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

    Abstract
Top
Abstract
References

Objective: To determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic 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 on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-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 greater at higher pretreatment blood homocysteine concentrations (P<0.001) and at lower pretreatment blood folate concentrations (P<0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 µmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P<0.001), with similar effects in the range of 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 additional effect.
Conclusions: Typically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 µmol/l to 8-9 µmol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.

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


    Introduction

Epidemiological studies have consistently reported that patients with occlusive vascular disease have higher blood homocysteine concentrations than control subjects, and that these differences precede the onset of disease and are independent of other risk factors.1-5 A meta-analysis of the observational studies of blood homocysteine and vascular disease indicated that a prolonged lowering of homocysteine concentration by 1 µmol/l was associated with about a 10% reduction in risk throughout the range 10-15 µmol/l.1 Blood concentrations of homocysteine are inversely related to blood concentrations of folate, vitamin B-12, and, to a lesser extent, vitamin B-6.6 Dietary supplements of these vitamins are used to reduce homocysteine concentrations in subjects with homozygous homocystinuria, who have particularly high blood concentrations of homocysteine.7 Several randomised controlled trials of the effects of folic acid based supplements on homocysteine concentrations have been conducted. Our study aimed, by a meta-analysis of data from individual participants in these trials, to determine more reliably the size of the reduction in blood homocysteine achieved with different doses of folic acid and with the addition of vitamin B-12 and vitamin B-6. This should help in the design of randomised trials of the effects of lowering homocysteine concentrations on vascular disease.

    Methods

Studies included
We aimed to identify all published and unpublished randomised trials that had assessed the effects on blood homocysteine concentrations of folic acid supplements, with or without the addition of vitamins B-12 or B-6. Studies were not eligible if they did not include an untreated control group, assessed treatment after methionine loading, or treated patients for less than 3 weeks.8-15 Eligible studies were identified by Medline searches (using search terms and widely used variants for folic acid, vitamin B-12, vitamin B-6, and homocysteine, and including the non-English language literature), scanning reference lists, and personal contact with relevant investigators. The 14 trials we identified that fulfilled the eligibility criteria16-24 included two completed trials (involving 50 and 144 subjects; V Howard, I Brouwer, personal communications) from which data are not available for collaborative analyses until their publication. The 12 available trials included 1114 subjects. Ten of these trials had a parallel group design16-24 and two had a crossover design21 (for which, to avoid any carryover effects, we used only data from the first period). The allocated treatment was blinded in all trials except two that had untreated controls. 16 23

Information collected
For each subject entered in these trials, we sought details of age, sex, smoking habits, history of vascular disease or hypertension, and vitamin use before randomisation, and of their randomly allocated treatment regimen (daily dose of folic acid, vitamin B-12 or vitamin B-6, and scheduled duration) and blood concentrations of homocysteine, folate, vitamin B-12, and vitamin B-6 before treatment and at the end of the scheduled treatment period.

                              
View this table:
[in this window]
[in a new window]
 

Table 1  Characteristics of the 12 available trials of treatment based on folic acid

                              
View this table:
[in this window]
[in a new window]
 

Table 2 Blood concentrations of homocysteine in individual trials

Statistical analysis
The proportional reductions in blood homocysteine in the treated groups compared with the control groups were determined by extending an analysis of covariance25 that estimated the differences in post-treatment, log transformed homocysteine values after adjustment for baseline values of homocysteine. The simple model was extended to allow the extent of this adjustment to vary between studies and to take account of factors such as folic acid dose, concomitant vitamin B-12 or vitamin B-6, age, sex, and duration of treatment. More complex models that allowed the effect of folic acid supplementation to differ in individual studies were used to investigate sources of heterogeneity.

    Results

Characteristics of individual trials
Among the 1114 subjects in the trials, the mean age was 52 years (range of trial means 23 to 75 years) and the mean duration of treatment was 6 weeks (range 3 to 12 weeks) (table 1). The median pretreatment blood concentration of homocysteine was 11.8 µmol/l and of folate was 11.6 nmol/l, but there were substantial differences between the trials. All of the trials compared folic acid alone versus control or folic acid plus vitamin B-6 or B-12, or both, versus control, although two trials 17 18 also involved within-trial comparisons of folic acid alone versus combination therapy (table 2). A correlation coefficient of 0.87 for homocysteine in pretreatment blood samples collected from 664 of these patients on two separate occasions shows that there was relatively little variation within subjects and that the homocysteine measurements were reliable. Compliance with the study protocols was good, with blood homocysteine measurements at the end of study treatment available from 98% of those randomised.

Exploration of heterogeneity between the results of different trials
The effect of folic acid on blood homocysteine concentrations seemed to differ among the trials. This heterogeneity of the homocysteine lowering effect was not explained by differences in age, sex, or duration of treatment (although the longest duration studied was only 12 weeks). The proportional and absolute reductions in blood homocysteine concentrations seemed, however, to be influenced by the pretreatment blood concentrations of homocysteine and folate, but not of vitamin B-12. Even after adjustment for differences in the folic acid regimen, the homocysteine lowering effect of folic acid ranged from a proportional reduction of 16% (11% to 20%) among subjects in the bottom fifth of pretreatment blood homocysteine concentrations to a 39% (36% to 43%) reduction among those in the top fifth (fig 1; P for trend <0.001). Conversely, the blood homocysteine lowering effect of folic acid was greater at lower pretreatment blood concentrations of folate (P for trend <0.001). These associations of the homocysteine lowering effect with pretreatment concentrations of blood homocysteine and blood folate remained significant (P<0.001) when both pretreatment measurements were included simultaneously in the model. The model provided no strong evidence that the variation in the homocysteine lowering effect with baseline homocysteine depended on baseline folate or vice versa. Figure 2 shows that the proportional reductions in blood homocysteine concentrations achieved by folic acid supplementation according to pretreatment blood levels of homocysteine and folate under this assumption. (Exclusion of the two trials 18 19 in subjects with very high pretreatment blood homocysteine concentrations did not materially alter these findings, and nor did inclusion of the two small completed but unpublished trials not yet formally available for these collaborative analyses: data not shown.)


View larger version (K):
[in this window]
[in a new window]
  		Fig 1.    Reductions in blood homocysteine concentrations with folic acid supplements according to pretreatment blood concentrations of homocysteine, folate, and vitamin B-12. Squares indicate the ratios of post-treatment blood homocysteine among subjects allocated folic acid supplements to those of controls; size of square is proportional to number of subjects, and horizontal line indicates 95% confidence interval


View larger version (35K):
[in this window]
[in a new window]
  		Fig 2.    Predicted proportional reduction in blood homocysteine concentrations with folic acid supplementation (0.5-5 mg daily)


View larger version (27K):
[in this window]
[in a new window]
  		Fig 3.    Reductions in blood homocysteine concentrations with varying doses of folic acid at pretreatment blood concentrations of homocysteine of 12 µmol/l and folate of 12 nmol/l. Squares indicate the ratios of post-treatment blood homocysteine among subjects allocated folic acid supplements to those of controls; size of square is proportional to number of subjects, and horizontal line indicates 95% confidence interval

Effects of different folic acid doses on blood homocysteine
After pretreatment blood concentrations of homocysteine and folate were adjusted for, there was no longer much evidence of heterogeneity between the separate blood homocysteine lowering effects in the different trials of daily folic acid doses of <1 mg (mean dose 0.5 mg; P value for heterogeneity=0.15), of 1-3 mg (mean dose 1.2 mg; P=0.05), or of >3 mg folic acid (mean dose 5.7 mg; P=0.69). Nor was there any evidence of differences between the blood homocysteine lowering effects of these different folic acid doses. For individuals with pretreatment blood concentrations of homocysteine of 12 µmol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), folic acid doses of <1 mg, 1-3 mg, and >3 mg daily were each associated with reductions in blood homocysteine of about one quarter (fig 3).

Effects of adding vitamin B-12 or vitamin B-6 to folic acid
The addition of vitamin B-12 (0.02-1 mg daily; mean 0.5 mg) to folic acid further reduced blood homocysteine concentrations by about 7% (3% to 10%). Hence, among people with pretreatment blood concentrations of homocysteine of 12 µmol/l and of folate of 12 nmol/l, adding vitamin B-12 to folic acid changed the reduction in homocysteine from 25% (23% to 28%) to 31% (27% to 35%). Adding vitamin B-6 (2-50 mg daily; mean 16.5 mg) to folic acid did not lower blood homocysteine any further.

    Discussion

Among the vitamins studied in these trials, folic acid had the dominant blood homocysteine lowering effect, and this effect was greater among subjects with higher blood homocysteine concentrations or lower blood folate concentrations before treatment. After standardisation for differences in pretreatment blood homocysteine and folate concentrations, the effect of folic acid was similar for daily doses ranging from 0.5 to 5 mg daily, and vitamin B-12 produced a small additional effect. Supplementation with vitamin B-6 did not seem to have any material effect on blood homocysteine concentrations, but these trials did not assess effects on blood homocysteine after methionine loading, which may be determined to a greater extent by the transulphuration pathway in which vitamin B-6 is a cofactor.8

Our results suggest that a daily dose of at least 0.5 mg of folic acid, along with a similar amount of vitamin B-12, would produce a proportional reduction in blood homocysteine of about a quarter to a third. The addition of about 1 mg daily of oral vitamin B-12 to folic acid would also be expected to avoid the theoretical risk of neuropathy due to unopposed folic acid therapy in patients deficient in vitamin B-12, even those with intrinsic factor deficiency or malabsorption states.26-28 Studies in the United States and Britain indicate that the average concentration of blood homocysteine in a typical Western population is about 12 µmol/l, 4 6 and so a reduction of about a quarter to a third would correspond to an absolute reduction of about 3-4 µmol/l. A previous meta-analysis of the observational studies suggests that a prolonged lower blood homocysteine concentration of 3-4 µmol/l would correspond to 30-40% less vascular disease.1 Consequently, even if as much as half of the epidemiologically predicted benefit is achieved within a few years of lowering blood homocysteine (as seems to be the case with cholesterol lowering29-31), trials of folic acid supplements may well need to be large, and to include people at high risk, to be able to detect the sort of reductions---15% to 20%---in cardiovascular risk that might realistically be anticipated.

Supplementation with folic acid is a cheap and effective method of lowering blood homocysteine concentrations. If large scale trials in high risk populations do show reliably that blood homocysteine reductions with such supplements can be sustained over time and that this strategy reduces the risk of vascular events (and is safe), this could have important public health implications. Higher dose supplements could be used in people at high risk, and population mean concentrations of blood homocysteine could be reduced by fortifying flour with folic acid. 1 32 Introducing fortified flour for the prevention of neural tube defects before trials of folic acid on vascular disease are conducted could, however, complicate the overall assessment of any benefits---or risks---of lowering homocysteine concentrations in this way.

    Acknowledgments

The following investigators were members of the Homocysteine Lowering Trialists' Collaboration. Abbreviated trial names are listed alphabetically, along with the institutions and names of the principal investigators. Brattström (University of Lund: L Brattström, F Landgren, B Israelsson, A Lindgren, B Hultberg, A Andersson); Cuskelly (University of Ulster: G Cuskelly, H McNulty, SS Strain; Trinity College, Dublin: J McPartlin, DG Weir, JM Scott); den Heijer (Leyenburg Hospital, the Hague, and University of Nijmegen: M den Heijer, IA Brouwer, HJ Blom, GMJ Bos, A Spaans, FR Rosendaal, CMG Thomas, HL Haak, PW Wijermans, WBJ Gerrits); Naurath (University of Leuven and Witten-Herdecke: HJ Naurath, E Joosten, R Riezler, SP Stabler, RH Allen, J Lindenbaum); Pietrzik (University of Bonn: K Pietrzik, R Prinz-Langenohl, J Dierkes); Saltzman (USDA-HNRC at Tufts University: E Saltzman, JB Mason, P Jacques, J Selhub, D Salem, E Schaefer, IH Rosenberg); Ubbink (University of Pretoria: J Ubbink, A van der Mere, WJH Vermack, R Delport, PJ Becker, HC Potgieter); Woodside (Queen's University of Belfast: JV Woodside, JWG Yarnell, D McMaster, IS Young, EE McCrum, SS Patterson, KF Gey, AE Evans).

Secretariat: Clinical Trial Service Unit, University of Oxford (R Clarke, P Appleby, P Harding, P Sherliker, R Collins) and Medical Statistics Unit, London School of Hygiene and Tropical Medicine (C Frost, V Leroy).

Writing committee and guarantors: R Clarke, C Frost, V Leroy, R Collins.

This paper is dedicated to the late Dr John Lindenbaum.

Funding: British Heart Foundation and Medical Research Council.

Conflict of interest: None.

    References
Top
Abstract
References

  1. Boushey CJ, Beresford SA, Omen GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049-1057[Abstract/Free Full Text].
  2. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991; 324: 1149-1155[Abstract].
  3. Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995; 24: 704-709[Abstract/Free Full Text].
  4. Perry I, Refsum H, Morris RW, Ebrahim S, Ueland PM, Shaper AG. A prospective study of serum homocysteine concentration and risk of stroke in middle-aged men. Lancet 1995; 346: 1395-1398[Medline].
  5. Graham IM, Daly LE, Refsum H, Robinson K, Brattström LE, Ueland PM, et al. Plasma homocysteine as a risk factor for vascular disease. JAMA 1997; 277: 1775-1781[Abstract/Free Full Text].
  6. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693-2698[Abstract/Free Full Text].
  7. Mudd SH, Skovby F, Levy HL, Pettigrew KD, Wilcken B, Pyeritz RE, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37: 1-31[Medline].
  8. van der Berg M, Franken DG, Boers GHJ, Blom HJ, Jakobs C, Stehouwer CDA, et al. Combined vitamin B6 and folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia. J Vasc Surg 1994; 20: 933-940[Medline].
  9. Franken DG, Boers GHJ, Blom HJ, Trijbels FJM Kloppenberg PW. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arteriosclerosis Thromb 1994;14:465-70.
  10. Wilcken DEL, Dudman NPB, Tyrell PA, Robertson MR. Folic acid lowers plasma homocysteine in chronic renal insufficiency: possible implications for the prevention of vascular disease. Metabolism 1988; 37: 697-701[Medline].
  11. Brattström L, Israelsson B, Jeppson JU, Hultberg BL. Folic acid---an innocuous means of reducing plasma homocysteine. Scand J Clin Lab Invest 1988; 48: 215-221[Medline].
  12. Arnadottir M, Brattström L, Simonsen O, Thysell H, Hultberg B, Andersson A, et al. The effect of high-dose pyridoxine and folic acid supplementation on serum lipids and plasma homocysteine. Clin Nephrol 1993; 40: 236-240[Medline].
  13. Bostom AG, Shemin D, Lapane KL, Hume AL, Yoburn D, Nadeau MR, et al. High dose B-vitamin treatment of hyperhomocysteinemia in dialysis patients. Kidney Int 1996; 49: 147-152[Medline].
  14. Chaveau P, Chadefoux-Vekemans B, Coude M, Aupetit J, Kamoun P, Jungers P. Hyperhomocysteinemia in chronic renal failure patients. Reduction of vascular risk factors by folate supplementation. Ir J Med Sci 1995; 164: 25.
  15. Ryan M, Robinson K, Clarke R, Refsum H, Ueland P, Graham I. Vitamin B6 and folate reduce homocysteine concentrations in coronary artery disease. Ir J Med Sci 1993; 162: 197.
  16. Landgren F, Israelsson B, Lindgren A, Hultberg B, Andersson A, Brattström L. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995; 237: 381-388[Medline].
  17. Den Heijer M, Brouwer IA, Bos GMJ, Blom HJ, Spaans AP, Rosendaal FR, et al. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arteriosclerosis Thromb Vascular Biol (in press).
  18. Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ, Delport R, Potgieter HC. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994,124:1927-33.
  19. Ubbink JB, van der Merwe A, Vermaak WJH, Delport R. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Invest 1993; 71: 993-998.
  20. Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995; 346: 85-89[Medline].
  21. Dierkes J. Vitamin requirements for the reduction of homocysteine blood levels in healthy young women [dissertation]. Bonn: University of Bonn , 1995.
  22. Woodside JV, Yarnell JWG, Young IS, McCrum EE, Patterson CC, Gey F, et al. The effects of oral vitamin supplementation on cardiovascular risk factors. Proc Nutr Soc 1997; 56: 149[Medline]A.
  23. Cuskelly G, McNulty W, McPartlin J, Strain JJ, Scott JM. Plasma homocysteine response to folate intervention in young women. Ir J Med Sci 1995; 164: 3.
  24. Saltzman E, Mason JB, Jacques PF, Selhub J, Salem D, Schaefer EJ, et al. B vitamin supplementation lowers homocysteine levels in heart disease. Clin Res 1994; 42: 172A.
  25. Frison L, Pocock SJ. Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Statistics in Medicine 1992; 11: 1685-1704[Medline].
  26. Lindenbaum J, Healton EB, Savage DG, Brust JCM, Garrett TJ, Podell ER, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318: 1720-1728[Abstract].
  27. Savage DG, Lindenbaum J. Folate-cobalamin interactions: In: Bailey LB, ed. Folate in health and disease. New York: Marcel Dekker, 1995:237-85.
  28. Cambell NRC. How safe are folic acid supplements? Arch Intern Med 1996; 156: 1638-1644[Abstract/Free Full Text].
  29. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet 1994; 344: 1383-1389[Medline].
  30. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effects of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001-1009[Abstract/Free Full Text].
  31. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, Macfarlane PW, et al for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-7.
  32. Tucker KL, Mahnken B, Wilson PWF, Jacques P, Selhub J. Folic acid fortification of the food supply: potential benefits and risks for the elderly population. JAMA 1996; 276: 1879-1885[Abstract/Free Full Text].

(Accepted 27 November 1997)

© BMJ 1998
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to StumbleUpon StumbleUpon   Add to Technorati 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]  
  • Wald, D. S, Law, M., Morris, J. K (2002). Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ 325: 1202-1206 [Abstract] [Full text]  

Rapid Responses:

Read all Rapid Responses

Betaine versus homocysteine
Eddie Vos
bmj.com, 8 May 1998 [Full text]
Access jobs at BMJ Careers
Whats new online at Student BMJ