A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease

Thambyrajah, Jeet; Landray, Martin J; Jones, Helen; McGlynn, Fiona J; Wheeler, DC; Townsend, J.N

doi:10.1016/s1062-1458(01)00465-2

Cited by 6 publications

(11 citation statements)

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“…Some suggested a beneficial effect, whereas others showed no effect at all. [11][12][13][14][15][16][17][18][19][20][32][33][34] Most of these studies had a short follow-up time (maximum of 40 weeks) and were done in specific study groups. If a treatment effect of homocysteine-lowering therapy with B-vitamins is present, it would conceivably be observed most clearly in subjects with increased levels of homocysteine.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16] There are also several small trials investigating the effects of B-vitamins on endothelial biomarkers, again with conflicting results. 13,[17][18][19][20] Most of these trials were performed in selected samples, such as patients with coronary artery disease or diabetes, and did not select patients with high baseline homocysteine. Also, these trials were of relatively short duration (up to 40 weeks), and included relatively few individuals (maximum of 90).…”

Section: Introductionmentioning

confidence: 99%

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Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia

et al. 2016

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B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia

et al. 2016

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“…[7][8][9][10] However, when we started our study, there was limited information in subjects with diabetes mellitus. Using forearm plethysmography, van Etten et al 17 demonstrated that subjects with type 2 diabetes have impaired endothelium-dependent, serotonin-induced vasodilation and mildly reduced endotheliumindependent vasodilation in response to sodium nitroprusside.…”

Section: Discussionmentioning

confidence: 99%

“…5 Thus, modulating endothelial function and reducing inflammation may be important in diabetes to prevent atherosclerotic complications. [1][2][3]6 We and others have demonstrated that folic acid can significantly improve endothelium-dependent vasodilation in patients with coronary artery disease, [7][8][9][10] asymptomatic hyperhomocysteinemia, 11,12 and asymptomatic familial hypercholesterolemia. 13,14 While this benefit may in part be related to homocysteinelowering, 7,8 other studies suggest that the restoration of endothelial function by folates may be independent of its homocysteine-lowering effect.…”

Section: Introductionmentioning

confidence: 99%

Folic acid improves endothelial dysfunction in type 2 diabetes - an effect independent of homocysteine-lowering

Title

Giddens

et al. 2006

Vasc Med

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Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10 mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 Ϯ 4.8% vs 3.2 Ϯ 2.7%, p ϭ 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteinelowering, but does not modulate markers of inflammation.

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“…Estudos retrospectivos mostram correlação entre homocistinúria, aterosclerose, tromboembolismo arterial e venoso (46) e HHe em pacientes com DCV (66) . A HHe tem se mostrado fator de risco importante e independente para doença vascular, trombose e aterosclerose, incluindo DAC (4,18,54,76) .…”

Section: Hiper-homocisteinemia E Doenças Vascularesunclassified

Homocisteína

Neves¹,

Macedo²,

Lopes³

2004

J. Bras. Patol. Med. Lab.

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A homocisteína, formada a partir da metionina hepática, é metabolizada nas vias de desmetilação e de transulfuração, sendo que seus valores plasmáticos e urinários refl etem a síntese celular. Sua determinação, realizada em jejum e após sobrecarga de metionina, caracteriza as diferenças dessas vias metabólicas, principalmente quando de natureza genética. A hiper-homocisteinemia tem sido associada a maior risco de eventos aterotrombóticos, e a literatura sugere associação causal, independente de outros fatores de risco para doença arterial. Diminuição da homocisteína plasmática para valores normais é seguida de redução signifi cante na incidência de doença aterotrombótica. A relação entre homocisteína e o fígado vem adquirindo importância nos dias atuais, uma vez que alterações das lipoproteínas e da depuração de metionina são comuns em pacientes com doença hepática crônica (hepatocelular e canalicular). O tratamento da hiper-homocisteinemia fundamenta-se na suplementação alimentar e medicamentosa de ácido fólico e vitaminas B 6 e B 12 . (49) , porém mais de 40% dos pacientes com doença primária da artéria coronária, cerebrovascular ou vascular periférica têm hiper-homocisteinemia (HHe) (25,51) .

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A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease

Cited by 6 publications

References 0 publications

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia

Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia

Folic acid improves endothelial dysfunction in type 2 diabetes - an effect independent of homocysteine-lowering

Homocisteína

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