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

L Brattstrom; F Landgren; B Israelsson; A Lindgren; B Hultberg; A Andersson; G Cuskelly; H McNulty; SS Strain; J McPartlin; DG Weir; JM Scott; M den Heijer; IA Brouwer; HJ Blom; GMJ Bos; A Spaans; FR Rosendaal; CMG Thomas; HL Haak; PW Wijermans; WBJ Gerrits; HJ Naurath; E Joosten; R Riezler; SP Stabler; RH Allen; J Lindenbaum; K Pietrzik; R Prinz-Langenohl; J Dierkes; E Saltzman; JB Mason; P Jacques; J Selhub; D Salem; E Schaefer; IH Rosenberg; J Ubbink; A van der Mere; WJH Vermack; R Delport; PJ Becker; HC Potgieter; JV Woodside; JWG Yarnell; D McMaster; IS Young; EE McCrum; SS Patterson; KF Gey; AE Evans; R Clarke; P Appleby; P Harding; P Sherliker; R Collins; C Frost; V Leroy

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

L Brattstrom, F Landgren, B Israelsson, A Lindgren, B Hultberg, A Andersson, G Cuskelly, H McNulty, SS Strain, J McPartlin, DG Weir, JM Scott, M den Heijer, IA Brouwer, HJ Blom, GMJ Bos, A Spaans, FR Rosendaal, CMG Thomas, HL HaakPW Wijermans, WBJ Gerrits, HJ Naurath, E Joosten, R Riezler, SP Stabler, RH Allen, J Lindenbaum, K Pietrzik, R Prinz-Langenohl, J Dierkes, E Saltzman, JB Mason, P Jacques, J Selhub, D Salem, E Schaefer, IH Rosenberg, J Ubbink, A van der Mere, WJH Vermack, R Delport, PJ Becker, HC Potgieter, JV Woodside, JWG Yarnell, D McMaster, IS Young, EE McCrum, SS Patterson, KF Gey, AE Evans, R Clarke, P Appleby, P Harding, P Sherliker, R Collins, C Frost, V Leroy

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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 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 pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mu mol/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 mu mol/l to 8-9 mu mol/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.

Original language	English
Pages (from-to)	894-898
Journal	BRITISH MEDICAL JOURNAL
Volume	316
Issue number	7135
Publication status	Published (in print/issue) - Mar 1998

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Brattstrom, L., Landgren, F., Israelsson, B., Lindgren, A., Hultberg, B., Andersson, A., Cuskelly, G., McNulty, H., Strain, SS., McPartlin, J., Weir, DG., Scott, JM., den Heijer, M., Brouwer, IA., Blom, HJ., Bos, GMJ., Spaans, A., Rosendaal, FR., Thomas, CMG., ... Leroy, V. (1998). Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. BRITISH MEDICAL JOURNAL, 316(7135), 894-898.

@article{68e1f692dcb944f8a5134088dee9bd08,

title = "Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials",

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 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 pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mu mol/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 mu mol/l to 8-9 mu mol/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.",

author = "L Brattstrom and F Landgren and B Israelsson and A Lindgren and B Hultberg and A Andersson and G Cuskelly and H McNulty and SS Strain and J McPartlin and DG Weir and JM Scott and {den Heijer}, M and IA Brouwer and HJ Blom and GMJ Bos and A Spaans and FR Rosendaal and CMG Thomas and HL Haak and PW Wijermans and WBJ Gerrits and HJ Naurath and E Joosten and R Riezler and SP Stabler and RH Allen and J Lindenbaum and K Pietrzik and R Prinz-Langenohl and J Dierkes and E Saltzman and JB Mason and P Jacques and J Selhub and D Salem and E Schaefer and IH Rosenberg and J Ubbink and {van der Mere}, A and WJH Vermack and R Delport and PJ Becker and HC Potgieter and JV Woodside and JWG Yarnell and D McMaster and IS Young and EE McCrum and SS Patterson and KF Gey and AE Evans and R Clarke and P Appleby and P Harding and P Sherliker and R Collins and C Frost and V Leroy",

year = "1998",

month = mar,

language = "English",

volume = "316",

pages = "894--898",

journal = "BRITISH MEDICAL JOURNAL",

issn = "1468-5833",

publisher = "BMJ Publishing Group",

number = "7135",

}

Brattstrom, L, Landgren, F, Israelsson, B, Lindgren, A, Hultberg, B, Andersson, A, Cuskelly, G, McNulty, H, Strain, SS, McPartlin, J, Weir, DG, Scott, JM, den Heijer, M, Brouwer, IA, Blom, HJ, Bos, GMJ, Spaans, A, Rosendaal, FR, Thomas, CMG, Haak, HL, Wijermans, PW, Gerrits, WBJ, Naurath, HJ, Joosten, E, Riezler, R, Stabler, SP, Allen, RH, Lindenbaum, J, Pietrzik, K, Prinz-Langenohl, R, Dierkes, J, Saltzman, E, Mason, JB, Jacques, P, Selhub, J, Salem, D, Schaefer, E, Rosenberg, IH, Ubbink, J, van der Mere, A, Vermack, WJH, Delport, R, Becker, PJ, Potgieter, HC, Woodside, JV, Yarnell, JWG, McMaster, D, Young, IS, McCrum, EE, Patterson, SS, Gey, KF, Evans, AE, Clarke, R, Appleby, P, Harding, P, Sherliker, P, Collins, R, Frost, C & Leroy, V 1998, 'Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials', BRITISH MEDICAL JOURNAL, vol. 316, no. 7135, pp. 894-898.

TY - JOUR

T1 - Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials

AU - Brattstrom, L

AU - Landgren, F

AU - Israelsson, B

AU - Lindgren, A

AU - Hultberg, B

AU - Andersson, A

AU - Cuskelly, G

AU - McNulty, H

AU - Strain, SS

AU - McPartlin, J

AU - Weir, DG

AU - Scott, JM

AU - den Heijer, M

AU - Brouwer, IA

AU - Blom, HJ

AU - Bos, GMJ

AU - Spaans, A

AU - Rosendaal, FR

AU - Thomas, CMG

AU - Haak, HL

AU - Wijermans, PW

AU - Gerrits, WBJ

AU - Naurath, HJ

AU - Joosten, E

AU - Riezler, R

AU - Stabler, SP

AU - Allen, RH

AU - Lindenbaum, J

AU - Pietrzik, K

AU - Prinz-Langenohl, R

AU - Dierkes, J

AU - Saltzman, E

AU - Mason, JB

AU - Jacques, P

AU - Selhub, J

AU - Salem, D

AU - Schaefer, E

AU - Rosenberg, IH

AU - Ubbink, J

AU - van der Mere, A

AU - Vermack, WJH

AU - Delport, R

AU - Becker, PJ

AU - Potgieter, HC

AU - Woodside, JV

AU - Yarnell, JWG

AU - McMaster, D

AU - Young, IS

AU - McCrum, EE

AU - Patterson, SS

AU - Gey, KF

AU - Evans, AE

AU - Clarke, R

AU - Appleby, P

AU - Harding, P

AU - Sherliker, P

AU - Collins, R

AU - Frost, C

AU - Leroy, V

PY - 1998/3

Y1 - 1998/3

N2 - 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 pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mu mol/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 mu mol/l to 8-9 mu mol/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.

AB - 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 pretreament blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mu mol/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 mu mol/l to 8-9 mu mol/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.

M3 - Article

SN - 1468-5833

VL - 316

SP - 894

EP - 898

JO - BRITISH MEDICAL JOURNAL

JF - BRITISH MEDICAL JOURNAL

IS - 7135

ER -

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

Abstract

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