Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

OBJECTIVES

To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.

BACKGROUND

Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.

METHODS

Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 ± 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 ± 2.8 μmol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation.

RESULTS

Compared with placebo, folic acid supplementation resulted in higher serum folate levels (66.2 ± 7.0 vs. 29.7 ± 14.8 nmol/liter; p < 0.001), lower total plasma homocystine levels (8.1 ± 3.1 vs. 9.5 ± 2.5 μmol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 ± 1.6% vs. 6 ± 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed.

CONCLUSION

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

Alteration in the redox state of plasma in heart-transplant patients with moderate hyperhomocysteinemia

Hyperhomocysteinemia has recently been suggested to contribute to the progression of the so-called chronic rejection or cardiac allograft vasculopathy (CAV) in heart-transplant patients in which the major determinant of the increase in homocysteine (Hcy) was the progressive decline of renal function. The exact mechanisms of tissue injury by Hcy is unknown, but some aspects of its toxicity have been related to its capacity for altering the redox state of plasma and forming protein adducts by intermediate lactone. To study the relationships between Hcy levels and variations in the redox state governed by thiols, plasma levels of Hcy, cysteine, glutathione, cysteinylglycine, and corresponding disulfides and protein-mixed disulfides were evaluated in subjects with moderate hyperhomocysteinemia represented by heart-transplant patients with (HTRF) and without (HT) renal failure, as well as patients with renal failure of different origin (RF), and compared with those of a control group (C) of normal subjects matched for age and sex. Plasma levels of Hcy and the corresponding protein mixed disulfides increased progressively in HTs, RFs, and HTRFs with respect to control. These changes were correlated with cysteine variations (as cystine and protein-mixed disulfides) but not with glutathione or cysteinylglycine that varied only as disulfides with a similar tendency. Moreover, an alteration in the plasma redox was evidenced by the decrease in thiol/disulfide ratios of cysteine, Hcy, and cysteinylglycine. In all groups, cysteine was directly correlated with Hcy but not with glutathione or cysteinylglycine, which in turn were correlated each other. Therefore levels of plasma cysteine were more linked to Hcy than to metabolism of glutathione. The clinical meaning of cysteine changes remains undefined and requires further study.     

血清同型半胱氨酸及亚甲基四氢叶酸还原酶与先兆流产相关性研究

目的探讨血清同型半胱氨酸(Hcy)水平及亚甲基四氢叶酸还原酶基因(MTHFR)C677T、A1298C位点多态性与先兆流产的关系。方法以93例先兆流产患者为病例组,99例健康孕妇为对照组,采用荧光定量PCR技术检测MTHFR基因C677T和A1298C位点多态性,同时应用酶循环法测定血清Hcy水平。比较病例组和对照组间基因型分布频率和血清Hcy水平差异。结果病例组血清Hcy水平明显高于对照组;高Hcy是先兆流产的危险因素(OR=2.056,P=0.016);MTHFR C677TT基因型携带者血清Hcy水平明显高于其他基因型;A1298CC基因型携带者血清Hcy水平明显高于AA野合型;病例组A1298CC纯合基因频率明显高于对照组;差异均有统计学意义(P0.05)。结论 Hcy升高是导致先兆流产的重要危险因素;MTHFR A1298CC纯合突变可致血清Hcy水平升高与先兆流产的发生有一定的相关性。     

Environmental validation of the homocystine theory of arteriosclerosis

It has been proposed that elevated concentrations of homocystine in vascular tissue could cause arterial damage leading to arteriosclerosis. This theory is indirectly supported by research in the area of environmental toxicology, which has revealed that carbon monoxide and carbon disulfide, agents whose prolonged exposure is known to result in the development of arteriosclerotic changes, induced vitamin B6 deficiency states which predictably lead to a homocystinuria-like state. Such information provides strong indirect support of the controversial homocystine theory of arteriosclerosis.     

The aminothiol redox status in haemodialysis patients does not improve with folate therapy

Background. Patients on haemodialysis suffer from high cardiovascular morbidity and mortality, and oxidative stress may play a role in the pathophysiology of cardiovascular disease in these patients. Hyperhomocysteinemia is common in dialysis patients and may have pro‐oxidant effects. Moreover, the redox status of the major plasma aminothiols (homocysteine [Hcy], cysteine and cysteinylglycine) may be regarded as a biomarker of oxidative stress. In the present study, we investigated the aminothiol redox status during a period of homocysteine‐lowering therapy with folinic acid. Material and methods. In the first part of the study, 32 stable patients receiving maintenance haemodialysis were compared with 32 reference subjects. In the second part, the patients were given folinic acid intravenously for 3 months. Results. Before intervention with folinic acid, the patients had elevated concentrations of all redox species of Hcy. The aminothiol redox ratios were low. Folinic acid therapy lowered the concentrations of all Hcy redox species; however, the redox ratios did not improve. Conclusions. The low aminothiol redox ratios indicate the presence of oxidative stress in haemodialysis patients. Therapy with folinic acid lowered total Hcy concentrations, but did not improve the redox status. Thus, hyperhomocysteinemia appears to be of little importance in regard to the total level of oxidative stress in uraemia.     

老年性痴呆患者血清肿瘤坏死因子α和同型半胱氨酸的观察

目的观察老年性痴呆患者血清肿瘤坏死因子α(TNF-α)和同型半胱氨酸(Hcy)的水平变化,探讨它们与老年性痴呆的关系。方法采用放射免疫法和化学发光免疫法测定35例老年性痴呆患者和30例健康人的外周血TNF-α、Hcy的含量水平。结果老年性痴呆患者血TNF-α、Hcy的含量水平显著高于正常人,且TNF-α、Hcy的含量呈正相关。结论 TNF-、Hcy与老年性痴呆的发生发展有关。     

血浆同型半胱氨酸水平对急性脑梗死预后的影响及干预治疗的作用

目的探讨血浆同型半胱氨酸(Hcy)水平对急性脑梗死(ACI)预后的影响及干预治疗的作用。方法采用荧光法检测152例ACI患者发病<24h(治疗前)、1个月和6个月时血浆Hcy水平。按发病<24h时血浆Hcy水平将患者分为正常Hcy组、高Hcy组,后者又分为干预治疗组[给予叶酸5mg/d、维生素(Vit)B620mg/d、VitB120.5mg/d,连续6个月]和常规治疗对照组(常规治疗组)。在发病后各时点对3组患者进行美国国立卫生研究院卒中量表(NIHSS)和Barthel指数(BI)评分。结果治疗6个月时,干预治疗组血浆Hcy水平比治疗前以及常规治疗组明显降低(均P<0.01);正常Hcy组和干预治疗组NIHSS评分明显低于、BI评分明显高于常规治疗组(均P<0.05)。结论血浆Hcy水平增高的ACI患者预后较差,对高Hcy血症干预治疗可以改善ACI的预后。     

尿液同型胱氨酸定量检测

以硝普银取代NaCN作为还原剂,同型胱氨酸被还原成同型半胱氨酸,而胱氨酸仍为氧化型不变。同型半胱氨酸与硝普钠显紫红色。我们在上述定性试验基础上作同型胱氨酸的定量测定,颜色稳定性、胱氨酸干扰、精密度、回收率和线性等结果均适用于同型胱氨酸尿症的诊断。     

急性脑梗死患者血浆同型半胱氨酸与NO水平相关性研究

目的探讨急性脑梗死患者血浆同型半胱氨酸（Hcy）与一氧化氮（NO）水平的相关性及其与急性脑梗死的关系。方法分别采用高效液相色谱法和G riess重氮化反应法检测62例急性脑梗死患者（起病24 h内）血浆Hcy及NO水平,分析两者的相关性及其与急性脑梗死的关系。结果急性脑梗死组血浆Hcy水平明显高于对照组（P〈0.01）,而NO水平则明显低于对照组（P〈0.01）。急性脑梗死组血浆Hcy水平与NO水平呈负相关（r=-0.904,P〈0.01）。结论在急性脑梗死的早期血浆NO水平降低,其原因可能与急性脑梗死前后的高Hcy水平有关。     

下肢深静脉血栓形成患者不同部位血同型半胱氨酸、叶酸和维生素B12水平测定及意义

目的探讨高同型半胱氨酸血症与下肢深静脉血栓形成（DVT）之间的关系。方法90例DVT患者为病例组,90例健康体检者为对照组,同时病例组中40例进行自身对照。血同型半胱氨酸（Hcy）、叶酸和维生素B12（VitB12）水平采用全自动化学发光免疫分析系统测定。结果病例组外周血Hcy总体水平高于对照组（P〈0．01）,血栓局部血浆Hcy总体水平高于对照组（P〈0．01）;血栓局部与外周血Hcy总体水平相比虽轻度升高,但无统计学意义。在原发性DVT患者中,高同型半胱氨酸血症发生率高于继发性DVT患者,差异有统计学意义。结论①高同型半胱氨酸血症是DVT的危险因素之一,对于原发性DVT致病作用更为显著。②采用导管局部采样测定的局部血浆Hcy数据能更加客观和真实地反映体内血浆Hcy水平。