The ketogenic diet as a treatment paradigm for diverse neurological disorders

Carl E Stafstrom, Jong M Rho, Carl E Stafstrom, Jong M Rho

Abstract

Dietary and metabolic therapies have been attempted in a wide variety of neurological diseases, including epilepsy, headache, neurotrauma, Alzheimer disease, Parkinson disease, sleep disorders, brain cancer, autism, pain, and multiple sclerosis. The impetus for using various diets to treat - or at least ameliorate symptoms of - these disorders stems from both a lack of effectiveness of pharmacological therapies, and also the intrinsic appeal of implementing a more "natural" treatment. The enormous spectrum of pathophysiological mechanisms underlying the aforementioned diseases would suggest a degree of complexity that cannot be impacted universally by any single dietary treatment. Yet, it is conceivable that alterations in certain dietary constituents could affect the course and impact the outcome of these brain disorders. Further, it is possible that a final common neurometabolic pathway might be influenced by a variety of dietary interventions. The most notable example of a dietary treatment with proven efficacy against a neurological condition is the high-fat, low-carbohydrate ketogenic diet (KD) used in patients with medically intractable epilepsy. While the mechanisms through which the KD works remain unclear, there is now compelling evidence that its efficacy is likely related to the normalization of aberrant energy metabolism. The concept that many neurological conditions are linked pathophysiologically to energy dysregulation could well provide a common research and experimental therapeutics platform, from which the course of several neurological diseases could be favorably influenced by dietary means. Here we provide an overview of studies using the KD in a wide panoply of neurologic disorders in which neuroprotection is an essential component.

Keywords: epilepsy; ketogenic diet; neurological disorders; neuroplasticity.

References

    1. Acharya M. M., Hattiangady B., Shetty A. K. (2008). Progress in neuroprotective startegies for preventing epilepsy. Prog. Neurobiol. 84, 363–40410.1016/j.pneurobio.2007.10.010
    1. Aft R. L., Zhang F. W., Gius D. (2002). Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death. Br. J. Cancer 87, 805–81210.1038/sj.bjc.6600547
    1. Appelberg K. S., Hovda D. A., Prins M. L. (2009). The effects of a ketogenic diet on behavioral outcome after controlled cortical impact injury in the juvenile and adult rat. J. Neurotrauma 26, 497–50610.1089/neu.2008.0664
    1. Balietti M., Casoli T., DiStefano G., Giorgetti B., Aicardi G., Fattoretti P. (2010a). Ketogenic diets: an historical antiepieptic therapy with promising potentialities for the aging brain. Ageing Res. Rev. 9, 273–27910.1016/j.arr.2010.02.003
    1. Balietti M., Giorgetti B., DiStefano G., Casoli T., Platano D., Solazzi M., Bertoni-Freddari C., Aicardi G., Lattanzio F., Fattoretti P. (2010b). A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats. Micron 41, 143–14810.1016/j.micron.2009.08.010
    1. Balietti M., Giorgetti B., Fattoretti P., Grossi Y., DiStefano G., Casoli T., Platano D., Solazzi M., Orlando F., Aicardi G., Bertoni-Freddari C. (2008). Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats. Rejuvenation Res. 11, 631–64010.1089/rej.2007.0650
    1. Baranano K. M., Hartman A. L. (2008). The ketogenic diet: uses in epilepsy and other neurologic illnesses. Curr. Treat. Options Neurol. 10, 410–41910.1007/s11940-008-0043-8
    1. Bough K. J., Stafstrom C. E. (2010). “The ketogenic diet: scientific principles underlying it use,” in Epilepsy: Mechanisms, Models, and Translational Perspectives, eds Rho J. M., Sankar R., Stafstrom C. E. (Boca Raton, FL: CRC Press; ), 417–439
    1. Bough K. J., Wetherington J., Hassel B., Pare J. F., Gawryluk J. W., Greene J. G., Shaw R., Smith Y., Geiger J. D., Dingledine R. J. (2006). Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann. Neurol. 60, 223–23510.1002/ana.20899
    1. Cardinali S., Canafoglia L., Bertoli S., Franceschetti S., Lanzi G., Tagliabue A., Veggiotti P. (2006). A pilot study of a ketogenic diet in patients with Lafora body disease. Epilepsy Res. 69, 129–13410.1016/j.eplepsyres.2006.01.007
    1. Chu-Shore C. J., Major P., Camposano S., Muzykewicz D., Thiele E. A. (2010). The natural history of epilepsy in tuberous sclerosis complex. Epilepsia 51, 1236–124110.1111/j.1528-1167.2009.02474.x
    1. Contestabile A. (2009). Benefits of caloric restriction on brain aging and related pathological states: understanding mechanisms to devise novel therapies. Curr. Med. Chem. 16, 350–36110.2174/092986709787002637
    1. Cullingford T. (2008). Peroxisome proliferator-activated receptor alpha and the ketogenic diet. Epilepsia 49(Suppl. 8), 70–7210.1111/j.1528-1167.2008.01840.x
    1. Davis L. M., Pauly J. R., Readnower R. D., Rho J. M., Sullivan P. G. (2008). Fasting is neuroprotective following traumatic brain injury. J. Neurosci. Res. 86, 1812–182210.1002/jnr.21628
    1. de Almeida Rabello Oliveira M., da Rocha Ataíde T., de Oliveira S. L., de Melo Lucena A. L., de Lira C. E., Soares A. A., de Almeida C. B., Ximenes da Silva A. (2008). Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats. Neurosci. Lett. 434, 66–7010.1016/j.neulet.2008.01.032
    1. Deng-Bryant Y., Prins M. L., Hovda D. A., Harris N. G. (2011). Ketogenic diet prevents alterations in brain metabolism in young but not adult rats after traumatic brain injury. J. Neurotrauma 28, 1813–182510.1089/neu.2011.1822
    1. El-Mallakh R. S., Paskitti M. E. (2001). The ketogenic diet may have mood-stabilizing properties. Med. Hypotheses 57, 724–72610.1054/mehy.2001.1446
    1. Evangeliou A., Vlachonikolis I., Mihailidou H., Spilioti M., Skarpalezou A., Makaronas N., Prokopiou A., Christodoulou P., Liapi-Adamidou G., Helidonis E., Sbyrakis S., Smeitink J. (2003). Application of a ketogenic diet in children with autistic behavior: pilot study. J. Child Neurol. 18, 113–11810.1177/08830738030180020501
    1. Freeman J. M., Kossoff E. H., Freeman J. B., Kelly M. T. (2007). The Ketogenic Diet – A Treatment for Children and Others with Epilepsy. New York: Demos Publications
    1. Freeman J. M., Vining E. P., Kossoff E. H., Pyzik P. L., Ye X., Goodman S. N. (2009). A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia 50, 322–32310.1111/j.1528-1167.2008.01757.x
    1. Freemantle E., Vandal M., TremblayMercier J., Plourde M., Poirier J., Cunnane S. C. (2009). Metabolic response to a ketogenic breakfast in the healthy elderly. J. Nutr. Health Aging 13, 293–29810.1007/s12603-009-0026-9
    1. Garriga-Canut M., Schoenike B., Qazi R., Bergendahl K., Daley T. J., Pfender R. M., Morrison J. F., Ockuly J., Stafstrom C., Sutula T., Roopra A. (2006). 2-Deoxy-D-glucose reduces epilepsy progression by NRSF-CtBP-dependent metabolic regulation of chromatin structure. Nat. Neurosci. 9, 1382–138710.1038/nn1791
    1. Gasior M., Rogawski M. A., Hartman A. L. (2006). Neuroprotective and disease-modifying effects of the ketogenic diet. Behav. Pharmacol. 17, 431–43910.1097/00008877-200609000-00009
    1. Grabacka M., Pierzchalska M., Reiss K. (2010). Peroxisome proliferator activated receptor α ligands as anti-cancer drugs targeting mitochondrial metabolism. Curr. Pharm. Biotechnol.
    1. Greene A. E., Todorova M. T., McGowan R., Seyfried T. N. (2001). Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose. Epilepsia 42, 1371–137810.1046/j.1528-1157.2001.17601.x
    1. Gu Y., Luchsinger J. A., Stern Y., Scarmeas N. (2010). Mediterranean diet, inflammatory and metabolic biomarkers, and risk of Alzheimer’s disease. J. Alzheimers Dis. 22, 483–492
    1. Hartman A. L., Gasior M., Vining E. P. G., Rogawski M. A. (2007). The neuropharmacology of the ketogenic diet. Pediatr. Neurol. 36, 281–29210.1016/j.pediatrneurol.2007.02.008
    1. Henderson S. T., Vogel J. L., Barr L. J., Garvin F., Jones J. J., Costantini L. C. (2009). Study of the ketogenic agent AC-1202 in mild to moderate Alzheimer’s disease: a randomized, double-blind, placebo-controlled, multicenter trial. Nutr. Metab. (Lond.) 6, 31.10.1186/1743-7075-6-31
    1. Hu Z. G., Wang H. D., Qiao L., Yan W., Tan Q. F., Yin H. X. (2009). The protective effect of the ketogenic diet on traumatic brain injury-induced cell death in juvenile rats. Brain Inj. 23, 459–46510.1080/02699050902788469
    1. Jeong E. A., Jeon B. T., Shin H. J., Kim N., Lee D. H., Kim H. J., Kang S. S., Cho G. J., Choi W. S., Roh G. S. (2011). Ketogenic diet-induced peroxisome proliferator-activated receptor-γ activation decreases neuroinflammation in the mouse hippocampus after kainic acid-induced seizures. Exp. Neurol. 232, 195–20210.1016/j.expneurol.2011.09.001
    1. Jiang Y., Yang Y., Wang S., Ding Y., Guo Y., Zhang M. M., Wen S. Q., Ding M. P. (2012). Ketogenic diet protects against epileptogenesis as well as neuronal loss in amygdaloid-kindling seizures. Neurosci. Lett. 508, 22–2610.1016/j.neulet.2011.12.002
    1. Kang H. C., Lee Y. M., Kim H. D., Lee J. S., Slama A. (2007). Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 48, 82–8810.1111/j.1528-1167.2006.00906.x
    1. Kapogiannis D., Mattson M. P. (2011). Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer’s disease. Lancet Neurol. 10, 187–19810.1016/S1474-4422(10)70277-5
    1. Kashiwaya Y., Takeshima T., Mori N., Nakashima K., Clarke K., Veech R. L. (2000). D-beta-hydroxybutyrate protects neurons in models of Alzheimer’s and Parkinson’s disease. Proc. Natl. Acad. Sci. U.S.A. 97, 5440–544410.1073/pnas.97.10.5440
    1. Kemnitz J. W. (2011). Calorie restriction and aging in nonhuman primates. ILAR J. 52, 66–77
    1. Kessler S. K., Neal E. G., Camfield C. S., Kossoff E. H. (2011). Dietary therapies for epilepsy: future research. Epilepsy Behav. 22, 17–2210.1016/j.yebeh.2011.02.018
    1. Kim do Y., Davis L. M., Sullivan P. G., Maalouf M., Simeone T. A., vanBrederode J., Rho J. M. (2007). Ketone bodies are protective against oxidative stress in neocortical neurons. J. Neurochem. 101, 1316–132610.1111/j.1471-4159.2007.04483.x
    1. Kim do Y., Rho J. M. (2008). The ketogenic diet and epilepsy. Curr. Opin. Clin. Nutr. Metab. Care 11, 113–12010.1097/MCO.0b013e3282f44c06
    1. Kim do Y., Vallejo J., Rho J. M. (2010). Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors. J. Neurochem. 114, 130–141
    1. Kossoff E. H., Huffman J., Turner Z., Gladstein J. (2010). Use of the modified Atkins diet for adolescents with chronic daily headache. Cephalalgia 30, 1014–1016
    1. Kossoff E. H., McGrogan J. R. (2005). Worldwide use of the ketogenic diet. Epilepsia 46, 280–28910.1111/j.1528-1167.2005.460801_30.x
    1. Kossoff E. H., Zupec-Kania B. A., Amark P. E., Ballaban-Gil K. R., Bergqvist C. A. G., Blackford R., Buchhalter J. R., Caraballo R. H., Cross H. J., Dahlin M. G., Donner E. J., Klepper J., Jehle R. S., Kim H. D., Liu C. Y. M., Nation J., Nordli D. R., Jr., Pfeifer H. H., Rho J. M., Stafstrom C. E., Thiele E. A., Turner Z., Wirrell E. C., Wheless J. W., Veggiotti P., Vining E. P. (2009). Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 50, 304–31710.1111/j.1528-1167.2008.01765.x
    1. Linard B., Ferrandon A., Koning E., Nehlig A., Raffo E. (2010). Ketogenic diet exhibits neuroprotective effects in hippocampus but fails to prevent epileptogenesis in the lithium-pilocarpine model of mesial temporal lobe epilepsy in adult rats. Epilepsia 51, 1829–183610.1111/j.1528-1167.2010.02667.x
    1. Ma W., Berg J., Yellen G. (2007). Ketogenic diet metabolites reduce firing in central neurons by opening K(ATP) channels. J. Neurosci. 27, 3618–362510.1523/JNEUROSCI.3593-07.2007
    1. Maalouf M., Rho J. M., Mattson M. P. (2009). The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 59, 293–31510.1016/j.brainresrev.2008.09.002
    1. Maggioni F., Margoni M., Zanchin G. (2011). Ketogenic diet in migraine treatment: a brief but ancient history. Cephalalgia 31, 1150–115110.1177/0333102411406753
    1. Masino S. A., Geiger J. D. (2008). Are purines mediators of the anticonvulsant/neuroprotective effects of ketogenic diets? Trends Neurosci. 31, 273–27810.1016/j.tins.2008.02.009
    1. Masino S. A., Kawamura M., Jr., Plotkin L. M., Svedova J., DiMario F. J., Jr., Eigsti I. M. (2011). The relationship between the neuromodulator adenosine and behavioral symptoms of autism. Neurosci. Lett. 500, 1–510.1016/j.neulet.2011.06.007
    1. McDaniel S. S., Rensing N. R., Thio L. L., Yamada K. A., Wong M. (2011). The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 52, e7–e1110.1111/j.1528-1167.2010.02905.x
    1. McDaniel S. S., Wong M. (2011). Therapeutic role of mammalian target of rapamycin (mTOR) inhibition in preventing epileptogenesis. Neurosci. Lett. 497, 231–23910.1016/j.neulet.2011.02.037
    1. Murphy P., Burnham W. M. (2006). The ketogenic diet causes a reversible decrease in activity level in Long-Evans rats. Exp. Neurol. 201, 84–8910.1016/j.expneurol.2006.03.024
    1. Murphy P., Likhodii S., Nylen K., Burnham W. M. (2004). The antidepressant properties of the ketogenic diet. Biol. Psychiatry 56, 981–98310.1016/j.biopsych.2004.09.019
    1. Neal E. G., Chaffe H., Schwartz R. H., Lawson M. S., Edwards N., Fitzsimmons G., Whitney A., Cross J. H. (2008). The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 7, 500–50610.1016/S1474-4422(08)70092-9
    1. Nebeling L. C., Miraldi F., Shurin S. B., Lerner E. (1995). Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J. Am. Coll. Nutr. 14, 202–208
    1. Nehlig A. (1999). Age-dependent pathways of brain energy metabolism: the suckling rat, a natural model of the ketogenic diet. Epilepsy Res. 37, 211–22110.1016/S0920-1211(99)00073-X
    1. Noebels J. L. (2011). A perfect storm: converging paths of epilepsy and Alzheimer’s dementia intersect in the hippocampal formation. Epilepsia 52(Suppl. 1), 39–4610.1111/j.1528-1167.2011.03233.x
    1. Otto C., Kaemmerer U., Illert B., Muehling B., Pfetzer N., Wittig R., Voelker H. U., Thiede A., Coy J. F. (2008). Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides. BMC Cancer 8, 122.10.1186/1471-2407-8-122
    1. Palop J. J., Chin J., Roberson E. D., Wang J., Thwin M. T., Bien-Ly N., Yoo J., Ho K. O., Yu G. Q., Kreitzer A., Finkbeiner S., Noebels J. L., Mucke L. (2007). Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer’s disease. Neuron 55, 697–71110.1016/j.neuron.2007.07.025
    1. Palop J. J., Mucke L. (2009). Epilepsy and cognitive impairments in Alzheimer disease. Arch. Neurol. 66, 435–44010.1001/archneurol.2009.15
    1. Pelicano H., Martin D. S., Xu R.-H., Huang P. (2006). Glycolysis inhibition for anticancer treatment. Oncogene 25, 4633–464610.1038/sj.onc.1209597
    1. Prins M. L. (2008a). Cerebral metabolic adaptation and ketone metabolism after brain injury. J. Cereb. Blood Flow Metab. 28, 1–1610.1038/sj.jcbfm.9600543
    1. Prins M. L. (2008b). Diet, ketones, and neurotrauma. Epilepsia 49(Suppl. 8), 111–11310.1111/j.1528-1167.2008.01852.x
    1. Prins M. L., Fujima L. S., Hovda D. A. (2005). Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J. Neurosci. Res. 82, 413–42010.1002/jnr.20633
    1. Puchowicz M. A., Zechel J. L., Valerio J., Emancipator D. S., Xu K., Pundik S., LaManna J. C., Lust W. D. (2008). Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J. Cereb. Blood Flow Metab. 28, 1907–191610.1038/jcbfm.2008.79
    1. Redman L. M., Ravussin E. (2011). Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid. Redox Signal. 14, 275–27810.1089/ars.2010.3253
    1. Rho J. M., Stafstrom C. E. (2011). The ketogenic diet: what has science taught us? Epilepsy Res.10.1016/j.eplepsyres.2011.05.021
    1. Roberson E. D., Halabisky B., Yoo J. W., Yao J., Chin J., Yanm F., Wu T., Hamto P., Devidze N., Yu G. Q., Palop J. J., Noebels J. L., Mucke L. (2011). Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J. Neurosci. 31, 700–71110.1523/JNEUROSCI.4152-10.2011
    1. Rogawski M. A. (2008). Common pathophysiologic mechanisms in migraine and epilepsy. Arch. Neurol. 65, 709–71410.1001/archneur.65.6.709
    1. Roth J., Szulc A. L., Danoff A. (2011). Energy, evolution, and human diseases: an overview. Am. J. Clin. Nutr. 93, 875S–883S10.3945/ajcn.110.001909
    1. Schiff M., Bénit P., Coulibaly A., Loublier S., El-Khoury R., Rustin P. (2011). Mitochondrial response to controlled nutrition in health and disease. Nutr. Rev. 69, 65–7510.1111/j.1753-4887.2010.00363.x
    1. Schmidt M., Pfetzer N., Schwab M., Strauss I., Kämmerer U. (2011). Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutr. Metab. (Lond.) 8, 54.10.1186/1743-7075-8-54
    1. Schnabel T. G. (1928). An experience with a ketogenic diet in migraine. Ann. Int. Med. 2, 341–347
    1. Schwartzkroin P. A., Wenzel H. J., Lyeth B. G., Poon C. C., Delance A., Van K. C., Campos L., Nguyen D. V. (2010). Does ketogenic diet alter seizure sensitivity and cell loss following fluid percussion injury? Epilepsy Res. 92, 74–8410.1016/j.eplepsyres.2010.08.009
    1. Seyfried T. N., Marsh J., Shelton L. M., Huysentruyt L. C., Mukherjee P. (2011). Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res.10.1016/j.eplepsyres.2011.06.017 [Epub ahead of print].
    1. Siva N. (2006). Can ketogenic diet slow progression of ALS? Lancet Neurol. 5, 476.10.1016/S1474-4422(06)70535-X
    1. Srikanth V., Maczurek A., Phan T., Steele M., Westcott B., Juskiw D., Münch G. (2011). Advanced glycation endproducts and their receptor RAGE in Alzheimer’s disease. Neurobiol. Aging 32, 763–77710.1016/j.neurobiolaging.2009.04.016
    1. Stafford P., Abdelwahab M. G., Kimdo Y., Preul M. C., Rho J. M., Scheck A. C. (2010). The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr. Metab. (Lond.) 7, 74.10.1186/1743-7075-7-74
    1. Stafstrom C. E. (2004). Dietary approaches to epilepsy treatment: old and new options on the menu. Epilepsy Curr. 4, 215–22210.1111/j.1535-7597.2004.04502.x
    1. Tai K. K., Nguyen N., Pham L., Truong D. D. (2008). Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration. J. Neural Transm. 115, 1011–101710.1007/s00702-008-0050-7
    1. Tai K. K., Pham L., Truong D. D. (2009). Intracisternal administration of glibenclamide or 5-hydroxydecanoate does not reverse the neuroprotective effect of ketogenic diet against ischemic brain injury-induced neurodegeneration. Brain Inj. 23, 1081–108810.3109/02699050903421123
    1. VanderAuwera I., Wera S., VanLeuven F., Henderson S. T. (2005). A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr. Metab. (Lond.) 2, 28.10.1186/1743-7075-2-28
    1. Vanitallie T. B., Nonas C., DiRocco A., Boyar K., Hyams K., Heymsfield S. B. (2005). Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 64, 728–73010.1212/01.WNL.0000152046.11390.45
    1. Vining E., Freeman J., Ballaban-Gil K., Camfield C., Camfield P., Holmes G., Shinnar S., Shuman R., Trevathan E., Wheless J. (1998). A multicenter study of the efficacy of the ketogenic diet. Arch. Neurol. 55, 1433–143710.1001/archneur.55.11.1433
    1. Vining E. P. G. (1999). Clinical efficacy of the ketogenic diet. Epilepsy Res. 37, 181–19010.1016/S0920-1211(99)00070-4
    1. Voskuyl R. A., Vreugdenhil M. (2001). “Effects of essential fatty acids on voltage-regulated ionic channels and seizure thresholds in animals,” in Fatty Acids: Physiological and Behavioral Functions, eds Mostofsky D., Yehuda S., Salem N., Jr. (Totowa, NJ: Humana Press; ), 63–78
    1. Waldbaum S., Patel M. (2010). Mitochondrial dysfunction and oxidative stress: a contributing link to acquired epilepsy? J. Bioenerg. Biomembr. 42, 449–45510.1007/s10863-010-9320-9
    1. Wallace D. C., Fan W., Procaccio V. (2010). Mitochondrial energetics and therapeutics. Annu. Rev. Pathol. 5, 297–34810.1146/annurev.pathol.4.110807.092314
    1. Wheless J. W. (2008). History of the ketogenic diet. Epilepsia 49(Suppl. 8), 3–510.1111/j.1528-1167.2008.01632.x
    1. Willis S., Stoll J., Sweetman L., Borges K. (2010). Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models. Neurobiol. Dis. 40, 565–57210.1016/j.nbd.2010.07.017
    1. Xu K., Sun X., Eroku B. O., Tsipis C. P., Puchowicz M. A., LaManna J. C. (2010). Diet-induced ketosis improves cognitive performance in aged rats. Adv. Exp. Med. Biol. 662, 71–7510.1007/978-1-4419-1241-1_9
    1. Yamada K. A. (2008). Calorie restriction and glucose regulation. Epilepsia 49(Suppl. 8), 94–9610.1111/j.1528-1167.2008.01847.x
    1. Yang X., Cheng B. (2010). Neuroprotective and anti-inflammatory activities of ketogenic diet on MPTP-induced neurotoxicity. J. Mol. Neurosci. 42, 145–15310.1007/s12031-010-9372-7
    1. Yao J., Chen S., Mao Z., Cadenas E., Brinton R. D. (2011). 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer’s disease. PLoS ONE 6, e21788.10.1371/journal.pone.0021788
    1. Zhao Z., Lange D. J., Voustianiouk A., MacGrogan D., Ho L., Suh J., Humala N., Thiyagarajan M., Wang J., Pasinetti G. M. (2006). A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 7, 29.10.1186/1471-2202-7-29
    1. Zuccoli G., Marcello N., Pisanello A., Servadei F., Vaccaro S., Mukherjee P., Seyfried T. N. (2010). Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case report. Nutr. Metab. (Lond.) 7, 33.10.1186/1743-7075-7-33

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