated with cancer risk. Am J Clin Nutr 2006;84:1456-62.
50. Mager DE, Wan R, Brown M, Cheng A, Wareski P, Abernethy DR, et al. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J 2006;20:631-7.
51. Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 2004;101:6659-63.
52. Kazemi A, Speakman JR, Soltani S, Djafarian K. Effect of calorie restriction or protein intake on circulating levels of insulin like growth factor I in humans: A systematic review and meta-analysis. Clin Nutr 2019;10:1-12.
53. Barja G. Aging in vertebrates, and the effect of caloric restriction: A mitochondrial free radical production-DNA damage mechanism? Biol Rev Camb Philos Soc 2004;79:235-51.
54. David CE, Lucas AM, Araújo MT, Coelho BN, Neto JB, Portela BR, et al. Calorie restriction attenuates hypertrophy-induced redox imbalance and mitochondrial ATP-sensitive K+ channel repression. J Nutr Biochem 2018;62:87-94.
55. Lu Y, Niu M, Qiu X, Cao H, Xing B, Sun Y, et al. Acute but not chronic calorie restriction defends against stress-related anxiety and despair in a GHS-R1a-dependent manner. Neuroscience 2019;412:94-104.
56. Tinkum KL, Stemler KM, White LS, Loza AJ, Jeter-Jones S, Michalski BM, et al. Fasting protects mice from lethal DNA damage by promoting small intestinal epithelial stem cell survival. Proc Natl Acad Sci U S A 2015;112:E7148-54.
57. Belkacemi L, Selselet-Attou G, Hupkens E, Nguidjoe E, Louchami K, Sener A, et al. Intermittent fasting modulation of the diabetic syndrome in streptozotocin-injected rats. Int J Endocrinol 2012;2012:962012.
58. Zarrinpar A, Chaix A, Panda S. Daily eating patterns and their impact on health and disease. Trends Endocrinol Metab 2016; 27:69-83.
59. Wellen KE, Thompson CB. Cellular metabolic stress: Considering how cells respond to nutrient excess. Mol Cell 2010;40:323-32.
60. Sherman H, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O. Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB J 2012;26:3493-502.
61. Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and Healthspan. Cell Metab 2015;22:86-99.
62. Smiljanic K, Todorovic S, Djordjevic AM, Vanmierlo T, Lütjohann D, Ivkovic S, et al. Limited daily feeding and intermittent feeding have different effects on regional brain energy homeostasis during aging. Biogerontology 2018;19:121-32.
63. Sequea DA, Sharma N, Arias EB, Cartee GD. Calorie restriction enhances insulin-stimulated glucose uptake and AKT phosphorylation in both fast-twitch and slow-twitch skeletal muscle of 24-month-old rats. J Gerontol A Biol Sci Med Sci 2012;67:1279-85.
64. Safdie FM, Dorff T, Quinn D, Fontana L, Wei M, Lee C, et al. Fasting and cancer treatment in humans: A case series report. Aging 2009;1:988-1007.
65. Premoselli F, Sesca E, Binasco V, Caderni G, Tessitore L. Fasting/re-feeding before initiation enhances the growth of aberrant crypt foci induced by azoxymethane in rat colon and rectum. Int J Cancer 1998;77:286-94.
66. Doyle C, Kushi LH, Byers T, Courneya KS, Demark-Wahnefried W, Grant B, et al. Nutrition and physical activity during and after cancer treatment: An American cancer society guide for informed choices. CA Cancer J Clin 2006;56:323-53.
67. Faber M, Coudray C, Hida H, Mousseau M, Favier A. Lipid peroxidation products, and vitamin and trace element status in patients with cancer before and after chemotherapy, including adriamycin a preliminary study. Biol Trace Elem Res 1995;47:117-23.
68. Lee C, Safdie F, Raffaghello L, Wei M. Reduced IGF-I differentially protects normal and cancer cells and improves chemotherapeutic index in mice. Cancer Res 2010;70:1564-72.
69. Bonorden MJ, Rogozina OP, Kluczny CM, Grossmann ME, Grambsch PL, Grande JP, et al. Intermittent calorie restriction delays prostate tumor detection and increases survival time in TRAMP mice. Nutr Cancer 2009;61:265-75.
70. Hursting SD, Lavigne JA, Berrigan D, Perkins SN, Barrett JC. Calorie restriction, aging, and cancer prevention: Mechanisms of action and applicability to humans. Ann Rev Med 2003;54:131-52.
71. Bartke A. Minireview: Role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology 2005;14:3718-23.
72. Shanley DP, Kirkwood TB. Calorie restriction and aging: A life-history analysis. Evolution 2000;54:740-50.
73. Berrigan D. Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis 2002;23:817-22.
74. Kritchevsky D. Caloric restriction and cancer. J Nutr Sci Vitaminol 2001;47:13-9.
75. Raffaghello L, Lee C, Safdie FM, 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;105:8215-20.
76. Siegel I, Liu TL, Nepomuceno N, Gleicher N. Effects of short-term dietary restriction on survival of mammary ascites tumor-bearing rats. Cancer Investig 1988;6:677-80.
77. Lee C, Longo VD. Fasting vs dietary restriction in cellular protection and cancer treatment: From model organisms to patients. Oncogene 2011;30:3305-16.
78. Sun P, Wang H, He Z, Chen X, Wu Q, Chen W, et al. Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages. Oncotarget 2017;8:74649-60.
79. Withers SS, Kass PH, Rodriguez CO, Skorupski KA, O’Brien D, Guerrero TA, et al. Fasting reduces the incidence of delayed-type vomiting associated with doxorubicin treatment in dogs with Lymphoma. Transl Oncol 2014;7:377-83.
80. Buschemeyer WC, Klink JC, Mavropoulos JC, Poulton SH, Demark-Wahnefried W, Hursting SD, et al. Effect of intermittent fasting with or without caloric restriction on prostate cancer growth and survival in SCID mice. Prostate 2010;70:1037-43.
81. Hursting SD, Perkins SN, Phang JM, Barrett JC. Diet and cancer prevention studies in p53-deficient mice. J Nutr 2001;131Suppl 11:3092S-4S.
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How to Cite
DATTA, T., and M. AZAMTHULLA. “FASTING TECHNIQUES – CHANGING THE WAY, YOU LOOK AT THERAPY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 5, Mar. 2020, pp. 38-43, doi:10.22159/ajpcr.2020.v13i5.36910.
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