Homocysteine, vitamin B12 and folate in vascular dementia and in Alzheimer disease.

The association between elevated plasma levels of homocysteine (Hcy) and nutritional status has been shown in Alzheimer disease (AD) patients and also in vascular dementia (VaD). Moreover, a previous study provided evidence that the relation between a high Hcy level and low vitamin B12 and folate levels in AD patients is due to biochemical damage, rather than a nutritional deficit. The purpose of this study was to investigate the relationship between plasma Hcy levels and vitamins involved in its metabolism in AD and VaD. Twenty-two VaD patients, 22 AD patients and 24 healthy subjects were studied for Hcy, vitamin B12, vitamin B6 and folate. All patients and control subjects were comparable for age, educational level, nutritional and socioeconomic status. None of them showed macrocytic anemia or impaired renal function. Hcy was significantly increased in VaD patients (26.0 +/- 6.58 micromol/l) as compared to controls (10.7 +/- 3.0 micromol/l) and AD patients (22.3 +/- 4.51 micromol/l; p<0.001); however, AD patients also showed increased levels of Hcy. Folates were significantly reduced in both VaD (10.8 +/- 2.81 nmol/l) and AD (10.0 +/- 2.72 nmol/l; p<0.001) patients, while vitamin B12 showed significantly reduced levels only in AD patients (392.1 +/- 65.32 pmol/l; p=0.02). Vitamin B6 was not significantly different in the three groups. Increased levels of Hcy associated with low vitamin B12 plasma levels were found only in AD patients. This observation led us to consider that vitamin B12 metabolism does not represent the direct consequence of the nutritional status and suggests that neuronal damage results in a functional vitamin B12 deficiency, as emphasized by recent reports. New therapeutic strategies are necessary, considering that available pharmaceutical forms of vitamin B12 are not utilized by neurons in oxidative stress conditions.     

同型半胱氨酸、叶酸及VitB12与血管性痴呆的相关性研究

目的:探讨血浆同型半胱氨酸(Hcy)、叶酸(FA)、VitB12与血管性痴呆(VaD)的相关性。方法:检测VaD患者86例(VaD组),非VaD患者87例(非VaD组),健康体检正常者90例(正常组)血浆Hcy、FA、VitB12浓度。并对3组受检者进行简易智能状态量表(MMSE)评定。结果:VaD组患者Hcy浓度显著高于非VaD组及正常组(P<0.01)。FA、VitB12浓度与Hcy浓度负相关。血浆Hcy、FA、VitB12水平与VaD、MMSE得分显著相关(P<0.01)。结论:VaD高危人群应定期检测Hcy浓度,推荐服用VitB12和FA可预防VaD的发生。     

Homocysteine, vitamin B 12 and folate in Alzheimer's and vascular dementias: the paradoxical effect of the superimposed type II diabetes mellitus condition

BACKGROUND: Increased concentration of plasmatic homocysteine (tHcy) and decreased vitamin B 12 (B12) and folate (FOL) are associated with Alzheimer's (AD) and vascular (VaD) dementias, with type II diabetes mellitus (DM), and reported as risk factors of these diseases. METHODS: The sample (n=122; males=60; mean age=73+/-7 years) comprised AD and VaD patients without DM, with a concomitant DM (AD+DM, VaD+DM), DM alone and controls (CTR), resulting in 6 groups. tHcy, B12 and FOL were determined in duplicate. RESULTS: The one-way ANOVA yielded significant differences between groups for all variables: tHcy p<10(-12); B12 p<10(-3); FOL p<10(-4). Significance for comparisons between groups was set at alpha=0.05, using the Bonferroni's statistic. The comparisons: DM vs. CTR, AD+DM vs. AD, VaD+DM vs. VaD, and DM demented vs. DM non-demented resulted significant for all variables, except for B12 in 2 comparisons. CONCLUSIONS: In demented and control subjects, tHcy and FOL exhibit extreme differences, not so marked between DM and controls. Demented patients with concomitant diabetes are closer to controls than their non-diabetic counterparts. Diabetes affects tHcy and FOL values, which are changed with opposite sign to non-demented. These results suggests a paradoxical phenomenon when diabetes is superimposed to dementias.     

阿尔茨海默病与维生素 B12及同型半胱氨酸的相关性

背景维生素 B12缺乏会产生神经功能障碍,影响中枢神经系统及全身的代谢,补充维生素 B12对预防及延缓阿尔茨海默病( Alzheimer disease, AD)的发展作用机制尚不清楚. 目的 研究 AD与血清维生素 B12,叶酸及血浆同型半胱氨酸水平之间的关系,探讨导致痴呆的机制. 设计以诊断为依据的非随机对照研究. 地点和对象 2002-10/2003-05于华中科技大学同济医学院附属协和医院住院治疗的 AD患者 30例( AD组),均符合美国神经病学语言障碍和卒中-阿尔茨海默病和相关疾病学会( NINCDS- ADRDA)的很可能 AD标准.对照组为同期参加体检的健康正常人 30例. 方法 采用简易精神状态量表( MMSE)对两组患者进行评分,并用放免分析法测定血清维生素 B12及叶酸水平,荧光偏振免疫法( fluorescence polarization immunoassay, FPIA)测定血浆同型半胱氨酸水平. 主要观察指标 ① AD组及对照组之间维生素 B12水平差异.② AD组及对照组之间 Hcy的水平差异.③ MMSE得分与维生素 B12及 Hcy之间的相关性. 结果 AD组维生素 B12水平( 217.3± 134.2) pmol/L明显低于对照组( 313.6± 184.7) pmol/L,二者差异有极显著性 (t=3.93,P< 0.001). AD组血浆同型半胱氨酸 (18.9± 6.8) μ mol/L高于对照组 (9.4± 4.1) μ mol/L,差异有极显著性意义 (t=7.66,P< 0.001). AD组叶酸水平( 29.2 ± 12.7) nmol/L低于对照组( 37.2± 21.2) nmol/L,但差异无显著性 (P >0.05). AD患者维生素 B12水平与 MMSE得分呈正相关( r=0.87).结论 AD患者血清维生素 B12水平与智能障碍及其程度有关.     

脑血管病患者高Hcy血症与叶酸和维生素B12的相关性研究

目的探讨脑血管病患者高同型半胱氨酸(Hcy)血症与叶酸、维生素B12之间的相关性。方法分别检测脑血管病患者和健康对照者血清Hcy、叶酸和维生素B12水平。结果脑血管病组血清Hcy水平显著高于对照组(P<0.01),其中脑梗塞组的血清Hcy水平明显高于脑出血组(P<0.01)。与之相反,脑血管病组的血清叶酸和维生素B12水平明显低于对照组(P<0.01)。相关分析结果显示,脑血管病组的血清叶酸和维生素B12水平与Hcy水平呈负相关(r1=-0.80,r2=-0.83)。结论高Hcy血症与叶酸、维生素B12之间存在负反馈的调节机制可能正是导致脑血管病发生的关键因素。     

血浆同型半胱氨酸、叶酸、维生素B12水平测定与脑卒中的关系

目的探讨血浆同型半胱氨酸(Hcy)、叶酸、维生素B12水平与脑卒中的关系及临床意义。方法用循环酶法和化学发光法检测168例脑卒中患者(脑梗死96例,脑出血42例,短暂性缺血发作30例)血浆中同型半胱氨酸、叶酸、维生素B12水平,并与同期40例健康体检者进行了对照。结果脑卒中患者血浆中Hcy含量均明显高于对照组(P<0.01);叶酸和维生素B12水平明显低于对照组(P<0.05)。结论高同型半胱氨酸血症为脑卒中发病的独立危险因素之一,与叶酸和维生素B12水平下降有关。     

The risk of venous thromboembolism associated with the factor V Leiden mutation and low B-vitamin status.

Venous thromboembolism (VTE) is a multi-factorial disease involving numerous genetic and environmental risk factors. In this study we investigated the occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and low folate and vitamin B12 levels in young patients with thrombosis. We studied 78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age 44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated in all subjects. Factor V Leiden was highly prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous in controls). An increase in the risk of idiopathic VTE was associated with Hcy levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR = 7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin B12 were independently and strongly associated with the risk of VTE in a multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76, respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels of vitamin B12, compared to 28% of patients who were non-carriers of the mutation (p = 0.03). In contrast, none of the control carriers of the mutation had a low level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12 and folate was stronger than that introduced by elevated Hcy levels. The increased risk of VTE, accompanied by factor V Leiden, may be related to confounding environmental factors.     

Erythrocyte membrane Na+,K+-ATPase and Mg2+-ATPase activities in subjects with methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype and moderate hyperhomocysteinaemia. The role of L-phenylalanine and L-alanine.

BACKGROUND: Increased homocysteine (Hcy) blood levels are correlated with vascular and neurological problems. The aim of our study was to investigate erythrocyte membrane Na(+),K(+)-ATPase and Mg(2+)-ATPase activities in patients with methylenetetrahydrofolate reductase (MTHFR) 677 C-->T genotype. METHODS: Blood was obtained from 25 patients before and after folic acid supplementation and from controls (n=30) once. Plasma folate, vitamin B(12) and total antioxidant status (TAS) were measured using commercial kits, Hcy was determined by HPLC and membrane enzyme activities were measured spectrophotometrically. RESULTS: Mg(2+)-ATPase remained unaltered. Membrane Na(+),K(+)-ATPase activity was remarkably increased in patients (0.77+/-0.06 micromol Pi/h x mg protein) and decreased to normal levels (0.52+/-0.05 micromol Pi/h x mg protein; p<0.001) after therapy. TAS did not differ significantly before and after treatment. Hcy levels were significantly higher before therapy (25.4+/-2.8 micromol/L) than levels after therapy (12.1+/-2.0 micromol/L; p<0.001) and in controls (10.5+/-2.5 micromol/L, p<0.001). In vitro, L-phenylalanine (Phe) reversed to normal the stimulated enzyme from patients before therapy. In addition, Phe incubation of the Hcy activated membrane Na(+),K(+)-ATPase from controls resulted in restoration of its activity, whereas L-alanine (Ala) incubation protected the enzyme from Hcy activation. CONCLUSIONS: The increased membrane Na(+),K(+)-ATPase activity may be due to high -SH group Hcy levels. In vitro, Phe reversed the increase in enzyme activity induced by Hcy in controls, as well as the stimulated membrane enzyme in untreated patients. Ala protected the enzyme from Hcy action.     

Homocysteine, vitamin B12, and serum and erythrocyte folate in peritoneal dialysis and hemodialysis patients.

BACKGROUND: Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. High levels of plasma Hcy have been observed in end-stage renal disease patients. Few studies have compared peritoneal dialysis (PD) and hemodialysis (HD) patients and few data are available on erythrocyte folate (ery-F) levels in dialysis patients. OBJECTIVES: To evaluate plasma Hcy concentrations, vitamin B12 (B12), and folate status in dialysis patients; to analyze the possible causes of high Hcy levels; to follow up changes in folate and B12 concentrations after 6 months. DESIGN: A cross-sectional observational study. SETTING: Nephrology division and laboratory of hematology in a university and clinical research hospital. PATIENTS: The study included 82 patients treated with PD for 37 + 37 months and 70 patients treated with HD for 136 + 95 months. LABORATORY METHODS: Plasma Hcy was measured by the immunoenzymatic IMx Hcy FPIA method (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, U.S.A.), serum folate (s-F) and ery-F by the Stratus folate fluorometric enzyme-linked assay, and B12 by the Stratus vitamin B12 fluorometric enzyme-linked assay (DADE-Behring, Newark, DE, U.S.A.). RESULTS: Ninety-six percent of PD and 97% of HD patients had Hcy levels above the cutoff (13.5 micromol/L). Homocysteine level was higher in HD than in PD patients, while the prevalence of hyperhomocysteinemia was similar with the two techniques. Erythrocyte folate was significantly higher in PD (1333 +/- 519 pmol/L) than in HD (1049 +/-511 pmol/L, p < 0.01). Statistically significant correlations were observed between Hcy and B12, s-F, ery-F, and dialysis duration. Multivariate analysis showed a strong correlation between s-F and Hcy. After 6 months there were no differences in Hcy, B12, s-F, and ery-F levels. CONCLUSIONS: Plasma Hcy levels were high in more than 95% of our dialysis patients, with no relation to the type of dialysis. Vitamin B12 and folate were normal in the majority of our patients. However, serum folate was the major determinant of Hcy levels. Such a relation between Hcy and folate suggests that levels of folate within the reference interval are inadequate for dialysis patients.     

同型半胱氨酸在缺血性脑血管病中的应用研究

目的探讨同型半胱氨酸(Hcy)与缺血性脑血管病的关系及B族维生素的干预作用。方法选择缺血性脑血管病（包括脑梗死、短暂性脑缺血发作）为观察组,对照组为体检正常的健康人,观察组中Hcy水平高者再分为观察A组、观察B组;两组均接受抗血小板等常规治疗,观察A组同时服用维生素B6、B12、叶酸,分别测定治疗前后脉搏波传导速度（PWV）、颈内动脉内膜中层厚度（CIMT）,同时比较两组患者1年内缺血性脑血管病的复发率。结果观察组血浆Hcy水平显著高于对照组(P<0.05）,且服用叶酸及维生素B6、B12能有效降低Hcy、PWV及CIMT(P<0.05）,观察1年内缺血性脑血管病复发率与未服用B族维生素者差异无统计学意义（P>0.05）。结论脑梗死的发生与血浆中 Hcy 浓度之间存在密切相关性,因此在脑血管病危险人群中广泛开展 Hcy的浓度筛查,超过正常值者积极予B族维生素干预,将会有效降低动脉粥样硬化及其并发症的发生率。     

Lowering homocysteine and modifying nutritional status with folic acid and vitamin B(12) in Indian patients of vascular disease

Hyperhomocysteinemia is more commonly associated with vascular disease in Indians than in the western populations. It is caused by genetic polymorphisms or dietary deficiencies of the B vitamins. We attempted to identify the association of hyperhomocysteinemia with vitamin B(12) and folate in Indian patients of vascular disease. Homocysteine, vitamin B(12) and folate levels were estimated in 100 controls and 100 patients of vascular disease. Homocysteine estimation was repeated in 73 patients on different vitamin supplements for 6 months. Homocysteine exhibited a significant negative correlation with B(12) only in cerebrovascular disease and peripheral vascular diseasepatients, and with folate in coronary artery disease and cerebrovascular disease patients as well as controls. Single daily dose of folate was as effective as a combination of folate and cobalamin in reducing plasma homocysteine concentrations. Low levels of B(12) contribute to the higher incidence of cerebrovascular disease and peripheral vascular disease, and low folate levels account for higher prevalence of hyperhomocysteinemia in coronary artery disease and cerebrovascular disease. Moreover, irrespective of the cause of hyperhomocysteinemia, folate is known to ameliorate it. Hence, large-scale corrective measures like food fortification or dietary supplementation with folate might benefit the Indian population and reduce the incidence and morbidity of vascular disease.     

Effective homocysteine-lowering vitamin B treatment in peritoneal dialysis patients.

BACKGROUND: Hyperhomocysteinemia, a risk factor for atherosclerosis, is frequently detected in patients with renal failure. Vitamin B supplementation reduces but rarely normalizes homocysteine (Hcy) levels in hemodialysis patients. There are no data about the effects of vitamin B therapy on Hcy levels in patients on peritoneal dialysis (PD). AIMS: We performed this trial both to observe baseline plasma Hcy levels in PD patients and to assess the effects of vitamin B therapy on Hcy levels in continuous ambulatory PD patients. METHODS: We conducted a 6-month prospective study of the effects of vitamin B therapy on plasma Hcy levels. Biochemical analyses were obtained at baseline and after every phase of treatment with folic acid, folic acid plus vitamin B12, and folic acid plus vitamin B12 plus vitamin B6. Eighteen of the 25 enrolled patients finished the study. RESULTS: Hyperhomocysteinemia was present in 83% of PD patients. We detected a trend toward a significant inverse relationship between baseline Hcy and folate levels. There were no significant correlations between baseline Hcy and vitamin B12, peritoneal membrane permeability, dialytic efficiency, or computed peritoneal Hcy clearance. We obtained an effective decrease in mean Hcy concentration from 20 to 14.8 micromol/L after folic acid and vitamin B12 treatment. We observed a further reduction in mean Hcy level to 12.8 micromol/L using the triple therapy; 72% of patients normalized their Hcy value. CONCLUSIONS: High doses of folic acid, vitamin B6, and vitamin B12 normalize Hcy values in the majority of PD patients. This treatment may be important in reducing cardiovascular morbidity and mortality.     

Plasma homocyst(e)ine,folate and vitamin B(12) levels among school children in Taiwan: The Taipei Children Heart Study

OBJECTIVE: The purpose of this study is to examine the association of plasma Hcy, folate and vitamin B(12) levels on CVD risk factors among children in Taiwan. METHODS: After multistage sampling, we selected randomly 1,235 children (609 boys and 626 girls) aged 12 to 15 yr. Plasma Hcy levels was measured using ABBOTT Imx analyzer, while plasma folate and vitamin B(12) were measured using ACS: 180 automated chemiluminescence analyzer. Anthropometric, blood pressure (BP) and other biochemical CVD risk factors including serum total cholesterol (CHOL), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (apoA1) and B (apoB) and lipoprotein(a) [Lp(a)]were measured using standard methods. We also calculated low density lipoprotein-cholesterol (LDL-C) and TCHR (total cholesterol to HDL-C ratio) as atherogenic indices. RESULTS: Boys were taller and heavier, having higher body mass index (BMI), systolic blood pressure (SBP) and plasma glucose levels but lower diastolic blood pressure (DBP), heart rate (HR), cholesterol, TG, HDL-C, LDL-C, TCHR, and Lp(a) levels than girls. Boys also had higher plasma Hcy and lower folate, vitamin B(12), levels than girls (for plasma Hcy, mean +/- SD, 10.50 +/- 4.13 vs. 8.95 +/- 2.61 micromol/L for boys vs. girls, respectively). Plasma Hcy levels were significantly correlated positively with body height, body weight, SBP and DBP in both genders. Body height, body weight, BMI and SBP levels were found to increase with trend among different quintile plasma Hcy subgroups on boys but not on girls. Plasma folate and vitamin B(12) were decreased significantly along with the higher quintile plasma Hcy subgroup in both genders. CONCLUSIONS: Boys had higher plasma Hcy levels than girls after adjusting for age. Furthermore, plasma Hcy levels were significantly associated with anthropometric parameters, such as body height and weight and blood pressure, but not related with lipid profiles among children in Taiwan.     

Impairment of homocysteine metabolism in patients with retinal vascular occlusion and non-arteritic ischemic optic neuropathy.

Mild hyperhomocysteinemia is established as an independent risk factor for atherothrombotic disease, including ocular pathologies such as retinal vascular occlusion and non-arteritic ischemic optic neuropathy (NAION). Low intake or low status of B-vitamins explains elevated total homocysteine (tHcy) concentrations only in part. The underlying cause for disturbed homocysteine metabolism requires further insight. We investigated whether the combined determinations of plasma tHcy, methylmalonic acid (MMA) and cystathionine provide more information on the causes of impaired homocysteine metabolism as compared with vitamin B12, vitamin B6 and folate in patients with ocular ischemic vascular disease. A total of 51 hyperhomocysteinemic (>12 micromol/L) patients with retinal vascular occlusion (n=42) and NAION (n=9) were included. Mild renal dysfunction was an important determinant of tHcy, indicated by the positive correlation between creatinine and tHcy (r=0.47, p=0.001). The assessment of MMA in addition to tHcy identified at least 12 out of 51 patients (23%) who were most likely to have a functional vitamin B12 deficiency. An additional 14 patients (27%) with elevated MMA and cystathionine levels also had slightly elevated concentrations of creatinine, pointing to the need for discrimination between renal dysfunction and vitamin B12 deficiency in this group. In contrast, measurement of cystathionine is very sensitive for renal dysfunction and this marker was strongly related to serum creatinine (r=0.56, p<0.001) and to tHcy (r=0.50, p<0.001). Measurement of the vitamins folate, vitamin B12 and vitamin B6 in plasma did not provide sufficient information on intracellular disturbances in homocysteine metabolism. In conclusion, the metabolites homocysteine, cystathionine and MMA are sensitive indicators and valuable for discrimination of the underlying cause of mild to moderate hyperhomocysteinemia, with implications for therapeutic targeting.     

脑血管病高Hcy血症与维生素B12和叶酸的相关性研究

目的：研究脑血管病患者的高同型半胱氨酸（Hcy）血症与血清维生素B12（VitB12）和叶酸（FA）水平的相关性。方法：采用酶法检测171例脑血管病患者和76例健康体检志愿的血清Hcy水平,用化学发光方法检测其血清FA和VitB12水平。结果：脑血管病组患者血清Hcy水平明显高于对照组（P＆lt;0.01）,其中脑梗死组患者的血清Hcy水平明显高于脑出血组（P＆lt;0.01）;而对照组的血清FA和VitB12水平明显高于脑血管病组（P＆lt;0.01）;脑血管病组患者血清的Hcy水平与其血清VitB12和FA的水平呈负相关（r1=-0.82,r2=-0.86）。结论：血浆Hcy水平升高与脑血管病的发病密切相关,是脑血管病的独立危险因素,而血清中的FA和VitB12的下降可能为导致高同型半胱氨酸血症的关键因素之一。     

The association of vitamin b 12 and folate blood levels with mortality and cardiovascular morbidity incidence in the old old: the Bronx aging study.

OBJECTIVE: An elevated homocysteine level in the blood has been identified as an independent risk factor for vascular disease, including coronary atherosclerosis and venoembolic disease. A deficiency of vitamins B ( 6 ), B ( 12 ), or folate in the blood can cause increased blood levels of homocysteine. We set out to determine whether there was a relationship between blood levels of folate and B ( 12 ) and the subsequent development of cardiovascular disease and mortality in old old ambulatory men and women. DESIGN: Four hundred forty subjects (mean age, 79 years; 64% female) were followed in the Bronx Longitudinal Aging Study, a prospective study of 10 years duration, designed to assess risk factors for cardiovascular and cerebrovascular diseases and dementia in an ambulatory old old cohort. METHODS: Serum levels of vitamin B ( 12 ) and folate were measured and related to the incidence of total all-cause mortality, stroke, myocardial infarction, coronary heart disease, and cardiovascular disease. RESULTS: No statistical gender- or age-related differences were found in the mean levels of folate or B ( 12 ). The concentration of folate in the blood was not related to the incidence of mortality, myocardial infarction, stroke, or overall cardiovascular disease. However, by logistical regression and Cox proportional-hazards regression analyses, there was an increased incidence of mortality and coronary heart disease in those subjects having increased vitamin B ( 12 ) levels in the blood. Each 100-pg increase in B ( 12 ) was associated with a 10% increase in mortality and coronary heart disease incidence. CONCLUSION: These results suggest that in elderly subjects, vitamin B ( 12 ) supplementation should not be routinely provided unless there are clear indications for doing so (a deficiency state), and then only to replace enough B ( 12 ) to correct the deficiency. A suggested treatment paradigm is provided for managing vitamin deficiency states and hyperhomocysteinemia in elderly subjects.     

Parenteral vitamin B12 therapy of hyperhomocysteinemia in end-stage renal disease

BACKGROUND: End-stage renal disease (ESRD) is associated with moderately severe hyperhomocysteinemia that is incompletely normalized by oral folic acid therapy and vitamin B12. METHOD: We administered 1 mg hydroxocobalamin parenterally at 14-day intervals to vitamin B12-replete hemodialysis patients who were already consuming 6 mg folic acid daily by mouth. Plasma total homocysteine (tHcy), serum folate, vitamin B12 and methylmalonate were measured immediately before and after 4 and 8 weeks of therapy. RESULTS: Serum folate concentrations were consistently over 25 times the upper normal limit. Hydroxocobalamin therapy increased serum vitamin B12 concentrations 14-fold (p < 0.001) and reduced plasma tHcy by 23% from 29.7 +/- 2.9 to 22.8 +/- 2.5 micromol/L (p < 0.01); serum methylmalonate decreased by one-third (p < 0.05). CONCLUSIONS: These results demonstrate the Hcy-lowering potential of parenteral vitamin B12 in folic acid supplemented vitamin B12-replete hemodialysis patients, and indicate the need for formal dose-optimization studies of this simple, inexpensive and promising approach to Hcy reduction in end-stage renal disease.     

Homocysteine measurements in geriatric patients

OBJECTIVE: Homocysteine measurements may be relevant in geriatric medicine as homocysteine has been identified as an independent risk factor for prevalent disorders such as occlusive arterial vascular disease, cognitive impairment and dementia. The aim of the present study was to study diagnostic correlates of plasma total homocysteine (tHcy) in geriatric in-patients. MATERIAL AND METHODS: Blood samples for the analysis of tHcy and related factors like serum vitamin B12, serum folate, red blood cell folate and clinical data were collected from geriatric patients (n=114) in stable clinical condition. RESULTS: Almost 40% of the patients had tHcy values above 20 micromol/L. tHcy correlated significantly with serum folate, serum vitamin B12, serum creatinine and congestive heart failure, but not with red blood cell folate, cerebrovascular disease, coronary heart disease or cognitive impairment. CONCLUSIONS: Hyperhomocysteinaemia seems to be frequent in geriatric patients and might primarily be an indicator of low folate and high creatinine values.     

Correlates of total homocysteine plasma concentration in type 2 diabetes

BACKGROUND: Although well-defined in the general population, correlates of total homocysteine (tHcy) plasma concentration have not been sufficiently evaluated in diabetes. We investigated factors potentially associated with tHcy concentration in a cohort of type 2 diabetic subjects. MATERIALS AND METHODS: The common methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism, fasting tHcy, vitamin B12 and folate plasma levels were assessed in 312 diabetic subjects, whose clinical, metabolic and lifestyle information was also available. RESULTS: The MTHFR genotype distribution was comparable to the Hardy-Weinberg equilibrium, with an overall TT homozygous frequency of 22%. Fasting tHcy concentration was significantly higher in men than in women (P < 0.001). Multivariate-adjusted tHcy concentration was significantly different across the quartiles of age (P < 0.001), folate (P = 0.01), vitamin B12 (P = 0.03), creatinine concentrations (P = 0.001) and smoking (P = 0.02). Overall, significant trends were noted for creatinine clearance (P for trend = 0.02) and systolic blood pressure (BP) (unadjusted P for trend = 0.01), whereas no differences were noted according to BMI, diastolic BP, presence of hypertension, and diabetes-related variables, such as diabetes duration, fasting glucose and glycated haemoglobin concentrations, current treatment and diabetes long-term complications. Total homocysteine levels significantly correlated with age, systolic BP, vitamin B12, creatinine and creatinine clearance, but only age, creatinine, folate and vitamin B12 levels were independently associated with tHcy concentration in stepwise regression analysis. CONCLUSIONS: Age, creatinine, folate, vitamin B12, and to a minor extent, sex, smoking, TT genotype and systolic BP were significantly associated with Hcy plasma concentration in type 2 diabetes, whereas no significant associations were noted with diabetes-related variables.     

Homocysteine--a newly recognised risk factor for osteoporosis.

Osteoporosis is a widespread problem, which frequently has devastating health consequences through its association with fragility fractures. The total number of fractures, and hence the cost to society, will increase dramatically over the next 50 years as a result of demographic changes in the number of elderly people. Thus, prevention of osteoporosis by identifying risk factors or risk indicators, as well as the development of new treatment strategies, are major issues. Recent data suggest that homocysteine (Hcy), folate, vitamin B6 and vitamin B12 affect bone metabolism, bone quality and fracture risk in humans. Since circulating Hcy depends on folate, vitamin B6 and vitamin B12, Hcy could be suitable as a risk indicator for micronutrient-deficiency-related osteoporosis. Initial experimental results indicate that Hcy is not only a risk indicator, but also a player in bone metabolism. Moreover, existing data open speculation that folate, vitamin B6 and vitamin B12 act not only via Hcy-dependent pathways, but also via Hcy-independent pathways. However, more studies are needed to clarify the mechanistic role of Hcy, folate, vitamin B6 and vitamin B12 in bone metabolism.