Intermittent Fasting Effects on the Central Nervous System: How Hunger Modulates Brain Function

  • Fernanda M. Cerqueira
  • Bruno Chausse
  • Alicia J. KowaltowskiEmail author
Living reference work entry


Fasting has been present throughout human history and is a regular practice in many cultures and religions. Currently, findings regarding beneficial effects of fasting on body mass control and health have largely stimulated the practice. The number of studies investigating intermittent fasting effects on different pathological states has grown steadily. Evidence suggests that this dietary intervention can delay or even prevent the onset of pathologies, such as neurodegenerative diseases. Indeed, several studies have reported intermittent fasting actions on brain integrity and function. However, fasting may also affect hunger control in less desirable manners. Indeed, the brain is highly sensitive to fasting practice due to its pronounced energy demand and its central role in the control of whole body energy balance. In this chapter, the effects of intermittent fasting on brain function are discussed along with a description of the history of human fasting practices.


Intermittent fasting Caloric restriction Energy homeostasis Brain function Hypothalamus Appetite control Energy expenditure Reproductive function Aging Cognition Neurogenerative diseases 

List of Abbreviations


Alzheimer’s disease


Agouti-related peptide


Cocaine- and amphetamine-regulated transcript


Gonadotropin-release hormone


High-density lipoprotein


Intermittent fasting


Low-density lipoprotein


Neuropeptide Y


Parkinson’s disease




Very-low-density lipoprotein


  1. Adlouni A, Ghalim N, Benslimane A et al (1997) Fasting during Ramadan induces a marked increase in high-density lipoprotein cholesterol and decrease in low-density lipoprotein cholesterol. Ann Nutr Metab 41:242–249CrossRefPubMedGoogle Scholar
  2. Amigo I, Kowaltowski AJ (2014) Dietary restriction in cerebral bioenergetics and redox state. Redox Biol 2:296–304CrossRefPubMedPubMedCentralGoogle Scholar
  3. Anderton BH (2002) Ageing of the brain. Mech Ageing Dev 123:811–817CrossRefPubMedGoogle Scholar
  4. Anson RM, Guo Z, de Cabo R et al (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci 100:6216–6220CrossRefPubMedPubMedCentralGoogle Scholar
  5. Armentero MT, Levandis G, Bramanti P et al (2008) Dietary restriction does not prevent nigrostriatal degeneration in the 6-hydroxydopamine model of Parkinson’s disease. Exp Neurol 212:548–551CrossRefPubMedGoogle Scholar
  6. Arumugam V, Phillips TM, Cheng A et al (2010) Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann Neurol 67:41–52CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bakhotmah BA (2011) The puzzle of self-reported weight gain in a month of fasting (Ramadan) among a cohort of Saudi families in Jeddah, western Saudi Arabia. Nutr J 10:84CrossRefPubMedPubMedCentralGoogle Scholar
  8. Barnosky AR, Hoddy KK, Unterman TG, Varady KA (2014) Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. Transl Res 164:302–311CrossRefPubMedGoogle Scholar
  9. Barsh GS, Schwartz MW (2002) Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet 3:589–600PubMedGoogle Scholar
  10. Bragg P, Bragg PC (2004) The miracle of fasting: proven throughout history for physical, mental & spiritual rejuvenation, 1st edn. Bragg Health Sciences, Santa BarbaraGoogle Scholar
  11. Carlson AJ, Hoelzel F (1946) Apparent prolongation of the life span of rats by intermittent fasting. J Nutr 31:363–375PubMedGoogle Scholar
  12. Castellani RJ, Rolston RK, Smith MA (2010) Alzheimer disease. Dis Mon 56:484–546CrossRefPubMedPubMedCentralGoogle Scholar
  13. Cerqueira FM, Kowaltowski AJ (2010) Commonly adopted caloric restriction protocols often involve malnutrition. Ageing Res Rev 9:424–430CrossRefPubMedGoogle Scholar
  14. Cerqueira FM, Da Cunha FM, Caldeira da Silva CC et al (2011) Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance. Free Radic Biol Med 51:1454–1460CrossRefPubMedGoogle Scholar
  15. Chaix A, Zarrinpar A, Miu P, Panda S (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20:991–1005CrossRefPubMedPubMedCentralGoogle Scholar
  16. Chausse B, Solon C, Caldeira da Silva CC et al (2014) Intermittent fasting induces hypothalamic modifications resulting in low feeding efficiency, low body mass and overeating. Endocrinology 155:2456–2466CrossRefPubMedGoogle Scholar
  17. Chausse B, Vieira-Lara MA, Sanchez AB et al (2015) Intermittent fasting results in tissue-specific changes in bioenergetics and redox state. PLoS One 10:e0120413CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cherif A, Roelands B, Meeusen R et al (2016) Effects of intermittent fasting, caloric restriction, and Ramadan intermittent fasting on cognitive performance at rest and during exercise in adults. Sports Med 46:35–47CrossRefPubMedGoogle Scholar
  19. Civitarese AE, Carling S, Heilbronn LK, Hulver MH, Ukropcova B, Deutsch WA, Smith SR, Ravussin E, CALERIE Pennington Team (2007) Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med 4:e76CrossRefPubMedPubMedCentralGoogle Scholar
  20. Dorff TB, Groshen S, Garcia A, Shah M, Tsao-Wei D, Pham H, Cheng CW, Brandhorst S, Cohen P, Wei M, Longo V, Quinn DI (2016) Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer 16:360CrossRefPubMedPubMedCentralGoogle Scholar
  21. Dorighello GG, Rovani JC, Luhman CJF et al (2013) Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice. Br J Nutr 111:979–986CrossRefPubMedGoogle Scholar
  22. Duan W, Mattson MP (1999) Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease. J Neurosci Res 57:195–206CrossRefPubMedGoogle Scholar
  23. Estour B, Germain N, Diconne E et al (2010) Hormonal profile heterogeneity and short-term physical risk in restrictive anorexia nervosa. J Clin Endocrinol Metab 95:2203–2210CrossRefPubMedGoogle Scholar
  24. Fontana L, Meyer TE, Klein S, Holloszy JO (2004) Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A 101:6659–6663CrossRefPubMedPubMedCentralGoogle Scholar
  25. Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO (2008) Long-term effects of calorie or protein. Aging Cell 7:681–687CrossRefPubMedPubMedCentralGoogle Scholar
  26. Franklin JS, Schiele BC, Brozek J et al (1948) Observations on human behavior in experimental starvation and rehabilitation. J Clin Psychol 4:28–45CrossRefPubMedGoogle Scholar
  27. Fredricks R (2013) Fasting: an exceptional human experience. All Things Well Publications, San Jose, 533 pGoogle Scholar
  28. French SA, Jeffery RW (1994) Consequences of dieting to lose weight: effects on physical and mental health. Health Psychol 13:195–212CrossRefPubMedGoogle Scholar
  29. Goscienski PJ (2005) Health secrets of the stone age. Better Life, ConcordGoogle Scholar
  30. Gotthardt JD, Verpeut JL, Yeomans BL et al (2016) Intermittent fasting promotes fat loss with lean mass retention, increased hypothalamic norepinephrine content, and increased neuropeptide Y gene expression in diet-induced obese male mice. Endocrinology 157:679–691CrossRefPubMedGoogle Scholar
  31. Green MW, Rogers PJ, Elliman NA et al (1994) Impairment of cognitive performance associated with dieting and high levels of dietary restraint. Physiol Behav 55:447–452CrossRefPubMedGoogle Scholar
  32. Griffioen KJ, Rothman SM, Ladenheim B et al (2013) Dietary energy intake modifies brainstem autonomic dysfunction caused by mutant α-synuclein. Neurobiol Aging 34:928–935CrossRefPubMedGoogle Scholar
  33. Halagappa VKM, Guo Z, Pearson M et al (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26:212–220CrossRefPubMedGoogle Scholar
  34. Harvie M, Wright C, Pegington M et al (2013) The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women. Br J Nutr 110:1534–1547CrossRefPubMedGoogle Scholar
  35. Heilbronn LK, Smith SR, Martin CK et al (2005) Alternate-day fasting in non-obese subjects: effects on body weight, body composition, and energy metabolism. Am J Clin Nutr 81:69–73PubMedGoogle Scholar
  36. Hill JW, Elmquist JK, Elias CF (2008) Hypothalamic pathways linking energy balance and reproduction. Am J Physiol Endocrinol Metab 294:E827–E832CrossRefPubMedGoogle Scholar
  37. Holmer HK, Keyghobadi M, Moore C et al (2005) Dietary restriction affects striatal glutamate in the MPTP-induced mouse model of nigrostriatal degeneration. Synapse 57:100–112CrossRefPubMedGoogle Scholar
  38. Hu Q, Wang G (2016) Mitochondrial dysfunction in Parkinson’s disease. Transl Neurodegener 5:14CrossRefPubMedPubMedCentralGoogle Scholar
  39. Ingram DK, Zhu M, Mamczarz J et al (2006) Calorie restriction mimetics: an emerging research field. Aging Cell 5:97–108CrossRefPubMedGoogle Scholar
  40. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376CrossRefPubMedGoogle Scholar
  41. Johnstone AM (2007) Fasting – the ultimate diet? Obes Rev 8:211–222CrossRefPubMedGoogle Scholar
  42. Kumar S, Kaur G (2013) Intermittent fasting dietary restriction regimen negatively influences reproduction in young rats: a study of hypothalamo-hypophysial-gonadal axis. PLoS One 8:1–15CrossRefGoogle Scholar
  43. Lauzurica N, García-García L, Pinto S et al (2010) Changes in NPY and POMC, but not serotonin transporter, following a restricted feeding/repletion protocol in rats. Brain Res 1313:103–112CrossRefPubMedGoogle Scholar
  44. Lee C, Longo VD (2011) Fasting vs dietary restriction in cellular protection and cancer treatment: from model organisms to patients. Oncogene 30:3305–3316CrossRefPubMedGoogle Scholar
  45. Lee J, Duan W, Long JM et al (2000) Dietary restriction increases the number of newly generated neural cells, and induces BDNF expression, in the dentate gyrus of rats. J Mol Neurosci 15:99–108CrossRefPubMedGoogle Scholar
  46. Lopez-Miranda J, Marin C (2010) Dietary, physiological, and genetic impacts on postprandial lipid metabolism. In: Montmayeur JP, le Coutre J (eds) Fat detection: taste, texture, and post ingestive effects. CRC Press/Taylor & Francis, Boca RatonGoogle Scholar
  47. Maislos M, Khamaysi N, Assali A et al (1993) Marked increase in plasma high-density-lipoprotein cholesterol after prolonged fasting during Ramadan. Am J Clin Nutr 57:640–642PubMedGoogle Scholar
  48. Marosi K, Mattson MP (2014) BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol Metab 25:89–98CrossRefPubMedGoogle Scholar
  49. Martin B, Pearson M, Kebejian L et al (2007) Sex-dependent metabolic, neuroendocrine, and cognitive responses to dietary energy restriction and excess. Endocrinology 148:4318–4333CrossRefPubMedPubMedCentralGoogle Scholar
  50. Mattson MP (2004) Pathways towards and away from Alzheimer’s disease. Nature 430:631–639CrossRefPubMedPubMedCentralGoogle Scholar
  51. Mattson MP (2015) Lifelong brain health is a lifelong challenge: from evolutionary principles to empirical evidence. Ageing Res Rev 20:37–45CrossRefPubMedGoogle Scholar
  52. Mattson MP, Longo VD, Harvie M (2017) Impact of intermittent fasting on health and disease processes. Ageing Res Rev S1568–1637(16)30251–3Google Scholar
  53. McCay CM (1935) The effect of retarded growth upon the length of life and upon ultimate size. J Nutr 10:63–79Google Scholar
  54. Méquinion M, Le Thuc O, Zgheib S et al (2017) Long-term energy deficit in mice causes long-lasting hypothalamic alterations after recovery. Neuroendocrinology. (in press)Google Scholar
  55. Morgulis S (1913) The influence of protracted and intermittent fasting upon growth. Am Nat 47:477–487CrossRefGoogle Scholar
  56. Morton GJ, Meek TH, Schwartz MW (2014) Neurobiology of food intake in health and disease. Nat Rev Neurosci 15:367–378CrossRefPubMedPubMedCentralGoogle Scholar
  57. Murphy T, Dias GP, Thuret S (2014) Effects of diet on brain plasticity in animal and human studies: mind the gap. Neural Plast 2014:32CrossRefGoogle Scholar
  58. National Center for Health Statistics (2016) Health, United States, 2015: with special feature on racial and ethnic health disparities. National Center for Health Statistics, HyattsvilleGoogle Scholar
  59. Pedersen W, Mattson MP (1999) No benefit of dietary restriction on disease onset or progression in amyotrophic lateral sclerosis Cu/Zn-superoxide dismutase mutant mice. Brain Res 833:117–120CrossRefPubMedGoogle Scholar
  60. Qiu G, Spangler EL, Wan R et al (2012) Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids. Neurobiol Aging 33:2398–2410CrossRefPubMedGoogle Scholar
  61. Raefsky SM, Mattson MP (2016) Adaptive responses of neuronal mitochondria to bioenergetic challenges: roles in neuroplasticity and disease resistance. Free Radic Biol Med 102:203–216CrossRefPubMedGoogle Scholar
  62. Seimon RV, Shi YC, Slack K et al (2016) Intermittent moderate energy restriction improves weight loss efficiency in diet-induced obese mice. PLoS One 11:e0145157CrossRefPubMedPubMedCentralGoogle Scholar
  63. Sellayah D, Cagampang FR, Cox RD (2014) On the evolutionary origins of obesity: a new hypothesis. Endocrinology 155:1573–1588CrossRefPubMedGoogle Scholar
  64. Singh R, Lakhanpal D, Kumar S et al (2012) Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age 34:917–933CrossRefPubMedGoogle Scholar
  65. Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59–63CrossRefPubMedPubMedCentralGoogle Scholar
  66. Stice E, Davis K, Miller NP et al (2008) Fasting increases the risk for onset binge eating and bulimic pathology: a 5-year prospective study. J Abnorm Psychol 117:941–946CrossRefPubMedPubMedCentralGoogle Scholar
  67. Tanaka H, Tomoto T, Sugawara J (2016) A week of Danjiki (Buddhist fasting ritual) on cardiometabolic health: a case report. J Physiol Sci 66:431–434CrossRefPubMedGoogle Scholar
  68. Temizhan A, Dönderici O, Ouz D et al (1999) Is there any effect of Ramadan fasting on acute coronary heart disease events? Int J Cardiol 70:149–153CrossRefPubMedGoogle Scholar
  69. Temizhan A, Tangodan I, Dönderici O et al (2000) The effects of Ramadan fasting on blood lipid levels. Am J Med 109:341–342CrossRefPubMedGoogle Scholar
  70. The NHS Information Centre (2012) Statistics on obesity, physical activity and diet – England: report. Lifestyles Statistics, LondonGoogle Scholar
  71. Varady KA (2011) Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss? Obes Rev 12:e593–e601CrossRefPubMedGoogle Scholar
  72. Von Seeland (1887) Ueber die Nachwirkung der Nahrungsentziehung auf die Ernährung. Biol Centralbl 7:145–271Google Scholar
  73. Wahl D, Cogger VC, Solon-Biet SM et al (2016) Nutritional strategies to optimise cognitive function in the aging brain. Ageing Res Rev 31:80–92CrossRefPubMedGoogle Scholar
  74. Weber M, Wu T, Hanson JE et al (2015) Cognitive deficits, changes in synaptic function, and brain pathology in a mouse model of normal aging (1,2,3). eNeuro 2:1–26CrossRefGoogle Scholar
  75. Wing RR, Phelan S (2005) Long-term weight loss maintenance. Am J Clin Nutr 82:222S–225SPubMedGoogle Scholar
  76. Wu T, Gao X, Chen M, van Dam RM (2009) Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev 10:313–323CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Fernanda M. Cerqueira
    • 1
  • Bruno Chausse
    • 2
  • Alicia J. Kowaltowski
    • 2
    Email author
  1. 1.The National Institute for Biotechnology in the Negev LtdBen-Gurion University of the NegevBeer-ShevaIsrael
  2. 2.Departamento de Bioquímica, Instituto de QuímicaUniversidade de São PauloSão PauloBrazil

Personalised recommendations