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

Clarke, Robert ; Brattström, L. ; Landgren, F. ; Israelsson, B. LU ; Lindgren, A. LU ; Hultberg, B. LU ; Andersson, A ; Cuskelly, G. ; McNulty, H. and Strain, S. S. , et al. (1998) In British Medical Journal 316(7135). p.894-898
Abstract

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 concentration. 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... (More)

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 concentration. 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.

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organization
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type
Contribution to journal
publication status
published
subject
in
British Medical Journal
volume
316
issue
7135
pages
894 - 898
publisher
BMJ Publishing Group
external identifiers
  • pmid:9569395
  • scopus:2242477014
ISSN
0959-8146
DOI
10.1136/bmj.316.7135.894
language
English
LU publication?
yes
id
0d370abc-9e82-4e95-9ea2-4d115e7071fb
alternative location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC28491/
date added to LUP
2019-07-01 09:50:48
date last changed
2024-05-30 06:18:28
@article{0d370abc-9e82-4e95-9ea2-4d115e7071fb,
  abstract     = {{<p>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 concentration. 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 &lt; 0.001) and at lower pretreatment blood folate concentrations (P &lt; 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 &lt; 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.</p>}},
  author       = {{Clarke, Robert and Brattström, L. and Landgren, F. and Israelsson, B. and Lindgren, A. and Hultberg, B. and Andersson, A and Cuskelly, G. and McNulty, H. and Strain, S. S. and McPartlin, J. and Weir, D. G. and Scott, J. M. and den Heijer, H. and Brouwer, I. A. and Blom, H. J. and Bos, G. M.J. and Spaans, A. and Rosendaal, F. R. and Thomas, C. M.G. and Haak, H. L. and Wijermans, P. W. and Gerrits, W. B.J. and Naurath, H. J. and Joosten, E. and Riezler, R. and Stabler, S. P. and Allen, R. H. and Lindenbaum, J. and Pietrzik, K. and Prinz­Langenohl, R. and Dierkes, J. and Saltz­man, E. and Mason, J. B. and Jacques, P. and Selhub, J. and Salem, D. and Schaefer, E. and Rosenberg, I. H. and Ubbink, J. and van der Mere, A. and Vermack, W. J.H. and Delport, R. and Becker, P. J. and Potgieter, H. C. and Woodside, J. V. and Yarnell, J. W.G. and McMaster, D. and Young, I. S. and McCrum, E. E.}},
  issn         = {{0959-8146}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{7135}},
  pages        = {{894--898}},
  publisher    = {{BMJ Publishing Group}},
  series       = {{British Medical Journal}},
  title        = {{Lowering blood homocysteine with folic acid based supplements : Meta-analysis of randomised trials}},
  url          = {{http://dx.doi.org/10.1136/bmj.316.7135.894}},
  doi          = {{10.1136/bmj.316.7135.894}},
  volume       = {{316}},
  year         = {{1998}},
}