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2000
Volume 24, Issue 28
  • ISSN: 1568-0266
  • E-ISSN: 1873-4294

Abstract

A stroke, also known as a cerebral hemorrhage, occurs when there is an interruption in the blood supply to a part of the brain, resulting in damage to brain cells. This issue is one of the leading causes of death in developed countries, currently killing about 5 million people annually. Individuals who survive ischemic stroke often face serious vision problems, paralysis, dementia, and other sequelae. The numerous efforts to prevent and/or treat stroke sequelae seem insufficient, which is concerning given the increasing global elderly population and the well-known association between aging and stroke risk. In this review, we aim to present and discuss the importance of vitamins in stroke prevention and/or incidence. Vitamins from diet or dietary supplements influence the body at various levels; they are a relevant factor but are reported only in isolated articles. This review reports and updates the multitarget role of vitamins involved in reducing stroke risk.

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2024-11-21
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References

  1. KunduS. SarkarD. Synthetic attempts towards A-tocopherol–An overview.J. Heterocycl. Chem.2022
    [Google Scholar]
  2. OnaolapoA.Y. OnaolapoO.J. Functional nutraceuticals: Past, present, and future.Handb. Nutraceuticals Nat. Prod. Biol. Med. Nutr. Prop. Appl.202211527
    [Google Scholar]
  3. YounessR.A. DawoudA. ElTahtawyO. FaragM.A. Fat-soluble vitamins: updated review of their role and orchestration in human nutrition throughout life cycle with sex differences.Nutr. Metab. (Lond.)20221916010.1186/s12986‑022‑00696‑y36064551
    [Google Scholar]
  4. LimketkaiB.N. MatareseL.E. MullinG.E. Vitamins and minerals.Yamada's Textbook of Gastroenterology202242645610.1002/9781119600206.ch22.
    [Google Scholar]
  5. KongJ. ChuR. WangY. Neuroprotective Treatments for Ischemic Stroke: Opportunities for Nanotechnology.Adv. Funct. Mater.20223252220940510.1002/adfm.202209405
    [Google Scholar]
  6. HuberC.C. WangX. WangH. Impact of Cardiovascular Diseases on Ischemic Stroke Outcomes.J. Integr. Neurosci.202221513810.31083/j.jin210513836137958
    [Google Scholar]
  7. CaplanL.R. SimonR.P. HassaniS. Cerebrovascular Disease—Stroke.Neurobiology of Brain Disorders.Academic Press202345747610.1016/B978‑0‑323‑85654‑6.00044‑7
    [Google Scholar]
  8. OmayeST. SchausEE. KutninkMA. HawkesWC. Measurement of vitamin C in blood components by high-performance liquid chromatography. Implication in assessing vitamin C status.Ann N Y Acad Sci198749838940110.1111/j.1749‑6632.1987.tb23776.x
    [Google Scholar]
  9. CerulloG. NegroM. ParimbelliM. PecoraroM. PernaS. LiguoriG. RondanelliM. CenaH. D’AntonaG. The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19.Front. Immunol.20201157402910.3389/fimmu.2020.57402933193359
    [Google Scholar]
  10. ChenQ. VissersM.C.M. Vitamin C: New Biochemical and Functional Insights.CRC Press2020110.1201/9780429442025
    [Google Scholar]
  11. Van GorkomG. Klein WolterinkR. Van ElssenC. WietenL. GermeraadW. BosG. Influence of Vitamin C on Lymphocytes: An Overview.Antioxidants2018734110.3390/antiox703004129534432
    [Google Scholar]
  12. LiuganM. CarrA.C. Vitamin C and Neutrophil Function: Findings from Randomized Controlled Trials.Nutrients2019119210210.3390/nu1109210231487891
    [Google Scholar]
  13. MinY.N. NiuZ.Y. SunT.T. WangZ.P. JiaoP.X. ZiB.B. ChenP.P. TianD.L. LiuF.Z. VitaminE. VitaminC. Vitamin E and vitamin C supplementation improves antioxidant status and immune function in oxidative-stressed breeder roosters by up-regulating expression of GSH-Px gene.Poult. Sci.20189741238124410.3382/ps/pex41729452404
    [Google Scholar]
  14. ChenG. ChangT.M.S. Dual antioxidant and pro-oxidation effects of ascorbic acid on bovine hemoglobin.Nanobiotherapeutic Based Blood SubstitutesWorld Scientific202257159510.1142/9789811228698_0023
    [Google Scholar]
  15. ChangC.Y. ChenJ.Y. WuM.H. HuM.L. Therapeutic treatment with vitamin C reduces focal cerebral ischemia-induced brain infarction in rats by attenuating disruptions of blood brain barrier and cerebral neuronal apoptosis.Free Radic. Biol. Med.2020155293610.1016/j.freeradbiomed.2020.05.01532450129
    [Google Scholar]
  16. O’NeillM.J. ClemensJ.A. Rodent models of focal cerebral ischemia.Curr. Protoc. Neurosci.2001Chapter 916918428554
    [Google Scholar]
  17. Orellana-UrzúaS. RojasI. LíbanoL. RodrigoR. Pathophysiology of Ischemic Stroke: Role of Oxidative Stress.Curr. Pharm. Des.202026344246426010.2174/138161282666620070813391232640953
    [Google Scholar]
  18. ZhaoX. HeY. ZhangY. WanH. WanH. YangJ. Inhibition of Oxidative Stress: An Important Molecular Mechanism of Chinese Herbal Medicine (Astragalus membranaceus, Carthamus tinctorius L., Radix Salvia Miltiorrhizae, etc.) in the Treatment of Ischemic Stroke by Regulating the Antioxidant System.Oxid. Med. Cell. Longev.2022202211010.1155/2022/142536935651725
    [Google Scholar]
  19. HillA. WendtS. BenstoemC. NeubauerC. MeybohmP. LangloisP. AdhikariN.K.J. HeylandD.K. StoppeC. Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach.Nutrients201810897410.3390/nu1008097430060468
    [Google Scholar]
  20. HuD. SerranoF. OuryT.D. KlannE. Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase.J. Neurosci.200626153933394110.1523/JNEUROSCI.5566‑05.200616611809
    [Google Scholar]
  21. JelinekM. JurajdaM. DurisK. Oxidative Stress in the Brain: Basic Concepts and Treatment Strategies in Stroke.Antioxidants20211012188610.3390/antiox1012188634942989
    [Google Scholar]
  22. JaganjacM. MilkovicL. ZarkovicN. ZarkovicK. Oxidative stress and regeneration.Free Radic. Biol. Med.202218115416510.1016/j.freeradbiomed.2022.02.00435149216
    [Google Scholar]
  23. KomsiiskaD. Oxidative stress and stroke: a review of upstream and downstream antioxidant therapeutic options.Comp. Clin. Pathol.201928491592610.1007/s00580‑019‑02940‑z
    [Google Scholar]
  24. JinT. LengB. Cynaropicrin Averts the Oxidative Stress and Neuroinflammation in Ischemic/Reperfusion Injury Through the Modulation of NF-KB.Appl. Biochem. Biotechnol.202211535838888
    [Google Scholar]
  25. VenøS.K. BorkC.S. JakobsenM.U. Lundbye-ChristensenS. McLennanP.L. BachF.W. OvervadK. SchmidtE.B. Marine n-3 Polyunsaturated Fatty Acids and the Risk of Ischemic Stroke.Stroke201950227428210.1161/STROKEAHA.118.02338430602356
    [Google Scholar]
  26. JurcauA. ArdeleanA.I. Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke.Biomedicines202210357410.3390/biomedicines1003057435327376
    [Google Scholar]
  27. MiaoR. LiJ. MengC. LiY. TangH. WangJ. DengP. LuY. Diet-derived circulating antioxidants and risk of stroke: A Mendelian randomization study.Oxid Med Cell Longev20222022645731810.1155/2022/6457318
    [Google Scholar]
  28. NageleP. The importance of definitive trials: The VIXIE trial.Anesthesiology2022136340340410.1097/ALN.0000000000004144.
    [Google Scholar]
  29. ChenX. LiH. ZhangB. DengZ. The synergistic and antagonistic antioxidant interactions of dietary phytochemical combinations.Crit. Rev. Food Sci. Nutr.202262205658567710.1080/10408398.2021.188869333612011
    [Google Scholar]
  30. DosedělM. JirkovskýE. MacákováK. KrčmováL. JavorskáL. PourováJ. MercoliniL. RemiãoF. NovákováL. MladěnkaP. Vitamin C—Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.Nutrients202113261510.3390/nu1302061533668681
    [Google Scholar]
  31. IcerM.A. ArslanN. Gezmen-KaradagM. Effects of vitamin E on neurodegenerative diseases: an update.Acta Neurobiol. Exp. (Warsz.)2021811213310.21307/ane‑2021‑00333949169
    [Google Scholar]
  32. ManossoL.M. CamargoA. DafreA.L. RodriguesA.L.S. Vitamin E for the management of major depressive disorder: possible role of the anti-inflammatory and antioxidant systems.Nutr. Neurosci.20222561310132410.1080/1028415X.2020.185341733314993
    [Google Scholar]
  33. RychterA.M. HryhorowiczS. SłomskiR. DobrowolskaA. Krela-KaźmierczakI. Antioxidant effects of vitamin E and risk of cardiovascular disease in women with obesity – A narrative review.Clin. Nutr.20224171557156510.1016/j.clnu.2022.04.03235667272
    [Google Scholar]
  34. JiangQ. Metabolism of natural forms of vitamin E and biological actions of vitamin E metabolites.Free Radic. Biol. Med.202217937538710.1016/j.freeradbiomed.2021.11.01234785321
    [Google Scholar]
  35. SimionA. JurcauA. The Role of Antioxidant Treatment in Acute Ischemic Stroke: Past, Present and Future.Neurology - Research & Surgery201921710.33425/2641‑4333.1017
    [Google Scholar]
  36. LohH.C. LimR. LeeK.W. OoiC.Y. ChuanD.R. LooiI. Kah HayY. Abdul Karim KhanN. Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis.Stroke Vasc. Neurol.20216110912010.1136/svn‑2020‑00051933109618
    [Google Scholar]
  37. VioliF. NocellaC. LoffredoL. CarnevaleR. PignatelliP. Interventional study with vitamin E in cardiovascular disease and meta-analysis.Free Radic. Biol. Med.2022178264110.1016/j.freeradbiomed.2021.11.02734838937
    [Google Scholar]
  38. Aranda-RiveraA.K. Cruz-GregorioA. Arancibia-HernándezY.L. Hernández-CruzE.Y. Pedraza-ChaverriJ. RONS and Oxidative Stress: An Overview of Basic Concepts.Oxygen20222443747810.3390/oxygen2040030
    [Google Scholar]
  39. de AlmeidaA. J. P. O. de OliveiraJ. C. P. L. da Silva PontesL. V. de Souza JúniorJ. F. GonçalvesT. A. F. DantasS. H. de Almeida FeitosaM. S. SilvaA. O. de MedeirosI. A. ROS: Basic concepts, sources, cellular signaling, and its implications in aging pathways.Oxid Med Cell Longev20222022122557810.1155/2022/1225578.
    [Google Scholar]
  40. NewmanM. ConneryH. BoydJ. Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants2022117126710.3390/antiox1107126735883757
    [Google Scholar]
  41. RasmussenK. MøllerJ. Total homocysteine measurement in clinical practice.Ann. Clin. Biochem.200037562764810.1258/000456300189991511026516
    [Google Scholar]
  42. KellyP.J. RosandJ. KistlerJ.P. ShihV.E. SilveiraS. PlomaritoglouA. FurieK.L. Homocysteine, MTHFR 677C→T polymorphism, and risk of ischemic stroke.Neurology200259452953610.1212/WNL.59.4.52912196644
    [Google Scholar]
  43. MoriyamaY. OkamuraT. KajinamiK. IsoH. InazuA. KawashiriM. MizunoM. TakedaY. SakamotoY. KimuraH. SuzukiH. MabuchiH. Effects of serum B vitamins on elevated plasma homocysteine levels associated with the mutation of methylenetetrahydrofolate reductase gene in Japanese.Atherosclerosis2002164232132810.1016/S0021‑9150(02)00105‑312204804
    [Google Scholar]
  44. EikelboomJ.W. LonnE. GenestJ.Jr HankeyG. YusufS. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence.Ann. Intern. Med.1999131536337510.7326/0003‑4819‑131‑5‑199909070‑0000810475890
    [Google Scholar]
  45. HerrmannW. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview.Clin. Chem. Lab. Med.200139866667410.1515/CCLM.2001.11011592431
    [Google Scholar]
  46. DurandP. ProstM. LoreauN. Lussier-CacanS. BlacheD. Impaired homocysteine metabolism and atherothrombotic disease.Lab. Invest.200181564567210.1038/labinvest.378027511351038
    [Google Scholar]
  47. TopalG. BrunetA. MillanvoyeE. BoucherJ.L. RenduF. DevynckM.A. David-DufilhoM. Homocysteine induces oxidative stress by uncoupling of no synthase activity through reduction of tetrahydrobiopterin.Free Radic. Biol. Med.200436121532154110.1016/j.freeradbiomed.2004.03.01915182855
    [Google Scholar]
  48. LynchS.M. FreiB. Physiological thiol compounds exert pro- and anti-oxidant effects, respectively, on iron- and copper-dependent oxidation of human low-density lipoprotein.Biochim. Biophys. Acta Lipids Lipid Metab.19971345221522110.1016/S0005‑2760(96)00182‑89106501
    [Google Scholar]
  49. PoddarR. SivasubramanianN. DiBelloP.M. RobinsonK. JacobsenD.W. Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease.Circulation2001103222717272310.1161/01.CIR.103.22.271711390343
    [Google Scholar]
  50. RefsumH. UelandP.M. NygårdO. VollsetS.E. Homocysteine and cardiovascular disease.Annu. Rev. Med.1998491316210.1146/annurev.med.49.1.319509248
    [Google Scholar]
  51. Homocysteine Studies CollaborationHomocysteine and risk of ischemic heart disease and stroke: A meta-analysis.JAMA2002288162015202210.1001/jama.288.16.201512387654
    [Google Scholar]
  52. FallonU.B. VirtamoJ. YoungI. McMasterD. Ben-ShlomoY. WoodN. WhiteheadA.S. SmithG.D. Homocysteine and cerebral infarction in finnish male smokers.Stroke20033461359136310.1161/01.STR.0000074035.64365.2D12750538
    [Google Scholar]
  53. IsoH. MoriyamaY. SatoS. KitamuraA. TanigawaT. YamagishiK. ImanoH. OhiraT. OkamuraT. NaitoY. ShimamotoT. Serum total homocysteine concentrations and risk of stroke and its subtypes in Japanese.Circulation2004109222766277210.1161/01.CIR.0000131942.77635.2D15159287
    [Google Scholar]
  54. WaldD.S. LawM. MorrisJ.K. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis.BMJ200232573741202120610.1136/bmj.325.7374.120212446535
    [Google Scholar]
  55. WangW.W. WangX.S. ZhangZ.R. HeJ.C. XieC.L. A Meta-Analysis of Folic Acid in Combination with Anti-Hypertension Drugs in Patients with Hypertension and Hyperhomocysteinemia.Front. Pharmacol.2017858510.3389/fphar.2017.0058528912716
    [Google Scholar]
  56. SaposnikG. RayJ.G. SheridanP. McQueenM. LonnE. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial.Stroke20094041365137210.1161/STROKEAHA.108.52950319228852
    [Google Scholar]
  57. BiswasA. RanjanR. MeenaA. AkhterM.S. YadavB.K. MunisamyM. SubbiahV. BehariM. SaxenaR. Homocystine levels, polymorphisms and the risk of ischemic stroke in young Asian Indians.J. Stroke Cerebrovasc. Dis.200918210311010.1016/j.jstrokecerebrovasdis.2008.09.01419251185
    [Google Scholar]
  58. SelhubJ. JacquesP.F. BostomA.G. D’AgostinoR.B. WilsonP.W.F. BelangerA.J. O’LearyD.H. WolfP.A. SchaeferE.J. RosenbergI.H. Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.N. Engl. J. Med.1995332528629110.1056/NEJM1995020233205027816063
    [Google Scholar]
  59. HackamD. PetersonJ.C. SpenceJ.D. What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 μmol/L.Am. J. Hypertens.200013110511010.1016/S0895‑7061(99)00180‑610678280
    [Google Scholar]
  60. JacquesP.F. SelhubJ. BostomA.G. WilsonP.W.F. RosenbergI.H. The effect of folic acid fortification on plasma folate and total homocysteine concentrations.N. Engl. J. Med.1999340191449145410.1056/NEJM19990513340190110320382
    [Google Scholar]
  61. MerrillA.H. HoriikeK. McCormickD.B. Evidence for the regulation of pyridoxal 5′-phosphate formation in liver by pyridoxamine (pyridoxine) 5′-phosphate oxidase.Biochem. Biophys. Res. Commun.197883398499010.1016/0006‑291X(78)91492‑4708447
    [Google Scholar]
  62. BarloweC.K. ApplingD.R. In vitro evidence for the involvement of mitochondrial folate metabolism in the supply of cytoplasmic one-carbon units.Biofactors1988121711762475123
    [Google Scholar]
  63. OhK-J. ChurchichJ.E. Binding of pyridoxal 5-phosphate to cystathionase.J. Biol. Chem.1973248217370737510.1016/S0021‑9258(19)43298‑54795694
    [Google Scholar]
  64. TaokaS. WestM. BanerjeeR. Characterization of the heme and pyridoxal phosphate cofactors of human cystathionine β-synthase reveals nonequivalent active sites.Biochemistry19993892738274410.1021/bi982605210052944
    [Google Scholar]
  65. JonesC.W.III PriestD.G. Interaction of pyridoxal 5-phosphate with apo-serine hydroxymethyltransferase.Biochimica et Biophysica Acta (BBA) - Enzymology1978526236937410.1016/0005‑2744(78)90128‑631178
    [Google Scholar]
  66. MartinezM. CuskellyG.J. WilliamsonJ. TothJ.P. GregoryJ.F.III Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine β-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration.J. Nutr.200013051115112310.1093/jn/130.5.111510801907
    [Google Scholar]
  67. PerryC. YuS. ChenJ. MatharuK.S. StoverP.J. Effect of vitamin B6 availability on serine hydroxymethyltransferase in MCF-7 cells.Arch. Biochem. Biophys.20074621212710.1016/j.abb.2007.04.00517482557
    [Google Scholar]
  68. ChenH. XiongL. Pyridoxine is required for post-embryonic root development and tolerance to osmotic and oxidative stresses.Plant J.200544339640810.1111/j.1365‑313X.2005.02538.x16236150
    [Google Scholar]
  69. ChumnantanaR. YokochiN. YagiT. Vitamin B6 compounds prevent the death of yeast cells due to menadione, a reactive oxygen generator.Biochim. Biophys. Acta, Gen. Subj.200517221849110.1016/j.bbagen.2004.11.01315716132
    [Google Scholar]
  70. EndoN. NishiyamaK. OkabeM. MatsumotoM. KanouchiH. OkaT. Vitamin B6 suppresses apoptosis of NM-1 bovine endothelial cells induced by homocysteine and copper.Biochim. Biophys. Acta, Gen. Subj.20071770457157710.1016/j.bbagen.2006.11.00917208380
    [Google Scholar]
  71. FukuiK.O. KubotaM. TerashimaH. IshiguroA. KashiiH. Early administration of vitamins B1 and B6 and l-carnitine prevents a second attack of acute encephalopathy with biphasic seizures and late reduced diffusion: A case control study.Brain Dev.201941761862410.1016/j.braindev.2019.02.01530862409
    [Google Scholar]
  72. WilckenD.E. WilckenB. The pathogenesis of coronary artery disease. A possible role for methionine metabolism.J. Clin. Invest.19765741079108210.1172/JCI108350947949
    [Google Scholar]
  73. PancharunitiN. LewisC.A. SauberlichH.E. PerkinsL.L. GoR.C. AlvarezJ.O. MacalusoM. ActonR.T. CopelandR.B. CousinsA.L. GoreT.B. CornwellP.E. RosemanJ.M. Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.Am. J. Clin. Nutr.199459494094810.1093/ajcn/59.4.9408147342
    [Google Scholar]
  74. RobinsonK. MayerE.L. MillerD.P. GreenR. van LenteF. GuptaA. Kottke-MarchantK. SavonS.R. SelhubJ. NissenS.E. KutnerM. TopolE.J. JacobsenD.W. Hyperhomocysteinemia and low pyridoxal phosphate. Common and independent reversible risk factors for coronary artery disease.Circulation199592102825283010.1161/01.CIR.92.10.28257586248
    [Google Scholar]
  75. GrahamI.M. DalyL.E. RefsumH.M. RobinsonK. BrattströmL.E. UelandP.M. Palma-ReisR.J. BoersG.H. SheahanR.G. IsraelssonB. UiterwaalC.S. MeleadyR. McMasterD. VerhoefP. WittemanJ. RubbaP. BelletH. WautrechtJ.C. de ValkH.W. Sales LúisA.C. Parrot-RoulandF.M. TanK.S. HigginsI. GarconD. AndriaG. Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project.JAMA1997277221775178110.1001/jama.1997.035404600390309178790
    [Google Scholar]
  76. BousheyC.J. BeresfordS.A. OmennG.S. MotulskyA.G. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes.JAMA1995274131049105710.1001/jama.1995.035301300550287563456
    [Google Scholar]
  77. GungorL. PolatM. OzberkM.B. AvciB. AburU. Which Ischemic Stroke Subtype Is Associated with Hyperhomocysteinemia?J. Stroke Cerebrovasc. Dis.20182771921192910.1016/j.jstrokecerebrovasdis.2018.02.03329661647
    [Google Scholar]
  78. BoersG.H.J. SmalsA.G.H. TrijbelsF.J.M. FowlerB. BakkerenJ.A.J.M. SchoonderwaldtH.C. KleijerW.J. KloppenborgP.W.C. Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease.N. Engl. J. Med.19853131270971510.1056/NEJM1985091931312014033695
    [Google Scholar]
  79. BrattströmL. IsraelssonB. NorrvingB. BergqvistD. ThörneJ. HultbergB. HamfeltA. Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease Effects of pyridoxine and folic acid treatment.Atherosclerosis1990811516010.1016/0021‑9150(90)90058‑Q2407253
    [Google Scholar]
  80. ClarkeR. DalyL. RobinsonK. NaughtenE. CahalaneS. FowlerB. GrahamI. Hyperhomocysteinemia: an independent risk factor for vascular disease.N. Engl. J. Med.1991324171149115510.1056/NEJM1991042532417012011158
    [Google Scholar]
  81. MalinowM.R. KangS.S. TaylorL.M. WongP.W. CoullB. InaharaT. MukerjeeD. SextonG. UpsonB. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial occlusive disease.Circulation19897961180118810.1161/01.CIR.79.6.11802785871
    [Google Scholar]
  82. TaylorL.M.Jr DeFrangR.D. HarrisE.J.Jr PorterJ.M. The association of elevated plasma homocyst(e)ine with progression of symptomatic peripheral arterial disease.J. Vasc. Surg.199113112813610.1016/0741‑5214(91)90020‑U1987384
    [Google Scholar]
  83. ArnesenE. RefsumH. BønaaK.H. UelandP.M. FørdeO.H. NordrehaugJ. Serum total homocysteine and coronary heart disease.Int. J. Epidemiol.199524470470910.1093/ije/24.4.7048550266
    [Google Scholar]
  84. BrattströmL. LindgrenA. IsraelssonB. MalinowM.R. NorrvingB. UpsonB. HamfeltA. Hyperhomocysteinaemia in stroke: prevalence, cause, and relationships to type of stroke and stroke risk factors.Eur. J. Clin. Invest.199222321422110.1111/j.1365‑2362.1992.tb01829.x1582447
    [Google Scholar]
  85. DudmanN.P. WilckenD.E. WangJ. LynchJ.F. MaceyD. LundbergP. Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology.Arterioscler. Thromb.19931391253126010.1161/01.ATV.13.9.12538364009
    [Google Scholar]
  86. StablerS.P. MarcellP.D. PodellE.R. AllenR.H. SavageD.G. LindenbaumJ. Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry.J. Clin. Invest.198881246647410.1172/JCI1133433339129
    [Google Scholar]
  87. BrattströmL. IsraelssonB. LindgärdeF. HultbergB. Higher total plasma homocysteine in vitamin B12 deficiency than in heterozygosity for homocystinuria due to cystathionine β-synthase deficiency.Metabolism198837217517810.1016/S0026‑0495(98)90014‑23340005
    [Google Scholar]
  88. SelhubJ. JacquesP.F. WilsonP.W. RushD. RosenbergI.H. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population.JAMA1993270222693269810.1001/jama.1993.035102200490338133587
    [Google Scholar]
  89. NaessH. NylandH. IdiculaT. Waje-AndreassenU. C-reactive protein and homocysteine predict long-term mortality in young ischemic stroke patients.J. Stroke Cerebrovasc. Dis.2013228e435e44010.1016/j.jstrokecerebrovasdis.2013.04.03123735372
    [Google Scholar]
  90. ShiZ. GuanY. HuoY.R. LiuS. ZhangM. LuH. YueW. WangJ. JiY. Elevated Total Homocysteine Levels in Acute Ischemic Stroke Are Associated With Long-Term Mortality.Stroke20154692419242510.1161/STROKEAHA.115.00913626199315
    [Google Scholar]
  91. ZhongC. LvL. LiuC. ZhaoL. ZhouM. SunW. XuT. TongW. High homocysteine and blood pressure related to poor outcome of acute ischemia stroke in Chinese population.PLoS One201499e10749810.1371/journal.pone.010749825265507
    [Google Scholar]
  92. KwonH.M. LeeY.S. BaeH.J. KangD.W. Homocysteine as a predictor of early neurological deterioration in acute ischemic stroke.Stroke201445387187310.1161/STROKEAHA.113.00409924448992
    [Google Scholar]
  93. YeZ. ZhangZ. ZhangH. HaoY. ZhangJ. LiuW. XuG. LiuX. Prognostic Value of C-Reactive Protein and Homocysteine in Large-Artery Atherosclerotic Stroke: a Prospective Observational Study.J. Stroke Cerebrovasc. Dis.201726361862610.1016/j.jstrokecerebrovasdis.2016.11.01627979431
    [Google Scholar]
  94. BosM.J. van GoorM.L.P.J. KoudstaalP.J. DippelD.W.J. Plasma homocysteine is a risk factor for recurrent vascular events in young patients with an ischaemic stroke or TIA.J. Neurol.2005252333233710.1007/s00415‑005‑0647‑915739046
    [Google Scholar]
  95. Del SerT. BarbaR. HerranzA.S. SeijasV. López- ManglanoC. DomingoJ. PondalM. Hyperhomocyst(e)inemia is a risk factor of secondary vascular events in stroke patients.Cerebrovasc. Dis.2001122919810.1159/00004768711490102
    [Google Scholar]
  96. LiZ. SunL. ZhangH. LiaoY. WangD. ZhaoB. ZhuZ. ZhaoJ. MaA. HanY. WangY. ShiY. YeJ. HuiR. Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke: a Multicenter Case-Control Study in China.Stroke20033492085209010.1161/01.STR.0000086753.00555.0D12907815
    [Google Scholar]
  97. HofmannM.A. LallaE. LuY. GleasonM.R. WolfB.M. TanjiN. FerranL.J.Jr KohlB. RaoV. KisielW. SternD.M. SchmidtA.M. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model.J. Clin. Invest.2001107667568310.1172/JCI1058811254667
    [Google Scholar]
  98. AikawaM. RabkinE. OkadaY. VoglicS.J. ClintonS.K. BrinckerhoffC.E. SukhovaG.K. LibbyP. Lipid lowering by diet reduces matrix metalloproteinase activity and increases collagen content of rabbit atheroma: a potential mechanism of lesion stabilization.Circulation199897242433244410.1161/01.CIR.97.24.24339641696
    [Google Scholar]
  99. MachF. SchönbeckU. BonnefoyJ.Y. PoberJ.S. LibbyP. Activation of monocyte/macrophage functions related to acute atheroma complication by ligation of CD40: induction of collagenase, stromelysin, and tissue factor.Circulation199796239639910.1161/01.CIR.96.2.3969244201
    [Google Scholar]
  100. Martí-CarvajalA.J. SolàI. LathyrisD. SalantiG. Homocysteine lowering interventions for preventing cardiovascular events.Cochrane Database Syst Rev20094CD00661210.1002/14651858.CD006612.pub2
    [Google Scholar]
  101. ParkJ.H. SaposnikG. OvbiageleB. MarkovicD. TowfighiA. Effect of B-vitamins on stroke risk among individuals with vascular disease who are not on antiplatelets: A meta-analysis.Int. J. Stroke201611220621110.1177/174749301561651226783312
    [Google Scholar]
  102. JiY. TanS. XuY. ChandraA. ShiC. SongB. QinJ. GaoY. VitaminB. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease.Neurology201381151298130710.1212/WNL.0b013e3182a823cc24049135
    [Google Scholar]
  103. ApelandT. FrøylandE.S. KristensenO. StrandjordR.E. MansoorM.A. Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: Improvement by B-vitamins.Epilepsy Res.20088211610.1016/j.eplepsyres.2008.06.00318644700
    [Google Scholar]
  104. SatoK. MorofujiY. HorieN. IzumoT. AndaT. MatsuoT. Hyperhomocysteinemia Causes Severe Intraoperative Thrombotic Tendency in Superficial Temporal Artery-middle Cerebral Artery Bypass.J. Stroke Cerebrovasc. Dis.202029510463310.1016/j.jstrokecerebrovasdis.2019.10463332122776
    [Google Scholar]
  105. EndoN. NishiyamaK. OtsukaA. KanouchiH. TagaM. OkaT. Antioxidant activity of vitamin B 6 delays homocysteine-induced atherosclerosis in rats.Br. J. Nutr.20069561088109310.1079/BJN2006176416768830
    [Google Scholar]
  106. RinehartJ.F. GreenbergL.D. Arteriosclerotic lesions in pyridoxine-deficient monkeys.Am. J. Pathol.194925348149118127137
    [Google Scholar]
  107. Chasan-TaberL. SelhubJ. RosenbergI.H. MalinowM.R. TerryP. TishlerP.V. WillettW. HennekensC.H. StampferM.J. A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians.J. Am. Coll. Nutr.199615213614310.1080/07315724.1996.107185788778142
    [Google Scholar]
  108. FolsomA.R. NietoF.J. McGovernP.G. TsaiM.Y. MalinowM.R. EckfeldtJ.H. HessD.L. DavisC.E. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study.Circulation199898320421010.1161/01.CIR.98.3.2049697819
    [Google Scholar]
  109. RobinsonK. ArheartK. RefsumH. BrattströmL. BoersG. UelandP. RubbaP. Palma-ReisR. MeleadyR. DalyL. WittemanJ. GrahamI. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease.Circulation199897543744310.1161/01.CIR.97.5.4379490237
    [Google Scholar]
  110. TietzN.W. Clinical Guide to Laboratory Tests. TietzN.W. PhiladelphiaW.B. Saunders1995
    [Google Scholar]
  111. LeklemJ.E. Vitamin B6.Modern Nutrition in Health and Disease. ShilsM. OlsonJ.A. ShikeM. RossA.C. BaltimoreWilliams & Wilkins1994383394
    [Google Scholar]
  112. KokF.J. SchrijverJ. HofmanA. WittemanJ.C.M. KruyssenD.A.C.M. RemmeW.J. ValkenburgH.A. Low vitamin B6 in patients with acute myocardial infarction.Am. J. Cardiol.198963951351610.1016/0002‑9149(89)90890‑42919556
    [Google Scholar]
  113. VermaakW.J. Barnard, H.; Potgieter, G.; du T. Theron, H. Vitamin B6 and Coronary Artery Disease.Atherosclerosis1987632–323523810.1016/0021‑9150(87)90126‑23827984
    [Google Scholar]
  114. VermaakW.J.H. BarnardH.C. DalenE.M.S.P. PotgieterG.M. JaarsveldH. MyburghS.J.S. Compartmentalization of pyridoxal-5′-phosphate during the acute phase of myocardial infarction.Klin. Wochenschr.1988661042843310.1007/BF017455113398428
    [Google Scholar]
  115. BrattströmL.E. IsraelssonB. JeppssonJ.O. HultbergB.L. Folic acid—an innocuous means to reduce plasma homocysteine.Scand. J. Clin. Lab. Invest.198848321522110.3109/003655188091674873375778
    [Google Scholar]
  116. LandgrenF. IsraelssonB. LindgrenA. HultbergB. AnderssonA. BrattströmL. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid.J. Intern. Med.1995237438138810.1111/j.1365‑2796.1995.tb01190.x7714461
    [Google Scholar]
  117. NaurathH.J. JoostenE. RiezlerR. StablerS. AllenR.H. LindenbaumJ. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.Lancet19953468967858910.1016/S0140‑6736(95)92113‑37603218
    [Google Scholar]
  118. UbbinkJ.B. VermaakW.J. van der MerweA. BeckerP.J. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia.Am. J. Clin. Nutr.1993571475310.1093/ajcn/57.1.478416664
    [Google Scholar]
  119. HeK. MerchantA. RimmE.B. RosnerB.A. StampferM.J. WillettW.C. AscherioA. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men.Stroke200435116917410.1161/01.STR.0000106762.55994.8614671243
    [Google Scholar]
  120. ChiM.S. Editorial commentary vitamin B6 in cholesterol metabolism.Nutr. Res.19844335936210.1016/S0271‑5317(84)80096‑2
    [Google Scholar]
  121. Di NapoliM. PapaF. BocolaV. C-reactive protein in ischemic stroke: an independent prognostic factor.Stroke200132491792410.1161/01.STR.32.4.91711283392
    [Google Scholar]
  122. RostN.S. WolfP.A. KaseC.S. Kelly-HayesM. SilbershatzH. MassaroJ.M. D’AgostinoR.B. FranzblauC. WilsonP.W.F. Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study.Stroke200132112575257910.1161/hs1101.09815111692019
    [Google Scholar]
  123. KellyP.J. ShihV.E. KistlerJ.P. BarronM. LeeH. MandellR. FurieK.L. Low vitamin B6 but not homocyst(e)ine is associated with increased risk of stroke and transient ischemic attack in the era of folic acid grain fortification.Stroke2003346e51e5410.1161/01.STR.0000071109.23410.AB12738890
    [Google Scholar]
  124. KellyP.J. KistlerJ.P. ShihV.E. MandellR. AtassiN. BarronM. LeeH. SilveiraS. FurieK.L. Inflammation, homocysteine, and vitamin B6 status after ischemic stroke.Stroke2004351121510.1161/01.STR.0000106481.59944.2F14657454
    [Google Scholar]
  125. DusitanondP. EikelboomJ.W. HankeyG.J. ThomJ. GilmoreG. LohK. YiQ. KlijnC.J.M. LangtonP. van BockxmeerF.M. BakerR. JamrozikK. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial.Stroke200536114414610.1161/01.STR.0000150494.91762.7015569860
    [Google Scholar]
  126. Younes-MhenniS. DerexL. BerruyerM. NighoghossianN. PhilippeauF. SalzmannM. TrouillasP. Large-artery stroke in a young patient with Crohn’s disease. Role of vitamin B6 deficiency-induced hyperhomocysteinemia.J. Neurol. Sci.20042211-211311510.1016/j.jns.2004.03.01615178225
    [Google Scholar]
  127. TillU. RöhlP. JentschA. TillH. MüllerA. BellstedtK. PlonnéD. FinkH.S. VollandtR. SliwkaU. HerrmannF.H. PetermannH. RiezlerR. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12.Atherosclerosis2005181113113510.1016/j.atherosclerosis.2004.12.04315939064
    [Google Scholar]
  128. MackoR.F. KittnerS.J. IveyF.M. EpsteinA. SparksM.J. HebelJ.R. JohnsonC.C. WitykR.J. UelandP.M. RefsumH. Effects of vitamin therapy on plasma total homocysteine, endothelial injury markers, and fibrinolysis in stroke patients.J. Stroke Cerebrovasc. Dis.20021111810.1053/jscd.2002.12396817903848
    [Google Scholar]
  129. VITATOPS Trial Study GroupB vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: A randomised, double-blind, parallel, placebo-controlled trial.Lancet Neurol.20109985586510.1016/S1474‑4422(10)70187‑320688574
    [Google Scholar]
  130. QinX. FanF. CuiY. ChenF. ChenY. ChengX. LiY. WangB. XuX. XuX. HuoY. WangX. Folic acid supplementation with and without vitamin B6 and revascularization risk: A meta-analysis of randomized controlled trials.Clin. Nutr.201433460361210.1016/j.clnu.2014.01.00624461473
    [Google Scholar]
  131. WangX. QinX. DemirtasH. LiJ. MaoG. HuoY. SunN. LiuL. XuX. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis.Lancet200736995761876188210.1016/S0140‑6736(07)60854‑X17544768
    [Google Scholar]
  132. HuoY. QinX. WangJ. SunN. ZengQ. XuX. LiuL. XuX. WangX. Efficacy of folic acid supplementation in stroke prevention: new insight from a meta-analysis.Int. J. Clin. Pract.201266654455110.1111/j.1742‑1241.2012.02929.x22607506
    [Google Scholar]
  133. QinX. HuoY. LangmanC.B. HouF. ChenY. MatossianD. XuX. WangX. Folic acid therapy and cardiovascular disease in ESRD or advanced chronic kidney disease: a meta-analysis.Clin. J. Am. Soc. Nephrol.20116348248810.2215/CJN.0531061021088292
    [Google Scholar]
  134. QinX. HuoY. XieD. HouF. XuX. WangX. Homocysteine-lowering therapy with folic acid is effective in cardiovascular disease prevention in patients with kidney disease: A meta-analysis of randomized controlled trials.Clin. Nutr.201332572272710.1016/j.clnu.2012.12.00923313356
    [Google Scholar]
  135. QinX. XuM. ZhangY. LiJ. XuX. WangX. XuX. HuoY. Effect of folic acid supplementation on the progression of carotid intima-media thickness: A meta-analysis of randomized controlled trials.Atherosclerosis2012222230731310.1016/j.atherosclerosis.2011.12.00722209480
    [Google Scholar]
  136. QinX. CuiY. ShenL. SunN. ZhangY. LiJ. XuX. WangB. XuX. HuoY. WangX. Folic acid supplementation and cancer risk: A meta-analysis of randomized controlled trials.Int. J. Cancer201313351033104110.1002/ijc.2803823338728
    [Google Scholar]
  137. KeeneK.L. ChenW.M. ChenF. WilliamsS.R. ElkhatibS.D. HsuF.C. MychaleckyjJ.C. DohenyK.F. PughE.W. LingH. LaurieC.C. GogartenS.M. MaddenE.B. WorrallB.B. SaleM.M. Genetic Associations with Plasma B12, B6, and Folate Levels in an Ischemic Stroke Population from the Vitamin Intervention for Stroke Prevention (VISP) Trial.Front. Public Health2014211210.3389/fpubh.2014.0011225147783
    [Google Scholar]
  138. SpenceJ.D. HowardV.J. ChamblessL.E. MalinowM.R. PettigrewL.C. StampferM. TooleJ.F. Vitamin Intervention for Stroke Prevention (VISP) trial: rationale and design.Neuroepidemiology2001201162510.1159/00005475311174041
    [Google Scholar]
  139. TooleJ.F. Vitamin intervention for stroke prevention.J. Neurol. Sci.2002203-20412112410.1016/S0022‑510X(02)00265‑412417369
    [Google Scholar]
  140. HazraA. KraftP. LazarusR. ChenC. ChanockS.J. JacquesP. SelhubJ. HunterD.J. Genome-wide significant predictors of metabolites in the one-carbon metabolism pathway.Hum. Mol. Genet.200918234677468710.1093/hmg/ddp42819744961
    [Google Scholar]
  141. SawułaW. Banecka-MajkutewiczZ. KadzińskiL. Jakóbkiewicz-BaneckaJ. WęgrzynG. NykaW. BaneckiB. Homocysteine level and metabolism in ischemic stroke in the population of Northern Poland.Clin. Biochem.200942644244710.1016/j.clinbiochem.2008.12.01919166826
    [Google Scholar]
  142. AgnatiL.F. GenedaniS. RasioG. GalantucciM. SaltiniS. FilaferroM. FrancoR. MoraF. FerréS. FuxeK. Studies on homocysteine plasma levels in Alzheimer’s patients. Relevance for neurodegeneration.J. Neural Transm. (Vienna)2005112116316910.1007/s00702‑004‑0154‑715599614
    [Google Scholar]
  143. SchneidermanJ.H. SharpeJ.A. SuttonD.M.C. Cerebral and retinal vascular complications of inflammatory bowel disease.Ann. Neurol.19795433133710.1002/ana.410050405443768
    [Google Scholar]
  144. PenixL.P. Ischemic strokes secondary to vitamin B 12 deficiency-induced hyperhomocystinemia.Neurology199851262262410.1212/WNL.51.2.6229710054
    [Google Scholar]
  145. LarssonS.C. MännistöS. VirtanenM.J. KonttoJ. AlbanesD. VirtamoJ. Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers.Am. J. Epidemiol.2008167895496110.1093/aje/kwm39518270369
    [Google Scholar]
  146. PietinenP. HartmanA.M. HaapaE. RäsänenL. HaapakoskiJ. PalmgrenJ. AlbanesD. VirtamoJ. HuttunenJ.K. REPRODUCIBILITY AND VALIDITY OF DIETARY ASSESSMENT INSTRUMENTS.Am. J. Epidemiol.1988128365566610.1093/oxfordjournals.aje.a1150132458036
    [Google Scholar]
  147. WaldN.J. WattH.C. LawM.R. WeirD.G. McPartlinJ. ScottJ.M. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention.Arch. Intern. Med.1998158886286710.1001/archinte.158.8.8629570171
    [Google Scholar]
  148. GangulyP. AlamS.F. Role of homocysteine in the development of cardiovascular disease.Nutr. J.2015141610.1186/1475‑2891‑14‑625577237
    [Google Scholar]
  149. RudreshkumarK.J. MajumdarV. NagarajaD. ChristopherR. Relevance of plasma levels of free homocysteine and methionine as risk predictors for ischemic stroke in the young.Clin. Nutr.20183751715172110.1016/j.clnu.2017.07.00528754404
    [Google Scholar]
  150. StipanukM.H. Metabolism of sulfur-containing amino acids.Annu. Rev. Nutr.19866117920910.1146/annurev.nu.06.070186.0011433524616
    [Google Scholar]
  151. GarciaG. TrejosJ. RestrepoB. LandázuriP. Homocisteína, folato e vitamina B12 em pacientes colombianos portadores de coronariopatia.Arq. Bras. Cardiol.2007892798510.1590/S0066‑782X200700140000217874011
    [Google Scholar]
  152. StamlerJ.S. OsborneJ.A. JarakiO. RabbaniL.E. MullinsM. SingelD. LoscalzoJ. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen.J. Clin. Invest.199391130831810.1172/JCI1161878380812
    [Google Scholar]
  153. WrennR.W. RaeuberC.L. HermanL.E. WaltonW.J. RosenquistT.H. Transforming growth factor-beta: Signal transduction via protein kinase C in cultured embryonic vascular smooth muscle cells. In Vitro Cell. Dev. Biol. Anim.1993291737810.1007/BF026343748444747
    [Google Scholar]
  154. DaltonM.L. GadsonP.F.Jr WrennR.W. RosenquistT.H. Homocysteine signal cascade: production of phospholipids, activation of protein kinase C, and the induction of c-fos and c-myb in smooth muscle cells.FASEB J.199711870371110.1096/fasebj.11.8.92409719240971
    [Google Scholar]
  155. LiW. ZhengT. WangJ. AlturaB.T. AlturaB.M. Extracellular magnesium regulates effects of vitamin B 6, B 12 and folate on homocysteinemia-induced depletion of intracellular free magnesium ions in canine cerebral vascular smooth muscle cells: possible relationship to [Ca2+] i, atherogenesis and stroke.Neurosci. Lett.19992742838610.1016/S0304‑3940(99)00683‑710553943
    [Google Scholar]
  156. SchwaningerM. RinglebP. WinterR. KohlB. FiehnW. RieserP.A. Walter-SackI. Elevated plasma concentrations of homocysteine in antiepileptic drug treatment.Epilepsia199940334535010.1111/j.1528‑1157.1999.tb00716.x10080517
    [Google Scholar]
  157. ApelandT. MansoorM.A. PentievaK. McNultyH. SeljeflotI. StrandjordR.E. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs.Epilepsy Res.200251323724710.1016/S0920‑1211(02)00153‑512399074
    [Google Scholar]
  158. McCullyK.S. Homocysteine and the pathogenesis of atherosclerosis.Expert Rev. Clin. Pharmacol.20158221121910.1586/17512433.2015.101051625653125
    [Google Scholar]
  159. HankeyG.J. B vitamins for stroke prevention.Stroke Vasc. Neurol.201832515810.1136/svn‑2018‑00015630022794
    [Google Scholar]
  160. StraßburgA. KremsC. LührmannP.M. HartmannB. Neuhäuser-BertholdM. Effect of age on plasma homocysteine concentrations in young and elderly subjects considering serum vitamin concentrations and different lifestyle factors.Int. J. Vitam. Nutr. Res.200474212913610.1024/0300‑9831.74.2.12915255449
    [Google Scholar]
  161. Orzechowska-PawilojcA. SworczakK. LewczukA. BabinskaA. Homocysteine, folate and cobalamin levels in hypothyroid women before and after treatment.Endocr. J.200754347147610.1507/endocrj.K06‑11217464093
    [Google Scholar]
  162. SobczakA. WardasW. Zielinska-DanchW. PawlickiK. The influence of smoking on plasma homocysteine and cysteine levels in passive and active smokers.Clinical Chemistry and Laboratory Medicine (CCLM)200442440841410.1515/CCLM.2004.07215147151
    [Google Scholar]
  163. SpenceJ.D. UrquhartB.L. BangH. Effect of renal impairment on atherosclerosis: only partially mediated by homocysteine.Nephrol. Dial. Transplant.201631693794410.1093/ndt/gfv38026567910
    [Google Scholar]
  164. KimJ. KimH. RohH. KwonY. Causes of hyperhomocysteinemia and its pathological significance.Arch. Pharm. Res.201841437238310.1007/s12272‑018‑1016‑429552692
    [Google Scholar]
  165. FallonU.B. ElwoodP. Ben-ShlomoY. UbbinkJ.B. GreenwoodR. SmithG.D. Homocysteine and ischaemic stroke in men: the Caerphilly study.J. Epidemiol. Community Health2001552919610.1136/jech.55.2.9111154247
    [Google Scholar]
  166. MaxwellC.J. HoganD.B. EblyE.M. Serum folate levels and subsequent adverse cerebrovascular outcomes in elderly persons.Dement. Geriatr. Cogn. Disord.200213422523410.1159/00005770112006733
    [Google Scholar]
  167. KocerA. InceN. CanbulatE.C. SarginM. Serum vitamin B12 and folic Acid levels in acute cerebral atherothrombotic infarction.Tohoku J. Exp. Med.2004204215516110.1620/tjem.204.15515383696
    [Google Scholar]
  168. WeikertC. DierkesJ. HoffmannK. BergerK. DroganD. Klipstein-GrobuschK. SprangerJ. MöhligM. LuleyC. BoeingH. B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort.Stroke200738112912291810.1161/STROKEAHA.107.48606817885260
    [Google Scholar]
  169. WaldD.S. WaldN.J. MorrisJ.K. LawM. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence.BMJ200633375781114111710.1136/bmj.39000.486701.6817124224
    [Google Scholar]
  170. CastroR. RiveraI. BlomH.J. JakobsC. de AlmeidaI.T. Homocysteine metabolism, hyperhomocysteinaemia and vascular disease: An overview.J. Inherit. Metab. Dis.200629132010.1007/s10545‑006‑0106‑516601863
    [Google Scholar]
  171. VerhoefP. HennekensC.H. MalinowM.R. KokF.J. WillettW.C. StampferM.J. A prospective study of plasma homocyst(e)ine and risk of ischemic stroke.Stroke199425101924193010.1161/01.STR.25.10.19248091435
    [Google Scholar]
  172. AlfthanG. PekkanenJ. JauhiainenM. PitkäniemiJ. KarvonenM. TuomilehtoJ. SalonenJ.T. EhnholmC. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study.Atherosclerosis1994106191910.1016/0021‑9150(94)90078‑78018111
    [Google Scholar]
  173. PerryI.J. MorrisR.W. EbrahimS.B. ShaperA.G. RefsumH. UelandP.M. Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men.Lancet199534689871395139810.1016/S0140‑6736(95)92407‑87475822
    [Google Scholar]
  174. StehouwerC.D.A. WeijenbergM.P. van den BergM. JakobsC. FeskensE.J.M. KromhoutD. Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up.Arterioscler. Thromb. Vasc. Biol.199818121895190110.1161/01.ATV.18.12.18959848881
    [Google Scholar]
  175. BostomA.G. RosenbergI.H. SilbershatzH. JacquesP.F. SelhubJ. D’AgostinoR.B. WilsonP.W.F. WolfP.A. Nonfasting plasma total homocysteine levels and stroke incidence in elderly persons: the Framingham Study.Ann. Intern. Med.1999131535235510.7326/0003‑4819‑131‑5‑199909070‑0000610475888
    [Google Scholar]
  176. AronowW.S. AhnC. GutsteinH. Increased plasma homocysteine is an independent predictor of new atherothrombotic brain infarction in older persons.Am. J. Cardiol.2000865585586, A1010.1016/S0002‑9149(00)01025‑011009289
    [Google Scholar]
  177. WengL.C. YehW.T. BaiC.H. ChenH.J. ChuangS.Y. ChangH.Y. LinB.F. ChenK.J. PanW.H. Is ischemic stroke risk related to folate status or other nutrients correlated with folate intake?Stroke200839123152315810.1161/STROKEAHA.108.52493418988909
    [Google Scholar]
  178. HoneinM.A. PaulozziL.J. MathewsT.J. EricksonJ.D. WongL.Y. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects.JAMA2001285232981298610.1001/jama.285.23.298111410096
    [Google Scholar]
  179. De WalsP. TairouF. Van AllenM.I. UhS.H. LowryR.B. SibbaldB. EvansJ.A. Van den HofM.C. ZimmerP. CrowleyM. FernandezB. LeeN.S. NiyonsengaT. Reduction in neural-tube defects after folic acid fortification in Canada.N. Engl. J. Med.2007357213514210.1056/NEJMoa06710317625125
    [Google Scholar]
  180. GilesW.H. KittnerS.J. AndaR.F. CroftJ.B. CasperM.L. Serum folate and risk for ischemic stroke. First National Health and Nutrition Examination Survey epidemiologic follow-up study.Stroke19952671166117010.1161/01.STR.26.7.11667604408
    [Google Scholar]
  181. SatoY. KajiM. KondoI. YoshidaH. SatohK. MetokiN. RETRACTED: Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: Effect of combined therapy with folic acid and mecobalamine.J. Neurol. Sci.20022021-2656810.1016/S0022‑510X(02)00210‑112220694
    [Google Scholar]
  182. de BreeA. VerschurenW.M.M. BlomH.J. NadeauM. TrijbelsF.J.M. KromhoutD. Coronary heart disease mortality, plasma homocysteine, and B-vitamins: a prospective study.Atherosclerosis2003166236937710.1016/S0021‑9150(02)00373‑812535751
    [Google Scholar]
  183. HuangX. LiY. LiP. LiJ. BaoH. ZhangY. WangB. SunN. WangJ. HeM. YinD. TangG. ChenY. CuiY. HuangY. HouF.F. QinX. HuoY. ChengX. Association between percent decline in serum total homocysteine and risk of first stroke.Neurology201789202101210710.1212/WNL.000000000000464829030456
    [Google Scholar]
  184. SpenceJ.D. YiQ. HankeyG.J. B vitamins in stroke prevention: time to reconsider.Lancet Neurol.201716975076010.1016/S1474‑4422(17)30180‑128816120
    [Google Scholar]
  185. BazzanoL.A. HeJ. OgdenL.G. LoriaC. VupputuriS. MyersL. WheltonP.K. Dietary intake of folate and risk of stroke in US men and women: NHANES I Epidemiologic Follow-up Study. National Health and Nutrition Examination Survey.Stroke20023351183118910.1161/01.STR.0000014607.90464.8811988588
    [Google Scholar]
  186. Van GuelpenB. HultdinJ. JohanssonI. StegmayrB. HallmansG. NilssonT.K. WeinehallL. WitthöftC. PalmqvistR. WinkvistA. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake.Stroke20053671426143110.1161/01.STR.0000169934.96354.3a15933256
    [Google Scholar]
  187. GalanP. Kesse-GuyotE. CzernichowS. BrianconS. BlacherJ. HercbergS. Effects of B Vitamins and Omega 3 Fatty Acids on Cardiovascular Diseases: A Randomised Placebo Controlled Trial.BMJ201134277873610.1136/bmj.c627321115589
    [Google Scholar]
  188. HolmesM.V. NewcombeP. HubacekJ.A. SofatR. RickettsS.L. CooperJ. BretelerM.M.B. BautistaL.E. SharmaP. WhittakerJ.C. SmeethL. FowkesF.G.R. AlgraA. ShmelevaV. SzolnokiZ. RoestM. LinnebankM. ZachoJ. NallsM.A. SingletonA.B. FerrucciL. HardyJ. WorrallB.B. RichS.S. MatarinM. NormanP.E. FlickerL. AlmeidaO.P. van BockxmeerF.M. ShimokataH. KhawK.T. WarehamN.J. BobakM. SterneJ.A.C. SmithG.D. TalmudP.J. van DuijnC. HumphriesS.E. PriceJ.F. EbrahimS. LawlorD.A. HankeyG.J. MeschiaJ.F. SandhuM.S. HingoraniA.D. CasasJ.P. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials.Lancet2011378979158459410.1016/S0140‑6736(11)60872‑621803414
    [Google Scholar]
  189. HuoY. LiJ. QinX. HuangY. WangX. GottesmanR.F. TangG. WangB. ChenD. HeM. FuJ. CaiY. ShiX. ZhangY. CuiY. SunN. LiX. ChengX. WangJ. YangX. YangT. XiaoC. ZhaoG. DongQ. ZhuD. WangX. GeJ. ZhaoL. HuD. LiuL. HouF.F. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: The CSPPT randomized clinical trial.JAMA2015313131325133510.1001/jama.2015.227425771069
    [Google Scholar]
  190. KongX. HuangX. ZhaoM. XuB. XuR. SongY. YuY. YangW. ZhangJ. LiuL. ZhangY. TangG. WangB. HouF.F. LiP. ChengX. ZhaoS. WangX. QinX. LiJ. HuoY. Platelet Count Affects Efficacy of Folic Acid in Preventing First Stroke.J. Am. Coll. Cardiol.201871192136214610.1016/j.jacc.2018.02.07229747834
    [Google Scholar]
  191. ZhaoM. WuG. LiY. WangX. HouF.F. XuX. QinX. CaiY. Meta-analysis of folic acid efficacy trials in stroke prevention.Neurology201788191830183810.1212/WNL.000000000000390928404799
    [Google Scholar]
  192. WangZ.M. ZhouB. NieZ.L. GaoW. WangY.S. ZhaoH. ZhuJ. YanJ.J. YangZ.J. WangL.S. Folate and risk of coronary heart disease: A meta-analysis of prospective studies.Nutr. Metab. Cardiovasc. Dis.2012221089089910.1016/j.numecd.2011.04.01121924595
    [Google Scholar]
  193. ZhouZ. LiJ. YuY. LiY. ZhangY. LiuL. SongY. ZhaoM. WangY. TangG. HeM. XuX. CaiY. DongQ. YinD. HuangX. ChengX. WangB. HouF.F. WangX. QinX. HuoY. Effect of Smoking and Folate Levels on the Efficacy of Folic Acid Therapy in Prevention of Stroke in Hypertensive Men.Stroke201849111412010.1161/STROKEAHA.117.01827329273594
    [Google Scholar]
  194. TianT. YangK.Q. CuiJ.G. ZhouL.L. ZhouX.L. Folic Acid Supplementation for Stroke Prevention in Patients With Cardiovascular Disease.Am. J. Med. Sci.2017354437938710.1016/j.amjms.2017.05.02029078842
    [Google Scholar]
  195. LiY. HuangT. ZhengY. MukaT. TroupJ. HuF.B. Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.J. Am. Heart Assoc.201658e00376810.1161/JAHA.116.00376827528407
    [Google Scholar]
  196. JungJ.Y. LeeH.S. KangD.G. KimN.S. ChaM.H. BangO.S. RyuD.H. HwangG.S. 1H-NMR-based metabolomics study of cerebral infarction.Stroke20114251282128810.1161/STROKEAHA.110.59878921474802
    [Google Scholar]
  197. DavisC.K. G KR. Postischemic supplementation of folic acid improves neuronal survival and regeneration in vitro.Nutr. Res.20207511410.1016/j.nutres.2019.12.00731955011
    [Google Scholar]
  198. VerhaarM.C. StroesE. RabelinkT.J. Folates and cardiovascular disease.Arterioscler. Thromb. Vasc. Biol.200222161310.1161/hq0102.10219011788454
    [Google Scholar]
  199. KellyP.J. FurieK.L. Management and prevention of stroke associated with elevated homocysteine.Curr. Treat. Options Cardiovasc. Med.20024536337110.1007/s11936‑002‑0016‑212194809
    [Google Scholar]
  200. MoatS.J. LangD. McDowellI.F.W. ClarkeZ.L. MadhavanA.K. LewisM.J. GoodfellowJ. Folate, homocysteine, endothelial function and cardiovascular disease.J. Nutr. Biochem.2004152647910.1016/j.jnutbio.2003.08.01014972346
    [Google Scholar]
  201. SpenceJ.D. Homocysteine-lowering therapy: a role in stroke prevention?Lancet Neurol.20076983083810.1016/S1474‑4422(07)70219‑317706567
    [Google Scholar]
  202. Martí-CarvajalA.J. SolàI. LathyrisD. Updated in: Homocysteine-lowering interventions for preventing cardiovascular events.Cochrane Database Syst. Rev.201511CD00661210.1002/14651858.CD006612.pub425590290
    [Google Scholar]
  203. SikorskiZ.E. Fennema's Food Chemistry (Fifth Edition) – Edited by Srinivasan Damodaran and Kirk L. Parkin.J. Food Biochem.201842210.1111/jfbc.12483
    [Google Scholar]
  204. GallieniM. RizzoM.A. MaggiS. RegaliaA. MolfinoI. CrepaldiG. FusaroM. Vitamin K and bone metabolism in the elderly with normal and reduced kidney function.Eur. Geriatr. Med.201341323810.1016/j.eurger.2012.10.001
    [Google Scholar]
  205. StaffordD.W. The vitamin K cycle.J. Thromb. Haemost.2005381873187810.1111/j.1538‑7836.2005.01419.x16102054
    [Google Scholar]
  206. OldenburgJ. MarinovaM. Müller-ReibleC. WatzkaM. The vitamin K cycle.Vitam. Horm.20087807356210.1016/S0083‑6729(07)00003‑918374189
    [Google Scholar]
  207. OverbeyD.M. JonesE.L. RobinsonT.N. How hemostatic agents interact with the coagulation cascade.AORN J.2014100214815910.1016/j.aorn.2013.12.01225080416
    [Google Scholar]
  208. FerlandG. Present Knowledge in Nutrition, Tenth Edition.Present Knowledge in Nutrition.Wiley201223024710.1002/9781119946045.ch15
    [Google Scholar]
  209. FerlandG. The discovery of vitamin K and its clinical applications.Ann. Nutr. Metab.201261321321810.1159/00034310823183291
    [Google Scholar]
  210. GriffinJ.H. ZlokovicB.V. MosnierL.O. Activated protein C: biased for translation.Blood2015125192898290710.1182/blood‑2015‑02‑35597425824691
    [Google Scholar]
  211. HealyL.D. RiggR.A. GriffinJ.H. McCartyO.J.T. Regulation of immune cell signaling by activated protein C.J. Leukoc. Biol.201810361197120310.1002/JLB.3MIR0817‑338R29601101
    [Google Scholar]
  212. FerlandG. Vitamin K and the nervous system: an overview of its actions.Adv. Nutr.20123220421210.3945/an.111.00178422516728
    [Google Scholar]
  213. GhozlanM.F. MohamedA.A.E.H. EissaD.S. EldawyH.S. Low Protein Z Level: A Thrombophilic Risk Biomarker for Acute Coronary Syndrome.Indian J. Hematol. Blood Transfus.201935233934610.1007/s12288‑018‑1002‑530988573
    [Google Scholar]
  214. NapolitanoM. MarianiG. LapecorellaM. Hereditary combined deficiency of the vitamin K-dependent clotting factors.Orphanet J. Rare Dis.2010512110.1186/1750‑1172‑5‑2120630065
    [Google Scholar]
  215. BereczkyZ. KovácsK.B. MuszbekL. ProteinC. ProteinS. Protein C and protein S deficiencies: similarities and differences between two brothers playing in the same game.Clin. Chem. Lab. Med.201048S53S6610.1515/CCLM.2010.36921054189
    [Google Scholar]
  216. HowardB.M. KornblithL.Z. CheungC.K. KutcherM.E. MiyazawaB.Y. VilardiR.F. CohenM.J. Inducing Acute Traumatic Coagulopathy In Vitro: The Effects of Activated Protein C on Healthy Human Whole Blood.PLoS One2016113e015093010.1371/journal.pone.015093027008408
    [Google Scholar]
  217. McQuillanA.M. EikelboomJ.W. HankeyG.J. BakerR. ThomJ. StatonJ. YiQ. ColeV. Protein Z in ischemic stroke and its etiologic subtypes.Stroke200334102415241910.1161/01.STR.0000092124.52084.4B12970515
    [Google Scholar]
  218. KobeltK. BiasiuttiF.D. MattleH.P. LämmleB. WuilleminW.A. Protein Z in ischaemic stroke.Br. J. Haematol.2001114116917310.1046/j.1365‑2141.2001.02913.x11472363
    [Google Scholar]
  219. WangJ.J. ShiK.L. LiJ.W. JiangL.Q. CaspiO. FangF. XiaoJ. JingH. ZouL.P. Risk factors for arterial ischemic and hemorrhagic stroke in childhood.Pediatr. Neurol.200940427728110.1016/j.pediatrneurol.2008.11.00219302940
    [Google Scholar]
  220. AydinliN. TatliB. ÇalişkanM. ÖzmenM. CitakA. UnuvarA. BaykalT. OmerogluR.E. AydinK. SencerS. SencerA. KırışT. Stroke in Childhood: Experience in Istanbul, Turkey.J. Trop. Pediatr.200652315816210.1093/tropej/fml01616636011
    [Google Scholar]
  221. JanssenR. VisserM.P.J. DofferhoffA.S.M. VermeerC. JanssensW. WalkJ. VitaminK. Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019.Br. J. Nutr.2021126219119810.1017/S000711452000397933023681
    [Google Scholar]
  222. AnastasiE. IalongoC. LabriolaR. FerragutiG. LucarelliM. AngeloniA. VitaminK. Vitamin K deficiency and covid-19.Scand. J. Clin. Lab. Invest.202080752552710.1080/00365513.2020.180512232779537
    [Google Scholar]
  223. VismaraL.A. RogersS.J. OgletreeB.T. OrenT. McphilemyC. DillenburgerK. HiltonJ.C. SealB.C. DekkerV. NautaM.H. Havioral.J. Autism Dev. Disord.20104011841
    [Google Scholar]
  224. IbaT. LevyJ.H. Sepsis-induced Coagulopathy and Disseminated Intravascular Coagulation.Anesthesiology202013251238124510.1097/ALN.000000000000312232044801
    [Google Scholar]
  225. CroftsT.S. SethE.C. HazraA.B. TagaM.E. Cobamide structure depends on both lower ligand availability and CobT substrate specificity.Chem. Biol.201320101265127410.1016/j.chembiol.2013.08.00624055007
    [Google Scholar]
  226. YajnikC.S. DeshmukhU.S. Fetal programming: Maternal nutrition and role of one-carbon metabolism.Rev. Endocr. Metab. Disord.201213212112710.1007/s11154‑012‑9214‑822415298
    [Google Scholar]
  227. PezziniA. Del ZottoE. PadovaniA. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications.Curr. Med. Chem.200714324926310.2174/09298670777994114017305530
    [Google Scholar]
  228. SpenceJ.D. Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke.Nutr. Res.201636210911610.1016/j.nutres.2015.10.00326597770
    [Google Scholar]
  229. AhmedS. BogiatziC. HackamD.G. RutledgeA.C. SposatoL.A. KhawA. MandziaJ. AzarpazhooM.R. HachinskiV. SpenceJ.D. Vitamin B 12 deficiency and hyperhomocysteinaemia in outpatients with stroke or transient ischaemic attack: a cohort study at an academic medical centre.BMJ Open201991e02656410.1136/bmjopen‑2018‑02656430670531
    [Google Scholar]
  230. KalitaJ. KumarG. BansalV. MisraU.K. Relationship of homocysteine with other risk factors and outcome of ischemic stroke.Clin. Neurol. Neurosurg.2009111436436710.1016/j.clineuro.2008.12.01019185985
    [Google Scholar]
  231. GilleD. SchmidA. Vitamin B12 in meat and dairy products.Nutr. Rev.201573210611510.1093/nutrit/nuu01126024497
    [Google Scholar]
  232. RajanS. WallaceJ.I. BeresfordS.A.A. BrodkinK.I. AllenR.A. StablerS.P. Screening for cobalamin deficiency in geriatric outpatients: prevalence and influence of synthetic cobalamin intake.J. Am. Geriatr. Soc.200250462463010.1046/j.1532‑5415.2002.50155.x11982661
    [Google Scholar]
  233. MatcharD.B. McCroryD.C. MillingtonD.S. FeussnerJ.R. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency.Am. J. Med. Sci.1994308527628310.1097/00000441‑199411000‑000047977446
    [Google Scholar]
  234. GilesW.H. CroftJ.B. GreenlundK.J. FordE.S. KittnerS.J. Total homocyst(e)ine concentration and the likelihood of nonfatal stroke: results from the Third National Health and Nutrition Examination Survey, 1988-1994.Stroke199829122473247710.1161/01.STR.29.12.24739836753
    [Google Scholar]
  235. ImpairedO. F. FunctionM. SizeI. D. MetaboliteC. GuH. BottiglieriT. JadavjiN. M. Ischemic stroke and dietary vitamin B12 deficiency in old-aged females: Impaired motor function, increased ischemic damage size, and changed metabolite profiles in brain and cecum tissue.Nutrients20221414296010.3390/nu14142960.
    [Google Scholar]
  236. UelandP.M. RefsumH. BeresfordS.A.A. VollsetS.E. The controversy over homocysteine and cardiovascular risk.Am. J. Clin. Nutr.200072232433210.1093/ajcn/72.2.32410919921
    [Google Scholar]
  237. ChristenW.G. AjaniU.A. GlynnR.J. HennekensC.H. Blood levels of homocysteine and increased risks of cardiovascular disease: causal or casual?Arch. Intern. Med.2000160442243410.1001/archinte.160.4.42210695683
    [Google Scholar]
  238. TanneD. HaimM. GoldbourtU. BoykoV. DoolmanR. AdlerY. BrunnerD. BeharS. SelaB.A. Prospective study of serum homocysteine and risk of ischemic stroke among patients with preexisting coronary heart disease.Stroke200334363263610.1161/01.STR.0000060203.58958.3512624283
    [Google Scholar]
  239. RiosM.Y. OrtegaA. DomínguezB. DécigaM. RosaV. Glaucacetalin E and galphimidin B from Galphimia glauca and their anxiolytic activity.J. Ethnopharmacol.202025925911293910.1016/j.jep.2020.11293932417425
    [Google Scholar]
  240. LiY. ZhengJ. ZhuY. QuY. SuoR. ZhuY. Neuroprotective effects of methylcobalamin in cerebral ischemia/reperfusion injury through activation of the ERK1/2 signaling pathway.Int. Immunopharmacol.202199May10804010.1016/j.intimp.2021.10804034435586
    [Google Scholar]
  241. SaposnikG. The role of vitamin B in stroke prevention: a journey from observational studies to clinical trials and critique of the VITAmins TO Prevent Stroke (VITATOPS).Stroke201142383884210.1161/STROKEAHA.110.60835621273566
    [Google Scholar]
  242. TanN.C.K. VenketasubramanianN. SawS.M. TjiaH.T.L. Hyperhomocyst(e)inemia and risk of ischemic stroke among young Asian adults.Stroke20023381956196210.1161/01.STR.0000021899.08659.C812154245
    [Google Scholar]
  243. BrattstromL.E. HardeboJ.E. HultbergB.L. Moderate homocysteinemia-a possible risk factor for arteriosclerotic cerebrovascular disease.Stroke19841561012101610.1161/01.STR.15.6.10126506111
    [Google Scholar]
  244. FurieK.L. KellyP.J. Homocyst(e)ine and stroke.Semin Neurol2006261243210.1055/s‑2006‑933306.
    [Google Scholar]
  245. LalouschekW. AullS. KorningerL. MannhalterC. Pabinger-FaschingI. SchmidR.W. Peter Schnider ZeilerK. 677C to T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and plasma homocyst(e)ine levels in patients with TIA or minor stroke.J. Neurol. Sci.1998155215616210.1016/S0022‑510X(97)00311‑09562260
    [Google Scholar]
  246. LalouschekW. AullS. SerlesW. SchniderP. MannhalterC. LangT. DeeckeL. ZeilerK. Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischemic cerebrovascular disease and in healthy control subjects.J. Lab. Clin. Med.1999133657558210.1016/S0022‑2143(99)90187‑710360632
    [Google Scholar]
  247. AyH. ArsavaE.M. TokgözoğluS.L. ÖzerN. SarıbaşO. Hyperhomocysteinemia is associated with the presence of left atrial thrombus in stroke patients with nonvalvular atrial fibrillation.Stroke200334490991210.1161/01.STR.0000060202.63475.BA12624219
    [Google Scholar]
  248. BecciaM. MeleM.C. FerrariM. RanieriM. BariniA. RasuraM. Young stroke and basal plasma and post-methionine load homocysteine and cysteine levels 1 year after the acute event: do plasma folates make the difference?Eur. J. Neurol.200411426927510.1046/j.1468‑1331.2003.00774.x15061829
    [Google Scholar]
  249. Karakurum GokselB. KaratasM. NebiogluA. SezginN. TanM. SeydaogluG. BenliS. KaracaS. ArlierZ. YerdelenD. Subclinical hypothyroidism, hyperhomocysteinemia and dyslipidemia: investigating links with ischemic stroke in Turkish patients.Neurol. Res.200729887187610.1179/016164107X18183317588311
    [Google Scholar]
  250. MoghaddasiM. MamarabadiM. MirzadehS. FreydoonnejadA.A. RazjouyanH. Homocysteine, vitamin B12 and folate levels in Iranian patients with ischemic stroke.Neurol. Res.201032995395610.1179/016164110X1264425226047520433777
    [Google Scholar]
  251. BayırA. AkA. ÖzdinçŞ. SeydanoğluA. KöstekçiŞ.K. KaraF. Acute-phase vitamin B12 and folic acid levels in patients with ischemic and hemorrhagic stroke: is there a relationship with prognosis?Neurol. Res.201032211511810.1179/016164109X1244561659620119825273
    [Google Scholar]
  252. OmraniH.Q. ShandizE.E. QabaiM. ChamanR. FardH.A. QaffarpoorM. Hyperhomocysteinemia, folateo and B12 vitamin in Iranian patients with acute ischemic stroke.ARYA Atheroscler.2011739710122577454
    [Google Scholar]
  253. HaririM. DarvishiL. MaghsoudiZ. KhorvashF. AghaeiM. IrajB. GhiasvandR. AskariG. Intakes of Vegetables and Fruits are Negatively Correlated with Risk of Stroke in Iran.Int. J. Prev. Med.20134S300S30523776742
    [Google Scholar]
  254. AshjazadehN. FathiM. ShariatA. Evaluation of Homocysteine Level as a Risk Factor among Patients with Ischemic Stroke and Its Subtypes.Iran. J. Med. Sci.201338323323924174694
    [Google Scholar]
  255. ChoeH. HwangJ.Y. YunJ.A. KimJ.M. SongT.J. ChangN. KimY.J. KimY. Intake of antioxidants and B vitamins is inversely associated with ischemic stroke and cerebral atherosclerosis.Nutr. Res. Pract.201610551652310.4162/nrp.2016.10.5.51627698959
    [Google Scholar]
  256. LarssonS.C. TraylorM. MarkusH.S. Homocysteine and small vessel stroke: A mendelian randomization analysis.Ann. Neurol.201985449550110.1002/ana.2544030785218
    [Google Scholar]
  257. RawashdehS.I. Al-MistarehiA.H. YassinA. Rabab’ahW. SkaffH. IbdahR. A Concurrent Ischemic Stroke, Myocardial Infarction, and Aortic Thrombi in a Young Patient with Hyperhomocysteinemia: A Case Report.Int. Med. Case Rep. J.20201358159010.2147/IMCRJ.S27960333192104
    [Google Scholar]
  258. QinX. SpenceJ.D. LiJ. ZhangY. LiY. SunN. LiangM. SongY. ZhangY. WangB. ChengX. ZhaoL. WangX. XuX. HuoY. Interaction of serum vitamin B 12 and folate with MTHFR genotypes on risk of ischemic stroke.Neurology20209411e1126e113610.1212/WNL.000000000000893231932513
    [Google Scholar]
  259. ChiuT.H.T. ChangH.R. WangL.Y. ChangC.C. LinM.N. LinC.L. Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.Neurology20209411e1112e112110.1212/WNL.000000000000909332102976
    [Google Scholar]
  260. KweonO.J. LimY.K. LeeM.K. KimH.R. Clinical Utility of Serum Holotranscobalamin Measurements in Patients with First-Ever Ischemic Stroke.Dis. Markers2021202111010.1155/2021/991429834545295
    [Google Scholar]
  261. YuanM. WangB. TanS. Mecobalamin and early functional outcomes of ischemic stroke patients with H-type hypertension.Rev. Assoc. Med. Bras.201864542843210.1590/1806‑9282.64.05.42830304141
    [Google Scholar]
  262. van OverbeekE.C. StaalsJ. van OostenbruggeR.J. Vitamin B12 and progression of white matter lesions. A 2-year follow-up study in first-ever lacunar stroke patients.PLoS One2013810e7810010.1371/journal.pone.007810024155983
    [Google Scholar]
  263. HuijtsM. DuitsA. StaalsJ. van OostenbruggeR.J. Association of vitamin B12 deficiency with fatigue and depression after lacunar stroke.PLoS One201271e3051910.1371/journal.pone.003051922276208
    [Google Scholar]
  264. Keat WeiL. SutherlandH. AuA. CamilleriE. HauptL.M. GanS.H. GriffithsL.R. A potential epigenetic marker mediating serum folate and vitamin B12 levels contributes to the risk of ischemic stroke.BioMed Res. Int.201520151410.1155/2015/16797625705649
    [Google Scholar]
  265. KaraN. SenesM. CoskunO. InanL. SaydamG. YucelD. Urinary methylmalonic acid levels in patients with acute ischemic stroke.Clin. Biochem.2009427-857858310.1016/j.clinbiochem.2009.02.01819269282
    [Google Scholar]
  266. RothW. MohamadzadehM. Vitamin B12 and gut-brain homeostasis in the pathophysiology of ischemic stroke.EBioMedicine20217310367610.1016/j.ebiom.2021.10367634749301
    [Google Scholar]
  267. SerefhanogluS. AydogduI. KekilliE. IlhanA. KukuI. Measuring holotranscobalamin II, an early indicator of negative vitamin B12 balance, by radioimmunoassay in patients with ischemic cerebrovascular disease.Ann. Hematol.200887539139510.1007/s00277‑007‑0406‑317992530
    [Google Scholar]
  268. MaruottiN. CantatoreF.P. Vitamin D and the immune system.J. Rheumatol.201037349149510.3899/jrheum.09079720080911
    [Google Scholar]
  269. WackerM. HolickM.F. Sunlight and Vitamin D - A global perspective for health.Dermatoendocrinol20135121121724494057
    [Google Scholar]
  270. SiottoM. SantoroM. AprileI. Vitamin D and Rehabilitation after Stroke: Status of Art.Appl. Sci. (Basel)2020106197310.3390/app10061973
    [Google Scholar]
  271. BikleD.D. VitaminD. Vitamin D metabolism, mechanism of action, and clinical applications.Chem. Biol.201421331932910.1016/j.chembiol.2013.12.01624529992
    [Google Scholar]
  272. MeyerV. SacconeD.S. TugizimanaF. AsaniF.F. JefferyT.J. BornmanL. Methylation of the Vitamin D Receptor (VDR) Gene, Together with Genetic Variation, Race, and Environment Influence the Signaling Efficacy of the Toll-Like Receptor 2/1-VDR Pathway.Front. Immunol.20178SEP104810.3389/fimmu.2017.0104828959253
    [Google Scholar]
  273. SchneiderM.A. The Importance of Educating Patients With Stroke About Vitamin D.J. Neurosci. Nurs.201749638738910.1097/JNN.000000000000032629117036
    [Google Scholar]
  274. ThapaL. PokhrelB. ShresthaA. PradhanM. BhandariT.R. ShresthaS. PoudelR.S. PoudelR. Status of Vitamin D and its Association with Stroke Risk Factors in Patients with Acute Ischemic Stroke in a Tertiary Care Hospital.JNMA J. Nepal Med. Assoc.19705219593593910.31729/jnma.271926982669
    [Google Scholar]
  275. MarekK. CichońN. Saluk-BijakJ. BijakM. MillerE. The Role of Vitamin D in Stroke Prevention and the Effects of Its Supplementation for Post-Stroke Rehabilitation: A Narrative Review.Nutrients20221413276110.3390/nu1413276135807941
    [Google Scholar]
  276. PrabhakarS. GuptaA. ModiM. BhadadaS. LalV. KhuranaD. VitaminD. Vitamin D status and risk of ischemic stroke in North Indian patients.Indian J. Endocrinol. Metab.201418572172510.4103/2230‑8210.13924125285293
    [Google Scholar]
  277. ZhouR. WangM. HuangH. LiW. HuY. WuT. Lower Vitamin D Status Is Associated with an Increased Risk of Ischemic Stroke: A Systematic Review and Meta-Analysis.Nutrients201810327710.3390/nu1003027729495586
    [Google Scholar]
  278. PooleK.E.S. LoveridgeN. BarkerP.J. HalsallD.J. RoseC. ReeveJ. WarburtonE.A. Reduced vitamin D in acute stroke.Stroke200637124324510.1161/01.STR.0000195184.24297.c116322500
    [Google Scholar]
  279. MomosakiR.. AboM. UrashimaM. Vitamin D supplementation and post-stroke rehabilitation: A randomized, double-blind, placebo-controlled trial.Nutrients2019116129510.3390/nu11061295.
    [Google Scholar]
  280. ParkJ.Y. KimJ.H. SimY.J. JeongH.J. LeeJ.H. KimG.C. The association between the serum vitamin D levels and the stroke lesion size, functional ability, and cognition in elderly Korean ischemic stroke patients.Medicine (Baltimore)202210135e0408610.1097/MD.000000000003040236107604
    [Google Scholar]
  281. MiaoH. ZhuH. LuanX. HuangG. ChenM. YuanZ. WangZ. Risk Factors of Vitamin D Deficiency in Chinese Ischemic Stroke Patients: A Cross-Sectional Study.Front. Aging Neurosci.202112January61349810.3389/fnagi.2020.61349833536895
    [Google Scholar]
  282. LibienJ. KupersmithM.J. BlanerW. McDermottM.P. GaoS. LiuY. CorbettJ. WallM. Role of vitamin A metabolism in IIH: Results from the idiopathic intracranial hypertension treatment trial.J. Neurol. Sci.2017372788410.1016/j.jns.2016.11.01428017254
    [Google Scholar]
  283. ConawayH.H. HenningP. LernerU.H. Vitamin a metabolism, action, and role in skeletal homeostasis.Endocr. Rev.201334676679710.1210/er.2012‑107123720297
    [Google Scholar]
  284. D’AmbrosioD.N. ClugstonR.D. BlanerW.S. VitaminA. Vitamin A metabolism: an update.Nutrients2011316310310.3390/nu301006321350678
    [Google Scholar]
  285. MinK.B. MinJ.Y. Relation of serum vitamin A levels to all- cause and cause-specific mortality among older adults in the NHANES III population.Nutr. Metab. Cardiovasc. Dis.201424111197120310.1016/j.numecd.2014.06.00425149896
    [Google Scholar]
  286. SatoY. MellerR. YangT. TakiW. SimonR.P. Stereo-selective neuroprotection against stroke with vitamin A derivatives.Brain Res.2008124118819210.1016/j.brainres.2008.09.02018824156
    [Google Scholar]
  287. RistP.M. JiménezM.C. TworogerS.S. HuF.B. MansonJ.E. SunQ. RexrodeK.M. Plasma Retinol-Binding Protein 4 Levels and the Risk of Ischemic Stroke among Women.J. Stroke Cerebrovasc. Dis.2018271687510.1016/j.jstrokecerebrovasdis.2017.08.00328888344
    [Google Scholar]
  288. CichonN. Saluk-BijakJ. MillerE. GorniakL. RedlickaJ. NiwaldM. BijakM. The Role of Supplementation with Natural Compounds in Post-Stroke Patients.Int. J. Mol. Sci.20212215789310.3390/ijms2215789334360658
    [Google Scholar]
  289. KadriA. SjahrirH. Juwita SembiringR. IchwanM. Combination of vitamin A and D supplementation for ischemic stroke: effects on interleukin-1ß and clinical outcome.Med. Glas.202017242543210.17392/1137‑2032567290
    [Google Scholar]
  290. SultanaA. RahmanK. HeyatM.B.B. AkhtarF. MuaadAY. ., Sumbul. Role of inflammation, oxidative stress, and mitochondrial changes in premenstrual psychosomatic behavioral symptoms with anti-inflammatory, antioxidant herbs, and nutritional supplements.Oxid Med Cell Longev.20222022359924610.1155/2022/3599246.
    [Google Scholar]
  291. da SilvaG.B. YamauchiM.A. BagatiniM.D. Oxidative Stress in Hashimoto’s Thyroiditis: Possible Adjuvant Therapies to Attenuate Deleterious Effects.Mol. Cell. Biochem.202211836168075
    [Google Scholar]
  292. Herranz-LópezM. Olivares-VicenteM. EncinarJ. Barrajón- CatalánE. Segura-CarreteroA. JovenJ. MicolV. Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.Nutrients20179890710.3390/nu908090728825642
    [Google Scholar]
  293. ShenM. ZhengY. LiG. ChenY. HuangL. WuJ. HongC. Dual Antioxidant DH-217 Mitigated Cerebral Ischemia–Reperfusion Injury by Targeting IKKβ/Nrf2/HO-1 Signal Axis.Neurochem. Res.2022112
    [Google Scholar]
  294. BrouwerI.A. van DusseldorpM. WestC.E. MeyboomS. ThomasC.M.G. DuranM. van het HofK.H. EskesT.K.A.B. HautvastJ.G.A.J. Steegers-TheunissenR.P.M. Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial.J. Nutr.199912961135113910.1093/jn/129.6.113510356077
    [Google Scholar]
  295. Homocysteine Lowering Trialists’ CollaborationDose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials.Am. J. Clin. Nutr.200582480681210.1093/ajcn/82.4.80616210710
    [Google Scholar]
  296. Homocysteine Lowering with Folic Acid and B Vitamins in Vascular DiseaseHomocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease.N. Engl. J. Med.2006354151567157710.1056/NEJMoa06090016531613
    [Google Scholar]
  297. KennedyD. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review.Nutrients2016826810.3390/nu802006826828517
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266316939240909070627
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  • Article Type:
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Keyword(s): Ischemic; Multitarget; Prevention; Risk; Stroke; Vitamins
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