The ketogenic diet and brain metabolism of amino acids: Relationship to the anticonvulsant effect

Annual Review of Nutrition

Volumn 27, Issue , 2007, Pages 415-430

  Yudkoff, Marc ^a   Daikhin, Yevgeny ^a   Melø, Torun Margareta ^b   Nissim, Ilana ^a   Sonnewald, Ursula ^b   Nissim, Itzhak ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

Author keywords

Anticonvulsant therapy; Brain amino acid metabolism; Epilepsy; Ketosis

Indexed keywords

4 AMINOBUTYRIC ACID; GLUTAMIC ACID; GLUTAMINE; KETONE; KETONE BODY; AMINO ACID; ANTICONVULSIVE AGENT;

AMINO ACID BRAIN LEVEL; AMINO ACID TRANSPORT; ANTICONVULSANT ACTIVITY; BRAIN FUNCTION; BRAIN METABOLISM; GLUCOSE METABOLISM; GLUCOSE OXIDATION; HUMAN; KETOACIDOSIS; KETOGENIC DIET; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; REVIEW; BRAIN; DIET; DIET THERAPY; METABOLISM; MULTIMODALITY CANCER THERAPY; SEIZURE; TREATMENT OUTCOME;

AMINO ACIDS; ANTICONVULSANTS; BRAIN; COMBINED MODALITY THERAPY; DIET; GLUTAMIC ACID; HUMANS; KETONE BODIES; KETOSIS; SEIZURES; TREATMENT OUTCOME;

EID: 38449086860     PISSN: 01999885     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.nutr.27.061406.093722     Document Type: Review

References (143)

1. Al-Mudallal AS, LaManna JC, Lust WD, Harik SI. 1996. Diet-induced ketosis does not cause cerebral acidosis. Epilepsia 37:258-61
2. Amara SG, Fontana AC. 2002. Excitatory amino acid transporters: keeping up with glutamate. Neurochem. Int. 41:313-18
3. Battaglioli G, Martin DL. 1990. Stimulation of synaptosomal γ-aminobutyric acid synthesis by glutamate and glutamine. J. Neurochem. 54:1179-87
4. Bergqvist AG, Schall JI, Gallagher PR, Cnaan A, Stallings VA. 2005. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 46:1810-19
5. Berl S, Takagaki G, Clarke DD, Waelsch H. 1962. Metabolic compartments in vivo. Ammonia and glutamic acid metabolism in brain and liver. J. Biol. Chem. 237:2562-69
6. Bixel MG, Hutson SM, Hamprecht B. 1997. Cellular distribution of branched-chain amino acid aminotransferase isoenzymes among rat brain glial cells in culture. J. Histochem. Cytochem.. 45:685-94
7. Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM. 1999. Selective expression of the large neutral amino acid transporter at the blood-brain barrier. Proc. Natl. Acad. Sci. USA 96:12079-84
8. Bough KJ, Schwartzkroin PA, Rho JM. 2003. Calorie restriction and ketogenic diet diminish neuronal excitability in rat dentate gyrus in vivo. Epilepsia 44:752-60
9. Bravata DM, Sanders L, Huang J, Krumholz HM, Olkin I, et al. 2003. Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 289:1837-50
10. Broer S, Brookes N. 2001. Transfer of glutamine between astrocytes and neurons. J. Neurochem. 77:705-19
11. Burdakov D, Gerasimenko O, Verkhratsky A. 2005. Physiological changes in glucose differentially modulate the excitability of hypothalamic melanin-concentrating hormone and orexin neurons in situ. J. Neurosci. 25:2429-33
12. Cahill GF Jr. 1998. Survival in starvation. Am. J. Clin. Nutr. 68:1-2
13. Camfield CR, Camfield CS. 1996. Antiepileptic drug therapy: When is epilepsy truly intractable? Epilepsia 37:S60-65
14. Carlson H, Ronne-Engstrum E, Ungerstedt U, Hillered L. 1992. Seizure-related elevations of extracellular amino acids in human focal epilepsy. Neurosci. Lett. 140:30-32
15. 13C NMR. J. Biol. Chem. 265:12916-26
16. Chaudhry FA, Reimber RJ, Edward RH. 2002. The glutamine commute: Take the N line and transfer to the A. J. Cell Biol. 157:349-55
17. Cheng CM, Kelley B, Wang J, Strauss D, Eagles DA, Bondy CA. 2003. A ketogenic diet increases brain insulin-like growth factor receptor and glucose transporter gene expression. Endocrinology 144:2676-82
18. Chiry O, Pellerin L, Monnet-Tschudi F, Fishbein WN, Merezhinskaya N, et al. 2006. Expression of the monocarboxylate transporter MCT1 in the adult human brain cortex. Brain Res. 1070:65-70
19. Clarke DD, Sokoloff L. 1999. Circulation and energy metabolism of the brain. In Basic Neurochemistry: Molecular, Cellular and Medical Aspects, ed. GJ Siegel, BW Agranoff, RW Albers, SK Fisher, MD Uhler, pp. 637-69. Philadelphia: Lippincott-Raven. 6th ed.
20. 13N-labeled ammonia in rat brain. J. Biol. Chem. 254:4982-92
21. Cunnane SC, Musa K, Ryan MA, Whiting S, Fraser DD. 2002. Potential role of polyunsaturates in seizure protection achieved with the ketogenic diet. Prostaglandins Leukot. Essent. Fatty Acids 67:131-35
22. Dahlin M, Elfving A, Ungerstedt U, Amark P. 2005. The ketogenic diet influences the levels of excitatory and inhibitory amino acids in the CSF in children with refractory epilepsy. Epilepsy Res. 64:115-25
23. Daikhin Y, Yudkoff M. 1998. Ketone bodies and brain glutamate and GABA metabolism. Dev. Neurosci. 20:358-64
24. Danbolt NC. 2001. Glutamate uptake. Prog. Neurobiol. 65:1-105
25. DeDeyn PP, Marescau B, MacDonald RL. 1990. Epilepsy and the GABA-hypothesis: a brief review and some samples. Acta Neurol. Belg. 90:65-81
26. DeVivo DC, Leckie MP, Ferrendelli JS, McDougal DB Jr. 1978. Chronic ketosis and cerebral metabolism. Ann. Neurol. 3:331-37
27. Do KQ, Klancnik J, Gahwiler BH. 1991. Release of EAA: animal studies and epileptic foci studies in humans. In Excitatory Amino Acids, ed. BS Meldrum, F Moroni, RP Simon, pp. 677-85. New York: Raven
28. Dombrowski GJ Jr, Swiatek KR, Chao KL. 1989. Lactate, 3-hydroxybutyrate and glucose as substrates for early postnatal rat brain. Neurochem. Res. 14:667-75
29. Eagles DA, Boyd SJ, Kotak A, Allan F. 2003. Calorie restriction of a high-carbohydrate diet elevates the threshold of PTZ-induced seizures to values equal to those seen with a ketogenic diet. Epilepsy Res. 54:41-52
30. + and adenosine triphosphate in isolated brain synaptosomes. J. Gen. Physiol. 95:591-616
31. Erecinska M, Nelson D, Daikhin Y, Yudkoff M. 1996. Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium and ketone bodies. J. Neurochem. 67:2325-34
32. Erecinska M, Silver IA. 1990. Metabolism and role of glutamate in mammalian brain. Prog. Neurobiol. 35:245-96
33. Escartin C, Valette J, Lebon V, Bonvento G. 2006. Neuron-astrocyte interactions in the regulation of brain energy metabolism: a focus on NMR spectroscopy. J. Neurochem. 99:393-401
34. Fleck MW, Henze DA, Barrionuevo G, Palmer AM. 1993. Aspartate and glutamate mediate excitatory synaptic transmission in area CA1 of the hippocampus. J. Neurosci. 13:3944-55
35. Freeman J, Veggiotti P, Lanzi G, Tagliabue A, Perucca E. 2006. The ketogenic diet: from molecular mechanisms to clinical effects. Epilepsy Res. 68:145-80
36. Freeman JM, Vining EP, Pillas DJ, Pyzik PL, Casey JC, Kelly LM. 1998. The efficacy of the ketogenic diet - 1998: a prospective evaluation of intervention in 150 children. Pediatrics 102:1358-63
37. Fuehrlein BS, Rutenberg MS, Silver JN, Warren MW, Theriaque DW, et al. 2004. Differential metabolic effects of saturated versus polyunsaturated fats in ketogenic diets. J Clin. Endocrinol. Metab. 89:1641-45
38. Fukao T, Song XQ, Mitchell GA, Yamaguchi S, Sukegawa K, et al. 1997. Enzymes of ketone body utilization in human tissues: protein and messenger RNA levels of succinyl-coenzyme A (CoA):3-ketoacid CoA transferase and mitochondrial and cytosolic acetoacetyl-CoA thiolases. Pediatr. Res. 42:498-502
39. Gegelashvili G, Schousboe A. 1998. Cellular distribution and kinetic properties of high-affinity glutamate transporters. Brain Res. Bull. 45:233-38
40. 11C]acetone as potential radiotracers for studying inhalant abuse. Nucl. Med. Biol. 32:201-8
41. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR. 1997. Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am. J. Physiol. 273:E207-13
42. Gould EM, Curto KA, Craig CR, Fleming WW, Taylor DA. 1995. The role of GABA-A receptors in the subsensitivity of Purkinje neurons to GABA in genetic epilepsy-prone rats. Brain Res. 698:62-68
43. Greene AE, Todorova MT, McGowan R, Seyfried TN. 2001. Caloric restriction inhibits seizure susceptibility in epileptic EL mice by reducing blood glucose. Epilepsia 42:1371-78
44. Grill V, Björkhem M, Gutniak M, Lindqvist M. 1992. Brain uptake and release of amino acids in nondiabetic and insulin-dependent diabetic subjects: important role of glutamine release for nitrogen balance. Metabolism 41:28-32
45. Hawkins RA, O'Kane RL, Simpson IA, Vina JR. 2006. Structure of the blood-brain barrier and its role in the transport of amino acids. J. Nutr. 136:218-26S
46. Hertz L, Peng L, Dienel GA. 2007. Energy metabolism in astrocytes: high rate of oxidative metabolism and spatiotemporal dependence on glycolysis/glycogenolysis. J. Cereb. Blood Flow Metab. 27(2):219-49
47. Hertz L, Peng L, Westergaard N, Yudkoff M, Schousboe A. 1992. Neuronal-astrocytic interactions in metabolism of transmitter amino acids of the glutamate family. In Drug Research Related to Neuroactive Amino Acids, Alfred Benzon Symposium. 32, ed. A Schousboe, NH Diemer, H Kofod, pp 30-48. Copenhagen: Munksgaard
48. Hovanics GE, DeLorey TM, Firestone LL, Quinlan JJ, Handforth A, et al. 1997. Mice devoid of gamma-aminobutyrate type A receptor beta3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc. Natl. Acad. Sci. USA 94:4143-48
49. Huang Y, Zielke HR, Tildon JT, Zielke CL, Baab PJ. 1996. Elevation of amino acids in the interstitial space of the rat brain following infusion of large neutral amino and keto acids by microdialysis: leucine infusion. Dev. Neurosci. 18:415-19
50. Hutson SM, Wallin R, Hall TR. 1992. Identification of mitochondrial branched chain aminotransferase and its isoforms in rat tissues. J. Biol. Chem. 267:15681-86
51. Kanamori K, Ross BD. 2004. Quantitative determination of extracellular glutamine concentration in rat brain, and its elevation in vivo by system A transport inhibitor, alpha-(methylamino)isobutyrate. J. Neurochem. 90:203-10
52. 15N NMR. J. Neurochem. 70:1304-15
53. Kety SS, Schmidt CF. 1948. The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure, and normal values. J. Clin. Invest. 27:476-83
54. Koper JW, Lopes-Cardozo M, Van Golde LM. 1981. Preferential utilization of ketone bodies for the synthesis of myelin cholesterol in vivo. Biochem. Biophys. Acta 666:411-17
55. Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. 2003. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology 61:1789-91
56. Kossoff EH, Pyzik PL, McGrogan JR, Vining EP, Freeman JM. 2002. Efficacy of the ketogenic diet for infantile spasms. Pediatrics 109:780-83
57. Kossoff EH, Thiele EA, Pfeifer HH, McGrogan JR, Freeman JM. 2005. Tuberous sclerosis complex and the ketogenic diet. Epilepsia 46:1684-86
58. Kwiterovich POJr, Vining EP, Pyzik P, Skolasky R Jr, Freeman JM. 2003. Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. JAMA 290:912-20
59. Lapidot A, Haber S. 2002. Effect of endogenous β-hydroxybutyrate on brain glucose metabolism in fetuses of diabetic rabbits, studied by 13C magnetic resonance spectroscopy. Dev. Brain Res. 135:87-99
60. Lasley SM, Yan QS. 1994. Diminished potassium-stimulated GABA release in vivo in genetically epilepsy-prone rats. Neurosci. Lett. 175:145-48
61. Lefevre F, Aronson A. 2000. Ketogenic diet for the treatment of refractory epilepsy in children: a systematic review of efficacy. Pediatrics 105:E46
62. Likhodii SS, Serbanescu I, Cortez MA, Murphy P, Snead OC 3rd, Burnham WM. 2003. Anticonvulsant properties of acetone, a brain ketone elevated by the ketogenic diet. Ann. Neurol. 54:219-26
63. Lopes-Cardozo M, Koper JW, Klein W, Van Golde LM. 1984. Acetoacetate is a cholesterogenic precursor for myelinating rat brain and spinal cord. Incorporation of label from [3-14C]acetoacetate, [14C]glucose and 3H2O. Biochem. Biophys. Acta 794:350-52
64. Loscher W, Swark WS. 1985. Evidence for impaired GABAergic activity in the substantia nigra of amygdaloid kindled rats. Brain Res. 339:146-50
65. Mady MA, Kossoff EH, McGregor AL, Wheless JW, Pyzik PL, Freeman JM. 2003. The ketogenic diet: Adolescents can do it, too. Epilepsia 44:847-51
66. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. 1999. Energy on demand. Science 283:496-97
67. Mantis JG, Centeno NA, Todorova MT, McGowan R, Seyfried TN. 2004. Management of multifactorial idiopathic epilepsy in EL mice with caloric restriction and the ketogenic diet: role of glucose and ketone bodies. Nutr. Metab. 1:1-11
68. Martin D, Bustos GA, Bowe MA, Bray SD, Nadler JV. 1991. Autoreceptor regulation of glutamate and aspartate release from slices of the hippocampal CA1 area. J. Neurochem. 56:1647-55
69. Martinez-Hernandez A, Bell KP, Norenberg MD. 1977. Glutamine synthetase: glial localization in brain. Science 195:1356-58
70. Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ. 1995. Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J. Cereb. Blood Flow Metab. 15:12-25
71. Mattson MP, Liu D. 2003. Mitochondrial potassium channels and uncoupling proteins in synaptic plasticity and neuronal cell death. Biochem. Biophys. Res. Comm. 304:539-49
72. McKenna MC, Tildon JT, Stevenson JH, Boatright R, Huang S. 1993. Regulation of energy metabolism in synaptic terminals and cultured rat brain astrocytes: Differences revealed using aminooxyacetate. Dev. Neurosci. 15:320-29
73. Meldrum BS. 1994. The role of glutamate in epilepsy and other CNS disorders. Neurology 44:S14-23
74. Meldrum BS. 2000. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J. Nutr. 130:1007-15S
75. Melo TM, Nehlig A, Sonnewald U. 2006. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochem. Int. 48:498-507
76. Nehlig A, Pereira de Vasconcelos A. 1993. Glucose and ketone body utilization by the brain of neonatal rats. Progr. Neurobiol. 40:163-221
77. Noh HS, Kim DW, Cho GJ, Choi WS, Kang SS. 2006. Increased nitric oxide caused by the ketogenic diet reduces the onset time of kainic acid-induced seizures in ICR mice. Brain Res. 1075:193-200
78. Nordli DR Jr, Kuroda MM, Carroll J, Koenigsberger DY, Hirsch LJ, et al. 2001. Experience with the ketogenic diet in infants. Pediatrics 108:129-33
79. Norenberg MD, Martinez-Hernandez A. 1979. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161:303-10
80. O'Kane RL, Martinez-Lopez I, DeJoseph MR, Vina JR, Hawkins RA. 1999. Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. J. Biol. Chem. 274:31891-95
81. O'Kane RL, Vina JR, Simpson I, Hawkins RA. 2004. Na+-dependent neutral amino acid transporters A, ASC, and N of the blood-brain barrier: mechanisms for neutral amino acid removal. Am. J. Physiol. Endocrinol. Metab. 287:E622-29
82. Olney JW. 2003. Excitotoxicity, apoptosis and neuropsychiatric disorders. Curr. Opin. Pharmacol. 3:101-9
83. Olsen RW, Avoli M. 1997. GABA and epileptogenesis. Epilepsia 38:399-407
84. Olstad E, Qu H, Sonnewald U. 2007. Glutamate is preferred over glutamine for intermediary metabolism in cultured cerebellar neurons. J. Cereb. Blood Flow Metab. 27:811-20
85. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF. 1967. Brain metabolism during fasting. J. Clin. Invest. 46:1589-95
86. 31P spectroscopic imaging at 4.1T. Epilepsia 40:703-7
87. Patel AJ, Balazs R, Richter D. 1970. Contribution of the GABA bypath to glucose oxidation, and the development of compartmentation in the brain. Nature 226:1160-61
88. Patel AJ, Johnson AL, Balazs R. 1974. Metabolic compartmentation of glutamate associated with the formation of γ-aminobutyrate. J. Neurochem. 23:1271-79
89. +-evoked release of transmitter amino acids investigated by microdialysis. J. Neurochem. 52:1823-29
90. Peng L, Hertz L. 1993. Potassium-induced stimulation of oxidative metabolism of glucose in cultures of intact cerebellar granule cells but not in corresponding cells with dendritic degeneration. Brain Res. 629:331-34
91. Petroff OA. 2002. GABA and glutamate in the human brain. Neuroscientist 8:562-73
92. Petroff OA, Rothman D, Behar KL, Mattson RH. 1996. Low brain GABA level is associated with poor seizure control. Ann. Neurol. 40:908-11
93. Pierre K, Pellerin L. 2005. Monocarboxylate transporters in the central nervous system: distribution, regulation and function. J. Neurochem. 94:1-14
94. Plaitakis A, Zaganas I. 2001. Regulation of human glutamate dehydrogenases: implications for glutamate, ammonia and energy metabolism in brain. J. Neurosci. Res. 66:899-908
95. Porter TG, Martin DL. 1988. Stability and activation of glutamate apodecarboxylase from pig brain. J. Neurochem. 51:1886-91
96. Prins ML, Lee SM, Fujima LS, Hovda DA. 2004. Increased cerebral uptake and oxidation of exogenous bHB improves ATP following traumatic brain injury in adult rats. J. Neurochem. 90:666-72
97. Raiteri M, Marchi M, Costi A, Volpe G. 1990. Endogenous aspartate release in the rat hippocampus inhibited by M2 "cardiac" muscarinic receptors. Eur. J. Pharmacol. 177:181-87
98. Ratnakumari L, Murthy CRK. 1989. Activities of pyruvate dehydrogenase, enzymes of citric acid cycle, and aminotransferases in the subcellular fractions of cerebral cortex in normal and hyperammonemic rats. Neurochem. Res. 14:221-28
99. Sato K, Kashiwaya Y, Keon CA, Tsuchiya N, King MT, et al. 1995. Insulin, ketone bodies, and mitochondrial energy transduction. FASEB J. 9:651-58
100. Scheppach W, Pomare EW, Elia M, Cummings JH. 1991. The contribution of the large intestine to blood acetate in man. Clin. Sci. 80:177-82
101. Schousboe A, Waagepetersen HS. 2005. Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotox. Res. 8:221-25
102. Schurr A, Miller JJ, Payne RS, Rigor BM. 1999. An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons. J. Neurosci. 19:34-39
103. Schwechter EM, Veliskova J, Velisek L. 2003. Correlation between extracellular glucose and seizure susceptibility in adult rats. Ann. Neurol. 53:91-101
104. Shank RP, Aprison MH. 1977. Present status and significance of the glutamine cycle in neural tissues. Life Sci. 28:837-42
105. Shank RP, Bennett GS, Freytag SO, Campbell GL. 1985. Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 329:364-67
106. Siesjo BK. 1997. Brain Energy Metabolism. New York: Wiley
107. Smith QR, Momma S, Aoyagi M, Rapoport SI. 1987. Kinetics of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 49:1651-58
108. Sonnewald U, Schousboe A, Qu H, Waagepetersen HS. 2004. Intracellular metabolic compartmentation assessed by 13C magnetic resonance spectroscopy. Neurochem. Int. 45:305-10
109. 13C]NMR spectroscopy that glutamine from astrocytes is a precursor for GABA synthesis in neurons. Neurochem. Int. 22:19-29
110. Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, et al. 1983. First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301:517-20
111. Storm-Mathisen J, Ottersen OP. 1986. Antibodies against amino acid neurotransmitters. In Neurohistochemistry: Modern Methods and Applications, ed. P Paunula, H Paivarinta, S Soinila, pp. 107-36. New York: Liss
112. Sullivan PG, Dube C, Dorenbos K, Steward O, Baram TZ. 2003. Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. Ann. Neurol. 53:711-17
113. Sullivan PG, Rippy NA, Dorenbos K, Concepcion RC, Agarwal AK, Rho JM. 2004. The ketogenic diet increases mitochondrial uncoupling protein levels and activity. Ann. Neurol. 55:576-80
114. Swink TD, Vining EP, Freeman JM. 1997. The ketogenic diet. Adv. Pediatr. 44:297-329
115. Szot P, Weinshenker D, Rho JM, Storey TW, Schwartzkroin PA. 2001. Norepinephrine is required for the anticonvulsant effect of the ketogenic diet. Brain Res. Dev. Brain Res. 129:211-14
116. Takahashi M, Billups B, Rossi D, Sarantis M, Hamann M, Attwell D. 1997. The role of glutamate transporters in glutamate homeostasis in the brain. J. Exper. Biol. 200:401-9
117. Thiele EA. 2003. Assessing the efficacy of antiepileptic treatments: the ketogenic diet. Epilepsia 44:26-29
118. Thurston JH, Hauhart RE, Schiro JA. 1986. Beta-hydroxybutyrate reverses insulin-induced hypoglycemic coma in suckling-weanling mice despite low blood and brain glucose levels. Metab. Brain Dis. 1:63-82
119. Tieu K, Perier C, Caspersen C, Teismann P, Wu DC, et al. 2003. D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Invest. 112:892-901
120. Vamecq J, Vallee L, Lesage F, Gressens P, Stables JP. 2005. Antiepileptic popular ketogenic diet: emerging twists in an ancient story. Prog. Neurobiol. 75:1-28
121. Veech RL. 2004. The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot. Essent. Fatty Acids 70:309-19
122. Veech RL, Chance B, Kashiwaya Y, Lardy HA, Cahill GF Jr. 2001. Ketone bodies, potential therapeutic uses. IUBMB Life 51:241-47
123. Vining EP. 1999. Clinical efficacy of the ketogenic diet. Epilepsy Res. 37:181-90
124. Vining EPG, Pyzik P, McGrogan J, Hladky H, Anand A, et al. 2002. Growth of children on the ketogenic diet. Dev. Med. Child Neurol. 44:796-802
125. 13C-NMR spectroscopy. Dev. Neurosci. 20:310-20
126. 13C MR spectroscopy. Neurochem. Int. 36:349-58
127. Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A. 2000. A possible role of alanine for ammonia transfer between astrocytes and glutamatergic neurons. J. Neurochem. 75:471-79
128. Waagepetersen HS, Sonnewald U, Schousboe A. 2003. Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and astrocytes: functional implications. Neuroscientist 9:398-403
129. Wang ZJ, Bergqvist C, Hunter JV, Jin D, Wang DJ, et al. 2003. In vivo measurement of brain metabolites using two-dimensional double-quantum MR spectroscopy-exploration of GABA levels in a ketogenic diet. Magn. Reson. Med. 49:615-19
130. Waniewski RA, Martin DL. 1998. Preferential utilization of acetate by astrocytes is attributable to transport. J. Neurosci. 18:5225-33
131. Waxman EA, Lynch DR. 2005. N-methyl-D-aspartate receptor subtypes: multiple roles in excitotoxicity and neurological disease. Neuroscientist 11:37-49
132. White HS. 1997. Clinical significance of animal seizure models and mechanism of action studies of potential antiepileptic drugs. Epilepsia 38(Suppl. 1):S9-17
133. Wilder RM. 1921. Effects of ketonuria on the course of epilepsy. Mayo Clin. Bull. 2:307-10
134. Wilkins L. 1937. Epilepsy in childhood. III. Results with the ketogenic diet. J. Pediatr. 10:341-57
135. Wu JY. 1976. Purification, characterization and kinetic studies of GAD and GABA-T from mouse brain. In GABA in Nervous System Function, ed. E Roberts, TN Chase, DB Tower, pp. 7-55. New York: Raven
136. Yanagida O, Kanai Y, Chairoungdua A, Kim DK, Segawa H, et al. 2001. Human L-type amino acid transporter 1. LAT1: characterization of function and expression in tumor cell lines. Biochem. Biophys. Acta 1514:291-302
137. Yudkoff M, Daikhin Y, Nelson D, Nissim I, Erecinska M. 1996. Neuronal metabolism of branched-chain amino acids: flux through the aminotransferase pathway in synaptosomes. J. Neurochem. 66:2136-45
138. Yudkoff M, Daikhin Y, Nissim I, Grunstein R, Nissim I. 1997. Effects of ketone bodies on astrocyte amino acid metabolism. J. Neurochem. 69:682-92
139. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Lazarow A, et al. 2005. Response of brain amino acid metabolism to ketosis. Neurochem. Int. 47:119-28
140. Yudkoff M, Daikhin Y, Nissim I, Lazarow A, Nissim I. 2001. Ketogenic diet, amino acid metabolism and seizure control. J. Neurosci. Res. 66:931-40
141. Yudkoff M, Daikhin Y, Nissim I, Lazarow A, Nissim I. 2004. Ketogenic diet, brain glutamate metabolism and seizure control. Prostaglandins Leukot. Essential Fatty Acids 70:277-85
142. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, et al. 2006. Short-term fasting, seizure control and brain amino acid metabolism. Neurochem. Int. 48:650-56
143. Yudkoff M, Nelson D, Daikhin Y, Erecinska M. 1994. Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle. J. Biol. Chem. 269:27414-20