Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers

M.R. Olthof, M.L. Bots, M.B. Katan, P. Verhoef

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status¿its main determinant¿is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design This was a randomized, placebo-controlled, double-blind, crossover study. Setting The study was performed at Wageningen University in Wageningen, the Netherlands. Participants Participants were 39 apparently healthy men and women, aged 50¿70 y. Interventions Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results Folic acid supplementation lowered fasting homocysteine by 20% (¿2.0 ¿mol/l, 95% confidence interval [CI]: ¿2.3; ¿1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (¿1.2 ¿mol/l; ¿1.6; ¿0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ¿0.4 FMD% (95%CI, ¿1.2; 0.4) and ¿0.1 FMD% (¿0.9; 0.7), respectively. Conclusions Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.
Original languageEnglish
Article numbere10
JournalPloS Clinical trials
Volume1
Issue number2
DOIs
Publication statusPublished - 2006

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Betaine
Homocysteine
Folic Acid
Dilatation
Healthy Volunteers
Placebos
Blood Vessels
Fasting
Cardiovascular Diseases
Confidence Intervals
Acids
Brachial Artery
Double-Blind Method
Netherlands
Cross-Over Studies
Biomarkers

Cite this

@article{9ca5b69e647a47379f38071e5c83740e,
title = "Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers",
abstract = "Objectives We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status¿its main determinant¿is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design This was a randomized, placebo-controlled, double-blind, crossover study. Setting The study was performed at Wageningen University in Wageningen, the Netherlands. Participants Participants were 39 apparently healthy men and women, aged 50¿70 y. Interventions Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results Folic acid supplementation lowered fasting homocysteine by 20{\%} (¿2.0 ¿mol/l, 95{\%} confidence interval [CI]: ¿2.3; ¿1.6), and betaine supplementation lowered fasting plasma homocysteine by 12{\%} (¿1.2 ¿mol/l; ¿1.6; ¿0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD{\%}. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ¿0.4 FMD{\%} (95{\%}CI, ¿1.2; 0.4) and ¿0.1 FMD{\%} (¿0.9; 0.7), respectively. Conclusions Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.",
author = "M.R. Olthof and M.L. Bots and M.B. Katan and P. Verhoef",
year = "2006",
doi = "10.1371/journal.pctr.0010010",
language = "English",
volume = "1",
journal = "PloS Clinical trials",
issn = "1555-5887",
publisher = "Public Library of Science",
number = "2",

}

Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers. / Olthof, M.R.; Bots, M.L.; Katan, M.B.; Verhoef, P.

In: PloS Clinical trials, Vol. 1, No. 2, e10, 2006.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Effect of folic acid and betaine supplementation on flow-mediated dilation: A randomized, controlled study in healthy volunteers

AU - Olthof, M.R.

AU - Bots, M.L.

AU - Katan, M.B.

AU - Verhoef, P.

PY - 2006

Y1 - 2006

N2 - Objectives We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status¿its main determinant¿is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design This was a randomized, placebo-controlled, double-blind, crossover study. Setting The study was performed at Wageningen University in Wageningen, the Netherlands. Participants Participants were 39 apparently healthy men and women, aged 50¿70 y. Interventions Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results Folic acid supplementation lowered fasting homocysteine by 20% (¿2.0 ¿mol/l, 95% confidence interval [CI]: ¿2.3; ¿1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (¿1.2 ¿mol/l; ¿1.6; ¿0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ¿0.4 FMD% (95%CI, ¿1.2; 0.4) and ¿0.1 FMD% (¿0.9; 0.7), respectively. Conclusions Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.

AB - Objectives We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status¿its main determinant¿is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. Design This was a randomized, placebo-controlled, double-blind, crossover study. Setting The study was performed at Wageningen University in Wageningen, the Netherlands. Participants Participants were 39 apparently healthy men and women, aged 50¿70 y. Interventions Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. Outcome Measures At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. Results Folic acid supplementation lowered fasting homocysteine by 20% (¿2.0 ¿mol/l, 95% confidence interval [CI]: ¿2.3; ¿1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (¿1.2 ¿mol/l; ¿1.6; ¿0.8) relative to placebo. Mean (± SD) FMD after placebo supplementation was 2.8 (± 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were ¿0.4 FMD% (95%CI, ¿1.2; 0.4) and ¿0.1 FMD% (¿0.9; 0.7), respectively. Conclusions Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.

U2 - 10.1371/journal.pctr.0010010

DO - 10.1371/journal.pctr.0010010

M3 - Article

VL - 1

JO - PloS Clinical trials

JF - PloS Clinical trials

SN - 1555-5887

IS - 2

M1 - e10

ER -