Folic acid improves vascular reactivity in humans: A meta-analysis of randomized controlled trials

American Journal of Clinical Nutrition

Volumn 86, Issue 3, 2007, Pages 610-617

  De Bree, Angelika ^a   Van Mierlo, Linda A ^a   Draijer, Richard ^a  

^a UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

Author keywords

Endothelial function; Flow mediated dilatation; FMD; Folic acid; Homocysteine; Meta analysis; Randomized trial

Indexed keywords

FOLIC ACID; PLACEBO;

ADULT; AGED; ARTICLE; BLOOD VESSEL REACTIVITY; CALCULATION; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; CONFIDENCE INTERVAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DATA EXTRACTION; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; ENDOTHELIUM; EVALUATION; FEMALE; FLOW MEDIATED DILATATION; HUMAN; MALE; MEDLINE; META ANALYSIS; OUTCOME ASSESSMENT; POST HOC ANALYSIS; PUBLISHING; RANDOMIZED CONTROLLED TRIAL; RISK REDUCTION; STATISTICAL SIGNIFICANCE; SYSTEMATIC REVIEW; TECHNIQUE;

EID: 34548707938     PISSN: 00029165     EISSN: None     Source Type: Journal    
DOI: 10.1093/ajcn/86.3.610     Document Type: Article

References (67)

1. The Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002;288:2015-22.
2. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 2002;325:1202.
3. Clarke R. Homocysteine-lowering trials for prevention of heart disease and stroke. Semin Vasc Med 2005;5:215-22.
4. Homocysteine Lowering Trialists' Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 2005;82:806-12.
5. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006;354:1578-88.
6. Toole JF, Malinow MR, Chambless LE 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;291:565-75.
7. The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77.
8. Baker F, Picton D, Blackwood S, et al. Blinded comparison of folic acid and placebo in patients with ischemic heart disease: an outcome trial. Circulation 2002;19:3642 (abstr).
9. Clarke R. Homocysteine, B vitamins, and the risk of dementia. Am J Clin Nutr 2007;85:329-30.
10. Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation 2006;113:1335-43.
11. Moat SJ, Lang D, McDowell IF, et al. Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem 2004;15:64-79.
12. Bots ML, Westerink J, Rabelink TJ, de Koning EJ. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J 2005;26:363-8.
13. Moher D, Cook DJ, Eastwood S, Olkin I, Rennie D, Stroup DF. Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of reporting of meta-analyses. Lancet 1999;354:1896-900.
14. Chao CL, Chien KL, Lee YT. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia. Am J Cardiol 1999;84:1359-61.
15. Guo H, Lee JD, Xing Y, et al. Changes of homocysteine levels and arterial endothelial function in patients with high risk of coronary artery disease after 6-month folic acid supplementation. Acta Cardiol 2004;59:503-6.
16. Usui M, Matsuoka H, Miyazaki H, Ueda S, Okuda S, Imaizumi T. Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clin Sci Colch 1999;96:235-9.
17. Dinckal MH, Aksoy N, Aksoy M, et al. Effect of homocysteine-lowering therapy on vascular endothelial function and exercise performance in coronary patients with hyperhomocysteinaemia. Acta Cardiol 2003;58:389-96.
18. Woodman RJ, Celermajer DE, Thompson PL, Hung J. Folic acid does not improve endothelial function in healthy hyperhomocysteinaemic subjects. Clin Sci (Lond) 2004;106:353-8.
19. Bellamy MF, McDowell IF, Ramsey MW, Brownlee M, Newcombe RG, Lewis MJ. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999;29:659-62.
20. Woo KS, Chook P, Lolin YI, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol 1999;34:2002-6.
21. Title LM, Cummings PM, Giddens K, Genest JJ Jr, Nassar BA. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000;36:758-65.
22. Chambers JC, Ueland PM, Obeid OA, Wrigley J, Refsum H, Kooner JS. Improved vascular endothelial function after oral B vitamins: an effect mediated through reduced concentrations of free plasma homocysteine. Circulation 2000;102:2479-83.
23. Thambyrajah J, Landray MJ, Jones HJ, McGlynn FJ, Wheeler DC, Townend JN. A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease. J Am Coll Cardiol 2001;37:1858-63.
24. Pullin CH, Ashfield-Watt PA, Burr ML, et al. Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype. J Am Coll Cardiol 2001;38:1799-805.
25. van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD. 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;21:2072-9.
26. Doshi SN, McDowell IF, Moat SJ, et al. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol 2001;21:1196-202.
27. Sydow K, Schwedhelm E, Arakawa N, et al. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: effects of L-arginine and B vitamins. Cardiovasc Res 2003;57:244-52.
28. Doshi SN, McDowell IF, Moat SJ, et al. Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation 2002;105:22-6.
29. Hirsch S, Pia DlM, Yanez P, et al. Hyperhomocysteinemia and endothelial function in young subjects: effects of vitamin supplementation. Clin Cardiol 2002;25:495-501.
30. Lekakis JP, Papamichael CM, Papaioannou TG, et al. Oral folic acid enhances endothelial function in patients with hypercholesterolaemia receiving statins. Eur J Cardiovasc Prev Rehabil 2004;11:416-20.
31. Olthof MR, Bots ML, Katan MB, Verhoef P. Effect of folic acid and betaine supplementation on flow-mediated dilation: a randomized, controlled study in healthy volunteers. PLoS Clin Trials 2006;1:e10.
32. Verhagen AP, de Vet HC, de Bie RA. et al. The Delphi list: a criteria list for quality assessment of randomized clinical trials for conducting systematic reviews developed by Delphi consensus. J Clin Epidemiol 1998;51:1235-41.
33. Gunter EW, Bowman BA, Caudill SP, Twite DB, Adams MJ, Sampson EJ. Results of an international round robin for serum and whole-blood folate. Clin Chem 1996;42:1689-94.
34. de Bree A, Verschuren WMM, Blom HJ, De Graaf-Hess A, Trijbels FJM, Kromhout D. The homocysteine distribution: (mis)judging the burden. J Clin Epidemiol 2001;54:462-9.
35. de Bree A, Verschuren WM, Bjorke-Monsen AL, et al. Effect of the methylenetetrahydrofolate reductase 677C→T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr 2003;77:687-93.
36. van Asselt DZB, de Groot LCPGM, van Staveren WA, et al. Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects. Am J Clin Nutr 1998;68:328-34.
37. Brussaard JH, Lowik MRH, vandenBerg H, Brants HAM, Goldbohm RA. Folate intake and status among adults in the Netherlands. Eur J Clin Nutr 1997;51(suppl):S46-50.
38. Follmann D, Elliott P, Suh I, Cutler J. Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 1992;45:769-73.
39. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.
40. van Houwelingen HC, Arends LR, Stijnen T. Advanced methods in meta-analysis: multivariate approach and meta-regression. Stat Med 2002;21:589-624.
41. Egger M, Davey SG, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.
42. Mangoni AA, Sherwood RA, Swift CG, Jackson SH. Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial. J Intern Med 2002;252:497-503.
43. Mangoni AA, Sherwood RA, Asonganyi B, Swift CG, Thomas S, Jackson SH. Short-term oral folic acid supplementation enhances endothelial function in patients with type 2 diabetes. Am J Hypertens 2005;18:220-6.
44. Gori T, Burstein JM, Ahmed S et al. Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study. Circulation 2001;104:1119-23.
45. Setola E, Monti LD, Galluccio E, et al. Insulin resistance and endothelial function are improved after folate and vitamin B12 therapy in patients with metabolic syndrome: relationship between homocysteine levels and hyperinsulinemia. Eur J Endocrinol 2004;151:483-9.
46. Willems FF, Aengevaeren WR, Boers GH, Blom HJ, Verheugt FW. Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease. J Am Coll Cardiol 2002;40:766-72.
47. Wilmink HW, Stroes ES, Erkelens WD, et al. Influence of folic acid on postprandial endothelial dysfunction. Arterioscler Thromb Vasc Biol 2000;20:185-8.
48. Verhaar MC, Wever RM, Kastelein JJ, van Dam T, Koomans HA, Rabelink TJ. 5-Methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 1998;97:237-41.
49. Verhaar MC, Wever RM, Kastelein JJ, et al. Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial. Circulation 1999;100:335-8.
50. Chia S, Wilson R, Ludlam CA, Webb DJ, Flapan AD, Newby DE. Endothelial dysfunction in patients with recent myocardial infarction and hyperhomocysteinaemia: effects of vitamin supplementation. Clin Sci (Lond) 2005;108:65-72.
51. Tawakol A, Migrino RQ, Aziz KS et al. High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease. J Am Coll Cardiol 2005;45:1580-4.
52. Brown AA, Hu FB. Dietary modulation of endothelial function: implications for cardiovascular disease. Am J Clin Nutr 2001;73:673-86.
53. Schachinger V, Britten MB, Zeiher AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899-906.
54. Antoniades C, Shirodaria C, Warrick N, et al. 5-Methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling. Circulation 2006;114:1193-201.
55. Halcox JP, Schenke WH, Zalos G, et al. Prognostic value of coronary vascular endothelial dysfunction. Circulation 2002;106:653-8.
56. Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Holmes DR Jr, Lerman A. Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 2000;101:948-54.
57. Gokce N, Keaney JF Jr, Hunter LM, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol 2003;41:1769-75.
58. Lind L, Fors N, Hall J, Marttala K, Stenborg A. A comparison of three different methods to evaluate endothelium-dependent vasodilation in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Arterioscler Thromb Vasc Biol 2005;25:2368-75.
59. Thambyrajah J, Townend JN. Homocysteine and atherothrombosis - mechanisms for injury. Eur Heart J 2000;21:967-74.
60. Jia L, Furchgott RF. Inhibition by sulfhydryl compounds of vascular relaxation induced by nitric oxide and endothelium-derived relaxing factor. J Pharmacol Exp Ther 1993;267:371-8.
61. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest 1996;98:5-7.
62. Upchurch GR Jr, Welch GN, Fabian AJ, et al. Homocyst(e)ine decreases bioavailable nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997;272:17012-7.
63. Stamler JS, Osborne JA, Jaraki O, et al. Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen. J Clin Invest 1993;91:308-18.
64. Upchurch GR Jr, Welch GN, Loscalzo J. Homocysteine, EDRF, and endothelial function. J Nutr 1996;126(suppl):1290S-4S.
65. Stuhlinger MC, Tsao PS, Her JH, Kimoto M, Balint RF, Cooke JP. Homocysteine impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine. Circulation 2001;104:2569-75.
66. Boger RH, Lentz SR, Bode-Boger SM, Knapp HR, Haynes WG. Elevation of asymmetrical dimethylarginine may mediate endothelial dysfunction during experimental hyperhomocyst(e)inaemia in humans. Clin Sci (Lond) 2001;100:161-7.
67. Stroes ES, van Faassen EE, Yo M, et al. Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res 2000;86:1129-34.