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Stroke prevention - B vitamins

Published online by Cambridge University Press:  11 September 2013

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In a nutshell

The association between elevated Hcy, the B vitamins linked to it, and stroke incidence and severity appears strong.

So far, a dozen RCTs, (almost all in patients with significant atherosclerosis), have tried to prevent stroke by reducing Hcy through various combinations of folate, B12 and B6. In only one trial did this clearly succeed.

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Brief Report
Information
Arbor Clinical Nutrition Updates , Volume 318 , March 2010 , pp. 1 - 5
Copyright
Copyright © Cambridge University Press 2010

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References

References:

1. Sánchez-Moreno, C. et al. Stroke: roles of B vitamins, homocysteine and antioxidants. Nutr Res Rev. 2009 Jun;22(1):49–67.Google Scholar
2. McNulty, H. et al. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008 May;67(2):232–7.Google Scholar
3. McNulty, H. et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006 Jan 3;113(1):74–80.Google Scholar
4. Narang, AP. et al. Homocysteine--risk factor for ischemic stroke? Indian J Physiol Pharmacol. 2009 Jan-Mar;53(1):34–8.Google Scholar
5. Dhamija, RK. et al. Homocysteine and lipoprotein (a) correlation in ischemic stroke patients. J Neurol Sci. 2009 Jun 15;281(1–2):64–8.CrossRefGoogle ScholarPubMed
6. Khan, U. et al. Homocysteine and its relationship to stroke subtypes in a UK black population: the south London ethnicity and stroke study. Stroke. 2008 Nov;39(11):2943–9.Google Scholar
7. Yang, LK. et al. Correlations between folate, B12, homocysteine levels, and radiological markers of neuropathology in elderly post-stroke patients. J Am Coll Nutr. 2007 Jun;26(3):272–8.Google Scholar
8. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002 Oct 23-30;288(16):2015–22.Google Scholar
9. Wald, DS. et al. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002 Nov 23;325(7374):1202.Google Scholar
10. Kelly, PJ. et al. Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology. 2002 Aug 27;59(4):529–36.Google Scholar
11. Weng, LC. et al. Is ischemic stroke risk related to folate status or other nutrients correlated with folate intake? Stroke. 2008 Dec;39(12):3152–8.Google Scholar
12. Larsson, SC. et al. Folate, vitamin B6, vitamin B12, and methionine intakes and risk of stroke subtypes in male smokers. Am J Epidemiol. 2008 Apr 15;167(8):954–61.Google Scholar
13. Weikert, C. et al. B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort. Stroke. 2007 Nov;38(11):2912–8.Google Scholar
14. Van Guelpen, B. et al. Folate, vitamin B12, and risk of ischemic and hemorrhagic stroke: a prospective, nested case-referent study of plasma concentrations and dietary intake. Stroke. 2005 Jul;36(7):1426–31.Google Scholar
15. Pieters, B. et al. Periventricular white matter lucencies relate to low vitamin B12 levels in patients with small vessel stroke. Stroke. 2009 May;40(5):1623–6.Google Scholar
16. He, K. et al. Folate, vitamin B6, and B12 intakes in relation to risk of stroke among men. Stroke. 2004 Jan;35(1):169–74.Google Scholar
17. Kelly, PJ. et al. Inflammation, homocysteine, and vitamin B6 status after ischemic stroke. Stroke. 2004 Jan;35(1):12–5.Google Scholar
18. Robinson, K. et al. Low circulating folate and vitamin B6 concentrations: risk factors for stroke, peripheral vascular disease, and coronary artery disease. European COMAC Group. Circulation. 1998 Feb 10;97(5):437–43.Google Scholar
19. Gariballa, S. et al. Riboflavin status in acute ischaemic stroke. Eur J Clin Nutr. 2007 Oct;61(10):1237–40.Google Scholar
20. Ross, RK. et al. Prospective evaluation of dietary and other predictors of fatal stroke in Shanghai, China. Circulation. 1997 Jul 1;96(1):50–5.CrossRefGoogle ScholarPubMed
21. Biswas, A. et al. Homocystine levels, polymorphisms and the risk of ischemic stroke in young Asian Indians. J Stroke Cerebrovasc Dis. 2009 Mar-Apr;18(2):103–10.CrossRefGoogle ScholarPubMed
22. Sánchez-Marín, B. et al. [Prevalence of methylenetetrahydrofolate reductase C677T mutation among patients with acute ischemic cerebrovascular disease in Aragon] An Med Interna. 2006 Apr;23(4):153–5.Google ScholarPubMed
23. Panigrahi, I. et al. Role of MTHFR C677T polymorphism in ischemic stroke. Neurol India. 2006 Mar;54(1):48–50.Google Scholar
24. Cantu, C. et al. Hyperhomocysteinemia, low folate and vitamin B12 concentrations, and methylene tetrahydrofolate reductase mutation in cerebral venous thrombosis. Stroke. 2004 Aug;35(8):1790–4.Google Scholar
25. Lim, PS. et al. Polymorphism in methylenetetrahydrofolate reductase gene: its impact on plasma homocysteine levels and carotid atherosclerosis in ESRD patients receiving hemodialysis. Nephron. 2001 Mar;87(3):249–56.Google Scholar
26. Demuth, K. et al. Opposite effects of plasma homocysteine and the methylenetetrahydrofolate reductase C677T mutation on carotid artery geometry in asymptomatic adults. Arterioscler Thromb Vasc Biol. 1998 Dec;18(12):1838–43.Google Scholar
27. Ho, GY. et al. Methylenetetrahydrofolate reductase polymorphisms and homocysteine-lowering effect of vitamin therapy in Singaporean stroke patients. Stroke. 2006 Feb;37(2):456–60.Google Scholar
28. Terwecoren, A. et al. Ischemic stroke and hyperhomocysteinemia: truth or myth? Acta Neurol Belg. 2009 Sep;109(3):181–8.Google Scholar
29. Pezzini, A. et al. Homocysteine and cerebral ischemia: pathogenic and therapeutical implications. Curr Med Chem. 2007;14(3):249–63.Google Scholar
30. Hankey, GJ. et al. Clinical usefulness of plasma homocysteine in vascular disease. Med J Aust. 2004 Sep 20;181(6):314–8.Google Scholar
31. Stanger, O. et al. DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med. 2003 Nov;41(11):1392–403.Google Scholar
32. Herrmann, W. et al. Hyperhomocysteinaemia: a critical review of old and new aspects. Curr Drug Metab. 2007 Jan;8(1):17–31.Google Scholar
33. Ntaios, GC. et al. Vitamins and stroke: the homocysteine hypothesis still in doubt. Neurologist. 2008 Jan;14(1):2–4.Google Scholar
34. Lonn, E. Homocysteine in the prevention of ischemic heart disease, stroke and venous thromboembolism: therapeutic target or just another distraction? Curr Opin Hematol. 2007 Sep;14(5):481–7.Google Scholar
35. Wierzbicki, AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007 Jun;4(2):143–50.Google Scholar
36. Osanai, T. et al. Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine. Ann Med. 2010;42(1):79–86.Google Scholar
37. Kumar, M. et al. Homocysteine decreases blood flow to the brain due to vascular resistance in carotid artery. Neurochem Int. 2008 Dec;53(6–8):214–9.Google Scholar
38. Stanger, O. et al. Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases. Z Kardiol. 2004 Jun;93(6):439–53.Google Scholar
39. Guilland, JC. et al. [Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease?. 1. Basic data] Pathol Biol (Paris). 2003 Mar;51(2):101–10.Google Scholar
40. Baptista, AP. et al. Inflammation, homocysteine and carotid intima-media thickness. Rev Port Cardiol. 2008 Jan;27(1):39–48.Google Scholar
41. Sabaliauskene, Z. et al. [Hyperhomocysteinemia in patients with atherosclerotic extracranial disease of the carotid artery] Klin Lab Diagn. 2006 Jun;(6):20–2, 35.Google Scholar
42. Wang, H. et al. Serum level of homocysteine is correlated to carotid artery atherosclerosis in Chinese with ischemic stroke. Neurol Res. 2006 Jan;28(1):25–30.Google Scholar
43. Silvestrini, M. et al. Carotid wall thickness and stroke risk in patients with asymptomatic internal carotid stenosis. Atherosclerosis. 2010 Jan 4. Epub.Google Scholar
44. Cobble, M. et al. Carotid intima-media thickness: knowledge and application to everyday practice. Postgrad Med. 2010 Jan;122(1):10–8.Google Scholar
45. Sahoo, R. et al. Common carotid intima-media thickness in acute ischemic stroke: A case control study. Neurol India. 2009 Sep-Oct;57(5):627–30.Google Scholar
46. Ntaios, G. et al. Homocysteine and carotid intima-media thickness in ischemic stroke patients are not correlated. Neuropsychiatr Dis Treat. 2008 Apr;4(2):477–9.Google Scholar
47. Held, C. et al. Correlations between plasma homocysteine and folate concentrations and carotid atherosclerosis in high-risk individuals: baseline data from the Homocysteine and Atherosclerosis Reduction Trial (HART). Vasc Med. 2008 Nov;13(4):245–53.Google Scholar
48. Nanayakkara, PW. et al. Effect of a treatment strategy consisting of pravastatin, vitamin E, and homocysteine lowering on carotid intima-media thickness, endothelial function, and renal function in patients with mild to moderate chronic kidney disease: results from the Anti-Oxidant Therapy in Chronic Renal Insufficiency (ATIC) Study. Arch Intern Med. 2007 Jun 25;167(12):1262–70.CrossRefGoogle ScholarPubMed
49. Fernández-Miranda, C. et al. Effect of folic acid treatment on carotid intima-media thickness of patients with coronary disease. Int J Cardiol. 2007 Jun 12;118(3):345–9.Google Scholar
50. Hodis, HN. et al. High-dose B vitamin supplementation and progression of subclinical atherosclerosis: a randomized controlled trial. Stroke. 2009 Mar;40(3):730–6.Google Scholar
51. Vianna, AC. et al. Uremic hyperhomocysteinemia: a randomized trial of folate treatment for the prevention of cardiovascular events. Hemodial Int. 2007 Apr;11(2):210–6.Google Scholar
52. Tungkasereerak, P. et al. Effect of short-term folate and vitamin B supplementation on blood homocysteine level and carotid artery wall thickness in chronic hemodialysis patients. J Med Assoc Thai. 2006 Aug;89(8):1187–93.Google ScholarPubMed
53. Till, U. et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, Vitamins B6 and B12. Atherosclerosis. 2005 Jul;181(1):131–5.Google Scholar
54. van Dijk, RA. et al. Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2072–9.Google Scholar
55. Alam, MM. et al. Homocysteine reduces endothelial progenitor cells in stroke patients through apoptosis. J Cereb Blood Flow Metab. 2009 Jan;29(1):157–65.Google Scholar
56. Hwang, IK. et al. Folic acid deficiency increases delayed neuronal death, DNA damage, platelet endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the hippocampus after transient cerebral ischemia. J Neurosci Res. 2008 Jul;86(9):2003–15.Google Scholar
57. Huang, GW. et al. [Effects of folic acid, vitamin B(6) and vitamin B(12) on learning and memory function in cerebral ischemia rats] Zhonghua Yu Fang Yi Xue Za Zhi. 2007 May;41(3):212–4.Google Scholar
58. Doshi, SN. et al. Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation. 2002 Jan 1;105(1):22–6.CrossRefGoogle ScholarPubMed
59. Hoane, MR. et al. Administration of riboflavin improves behavioral outcome and reduces edema formation and glial fibrillary acidic protein expression after traumatic brain injury. J Neurotrauma. 2005 Oct;22(10):1112–22.Google Scholar
60. Ebbing, M. et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008 Aug 20;300(7):795–804.Google Scholar
61. Albert, CM. et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008 May 7;299(17):2027–36.Google Scholar
62. Bønaa, KH. et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13;354(15):1578–88.Google Scholar
63. Lonn, E. et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006 Apr 13;354(15):1567–77.Google Scholar
64. Zoungas, S. et al. Cardiovascular morbidity and mortality in the Atherosclerosis and Folic Acid Supplementation Trial (ASFAST) in chronic renal failure: a multicenter, randomized, controlled trial. J Am Coll Cardiol. 2006 Mar 21;47(6):1108–16.Google Scholar
65. Righetti, M. et al. Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients. Blood Purif. 2006;24(4):379–86.Google Scholar
66. Spence, JD. et al. Vitamin Intervention For Stroke Prevention trial: an efficacy analysis. Stroke. 2005 Nov;36(11):2404–9.CrossRefGoogle ScholarPubMed
67. Toole, JF. et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004 Feb 4;291(5):565–75.CrossRefGoogle ScholarPubMed
68. Liem, A. et al. Secondary prevention with folic acid: results of the Goes extension study. Heart. 2005 Sep;91(9):1213–4.Google Scholar
69. Liem, AH. et al. Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial. Int J Cardiol. 2004 Feb;93(2–3):175–9.Google Scholar
70. Wrone, EM. et al. Randomized trial of folic acid for prevention of cardiovascular events in end-stage renal disease. J Am Soc Nephrol. 2004 Feb;15(2):420–6.Google Scholar
71. Mark, SD. et al. Lowered risks of hypertension and cerebrovascular disease after vitamin/mineral supplementation: the Linxian Nutrition Intervention Trial. Am J Epidemiol. 1996 Apr 1;143(7):658–64.Google Scholar
72. Martí-Carvajal, AJ. et al. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD006612.Google Scholar
73. Bazzano, LA. et al. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006 Dec 13;296(22):2720–6.Google Scholar
74. Wang, X. et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007 Jun 2;369(9576):1876–82.Google Scholar
75. SEARCH Study Collaborative Group. et al. Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors. Am Heart J. 2007 Nov;154(5):815-23, 823.Google Scholar
76. Amritage, J. et al. SEARCH Study Collaborative Group. SEARCH (Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine): randomized comparison of folic acid 2 mg plus vitamin b12 1 mg daily versus placebo for 7 years in 12,064 myocardial infarction survivors. Circulation 2008 Nov;118(22);2309–2317.Google Scholar
77. Marcus, J. et al. Homocysteine lowering and cardiovascular disease risk: lost in translation. Can J Cardiol. 2007 Jul;23(9):707–10.Google Scholar
78. Pietrzik, K. Opinion on the COCHRANE Review ‘’Homocysteine-lowering interventions for preventing cardiovascular events. European Nutraceutical Association website at: http://www.enaonline.org Google Scholar
79. Spence, JD. Perspective on the efficacy analysis of the Vitamin Intervention for Stroke Prevention trial. Clin Chem Lab Med. 2007;45(12):1582–5.CrossRefGoogle ScholarPubMed
80. Ueland, PM. et al. Homocysteine and folate status in an era of folic acid fortification: balancing benefits, risks, and B-vitamins. Clin Chem. 2008 May;54(5):779–81.Google Scholar
81. Wald, DS. et al. Folic acid, homocysteine, and cardiovascular disease: judging causality in the face of inconclusive trial evidence. BMJ. 2006 Nov 25;333(7578):1114–7.Google Scholar
82. Nainggolan, L. Folic acid modestly protects against cardiovascular events Heartwire 2006 reproduced in Medscape web site www.medscape.com.Google Scholar
83. Bazzano, LA. Folic acid supplementation and cardiovascular disease: the state of the art. Am J Med Sci. 2009 Jul;338(1):48–9.Google Scholar
84. Galan, P. et al. The SU.FOL.OM3 Study: a secondary prevention trial testing the impact of supplementation with folate and B-vitamins and/or Omega-3 PUFA on fatal and non fatal cardiovascular events, design, methods and participants characteristics. Trials. 2008 Jun 10;9:35.Google Scholar
85. VITATOPS Trial Study Group. et al. VITATOPS, the VITAmins TO prevent stroke trial: rationale and design of a randomised trial of B-vitamin therapy in patients with recent transient ischaemic attack or stroke (NCT00097669) (ISRCTN74743444). Int J Stroke. 2007 May;2(2):144–50.Google Scholar
86. Clarke, R. et al. Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis. Clin Chem Lab Med. 2007;45(12):1575–81.Google Scholar