American Heart Journal
Volume 148, Issue 3 , Page 517 , September 2004

Effects of multivitamins and low-dose folic acid supplements on flow-mediated vasodilation and plasma homocysteine levels in older adults

  • Cynthia M. Carlsson, MD

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA
    • Corresponding Author InformationReprint requests: Cynthia M. Carlsson, MD, VA GRECC, 2500 Overlook Terrace, Madison, WI 53705, USA.
    • ,
  • Lisa M. Pharo, RN, BSN

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA
    • ,
  • Susan E. Aeschlimann, RVT

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA
    • ,
  • Carol Mitchell, PhD, RVT

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA
    • ,
  • Gail Underbakke, RD, MS

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA
    • ,
  • James H. Stein, MD, FACC

      Affiliations

    • Sections of Cardiovascular Medicine and Geriatrics and Gerontology, University of Wisconsin Medical School, and the Veterans Affairs Geriatrics Research, Education, and Clinical Center (GRECC), Madison, Wis, USA

Received 15 September 2003 ,Accepted 11 January 2004.

References 

  1. Celermajer DS, Sorensen KE, Spiegelhalter DJ, et al.  Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J Am Coll Cardiol. 1994;24:471–476
  2. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev. 1993;73:413–467
  3. Lakatta EG, Levy D. Arterial and cardiac aging (major shareholders in cardiovascular disease enterprises, I: aging arteries: a “set up” for vascular disease). Circulation. 2003;107:139–146
  4. Selhub J, Jacques PF, Wilson PW, et al.  Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993;270:2693–2698
  5. Bostom AG, Silbershatz H, Rosenberg IH, et al.  Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999;159:1077–1080
  6. Aronow WS, Ahn C. Association between plasma homocysteine and coronary artery disease in older persons. Am J Cardiol. 1997;80:1216–1218
  7. Tawakol A, Omland T, Gerhard M, et al.  Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation. 1997;95:1119–1121
  8. Woo KS, Chook P, Lolin YI, et al.  Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation. 1997;96:2542–2544
  9. Tsai JC, Perrella MA, Yoshizumi M, et al.  Promotion of vascular smooth muscle cell growth by homocysteine (a link to atherosclerosis). Proc Natl Acad Sci U S A. 1994;91:6369–6373
  10. McKay DL, Perrone G, Rasmussen H, et al.  Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. J Nutr. 2000;130:3090–3096
  11. McKinley MC, McNulty H, McPartlin J, et al.  Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr. 2001;73:759–764
  12. Rydlewicz A, Simpson JA, Taylor RJ, et al.  The effect of folic acid supplementation on plasma homocysteine in an elderly population. QJM. 2002;95:27–35
  13. Henning BF, Tepel M, Riezler R, et al.  Long-term effects of vitamin B(12), folate, and vitamin B(6) supplements in elderly people with normal serum vitamin B(12) concentrations. Gerontology. 2001;47:30–35
  14. Woo KS, Chook P, Lolin YI, et al.  Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol. 1999;34:2002–2006
  15. Bellamy MF, McDowell IF, Ramsey MW, et al.  Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest. 1999;29:659–662
  16. Title LM, Cummings PM, Giddens K, et al.  Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol. 2000;36:758–765
  17. Chambers JC, Ueland PM, Obeid OA, et al.  Improved vascular endothelial function after oral B vitamins (an effect mediated through reduced concentrations of free plasma homocysteine). Circulation. 2000;102:2479–2483
  18. Doshi SN, Naka KK, Payne N, et al.  Flow-mediated dilatation following wrist and upper arm occlusion in humans (the contribution of nitric oxide). Clin Sci (Lond). 2001;101:629–635
  19. Woo KS, Chook P, Chan LL, et al.  Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med. 2002;112:535–539
  20. Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2002;22:6–13
  21. Neunteufl T, Heher S, Katzenschlager R, et al.  Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol. 2000;86:207–210
  22. Homocysteine Lowering Trialists' Collaboration . Lowering blood homocysteine with folic acid based supplements (meta-analysis of randomised trials). BMJ. 1998;316:894–898
  23. Murua AL, Quintana I, Janson J, et al.  Plasmatic homocysteine response to vitamin supplementation in elderly people. Thromb Res. 2000;100:495–500
  24. Thambyrajah J, Landray MJ, Jones HJ, et al.  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;37:1858–1863
  25. 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;38:1799–1805
  26. 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;105:22–26
  27. Ueland PM, Refsum H, Stabler SP, et al.  Total homocysteine in plasma or serum (methods and clinical applications). Clin Chem. 1993;39:1764–1779
  28. Ubbink JB, Hayward Vermaak WJ, Bissbort S. Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr. 1991;565:441–446
  29. Fortin LJ, Genest J. Measurement of homocyst(e)ine in the prediction of arteriosclerosis. Clin Biochem. 1995;28:155–162
  30. Stein JH, Keevil JG, Wiebe DA, et al.  Purple grape juice improves endothelial function and reduces the susceptibility of LDL cholesterol to oxidation in patients with coronary artery disease. Circulation. 1999;100:1050–1055
  31. Stein JH, Carlsson CM, Papcke-Benson K, et al.  The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol. 2001;38:1806–1813
  32. Sorensen KE, Celermajer DS, Spiegelhalter DJ, et al.  Non-invasive measurement of human endothelium dependent arterial responses (accuracy and reproducibility). Br Heart J. 1995;74:247–253
  33. Egashira K, Hirooka Y, Kai H, et al.  Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia. Circulation. 1994;89:2519–2524
  34. Treasure CB, Klein JL, Weintraub WS, et al.  Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487
  35. O'Driscoll G, Green D, Taylor RR. Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation. 1997;95:1126–1131
  36. Lind L, Sarabi M, Millgard J, et al.  Endothelium-dependent vasodilation and structural and functional changes in the cardiovascular system are dependent on age in healthy subjects. Clin Physiol. 1999;19:400–409
  37. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 2002;360:7–22
  38. Shepherd J, Blauw GJ, Murphy MB, et al.  Pravastatin in elderly individuals at risk of vascular disease (PROSPER) (a randomised controlled trial). Lancet. 2002;360:1623–1630
  39. Carlsson CM, Pharo LM, Stein JH. Effect of folic acid fortification of cereal grain flour on the prevalence of hyperhomocysteinemia in older adults. J Am Geriatr Soc. 2002;50:S135
  40. Jacques PF, Selhub J, Bostom AG, et al.  The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340:1449–1454
  41. American Heart Association . Heart Disease and Stroke Statistics, 2003 Update. Dallas, Tex: American Heart Association; 2002;
  42. 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;106(Suppl II):II–741
  43. Lange H, Suryapranata H, DeLuca G. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med; 2004; 350:2673–81
  44. Schnyder G, Roffi M, Pin R, et al.  Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med. 2001;345:1593–1600
  45. Schnyder G, Roffi M, Flammer Y, et al.  Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention (the Swiss Heart Study: a randomized controlled trial). JAMA. 2002;288:973–979
  46. Jacques PF, Bostom AG, Williams RR, et al.  Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996;93:7–9
  47. Clark ZE, Bowen DJ, Whatley SD, et al.  Genotyping method for methylenetetrahydrofolate reductase (C677T thermolabile variant) using heteroduplex technology. Clin Chem. 1998;44:2360–2362
  48. Basu TK, Makhani N, Sedgwick G. Niacin (nicotinic acid) in non-physiological doses causes hyperhomocysteineaemia in Sprague-Dawley rats. Br J Nutr. 2002;87:115–119
  49. Kuvin JT, Ramet ME, Patel AR, et al.  A novel mechanism for the beneficial vascular effects of high-density lipoprotein cholesterol (enhanced vasorelaxation and increased endothelial nitric oxide synthase expression). Am Heart J. 2002;144:165–172
  50. Taddei S, Virdis A, Ghiadoni L, et al.  Effects of antihypertensive drugs on endothelial dysfunction (clinical implications). Drugs. 2002;62:265–284

☆ Supported by the John A. Hartford Foundation/American Federation for Aging Research (AFAR) Academic Geriatrics Fellowship Program. Dr Carlsson also was funded by the Veterans Affairs Special Fellowships Program in Health Issues of Women Veterans and the National Institute on Aging (K12 AG19247). Dr Stein was funded by the National Center for Research Resources (K23 RR16176-01).

PII: S0002-8703(04)00163-2

doi: 10.1016/j.ahj.2004.01.023

American Heart Journal
Volume 148, Issue 3 , Page 517 , September 2004

Article Tools

* Image Usage & Resolution