Cited by 1,729Folate and B Vitamins ResearchLipoproteins and Cardiovascular HealthMenopause: Health Impacts and Treatments

The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.

Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Open access

The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators·2006·New England Journal of Medicine

DOI 10.1056/nejmoa060900

Open this paper in CoChat — free account Open PDF

Abstract

BACKGROUND: In observational studies, lower homocysteine levels are associated with lower rates of coronary heart disease and stroke. Folic acid and vitamins B6 and B12 lower homocysteine levels. We assessed whether supplementation reduced the risk of major cardiovascular events in patients with vascular disease. METHODS: We randomly assigned 5522 patients 55 years of age or older who had vascular disease or diabetes to daily treatment either with the combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12 or with placebo for an average of five years. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, and stroke. RESULTS: Mean plasma homocysteine levels decreased by 2.4 micromol per liter (0.3 mg per liter) in the active-treatment group and increased by 0.8 micromol per liter (0.1 mg per liter) in the placebo group. Primary outcome events occurred in 519 patients (18.8 percent) assigned to active therapy and 547 (19.8 percent) assigned to placebo (relative risk, 0.95; 95 percent confidence interval, 0.84 to 1.07; P=0.41). As compared with placebo, active treatment did not significantly decrease the risk of death from cardiovascular causes (relative risk, 0.96; 95 percent confidence interval, 0.81 to 1.13), myocardial infarction (relative risk, 0.98; 95 percent confidence interval, 0.85 to 1.14), or any of the secondary outcomes. Fewer patients assigned to active treatment than to placebo had a stroke (relative risk, 0.75; 95 percent confidence interval, 0.59 to 0.97). More patients in the active-treatment group were hospitalized for unstable angina (relative risk, 1.24; 95 percent confidence interval, 1.04 to 1.49). CONCLUSIONS: Supplements combining folic acid and vitamins B6 and B12 did not reduce the risk of major cardiovascular events in patients with vascular disease. (ClinicalTrials.gov number, NCT00106886; Current Controlled Trials number, ISRCTN14017017.).

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1056/nejmoa060900

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women
Hulley, S. (1998) · JAMA · doi:10.1001/jama.280.7.605 · Cited by 6,216
Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction
Antman, E. M., Bassand, J., Klein, W. W., Ohman, M. E., Sendón, J. L. L., Rydén, L., Simoons, M. L., & Tendera, M. (2000) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)00804-4 · Cited by 4,824
A Quantitative Assessment of Plasma Homocysteine as a Risk Factor for Vascular Disease
Boushey, C. J. (1995) · JAMA · doi:10.1001/jama.1995.03530130055028 · Cited by 3,708
Homocysteine and Risk of Ischemic Heart Disease and Stroke: A Meta-analysis
Homocysteine Studies Collaboration (2002) · JAMA · doi:10.1001/jama.288.16.2015 · Cited by 2,059
Homocysteine and Atherothrombosis
Welch, G. N., & Loscalzo, J. (1998) · New England Journal of Medicine · doi:10.1056/nejm199804093381507 · Cited by 1,997
Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Wald, D. S., Law, M., & Morris, J. K. (2002) · BMJ · doi:10.1136/bmj.325.7374.1202 · Cited by 1,945
Homocysteine Lowering and Cardiovascular Events after Acute Myocardial Infarction
Bønaa, K. H., Njølstad, I., Ueland, P. M., Schirmer, H., Tverdal, A., Steigen, T., Wang, H., Nordrehaug, J. E., Arnesen, E., & Rasmussen, K. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa055227 · Cited by 1,442
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
Toole, J. F., Malinow, M. R., Chambless, L. E., Spence, J. D., Pettigrew, L. C., Howard, V. J., Sides, E. G., Wang, C.-H., & Stampfer, M. (2004) · JAMA · doi:10.1001/jama.291.5.565 · Cited by 1,391
Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials
Vivekananthan, D. P., Penn, M. S., Sapp, S. K., Hsu, A., & Topol, E. J. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13637-9 · Cited by 1,083
MTHFR 677C→T Polymorphism and Risk of Coronary Heart Disease
Klerk, M., Verhoef, P., Clarke, R., Blom, H. J., Kok, F. J., & Schouten, E. G. (2002) · JAMA · doi:10.1001/jama.288.16.2023 · Cited by 932

Show all 20 references

Sorted by citations

Items 301–400 of 1,000

Hemoglobin, iron, and vitamin B12 deficiencies and high blood homocysteine levels in patients with anti-thyroid autoantibodies
Wang, Y., Lin, H., Chen, H., Kuo, Y., Lang, M.-J., & Sun, A. (2012) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2012.04.003 · Cited by 80
Betaine and Secondary Events in an Acute Coronary Syndrome Cohort
Lever, M., George, P. M., Elmslie, J. L., Atkinson, W., Slow, S., Molyneux, S. L., Troughton, R. W., Richards, M., FRAMPTON, C. M. A., & Chambers, S. T. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037883 · Cited by 80
Effect of folic acid supplementation on plasma total homocysteine levels and glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis
Sudchada, P., Saokaew, S., Sridetch, S., Incampa, S., Jaiyen, S., & Khaithong, W. (2012) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2012.05.027 · Cited by 80
High Dietary Taurine Reduces Apoptosis and Atherosclerosis in the Left Main Coronary Artery
Zulli, A., Lau, E., Wijaya, B. P. P., Jin, X., Sutarga, K., Schwartz, G. D., Learmont, J., Wookey, P. J., Zinellu, A., Carru, C., et al. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.129924 · Cited by 79
Air Pollution, Smoking, and Plasma Homocysteine
Baccarelli, A., Zanobetti, A., Martinelli, I., Grillo, P., Hou, L., Lanzani, G. G., Mannucci, P. M., Bertazzi, P. A., & Schwartz, J. D. (2006) · Environmental Health Perspectives · doi:10.1289/ehp.9517 · Cited by 79
Efficacy of Oral Mixed Tocotrienols in Diabetic Peripheral Neuropathy
The Vitamin E in Neuroprotection Study (VENUS) Investigators, Hor, C. P., Fung, W.-Y., Ang, H. A., Lim, S. C., Kam, L. Y., Sim, S.-W., Lim, L. H., Choon, W. Y., Wong, J. W., et al. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4609 · Cited by 80
Self-citation
Genome-Wide Meta-Analysis of Homocysteine and Methionine Metabolism Identifies Five One Carbon Metabolism Loci and a Novel Association of ALDH1L1 with Ischemic Stroke
Williams, S. R., Yang, Q., Fang, C., Liu, X., Keene, K. L., Jacques, P. F., Chen, W., Weinstein, G., Hsu, F., Beiser, A., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004214 · Cited by 78
Effects of Metformin With or Without Supplementation With Folate on Homocysteine Levels and Vascular Endothelium of Women With Polycystic Ovary Syndrome
Palomba, S., Falbo, A. I., Giallauria, F., Russo, T., Tolino, A., Zullo, F., Colao, A. A. L., & Orio, F. (2009) · Diabetes Care · doi:10.2337/dc09-1516 · Cited by 81
Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects
Atkinson, W., Elmslie, J. L., Lever, M., Chambers, S. T., & George, P. M. (2008) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.3.577 · Cited by 80
Do all the patients with gastric parietal cell antibodies have pernicious anemia?
Sun, A., Wang, Y., Lin, H., Chia, J., & Chiang, C. (2012) · Oral Diseases · doi:10.1111/odi.12014 · Cited by 78
Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee
Abola, M. T. B., Golledge, J., Miyata, T., Rha, S., Yan, B. P., Dy, T. C., Ganzon, M. S. V., Handa, P. K., Harris, S., Jiang, Z., et al. (2020) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.53660 · Cited by 81
Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney
Hwang, S., Siow, Y. L., Au-Yeung, K. K. W., House, J. D., & Karmin, O. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00272.2010 · Cited by 78
“However, data from large prospective randomized clinical trials failed to demonstrate a beneficial effect of folic acid supplementation in reducing the mortality of cardiovascular disease (5, 20).”
Background
Folate, Related B Vitamins, and Homocysteine in Childhood and Adolescence: Potential Implications for Disease Risk in Later Life
Kerr, M. A., Livingstone, M. B. E., Bates, C. J., Bradbury, I., Scott, J. M., Ward, M., Pentieva, K. D., Mansoor, M. A., & McNulty, H. (2009) · PEDIATRICS · doi:10.1542/peds.2008-1049 · Cited by 80
Do all the patients with vitamin B12 deficiency have pernicious anemia?
Sun, A., Chang, J. Y., Wang, Y., Cheng, S., Chen, H., & Chiang, C. (2015) · Journal of Oral Pathology and Medicine · doi:10.1111/jop.12330 · Cited by 77
Vitamin B12 deficiency, hyperhomocysteinemia and thrombosis: a case and control study
Remacha, A. F., Souto, J. C., Piñana, J. L., Sardà, M. P., Queraltó, J. M., Martí‐Fábregas, J., García–Moll, X., Fernández, C., Rodríguez, Á., & Cuesta, J. (2011) · International Journal of Hematology · doi:10.1007/s12185-011-0825-8 · Cited by 77
Effect of folic acid supplementation on the progression of colorectal aberrant crypt foci
Lindzon, G., Medline, A., Sohn, K., Dépeint, F., Croxford, R., & Kim, Y. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp152 · Cited by 77
“5x RDA increased plasma folate concentrations only by 2-7-folds compared with controls [52,53].”
Background
Midlife homocysteine and late-life dementia in women. A prospective population study
Zylberstein, D. E., Lissner, L., Björkelund, C., Mehlig, K., Thelle, D. S., Gustafson, D., Östling, S., Waern, M., Guo, X., & Skoog, I. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.02.024 · Cited by 76
Transiently positive anticardiolipin antibodies and risk of thrombosis in patients with systemic lupus erythematosus
Martinez-Berriotxoa, A., Ruiz-Irastorza, G., Egurbide, M.-V., Garmendia, M., Gabriel Erdozain, J., Villar, I., & Aguirre, C. (2007) · Lupus · doi:10.1177/0961203307083316 · Cited by 76
Efficacy of Flour Fortification with Folic Acid in Women of Childbearing Age in Iran
Abdollahi, Z., Elmadfa, I., Djazayery, A., Golalipour, M. J., Sadighi, J., Salehi, F., & Sharif, S. S. (2011) · Annals of Nutrition and Metabolism · doi:10.1159/000329726 · Cited by 77
The association between coeliac disease and cardiovascular disease
Li, W., Spiers, E. M., REYNOLDS, N., WALSH, S., Fahey, T. P., & MacDonald, T. M. (2007) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2007.03594.x · Cited by 75
High plasma homocysteine levels contribute to the risk of stroke recurrence and all-cause mortality in a large prospective stroke population
Zhang, W., Sun, K., Chen, J.-X., Liao, Y., Qin, Q., Ma, A., Wang, D. W., Zhu, Z., Wang, Y., & Hui, R. (2009) · Clinical Science · doi:10.1042/cs20090142 · Cited by 75
EGCG protects against homocysteine-induced human umbilical vein endothelial cells apoptosis by modulating mitochondrial-dependent apoptotic signaling and PI3K/Akt/eNOS signaling pathways
Liu, S., Sun, Z., Chu, P., Li, H., Ahsan, A., Zhou, Z., Zhang, Z., Sun, B., Wu, J., Xi, Y., et al. (2017) · APOPTOSIS · doi:10.1007/s10495-017-1360-8 · Cited by 76
Significant association of deficiency of hemoglobin, iron and vitamin B12, high homocysteine level, and gastric parietal cell antibody positivity with atrophic glossitis
Sun, A., Lin, H., Wang, Y., & Chiang, C. (2011) · Journal of Oral Pathology and Medicine · doi:10.1111/j.1600-0714.2011.01122.x · Cited by 75
S-Adenosylhomocysteine—a better indicator of vascular disease than homocysteine?
Wagner, C., & Koury, M. J. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.5.1581 · Cited by 75
Homocysteine, methylenetetrahydrofolate reductase, folate status and atherothrombosis: A mechanistic and clinical perspective
Santilli, F., Davı̀, G., & Patrono, C. (2015) · Vascular Pharmacology · doi:10.1016/j.vph.2015.06.009 · Cited by 78
Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology
Joseph, J., & Loscalzo, J. (2013) · Nutrients · doi:10.3390/nu5083235 · Cited by 77
Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype
Rutten‐Jacobs, L. C. A., Traylor, M., Adib‐Samii, P., Thijs, V., Sudlow, C. L. M., Rothwell, P. M., Boncoraglio, G. B., Dichgans, M., Meschia, J. F., Maguire, J. M., et al. (2016) · Stroke · doi:10.1161/strokeaha.115.011545 · Cited by 74
Sulfur-Containing Amino Acids and Lipid Metabolism
Blachier, F., Andriamihaja, M., & Blais, A. (2020) · Journal of Nutrition · doi:10.1093/jn/nxaa243 · Cited by 79
Homocysteine and Glutathione Peroxidase-1
Lubos, E., Loscalzo, J., & Handy, D. E. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1771 · Cited by 71
Hyperhomocysteinemia Alters Cardiac Substrate Metabolism by Impairing Nitric Oxide Bioavailability Through Oxidative Stress
Suematsu, N., Ojaimi, C., Kinugawa, S., Wang, Z., Xu, X., Koller, Á., Recchia, F. A., & Hintze, T. H. (2007) · Circulation · doi:10.1161/circulationaha.106.652693 · Cited by 74
Folic acid inhibits lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages by suppressing MAPKs and NF-κB activation
Feng, D., Zhou, Y., Xia, M., & Ma, J. (2011) · Inflammation Research · doi:10.1007/s00011-011-0337-2 · Cited by 74
“Regarding mechanisms for these beneficial effects of folic acid, most studies have focused on the homocysteine-lowering effects of folic acid [9].”
Background
Fat Fuels the Flame
Libby, P. (2007) · Circulation Research · doi:10.1161/01.res.0000259393.89870.58 · Cited by 74
Epigenetic associations in relation to cardiovascular prevention and therapeutics
Voelter‐Mahlknecht, S. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0170-0 · Cited by 73
Randomized Trials Versus Common Sense and Clinical Observation
Fanaroff, A. C., Califf, R. M., Harrington, R. A., Granger, C. B., McMurray, J. J. V., Patel, M. R., Bhatt, D. L., Windecker, S., Hernandez, A. F., Gibson, C. M., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.05.069 · Cited by 77
The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation
Suliman, M., Stenvinkel, P., Qureshi, A. R., Kalantar‐Zadeh, K., Barany, P. F., Heimbürger, O., Vonesh, E. F., & Lindholm, B. (2006) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfl510 · Cited by 74
Gender differences in homocysteine concentrations, a population-based cross-sectional study
Cohen, E., Margalit, I., Shochat, T., Goldberg, E., & Krause, I. (2018) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2018.09.003 · Cited by 73
Hematinic deficiencies and pernicious anemia in oral mucosal disease patients with macrocytosis
Chang, J. Y., Wang, Y., Wu, Y., Cheng, S., Chen, H., & Sun, A. (2015) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2015.03.015 · Cited by 72
“The high blood homocysteine level in patients is found to be due to deficiencies in folic acid, vitamin B12, and vitamin B6, because a supplement therapy with folic acid, vitamin B12, and vitamin B6 to patients can reduce blood homocysteine levels.(19,20,27) Our study showed a significantly higher frequency of vitamin…”
Background
Reduced-energy cranberry juice increases folic acid and adiponectin and reduces homocysteine and oxidative stress in patients with the metabolic syndrome
Simão, T. N. C., Lozovoy, M. A. B., Simão, A. N. C., Oliveira, S. R., Venturini, D., Morimoto, H. K., Miglioranza, L. H. D. S., & Dichi, I. (2013) · British Journal Of Nutrition · doi:10.1017/s0007114513001207 · Cited by 83
The role of vitamin D in cardiovascular disease: From present evidence to future perspectives
Brandenburg, V. M., Vervloet, M. G., & Marx, N. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.08.005 · Cited by 73
Safety and Risks of Nitrous Oxide Labor Analgesia: A Review
Rooks, J. P. (2011) · Journal of Midwifery & Women s Health · doi:10.1111/j.1542-2011.2011.00122.x · Cited by 72
Homocysteine-Induced Apoptosis in Endothelial Cells Coincides With Nuclear NOX2 and Peri-nuclear NOX4 Activity
Sipkens, J. A., Hahn, N. E., den Brand, C. S., Meischl, C., Cillessen, S. A. G. M., Smith, D. E. C., Juffermans, L. J. M., Musters, R. J. P., Roos, D., Jakobs, C., et al. (2011) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-011-9297-y · Cited by 71
Combined analyses and extended follow‐up of two randomized controlled homocysteine‐lowering B‐vitamin trials
Ebbing, M., Bønaa, K. H., Arnesen, E., Ueland, P. M., Nordrehaug, J. E., Rasmussen, K., Njølstad, I., Nilsen, D. W. T., Refsum, H., Tverdal, A., et al. (2010) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02259.x · Cited by 72
The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis
Zeng, R., Xu, C.-H., Xu, Y., Wang, Y., & Wang, M. (2014) · Public Health Nutrition · doi:10.1017/s1368980014002134 · Cited by 71
Effect of Folic Acid on Endothelial Function Following Acute Myocardial Infarction
Moens, A. L., Claeys, M. J., Wuyts, F. L., Goovaerts, I., Hertbruggen, E. V., Wendelen, L. C., Hoof, V. O. V., & Vrints, C. J. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2006.08.057 · Cited by 71
Role of vitamins in gastrointestinal diseases
Masri, O. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i17.5191 · Cited by 75
Effects of B-vitamins on plasma homocysteine concentrations and on risk of cardiovascular disease and dementia
Clarke, R., Lewington, S., Sherliker, P., & Armitage, J. (2006) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e328011aa71 · Cited by 71
Hematinic deficiencies and anemia statuses in recurrent aphthous stomatitis patients with or without atrophic glossitis
Wu, Y., Wu, Y.-H., Wang, Y., Chang, J. Y., Chen, H., & Sun, A. (2016) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2016.10.007 · Cited by 70
Venous and arterial disease in inflammatory bowel disease
Tan, V. P. Y., Chung, A., Yan, B. P., & Gibson, P. R. (2013) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.12260 · Cited by 70
Homocysteine and related B-vitamin status in coeliac disease: Effects of gluten exclusion and histological recovery
Dickey, W., Ward, M., Whittle, C. R., Kelly, M. T., Pentieva, K. D., Horigan, G., Patton, S., & McNulty, H. (2008) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365520701881118 · Cited by 70
Peripheral Arterial Disease
Mascarenhas, J. V., Albayati, M. A., Shearman, C. P., & Jude, E. B. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.09.003 · Cited by 70
The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis
Potter, K., Hankey, G. J., GREEN, D. J., Eikelboom, J. W., Jamrozik, K. D., & Arnolda, L. (2008) · BMC Cardiovascular Disorders · doi:10.1186/1471-2261-8-24 · Cited by 68
B-vitamin and choline supplementation increases neuroplasticity and recovery after stroke
Jadavji, N. M., Emmerson, J. T., MacFarlane, A. J., Willmore, W. G., & Smith, P. D. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.04.001 · Cited by 68
Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES
Wang, S., Wang, Y., Wan, X. H., Guo, J., Zhang, Y., Tian, M., Fang, S., & Yu, B. (2021) · Diabetes Care · doi:10.2337/dc21-1674 · Cited by 70
Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis
Papaioannou, D. E., Cooper, K. L., Carroll, C., Hind, D., Squires, H., Tappenden, P., & Logan, R. F. (2010) · Colorectal Disease · doi:10.1111/j.1463-1318.2010.02289.x · Cited by 69
A metabonomic approach applied to predict patients with cerebral infarction
Jiang, Z., Sun, J., Liang, Q., Cai, Y., Li, S., Huang, Y. X., Wang, Y., & Luo, G. (2011) · Talanta · doi:10.1016/j.talanta.2011.01.015 · Cited by 69
Risk Factor Management to Prevent First Stroke
Rundek, T., & Sacco, R. L. (2008) · Neurologic Clinics · doi:10.1016/j.ncl.2008.09.001 · Cited by 68
Folic Acid and Vitamin B-12 Supplementation Does Not Favorably Influence Uracil Incorporation and Promoter Methylation in Rectal Mucosa DNA of Subjects with Previous Colorectal Adenomas ,
van den Donk, M., Pellis, L., Crott, J. W., van Engeland, M., Friederich, P., Nagengast, F. M., van Bergeijk, J. D., de Boer, S. Y., Mason, J. B., Kok, F. J., et al. (2007) · Journal of Nutrition · doi:10.1093/jn/137.9.2114 · Cited by 68
Assessing the association between homocysteine and cognition: reflections on Bradford Hill, meta-analyses, and causality
McCaddon, A., & Miller, J. W. (2015) · Nutrition Reviews · doi:10.1093/nutrit/nuv022 · Cited by 69
Role of vitamin B12 deficiency in ischemic stroke risk and outcome
Yahn, G. B., Abato, J. E., & Jadavji, N. M. (2020) · Neural Regeneration Research · doi:10.4103/1673-5374.291381 · Cited by 68
Comprehensive Plasma Thiol Redox Status Determination for Metabolomics
D’Agostino, L. A., Lam, K. P., Lee, R., & Britz‐McKibbin, P. (2010) · Journal of Proteome Research · doi:10.1021/pr100771g · Cited by 68
Blood levels of homocysteine, cysteine, glutathione, folic acid, and vitamin B12 in the acute phase of atherothrombotic stroke
Salemi, G., Gueli, M. C., D’Amelio, M., Saia, V., Mangiapane, P., Aridon, P., Ragonese, P., & Lupo, I. (2009) · Neurological Sciences · doi:10.1007/s10072-009-0090-2 · Cited by 67
Homocysteine, 5,10-Methylenetetrahydrofolate Reductase 677C > T Polymorphism, Nutrient Intake, and Incident Cardiovascular Disease in 24 968 Initially Healthy Women
Zee, R. Y. L., Mora, S., Cheng, S., Erlich, H. A., Lindpaintner, K., Rifai, N., Buring, J. E., & Ridker, P. M. (2007) · Clinical Chemistry · doi:10.1373/clinchem.2006.083881 · Cited by 67
Elevated serum levels of S-adenosylhomocysteine, but not homocysteine, are associated with cardiovascular disease in stage 5 chronic kidney disease patients
Valli, A., Carrero, J. J., Qureshi, A. R., Garibotto, G., Barany, P. F., Axelsson, J., Lindholm, B., Stenvinkel, P., Anderstam, B., & Suliman, M. E. (2008) · Clinica Chimica Acta · doi:10.1016/j.cca.2008.05.018 · Cited by 67
“This hypothesis was recently reviewed [12] and is worth mentioning in view of some reports showing that folate supplementation reduced, but did not normalize Hcy levels in CKD patients [32,33] while at the same time did not diminish the vascular risk in non-CKD populations with established CVD [34,35].”
Background
Significant reduction of homocysteine level with multiple B vitamins in atrophic glossitis patients
Sun, A., Wang, Y., Lin, H., Chen, H., Cheng, S., & Chiang, C. (2012) · Oral Diseases · doi:10.1111/odi.12035 · Cited by 66
Epigenetic Upregulation of H19 and AMPK Inhibition Concurrently Contribute to S-Adenosylhomocysteine Hydrolase Deficiency-Promoted Atherosclerotic Calcification
Dai, X., Liu, S., Cheng, L., Huang, T., Guo, H., Wang, D., Xia, M., Ling, W., & Xiao, Y. (2022) · Circulation Research · doi:10.1161/circresaha.121.320251 · Cited by 70
Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials
Guéant, J., Guéant‐Rodriguez, R., Oussalah, A., Zuily, S., & Rosenberg, I. H. (2022) · Thrombosis and Haemostasis · doi:10.1055/a-1952-1946 · Cited by 71
Homocysteine—a retrospective and prospective appraisal
McCaddon, A., & Miller, J. W. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1179807 · Cited by 66
“An informative example worth considering is the HOPE-2 trial (49).”
Background
Perinatal folate supply: relevance in health outcome parameters
Fekete, K., Berti, C., Cetin, I., Hermoso, M., Koletzko, B. V., & Décsi, T. (2010) · Maternal and Child Nutrition · doi:10.1111/j.1740-8709.2010.00261.x · Cited by 65
A cost-effectiveness analysis of folic acid fortification policy in the United States
Bentley, T. G. K., Weinstein, M. C., Willett, W. C., & Kuntz, K. M. (2008) · Public Health Nutrition · doi:10.1017/s1368980008002565 · Cited by 64
Diet and incident venous thromboembolism: The Iowa Women's Health Study
Lutsey, P. L., Steffen, L. M., Virnig, B. A., & Folsom, A. R. (2009) · American Heart Journal · doi:10.1016/j.ahj.2009.04.003 · Cited by 66
Hypercoagulable States
Anderson, J. A. M., & Weitz, J. I. (2011) · Critical Care Clinics · doi:10.1016/j.ccc.2011.09.007 · Cited by 67
Folic acid supplementation and colorectal cancer risk: a meta-analysis
Fife, J., Raniga, S., Hider, P., & Frizelle, F. (2009) · Colorectal Disease · doi:10.1111/j.1463-1318.2009.02089.x · Cited by 64
H‐Type hypertension, stroke and diabetes in China: Opportunities for primary prevention
Qin, X., & Huo, Y. (2015) · Journal of Diabetes · doi:10.1111/1753-0407.12333 · Cited by 65
Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition
Görman, U., Mathers, J. C., Grimaldi, K. A., Ahlgren, J., & Nordström, K. (2013) · Genes & Nutrition · doi:10.1007/s12263-013-0338-6 · Cited by 65
“…this the majority opinion in the clinical world is to conclude that the ‘‘results do not support the use of folic acid … as a preventive treatment’’ (Lonn et al. 2006), and ‘‘randomized trials of vitamin therapy with folate, vitamin B6, vitamin B12 … demonstrated that none … are effective for…”
Background
The Effects of Folate Supplementation on Diabetes Biomarkers Among Patients with Metabolic Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Akbari, M., Tabrizi, R., Lankarani, K. B., Heydari, S. T., Karamali, M., Keneshlou, F., Niknam, K., Kolahdooz, F., & Asemi, Z. (2018) · Hormone and Metabolic Research · doi:10.1055/s-0043-125148 · Cited by 70
Atrophic glossitis: Etiology, serum autoantibodies, anemia, hematinic deficiencies, hyperhomocysteinemia, and management
Chiang, C., Chang, J. Y., Wang, Y., Wu, Y., Wu, Y., & Sun, A. (2019) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2019.04.015 · Cited by 65
Effect of Combined Diclofenac and B Vitamins (Thiamine, Pyridoxine, and Cyanocobalamin) for Low Back Pain Management: Systematic Review and Meta-analysis
Calderón‐Ospina, C., Nava-Mesa, M. O., & Ariza, C. E. A. (2019) · Pain Medicine · doi:10.1093/pm/pnz216 · Cited by 70
“In general, it is well accepted that B vitamins have a favourable safety profile [45].”
Background
Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment
Inglés, D. P., Rodriguez, J. B. C., & García, H. (2020) · Current Cardiology Reports · doi:10.1007/s11886-020-1270-1 · Cited by 69
The metabolic syndrome and endothelial dysfunction: Common highway to type 2 diabetes and CVD?
Diamant, M., & Tushuizen, M. E. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0061-4 · Cited by 64
“Of note are the two recently published trials reporting no beneficial effect of plasma homocysteine lowering by combined intervention of folic acid and vitamins B 12 and B 6 on CVD morbidity in a total of 8000 high-risk individuals [ 54 ,55].”
Background
Food and Western Disease Health and Nutrition from an Evolutionary Perspective
Lindeberg, S. (2009) · Cited by 64
The Controversial Role of HCY and Vitamin B Deficiency in Cardiovascular Diseases
Herrmann, W., & Herrmann, M. (2022) · Nutrients · doi:10.3390/nu14071412 · Cited by 69
“In contrast to the lacking effect on CVD mortality, the HOPE-2 trial showed a 25% risk reduction in stroke during 5 years of B vitamin supplementation [54].”
Result
Both Paraoxonase-1 Genotype and Activity Do Not Predict the Risk of Future Coronary Artery Disease; the EPIC-Norfolk Prospective Population Study
Birjmohun, R. S., Vergeer, M., Stroes, E. S. G., Sandhu, M. S., Ricketts, S. L., Tanck, M. W. T., Wareham, N. J., Jukema, J. W., Kastelein, J. J. P., Khaw, K., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006809 · Cited by 62
Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE−/− mice
Luo, X., Xiao, Y., Song, F.-L., Yang, Y., Xia, M., & Ling, W. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs130 · Cited by 64
Epigenetics in hyperhomocysteinemic states. A special focus on uremia
Ingrosso, D., & Perna, A. F. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.11.010 · Cited by 62
Hyperhomocysteinemia is one of the risk factors associated with cerebrovascular stiffness in hypertensive patients, especially elderly males
Okura, T., Miyoshi, K., Irita, J., Enomoto, D., Nagao, T., Kukida, M., Tanino, A., Kudo, K., Pei, Z., & Higaki, J. (2014) · Scientific Reports · doi:10.1038/srep05663 · Cited by 61
Intake of Folate, Vitamin B 6 and Vitamin B 12 and the Risk of CHD: The Japan Public Health Center-Based Prospective Study Cohort I
Ishihara, J., Iso, H., Inoue, M., Iwasaki, M., Okada, K., Kita, Y., Kokubo, Y., Okayama, A., Tsugane, S., & for the JPHC Study Group (2008) · Journal of the American College of Nutrition · doi:10.1080/07315724.2008.10719684 · Cited by 61
Circulating homocysteine levels in patients with type 2 diabetes mellitus
Ndrepepa, G., Kastrati, A., Braun, S., Koch, W., Kölling, K., Mehilli, J., & Schömig, A. (2006) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2006.03.007 · Cited by 60
New and Emerging Risk Factors for Coronary Heart Disease
Akhabue, E., Thiboutot, J. P., Cheng, J.-W., Lerakis, S., Vittorio, T. J., Christodoulidis, G., Grady, K. M., & Kosmas, C. E. (2013) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e31828aab45 · Cited by 64
Medical management of critical limb ischaemia: where do we stand today?
Lambert, M. A., & Belch, J. J. F. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12102 · Cited by 68
Nonvertebral "osteoporotic" fractures
Birge, S. J. (2006) · Menopause The Journal of The North American Menopause Society · doi:10.1097/01.gme.0000248705.07333.27 · Cited by 61
Cardiovascular risk in South Asians
Ramaraj, R., & Chellappa, P. (2008) · Postgraduate Medical Journal · doi:10.1136/pgmj.2007.066381 · Cited by 62
Homocysteine, small-vessel disease, and atherosclerosis
Jeon, S., Kang, D., Kim, J. S., & Kwon, S. U. (2014) · Neurology · doi:10.1212/wnl.0000000000000720 · Cited by 61
A dose-finding trial of the effect of long-term folic acid intervention: implications for food fortification policy
Tighe, P., Ward, M., McNulty, H., Finnegan, O., Dunne, A., Strain, J., Molloy, A. M., Duffy, M. E., Pentieva, K. D., & Scott, J. M. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2010.29427 · Cited by 59
B Vitamin Plasma Levels and the Risk of Ischemic Stroke and Transient Ischemic Attack in a German Cohort
Weikert, C., Dierkes, J., Hoffmann, K., Berger, K., Drogan, D., Klipstein‐Grobusch, K., Spranger, J., Möhlig, M., Luley, C. H., & Boeing, H. (2007) · Stroke · doi:10.1161/strokeaha.107.486068 · Cited by 59
Immunohistochemical detection of N-homocysteinylated proteins in humans and mice
Perła‐Kaján, J., Stanger, O., Łuczak, M. W., Ziółkowska, A., Malendowicz, L. K., Twardowski, T., Lhoták, Š., Austin, R. C., & Jakubowski, H. (2008) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2008.04.001 · Cited by 58
Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials
Qin, T., Du, M., Du, H., Shu, Y., Wang, M., & Zhu, L. (2015) · Scientific Reports · doi:10.1038/srep12044 · Cited by 60
Homocysteine plasma levels in patients with migraine with aura
Moschiano, F., D’Amico, D., Usai, S., Grazzi, L., Stefano, M. D., Ciusani, E., Erba, N., & Bussone, G. (2008) · Neurological Sciences · doi:10.1007/s10072-008-0917-2 · Cited by 59
Significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody positivity in atrophic glossitis patients
Chiang, C., Chang, J. Y., Wang, Y., Wu, Y., Wu, Y.-H., & Sun, A. (2018) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2018.07.016 · Cited by 59
Antiepileptic drugs, hyperhomocysteinemia and B-vitamins supplementation in patients with epilepsy
Belcastro, V., & Striano, P. (2012) · Epilepsy Research · doi:10.1016/j.eplepsyres.2012.07.003 · Cited by 60
Homocysteine, Vitamin B 12 and Folic Acid Levels in Psoriatic Patients and Correlation with Disease Severity
Brazzelli, V., Grasso, V., Fornara, L., Moggio, E., Gamba, G., Villani, S., & Borroni, G. (2010) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201002300327 · Cited by 59

Authors: The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
Affiliations: Hamilton General Hospital (CA)
Corresponding author: The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2006-04-13
Volume: 354
Issue: 15
Pages: 1567-1577
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa060900
OpenAlex: W2109544293
Cited by: 1,729
References: 20
Citations by year: 2026: 43 · 2025: 46 · 2024: 33 · 2023: 30 · 2022: 43 · 2021: 37 · 2020: 52 · 2019: 46 · 2018: 46 · 2017: 70 · 2016: 81 · 2015: 77 · 2014: 84 · 2013: 85 · 2012: 104
FWCI: 136.11
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: University of Pittsburgh
Massachusetts Medical Society
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
Keywords: homocysteine lowering, folic acid, vitamin B6, vitamin B12, vascular disease, cardiovascular events, stroke, myocardial infarction, cardiovascular mortality, unstable angina, diabetes mellitus, older adults
MeSH terms: Aged, Cardiovascular Diseases, Diabetes Mellitus, Double-Blind Method, Drug Therapy, Combination, Female, Folic Acid, Follow-Up Studies, Humans, Male, Middle Aged, Myocardial Infarction, Risk Factors, Vascular Diseases, Vitamin B 12, Hyperhomocysteinemia, Stroke, Vitamin B 6

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Homocysteine Lowering with Folic Acid and B Vitamins in Vascular Disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks