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MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?

Year 2020, Volume: 21 Issue: 4, 362 - 369, 14.10.2020
https://doi.org/10.18229/kocatepetip.605508

Abstract

Multipl skleroz, etiyolojisi bilinmeyen inflamatuar ve nörodejeneratif bir hastalıktır. Hasta bireylerde, zamanla ilerleyen nörolojik bozulma ile takip edilen, geri dönüşümlü dönemler ile karakterize olan merkezi sinir sisteminin kronik bir demiyelinizan hastalığıdır. Tipik olarak 20-45 yaş arası yetişkinlerde görülmekle birlikte, kadınlarda erkeklerden iki kat daha fazla görülmektedir. Belirtilen semptomlar arasında uyuşukluk, halsizlik, görme bozukluğu, denge kaybı, baş dönmesi, yorgunluk ve depresyon bulunmaktadır. Vitaminlerin, vücutta farklı işlevlere sahip önemli mikro besinler olarak multipl skleroz patogenezinde önemli rolleri vardır. İn vitro, in vivo ve insan çalışmaları, bazı vitaminlerin multipl skleroz oluşumunda veya ilerlemesinde koruyucu rolünü desteklemektedir. Kan pıhtılaşmasındaki klasik rolünün dışında, K vitamini merkezi sinir sisteminin fizyolojisinde görev alan yağda çözünen bir besin ögesidir. K vitamini özellikle nöronal proliferasyon, farklılaşma, yaşlanma, transformasyon ve hücre-hücre etkileşiminde rol oynayan miyelin kılıfı ve nöron membranlarının temel bir bileşeni olan sfingolipidlerin sentezini düzenlemektedir. K vitamini ayrıca nöron fizyolojisi ve sağ kalımı etkileyen K vitamini bağımlı proteinlerin biyolojik olarak aktivasyonunu da kontrol etmektedir. K vitamini beyinde yüksek oranlarda bulunmakta ve sülfatid metabolizmasının düzenlenmesinde rol oynamaktadır. Deney hayvanları üzerinde yapılan çalışmalar, beyinde yüksek konsantrasyonlarda bulunan sfingolipidlerin biyosentezinde K vitamini rolünü desteklemektedir. Farelerde ve sıçanlarda, K vitamini eksikliğinin beyinde sülfatid seviyelerini düşürdüğü ve davranışsal değişikliklere neden olduğu belirtilmiştir. Bu derlemede yağda çözünen vitaminlerden olan ve beyinde sfingolipidlerin sentezine katılan K vitaminin multipl skleroz patogenezi, progresyonu ve tedavisindeki rolünün değerlendirilmesi amaçlanmıştır.

References

  • Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. Disruption of large-scale brain systems in advanced aging. Neuron. 2007;56(5):924-35.
  • Head D, Buckner RL, Shimony JS, et al. Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cereb Cortex. 2004;14(4):410-23.
  • O'Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS. Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline. Neurology. 2001;57(4):632-8.
  • Baumann N, Pham-Dinh D. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev. 2001;81(2):871-927.
  • Marcus J, Honigbaum S, Shroff S, Honke K, Rosenbluth J, Dupree JL. Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia. 2006;53(4):372-81.
  • Peters A, Rosene DL. In aging, is it gray or white? J Comp Neurol 2003;462(2):139-43.
  • Duce JA, Podvin S, Hollander W, Kipling D, Rosene DL, Abraham CR. Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia. 2008;56(1):106-17.
  • Denisova NA, Booth SL. Vitamin K and sphingolipid metabolism: evidence to date. Nutr Rev. 2005;63(4):111-21.
  • Carrie I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr. 2004;134(1):167-72.Crivello NA, Casseus SL, Peterson JW, Smith DE, Booth SL. Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides. J. Nutr. Biochem. 2010;21(11):1083-8.
  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J Med. 2000;343(13):938-52.
  • Raffel J, Wakerley B, Nicholas R. Multiple sclerosis. Medicine. 2016;44(9):537-41.
  • Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. The Lancet Neurology. 2010;9(7):727-39.
  • Irish AK, Erickson CM, Wahls TL, Snetselaar LG, Darling WG. Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2017;7:1-18.
  • Hafler DA, Compston A, Sawcer S, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357(9):851-62.
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302.
  • Beecham AH, Patsopoulos NA, Xifara DK, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353-60.
  • Miller AE, Rhoades RW. Treatment of relapsing-remitting multiple sclerosis: current approaches and unmet needs. Curr Opin Neurol. 2012;25 Suppl:S4-10.
  • Hauser SL, Goodin DS. Multiple Sclerosis and Other Demyelinating Diseases. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill Education; 2014.
  • Dulamea AO. Role of Oligodendrocyte Dysfunction in Demyelination, Remyelination and Neurodegeneration in Multiple Sclerosis. Adv Exp Med Biol. 2017;958:91-127.
  • Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70(10):1935-44.
  • Goldenberg MM. Multiple sclerosis review. Pharmacol Ther. 2012;37(3):175-84.
  • Ferland G. The discovery of vitamin K and its clinical applications. Ann Nutr Metab. 2012;61(3):213-8.
  • Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014;55(3):345-62.
  • Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012;3(2):182-95.
  • Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100(4):530-47.
  • Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K(2)) in human health. Br J Nutr. 2013;110(8):1357-68.
  • Holmes MV, Hunt BJ, Shearer MJ. The role of dietary vitamin K in the management of oral vitamin K antagonists. Blood Rev. 2012;26(1):1-14.
  • Ferland G. Vitamin K and the nervous system: an overview of its actions. Adv Nutr. 2012;3(2):204-12.
  • Stoffel W, Bosio A. Myelin glycolipids and their functions. Curr Opin Neurobiol. 1997;7(5):654-61.
  • Davidson RT, Foley AL, Engelke JA, Suttie JW. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr. 1998;128(2):220-3.
  • Moriya M, Nakatsuji Y, Okuno T, Hamasaki T, Sawada M, Sakoda S. Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats. J Neuroimmunol. 2005;170(1-2):11-20.
  • Compston A, Coles A. Multiple sclerosis. Lancet (London, England). 2008;372(9648):1502-17.
  • Pugliatti M, Harbo HF, Holmoy T, et al. Environmental risk factors in multiple sclerosis. Acta Neurol Scand Suppl. 2008;188:34-40.
  • Torkildsen O, Loken-Amsrud KI, Wergeland S, Myhr KM, Holmoy T. Fat-soluble vitamins as disease modulators in multiple sclerosis. Acta Neurol Scand Suppl. 2013(196):16-23.
  • Rolf L, Muris AH, Hupperts R, Damoiseaux J. Illuminating vitamin D effects on B cells--the multiple sclerosis perspective. Immunology. 2016;147(3):275-84.
  • Lev M, Milford AF. Vitamin K stimulation of sphingolipid synthesis. Biochem Biophys Res Commun. 1971;45(2):358-62.
  • Binder MD, Xiao J, Kemper D, Ma GZ, Murray SS, Kilpatrick TJ. Gas6 increases myelination by oligodendrocytes and its deficiency delays recovery following cuprizone-induced demyelination. PloS one. 2011;6(3):e17727.
  • Sainaghi PP, Collimedaglia L, Alciato F, et al. Growth arrest specific gene 6 protein concentration in cerebrospinal fluid correlates with relapse severity in multiple sclerosis. Mediators Inflamm. 2013;2013:406483-.
  • Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med. 1980;68(1):122-40.
  • Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283(17):11270-9.
  • Josey BJ, Inks ES, Wen X, Chou CJ. Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents. J Med Chem. 2013;56(3):1007-22.
  • Lasemi R, Kundi M, Moghadam NB, Moshammer H, Hainfellner JA. Vitamin K2 in multiple sclerosis patients. Wien Klin Wochenschr. 2018;130(9-10):307-13.
  • Popescu DC, Huang H, Singhal NK, et al. Vitamin K enhances the production of brain sulfatides during remyelination. PloS one. 2018;13(8):e0203057.

DOES VITAMIN K PLAY A ROLE IN MULTIPLE SCLEROSIS?

Year 2020, Volume: 21 Issue: 4, 362 - 369, 14.10.2020
https://doi.org/10.18229/kocatepetip.605508

Abstract

Multiple sclerosis is an inflammatory and neurodegenerative disease of unknown etiology. In most patients, it is characterized by reversible periods followed by a progressive neurological deterioration. It is typically seen in adults between the ages of 20 and 45. It is twice as common in women than in men. Symptoms include drowsiness, weakness, visual impairment, loss of balance, dizziness, fatigue and depression. Vitamins have important roles in the pathogenesis of multiple sclerosis as important micronutrients with different functions in the body. In vitro, in vivo, and human studies support the protective role of certain vitamins in the formation or progression of multiple sclerosis. Apart from its classic role in blood clotting, vitamin K is a fat-soluble nutrient involved in the physiology of the central nervous system. Vitamin K specifically regulates the synthesis of sphingolipids, major components of myelin sheath and neuron membranes, which play a role in neuronal proliferation, differentiation, aging, transformation and cell-cell interaction. Vitamin K also controls the biological activation of vitamin K-dependent proteins that affect neuronal physiology and survival. Vitamin K is found in high levels in the brain and plays a role in the regulation of sulfatide metabolism. Studies on experimental animals support the role of vitamin K in the biosynthesis of high concentrations of sphingolipids in the brain. In mice and rats, vitamin K deficiency has been reported to reduce sulfatide levels in the brain and cause behavioral changes. In this review, we aimed to evaluate the role of vitamin K, one of the fat soluble vitamins and involved in the synthesis of sphingolipids in the brain, in the pathogenesis, progression and treatment of multiple sclerosis.

References

  • Andrews-Hanna JR, Snyder AZ, Vincent JL, et al. Disruption of large-scale brain systems in advanced aging. Neuron. 2007;56(5):924-35.
  • Head D, Buckner RL, Shimony JS, et al. Differential vulnerability of anterior white matter in nondemented aging with minimal acceleration in dementia of the Alzheimer type: evidence from diffusion tensor imaging. Cereb Cortex. 2004;14(4):410-23.
  • O'Sullivan M, Jones DK, Summers PE, Morris RG, Williams SC, Markus HS. Evidence for cortical "disconnection" as a mechanism of age-related cognitive decline. Neurology. 2001;57(4):632-8.
  • Baumann N, Pham-Dinh D. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev. 2001;81(2):871-927.
  • Marcus J, Honigbaum S, Shroff S, Honke K, Rosenbluth J, Dupree JL. Sulfatide is essential for the maintenance of CNS myelin and axon structure. Glia. 2006;53(4):372-81.
  • Peters A, Rosene DL. In aging, is it gray or white? J Comp Neurol 2003;462(2):139-43.
  • Duce JA, Podvin S, Hollander W, Kipling D, Rosene DL, Abraham CR. Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey. Glia. 2008;56(1):106-17.
  • Denisova NA, Booth SL. Vitamin K and sphingolipid metabolism: evidence to date. Nutr Rev. 2005;63(4):111-21.
  • Carrie I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr. 2004;134(1):167-72.Crivello NA, Casseus SL, Peterson JW, Smith DE, Booth SL. Age- and brain region-specific effects of dietary vitamin K on myelin sulfatides. J. Nutr. Biochem. 2010;21(11):1083-8.
  • Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J Med. 2000;343(13):938-52.
  • Raffel J, Wakerley B, Nicholas R. Multiple sclerosis. Medicine. 2016;44(9):537-41.
  • Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. The Lancet Neurology. 2010;9(7):727-39.
  • Irish AK, Erickson CM, Wahls TL, Snetselaar LG, Darling WG. Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2017;7:1-18.
  • Hafler DA, Compston A, Sawcer S, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357(9):851-62.
  • Polman CH, Reingold SC, Banwell B, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292-302.
  • Beecham AH, Patsopoulos NA, Xifara DK, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45(11):1353-60.
  • Miller AE, Rhoades RW. Treatment of relapsing-remitting multiple sclerosis: current approaches and unmet needs. Curr Opin Neurol. 2012;25 Suppl:S4-10.
  • Hauser SL, Goodin DS. Multiple Sclerosis and Other Demyelinating Diseases. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson JL, Loscalzo J, editors. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill Education; 2014.
  • Dulamea AO. Role of Oligodendrocyte Dysfunction in Demyelination, Remyelination and Neurodegeneration in Multiple Sclerosis. Adv Exp Med Biol. 2017;958:91-127.
  • Calabresi PA. Diagnosis and management of multiple sclerosis. Am Fam Physician. 2004;70(10):1935-44.
  • Goldenberg MM. Multiple sclerosis review. Pharmacol Ther. 2012;37(3):175-84.
  • Ferland G. The discovery of vitamin K and its clinical applications. Ann Nutr Metab. 2012;61(3):213-8.
  • Shearer MJ, Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J Lipid Res. 2014;55(3):345-62.
  • Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr. 2012;3(2):182-95.
  • Shearer MJ, Newman P. Metabolism and cell biology of vitamin K. Thromb Haemost. 2008;100(4):530-47.
  • Beulens JW, Booth SL, van den Heuvel EG, Stoecklin E, Baka A, Vermeer C. The role of menaquinones (vitamin K(2)) in human health. Br J Nutr. 2013;110(8):1357-68.
  • Holmes MV, Hunt BJ, Shearer MJ. The role of dietary vitamin K in the management of oral vitamin K antagonists. Blood Rev. 2012;26(1):1-14.
  • Ferland G. Vitamin K and the nervous system: an overview of its actions. Adv Nutr. 2012;3(2):204-12.
  • Stoffel W, Bosio A. Myelin glycolipids and their functions. Curr Opin Neurobiol. 1997;7(5):654-61.
  • Davidson RT, Foley AL, Engelke JA, Suttie JW. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr. 1998;128(2):220-3.
  • Moriya M, Nakatsuji Y, Okuno T, Hamasaki T, Sawada M, Sakoda S. Vitamin K2 ameliorates experimental autoimmune encephalomyelitis in Lewis rats. J Neuroimmunol. 2005;170(1-2):11-20.
  • Compston A, Coles A. Multiple sclerosis. Lancet (London, England). 2008;372(9648):1502-17.
  • Pugliatti M, Harbo HF, Holmoy T, et al. Environmental risk factors in multiple sclerosis. Acta Neurol Scand Suppl. 2008;188:34-40.
  • Torkildsen O, Loken-Amsrud KI, Wergeland S, Myhr KM, Holmoy T. Fat-soluble vitamins as disease modulators in multiple sclerosis. Acta Neurol Scand Suppl. 2013(196):16-23.
  • Rolf L, Muris AH, Hupperts R, Damoiseaux J. Illuminating vitamin D effects on B cells--the multiple sclerosis perspective. Immunology. 2016;147(3):275-84.
  • Lev M, Milford AF. Vitamin K stimulation of sphingolipid synthesis. Biochem Biophys Res Commun. 1971;45(2):358-62.
  • Binder MD, Xiao J, Kemper D, Ma GZ, Murray SS, Kilpatrick TJ. Gas6 increases myelination by oligodendrocytes and its deficiency delays recovery following cuprizone-induced demyelination. PloS one. 2011;6(3):e17727.
  • Sainaghi PP, Collimedaglia L, Alciato F, et al. Growth arrest specific gene 6 protein concentration in cerebrospinal fluid correlates with relapse severity in multiple sclerosis. Mediators Inflamm. 2013;2013:406483-.
  • Hall JG, Pauli RM, Wilson KM. Maternal and fetal sequelae of anticoagulation during pregnancy. Am J Med. 1980;68(1):122-40.
  • Okano T, Shimomura Y, Yamane M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283(17):11270-9.
  • Josey BJ, Inks ES, Wen X, Chou CJ. Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents. J Med Chem. 2013;56(3):1007-22.
  • Lasemi R, Kundi M, Moghadam NB, Moshammer H, Hainfellner JA. Vitamin K2 in multiple sclerosis patients. Wien Klin Wochenschr. 2018;130(9-10):307-13.
  • Popescu DC, Huang H, Singhal NK, et al. Vitamin K enhances the production of brain sulfatides during remyelination. PloS one. 2018;13(8):e0203057.
There are 43 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Review
Authors

Merve Özdemir 0000-0001-7955-9154

Aylin Ayaz 0000-0002-3543-7881

Publication Date October 14, 2020
Acceptance Date November 13, 2019
Published in Issue Year 2020 Volume: 21 Issue: 4

Cite

APA Özdemir, M., & Ayaz, A. (2020). MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?. Kocatepe Tıp Dergisi, 21(4), 362-369. https://doi.org/10.18229/kocatepetip.605508
AMA Özdemir M, Ayaz A. MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?. KTD. October 2020;21(4):362-369. doi:10.18229/kocatepetip.605508
Chicago Özdemir, Merve, and Aylin Ayaz. “MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?”. Kocatepe Tıp Dergisi 21, no. 4 (October 2020): 362-69. https://doi.org/10.18229/kocatepetip.605508.
EndNote Özdemir M, Ayaz A (October 1, 2020) MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?. Kocatepe Tıp Dergisi 21 4 362–369.
IEEE M. Özdemir and A. Ayaz, “MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?”, KTD, vol. 21, no. 4, pp. 362–369, 2020, doi: 10.18229/kocatepetip.605508.
ISNAD Özdemir, Merve - Ayaz, Aylin. “MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?”. Kocatepe Tıp Dergisi 21/4 (October 2020), 362-369. https://doi.org/10.18229/kocatepetip.605508.
JAMA Özdemir M, Ayaz A. MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?. KTD. 2020;21:362–369.
MLA Özdemir, Merve and Aylin Ayaz. “MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?”. Kocatepe Tıp Dergisi, vol. 21, no. 4, 2020, pp. 362-9, doi:10.18229/kocatepetip.605508.
Vancouver Özdemir M, Ayaz A. MULTİPL SKLEROZ’DA K VİTAMİNİNİN ROLÜ VAR MIDIR?. KTD. 2020;21(4):362-9.

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