Subscribe to RSS
DOI: 10.1055/a-1957-8449
Prevention of Neurologic Disease with Fasting
Abstract
Fasting has been widely studied in both prevention and treatment of many neurologic disorders. Some conditions may be prevented with any type of fasting, while some may require a stricter regimen. Fasting reduces weight, fasting blood glucose, and insulin resistance, and favorably alters the gut biome and the immune system. This article discusses various versions of fasting that have been studied as well as the known and theoretical mechanisms of how fasting effects the body and the brain. This article will then review evidence supporting the potential preventive and treatment effects of fasting in specific neurologic disorders including ameliorating the symptoms of Parkinson's disease, improving cognition in Alzheimer's disease, reducing migraine frequency and intensity, and reducing seizure frequency in epilepsy.
Publication History
Accepted Manuscript online:
10 October 2022
Article published online:
17 November 2022
© 2022. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1 Phillips MCL. Fasting as a therapy in neurological disease. Nutrients 2019; 11 (10) 2501
- 2 Fung J, Moore J. The Complete Guide to Fasting. 1st ed.. Las Vegas: Victory Belt Publishing; 2016
- 3 Owen OE, Felig P, Morgan AP, Wahren J, Cahill Jr GF. Liver and kidney metabolism during prolonged starvation. J Clin Invest 1969; 48 (03) 574-583
- 4 Schmeisser K, Parker JA. Pleiotropic effects of mTOR and autophagy during development and aging. Front Cell Dev Biol 2019; 7: 192
- 5 Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011; 13 (02) 132-141
- 6 de Cabo R, Mattson MP. Effects of intermittent fasting on health, aging, and disease. N Engl J Med 2019; 381 (26) 2541-2551
- 7 Park S, Zhang T, Wu X, Yi Qiu J. Ketone production by ketogenic diet and by intermittent fasting has different effects on the gut microbiota and disease progression in an Alzheimer's disease rat model. J Clin Biochem Nutr 2020; 67 (02) 188-198
- 8 Maifeld A, Bartolomaeus H, Löber U. et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nat Commun 1970; 2020: 12
- 9 Liu Z, Dai X, Zhang H. et al. Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment. Nat Commun 2020; 11 (01) 855
- 10 Kossof E. Dietary Therapies for Seizures. Epilepsy Foundation. October 25, 2017. Accessed June 15, 2022 at: https://www.epilepsy.com/treatment/dietary-therapies
- 11 Jensen NJ, Wodschow HZ, Nilsson M, Rungby J. Effects of ketone bodies on brain metabolism and function in neurodegenerative diseases. Int J Mol Sci 2020; 21 (22) 8767
- 12 Morris AAM. Cerebral ketone body metabolism. J Inherit Metab Dis 2005; 28 (02) 109-121
- 13 Auestad N, Korsak RA, Morrow JW, Edmond J. Fatty acid oxidation and ketogenesis by astrocytes in primary culture. J Neurochem 1991; 56 (04) 1376-1386
- 14 Bixel MG, Hamprecht B. Generation of ketone bodies from leucine by cultured astroglial cells. J Neurochem 1995; 65 (06) 2450-2461
- 15 Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 1987; 18 (04) 551-561
- 16 Oldendorf WH. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids. Am J Physiol 1973; 224 (06) 1450-1453
- 17 Kolb H, Kempf K, Röhling M, Lenzen-Schulte M, Schloot NC, Martin S. Ketone bodies: from enemy to friend and guardian angel. BMC Med 2021; 19 (01) 313
- 18 Francis N. Intermittent fasting and brain health: efficacy and potential mechanisms of action. OBM Geriat 2020; 4 (02) 121
- 19 Seidler K, Barrow M. Intermittent fasting and cognitive performance - Targeting BDNF as potential strategy to optimise brain health. Front Neuroendocrinol 2022; 65: 100971
- 20 Facts and Figures. Alzheimer's Association. Accessed January 22, 2022 at: https://www.alz.org/alzheimers-dementia/facts-figures
- 21 Statistics. Parkinson's Foundation. Accessed January 22, 2022 at: https://www.parkinson.org/Understanding-Parkinsons/Statistics
- 22 Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev 2017; 39: 46-58
- 23 Broom GM, Shaw IC, Rucklidge JJ. The ketogenic diet as a potential treatment and prevention strategy for Alzheimer's disease. Nutrition 2019; 60: 118-121
- 24 Swerdlow R, Marcus DL, Landman J, Kooby D, Frey II W, Freedman ML. Brain glucose metabolism in Alzheimer's disease. Am J Med Sci 1994; 308 (03) 141-144
- 25 Marcus DL, Freedman ML. Decreased brain glucose metabolism in microvessels from patients with Alzheimer's disease. Ann N Y Acad Sci 1997; 826: 248-253
- 26 Simpson IA, Chundu KR, Davies-Hill T, Honer WG, Davies P. Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer's disease. Ann Neurol 1994; 35 (05) 546-551
- 27 Whitesell RR, Ward M, McCall AL, Granner DK, May JM. Coupled glucose transport and metabolism in cultured neuronal cells: determination of the rate-limiting step. J Cereb Blood Flow Metab 1995; 15 (05) 814-826
- 28 Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer's disease. Alzheimers Dement (N Y) 2017; 4: 28-36
- 29 Mahley RW. Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders. J Mol Med (Berl) 2016; 94 (07) 739-746
- 30 Seneff S, Wainwright G, Mascitelli L. Nutrition and Alzheimer's disease: the detrimental role of a high carbohydrate diet. Eur J Intern Med 2011; 22 (02) 134-140
- 31 Whitmer RA, Karter AJ, Yaffe K, Quesenberry Jr CP, Selby JV. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 2009; 301 (15) 1565-1572
- 32 Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton JL, Kiosses WB. Short-term fasting induces profound neuronal autophagy. Autophagy 2010; 6 (06) 702-710
- 33 Cherbuin N, Sachdev P, Anstey KJ. Higher normal fasting plasma glucose is associated with hippocampal atrophy: the PATH Study. Neurology 2012; 79 (10) 1019-1026
- 34 Li L, Wang Z, Zuo Z. Chronic intermittent fasting improves cognitive functions and brain structures in mice. PLoS One 2013; 8 (06) e66069
- 35 Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab 2014; 19 (02) 181-192
- 36 Włodarek D. Role of ketogenic diets in neurodegenerative diseases (Alzheimer's disease and Parkinson's disease). Nutrients 2019; 11 (01) 169
- 37 Ou YN, Shen XN, Hu HY. et al. Fasting blood glucose and cerebrospinal fluid Alzheimer's biomarkers in non-diabetic cognitively normal elders: the CABLE study. Aging (Albany NY) 2020; 12 (06) 4945-4952
- 38 Brandhorst S, Longo VD. Protein quantity and source, fasting-mimicking diets, and longevity. Adv Nutr 2019; 10 (Suppl. 04) S340-S350
- 39 Keshavarzian A, Green SJ, Engen PA. et al. Colonic bacterial composition in Parkinson's disease. Mov Disord 2015; 30 (10) 1351-1360
- 40 Scheperjans F, Aho V, Pereira PA. et al. Gut microbiota are related to Parkinson's disease and clinical phenotype. Mov Disord 2015; 30 (03) 350-358
- 41 Unger MM, Spiegel J, Dillmann KU. et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord 2016; 32: 66-72
- 42 Greenamyre JT, Sherer TB, Betarbet R, Panov AV. Complex I and Parkinson's disease. IUBMB Life 2001; 52 (3-5): 135-141
- 43 Tieu K, Perier C, Caspersen C. et al. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Invest 2003; 112 (06) 892-901
- 44 González-Rodríguez P, Zampese E, Stout KA. et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature 2021; 599 (7886): 650-656
- 45 Leading Causes of Death. National Center for Health Statistics. Accessed January 22, 2022 at: https://www.cdc.gov/nchs/fastats/leading-causes-of-death.htm
- 46 Jenny NS, Callas PW, Judd SE. et al. Inflammatory cytokines and ischemic stroke risk: the REGARDS cohort. Neurology 2019; 92 (20) e2375-e2384
- 47 Zhou Y, Han W, Gong D, Man C, Fan Y. Hs-CRP in stroke: a meta-analysis. Clin Chim Acta 2016; 453: 21-27
- 48 Boysen G, Brander T, Christensen H, Gideon R, Truelsen T. Homocysteine and risk of recurrent stroke. Stroke 2003; 34 (05) 1258-1261
- 49 Aksungar FB, Topkaya AE, Akyildiz M. Interleukin-6, C-reactive protein and biochemical parameters during prolonged intermittent fasting. Ann Nutr Metab 2007; 51 (01) 88-95
- 50 Khatri JJ, Johnson C, Magid R. et al. Vascular oxidant stress enhances progression and angiogenesis of experimental atheroma. Circulation 2004; 109 (04) 520-525
- 51 Gerich JE. Clinical significance, pathogenesis, and management of postprandial hyperglycemia. Arch Intern Med 2003; 163 (11) 1306-1316
- 52 van Popele NM, Elizabeth Hak A, Mattace-Raso FU. et al. Impaired fasting glucose is associated with increased arterial stiffness in elderly people without diabetes mellitus: the Rotterdam Study. J Am Geriatr Soc 2006; 54 (03) 397-404
- 53 Selwaness M, van den Bouwhuijsen Q, Mattace-Raso FU. et al. Arterial stiffness is associated with carotid intraplaque hemorrhage in the general population: the Rotterdam study. Arterioscler Thromb Vasc Biol 2014; 34 (04) 927-932
- 54 Boehme AK, McClure LA, Zhang Y. et al. Inflammatory markers and outcomes after lacunar stroke: levels of inflammatory markers in treatment of stroke study. Stroke 2016; 47 (03) 659-667
- 55 Liu J, Rutten-Jacobs L, Liu M, Markus HS, Traylor M. Causal impact of type 2 diabetes mellitus on cerebral small vessel disease: a Mendelian randomization analysis. Stroke 2018; 49 (06) 1325-1331
- 56 Ochi N, Kohara K, Tabara Y. et al. Association of central systolic blood pressure with intracerebral small vessel disease in Japanese. Am J Hypertens 2010; 23 (08) 889-894
- 57 Chuang SY, Wang PN, Chen LK. et al. Associations of blood pressure and carotid flow velocity with brain volume and cerebral small vessel disease in a community-based population. Transl Stroke Res 2021; 12 (02) 248-258
- 58 Inzitari D, Eliasziw M, Sharpe BL, Fox AJ, Barnett HJ. North American Symptomatic Carotid Endarterectomy Trial Group. Risk factors and outcome of patients with carotid artery stenosis presenting with lacunar stroke. Neurology 2000; 54 (03) 660-666
- 59 Johnson JB, Summer W, Cutler RG. et al. Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med 2007; 42 (05) 665-674
- 60 Moro T, Tinsley G, Bianco A. et al. Effects of eight weeks of time-restricted feeding (16/8) on basal metabolism, maximal strength, body composition, inflammation, and cardiovascular risk factors in resistance-trained males. J Transl Med 2016; 14 (01) 290
- 61 Sävendahl L, Underwood LE. Fasting increases serum total cholesterol, LDL cholesterol and apolipoprotein B in healthy, nonobese humans. J Nutr 1999; 129 (11) 2005-2008
- 62 Yan Z, Fu B, He D, Zhang Y, Liu J, Zhang X. The relationship between oxidized low-density lipoprotein and related ratio and acute cerebral infarction. Medicine (Baltimore) 2018; 97 (39) e12642
- 63 Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 1988; 260 (13) 1917-1921
- 64 de Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN, Hendriks JC, Stalenhoef AF. Enhanced susceptibility to in vitro oxidation of the dense low density lipoprotein subfraction in healthy subjects. Arterioscler Thromb 1991; 11 (02) 298-306
- 65 Sharman MJ, Kraemer WJ, Love DM. et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr 2002; 132 (07) 1879-1885
- 66 Griffin BA, Freeman DJ, Tait GW. et al. Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 1994; 106 (02) 241-253
- 67 D'Andrea Meira I, Romão TT, Pires do Prado HJ, Krüger LT, Pires MEP, da Conceição PO. Ketogenic diet and epilepsy: what we know so far. Front Neurosci 2019; 13: 5
- 68 Liu H, Yang Y, Wang Y. et al. Ketogenic diet for treatment of intractable epilepsy in adults: a meta-analysis of observational studies. Epilepsia Open 2018; 3 (01) 9-17
- 69 Cervenka MC, Henry BJ, Felton EA, Patton K, Kossoff EH. Establishing an adult epilepsy diet center: experience, efficacy and challenges. Epilepsy Behav 2016; 58: 61-68
- 70 Landgrave-Gómez J, Mercado-Gómez OF, Vázquez-García M. et al. Anticonvulsant effect of time-restricted feeding in a pilocarpine-induced seizure model: metabolic and epigenetic implications. Front Cell Neurosci 2016; 10: 7
- 71 Wheless JW. History of the ketogenic diet. Epilepsia 2008; 49 (Suppl. 08) 3-5
- 72 Kossoff EH, Cervenka MC, Henry BJ, Haney CA, Turner Z. A decade of the modified Atkins diet (2003–2013): results, insights, and future directions. Epilepsy Behav 2013; 29 (03) 437-442
- 73 Bergqvist AG, Schall JI, Gallagher PR, Cnaan A, Stallings VA. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 2005; 46 (11) 1810-1819
- 74 Pfleger CC, Flachs EM, Koch-Henriksen N. Social consequences of multiple sclerosis (1): early pension and temporary unemployment – a historical prospective cohort study. Mult Scler 2010; 16 (01) 121-126
- 75 Krieger SC, Cook K, De Nino S, Fletcher M. The topographical model of multiple sclerosis: a dynamic visualization of disease course. Neurol Neuroimmunol Neuroinflamm 2016; 3 (05) e279
- 76 Kingwell E, Marriott JJ, Jetté N. et al. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC Neurol 2013; 13: 128
- 77 Dörr J, Paul F. The transition from first-line to second-line therapy in multiple sclerosis. Curr Treat Options Neurol 2015; 17 (06) 354
- 78 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
- 79 Fitzgerald KC, Bhargava P, Smith MD. et al. Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis. EBioMedicine 2022; 82: 104124
- 80 Smitherman TA, Burch R, Sheikh H, Loder E. The prevalence, impact, and treatment of migraine and severe headaches in the United States: a review of statistics from national surveillance studies. Headache 2013; 53 (03) 427-436
- 81 Schnabel T. An Experience with a Ketogenic Dietary in Migraine. Ann Intern Med 1928; 2: 341-347
- 82 Barborka C. Migraine: results of treatment by ketogenic diet in fifty cases. JAMA 1930; 95: 1825-1828
- 83 Di Lorenzo C, Coppola G, Sirianni G. et al. Migraine improvement during short lasting ketogenesis: a proof-of-concept study. Eur J Neurol 2015; 22 (01) 170-177
- 84 Di Lorenzo C, Pinto A, Ienca R. et al. A randomized double-blind, crossover trial of very low-calorie diet in overweight migraine patients: a possible role for ketones?. Nutrients 2019; 11 (08) 11
- 85 Di Lorenzo C, Coppola G, Bracaglia M. et al. Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study. J Headache Pain 2016; 17: 58