高同型半胱氨酸血症及其相关因素与青年脑梗死的关系

目的探讨同型半胱氨酸(homocysteine,Hcy)及其相关因素与青年脑梗死的关系。方法比较40例青年脑梗死患者(初发年龄<=45岁),30例神经系统非血管性疾病(NVD)患者和30例健康人血浆Hcy水平。分析年龄、性别、体重指数、肝肾功能、吸烟、嗜酒、血清VitBl2、叶酸水平的影响。结果脑梗死组血浆Hcy水平(21.4±18.8umol/L)分别与神经系统非血管疾病组(10.2±5.0umol/L)和健康对照组(12.9±8.6umol/L)比较差异均有显著性(P<0.01)。叶酸、VitB12与Hcy呈负相关,二者的降低与青年脑梗死关系密切(P<0.01)。血肌苷增高和吸烟与Hcy增高有关(P<0.05)。男性Hcy显著高于女性(P<0.05)。结论Hcy和青年脑梗死密切相关,与叶酸、VitBl2呈负相关,与肌苷呈正相关。男性、吸烟也与Hcy增高有关。     

Elevated plasma concentrations of homocysteine in antiepileptic drug treatment

PURPOSE: Homocysteine is an experimental convulsant and an established risk factor in atherosclerosis. A nutritional deficiency of vitamin B6, vitamin B12, or folate leads to increased homocysteine plasma concentrations. During treatment with carbamazepine (CBZ), phenytoin, or phenobarbital, a deficiency in these vitamins is common. The objective of the study was to test the hypothesis that antiepileptic drug (AED) treatment is associated with increased homocysteine plasma concentrations. METHODS: A total of 51 consecutive outpatients of our epilepsy clinic receiving stable, individually adjusted AED treatment and 51 sex- and age-matched controls were enrolled in the study. Concentrations of total homocysteine and vitamin B6 were measured in plasma; vitamin B12 and folate were measured in the serum of fasted subjects. RESULTS: Patients and controls differed significantly in concentrations of folate ( 13.5+/-1.0 vs. 17.4+/-0.8 nM and vitamin B6 (39.7+/-3.4 vs. 66.2+/-7.5 nM), whereas serum concentrations of vitamin B12 were similar. The homocysteine plasma concentration was significantly increased to 14.7+/-3.0 microM in patients compared with controls (9.5+/-0.5 microM; p < 0.05, Wilcoxon rank-sum test). The number of patients with concentrations of >15 microM was significantly higher in the patient group than among controls. The same result was obtained if only patients with CBZ monotherapy were included. Patients with increased homocysteine plasma concentrations had lower folate concentrations. CONCLUSIONS: These data support the hypothesis that prolonged AED treatment may increase plasma concentrations of homocysteine, although the alternative explanation that increased homocysteine plasma concentrations are associated with the disease and not the treatment cannot be completely excluded at the moment.     

Relation of serum levels of homocysteine,vitamin B12 and folate to cognitive functions in multiple sclerosis patients

Background: Hyperhomocysteinemia, vitamin B12 and folate deficiency have been linked to cognitive dysfunction in multiple sclerosis (MS) patients.

Objective: This study aimed to investigate the relation of serum homocysteine (Hcy), vitamin B12 and folate to cognitive functions in MS patients.

Subjects and Methods: Forty-five MS patients and twenty matched healthy controls were included. Subjects were submitted to cognitive assessment using a selected psychometric battery and measurement of serum levels of homocysteine, B12 and folic acid.

Results: MS patients showed significant worse performance in cognitive scales compared to controls (P ≤ 0.05). Serum homocysteine, vitamin B12 and folate showed no significant difference between patients and controls (P > 0.05). Serum homocysteine was negatively correlated with total score of Addenbrooke's Cognitive Examination (ACE), paced auditory serial addition test and controlled oral word association test scores. Serum vitamin B12 was positively correlated with ACE language, visuospatial and total scores and negatively correlated with trail making B score. Serum folate was significantly positively correlated with ACE language and total scores. Homocysteine was the only significant predictor for cognitive impairment in MS patients.

Conclusion: Serum homocysteine may play a role in cognitive dysfunction in MS patients.     

Effect of MTHFR Polymorphisms on Hyperhomocysteinemia in Levodopa-treated Parkinsonian Patients

High plasma homocysteine levels have been observed in Parkinson’s disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with l-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 l-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 ± 5.7 vs. 11.7 ± 2.7 μmol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0–5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 ± 4.9 μmol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 ± 1.6 μmol/l; OR = 0.19, CI = 0.06–0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 ± 3.6 μmol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.     

Effects of vitamin B12, folate,and entacapone on homocysteine levels in levodopa-treated Parkinson’s disease patients: A randomized controlled study

IntroductionPrevious studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson’s disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients.MethodsWe analyzed and compared plasma Hcy levels in 20 levodopa-naïve PD patients and 42 levodopa-treated PD patients, followed by randomized assignment of 42 levodopa-treated patients to treatment groups with either vitamin B12 and folate, entacapone, or no medication.ResultsPlasma Hcy levels in levodopa-treated PD patients were higher than those in the control group, but the difference was not statistical significant (15.25 ± 6.70 and 13.13 ± 4.68, P = 0.216). Patients treated with vitamin B12 and folate had a significant decrease in plasma Hcy levels (P < 0.001). In the entacapone group, Hcy levels were mildly decreased, but the change did not reach statistical significance.ConclusionLevodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. Unlike entacapone, combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma Hcy. We suggest that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated patients.     

Plasma homocysteine, MTHFR C677T, CBS 844ins68bp, and MTHFD1 G1958A polymorphisms in spontaneous cervical artery dissections

Abstract. Mild hyperhomocysteinemia is a probable risk factor for atherosclerotic diseases and stroke. Recently, associations of elevated plasma homocysteine concentrations in the acute phase and of MTHFR 677 TT genotype with spontaneous cervical artery dissections (sCAD) have been reported. The purpose of this study was to test this hypothesis in the currently largest sample of patients with sCAD, taking into account known factors influencing plasma homocysteine levels. Ninety-five patients with past sCAD were compared with 95 age- and sex-matched healthy individuals. Homocysteine, vitamin B6, B12, folate, and polymorphisms of methylenetetrahydrofolate reductase (MTHFR C677T), cystathionine -synthase (CBS 844ins68bp) and methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase (MTHFD1 G1958A) were assessed and any associations were analysed using multivariate statistics. The occurrence of sCAD was associated with elevated homocysteine levels with an odds ratio of 1.327 per 20 % percentile. Homocysteine levels were influenced by gender, smoking status, occurrence of hypertension, vitamin B12 and folate levels, and by the MTHFR TT genotype. MTHFR, CBS 844ins68bp, and MTHFD1 G1958A genotype were not independently associated with the occurrence of sCAD. These data suggest that elevated homocysteine is associated with the occurrence of sCAD. The MTHFR C677T polymorphism is associated with the homocysteine level.     

MTHFR基因多态性及同型半胱氨酸与青年脑血管病的关系

目的:研究Ns,N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血浆同型半胱氨酸(Hcy)水平与青年脑血管病的关系。方法:研究对比40例青年脑血管病患者(首次发病年龄≤50岁)及32例健康青年人的MTHFR基因多态性及血浆Hcy水平。结果:(1)对照组及病例组T/T纯合子率分别为37.5％和22.5％;T等位基因频率分别为60.9％和51.3％,差异均无显著统计意义(均P>0.05)。(2)病例组血浆Hcy几何均值(11.0±2.3μmol/L)显著高于对照组(8.0±1.4μmol/L,P<0.05)。(3)所有受试者中T/T组Hcy值高于C/C组(10.4μmol/L和7.6μmol/L),但差异无显著性(P>0.05)。结合叶酸考虑,进一步将所有受试者按叶酸中位数水平分组。叶酸中位数以下组中,T/T组Hcy值显著高于C/C组(P<0.05);而叶酸中位数以上组中,T/T组Hcy值与C/C组无显著差异。(4)血浆Hcy与叶酸、维生素B12呈显著负相关,与肌酐呈显著正相关。吸烟者血浆Hcy水平显著高于不吸烟者(P<0.05)。结论:(1)本组人群MTHFR基因C677T突变的纯合子在低叶酸状态下可引起血浆Hcy水平显著增高,但与青年脑血管病无显著关系。MTHFR基因677TT纯合突变可能为健康青年人脑血管的保护因素。(2)血浆Hcy水平与青年脑血管病的发生密切相关。(3)叶酸、维生素B12肌酐、吸烟是Hcy的非遗传影响因素。     

Homocysteine,vitamin B12 and folate levels in Iranian patients with Multiple Sclerosis: A case control study

Background

Recently, homocysteine (Hcy), folate, and vitamin B12 have been proposed to have several roles on MS pathogenesis.

Objective

We performed this study to determine the role of serum levels of Hcy, vitamin B12, and folate in patients with relapsing remitting MS (RRMS) and compared them with healthy controls.

Methods

We recruited 75 RRMS patients and 75 subjects as controls with the same age and sex. Homocysteine was measured using fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured through ion-capture method.

Results

Mean plasma levels of vitamin B12, folate, and Hcy in cases were 342.64 ± 210.66 pg/ml, 9.74 ± 4.77 ng/ml, and 22.73 ± 11.63 μM/L, respectively, which showed significant difference in comparison with the controls. In addition, there were significant correlations between mean serum Hcy levels and duration of disease (r = 0.2, p = 0.05) and treatment with interferon (r = 0.21, p = 0.01). In cases, Hcy level was higher among those on β interferon (24.56 ± 11.87 vs. 19.71 ± 10.75, p = 0.01).

Conclusions

We concluded that serum levels of vitamin B12 and folate decreased in RRMS patients, but Hcy levels increased significantly. It seems necessary to conduct prospective trials to determine whether the treatment with supplements and correct biomarker levels in the early stage of the disease can change the course of the disease. We recommend regular checking of the serum level of Hcy in patients who use disease-modifying drugs.     

Hospital Anxiety and Depression Scale (HADS): validation in a Greek general hospital sample

Background

The aim of the study was to assess the plasma levels of homocysteine in patients with multiple sclerosis (MS) and to investigate whether an association with depression exists.

Methods

Plasma homocysteine (Hcy), vitamin B12 and plasma folate were measured in 65 moderately disabled patients with relapsing/remitting MS (RR-MS) and 60 healthy controls. All subjects were assessed with the Beck Depression Inventory (BDI).

Results

Hcy levels were significantly increased in MS patients compared to controls (13.5 ± 4.7 μmol/l vs 8.5 ± 3.1, p < 0.001). A significant correlation was found between Hcy levels and BDI scores (Pearson r = 0.3025, p < 0.05). Plasma Hcy was not related to Extended Disability Status Scale (EDSS) score, age, disease duration or vitamin B12 and folate.

Conclusion

Moderately disabled MS patients with elevated Hcy levels are particularly prone to develop depressive symptomatology. Further study is warranted in order to elucidate the prognostic and therapeutic implications of this novel finding.     

Hyperhomocysteinemia and schizophrenia: case control study

Objectives

Homocysteine (Hcys) is a sulphur-containing amino acid that has been widely investigated for its putative role in neuropsychiatric disorders. Elevated plasma homocysteine levels have been associated with schizophrenia. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. The aim of the study was to determine plasma Hcys, folate and vitamin B12, and the frequency and severity of hyperhomocysteinemia in patients with schizophrenia, and to investigate the association between Hcys and clinical features and its relationship with folate and vitamin B12 levels.

Methods

This was a case-control study carried out on 61 (54 males and seven females, mean age = 33.3 ± 9.2) inpatients with chronic schizophrenia according to DSM-IV criteria and 46 (25 males and 21 females, mean age = 45.9 ± 14.2) healthy controls. Most of patients (90.2%) were treated by first generation antipsychotics with a mean daily dosage of 401.6 mg chlorpromazine equivalents. Total homocysteine serum levels were determined quantitatively by fluorescence-polarization immunoassay (FPIA) with an AxSYM analyzer™ (Abbott). Quantitative vitamin B12 and folate serum levels were measured with an Elecsys 2010 analyzer™ (Roche Diagnostics). Differences between patients and controls were examined using a two-way Ancova with gender and diagnosis as independent variables, adjusting for age.

Results

Patients with schizophrenia showed higher plasma Hycs and lower plasma folate than controls (mean = 16.1 μmol/L in patients versus 10.9 μmol/L in controls; P = 0.028 for Hycs and 4.2 μg/L in patients versus 8.2 μg/L in controls; P < 0.001 for folate). Patients and controls did not differ in vitamin B12 levels. Both male and female patients had increased plasma Hcys compared to controls. Hyperhomocysteinemia (Hcys levels > 15 μmol/L) was present in 34.4% of the patients versus 15.2% in controls. The prevalence of moderate hyperhomocysteinemia (Hcys levels: 15–29 μmo/L) was 26.2% and that of intermediate hyperhomocysteinemia (Hcys levels: 30–100 μmol/L) was 8.2%. In patients with schizophrenia, plasma Hcys was not correlated with age (r = 0.07; P = 0.56), duration of illness (r = –0.04; P = 0.78) and did not differ with gender and clinical sub-types. Moreover, plasma Hcys was higher in patients without family history of psychiatric disorders (19.2 μmol/L) versus 12.7 μmol/L in patients with family history of psychiatric disorders (P = 0.032). Concerning therapeutic features, plasma Hcys did not differ with type of antipsychotic and was not related to daily dosage of antipsychotics. A negative correlation was found between plasma Hcys and vitamin B12 levels (r = –0.26; P = 0.04).

Conclusion

These results confirm an increase of Hcys levels in schizophrenic patients and suggest that it is associated with absence of family history of psychiatric disorders and with low vitamin B12 levels. Hyperhomocyteinemia could be related to the pathophysiology of aspects of this illness. Homocysteine should be considered as a factor to consider in monitoring and management of patients with schizophrenia.     

Plasma homocysteine levels in patients treated with levodopa: motor and cognitive associations

OBJECTIVE: The aim of this study was to determine whether hyperhomocysteinemia caused by levodopa used in idiopathic Parkinson's disease (IPD) is associated with cognitive or physical impairments. The role of folate and vitamin B12 levels in this context was also ascertained. METHODS: Thirty-nine patients who had been followed with the diagnosis of IPD in our clinic for > 2 years and 28 healthy control subjects with similar demographic features were included in the study. The homocysteine, folic acid and vitamin B12 levels and the results of the short test of mental status (STMS) and the clock drawing test of IPD patients were compared with those of the controls. Subsequently, the patients with a homocysteine level of >14 micromol/l were compared with those having a homocysteine level of <14 micromol/l by means of detailed neuropsychometric test batteries. RESULTS: Homocysteine levels were significantly higher in the patient group in comparison with the controls. There was a negative correlation between hyperhomocysteinemia and the levels of vitamin B12 and folate. On the other hand, a positive correlation between hyperhomocysteinemia and the levodopa dose was detected. There was a positive correlation between hyperhomocysteinemia and unified Parkinson's disease rating scale (UPDRS) motor section. The critical dose of levodopa was observed to be 300 mg/d. In terms of cognitive and frontal functions, no significant difference was detected between the patients and control group. The subgroup with a homocysteine level of >14 micromol/l had a significantly poorer performance in frontal and memory tests. DISCUSSION: In patients with IPD who are detected to have hyperhomocysteinemia, the assessment of the cognitive performance, folic acid and vitamin B12 levels and the supplementation of folic acid and vitamin B12 to the treatment regimen might be appropriate.     

叶酸、B族维生素对青年脑卒中高同型半胱氨酸血症的干预作用

目的:了解石家庄地区青年脑梗死和TIA患者(年龄≤45岁〉血清同型半胱氨酸(homocysteine,HCY)水平及给予叶酸、B族维生素治疗后HCY含量的变化。方法:采用荧光偏振免疫分析法,对80例脑梗死患者,80例TIA患者及80例健康人进行血清HCY的检测,同时测定其叶酸、维生素B12水平后,各组均随机分成干预治疗组与非干预治疗组,每组40例,干预治疗组给予叶酸5mg,隔日1次,维生素B12250ug,1日1次,维生素B610mg,1日1次,口服6个月后复查上述各指标。结果:治疗前三组血清HCY水平各不相同,脑梗死组为(16.5±5.4)mmol/L,TIA组为(14.4±5.0)mmol/L,与正常对照组(12.1±2.9)mmol/L比较,具有显著性差异(P<0.01)。相关分析发现,血HCY水平与叶酸、维生素B12呈负相关。干预治疗后,治疗组患者的血HCY水平均有下降。结论:高HCY血症是青年脑梗死及TIA患者的独立致病因素,补充营养元素有助于降低血HCY水平。     

Hyperhomocysteinemia in Tunisian bipolar I patients

Aims: The aim of the present study was to investigate hyperhomocysteinemia in Tunisian bipolar I patients according to 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism. Methods: The subjects consisted of 92 patients with bipolar I disorder diagnosed according to DSM‐IV, and 170 controls. Plasma total homocysteine, folate and vitamin B12 were measured. MTHFR C677T polymorphism was determined by polymerase chain reaction–restriction fragment length polymorphism. Results: Compared with controls, patients had a significantly higher homocysteine level (16.4 ± 9.8 vs 9.6 ± 4.5 µmol/L; P < 0.001) and a significantly lower folate level (3.2 ± 0.9 vs 6.5 ± 3.2 µg/L; P < 0.001). C677T MTHFR polymorphism genotype frequencies were in Hardy–Weinberg equilibrium. After adjustment for MTHFR C677T genotypes, hypofolatemia, hypovitamin B12 and for potential confounding factors, the odds ratio (OR) of hyperhomocysteinemia associated with bipolar disorder remained significant (OR, 5.53; 95% confidence interval: 1.92–15.86; P = 0.001). In patients, there was no significant change in hyperhomocysteinemia, hypofolatemia and hypovitamin B12 with regard to the clinical and therapeutic characteristics, whereas the highest prevalence of hyperhomocysteinemia was found in depressive patients and when illness duration was >12 years. Hypofolatemia was seen in all patients on lithium and in the majority of patients on carbamazepine, and the highest prevalence of hypovitamin B12 was noted in patients taking carbamazepine. Conclusion: Hyperhomocysteinemia was more frequent in bipolar I patients independent of C677T polymorphism. Patients had reduced levels of folate, which modulates homocysteine metabolism. Indeed, this finding indicates that folate supplementation may be appropriate for bipolar patients with hyperhomocysteinemia.     

Plasma homocysteine, folate and B12 in chronic schizophrenia

Elevated plasma levels of the amino acid homocysteine have been associated with schizophrenia, particularly in young male patients. Among other factors, low folate and vitamin B12 levels have been implicated in the increase in homocysteine. In order to investigate this association, we determined plasma homocysteine, folate and B12 levels in 97 (67 males and 30 females) inpatients with chronic schizophrenia and 103 (46 males and 57 females) controls. Patients and controls did not differ in folate or B12 levels, after adjusting for age. Patients with schizophrenia had higher plasma homocysteine than controls (mean=15.42 micromol/l in cases versus 11.54 micromol/l in controls: F(1,195)=17.978; p<0.001). This difference persisted after controlling for folate and B12 concentrations. Both male and female patients had increased plasma homocysteine compared to controls [(males: mean=16.61 micromol/l in cases versus mean=13.72 in controls: F(1,110)=5.54; p=0.020) (females: mean=12.78 micromol/l in cases versus mean=9.79 micromol/l in controls: F(1,84)=13.54; p<0.001)]. When dividing our sample into two age groups (age < and > or =50 years), both young and older females and younger males with schizophrenia had increased plasma homocysteine compared to controls. We therefore suggest that homocysteinemia is a general risk factor for schizophrenia. We further suggest that it is not limited to young male patients and is not necessarily associated with low folate or B12 levels.     

轻度认知障碍患者血浆同型半胱氨酸和血清维生素B12及叶酸水平变化研究

目的 探讨轻度认知障碍(MCI)患者血浆同型半胱氨酸(Hcy)、血清维生素B12及叶酸水平的变化及相互关系.方法 MCI组80例,正常对照组80例,检测所有观察对象的血浆同型半胱氨酸、血清VitB12及叶酸水平并分析相互关系.结果 MCI组血浆Hey水平较正常组显著增高为(18.9±8.8)μmol/L vs(14.35±5.7)μmol/L,而血清叶酸和VitB12水平在正常组和MCI组之间并没有显著差异;相对于血浆Hey正常组,MCI比值比(0R)在轻、中度高同型半胱氨酸血症组中增高(OR=1.85,95%CI=1.56～2.95;OR=3.32,95%CI=1.61～6.48;P=0.001);无论在MCI组还是在正常组中,血浆Hey与血清叶酸及Vit B12的水平均呈负相关.结论 血浆Hey水平升高与MCI相关,叶酸和VitB122缺乏可能导致血浆Hcy水平升高.     

Folate,vitamin B12, homocysteine,and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine Study

BACKGROUND: An association between depression and folate status has been demonstrated in clinical studies, whereas data are sparse on the relationship between depression and other components of 1-carbon metabolism such as vitamin B12, homocysteine, and the methylenetetrahydrofolate reductase 677C-->T polymorphism. The relationship between anxiety and these components is less well known. This study examined the associations between folate, total homocysteine, vitamin B12, and the methylenetetrahydrofolate reductase 677C-->T polymorphism, and anxiety and depression in a large population-based study. METHODS: Anxiety and depression, measured by the Hospital Anxiety and Depression Scale, were assessed in 5948 subjects aged 46 to 49 years (mean, 47.4 years) and 70 to 74 years (mean, 71.9 years) from the Hordaland Homocysteine Study cohort. By means of logistic regression models, anxiety and depression scores were examined in relation to the factors listed above. RESULTS: Overall, hyperhomocysteinemia (plasma total homocysteine level > or =15.0 micro mol/L [> or =2.02 mg/dL]) (odds ratio, 1.90; 95% confidence interval, 1.11-3.25) and T/T methylenetetrahydrofolate reductase genotype (odds ratio, 1.69; 95% confidence interval, 1.09-2.62), but not low plasma folate or vitamin B12 levels, were significantly related to depression without comorbid anxiety disorder. Plasma folate level was inversely associated with depression only in the subgroup of middle-aged women. None of the investigated parameters showed a significant relationship to anxiety. CONCLUSION: Our results provide further evidence of a role of impaired 1-carbon metabolism in depression.     

Plasma homocysteine levels in multiple sclerosis

BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.     

Serum folate, vitamin B12, and homocysteine in major depressive disorder, Part 2: predictors of relapse during the continuation phase of pharmacotherapy

OBJECTIVE: In the present study, we assessed the relationship between serum folate, vitamin B12, and homocysteine levels on the rate of relapse in outpatients with remitted major depressive disorder (MDD) during a 28-week continuation phase of treatment with fluoxetine. METHOD: Seventy-one outpatients (mean +/- SD age = 40.2 +/- 11.1 years; 56.3% women) with MDD (as assessed with the Structured Clinical Interview for DSM-III-R) who had remitted and who were enrolled in the continuation phase of treatment with fluoxetine had serum folate, vitamin B12, and homocysteine measurements completed at baseline (prior to acute-phase treatment). Patients were followed for 28 weeks of continued treatment with fluoxetine 40 mg/day to monitor for depressive relapse. Folate levels were classified as either low (< or = 2.5 ng/mL) or normal. Vitamin B12 levels were classified as either low (< or = 200 pg/mL) or normal. Homocysteine levels were classified as either elevated (> or = 13.2 micromol/L) or normal. With the use of separate logistic regressions, we then assessed the relationship between folate, vitamin B12, and homocysteine level status and relapse. The study was conducted from November 1992 to January 1999. RESULTS: The presence of low serum folate levels (p =.004), but not low B12 (p >.05) or elevated homocysteine levels (p >.05), was associated with relapse during continuation treatment with fluoxetine. The relapse rates for patients with (N = 7) and without (N = 64) low folate levels were 42.9% versus 3.2%, respectively. CONCLUSION: Low serum folate levels were found to place patients with remitted MDD at risk for depressive relapse during the continuation phase of treatment with fluoxetine.     

Association of hyperhomocysteinemia in Alzheimer disease with elevated neopterin levels

In patients with dementias including Alzheimer disease (AD), elevated blood concentrations of homocysteine are common, often going along with low normal folate and vitamin B12. Immune activation leading to oxidative stress also seems to play an important role in the pathogenesis of AD. To find out a possible relationship between immune activation and the development of moderate hyperhomocysteinemia, we determined serum concentrations of homocysteine, folate, vitamin B12 and immune activation markers 75 kD soluble TNF receptor (sTNF-R75) and neopterin in 38 patients with clinically diagnosed AD. A subgroup of patients (45%) presented with increased homocysteine concentrations in comparison to reference ranges in healthy controls of similar age. Also, concentrations of immune activation markers were elevated in a significant proportion of patients. In 17 patients with moderate hyperhomocysteinemia, concentrations of neopterin were higher than in those with lower homocysteine (p < 0.001). Homocysteine correlated with folate (rs= -0.43; p < 0.01) and neopterin (rs= 0.506; p < 0.001). The data suggest that immune activation and concomitant production of reactive oxygen species in patients with AD could be involved in the development of hyperhomocysteinemia via an enhanced decomposition of folate.     

Plasma homocysteine, vitamin B12 and folate in Alzheimer's patients and healthy Arabs in Israel

High plasma homocysteine (tHcy) is a risk factor for cardiovascular disease and stroke and Alzheimer's disease (AD). An inverse relationship has been reported between tHcy and plasma B12 and folate levels. Seventy-nine AD patients and 156 controls from three Arab villages in northern Israel participated. Plasma tHcy, B12 and folate levels were determined. Data were analyzed using univariate statistical tests and logistical regression with confounders. tHcy was significantly higher in AD patients (20.6+/-8.7 micromol/l) than in controls (16.4+/-6.5 micromol/l) (p=0.03) after correction for year of birth, gender and smoking status. Plasma B12 (322.9+/-136.0/350.5+/-175.3 pmol/l) and plasma folate (4.5+/-3.8/4.9+/-2.6 nmol/l) levels did not differ significantly between AD patients and controls. Subjects in the highest tHcy tertile or in the lowest B12 and folate tertiles did not have greater risk to develop AD. In this population residing in Arab villages in northern Israel, tHcy levels were significantly higher among AD patients than in controls. Plasma B12 and folate levels were lower among cases but were not significant. There was not a significant association between plasma tHcy, B12 and folate levels in controls or AD patients. High levels of tHcy may suggest the need for folate and vitamin B12 supplementation in this population.