Ketogenic diets: From cancer to mitochondrial diseases and beyond

European Journal of Clinical Investigation

Volumn 46, Issue 3, 2016, Pages 285-298

  Branco, Ana F ^a   Ferreira, André ^a   Simões, Rui F ^a   Magalhães Novais, Sílvia ^a   Zehowski, Cheryl ^b   Cope, Elisabeth ^c   Silva, Ana Marta ^a   Pereira, Daniela ^a   Sardão, Vilma A ^a   Cunha Oliveira, Teresa ^a  

^a UNIVERSITY OF COIMBRA   (Portugal)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^c UNIVERSITY OF SOUTHERN MAINE   (United States)

Author keywords

Cancer; High fat diet; Ketogenic diet; Mitochondria; Neurological diseases

Indexed keywords

3 HYDROXYBUTYRATE DEHYDROGENASE; 3 HYDROXYBUTYRIC ACID; ACETOACETIC ACID; ACETYL COENZYME A; ACETYL COENZYME A ACETYLTRANSFERASE; BRANCHED CHAIN AMINO ACID; CARNITINE PALMITOYLTRANSFERASE I; GLUCOSE TRANSPORTER; HYDROXYMETHYLGLUTARYL COENZYME A LYASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; ICOSAPENTAENOIC ACID; KETONE BODY; LONG CHAIN TRIACYLGLYCEROL; MAMMALIAN TARGET OF RAPAMYCIN; MEDIUM CHAIN TRIACYLGLYCEROL; MITOCHONDRIAL PERMEABILITY TRANSITION PORE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; SOMATOMEDIN C;

ADJUVANT CHEMORADIOTHERAPY; AEROBIC METABOLISM; ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; ANTINEOPLASTIC ACTIVITY; BREAST CANCER; CANCER CELL; CARDIOMYOPATHY; CITRIC ACID CYCLE; DISORDERS OF MITOCHONDRIAL FUNCTIONS; EPILEPSY; FATTY ACID OXIDATION; FOOD COMPOSITION; GASTROINTESTINAL SYMPTOM; GLIOBLASTOMA; GLYCOLYSIS; HEAD AND NECK CANCER; HUMAN; HYPERCHOLESTEROLEMIA; HYPOGLYCEMIA; KETOGENIC DIET; LIPID DIET; LIVER MITOCHONDRION; LOW CARBOHYDRATE DIET; MITOCHONDRIAL RESPIRATION; NEOPLASM; NON SMALL CELL LUNG CANCER; NONHUMAN; OUTCOME ASSESSMENT; OXIDATIVE PHOSPHORYLATION; PANCREAS CANCER; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; DIET THERAPY; ENERGY METABOLISM; METABOLISM; MITOCHONDRION; NEUROLOGIC DISEASE; PROCEDURES;

ENERGY METABOLISM; EPILEPSY; GLYCOLYSIS; HUMANS; KETOGENIC DIET; MITOCHONDRIA; MITOCHONDRIAL DISEASES; NEOPLASMS; NERVOUS SYSTEM DISEASES;

EID: 84957972055     PISSN: 00142972     EISSN: 13652362     Source Type: Journal    
DOI: 10.1111/eci.12591     Document Type: Review

References (133)

1. Stafford P, Abdelwahab MG, Kim do Y, Preul MC, Rho JM, Scheck AC. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab 2010;7:74.
2. Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012;3:59.
3. Lutas A, Yellen G. The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends Neurosci 2013;36:32-40.
4. Hassani A, Horvath R, Chinnery PF. Mitochondrial myopathies: developments in treatment. Curr Opin Neurol 2010;23:459-65.
5. Ahola-Erkkilä S, Carroll CJ, Peltola-Mjösund K, Tulkki V, Mattila I, Seppänen-Laakso T et al. Ketogenic diet slows down mitochondrial myopathy progression in mice. Hum Mol Genet 2010;19:1974-84.
6. Sharman MJ, Kraemer WJ, Love DM, Avery NG, Gomez AL, Scheett TP et al. A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J Nutr 2002;132:1879-85.
7. Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 2013;67:789-96.
8. Woolf EC, Curley KL, Liu Q, Turner GH, Charlton JA, Preul MC et al. The ketogenic diet alters the hypoxic response and affects expression of proteins associated with angiogenesis, invasive potential and vascular permeability in a mouse glioma model. PLoS ONE 2015;10:e0130357.
9. Lima PA, Sampaio LP, Damasceno NR. Neurobiochemical mechanisms of a ketogenic diet in refractory epilepsy. Clinics (Sao Paulo) 2014;69:699-705.
10. Allen BG, Bhatia SK, Anderson CM, Eichenberger-Gilmore JM, Sibenaller ZA, Mapuskar KA et al. Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism. Redox Biol 2014;2C:963-70.
11. Krebs HA. The regulation of the release of ketone bodies by the liver. Adv Enzyme Regul 1966;4:339-54.
12. Paoli A, Bosco G, Camporesi EM, Mangar D. Ketosis, ketogenic diet and food intake control: a complex relationship. Front Psychol 2015;6:27.
13. Giordano C, Marchio M, Timofeeva E, Biagini G. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets. Front Neurol 2014;5:63.
14. Wilder R. The effects of ketonemia on the course of epilepsy. Mayo Clin Proc 1921;2:307-8.
15. The Charlie Foundation. What is the Ketogenic Diet? The Charlie Foundation; 2014. https://www.charliefoundation.org/explore-ketogenic-diet/explore-1/introducing-the-diet. Accessed on 15 September 2015.
16. Huttenlocher PR, Wilbourn AJ, Signore JM. Medium-chain triglycerides as a therapy for intractable childhood epilepsy. Neurology 1971;21:1097-103.
17. Liu YM, Wang HS. Medium-chain triglyceride ketogenic diet, an effective treatment for drug-resistant epilepsy and a comparison with other ketogenic diets. Biomed J 2013;36:9-15.
18. Ferreira L, Lisenko K, Barros B, Zangeronimo M, Pereira L, Sousa R. Influence of medium-chain triglycerides on consumption and weight gain in rats: a systematic review. J Anim Physiol Anim Nutr (Berl) 2014;98:1-8.
19. Wibisono C, Rowe N, Beavis E, Kepreotes H, Mackie FE, Lawson JA et al. Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance. J Pediatr 2015;166:1030 e1-1030 e6.
20. Auvin S. Should we routinely use modified Atkins diet instead of regular ketogenic diet to treat children with epilepsy? Seizure 2012;21:237-40.
21. Sharma S, Jain P. The modified atkins diet in refractory epilepsy. Epilepsy Res Treat 2014;2014:404202.
22. Miranda MJ, Turner Z, Magrath G. Alternative diets to the classical ketogenic diet-can we be more liberal? Epilepsy Res 2012;100:278-85.
23. Coppola G, D'Aniello A, Messana T, Di Pasquale F, della Corte R, Pascotto A et al. Low glycemic index diet in children and young adults with refractory epilepsy: first Italian experience. Seizure 2011;20:526-8.
24. Paoli A, Moro T, Bosco G, Bianco A, Grimaldi KA, Camporesi E et al. Effects of n-3 polyunsaturated fatty acids (omega-3) supplementation on some cardiovascular risk factors with a ketogenic Mediterranean diet. Marine Drugs 2015;13:996-1009.
25. Bender DA. Energy Nutrition. The Metabolism of Carbohydrates and Fats. Introduction to Nutrition and Metabolism. Boca Raton, FL, USA: CRC Press; 2014: pp 115-63.
26. Courchesne-Loyer A, Fortier M, Tremblay-Mercier J, Chouinard-Watkins R, Roy M, Nugent S et al. Stimulation of mild, sustained ketonemia by medium-chain triacylglycerols in healthy humans: estimated potential contribution to brain energy metabolism. Nutrition 2013;29:635-40.
27. Chriett S, Pirola L. Essential roles of four-carbon backbone chemicals in the control of metabolism. World J Biol Chem 2015;6:223-30.
28. Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, Yan SD et al. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J Clin Investig 2003;112:892-901.
29. Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN. The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer. Nutr Metab 2007;4:5.
30. Sullivan PG, Rippy NA, Dorenbos K, Concepcion RC, Agarwal AK, Rho JM. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann Neurol 2004;55:576-80.
31. Warburg O, Wind F, Negelein E. The Metabolism of Tumors in the Body. J Gen Physiol 1927;8:519-30.
32. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-33.
33. Aykin-Burns N, Ahmad IM, Zhu Y, Oberley LW, Spitz DR. Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation. Biochem J 2009;418:29-37.
34. Peppicelli S, Bianchini F, Calorini L. Extracellular acidity, a "reappreciated" trait of tumor environment driving malignancy: perspectives in diagnosis and therapy. Cancer Metastasis Rev 2014;33:823-32.
35. Baserga R. The contradictions of the insulin-like growth factor 1 receptor. Oncogene 2000;19:5574-81.
36. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11-20.
37. Robey RB, Hay N. Is Akt the "Warburg kinase"?-Akt-energy metabolism interactions and oncogenesis. Semin Cancer Biol 2009;19:25-31.
38. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer 2009;9:550-62.
39. Klement RJ, Kammerer U. Is there a role for carbohydrate restriction in the treatment and prevention of cancer? Nutr Metab 2011;8:75.
40. Makinoshima H, Takita M, Saruwatari K, Umemura S, Obata Y, Ishii G et al. Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma. J Biol Chem 2015;290:17495-504.
41. Parajuli P, Tiwari RV, Sylvester PW. Anticancer effects of gamma-tocotrienol are associated with a suppression in aerobic glycolysis. Biol Pharm Bull 2015;38:1352-60.
42. Schlaepfer IR, Rider L, Rodrigues LU, Gijon MA, Pac CT, Romero L et al. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. Mol Cancer Ther 2014;13:2361-71.
43. Kunkel M, Reichert TE, Benz P, Lehr HA, Jeong JH, Wieand S et al. Overexpression of Glut-1 and increased glucose metabolism in tumors are associated with a poor prognosis in patients with oral squamous cell carcinoma. Cancer 2003;97:1015-24.
44. Derr RL, Ye X, Islas MU, Desideri S, Saudek CD, Grossman SA. Association between hyperglycemia and survival in patients with newly diagnosed glioblastoma. J Clin Oncol 2009;27:1082-6.
45. Seyfried TN, Kiebish MA, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Metabolic management of brain cancer. Biochim Biophys Acta 2011;1807:577-94.
46. Meidenbauer JJ, Mukherjee P, Seyfried TN. The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer. Nutr Metab 2015;12:12.
47. Tisdale MJ, Brennan RA. Loss of acetoacetate coenzyme A transferase activity in tumours of peripheral tissues. Br J Cancer 1983;47:293-7.
48. Skinner R, Trujillo A, Ma X, Beierle EA. Ketone bodies inhibit the viability of human neuroblastoma cells. J Pediatr Surg 2009;44:212-6; discussion 6.
49. Seyfried TN, Marsh J, Shelton LM, Huysentruyt LC, Mukherjee P. Is the restricted ketogenic diet a viable alternative to the standard of care for managing malignant brain cancer? Epilepsy Res 2012;100:310-26.
50. Fine EJ, Segal-Isaacson CJ, Feinman RD, Herszkopf S, Romano MC, Tomuta N et al. Targeting insulin inhibition as a metabolic therapy in advanced cancer: a pilot safety and feasibility dietary trial in 10 patients. Nutrition 2012;28:1028-35.
51. Bonuccelli G, Tsirigos A, Whitaker-Menezes D, Pavlides S, Pestell RG, Chiavarina B et al. Ketones and lactate "fuel" tumor growth and metastasis: evidence that epithelial cancer cells use oxidative mitochondrial metabolism. Cell Cycle 2010;9:3506-14.
52. Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S et al. Ketones and lactate increase cancer cell "stemness", driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 2011;10:1271-86.
53. Fearon K, Arends J, Baracos V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 2013;10:90-9.
54. Tisdale MJ. Mechanisms of cancer cachexia. Physiol Rev 2009;89:381-410.
55. Fearon KC, Borland W, Preston T, Tisdale MJ, Shenkin A, Calman KC. Cancer cachexia: influence of systemic ketosis on substrate levels and nitrogen metabolism. Am J Clin Nutr 1988;47:42-8.
56. Peres RC, Nogueira DB, de PGG, da CE, Ribeiro DA. Implications of ketogenic diet on weight gain, motor activity and cicatrization in Wistar rats. Toxicol Mech Methods 2013;23:144-9.
57. Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer. Br J Cancer 2003;89:1375-82.
58. Marsh J, Mukherjee P, Seyfried TN. Drug/diet synergy for managing malignant astrocytoma in mice: 2-deoxy-D-glucose and the restricted ketogenic diet. Nutr Metab 2008;5:33.
59. Otto C, Kaemmerer U, Illert B, Muehling B, Pfetzer N, Wittig R et al. 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 2008;8:122.
60. Abdelwahab MG, Fenton KE, Preul MC, Rho JM, Lynch A, Stafford P et al. The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. PLoS ONE 2012;7:e36197.
61. Poff AM, Ari C, Seyfried TN, D'Agostino DP. The ketogenic diet and hyperbaric oxygen therapy prolong survival in mice with systemic metastatic cancer. PLoS ONE 2013;8:e65522.
62. Kim M, Lee JH. Identification of an AMPK phosphorylation site in Drosophila TSC2 (gigas) that regulate cell growth. Int J Mol Sci 2015;16:7015-26.
63. Rattan R, Giri S, Singh AK, Singh I. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase. J Biol Chem 2005;280:39582-93.
64. Nebeling LC, Miraldi F, Shurin SB, Lerner E. Effects of a ketogenic diet on tumor metabolism and nutritional status in pediatric oncology patients: two case reports. J Am Coll Nutr 1995;14:202-8.
65. Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P et al. Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: case Report. Nutr Metab 2010;7:33.
66. Schmidt M, Pfetzer N, Schwab M, Strauss I, Kammerer U. Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: a pilot trial. Nutr Metab 2011;8:54.
67. Champ CE, Palmer JD, Volek JS, Werner-Wasik M, Andrews DW, Evans JJ et al. Targeting metabolism with a ketogenic diet during the treatment of glioblastoma multiforme. J Neurooncol 2014;117:125-31.
68. Rieger J, Bahr O, Maurer GD, Hattingen E, Franz K, Brucker D et al. ERGO: a pilot study of ketogenic diet in recurrent glioblastoma. Int J Oncol 2014;44:1843-52.
69. Wallace DC, Fan W, Procaccio V. Mitochondrial energetics and therapeutics. Ann Rev Pathol 2010;5:297-348.
70. Wenz T, Williams SL, Bacman SR, Moraes CT. Emerging therapeutic approaches to mitochondrial diseases. Dev Disabil Res Rev 2010;16:219-29.
71. Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF. The epidemiology of mitochondrial disorders-past, present and future. Biochim Biophys Acta 2004;1659:115-20.
72. Elliott HR, Samuels DC, Eden JA, Relton CL, Chinnery PF. Pathogenic mitochondrial DNA mutations are common in the general population. Am J Hum Genet 2008;83:254-60.
73. Kang H-C, Lee Y-M, Kim HD. Mitochondrial disease and epilepsy. Brain Dev 2013;35:757-61.
74. Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R et al. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol 2009;11:414-30.
75. Schon EA, DiMauro S, Hirano M, Gilkerson RW. Therapeutic prospects for mitochondrial disease. Trends Mol Med 2010;16:268-76.
76. DiMauro S, Mancuso M. Mitochondrial diseases: therapeutic approaches. Biosci Rep 2007;27:125-37.
77. Koene S, Smeitink J. Metabolic manipulators: a well founded strategy to combat mitochondrial dysfunction. J Inherit Metab Dis 2011;34:315-25.
78. Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012;3:1-8.
79. Bough KJ, Wetherington J, Hassel B, Pare JF, Gawryluk JW, Greene JG et al. Mitochondrial biogenesis in the anticonvulsant mechanism of the ketogenic diet. Ann Neurol 2006;60:223-35.
80. Danial NN, Hartman AL, Stafstrom CE, Thio LL. How does the ketogenic diet work? Four potential mechanisms. J Child Neurol 2013;28:1027-33.
81. Santra S, Gilkerson RW, Davidson M, Schon EA. Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann Neurol 2004;56:662-9.
82. Joshi CN, Greenberg CR, Mhanni AA, Salman MS. Ketogenic diet in Alpers-Huttenlocher syndrome. Pediatr Neurol 2009;40:314-6.
83. Kang HC, Lee YM, Kim HD, Lee JS, Slama A. Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 2007;48:82-8.
84. Kossoff EH, Zupec-Kania BA, Amark PE, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group. Epilepsia 2009;50:304-17.
85. Sperl W, Fleuren L, Freisinger P, Haack TB, Ribes A, Feichtinger RG et al. The spectrum of pyruvate oxidation defects in the diagnosis of mitochondrial disorders. J Inherit Metab Dis 2015;38:391-403.
86. Wexler ID, Hemalatha SG, McConnell J, Buist NR, Dahl HH, Berry SA et al. Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 1997;49:1655-61.
87. Bastin J. Regulation of mitochondrial fatty acid beta-oxidation in human: what can we learn from inborn fatty acid beta-oxidation deficiencies? Biochimie 2014;96:113-20.
88. Bennett MJ. Pathophysiology of fatty acid oxidation disorders. J Inherit Metab Dis 2010;33:533-7.
89. Rahman S. Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus. Epilepsy Behav 2015;49:71-5.
90. Jarrett SG, Milder JB, Liang LP, Patel M. The ketogenic diet increases mitochondrial glutathione levels. J Neurochem 2008;106:1044-51.
91. Cardenas JF, Amato RS. Compound heterozygous polymerase gamma gene mutation in a patient with Alpers disease. Semin Peadiatr Neurol 2010;17:62-4.
92. Spiegler J, Stefanova I, Hellenbroich Y, Sperner J. Bowel obstruction in patients with Alpers-Huttenlocher syndrome. Neuropediatrics 2011;42:194-6.
93. Martikainen MH, Paivarinta M, Jaaskelainen S, Majamaa K. Successful treatment of POLG-related mitochondrial epilepsy with antiepileptic drugs and low glycaemic index diet. Epileptic Disord 2012;14:438-41.
94. Khan A, Trevenen C, Wei XC, Sarnat HB, Payne E, Kirton A. Alpers syndrome: the natural history of a case highlighting neuroimaging, neuropathology, and fat metabolism. J Child Neurol 2012;27:636-40.
95. Krebs P, Fan W, Chen YH, Tobita K, Downes MR, Wood MR et al. Lethal mitochondrial cardiomyopathy in a hypomorphic Med30 mouse mutant is ameliorated by ketogenic diet. Proc Natl Acad Sci USA 2011;108:19678-82.
96. Coppola G, Veggiotti P, Cusmai R, Bertoli S, Cardinali S, Dionisi-Vici C et al. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res 2002;48:221-7.
97. Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G et al. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol 2008;7:500-6.
98. Groomes LB, Pyzik PL, Turner Z, Dorward JL, Goode VH, Kossoff EH. Do patients with absence epilepsy respond to ketogenic diets? J Child Neurol 2011;26:160-5.
99. Kossoff EH, Rowley H, Sinha SR, Vining EP. A prospective study of the modified Atkins diet for intractable epilepsy in adults. Epilepsia 2008;49:316-9.
100. Kim DY, Simeone KA, Simeone TA, Pandya JD, Wilke JC, Ahn Y et al. Ketone bodies mediate antiseizure effects through mitochondrial permeability transition. Ann Neurol 2015;78:77-87.
101. Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR et al. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol Aging 2013;34:1530-9.
102. Newport MT, VanItallie TB, Kashiwaya Y, King MT, Veech RL. A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease. Alzheimer's Dement 2015;11:99-103.
103. Vanitallie TB, Nonas C, Di Rocco A, Boyar K, Hyams K, Heymsfield SB. Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study. Neurology 2005;64:728-30.
104. de Lau LM, Bornebroek M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. Neurology 2005;64:2040-5.
105. Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J et al. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci 2006;7:29.
106. Dorst J, Kuhnlein P, Hendrich C, Kassubek J, Sperfeld AD, Ludolph AC. Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis. J Neurol 2011;258:613-7.
107. Ramm-Pettersen A, Nakken KO, Skogseid IM, Randby H, Skei EB, Bindoff LA et al. Good outcome in patients with early dietary treatment of GLUT-1 deficiency syndrome: results from a retrospective Norwegian study. Dev Med Child Neurol 2013;55:440-7.
108. Almuqbil M, Go C, Nagy LL, Pai N, Mamak E, Mercimek-Mahmutoglu S. New paradigm for the treatment of glucose transporter 1 deficiency syndrome: low glycemic index diet and modified high amylopectin cornstarch. Pediatr Neurol 2015;53:243-6.
109. Moshe SL, Perucca E, Ryvlin P, Tomson T. Epilepsy: new advances. Lancet 2014;385:884-98.
110. Rho JM. How does the ketogenic diet induce anti-seizure effects? Neurosci Lett 2015;15:30054-59.
111. Wulff H, Castle NA, Pardo LA. Voltage-gated potassium channels as therapeutic targets. Nat Rev Drug Discov 2009;8:982-1001.
112. Ueno S, Bracamontes J, Zorumski C, Weiss DS, Steinbach JH. Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor. J Neurosci 1997;17:625-34.
113. Stafstrom CE, Ockuly JC, Murphree L, Valley MT, Roopra A, Sutula TP. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol 2009;65:435-47.
114. Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C et al. Metabolic control of vesicular glutamate transport and release. Neuron 2010;68:99-112.
115. Hartman AL, Santos P, Dolce A, Hardwick JM. The mTOR inhibitor rapamycin has limited acute anticonvulsant effects in mice. PLoS ONE 2012;7:e45156.
116. McDaniel SS, Rensing NR, Thio LL, Yamada KA, Wong M. The ketogenic diet inhibits the mammalian target of rapamycin (mTOR) pathway. Epilepsia 2011;52:e7-11.
117. Yamada KA. Calorie restriction and glucose regulation. Epilepsia 2008;49(Suppl. 8):94-6.
118. Bough K. Energy metabolism as part of the anticonvulsant mechanism of the ketogenic diet. Epilepsia 2008;49(Suppl. 8):91-3.
119. Danial NN. BAD: undertaker by night, candyman by day. Oncogene 2008;27(Suppl. 1):S53-70.
120. Gimenez-Cassina A, Martinez-Francois JR, Fisher JK, Szlyk B, Polak K, Wiwczar J et al. BAD-dependent regulation of fuel metabolism and K(ATP) channel activity confers resistance to epileptic seizures. Neuron 2012;74:719-30.
121. Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F, Forte M et al. Dimers of mitochondrial ATP synthase form the permeability transition pore. Proc Natl Acad Sci USA 2013;110:5887-92.
122. Brenner C, Moulin M. Physiological roles of the permeability transition pore. Circ Res 2012;111:1237-47.
123. Kashiwaya Y, Takeshima T, Mori N, Nakashima K, Clarke K, Veech RL. D-beta-hydroxybutyrate protects neurons in models of Alzheimer's and Parkinson's disease. Proc Natl Acad Sci USA 2000;97:5440-4.
124. Perfeito R, Cunha-Oliveira T, Rego AC. Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease-resemblance to the effect of amphetamine drugs of abuse. Free Radic Biol Med 2012;53:1791-806.
125. Dhamija R, Eckert S, Wirrell E. Ketogenic diet. Can J Neurol Sci 2013;40:158-67.
126. Bansal S, Cramp L, Blalock D, Zelleke T, Carpenter J, Kao A. The ketogenic diet: initiation at goal calories versus gradual caloric advancement. Pediatr Neurol 2014;50:26-30.
127. Freeman JM, Kossoff EH, Hartman AL. The ketogenic diet: one decade later. Pediatrics 2007;119:535-43.
128. Sampath A, Kossoff EH, Furth SL, Pyzik PL, Vining EP. Kidney stones and the ketogenic diet: risk factors and prevention. J Child Neurol 2007;22:375-8.
129. Kang HC, Chung DE, Kim DW, Kim HD. Early- and late-onset complications of the ketogenic diet for intractable epilepsy. Epilepsia 2004;45:1116-23.
130. Keene DL. A systematic review of the use of the ketogenic diet in childhood epilepsy. Pediatr Neurol 2006;35:1-5.
131. Ballaban-Gil K, Callahan C, O'Dell C, Pappo M, Moshe S, Shinnar S. Complications of the ketogenic diet. Epilepsia 1998;39:744-8.
132. Manninen V, Tenkanen L, Koskinen P, Huttunen JK, Manttari M, Heinonen OP et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Implications for treatment. Circulation 1992;85:37-45.
133. Bergqvist AG. Long-term monitoring of the ketogenic diet: Do's and Don'ts. Epilepsy Res 2012;100:261-6.