Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

Woo, Kam S.; Chook, Ping; Lolin, Y. I.; Sanderson, John E.; Metreweli, C.; Celermajer, David S.

doi:10.1016/s0735-1097(99)00469-6

Cited by 282 publications

(162 citation statements)

References 28 publications

Supporting

Mentioning

147

Contrasting

Unclassified

Order By: Relevance

“…Oral folic acid supplementation has been shown to improve brachial artery endothelial function in subjects with hyperhomocysteinemia, 11,12 familial hypercholesterolemia, 13,14 and coronary artery disease. [7][8][9][10] However, when we started our study, there was limited information in subjects with diabetes mellitus.…”

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%

See 1 more Smart Citation

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

Title

Giddens

et al. 2006

Vasc Med

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…We found that, as with folate deficiency (which may effectively alter methylation reactions and deoxyribonucleotide biosynthesis), methionine loading (which maintains an efficient transmethylation pathway) promotes the occurrence of an oxidant stress-mediated prethrombotic state that is correlated with total plasma homocysteine concentration (Durand et al, 1997a;Durand and Blache, 1996). Several studies report that by altering flow-mediated endothelium-dependent vasodilation (Bellamy et al, 1998;Chambers et al, 1999aChambers et al, , 1999bKanani et al, 1999;Ungvari et al, 1999;Woo et al, 1999) and by affecting the blood coagulation system (Constant et al, 1999;Nappo et al, 1999), methionine load-induced hyperhomocysteinemia favors the occurrence of vascular spasm and thrombosis, and that endothelial dysfunction can be prevented by an antioxidant treatment (Chambers et al, 1999a;Kanani et al, 1999). These findings suggest that impaired methylation reactions and/or protein synthesis may not be the main mechanisms underlying moderate hyperhomocysteinemia-induced vascular disease.…”

Section: Durand Et Almentioning

confidence: 96%

“…Moreover, the decreased thrombomodulin-dependent activation of protein C observed in hyperhomocysteinemic primates suggests that a moderate increase in circulating homocysteine alters endothelial antithrombotic properties (Lentz et al, 1996). Furthermore, recent studies in both laboratory animals and humans increasingly suggest that moderate hyperhomocysteinemia impairs endothelial-dependent vasodilation (Bellamy et al, 1999;Chambers et al, 1999aChambers et al, , 1999bKanani et al, 1999;Nappo et al, 1999;Ungvari et al, 1999;Woo et al, 1999). Despite normalization of plasma homocysteine concentration, administration of folic acid, vitamin B 6 , and vitamin B 12 for 6 months was insufficient to restore normal vascular function in monkeys maintained for 17 months on an atherosclerotic diet that produced both hypercholesterolemia and hyperhomocysteinemia .…”

Section: Alterations Of Vascular Thromboresistancementioning

confidence: 99%

“…In this case, a dietary reduction of methionine in conjunction with pyridoxine treatment should be instituted to correct hyperhomocysteinemia. Moreover, some studies show that a folate supplement improves endothelial function in hyperhomocysteinemic subjects (Bellamy et al, 1999;Woo et al, 1999). Furthermore, encouraging data from recent interventional studies favor the benefit of homocysteine-lowering therapy in the prevention and correction of vascular disorders related to elevated homocysteine levels.…”

Section: Vitamin Treatment Of Hyperhomocysteinemiamentioning

confidence: 99%

See 1 more Smart Citation

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Durand

Prost²,

Loreau

et al. 2001

Laboratory Investigation

224

147

View full text Add to dashboard Cite

SUMMARY:Based on recent retrospective, prospective, and experimental studies, mild to moderate elevation of fasting or postmethionine-load plasma homocysteine is accepted as an independent risk factor for cardiovascular disease and thrombosis in both men and women. Hyperhomocysteinemia results from an inhibition of the remethylation pathway or from an inhibition or a saturation of the transsulfuration pathway of homocysteine metabolism. The involvement of a high dietary intake of methionine-rich animal proteins has not yet been investigated and cannot be ruled out. However, folate deficiency, either associated or not associated with the thermolabile mutation of the N 5,10 -methylenetetrahydrofolate reductase, and vitamin B 6 deficiency, perhaps associated with cystathionine ␤-synthase defects or with methionine excess, are believed to be major determinants of the increased risk of cardiovascular disease related to hyperhomocysteinemia. Recent experimental studies have suggested that moderately elevated homocysteine levels are a causal risk factor for atherothrombotic disease because they affect both the vascular wall structure and the blood coagulation system. The oxidant stress that results from impaired homocysteine metabolism, which modifies the intracellular redox status, might play a central role in the molecular mechanisms underlying moderate hyperhomocysteinemia-mediated vascular disorders. Because folate supplementation can efficiently reduce plasma homocysteine levels, both in the fasting state and after methionine loading, results from further prospective cohort studies and from on-going interventional trials will determine whether homocysteine-lowering therapies can contribute to the prevention and reduction of cardiovascular risk. Additionally, these studies will provide unequivocal arguments for the independent and causal relationship between hyperhomocysteinemia and atherothrombotic disease. (Lab Invest 2001, 81:645-672).C ardiovascular diseases remain the leading cause of mortality in Western populations. Hyperlipoproteinemia, hypertension, diabetes, obesity, and tobacco smoking are the main risk factors for atherosclerosis and its thrombotic complications. However, these factors alone cannot account for all of the deaths caused by vascular pathologies.As early as 1969, clinical studies conducted in homocystinuric children revealed the importance of severe hyperhomocysteinemia in premature development of atherosclerosis and thromboembolism (McCully, 1983). According to numerous retrospective case-controlled studies, moderate increases in plasma homocysteine, which can be precisely quantitated by high performance liquid chromatography (HPLC), raise the risk for cardiovascular disease 2-fold, after adjusting for classic risk factors. Moreover, up to 20% to 40% of patients with vascular pathologies present moderate to intermediate hyperhomocysteinemia. However, results from prospective studies are inconsistent. Additionally, molecular mechanisms underlying hyperhomocysteinemia-induced vascular diseas...

show abstract

Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women

Christen¹,

Glynn²,

Chew³

et al. 2009

Arch Intern Med

146

View full text Add to dashboard Cite

Context Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of homocysteine-lowering in AMD are lacking. Objective To examine incidence of AMD in a trial of folic acid/vitamin B6/vitamin B12. Design Randomized, double-masked, placebo-controlled trial. Participants 5,442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or 3 or more CVD risk factors. A total of 5,205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Intervention Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d), and vitamin B12 (1 mg/d), or placebo. Main Outcome Measures Total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually-significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the folic acid/B6/B12 group and 82 in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.02). For visually-significant AMD, there were 26 cases in the folic acid/B6/B12 group and 44 in the placebo group (RR, 0.59; 95% CI, 0.36–0.95; p=0.03). Conclusions These randomized trial data from a large cohort of women at high risk of CVD indicate that daily supplementation with folic acid/B6/B12 may reduce the risk of AMD.

show abstract

Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

Abstract: Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.

Cited by 282 publications

References 28 publications

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

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

Impaired Homocysteine Metabolism and Atherothrombotic Disease

Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women

Contact Info

Product

Resources

About