Fasting as a Therapy in Neurological Disease

Matthew C L Phillips, Matthew C L Phillips

Abstract

Fasting is deeply entrenched in evolution, yet its potential applications to today's most common, disabling neurological diseases remain relatively unexplored. Fasting induces an altered metabolic state that optimizes neuron bioenergetics, plasticity, and resilience in a way that may counteract a broad array of neurological disorders. In both animals and humans, fasting prevents and treats the metabolic syndrome, a major risk factor for many neurological diseases. In animals, fasting probably prevents the formation of tumors, possibly treats established tumors, and improves tumor responses to chemotherapy. In human cancers, including cancers that involve the brain, fasting ameliorates chemotherapy-related adverse effects and may protect normal cells from chemotherapy. Fasting improves cognition, stalls age-related cognitive decline, usually slows neurodegeneration, reduces brain damage and enhances functional recovery after stroke, and mitigates the pathological and clinical features of epilepsy and multiple sclerosis in animal models. Primarily due to a lack of research, the evidence supporting fasting as a treatment in human neurological disorders, including neurodegeneration, stroke, epilepsy, and multiple sclerosis, is indirect or non-existent. Given the strength of the animal evidence, many exciting discoveries may lie ahead, awaiting future investigations into the viability of fasting as a therapy in neurological disease.

Keywords: cancer; epilepsy; fasting; metabolic syndrome; multiple sclerosis; neurodegeneration; neurological disease; stroke; therapy.

Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Fasting-induced metabolic and transcriptional mechanisms and their effects on neurons (BHB—beta-hydroxybutyrate; BDNF—brain-derived neurotrophic factor; PGC1α—peroxisome proliferator-activated receptor γ coactivator 1α; AMPK—AMP-activated protein kinase; mTOR—mammalian target of rapamycin; IL6—interleukin 6; TNFα—tumor necrosis factor α).

References

    1. Longo V.D., Mattson M.P. Fasting: Molecular Mechanisms and Clinical Applications. Cell Metab. 2014;19:181–192. doi: 10.1016/j.cmet.2013.12.008.
    1. Patterson R.E., Sears D.D. Metabolic Effects of Intermittent Fasting. Annu. Rev. Nutr. 2017;37:371–393. doi: 10.1146/annurev-nutr-071816-064634.
    1. Mattson M.P., Longo V.D., Harvie M. Impact of Intermittent Fasting on Health and Disease Processes. Ageing Res. Rev. 2017;39:46–58. doi: 10.1016/j.arr.2016.10.005.
    1. Anton S.D., Moehl K., Donahoo W.T., Marosi K., Lee S.A., Mainous A.G., 3rd, Leeuwenburgh C., Mattson M.P. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity. 2018;26:254–268. doi: 10.1002/oby.22065.
    1. Mattson M.P., Moehl K., Ghena N., Schmaedick M., Cheng A. Intermittent Metabolic Switching, Neuroplasticity and Brain Health. Nat. Rev. Neurosci. 2018;19:63–80. doi: 10.1038/nrn.2017.156.
    1. Brandhorst S., Longo V.D. Fasting and Caloric Restriction in Cancer Prevention and Treatment. Recent Results Cancer Res. 2016;207:241–266.
    1. Gonidakis S., Finkel S.E., Longo V.D. Genome-wide screen identifies Escherichia coli TCA-cycle related mutants with extended chronological lifespan dependent on acetate metabolism and the hypoxia-inducible transcription factor ArcA. Aging Cell. 2010;9:868–881. doi: 10.1111/j.1474-9726.2010.00618.x.
    1. Longo V.D., Ellerby L.M., Bredesen D.E., Valentine J.S., Gralla E.B. Human Bcl-2 Reverses Survival Defects in Yeast Lacking Superoxide Dismutase and Delays Death of Wild-Type Yeast. J. Cell Biol. 1997;137:1581–1588. doi: 10.1083/jcb.137.7.1581.
    1. Longo V.D., Shadel G., Kaeberlein M., Kennedy B. Replicative and Chronological Aging in Saccharomyces cerevisiae. Cell Metab. 2012;16:18–31. doi: 10.1016/j.cmet.2012.06.002.
    1. Calixto A. Life without Food and the Implications for Neurodegeneration. Adv. Genet. 2015;92:53–74.
    1. McCue M.D., Terblanche J.S., Benoit J.B. Learning to Starve: Impacts of Food Limitation beyond the Stress Period. J. Exp. Biol. 2017;220:4330–4338. doi: 10.1242/jeb.157867.
    1. Weindruch R., Sohal R.S. Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N. Engl. J. Med. 1997;337:986–994. doi: 10.1056/NEJM199710023371407.
    1. Singh R., Lakhanpal D., Kumar S., Sharma S., Kataria H., Kaur M., Kaur G. Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age. 2012;34:917–933. doi: 10.1007/s11357-011-9289-2.
    1. Fontan-Lozano A., Saez-Cassanelli J.L., Inda M.C., De los Santos-Arteaga M., Sierra-Dominguez S.A., Lopez-Lluch G., Delgado-Garcia J.M., Carrion A.M. Caloric Restriction Increases Learning Consolidation and Facilitates Synaptic Plasticity through Mechanisms Dependent on NR2B Subunits of the NMDA Receptor. J. Neurosci. 2007;27:10185–10195. doi: 10.1523/JNEUROSCI.2757-07.2007.
    1. Altman J.D., Gross K.L., Lowry S.R. Nutritional and Behavioral Effects of Gorge and Fast Feeding in Captive Lions. J. Appl. Anim. Welf. Sci. 2005;8:47–57. doi: 10.1207/s15327604jaws0801_4.
    1. Crittenden A.N., Schnorr S.L. Current views on hunter-gatherer nutrition and the evolution of the human diet. Am. J. Phys. Anthropol. 2017;162:84–109. doi: 10.1002/ajpa.23148.
    1. Harari Y.N. Sapiens: A Brief History of Humankind. 1st ed. Harper; New York, NY, USA: 2015.
    1. Arbesmann R. Fasting and Prophecy in Pagan and Christian Antiquity. Traditio. 1951;7:1–71. doi: 10.1017/S0362152900015117.
    1. Paoli A., Tinsley G., Bianco A., Moro T. The Influence of Meal Frequency and Timing on Health in Humans: The Role of Fasting. Nutrients. 2019;11:719. doi: 10.3390/nu11040719.
    1. Kerndt P.R., Naughton J.L., Driscoll C.E., Loxterkamp D.A. Fasting: The history, pathophysiology and complications. West. J. Med. 1982;137:379–399.
    1. Dewey E.H. The True Science of Living. The Henry Bill Publishing Company; London, England: 1894.
    1. Buchinger O. Das Heilfasten. Georg Thieme Verlag; Stuttgart, Germany: 1935.
    1. Longo V.D. Programmed longevity, youthspan, and juventology. Aging Cell. 2019;18:e12843. doi: 10.1111/acel.12843.
    1. World Health Statistics 2018: Monitoring Health for the SDGs. [(accessed on 12 September 2019)]; Available online:
    1. Pringsheim T., Fiest K., Jette N. The International Incidence and Prevalence of Neurologic Conditions. Neurology. 2014;8:1661–1664. doi: 10.1212/WNL.0000000000000929.
    1. Puchalska P., Crawford P.A. Multi-Dimensional Roles of Ketone Bodies in Fuel Metabolism, Signaling, and Therapeutics. Cell Metab. 2017;25:262–284. doi: 10.1016/j.cmet.2016.12.022.
    1. Auestad N., Korsak R.A., Morrow J.W., Edmond J. Fatty Acid Oxidation and Ketogenesis by Astrocytes in Primary Culture. J. Neurochem. 1991;56:1376–1386. doi: 10.1111/j.1471-4159.1991.tb11435.x.
    1. Blázquez C., Woods A., De Ceballos M.L., Carling D., Guzmán M. The AMP-Activated Protein Kinase Is Involved in the Regulation of Ketone Body Production by Astrocytes. J. Neurochem. 1999;73:1674–1682. doi: 10.1046/j.1471-4159.1999.731674.x.
    1. White H., Venkatesh B. Clinical Review: Ketones and Brain Injury. Crit. Care. 2011;15:219. doi: 10.1186/cc10020.
    1. Sato K., Kashiwaya Y., Keon C.A., Tsuchiya N., King M.T., Radda G.K., Chance B., Clarke K., Veech R.L. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 1995;9:651–658. doi: 10.1096/fasebj.9.8.7768357.
    1. Masuda T., Dobson G.P., Veech R.L. The Gibbs–Donnan near-equilibrium system of heart. J. Biol. Chem. 1990;265:20321–20334.
    1. Veech R.L., Chance B., Kashiwaya Y., Lardy H.A., Cahill G.F., Jr. Ketone Bodies, Potential Therapeutic Uses. IUBMB Life. 2001;51:241–247.
    1. Murray A.J., Knight N.S., Cole M.A., Cochlin L.E., Carter E., Tchabanenko K., Pichulik T., Gulston M.K., Atherton H.J., Schroeder M.A., et al. Novel ketone diet enhances physical and cognitive performance. FASEB J. 2016;30:4021–4032. doi: 10.1096/fj.201600773R.
    1. Shimazu T., Hirschey M.D., Newman J., He W., Shirakawa K., Le Moan N., Grueter C.A., Lim H., Saunders L.R., Stevens R.D., et al. Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor. Science. 2013;339:211–214.
    1. Marosi K., Mattson M.P. BDNF mediates adaptive brain and body responses to energetic challenges. Trends Endocrinol. Metab. 2014;25:89–98. doi: 10.1016/j.tem.2013.10.006.
    1. Austin S., St-Pierre J. PGC1 and Mitochondrial Metabolism—Emerging Concepts and Relevance in Ageing and Neurodegenerative Disorders. J. Cell Sci. 2012;125:4963–4971. doi: 10.1242/jcs.113662.
    1. St-Pierre J., Lin J., Krauss S., Tarr P.T., Yang R., Newgard C.B., Spiegelman B.M. Bioenergetic Analysis of Peroxisome Proliferator-Activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle Cells. J. Biol. Chem. 2003;278:26597–26603. doi: 10.1074/jbc.M301850200.
    1. Unger R.H., Eisentraut A.M., Madison L.L. The Effects of Total Starvation Upon the Levels of Circulating Glucagon and Insulin in Man. J. Clin. Investig. 1963;42:1031–1039. doi: 10.1172/JCI104788.
    1. Ho K.Y., Veldhuis J.D., Johnson M.L., Furlanetto R., Evans W.S., Alberti K.G., Thorner M.O. Fasting Enhances Growth Hormone Secretion and Amplifies the Complex Rhythms of Growth Hormone Secretion in Man. J. Clin. Investig. 1988;81:968–975. doi: 10.1172/JCI113450.
    1. Castillo C.E., Katz A., Spencer M.K., Yan Z., Nyomba B.L. Fasting Inhibits Insulin-Mediated Glycolysis and Anaplerosis in Human Skeletal Muscle. Am. J. Physiol. Endocrinol. Metab. 1991;261:E598–E605. doi: 10.1152/ajpendo.1991.261.5.E598.
    1. Heilbronn L.K., Smith S.R., Martin C.K., Anton S.D., Ravussin E. Alternate-Day Fasting in Nonobese Subjects: Effects on Body Weight, Body Composition, and Energy Metabolism. Am. J. Clin. Nutr. 2005;81:69–73. doi: 10.1093/ajcn/81.1.69.
    1. Thissen J.P. Nutritional Regulation of the Insulin-like Growth Factors. Endocr. Rev. 1994;15:80–101.
    1. Merimee T.J., Fineberg S.E. Growth Hormone Secretion in Starvation: A Reassessment. J. Clin. Endocrinol. Metab. 1974;39:385–386. doi: 10.1210/jcem-39-2-385.
    1. Herzig S., Shaw R.J. AMPK: Guardian of Metabolism and Mitochondrial Homeostasis. Nat. Rev. Mol. Cell Biol. 2018;19:121–135. doi: 10.1038/nrm.2017.95.
    1. Antunes F., Erustes A., Costa A., Nascimento A., Bincoletto C., Ureshino R., Pereira G., Smaili S. Autophagy and Intermittent Fasting: The Connection for Cancer Therapy? Clinics. 2018;73(Suppl. 1):e814s. doi: 10.6061/clinics/2018/e814s.
    1. Stern J.H., Rutkowski J., Scherer P. Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk. Cell Metab. 2016;23:770–784. doi: 10.1016/j.cmet.2016.04.011.
    1. Yamauchi T., Kamon J., Waki H., Terauchi Y., Kubota N., Hara K., Mori Y., Ide T., Murakami K., Tsuboyama-Kasaoka N. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7:941–946. doi: 10.1038/90984.
    1. Baatar D., Patel K., Taub D.D. The effects of ghrelin on inflammation and the immune system. Mol. Cell Endocrinol. 2011;340:44–58. doi: 10.1016/j.mce.2011.04.019.
    1. Kim Y., Kim S., Kim C., Sato T., Kojima M., Park S. Ghrelin is required for dietary restriction-induced enhancement of hippocampal neurogenesis: Lessons from ghrelin knockout mice. Endocr. J. 2015;62:269–275. doi: 10.1507/endocrj.EJ14-0436.
    1. Arumugam T.V., Phillips T.M., Cheng A., Morrell C.H., Mattson M.P., Wan R. Age and energy intake interact to modify cell stress pathways and stroke outcome. Ann. Neurol. 2010;67:41–52. doi: 10.1002/ana.21798.
    1. Aksungar F.B., Topkaya A.E., Akyildiz M. Interleukin-6, C-Reactive Protein and Biochemical Parameters during Prolonged Intermittent Fasting. Ann. Nutr. Metab. 2007;51:88–95. doi: 10.1159/000100954.
    1. Degan D., Ornello R., Tiseo C., Carolei A., Sacco S., Pistoia F. The Role of Inflammation in Neurological Disorders. Curr. Pharm. Des. 2018;24:1485–1501. doi: 10.2174/1381612824666180327170632.
    1. Weindruch R. The Retardation of Aging by Caloric Restriction: Studies in Rodents and Primates. Toxicol. Pathol. 1996;24:742–745. doi: 10.1177/019262339602400618.
    1. Anson R.M., Guo Z., De Cabo R., Iyun T., Rios M., Hagepanos A., Ingram D.K., Lane M.A., Mattson M.P. Intermittent Fasting Dissociates Beneficial Effects of Dietary Restriction on Glucose Metabolism and Neuronal Resistance to Injury from Calorie Intake. Proc. Natl. Acad. Sci. USA. 2003;100:6216–6220. doi: 10.1073/pnas.1035720100.
    1. Harvie M.N., Pegington M., Mattson M.P., Frystyk J., Dillon B., Evans G., Cuzick J., Jebb S.A., Martin B., Cutler R.G., et al. The Effects of Intermittent or Continuous Energy Restriction on Weight Loss and Metabolic Disease Risk Markers: A Randomized Trial in Young Overweight Women. Int. J. Obes. 2011;35:714–727. doi: 10.1038/ijo.2010.171.
    1. Harvie M., Wright C., Pegington M., McMullan D., Mitchell E., Martin B., Cutler R.G., Evans G., Whiteside S., Maudsley S., et al. 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. 2013;110:1534–1547. doi: 10.1017/S0007114513000792.
    1. Sutton E.F., Beyl R., Early K.S., Cefalu W.T., Ravussin E., Peterson C.M. Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. Cell Metab. 2018;27:1212–1221. doi: 10.1016/j.cmet.2018.04.010.
    1. Saxton R.A., Sabatini D.M. MTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017;168:960–976. doi: 10.1016/j.cell.2017.02.004.
    1. Bodine S.C., Stitt T.N., Gonzalez M., Kline W.O., Stover G.L., Bauerlein R., Zlotchenko E., Scrimgeour A., Lawrence J.C., Glass D.J., et al. Akt/MTOR Pathway Is a Crucial Regulator of Skeletal Muscle Hypertrophy and Can Prevent Muscle Atrophy in Vivo. Nat. Cell Biol. 2001;3:1014–1019. doi: 10.1038/ncb1101-1014.
    1. Castets P., Lin S., Rion N., Di Fulvio S., Romanino K., Guridi M., Frank S., Tintignac L.A., Sinnreich M., Rüegg M.A. Sustained Activation of MTORC1 in Skeletal Muscle Inhibits Constitutive and Starvation-Induced Autophagy and Causes a Severe, Late-Onset Myopathy. Cell Metab. 2013;17:731–744. doi: 10.1016/j.cmet.2013.03.015.
    1. Ramamurthy S., Chang E., Cao Y., Zhu J., Ronnett G. AMPK activation regulates neuronal structure in developing hippocampal neurons. Neuroscience. 2014;259:13–24. doi: 10.1016/j.neuroscience.2013.11.048.
    1. Trepanowski J.F., Bloomer R.J. The Impact of Religious Fasting on Human Health. Nutr. J. 2010;9:57. doi: 10.1186/1475-2891-9-57.
    1. Runcie J., Thomson T.J. Prolonged starvation - A dangerous procedure? Br. Med. J. 1970;3:432–435. doi: 10.1136/bmj.3.5720.432.
    1. Stewart W.K., Fleming L.W. Features of a successful therapeutic fast of 382 days’ duration. Postgrad. Med. J. 1973;49:203–209. doi: 10.1136/pgmj.49.569.203.
    1. Wilhelmi de Toledo F., Buchinger A., Burggrabe H., Hölz G., Kuhn C., Lischka E., Lischka N., Lützner H., May W., Ritzmann-Widderich M., et al. Fasting Therapy - an Expert Panel Update of the 2002 Consensus Guidelines. Forsch Komplementmed. 2013;20:434–443. doi: 10.1159/000357602.
    1. Furmli S., Elmasry R., Ramos M., Fung J. Therapeutic Use of Intermittent Fasting for People with Type 2 Diabetes as an Alternative to Insulin. BMJ Case Rep. 2018;2018:bcr-2017-221854. doi: 10.1136/bcr-2017-221854.
    1. Tinsley G.M., La Bounty P.M. Effects of Intermittent Fasting on Body Composition and Clinical Health Markers in Humans. Nutr. Rev. 2015;73:661–674. doi: 10.1093/nutrit/nuv041.
    1. Di Francesco A., Di Germanio C., Bernier M., de Cabo R. A Time to Fast. Science. 2018;362:770–775. doi: 10.1126/science.aau2095.
    1. Drenick E.J., Swendseid M.E., Blahd W.H., Tuttle S.G. Prolonged Starvation as Treatment for Severe Obesity. JAMA. 1964;187:100–105. doi: 10.1001/jama.1964.03060150024006.
    1. Thomson T.J., Runcie J., Miller V. Treatment of obesity by total fasting for up to 249 days. Lancet. 1966;2:992–996. doi: 10.1016/S0140-6736(66)92925-4.
    1. Farooqui A.A., Farooqui T., Panza F., Frisardi V. Metabolic Syndrome as a Risk Factor for Neurological Disorders. Cell. Mol. Life Sci. 2012;69:741–762. doi: 10.1007/s00018-011-0840-1.
    1. Grundy S.M., Hansen B., Smith S.C., Jr., Cleeman J.I., Kahn R.A., American Heart Association. National Heart, Lung, and Blood Institute. American Diabetes Association Clinical management of metabolic syndrome: Report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Arterioscler. Thromb. Vasc Biol. 2004;24:e19–e24.
    1. Rothschild J., Hoddy K.K., Jambazian P., Varady K.A. Time-Restricted Feeding and Risk of Metabolic Disease: A Review of Human and Animal Studies. Nutr. Rev. 2014;72:308–318. doi: 10.1111/nure.12104.
    1. Goodrick C.L., Ingram D.K., Reynolds M.A., Freeman J.R., Cider N.L. Differential Effects of Intermittent Feeding and Voluntary Exercise on Body Weight and Lifespan in Adult Rats. J. Gerontol. 1983;38:36–45. doi: 10.1093/geronj/38.1.36.
    1. Wan R., Camandola S., Mattson M.P. Intermittent Food Deprivation Improves Cardiovascular and Neuroendocrine Responses to Stress in Rats. J. Nutr. 2003;133:1921–1929. doi: 10.1093/jn/133.6.1921.
    1. Pedersen C.R., Hagemann I., Bock T., Buschard K. Intermittent Feeding and Fasting Reduces Diabetes Incidence in BB Rats. Autoimmunity. 1999;30:243–250. doi: 10.3109/08916939908993805.
    1. 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. doi: 10.1016/j.cmet.2014.11.001.
    1. Gotthardt J.D., Verpeut J.L., Yeomans B.L., Yang J.A., Yasrebi A., Roepke T.A., Bello N.T. 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. 2016;157:679–691. doi: 10.1210/en.2015-1622.
    1. Belkacemi L., Selselet-Attou G., Hupkens E., Nguidjoe E., Louchami K., Sener A., Malaisse W.J. Intermittent fasting modulation of the diabetic syndrome in streptozotocin-injected rats. Int. J. Endocrinol. 2012;2012:962012. doi: 10.1155/2012/962012.
    1. Hatori M., Vollmer C., Zarrinpar A., Di Tacchio L., Bushong E.A., Gill S., Leblanc M., Chaix A., Joens M., Fitzpatrick J.A., et al. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012;15:848–860. doi: 10.1016/j.cmet.2012.04.019.
    1. Mager D.E., Wan R., Brown M., Cheng A., Wareski P., Abernethy D.R., Mattson M.P. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. FASEB J. 2006;20:631–637. doi: 10.1096/fj.05-5263com.
    1. Harvie M., Howell A. Potential Benefits and Harms of Intermittent Energy Restriction and Intermittent Fasting Amongst Obese, Overweight and Normal Weight Subjects—A Narrative Review of Human and Animal Evidence. Behav. Sci. 2017;17:4. doi: 10.3390/bs7010004.
    1. Kul S., Savaş E., Öztürk Z.A., Karadağ G. Does Ramadan Fasting Alter Body Weight and Blood Lipids and Fasting Blood Glucose in a Healthy Population? A Meta-Analysis. J. Relig. Health. 2014;53:929–942. doi: 10.1007/s10943-013-9687-0.
    1. Sadeghirad B., Motaghipisheh S., Kolahdooz F., Zahedi M.J., Haghdoost A.A. Islamic fasting and weight loss: A systematic review and meta-analysis. Public Health Nutr. 2014;17:396–406. doi: 10.1017/S1368980012005046.
    1. Varady K.A. Intermittent versus Daily Calorie Restriction: Which Diet Regimen Is More Effective for Weight Loss? Obes. Rev. 2011;12:e593–e601. doi: 10.1111/j.1467-789X.2011.00873.x.
    1. Schübel R., Nattenmüller J., Sookthai D., Nonnenmacher T., Graf M.E., Riedl L., Schlett C.L., von Stackelberg O., Johnson T., Nabers D., et al. Effects of Intermittent and Continuous Calorie Restriction on Body Weight and Metabolism over 50 Wk: A Randomized Controlled Trial. Am. J. Clin. Nutr. 2018;108:933–945. doi: 10.1093/ajcn/nqy196.
    1. Allen F.M. Studies Concerning Diabetes. JAMA. 1914;LXIII:939. doi: 10.1001/jama.1914.02570110041011.
    1. Gilliland I.C. Total Fasting in the Treatment of Obesity. Postgrad. Med. J. 1968;44:58–61. doi: 10.1136/pgmj.44.507.58.
    1. Jackson I.M.D., Mckiddie M., Buchanan K. Effect of Fasting on Glucose and Insulin Metabolism of Obese Patients. Lancet. 1969;293:285–287. doi: 10.1016/S0140-6736(69)91039-3.
    1. Williams K.V., Mullen M.L., Kelley D.E., Wing R.R. The Effect of Short Periods of Caloric Restriction on Weight Loss and Glycemic Control in Type 2 Diabetes. Diabetes Care. 1998;21:2–8. doi: 10.2337/diacare.21.1.2.
    1. Halberg N., Henriksen M., Söderhamn N., Stallknecht B., Ploug T., Schjerling P., Dela F. Effect of Intermittent Fasting and Refeeding on Insulin Action in Healthy Men. J. Appl. Physiol. 2005;99:2128–2136. doi: 10.1152/japplphysiol.00683.2005.
    1. Eshghinia S., Mohammadzadeh F. The Effects of Modified Alternate-Day Fasting Diet on Weight Loss and CAD Risk Factors in Overweight and Obese Women. J. Diabetes Metab. Disord. 2013;12:4. doi: 10.1186/2251-6581-12-4.
    1. Varady K.A., Bhutani S., Klempel M.C., Kroeger C.M., Trepanowski J.F., Haus J.M., Hoddy K.K., Calvo Y. Alternate Day Fasting for Weight Loss in Normal Weight and Overweight Subjects: A Randomized Controlled Trial. Nutr. J. 2013;12:146. doi: 10.1186/1475-2891-12-146.
    1. Goldhamer A., Lisle D., Parpia B., Anderson S.V., Campbell T. Medically Supervised Water-Only Fasting in the Treatment of Hypertension. J. Manip. Physiol. Ther. 2001;24:335–339. doi: 10.1067/mmt.2001.115263.
    1. Goldhamer A.C., Lisle D.J., Sultana P., Anderson S.V., Parpia B., Hughes B., Campbell T.C. Medically Supervised Water-Only Fasting in the Treatment of Borderline Hypertension. J. Altern. Complement. Med. 2002;8:643–650. doi: 10.1089/107555302320825165.
    1. Warburg O., Posener K., Negelein E. Ueber den stoffwechsel der tumoren. Biochem. Z. 1924;152:319–344.
    1. Hanahan D., Weinberg R.A. Hallmarks of Cancer: The Next Generation. Cell. 2011;144:646–674. doi: 10.1016/j.cell.2011.02.013.
    1. Epstein T., Gatenby R.A., Brown J.S. The Warburg Effect as an Adaptation of Cancer Cells to Rapid Fluctuations in Energy Demand. PLoS ONE. 2017;12:e0185085. doi: 10.1371/journal.pone.0185085.
    1. Eagle H. Nutrition Needs of Mammalian Cells in Tissue Culture. Science. 1955;122:501–504. doi: 10.1126/science.122.3168.501.
    1. Wise D.R., Thompson C.B. Glutamine Addiction: A New Therapeutic Target in Cancer. Trends Biochem. Sci. 2010;35:427–433. doi: 10.1016/j.tibs.2010.05.003.
    1. Seyfried T.N., Flores R.E., Poff A.M., D’Agostino D.P. Cancer as a Metabolic Disease: Implications for Novel Therapeutics. Carcinogenesis. 2014;35:515–527. doi: 10.1093/carcin/bgt480.
    1. Hursting S.D., Dunlap S.M., Ford N.A., Hursting M.J., Lashinger L.M. Calorie Restriction and Cancer Prevention: A Mechanistic Perspective. Cancer Metab. 2013;1:10. doi: 10.1186/2049-3002-1-10.
    1. O’Flanagan C.H., Smith L.A., McDonell S.B., Hursting S.D. When Less May Be More: Calorie Restriction and Response to Cancer Therapy. BMC Med. 2017;15:106. doi: 10.1186/s12916-017-0873-x.
    1. Rous P. The Influence of Diet on Transplanted and Spontaneous Mouse Tumors. J. Exp. Med. 1914;20:433–451. doi: 10.1084/jem.20.5.433.
    1. Lv M., Zhu X., Wang H., Wang F., Guan W. Roles of Caloric Restriction, Ketogenic Diet and Intermittent Fasting during Initiation, Progression and Metastasis of Cancer in Animal Models: A Systematic Review and Meta-Analysis. PLoS ONE. 2014;9:e115147. doi: 10.1371/journal.pone.0115147.
    1. Colman R.J., Anderson R.M., Johnson S.C., Kastman E.K., Kosmatka K.J., Beasley T.M., Allison D.B., Cruzen C., Simmons H.A., Kemnitz J.W., et al. Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys. Science. 2009;325:201–204. doi: 10.1126/science.1173635.
    1. Lee C., Raffaghello L., Brandhorst S., Safdie F.M., Bianchi G., Martin-Montalvo A., Pistoia V., Wei M., Hwang S., Merlino A., et al. Fasting Cycles Retard Growth of Tumors and Sensitize a Range of Cancer Cell Types to Chemotherapy. Sci. Transl. Med. 2012;4:124ra127. doi: 10.1126/scitranslmed.3003293.
    1. Cleary M.C., Grossmann M.E. The Manner in Which Calories Are Restricted Impacts Mammary Tumor Cancer Prevention. J. Carcinog. 2011;10:21. doi: 10.4103/1477-3163.85181.
    1. Cleary M.P., Jacobson M.K., Phillips F.C., Getzin S.C., Grande J.P., Maihle N.J. 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. Biomark. Prev. 2002;11:836–843.
    1. Cleary M.P., Hu X., Grossmann M.E., Juneja S.C., Dogan S., Grande J.P., Maihle N.J. Prevention of mammary tumorigenesis by intermittent caloric restriction: Does caloric intake during refeeding modulate the response? Exp. Biol. Med. 2007;232:70–80.
    1. Rogozina O.P., Bonorden M.J.L., Grande J.P., Cleary M.P. Serum Insulin-like Growth Factor-I and Mammary Tumor Development in Ad libitum–Fed, Chronic Calorie–Restricted, and Intermittent Calorie–Restricted MMTV-TGF-α Mice. Cancer Prev. Res. 2009;2:712–719. doi: 10.1158/1940-6207.CAPR-09-0028.
    1. 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. doi: 10.1038/icb.1979.54.
    1. Zhou W., Mukherjee P., Kiebish M.A., Markis W.T., Mantis J.G., Seyfried T.N. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr. Metab. 2007;4:5. doi: 10.1186/1743-7075-4-5.
    1. 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. doi: 10.1186/1475-2867-9-14.
    1. Siegel I., Liu T.L., Nepomuceno N., Gleicher N. Effects of Short-Term Dietary Restriction on Survival of Mammary Ascites Tumor-Bearing Rats. Cancer Investig. 1988;6:677–680. doi: 10.3109/07357908809078034.
    1. Safdie F., Brandhorst S., Wei M., Wang W., Lee C., Hwang S., Conti P.S., Chen T.C., Longo V.D. Fasting Enhances the Response of Glioma to Chemo- and Radiotherapy. PLoS ONE. 2012;7:e44603. doi: 10.1371/journal.pone.0044603.
    1. Pierce J.P., Natarajan L., Caan B.J., Parker B.A., Greenberg E.R., Flatt S.W., Rock C.L., Kealey S., Al-Delaimy W.K., Bardwell W.A., et al. Influence of a Diet Very High in Vegetables, Fruit, and Fiber and Low in Fat on Prognosis Following Treatment for Breast Cancer: The Women’s Healthy Eating and Living (WHEL) Randomized Trial. JAMA. 2007;298:289. doi: 10.1001/jama.298.3.289.
    1. Stupp R., Hegi M.E., Mason W.P., van den Bent M.J., Taphoorn M.J., Janzer R.C., Ludwin S.K., Allgeier A., Fisher B., Belanger K., et al. Effects of Radiotherapy with Concomitant and Adjuvant Temozolomide versus Radiotherapy Alone on Survival in Glioblastoma in a Randomised Phase III Study: 5-Year Analysis of the EORTC-NCIC Trial. Lancet Oncol. 2009;10:459–466. doi: 10.1016/S1470-2045(09)70025-7.
    1. Zuccoli G., Marcello N., Pisanello A., Servadei F., Vaccaro S., Mukherjee P., Seyfried T.N. Metabolic Management of Glioblastoma Multiforme Using Standard Therapy Together with a Restricted Ketogenic Diet: Case Report. Nutr. Metab. 2010;7:33. doi: 10.1186/1743-7075-7-33.
    1. Elsakka A.M.A., Bary M.A., Abdelzaher E., Elnaggar M., Kalamian M., Mukherjee P., Seyfried T.N. Management of Glioblastoma Multiforme in a Patient Treated with Ketogenic Metabolic Therapy and Modified Standard of Care: A 24-Month Follow-Up. Front. Nutr. 2018;5:20. doi: 10.3389/fnut.2018.00020.
    1. Safdie F.M., Dorff T., Quinn D., Fontana L., Wei M., Lee C., Cohen P., Longo V.D. Fasting and Cancer Treatment in Humans: A Case Series Report. Aging. 2009;1:988–1007. doi: 10.18632/aging.100114.
    1. de Groot S., Vreeswijk M.P., Welters M.J., Gravesteijn G., Boei J.J., Jochems A., Houtsma D., Putter H., van der Hoeven J.J., Nortier J.W., et al. The Effects of Short-Term Fasting on Tolerance to (Neo) Adjuvant Chemotherapy in HER2-Negative Breast Cancer Patients: A Randomized Pilot Study. BMC Cancer. 2015;15:652. doi: 10.1186/s12885-015-1663-5.
    1. Dorff T.B., Groshen S., Garcia A., Shah M., Tsao-Wei D., Pham H., Cheng C., Brandhorst S., Cohen P., Wei M., et al. Safety and Feasibility of Fasting in Combination with Platinum-Based Chemotherapy. BMC Cancer. 2016;16:360. doi: 10.1186/s12885-016-2370-6.
    1. Onyango I.G. Mitochondria in the Pathophysiology of Alzheimer’s and Parkinson’s Diseases. Front. Biosci. 2017;22:854–872. doi: 10.2741/4521.
    1. Schapira A.H., Cooper J., Dexter D., Jenner P., Clark J., Marsden C. Mitochondrial complex I deficiency in Parkinson’s disease. J. Neurochem. 1990;54:823–827. doi: 10.1111/j.1471-4159.1990.tb02325.x.
    1. Borghammer P., Chakravarty M., Jonsdottir K.Y., Sato N., Matsuda H., Ito K., Arahata Y., Kato T., Gjedde A. Cortical Hypometabolism and Hypoperfusion in Parkinson’s Disease Is Extensive: Probably Even at Early Disease Stages. Brain Struct. Funct. 2010;214:303–317. doi: 10.1007/s00429-010-0246-0.
    1. Hoyer S. Oxidative Energy Metabolism in Alzheimer Brain. Studies in Early-Onset and Late-Onset Cases. Mol. Chem. Neuropathol. 1992;16:207–224. doi: 10.1007/BF03159971.
    1. De la Monte S.M. Type 3 Diabetes Is Sporadic Alzheimer’s Disease: Mini-Review. Eur. Neuropsychopharmacol. 2014;24:1954–1960. doi: 10.1016/j.euroneuro.2014.06.008.
    1. Li L., Wang Z., Zuo Z. Chronic Intermittent Fasting Improves Cognitive Functions and Brain Structures in Mice. PLoS ONE. 2013;8:e66069. doi: 10.1371/journal.pone.0066069.
    1. Kuhla A., Lange S., Holzmann C., Maass F., Petersen J., Vollmar B., Wree A. Lifelong Caloric Restriction Increases Working Memory in Mice. PLoS ONE. 2013;8:e68778. doi: 10.1371/journal.pone.0068778.
    1. Guo J., Bakshi V., Lin A. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice. Front. Aging Neurosci. 2015;7:213. doi: 10.3389/fnagi.2015.00213.
    1. Lee J., Duan W., Mattson M.P. Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice. J. Neurochem. 2002;82:1367–1375. doi: 10.1046/j.1471-4159.2002.01085.x.
    1. Talani G., Licheri V., Biggio F., Locci V., Mostallino M.C., Secci P.P., Melis V., Dazzi L., Carta G., Banni S., et al. Enhanced Glutamatergic Synaptic Plasticity in the Hippocampal CA1 Field of Food-Restricted Rats: Involvement of CB1 Receptors. Neuropsychopharmacology. 2016;41:1308–1318. doi: 10.1038/npp.2015.280.
    1. Duan W., Guo Z., Jiang H., Ware M., Li X., Mattson M.P. Dietary Restriction Normalizes Glucose Metabolism and BDNF Levels, Slows Disease Progression, and Increases Survival in Huntingtin Mutant Mice. Proc. Natl. Acad. Sci. USA. 2003;100:2911–2916. doi: 10.1073/pnas.0536856100.
    1. Duan W., Mattson M.P. Dietary Restriction and 2-Deoxyglucose Administration Improve Behavioral Outcome and Reduce Degeneration of Dopaminergic Neurons in Models of Parkinson’s Disease. J. Neurosci. Res. 1999;57:195–206. doi: 10.1002/(SICI)1097-4547(19990715)57:2<195::AID-JNR5>;2-P.
    1. Tieu K., Perier C., Caspersen C., Teismann P., Wu D., Yan S., Naini A., Vila M., Jackson-Lewis V., Ramasamy R., et al. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Investig. 2003;112:892–901. doi: 10.1172/JCI200318797.
    1. Bruce-Keller A.J., Umberger G., McFall R., Mattson M.P. Food Restriction Reduces Brain Damage and Improves Behavioral Outcome Following Excitotoxic and Metabolic Insults. Ann. Neurol. 1999;45:8–15. doi: 10.1002/1531-8249(199901)45:1<8::AID-ART4>;2-V.
    1. Halagappa V.K.M., Guo Z., Pearson M., Matsuoka Y., Cutler R.G., LaFerla F.M., Mattson M.P. Intermittent Fasting and Caloric Restriction Ameliorate Age-Related Behavioral Deficits in the Triple-Transgenic Mouse Model of Alzheimer’s Disease. Neurobiol. Dis. 2007;256:212–220. doi: 10.1016/j.nbd.2006.12.019.
    1. Włodarek D. Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer’s Disease and Parkinson’s Disease) Nutrients. 2019;11:169. doi: 10.3390/nu11010169.
    1. VanItallie T.B., Nonas C., Di Rocco A., Boyar K., Hyams K., Heymsfield S.B. Treatment of Parkinson Disease with Diet-Induced Hyperketonemia: A Feasibility Study. Neurology. 2005;64:728–730. doi: 10.1212/01.WNL.0000152046.11390.45.
    1. Phillips M.C.L., Murtagh D.K., Gilbertson L.J., Asztely F.J., Lynch C.D. Low-Fat versus Ketogenic Diet in Parkinson’s Disease: A Pilot Randomized Controlled Trial. Mov. Disord. 2018;33:1306–1314. doi: 10.1002/mds.27390.
    1. Taylor M.K., Sullivan D.K., Mahnken J.D., Burns J.M., Swerdlow R.H. Feasibility and Efficacy Data from a Ketogenic Diet Intervention in Alzheimer’s Disease. Alzheimers Dement. 2018;4:28–36. doi: 10.1016/j.trci.2017.11.002.
    1. Castellano C., Nugent S., Paquet N., Tremblay S., Bocti C., Lacombe G., Imbeault H., Turcotte É, Fulop T., Cunnane S.C. Lower Brain 18F-Fluorodeoxyglucose Uptake but Normal 11C-Acetoacetate Metabolism in Mild Alzheimer’s Disease Dementia. J. Alzheimers Dis. 2015;43:1343–1353. doi: 10.3233/JAD-141074.
    1. Sacco R.L., Kasner S.E., Broderick J.P., Caplan L.R., Connors J.J., Culebras A., Elkind M.S.V., George M.G., Hamdan A.D., Higashida R.T., et al. An Updated Definition of Stroke for the 21st Century. Stroke. 2013;44:2064–2089. doi: 10.1161/STR.0b013e318296aeca.
    1. Yu Z.F., Mattson M.P. Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: Evidence for a preconditioning mechanism. J. Neurosci. Res. 1999;57:830–839. doi: 10.1002/(SICI)1097-4547(19990915)57:6<830::AID-JNR8>;2-2.
    1. Manzanero S., Erion J.R., Santro T., Steyn F.J., Chen C., Arumugam T.V., Stranahan A.M. Intermittent Fasting Attenuates Increases in Neurogenesis after Ischemia and Reperfusion and Improves Recovery. J. Cereb. Blood Flow Metab. 2014;34:897–905. doi: 10.1038/jcbfm.2014.36.
    1. Roberge M., Messier C., Staines W., Plamondon H. Food Restriction Induces Long-Lasting Recovery of Spatial Memory Deficits Following Global Ischemia in Delayed Matching and Non-Matching-to-Sample Radial Arm Maze Tasks. Neuroscience. 2008;156:11–29. doi: 10.1016/j.neuroscience.2008.05.062.
    1. Davis L.M., Pauly J.R., Readnower R.D., Rho J.M., Sullivan P.G. Fasting Is Neuroprotective Following Traumatic Brain Injury. J. Neurosci. Res. 2008;86:1812–1822. doi: 10.1002/jnr.21628.
    1. Plunet W.T., Streijger F., Lam C.K., Lee J.H., Liu J., Tetzlaff W. Dietary restriction started after spinal cord injury improves functional recovery. Exp. Neurol. 2008;213:28–35. doi: 10.1016/j.expneurol.2008.04.011.
    1. Prins M.L., Lee S.M., Fujima L.S., Hovda D.A. Increased Cerebral Uptake and Oxidation of Exogenous BetaHB Improves ATP Following Traumatic Brain Injury in Adult Rats. J. Neurochem. 2004;909:666–672. doi: 10.1111/j.1471-4159.2004.02542.x.
    1. Fisher R.S., Boas W.V., Blume W., Elger C., Genton P., Lee P., Engel J. Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE) Epilepsia. 2005;46:470–472. doi: 10.1111/j.0013-9580.2005.66104.x.
    1. Landgrave-Gómez J., Mercado-Gómez O.F., Vázquez-García M., Rodríguez-Molina V., Córdova-Dávalos L., Arriaga-Ávila V., Miranda-Martínez A., Guevara-Guzmán R. Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications. Front. Cell. Neurosci. 2016;10:296. doi: 10.3389/fncel.2016.00007.
    1. Yum M.S., Ko T., Kim D.W. Anticonvulsant Effects of β-Hydroxybutyrate in Mice. J. Epilepsy Res. 2012;2:29–32. doi: 10.14581/jer.12008.
    1. Yum M.S., Ko T., Kim D.W. β-Hydroxybutyrate Increases the Pilocarpine-Induced Seizure Threshold in Young Mice. Brain Dev. 2012;34:181–184. doi: 10.1016/j.braindev.2011.05.012.
    1. Kim J.M. Ketogenic Diet: Old Treatment, New Beginning. Clin. Neurophysiol. Pract. 2017;2:161–162. doi: 10.1016/j.cnp.2017.07.001.
    1. Guelpa G., Marie A. A lutte contre l’epilepsie par la desintoxication et par la reduction altimentaire. Rev. Ther. Med. Chir. 1911;78:8–13.
    1. Hartman A.L., Rubenstein J.E., Kossoff E.H. Intermittent Fasting: A ‘New’ Historical Strategy for Controlling Seizures? Epilepsy Res. 2013;104:275–279. doi: 10.1016/j.eplepsyres.2012.10.011.
    1. Huttenlocher P.R. Ketonemia and Seizures: Metabolic and Anticonvulsant Effects of Two Ketogenic Diets in Childhood Epilepsy. Pediatr. Res. 1976;10:536–540. doi: 10.1203/00006450-197605000-00006.
    1. van Delft R., Lambrechts D., Verschuure P., Hulsman J., Majoie M. Blood Beta-Hydroxybutyrate Correlates Better with Seizure Reduction Due to Ketogenic Diet than Do Ketones in the Urine. Seizure. 2010;19:36–39. doi: 10.1016/j.seizure.2009.10.009.
    1. Compston A., Coles A. Multiple Sclerosis. Lancet. 2008;372:1502–1517. doi: 10.1016/S0140-6736(08)61620-7.
    1. Katz Sand I. The Role of Diet in Multiple Sclerosis: Mechanistic Connections and Current Evidence. Curr. Nutr. Rep. 2018;7:150–160. doi: 10.1007/s13668-018-0236-z.
    1. Steinman L., Zamvil S.S. Virtues and Pitfalls of EAE for the Development of Therapies for Multiple Sclerosis. Trends Immunol. 2005;26:565–571. doi: 10.1016/j.it.2005.08.014.
    1. Cignarella F., Cantoni C., Ghezzi L., Salter A., Dorsett Y., Chen L., Phillips D., Weinstock G.M., Fontana L., Cross A.H., et al. Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metab. 2018;27:1222–1235. doi: 10.1016/j.cmet.2018.05.006.
    1. Choi I.Y., Piccio L., Childress P., Bollman B., Ghosh A., Brandhorst S., Suarez J., Michalsen A., Cross A.H., Morgan T.E., et al. Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep. 2016;15:2136–2146. doi: 10.1016/j.celrep.2016.05.009.
    1. Müller H., Wilhelmi de Toledo K. Fasting Followed by Vegetarian Diet in Patients with Rheumatoid Arthritis: A Systematic Review. Scand. J. Rheumatol. 2001;30:1–10.
    1. Johnson J.B., Summer W., Cutler R.G., Martin B., Hyun D., Dixit V.D., Pearson M., Nassar M., Maudsley S., Carlson O., 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;42:665–674. doi: 10.1016/j.freeradbiomed.2006.12.005.
    1. Wang A., Huen S.C., Luan H.H., Yu S., Zhang C., Gallezot J., Booth C.J., Medzhitov R. Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation. Cell. 2016;166:1512–1525. doi: 10.1016/j.cell.2016.07.026.
    1. Corley B.T., Carroll R.W., Hall R.M., Weatherall M., Parry-Strong A., Krebs J.D. Intermittent Fasting in Type 2 Diabetes Mellitus and the Risk of Hypoglycaemia: A Randomized Controlled Trial. Diabet. Med. 2018;35:588–594. doi: 10.1111/dme.13595.
    1. Finnell J.S., Saul B.C., Goldhamer A.C., Myers T.R. Is Fasting Safe? A Chart Review of Adverse Events during Medically Supervised, Water-Only Fasting. BMC Complement. Altern. Med. 2018;18:67. doi: 10.1186/s12906-018-2136-6.
    1. Sigler M.H. The Mechanism of the Natriuresis of Fasting. J. Clin. Investig. 1975;55:377–387. doi: 10.1172/JCI107941.
    1. Spencer I.O.B. Death during Therapeutic Starvation for Obesity. Lancet. 1968;291:1288–1290. doi: 10.1016/S0140-6736(68)92299-X.
    1. Cubberley P.T., Polster S.A., Schulman C.L. Lactic Acidosis and Death after the Treatment of Obesity by Fasting. N. Engl. J. Med. 1965;272:628–630. doi: 10.1056/NEJM196503252721208.
    1. Duncan G.G., Jenson W.K., Cristofori F.C., Schless G.L. Intermittent fasts in the correction and control of intractable obesity. Am. J. Med. Sci. 1963;245:515–520. doi: 10.1097/00000441-196305000-00001.
    1. Keys A., Brozek J., Henschel A., Mickelsen O., Taylor H.L. The Biology of Human Starvation. University of Minnesota Press; Minneapolis, MN, USA: 1950.
    1. Benedict F.G., Miles W.R., Roth P., Smith H.M. Human Vitality and Efficiency under a Prolonged Restricted Diet. Carnegie Institute; Washington DC, USA: 1919.
    1. Schneeweiss B., Schoder M., Graninger W., Roth E., Fischer M., Lenz K. Increased Energy Expenditure and Protein Catabolic Rate in Early Starvation. Clin. Nutr. 1991;10:8. doi: 10.1016/0261-5614(91)90142-Y.
    1. Catenacci V.A., Pan Z., Ostendorf D., Brannon S., Gozansky W.S., Mattson M.P., Martin B., Maclean P.S., Melanson E.L., Troy Donahoo W. A Randomized Pilot Study Comparing Zero-Calorie Alternate-Day Fasting to Daily Caloric Restriction in Adults with Obesity: Alternate-Day Fasting Versus Caloric Restriction. Obesity. 2016;24:1874–1883. doi: 10.1002/oby.21581.
    1. Zauner C., Schneeweiss B., Kranz A., Madl C., Ratheiser K., Kramer L., Roth E., Schneider B., Lenz K. Resting Energy Expenditure in Short-Term Starvation Is Increased as a Result of an Increase in Serum Norepinephrine. Am. J. Clin. Nutr. 2000;71:1511–1515. doi: 10.1093/ajcn/71.6.1511.
    1. Effect of Starvation and Very Low Calorie Diets on Protein-Energy Interrelationships in Lean and Obese Subjects. [(accessed on 12 September 2019)]; Available online: .
    1. Elia M., Lammert O., Zed C., Neale G. Energy Metabolism during Exercise in Normal Subjects Undergoing Total Starvation. Hum. Nutr. Clin. Nutr. 1984;38:355–362.
    1. Nair K.S., Woolf P.D., Welle S.L., Matthews D.E. Leucine, Glucose, and Energy Metabolism after 3 Days of Fasting in Healthy Human Subjects. Am. J. Clin. Nutr. 1987;46:557–562. doi: 10.1093/ajcn/46.4.557.
    1. Siervo M., Faber P., Lara J., Gibney E.R., Milne E., Ritz P., Lobley G.E., Elia M., Stubbs R.J., Johnstone A.M. Imposed Rate and Extent of Weight Loss in Obese Men and Adaptive Changes in Resting and Total Energy Expenditure. Metabolism. 2015;64:896–904. doi: 10.1016/j.metabol.2015.03.011.
    1. Højlund K., Wildner-Christensen M., Eshøj O., Skjærbæk C., Holst J.J., Koldkjær O., Jensen D.M., Beck-Nielsen H. Reference Intervals for Glucose, β-Cell Polypeptides, and Counterregulatory Factors during Prolonged Fasting. Am. J. Physiol. Endocrinol. Metab. 2001;280:e5–e58. doi: 10.1152/ajpendo.2001.280.1.E50.
    1. Schwartz M.W., Seeley R.J. Neuroendocrine responses to starvation and weight loss. N. Engl. J. Med. 1997;336:1802–1811. doi: 10.1056/NEJM199706193362507.
    1. Chaston T.B., Dixon J.B., O’Brien P.B. Changes in Fat-Free Mass during Significant Weight Loss: A Systematic Review. Int. J. Obes. 2007;31:743–750. doi: 10.1038/sj.ijo.0803483.
    1. Soenen S., Martens E.A., Hochstenbach-Waelen A., Lemmens S.G., Westerterp-Plantenga M.S. Normal Protein Intake Is Required for Body Weight Loss and Weight Maintenance, and Elevated Protein Intake for Additional Preservation of Resting Energy Expenditure and Fat Free Mass. J. Nutr. 2013;143:591–596. doi: 10.3945/jn.112.167593.
    1. Bhutani S., Klempel M.C., Kroeger C.M., Trepanowski J.F., Varady K.A. Alternate Day Fasting and Endurance Exercise Combine to Reduce Body Weight and Favorably Alter Plasma Lipids in Obese Humans: Alternate Day Fasting and Exercise for Weight Loss. Obesity. 2013;21:1370–1379. doi: 10.1002/oby.20353.
    1. Moro T., Tinsley G., Bianco A., Marcolin G., Pacelli Q.F., Battaglia G., Palma A., Gentil P., Neri M., Paoli A. 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;14:290. doi: 10.1186/s12967-016-1044-0.
    1. Tinsley G.M., Forsse J.S., Butler N.K., Paoli A., Bane A.A., La Bounty P.M., Morgan G.B., Grandjean P.W. Time-Restricted Feeding in Young Men Performing Resistance Training: A Randomized Controlled Trial. Eur. J. Sport Sci. 2017;17:200–207. doi: 10.1080/17461391.2016.1223173.
    1. Hoeks J., van Herpen N.A., Mensink M., Moonen-Kornips E., van Beurden D., Hesselink M.K., Schrauwen P. Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance. Diabetes. 2010;59:2117–2125. doi: 10.2337/db10-0519.
    1. Dulloo A.G., Jacquet J., Girardier L. Poststarvation Hyperphagia and Body Fat Overshooting in Humans: A Role for Feedback Signals from Lean and Fat Tissues. Am. J. Clin. Nutr. 1997;65:717–723. doi: 10.1093/ajcn/65.3.717.
    1. Doucet É., Cameron J. Appetite Control after Weight Loss: What Is the Role of Bloodborne Peptides? Appl. Physiol. Nutr. Metab. 2007;32:523–532. doi: 10.1139/H07-019.
    1. Johnstone A.M., Faber P., Gibney E., Elia M., Horgan G., Golden B., Stubbs R. Effect of an Acute Fast on Energy Compensation and Feeding Behaviour in Lean Men and Women. Int. J. Obes. Relat. Metab. Disord. 2002;26:1623–1628. doi: 10.1038/sj.ijo.0802151.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa