Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

BMJ 1998;316:894-898 ( 21 March )

Papers

Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

Homocysteine Lowering Trialists' Collaboration.

Correspondence to: Dr Robert Clarke, Homocysteine Lowering Trialists' Collaboration, Clinical Trial Service Unit, Radcliffe Infirmary, Oxford OX2 6HE robert.clarke{at}ctsu.ox.ac.uk

Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation withfolic acid and with vitamins B-12 or B-6.
Design: Meta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements onblood homocysteine concentrations. Multivariate regression analysiswas used to determine the effects on homocysteine concentrationsof different doses of folic acid and of the addition of vitaminB-12 or B-6.
Subjects: Individual data on 1114 people included in 12 trials.
Findings: The proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greaterat higher pretreatment blood homocysteine concentrations (P<0.001)and at lower pretreatment blood folate concentrations (P<0.001).After standardisation to pretreatment blood concentrations ofhomocysteine of 12 µmol/l and of folate of 12 nmol/l (approximateaverage concentrations for Western populations), dietary folicacid reduced blood homocysteine concentrations by 25% (95% confidenceinterval 23% to 28%; P<0.001), with similar effects in the rangeof 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily)produced an additional 7% (3% to 10%) reduction in blood homocysteine.Vitamin B-6 (mean 16.5 mg daily) did not have a significant additionaleffect.
Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mgvitamin B-12 would be expected to reduce blood homocysteine concentrationsby about a quarter to a third (for example, from about 12 µmol/lto 8-9 µmol/l). Large scale randomised trials of such regimensin high risk populations are now needed to determine whether loweringblood homocysteine concentrations reduces the risk of vasculardisease.

Key messages

Higher blood homocysteine concentrations seem to be associated with higher risks of occlusive vascular disease and with lower blood concentrations of folate and vitamins B-12 and B-6
Proportional and absolute reductions in blood homocysteine concentrations with folic acid supplements are greater at higher pretreatment blood homocysteine concentrations and at lower pretreatment blood folate concentrations
In typical Western populations, supplementation with both 0.5-5 mg daily folic acid and about 0.5 mg daily vitamin B-12 should reduce blood homocysteine concentrations by about a quarter to a third
Large scale randomised trials of such regimens in people at high risk are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease

© BMJ 1998

CiteULike

Complore

Connotea

Del.icio.us Add to Digg

Digg

Technorati What's this?

Relevant Articles

Folic acid and birth malformations: C Bille, J C Murray, and S F Olsen
BMJ 2007 334: 433-434. [Extract] [Full Text] [PDF]

Meta-analysis of MTHFR 677C $->$ T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?: Sarah J Lewis, Shah Ebrahim, and George Davey Smith
BMJ 2005 331: 1053. [Abstract] [Full Text] [PDF]

Folic acid and vitamin B-12 and B-6 supplements reduce blood homocysteine concentrations
BMJ 1998 316: 0. [Full Text]

This article has been cited by other articles:

Cetin, I., Berti, C., Calabrese, S. (2009). Role of micronutrients in the periconceptional period. Hum Reprod Update 0: dmp025v1-dmp025 [Abstract] [Full text]
Kasiman, K., Eikelboom, J. W., Hankey, G. J., Lee, S. P.-K., Lim, J. P.-Z., Lee, J. H.-Q., Chang, H.-M., Wong, M.-C., Chen, C. P.L.-H. (2009). Ethnicity Does Not Affect the Homocysteine-Lowering Effect of B-Vitamin Therapy in Singaporean Stroke Patients. Stroke 40: 2209-2211 [Abstract] [Full text]
Chung, M., Balk, E. M, Ip, S., Raman, G., Yu, W. W, Trikalinos, T. A, Lichtenstein, A. H, Yetley, E. A, Lau, J. (2009). Reporting of systematic reviews of micronutrients and health: a critical appraisal. Am. J. Clin. Nutr. 89: 1099-1113 [Abstract] [Full text]
Imasa, M. S. B, Gomez, N. T, Nevado, J. B Jr (2009). Folic Acid-Based Intervention in Non-ST Elevation Acute Coronary Syndromes. Asian Cardiovasc. Thorac. Ann. 17: 13-21 [Abstract] [Full text]
Ntaios, G., Savopoulos, C., Hatzitolios, A. (2008). Lowering Homocysteine With B Vitamins in Patients With Coronary Artery Disease. JAMA 300: 2852-2853 [Full text]
Milani, R. V., Lavie, C. J. (2008). Homocysteine: The Rubik's Cube of Cardiovascular Risk Factors. Mayo Clin Proc. 83: 1200-1202 [Full text]
Aisen, P. S., Schneider, L. S., Sano, M., Diaz-Arrastia, R., van Dyck, C. H., Weiner, M. F., Bottiglieri, T., Jin, S., Stokes, K. T., Thomas, R. G., Thal, L. J., for the Alzheimer Disease Cooperative Study, (2008). High-Dose B Vitamin Supplementation and Cognitive Decline in Alzheimer Disease: A Randomized Controlled Trial. JAMA 300: 1774-1783 [Abstract] [Full text]
Schwartzfarb, E. M., Romanelli, P. (2008). Hyperhomocysteinemia and Lower Extremity Wounds. INT J LOW EXTREM WOUNDS 7: 126-136 [Abstract]
Albert, C. M., Cook, N. R., Gaziano, J. M., Zaharris, E., MacFadyen, J., Danielson, E., Buring, J. E., Manson, J. E. (2008). 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 299: 2027-2036 [Abstract] [Full text]
Moens, A. L., Vrints, C. J., Claeys, M. J., Timmermans, J.-P., Champion, H. C., Kass, D. A. (2008). Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol. 294: H1971-H1977 [Abstract] [Full text]
Nilsen, R. M., Vollset, S. E., Rasmussen, S. A., Ueland, P. M., Daltveit, A. K. (2008). Folic Acid and Multivitamin Supplement Use and Risk of Placental Abruption: A Population-based Registry Study. Am J Epidemiol 167: 867-874 [Abstract] [Full text]
Wallace, J. M., Bonham, M. P, Strain, J., Duffy, E. M, Robson, P. J, Ward, M., McNulty, H., Davidson, P. W, Myers, G. J, Shamlaye, C. F, Clarkson, T. W, Molloy, A. M, Scott, J. M, Ueland, P. M (2008). Homocysteine concentration, related B vitamins, and betaine in pregnant women recruited to the Seychelles Child Development Study. Am. J. Clin. Nutr. 87: 391-397 [Abstract] [Full text]
Ishihara, J., Iso, H., Inoue, M., Iwasaki, M., Okada, K., Kita, Y., Kokubo, Y., Okayama, A., Tsugane, S., for the JPHC Study Group, (2008). Intake of Folate, Vitamin B6 and Vitamin B12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I. J. Am. Coll. Nutr. 27: 127-136 [Abstract] [Full text]
Dodds, L., Fell, D. B., Dooley, K. C., Armson, B. A., Allen, A. C., Nassar, B. A., Perkins, S., Joseph, K.S. (2008). Effect of Homocysteine Concentration in Early Pregnancy on Gestational Hypertensive Disorders and Other Pregnancy Outcomes. Clin. Chem. 54: 326-334 [Abstract] [Full text]
Hoey, L., McNulty, H., Askin, N., Dunne, A., Ward, M., Pentieva, K., Strain, J., Molloy, A. M, Flynn, C. A, Scott, J. M (2007). Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults. Am. J. Clin. Nutr. 86: 1405-1413 [Abstract] [Full text]
Jamison, R. L., Hartigan, P., Kaufman, J. S., Goldfarb, D. S., Warren, S. R., Guarino, P. D., Gaziano, J. M., For the Veterans Affairs Site Investigators, (2007). Effect of Homocysteine Lowering on Mortality and Vascular Disease in Advanced Chronic Kidney Disease and End-stage Renal Disease: A Randomized Controlled Trial. JAMA 298: 1163-1170 [Abstract] [Full text]
Abularrage, C. J., Sidawy, A. N., White, P. W., Aidinian, G., DeZee, K. J., Weiswasser, J. M., Arora, S. (2007). Effect of Folic Acid and Vitamins B6 and B12 on Microcirculatory Vasoreactivity in Patients With Hyperhomocysteinemia. VASC ENDOVASCULAR SURG 41: 339-345 [Abstract]
Ray, J. G., Kearon, C., Yi, Q., Sheridan, P., Lonn, E., for the Heart Outcomes Prevention Evaluation 2 (HO, (2007). Homocysteine-Lowering Therapy and Risk for Venous Thromboembolism: A Randomized Trial. ANN INTERN MED 146: 761-767 [Abstract] [Full text]
Kuo, H.-K., Liao, K.-C., Leveille, S. G., Bean, J. F., Yen, C.-J., Chen, J.-H., Yu, Y.-H., Tai, T.-Y. (2007). Relationship of Homocysteine Levels to Quadriceps Strength, Gait Speed, and Late-Life Disability in Older Adults. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 62: 434-439 [Abstract] [Full text]
Bille, C, Murray, J C, Olsen, S F (2007). Folic acid and birth malformations. BMJ 334: 433-434 [Full text]
Hao, L., Ma, J., Zhu, J., Stampfer, M. J., Tian, Y., Willett, W. C., Li, Z. (2007). High Prevalence of Hyperhomocysteinemia in Chinese Adults Is Associated with Low Folate, Vitamin B-12, and Vitamin B-6 Status. J. Nutr. 137: 407-413 [Abstract] [Full text]
Steffen, L. M., Folsom, A. R., Cushman, M., Jacobs, D. R. Jr, Rosamond, W. D. (2007). Greater Fish, Fruit, and Vegetable Intakes Are Related to Lower Incidence of Venous Thromboembolism: The Longitudinal Investigation of Thromboembolism Etiology. Circulation 115: 188-195 [Abstract] [Full text]
Durga, J., Verhoef, P., Anteunis, L. J.C., Schouten, E., Kok, F. J. (2007). Effects of Folic Acid Supplementation on Hearing in Older Adults: A Randomized, Controlled Trial. ANN INTERN MED 146: 1-9 [Abstract] [Full text]
Rippe, J. M., Angelopoulos, T. J., Zukley, L. (2007). The Rationale for Intervention to Reduce the Risk of Coronary Heart Disease. AMERICAN JOURNAL OF LIFESTYLE MEDICINE 1: 10-19 [Abstract]
den Heijer, M., Willems, H. P. J., Blom, H. J., Gerrits, W. B. J., Cattaneo, M., Eichinger, S., Rosendaal, F. R., Bos, G. M. J. (2007). Homocysteine lowering by B vitamins and the secondary prevention of deep vein thrombosis and pulmonary embolism: a randomized, placebo-controlled, double-blind trial. Blood 109: 139-144 [Abstract] [Full text]
Bazzano, L. A., Reynolds, K., Holder, K. N., He, J. (2006). Effect of Folic Acid Supplementation on Risk of Cardiovascular Diseases: A Meta-analysis of Randomized Controlled Trials. JAMA 296: 2720-2726 [Abstract] [Full text]
Bleys, J., Miller, E. R III, Pastor-Barriuso, R., Appel, L. J, Guallar, E. (2006). Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials.. Am. J. Clin. Nutr. 84: 880-887 [Abstract] [Full text]
Rosenberg, I. H., Mulrow, C. D. (2006). Trials that matter: should we routinely measure homocysteine levels and "treat" mild hyperhomocysteinemia?. ANN INTERN MED 145: 226-227 [Full text]
McMahon, J. A., Green, T. J., Skeaff, C. M., Knight, R. G., Mann, J. I., Williams, S. M. (2006). A controlled trial of homocysteine lowering and cognitive performance.. NEJM 354: 2764-2772 [Abstract] [Full text]
Cho, E., Zeisel, S. H, Jacques, P., Selhub, J., Dougherty, L., Colditz, G. A, Willett, W. C (2006). Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study.. Am. J. Clin. Nutr. 83: 905-911 [Abstract] [Full text]
Flicker, L., Vasikaran, S. D., Thomas, J., Acres, J. M., Norman, P., Jamrozik, K., J. Hankey, G., Almeida, O. P. (2006). Efficacy of B Vitamins in Lowering Homocysteine in Older Men: Maximal Effects for Those With B12 Deficiency and Hyperhomocysteinemia. Stroke 37: 547-549 [Abstract] [Full text]
Ho, G. Y.-H., Eikelboom, J. W., Hankey, G. J., Wong, C.-R., Tan, S.-L., Chan, J. B.-C., Chen, C. P.L.-H. (2006). Methylenetetrahydrofolate Reductase Polymorphisms and Homocysteine-Lowering Effect of Vitamin Therapy in Singaporean Stroke Patients. Stroke 37: 456-460 [Abstract] [Full text]
McNulty, H., Dowey, L. R. C., Strain, J.J., Dunne, A., Ward, M., Molloy, A. M., McAnena, L. B., Hughes, J. P., Hannon-Fletcher, M., Scott, J. M. (2006). Riboflavin Lowers Homocysteine in Individuals Homozygous for the MTHFR 677C->T Polymorphism. Circulation 113: 74-80 [Abstract] [Full text]
Lewis, S. J, Ebrahim, S., Davey Smith, G. (2005). Meta-analysis of MTHFR 677C->T polymorphism and coronary heart disease: does totality of evidence support causal role for homocysteine and preventive potential of folate?. BMJ 331: 1053- [Abstract] [Full text]
Spence, J. D., Bang, H., Chambless, L. E., Stampfer, M. J. (2005). Vitamin Intervention for Stroke Prevention Trial: An Efficacy Analysis. Stroke 36: 2404-2409 [Abstract] [Full text]
Bailey, L. B (2005). Do low doses of folic acid result in maximum lowering of homocysteine?. Am. J. Clin. Nutr. 82: 717-718 [Full text]
Homocysteine Lowering Trialists' Collaboration, (2005). Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am. J. Clin. Nutr. 82: 806-812 [Abstract] [Full text]
Dhonukshe-Rutten, R. A., van Zutphen, M., de Groot, L. C., Eussen, S. J., Blom, H. J, van Staveren, W. A (2005). Effect of supplementation with cobalamin carried either by a milk product or a capsule in mildly cobalamin-deficient elderly Dutch persons. Am. J. Clin. Nutr. 82: 568-574 [Abstract] [Full text]
Kuo, H.-K., Sorond, F. A., Chen, J.-H., Hashmi, A., Milberg, W. P., Lipsitz, L. A. (2005). The Role of Homocysteine in Multisystem Age-Related Problems: A Systematic Review. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60: 1190-1201 [Abstract] [Full text]
Weikert, C., Hoffmann, K., Dierkes, J., Zyriax, B.-C., Klipstein-Grobusch, K., Schulze, M. B., Jung, R., Windler, E., Boeing, H. (2005). A Homocysteine Metabolism-Related Dietary Pattern and the Risk of Coronary Heart Disease in Two Independent German Study Populations. J. Nutr. 135: 1981-1988 [Abstract] [Full text]
Williams, C., Kingwell, B. A, Burke, K., McPherson, J., Dart, A. M (2005). Folic acid supplementation for 3 wk reduces pulse pressure and large artery stiffness independent of MTHFR genotype. Am. J. Clin. Nutr. 82: 26-31 [Abstract] [Full text]
Chiuve, S. E, Giovannucci, E. L, Hankinson, S. E, Hunter, D. J, Stampfer, M. J, Willett, W. C, Rimm, E. B (2005). Alcohol intake and methylenetetrahydrofolate reductase polymorphism modify the relation of folate intake to plasma homocysteine. Am. J. Clin. Nutr. 82: 155-162 [Abstract] [Full text]
Merchant, A. T., Msamanga, G., Villamor, E., Saathoff, E., O'Brien, M., Hertzmark, E., Hunter, D. J., Fawzi, W. W. (2005). Multivitamin Supplementation of HIV-Positive Women during Pregnancy Reduces Hypertension. J. Nutr. 135: 1776-1781 [Abstract] [Full text]
Durga, J., van Tits, L. J. H., Schouten, E. G., Kok, F. J., Verhoef, P. (2005). Effect of Lowering of Homocysteine Levels on Inflammatory Markers: A Randomized Controlled Trial. Arch Intern Med 165: 1388-1394 [Abstract] [Full text]
Melse-Boonstra, A., Holm, P. I, Ueland, P. M, Olthof, M., Clarke, R., Verhoef, P. (2005). Betaine concentration as a determinant of fasting total homocysteine concentrations and the effect of folic acid supplementation on betaine concentrations. Am. J. Clin. Nutr. 81: 1378-1382 [Abstract] [Full text]
Ernest, S., Hosack, A., O'Brien, W. E., Rosenblatt, D. S., Nadeau, J. H. (2005). Homocysteine levels in A/J and C57BL/6J mice: genetic, diet, gender, and parental effects. Physiol. Genomics 21: 404-410 [Abstract] [Full text]
Lewerin, C., Matousek, M., Steen, G., Johansson, B., Steen, B., Nilsson-Ehle, H. (2005). Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am. J. Clin. Nutr. 81: 1155-1162 [Abstract] [Full text]
Papoutsakis, C., Yiannakouris, N., Manios, Y., Papaconstantinou, E., Magkos, F., Schulpis, K. H., Zampelas, A., Matalas, A. L. (2005). Plasma Homocysteine Concentrations in Greek Children Are Influenced by an Interaction between the Methylenetetrahydrofolate Reductase C677T Genotype and Folate Status. J. Nutr. 135: 383-388 [Abstract] [Full text]
Holmes, V. A., Wallace, J. M.W., Alexander, H. D., Gilmore, W. S., Bradbury, I., Ward, M., Scott, J. M., McFaul, P., McNulty, H. (2005). Homocysteine Is Lower in the Third Trimester of Pregnancy in Women with Enhanced Folate Status from Continued Folic Acid Supplementation. Clin. Chem. 51: 629-634 [Abstract] [Full text]
Brevik, A., Vollset, S. E., Tell, G. S, Refsum, H., Ueland, P. M., Loeken, E. B., Drevon, C. A, Andersen, L. F. (2005). Plasma concentration of folate as a biomarker for the intake of fruit and vegetables: the Hordaland Homocysteine Study. Am. J. Clin. Nutr. 81: 434-439 [Abstract] [Full text]
Coppen, A., Bolander-Gouaille, C. (2005). Treatment of depression: time to consider folic acid and vitamin B12. J Psychopharmacol 19: 59-65 [Abstract]
Kelly, C. B., McDonnell, A. P., Johnston, T. G., Mulholland, C., Cooper, S. J., McMaster, D., Evans, A., Whitehead, A. S. (2004). The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland. J Psychopharmacol 18: 567-571 [Abstract]
Garcia, A., Zanibbi, K. (2004). Homocysteine and cognitive function in elderly people. CMAJ 171: 897-904 [Abstract] [Full text]
Jamison, R. L, Hartigan, P., Gaziano, J M., Fortmann, S. P, Goldfarb, D. S, Haroldson, J. A, Kaufman, J., Lavori, P., McCully, K. S, Robinson, K. (2004). Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study. Clin Trials 1: 451-460 [Abstract]
Bleie, O., Refsum, H., Ueland, P. M., Vollset, S. E., Guttormsen, A. B., Nexo, E., Schneede, J., Nordrehaug, J. E., Nygard, O. (2004). Changes in basal and postmethionine load concentrations of total homocysteine and cystathionine after B vitamin intervention. Am. J. Clin. Nutr. 80: 641-648 [Abstract] [Full text]
Minelli, C., Thompson, J. R., Tobin, M. D., Abrams, K. R. (2004). An Integrated Approach to the Meta-Analysis of Genetic Association Studies using Mendelian Randomization. Am J Epidemiol 160: 445-452 [Abstract] [Full text]
Hankey, G.J., Eikelboom, J.W., Loh, K., Yi, Q., Pizzi, J., Tang, M., Hickling, S., Le, M., Klijn, C.J. M., Dusitanond, P., van Bockxmeer, F., Gelavis, A., Baker, R., Jamrozik, K. (2004). Is There Really a Power Shortage in Clinical Trials Testing the "Homocysteine Hypothesis?". Arterioscler. Thromb. Vasc. Bio. 24: e147-e147 [Full text]
Quadri, P., Fragiacomo, C., Pezzati, R., Zanda, E., Forloni, G., Tettamanti, M., Lucca, U. (2004). Homocysteine, folate, and vitamin B-12 in mild cognitive impairment, Alzheimer disease, and vascular dementia. Am. J. Clin. Nutr. 80: 114-122 [Abstract] [Full text]
Moat, S. J., Doshi, S. N., Lang, D., McDowell, I. F. W., Lewis, M. J., Goodfellow, J. (2004). Treatment of coronary heart disease with folic acid: is there a future?. Am. J. Physiol. Heart Circ. Physiol. 287: H1-H7 [Full text]
Perry, C. A., Renna, S. A., Khitun, E., Ortiz, M., Moriarty, D. J., Caudill, M. A. (2004). Ethnicity and Race Influence the Folate Status Response to Controlled Folate Intakes in Young Women. J. Nutr. 134: 1786-1792 [Abstract] [Full text]
Al-Delaimy, W. K., Rexrode, K. M., Hu, F. B., Albert, C. M., Stampfer, M. J., Willett, W. C., Manson, J. E. (2004). Folate Intake and Risk of Stroke Among Women. Stroke 35: 1259-1263 [Abstract] [Full text]
van Meurs, J. B.J., Dhonukshe-Rutten, R. A.M., Pluijm, S. M.F., van der Klift, M., de Jonge, R., Lindemans, J., de Groot, L. C.P.G.M., Hofman, A., Witteman, J. C.M., van Leeuwen, J. P.T.M., Breteler, M. M.B., Lips, P., Pols, H. A.P., Uitterlinden, A. G. (2004). Homocysteine Levels and the Risk of Osteoporotic Fracture. NEJM 350: 2033-2041 [Abstract] [Full text]
Nurk, E., Tell, G. S, Vollset, S. E, Nygard, O., Refsum, H., Nilsen, R. M, Ueland, P. M (2004). Changes in lifestyle and plasma total homocysteine: the Hordaland Homocysteine Study. Am. J. Clin. Nutr. 79: 812-819 [Abstract] [Full text]
Martinez, M. E., Henning, S. M, Alberts, D. S (2004). Folate and colorectal neoplasia: relation between plasma and dietary markers of folate and adenoma recurrence. Am. J. Clin. Nutr. 79: 691-697 [Abstract] [Full text]
Melse-Boonstra, A., West, C. E, Katan, M. B, Kok, F. J, Verhoef, P. (2004). Bioavailability of heptaglutamyl relative to monoglutamyl folic acid in healthy adults. Am. J. Clin. Nutr. 79: 424-429 [Abstract] [Full text]
Scholze, A., Rinder, C., Beige, J., Riezler, R., Zidek, W., Tepel, M. (2004). Acetylcysteine Reduces Plasma Homocysteine Concentration and Improves Pulse Pressure and Endothelial Function in Patients With End-Stage Renal Failure. Circulation 109: 369-374 [Abstract] [Full text]
Refsum, H., Smith, A. D., Ueland, P. M., Nexo, E., Clarke, R., McPartlin, J., Johnston, C., Engbaek, F., Schneede, J., McPartlin, C., Scott, J. M. (2004). Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion. Clin. Chem. 50: 3-32 [Abstract] [Full text]
Hassan, A., Hunt, B. J., O'Sullivan, M., Bell, R., D'Souza, R., Jeffery, S., Bamford, J. M., Markus, H. S. (2004). Homocysteine is a risk factor for cerebral small vessel disease, acting via endothelial dysfunction. Brain 127: 212-219 [Abstract] [Full text]
Kim, N. K., Choi, B. O., Jung, W. S., Choi, Y. J., Choi, K. G. (2003). Hyperhomocysteinemia as an independent risk factor for silent brain infarction. Neurology 61: 1595-1599 [Abstract] [Full text]
Qureshi, M., Khsandwala, H., Ul Haq, I., Prasad, K. (2003). Elevated Levels of Plasma Homocysteine in Hypertensive Patients with Diabetes Mellitus. J CARDIOVASC PHARMACOL THER 8: 261-266 [Abstract]
Olthof, M. R., van Vliet, T., Boelsma, E., Verhoef, P. (2003). Low Dose Betaine Supplementation Leads to Immediate and Long Term Lowering of Plasma Homocysteine in Healthy Men and Women. J. Nutr. 133: 4135-4138 [Abstract] [Full text]
Earnest, C. P., Wood, K. A., Church, T. S. (2003). Complex Multivitamin Supplementation Improves Homocysteine and Resistance to LDL-C Oxidation. J. Am. Coll. Nutr. 22: 400-407 [Abstract] [Full text]
Tolmunen, T., Voutilainen, S., Hintikka, J., Rissanen, T., Tanskanen, A., Viinamaki, H., Kaplan, G. A., Salonen, J. T. (2003). Dietary Folate and Depressive Symptoms Are Associated in Middle-Aged Finnish Men. J. Nutr. 133: 3233-3236 [Abstract] [Full text]
Wotherspoon, F., Laight, D. W, Shaw, K. M, Cummings, M. H (2003). Review: Homocysteine, endothelial dysfunction and oxidative stress in type 1 diabetes mellitus. British Journal of Diabetes & Vascular Disease 3: 334-340 [Abstract]
Hackam, D. G., Anand, S. S. (2003). Emerging Risk Factors for Atherosclerotic Vascular Disease: A Critical Review of the Evidence. JAMA 290: 932-940 [Abstract] [Full text]
Martinelli, I., Battaglioli, T., Pedotti, P., Cattaneo, M., Mannucci, P. M. (2003). Hyperhomocysteinemia in cerebral vein thrombosis. Blood 102: 1363-1366 [Abstract] [Full text]
Holmquist, C., Larsson, S., Wolk, A., de Faire, U. (2003). Multivitamin Supplements Are Inversely Associated with Risk of Myocardial Infarction in Men and Women--Stockholm Heart Epidemiology Program (SHEEP). J. Nutr. 133: 2650-2654 [Abstract] [Full text]
Wald, N J, Law, M R (2003). A strategy to reduce cardiovascular disease by more than 80%. BMJ 326: 1419- [Abstract] [Full text]
Powers, H. J (2003). Riboflavin (vitamin B-2) and health. Am. J. Clin. Nutr. 77: 1352-1360 [Abstract] [Full text]
Bailey, L. B., Rampersaud, G. C., Kauwell, G. P. A. (2003). Folic Acid Supplements and Fortification Affect the Risk for Neural Tube Defects, Vascular Disease and Cancer: Evolving Science,. J. Nutr. 133: 1961S-1968 [Abstract] [Full text]
Fallon, U. B., Virtamo, J., Young, I., McMaster, D., Ben-Shlomo, Y., Wood, N., Whitehead, A. S., Smith, G. D. (2003). Homocysteine and Cerebral Infarction in Finnish Male Smokers. Stroke 34: 1359-1363 [Abstract] [Full text]
van Oort, F. V., Melse-Boonstra, A., Brouwer, I. A, Clarke, R., West, C. E, Katan, M. B, Verhoef, P. (2003). Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study. Am. J. Clin. Nutr. 77: 1318-1323 [Abstract] [Full text]
Girelli, D., Martinelli, N., Pizzolo, F., Friso, S., Olivieri, O., Stranieri, C., Trabetti, E., Faccini, G., Tinazzi, E., Pignatti, P. F., Corrocher, R. (2003). The Interaction between MTHFR 677 C->T Genotype and Folate Status Is a Determinant of Coronary Atherosclerosis Risk. J. Nutr. 133: 1281-1285 [Abstract] [Full text]
Ay, H., Arsava, E. M., Tokgozoglu, S. L., Ozer, N., Saribas, O. (2003). Hyperhomocysteinemia Is Associated With the Presence of Left Atrial Thrombus in Stroke Patients With Nonvalvular Atrial Fibrillation. Stroke 34: 909-912 [Abstract] [Full text]
Eikelboom, J. (2003). Homocysteine lowering treatment improved outcomes after percutaneous coronary intervention. Evid. Based Med. 8: 48-48 [Full text]
Venn, B. J, Green, T. J, Moser, R., Mann, J. I (2003). Comparison of the effect of low-dose supplementation with L-5-methyltetrahydrofolate or folic acid on plasma homocysteine: a randomized placebo-controlled study. Am. J. Clin. Nutr. 77: 658-662 [Abstract] [Full text]
Tanne, D., Haim, M., Goldbourt, U., Boyko, V., Doolman, R., Adler, Y., Brunner, D., Behar, S., Sela, B.-A. (2003). Prospective Study of Serum Homocysteine and Risk of Ischemic Stroke Among Patients With Preexisting Coronary Heart Disease. Stroke 34: 632-636 [Abstract] [Full text]
Davey Smith, G., Ebrahim, S. (2003). 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?. Int J Epidemiol 32: 1-22 [Abstract] [Full text]
Rampersaud, G. C., Kauwell, G. P.A., Bailey, L. B. (2003). Folate: A Key to Optimizing Health and Reducing Disease Risk in the Elderly. J. Am. Coll. Nutr. 22: 1-8 [Abstract] [Full text]
Fallon, U. B (2003). Commentary: Colon cancer, folate and genetic status. Int J Epidemiol 32: 67-70 [Full text]
Moat, S. J., Ashfield-Watt, P. A.L., Powers, H. J., Newcombe, R. G., McDowell, I. F.W. (2003). Effect of Riboflavin Status on the Homocysteine-lowering Effect of Folate in Relation to the MTHFR (C677T) Genotype. Clin. Chem. 49: 295-302 [Abstract] [Full text]
Hung, J., Beilby, J. P, Knuiman, M. W, Divitini, M. (2003). Folate and vitamin B-12 and risk of fatal cardiovascular disease: cohort study from Busselton, Western Australia. BMJ 326: 131-131 [Abstract] [Full text]
Mooradian, A. D. (2003). Cardiovascular Disease in Type 2 Diabetes Mellitus: Current Management Guidelines. Arch Intern Med 163: 33-40 [Abstract] [Full text]
Afman, L. A., Trijbels, F. J. M., Blom, H. J. (2003). The H475Y Polymorphism in the Glutamate Carboxypeptidase II Gene Increases Plasma Folate without Affecting the Risk for Neural Tube Defects in Humans. J. Nutr. 133: 75-77 [Abstract] [Full text]
Mennen, L. I, de Courcy, G. P., Guilland, J.-C., Ducros, V., Bertrais, S., Nicolas, J.-P., Maurel, M., Zarebska, M., Favier, A., Franchisseur, C., Hercberg, S., Galan, P. (2002). Homocysteine, cardiovascular disease risk factors, and habitual diet in the French Supplementation with Antioxidant Vitamins and Minerals Study. Am. J. Clin. Nutr. 76: 1279-1289 [Abstract] [Full text]
De Bree, A., Verschuren, W. M. M., Kromhout, D., Kluijtmans, L. A. J., Blom, H. J. (2002). Homocysteine Determinants and the Evidence to What Extent Homocysteine Determines the Risk of Coronary Heart Disease. Pharmacol. Rev. 54: 599-618 [Abstract] [Full text]