维生素 D 在生酮饮食治疗癫痫中的意义_Journal of Epilepsy

Authors：

刘丽琴 ¹ , 廖建湘 ²

1. ;
2. ;

Corresponding author：

Keywords：

维生素 D; 神经系统; 癫痫; 生酮饮食

DOI：

10.7507/2096-0247.20200040

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研究表明，维生素 D（Vitamin D，Vit D）在人类大脑和神经系统中扮演着重要角色。已有研究探索了 Vit D 在阿尔茨海默病、帕金森病、多发性硬化症、精神分裂症、情感障碍、认知衰退和癫痫等方面的作用，同时 Vit D 在神经系统中也起着神经营养、神经保护、神经传递等作用。研究证明，维生素 D 受体（Vitamin D receptor，VDR）普遍存在于神经元和神经胶质细胞乃至整个大脑、脊髓和周围神经系统中，故 Vit D 在神经系统中的作用从 VDR 也得到了证实。Vit D 在神经系统中的广泛作用提示了其在大脑中可能存在抗惊厥作用，而既往研究证明癫痫患者的 Vit D 水平普遍较低，且生酮饮食可能会进一步导致 Vit D 水平下降，因此，Vit D 的补充对于癫痫患儿以及生酮饮食治疗癫痫的疗效具有重要意义。

Citation： 刘丽琴, 廖建湘. 维生素 D 在生酮饮食治疗癫痫中的意义. Journal of Epilepsy, 2020, 6(3): 224-227. doi: 10.7507/2096-0247.20200040 Copy

1.	Annweiler C, Schott AM, Berrut G, et al. Vitamin D and ageing: neurological issuess. Neuropsychobiology, 2010, 62(3): 139-150.
2.	Eyles DW, Smith S, Kinobe Rl, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. Journal of Chemmical Neuroanatomy, 2005, 29(1): 21-30.
3.	Bergqvist AGC, Schall JI, Virginia AS. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia, 2007, 48(1): 66-71.
4.	Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys, 2012, 523(1): 123-133.
5.	Marini F, Bartoccini E, Cascianelli G, et al. Effect of 1alpha, 25-dihydroxy vitamin D₃ in embryonic hippocampal cells. Hippocampus, 2010, 20(6): 696-705.
6.	Wang Y, Chiang YH, Su TP, et al. Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation inrats. Neuropharmacology, 2000, 39(5): 873-880.
7.	Naveilhan P, Neveu I, Wion D, et al. 1,25-Dihydroxy vitaminD3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport, 1996, 7(13): 2171-2175.
8.	Brewer LD, Thibault V, Chen KC, et al. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type Ca²⁺ channel expression in hippocampal neurons. The Journal of Neuroscience, 2001, 21: 98-108.
9.	Viragh PA. Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis. Proc Natl Acad Sci USA, 1989, 86: 3887-3890.
10.	Garcion, E, Nataf S, berod A, et al. 1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat nervous system during experimental allergic encephalomyelitis. Molecular Brain Research, 1997, 45(2): 255-267.
11.	Garcion, E. et al Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxy vitamin D3. Glia, 1998, 22: 282-294.
12.	Dawson VL, Dawson TM. Nitric oxide actions in neurochemistry. Neurochemistry International, 1996, 29: 97-110.
13.	Mitrovic B, Pierre BAS, Allan JMG, et al. The role of nitric oxide in glial pathology. Annals of the New York Academy of Science, 1994, 738(1): 436-446.
14.	Shinpo K, Kikuchi S, Sasaki H, et al. Effect of 1,25-dihydroxy vitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine. Journal of Neuroscience Research, 2000, 62(3): 374-382.
15.	Taniera H, Ito M, Sanada N, et al. Chronic vitamin D₃ treatment protects against neurotoxicity by glutamate in association with upregulation of vitamin D receptor mRNA expression incultured rat cortical neurons. Journal of Neuroscience Research, 2006, 83(7): 1179-1189.
16.	Dringen R, Gutterer JM, Hirrlinger J, et al. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem, 2000, 267(16): 4912-4916.
17.	Garcion E, Thanh XD, Bled F, et al. 1,25-Dihydroxyvitamin D3 regulates γ-glutamyl transpeptidase activity in rat brain. Neuroscience Letters, 1996, 216(3): 183-186.
18.	Garcion E, Sindji L, Leblondel G, et al. 1,25-Dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem, 1999, 73(2): 859-866.
19.	Sonnenberg J, Luine VN, Krey LC, et al. 1,25dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology, 1986, 118: 1433-1439.
20.	Baksi SN, Hughes MJ. Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Research, 1982, 242(2): 387-390.
21.	Puchacz E, Stumpf W E, Stachowiak E K, et al. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Mollecular Brain Research, 1996, 36(1): 193-196.
22.	Almeras L, Eyles D, Benech P, et al. Developmental vitamin Ddeficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics, 2007, 7(5): 769-780.
23.	Christiansen C, Paul Rødbro, Ole Sjö. “Anticonvulsant Action” of Vitamin D in Epileptic Patients? A Controlled Pilot Study. British Medical Journal, 1974, 2(5913): 258-259.
24.	András, Holló, et al. Correction of vitaminD deficiency improves seizure control in epilepsy: A pilot study. Epilepsy Behavior, 2012, 24(1): 131-133.
25.	Kalueff AV, Eremin KO, Tuohimaa P. Mechanisms of neuroprotective action of vitamin D3. Biochemistry, 2004, 69: 738-41.
26.	Vezzani A, Balosso S, Ravizza T. The role of cytokines in the pathophysiology of epilepsy. Brain, Behavior, and Immunity, 2008, 22(6): 0-803.
27.	Beattie, E. C Control of Synaptic Strength by Glial TNFalpha. Science (Washington D C), 2002, 295(5563): 2282-2285.
28.	Stellwagen D, Beattie E C, Seo J Y, et al. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. Journal of Neuroscience the Official Journal of the Society for Neuroscience, 2005, 25(12): 3219-28.
29.	Xu B, Michalski B, Racine R J, et al. Continuous infusion of neurotrophin-3 triggers sprouting, decreases the levels of TrkA and TrkC, and inhibits epileptogenesis and activity-dependent axonal growth in adult rats. Neuroscience, 2002, 115(4): 0-1308.
30.	Leranth C, Ribak CE. Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: a possible key to this region's resistance to epileptic damage. Experimental Brain Research, 1991, 85(1): 129-136.
31.	Kanter-Schlifke I, Georgievska B, Kirik D, et al. Seizure suppression by GDNF gene therapy in animal models of epilepsy. Molecular Therapy the Journal of the American Society of Gene Therapy, 2007, 15(6): 1106-1113.
32.	Norman AW, Okamura WH, Bishop JE, et al. Update on biological actions of 1??, 25(OH)2-vitamin D3 (rapid effects) and 24R, 25(OH)2-vitamin D3. Molecular and Cellular Endocrinology, 2002, 197(1-2): 1-13.
33.	Zanello LP, Norman AW. Rapid modulation of osteoblast ion channel responses by 1? 25(OH)2-vitamin D3 requires the presence of a functional vitamin D nuclear receptor. Proceedings of the National Academy of Sciences, 2004, 101(6): 1589-1594.
34.	车千红, 周佳任, 张莹. 154 例初诊癫痫患儿免疫功能及营养指标的变化. 实用预防医学, 2015, 22(7).
35.	Tosun A, Karaca SE, Unuvar T, et al. Bone mineral density and vitamin D status in children with epilepsy, cerebral palsy, and cerebral palsy with epilepsy. Childs Nervous System, 2016, 33(1): 1-6.
36.	Sonmez FM, Donmez A, Namuslu M, et al. Vitamin D Deficiency in Children With Newly Diagnosed Idiopathic Epilepsy. Journal of Child Neurology, 2015, 30(11): 1428-1432.
37.	Holló A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci, 2014, 124(6): 387-93.
38.	Kruse R. Osteopathies in antiepileptic long-term therapy. Monatsschr Kinderheilkd, 1968, 116: 378-81.
39.	Nettekoven S, Strohle A, Trunz B,, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. European Journal of Pediatrics, 2008, 167: 1369-1377.
40.	Teagarden DL, Meador KJ, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy Res, 2014, 108: 1352-6.
41.	Lee YJ, Park KM, Kim YM, et al. Longitudinal change of vitamin D status in children with epilepsy on antiepileptic drugs: prevalence and risk factors. Pediatric Neurology, 2015, 52: 153-159.
42.	Hahn TJ, Birge SJ, Scharp CR, et al. Phenobarbital-induced alterations in vitamin D metabolism. Journal of Clinical Investigation, 1972, 51: 741-748.
43.	Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. Journal of Clinical Investigation, 2005, 115: 177-186.
44.	Neal E G, Chaffe H, Schwartz R H, et al. The Ketogenic Diet for the treatment of childhood epilepsy: A randomised controlled trial. The Lancet Neurology, 2008, 7(6): 500-506.
45.	Sampath A, Kossoff E H, Furth S L, et al. Kidney Stones and the Ketogenic Diet: Risk Factors and Prevention. Journal of Child Neurology, 2007, 22(4): 375-378.
46.	Bergqvist AC, Schall JI, Stallings VA, et al. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. American Journal of Clinical Nutrition, 2008, 88(6): 1678-1684.
47.	Simm PJ, Bicknellroyle J, Lawrie J, et al. The effect of the ketogenic diet on the developing skeleton. Epilepsy Research, 2017, 136(6): 62-66.
48.	Hahn TJ, Halstead LR, Devivo DC. Disordered mineral metabolism produced by ketogenic diet therapy. Calcified Tissue International, 1979, 28(1): 17-22.

1. Annweiler C, Schott AM, Berrut G, et al. Vitamin D and ageing: neurological issuess. Neuropsychobiology, 2010, 62(3): 139-150.
2. Eyles DW, Smith S, Kinobe Rl, et al. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. Journal of Chemmical Neuroanatomy, 2005, 29(1): 21-30.
3. Bergqvist AGC, Schall JI, Virginia AS. Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. Epilepsia, 2007, 48(1): 66-71.
4. Wang Y, Zhu J, DeLuca HF. Where is the vitamin D receptor? Arch Biochem Biophys, 2012, 523(1): 123-133.
5. Marini F, Bartoccini E, Cascianelli G, et al. Effect of 1alpha, 25-dihydroxy vitamin D₃ in embryonic hippocampal cells. Hippocampus, 2010, 20(6): 696-705.
6. Wang Y, Chiang YH, Su TP, et al. Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation inrats. Neuropharmacology, 2000, 39(5): 873-880.
7. Naveilhan P, Neveu I, Wion D, et al. 1,25-Dihydroxy vitaminD3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport, 1996, 7(13): 2171-2175.
8. Brewer LD, Thibault V, Chen KC, et al. Vitamin D hormone confers neuroprotection in parallel with downregulation of L-type Ca²⁺ channel expression in hippocampal neurons. The Journal of Neuroscience, 2001, 21: 98-108.
9. Viragh PA. Parvalbumin increases in the caudate putamen of rats with vitamin D hypervitaminosis. Proc Natl Acad Sci USA, 1989, 86: 3887-3890.
10. Garcion, E, Nataf S, berod A, et al. 1,25-Dihydroxyvitamin D3 inhibits the expression of inducible nitric oxide synthase in rat nervous system during experimental allergic encephalomyelitis. Molecular Brain Research, 1997, 45(2): 255-267.
11. Garcion, E. et al Expression of inducible nitric oxide synthase during rat brain inflammation: regulation by 1,25-dihydroxy vitamin D3. Glia, 1998, 22: 282-294.
12. Dawson VL, Dawson TM. Nitric oxide actions in neurochemistry. Neurochemistry International, 1996, 29: 97-110.
13. Mitrovic B, Pierre BAS, Allan JMG, et al. The role of nitric oxide in glial pathology. Annals of the New York Academy of Science, 1994, 738(1): 436-446.
14. Shinpo K, Kikuchi S, Sasaki H, et al. Effect of 1,25-dihydroxy vitamin D(3) on cultured mesencephalic dopaminergic neurons to the combined toxicity caused by L-buthionine sulfoximine and 1-methyl-4-phenylpyridine. Journal of Neuroscience Research, 2000, 62(3): 374-382.
15. Taniera H, Ito M, Sanada N, et al. Chronic vitamin D₃ treatment protects against neurotoxicity by glutamate in association with upregulation of vitamin D receptor mRNA expression incultured rat cortical neurons. Journal of Neuroscience Research, 2006, 83(7): 1179-1189.
16. Dringen R, Gutterer JM, Hirrlinger J, et al. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem, 2000, 267(16): 4912-4916.
17. Garcion E, Thanh XD, Bled F, et al. 1,25-Dihydroxyvitamin D3 regulates γ-glutamyl transpeptidase activity in rat brain. Neuroscience Letters, 1996, 216(3): 183-186.
18. Garcion E, Sindji L, Leblondel G, et al. 1,25-Dihydroxyvitamin D3 regulates the synthesis of γ-glutamyl transpeptidase and glutathione levels in rat primary astrocytes. J Neurochem, 1999, 73(2): 859-866.
19. Sonnenberg J, Luine VN, Krey LC, et al. 1,25dihydroxyvitamin D3 treatment results in increased choline acetyltransferase activity in specific brain nuclei. Endocrinology, 1986, 118: 1433-1439.
20. Baksi SN, Hughes MJ. Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex. Brain Research, 1982, 242(2): 387-390.
21. Puchacz E, Stumpf W E, Stachowiak E K, et al. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Mollecular Brain Research, 1996, 36(1): 193-196.
22. Almeras L, Eyles D, Benech P, et al. Developmental vitamin Ddeficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics, 2007, 7(5): 769-780.
23. Christiansen C, Paul Rødbro, Ole Sjö. “Anticonvulsant Action” of Vitamin D in Epileptic Patients? A Controlled Pilot Study. British Medical Journal, 1974, 2(5913): 258-259.
24. András, Holló, et al. Correction of vitaminD deficiency improves seizure control in epilepsy: A pilot study. Epilepsy Behavior, 2012, 24(1): 131-133.
25. Kalueff AV, Eremin KO, Tuohimaa P. Mechanisms of neuroprotective action of vitamin D3. Biochemistry, 2004, 69: 738-41.
26. Vezzani A, Balosso S, Ravizza T. The role of cytokines in the pathophysiology of epilepsy. Brain, Behavior, and Immunity, 2008, 22(6): 0-803.
27. Beattie, E. C Control of Synaptic Strength by Glial TNFalpha. Science (Washington D C), 2002, 295(5563): 2282-2285.
28. Stellwagen D, Beattie E C, Seo J Y, et al. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. Journal of Neuroscience the Official Journal of the Society for Neuroscience, 2005, 25(12): 3219-28.
29. Xu B, Michalski B, Racine R J, et al. Continuous infusion of neurotrophin-3 triggers sprouting, decreases the levels of TrkA and TrkC, and inhibits epileptogenesis and activity-dependent axonal growth in adult rats. Neuroscience, 2002, 115(4): 0-1308.
30. Leranth C, Ribak CE. Calcium-binding proteins are concentrated in the CA2 field of the monkey hippocampus: a possible key to this region's resistance to epileptic damage. Experimental Brain Research, 1991, 85(1): 129-136.
31. Kanter-Schlifke I, Georgievska B, Kirik D, et al. Seizure suppression by GDNF gene therapy in animal models of epilepsy. Molecular Therapy the Journal of the American Society of Gene Therapy, 2007, 15(6): 1106-1113.
32. Norman AW, Okamura WH, Bishop JE, et al. Update on biological actions of 1??, 25(OH)2-vitamin D3 (rapid effects) and 24R, 25(OH)2-vitamin D3. Molecular and Cellular Endocrinology, 2002, 197(1-2): 1-13.
33. Zanello LP, Norman AW. Rapid modulation of osteoblast ion channel responses by 1? 25(OH)2-vitamin D3 requires the presence of a functional vitamin D nuclear receptor. Proceedings of the National Academy of Sciences, 2004, 101(6): 1589-1594.
34. 车千红, 周佳任, 张莹. 154 例初诊癫痫患儿免疫功能及营养指标的变化. 实用预防医学, 2015, 22(7).
35. Tosun A, Karaca SE, Unuvar T, et al. Bone mineral density and vitamin D status in children with epilepsy, cerebral palsy, and cerebral palsy with epilepsy. Childs Nervous System, 2016, 33(1): 1-6.
36. Sonmez FM, Donmez A, Namuslu M, et al. Vitamin D Deficiency in Children With Newly Diagnosed Idiopathic Epilepsy. Journal of Child Neurology, 2015, 30(11): 1428-1432.
37. Holló A, Clemens Z, Lakatos P. Epilepsy and vitamin D. Int J Neurosci, 2014, 124(6): 387-93.
38. Kruse R. Osteopathies in antiepileptic long-term therapy. Monatsschr Kinderheilkd, 1968, 116: 378-81.
39. Nettekoven S, Strohle A, Trunz B,, et al. Effects of antiepileptic drug therapy on vitamin D status and biochemical markers of bone turnover in children with epilepsy. European Journal of Pediatrics, 2008, 167: 1369-1377.
40. Teagarden DL, Meador KJ, Loring DW. Low vitamin D levels are common in patients with epilepsy. Epilepsy Res, 2014, 108: 1352-6.
41. Lee YJ, Park KM, Kim YM, et al. Longitudinal change of vitamin D status in children with epilepsy on antiepileptic drugs: prevalence and risk factors. Pediatric Neurology, 2015, 52: 153-159.
42. Hahn TJ, Birge SJ, Scharp CR, et al. Phenobarbital-induced alterations in vitamin D metabolism. Journal of Clinical Investigation, 1972, 51: 741-748.
43. Pascussi JM, Robert A, Nguyen M, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. Journal of Clinical Investigation, 2005, 115: 177-186.
44. Neal E G, Chaffe H, Schwartz R H, et al. The Ketogenic Diet for the treatment of childhood epilepsy: A randomised controlled trial. The Lancet Neurology, 2008, 7(6): 500-506.
45. Sampath A, Kossoff E H, Furth S L, et al. Kidney Stones and the Ketogenic Diet: Risk Factors and Prevention. Journal of Child Neurology, 2007, 22(4): 375-378.
46. Bergqvist AC, Schall JI, Stallings VA, et al. Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. American Journal of Clinical Nutrition, 2008, 88(6): 1678-1684.
47. Simm PJ, Bicknellroyle J, Lawrie J, et al. The effect of the ketogenic diet on the developing skeleton. Epilepsy Research, 2017, 136(6): 62-66.
48. Hahn TJ, Halstead LR, Devivo DC. Disordered mineral metabolism produced by ketogenic diet therapy. Calcified Tissue International, 1979, 28(1): 17-22.

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维生素 D 在生酮饮食治疗癫痫中的意义

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