Multiple sclerosis and vitamin B12 metabolism

Multiple sclerosis (MS) is occasionally associated with vitamin B12 deficiency. Recent studies have shown and increase risk of macrocytosis, low serum and/or CSF vitamin B12 levels, raised plasma homocysteine and raised unsaturated R-binder capacity in MS. The aetiology of the vitamin B12 deficiency in MS is often uncertain and a disorder of vitamin B12 binding or transport is suspected. The nature of the association of vitamin B12 deficiency and MS is unclear but is likely to be more than coincidental. There is a remarkable similarity in the epidemiology of MS and pernicious anaemia. Vitamin B12 deficiency should always be looked for in MS. The deficiency may aggravate MS or impair recovery. There is evidence that vitamin B12 is important for myelin synthesis and integrity but further basic studies are required.     

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.     

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.     

同型半胱氨酸与兔脑动脉损伤的关系及维生素B6、B12、叶酸对其预防作用的探讨

目的探讨高蛋氨酸(Met)喂饲兔引发高同型半胱氨酸(Hcy)血症与脑动脉损伤的关系,同时观察补充VitB6、VitB12、叶酸对血Hcy水平和动脉损伤的影响.方法采用纯种雄性新西兰兔26只,分为三组对照组、高蛋氨酸组、干预组,分别喂以普通兔饲料每只200g/d、普通饲料添加0.5%Met、普通饲料每天每只兔添加0.5%Met、叶酸2.5mg、VitB6 10mg、VitB12 200mg,喂养6个月,测定血浆总Hcy(tHcy),光镜检测脑动脉组织学改变.结果实验前血浆tHcy浓度三组间无明显差异,实验后断食2 h和7 h血tHcy浓度高Met组明显高于对照组(P＜0.01),而干预组血tHcy浓度明显低于高Met组(P＜0.01),但仍高于对照组.光镜组织学检测发现高Met组和干预组脑动脉可见内皮细胞坏死、脱落、溃疡形成,附壁血栓,中膜平滑肌散乱疏松.结论高Met引发高Hcy血症对脑动脉有损伤,且VitB6、VitB12、叶酸的补充可以降低高Met引发的高Hcy浓度的水平.     

丙戊酸钠对癫痫患者血同型半胱氨酸、叶酸、维生素B_(12)水平的影响

目的探讨丙戊酸钠(VPA)对血同型半胱氨酸(Hcy)、叶酸(Fol)、维生素B12(VitB12)浓度的影响。方法分别检测VPA单药治疗癫痫患者的血Hcy、Fol、VitB12浓度,并与未服用抗癫痫药的癫痫患者组及健康对照组比较。结果 VPA组患者血Hcy浓度明显高于癫痫对照组和正常对照组(P<0.01),Fol浓度低于癫痫对照组和正常对照组(P<0.05),VitB12浓度在VPA组有升高趋势。结论 VPA可引起癫痫患者血Hcy水平升高和Fol水平降低,长期服用VPA的癫痫患者应监测血Hcy、Fol、VitB12浓度,及时补充B族维生素、Fol有利于减少血栓事件的发生。     

急性脑梗死患者血浆同型半胱氨酸、叶酸、维生素B12水平的测定及其临床意义

目的 探讨血浆同型半胱氨酸(Hcy)在急性脑梗死发病过程中的临床意义以及与病情、伴发症、叶酸、维生素B_(12)之间的关系。方法 采用化学发光法测定急性脑梗死患者血浆Hcy、叶酸、维生素B_(12)水平,并与对照组进行比较。结果急性脑梗死组血浆Hcy水平明显高于对照组(P<0.001),叶酸明显低于对照组(P<0.001);重型患者血浆Hcy水平明显高于中型及轻型患者(P<0.01,0.01),叶酸明显低于中型及轻型患者(P<0.01,0.05);伴发高血压病的患者血浆Hcy水平明显高于非高血压病的患者(P<0.05);急性脑梗死组血浆Hcy与叶酸、维生素B_(12)呈负相关(P<0.01,0.01);对照组血浆Hcy与叶酸呈负相关(P<0.05)。结论高Hcy血症是脑梗死的一个新的重要危险因素;Hcy水平与病情密切相关,与叶酸、维生素B_(12)呈负相关。     

AD患者血清Hcy叶酸及维生素B_(12)与认知功能减退的关系研究

目的研究维生素B_(12)和叶酸水平以及同型半胱氨酸是否对阿尔茨海默症(AD)患者存在潜在影响。方法运用美国国立神经病学、语言障碍和卒中-阿尔茨海默病和相关疾病学会(NINCDS-ADRDA)标准严格筛选AD患者95例。从体检中心选取年龄、性别及受教育程度匹配的无脑血管病、无认知障碍的健康对照组76例。采用化学发光微粒子免疫分析法检测171例年龄≥50岁的老年痴呆患者血清维生素B_(12)和叶酸水平。采用肝素抗凝的血浆进行循环酶法Hcy测定。探讨血清低水平维生素B_(12)和叶酸以及高水平同型半胱氨酸是否是老年痴呆发生的危险因素。认知功能的评价采用目前通用的神经心理测试:中文版简易精神状态检查表(MMSE)。采用Logistic回归分析评估血清维生素B_(12)、叶酸以及同型半胱氨酸与老年痴呆患病风险的关系。结果 171例中153例叶酸正常,其中对照组79例(51.63%),实验组74例(43.27%);124例维生素B_(12)正常,其中对照组60例(48.39%),实验组64例(51.61%);101例同型半胱氨酸正常,其中对照组51例(50.50%),实验组50例(49.50%)。作各协变量调整后,AD患者血清维生素B_(12)及叶酸水平以及同型半胱氨酸与CMMES评分无相关性(P0.05)。但低血清维生素B_(12)水平以及低叶酸水平与AD患病风险相关。结论血清维生素B_(12)和叶酸水平以及同型半胱氨酸水平与AD患者认知功能之间无明显关联。低水平维生素B_(12)以及低水平叶酸可能通过某种机制增加AD患病风险,低水平同型半胱氨酸可能通过某种机制降低AD患病风险。     

Cobalamin (vitamin B(12)) in subacute combined degeneration and beyond: traditional interpretations and novel theories

Subacute combined degeneration (SCD) is a neuropathy due to cobalamin (Cbl) (vitamin B(12)) deficiency acquired in adult age. Hitherto, the theories advanced to explain the pathogenesis of SCD have postulated a causal relationship between SCD lesions and the impairment of either or both of two Cbl-dependent reactions. We have identified a new experimental model, the totally gastrectomized rat, to reproduce the key morphological features of the disease [spongy vacuolation, intramyelinic and interstitial edema of the white matter of the central nervous system (CNS), and astrogliosis], and found new mechanisms responsible for the pathogenesis of SCD: the neuropathological lesions in TGX rats are not only due to mere vitamin withdrawal but also to the overproduction of the myelinolytic tumor necrosis factor (TNF)-alpha and the reduced synthesis of the two neurotrophic agents, epidermal growth factor (EGF) and interleukin-6. This deregulation of the balance between TNF-alpha and EGF synthesis induced by Cbl deficiency has been verified in the sera of patients with pernicious anemia (but not in those with iron-deficient anemia), and in the cerebrospinal fluid (CSF) of SCD patients. These new functions are not linked to the coenzyme functions of the vitamin, but it is still unknown whether they involve genetic or epigenetic mechanisms. Low Cbl levels have also been repeatedly observed in the sera and/or CSF of patients with Alzheimer's disease or multiple sclerosis, but whether Cbl deficit plays a role in the pathogenesis of these diseases is still unclear.     

慢性精神分裂症住院患者血清叶酸、维生素B12 及铁蛋白水平的研究

目的 探讨精神分裂症患者的血清叶酸、维生素B12及铁蛋白水平分布特点.方法 对1042例精神分裂患者进行血液采样,采用电化学发光技术检测血清叶酸、维生素B12、铁蛋白水平,并比较不同性别、年龄患者的水平差异.结果 精神分裂症患者中,较低维生素B12、叶酸及铁蛋白水平的发生率普遍>5%,低叶酸水平发生率高达38.29%,低维生素B12的发生率为18.14%.精神分裂症患者的叶酸水平存在性别差异(t=-5.83,P<0.01),维生素B12水平存在年龄差异(t=2.08,P<0.05).结论 慢性精神分裂症患者低血清维生素B12、叶酸及铁蛋白水平的发生率高,需要予以积极关注.     

血清叶酸、维生素B12水平与脑梗死的关系

目的为探讨血清叶酸、维生素B12水平与脑梗死的关系.方法运用放射免疫分析法检测50例脑梗死患者和44例正常对照组的血清叶酸、维生素B12浓度.结果脑梗死组血清叶酸、维生素B12浓度分别为(5.97±1.96)μg/ml、(511.47±212.06)μg/ml;对照组分别为(8.08±2.25)μg/ml、(806.91±254.60)μg/ml.脑梗死组血清叶酸、维生素B12水平均明显低于对照组,两组有显著性差异(P＜0.01).结论提示血清叶酸、维生素B12水平下降与脑梗死的发生有关,可能是其中又一危险因素.     

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.     

氟桂利嗪与维生素B_(12)对高同型半胱氨酸血症干预治疗的效果

目的考察氟桂利嗪与维生素B_(12)对高同型半胱氨酸血症干预治疗的效果。方法将100例高同型半胱氨酸血症患者随机分为观察组和对照组,每组50例。对照组在给予常规叶酸治疗的基础上加用维生素B12治疗,观察组在此基础上加用氟桂利嗪治疗。比较2组患者治疗前后半胱氨酸水平、血管内皮细胞损伤水平及血流动力学变化。结果 2组患者治疗后半胱氨酸水平与治疗前比较差异具有统计学意义(P0.01),2组间差异无统计学意义(P0.05)。2组患者治疗后血浆内皮素(ET-1)、一氧化氮代谢产物(NO_2~-/NO_3~-)、一氧化氮合酶(NOS)水平与治疗前比较差异具有统计学意义(P0.01),观察组与对照组比较差异具有统计学意义(P0.01)。2组患者治疗后脑动脉最大血流速度(MCAVs)与治疗前比较差异具有统计学意义(P0.01),观察组与对照组比较差异具有统计学意义(P0.01)。结论氟桂利嗪有助于降低血管内皮细胞损伤进而改善患者血流动力学,具有临床应用价值。     

Involuntary movements due to vitamin B12 deficiency

Abstract

Deficiency of vitamin B₁₂ produces protean effects on the nervous system, most commonly neuropathy, myelopathy, cognitive and behavioural symptoms, and optic atrophy. Involuntary movements comprise a relatively rare manifestation of this readily treatable disorder. Both adults and infants deficient in vitamin B₁₂ may present with chorea, tremor, myoclonus, Parkinsonism, dystonia, or a combination of these, which may precede diagnosis or become apparent only a few days after parenteral replacement therapy has begun. The pathogenesis of these movement disorders shows interesting parallels to certain neurodegenerative conditions. The clinical syndrome responds well to vitamin B₁₂ supplementation in most cases, and an early diagnosis is essential to reverse the haematological and neurological dysfunction characteristic of this disorder. In this article, we elucidate the association of vitamin B₁₂ deficiency with movement disorders in adults and in infants, discuss the pathogenesis of this association, review previously reported cases, and present a young adult male with severe generalized chorea that showed a salutary response to vitamin B₁₂ supplementation.     

B族维生素干预高同型半胱氨酸血症在缺血性卒中二级预防中的效果评价

目的评价B族维生素干预Hhcy在IS二级预防中的效果,为IS的二级预防提供更多的临床证据。方法 141例符合试验条件的汉族男性IS患者,随机纳入安慰剂对照组（在常规治疗的基础上添加安慰剂）或维生素干预组（在常规治疗的基础之上添加叶酸5mg/d＋维生素B620mg/d＋甲钴胺1.0mg/d）,检测入组后4周和6月时的血浆Hcy水平,同时追踪观察2组患者2a内IS再发及IS相关性死亡事件发生的情况。结果在入组后4周和6月时,维生素干预组的血浆Hcy水平明显低于安慰剂对照组（P〈0.01）;至2a随访期末,安慰剂对照组与维生素干预组IS的再发率分别为25.00%和8.82%（P〈0.05）,其中TIA的再发率分别为8.33%和2.94%（P〉0.05）,脑梗死的再发率分别为16.67%和5.88%（P〉0.05）;安慰剂对照组与维生素干预组IS相关性死亡事件的发生率分别为3.33%和1.47%（P〉0.05）。Logistic回归分析显示B族维生素干预Hhcy是IS再发的独立保护因素（OR=0.258,P〈0.05）。结论 B族维生素干预能有效降低合并Hhcy的汉族老年男性IS患者的血浆Hcy水平及IS的再发风险。     

叶酸和维生素B_(12)对高Hcy急性脑梗死患者血Hcy水平及神经功能的影响

目的观察叶酸和维生素B12对高同型半胱氨酸(Hcy)急性脑梗死(ACI)患者血Hcy水平及神经功能的影响。方法选取100例高Hcy水平ACI患者为研究对象,随机分为观察组和对照组各50例。对照组患者给予常规治疗,观察组患者在常规治疗的基础上加用口服叶酸和维生素B12治疗。观察和比较2组患者治疗前后的血浆Hcy水平、血清一氧化氮(NO)水平、血清内皮素(ET)水平、日常生活能力量表(ADL)评分、美国国立卫生研究院卒中量表(NIHSS)评分。结果观察组患者治疗后血浆Hcy水平、血清NO水平、血清ET水平均较治疗前显著改善(t=25.146、-11.405、15.493,P0.05),且均优于对照组(t=-26.364、10.550、-15.181,P0.05);2组患者治疗后NIHSS评分、ADL评分均较治疗前显著改善(t=22.802、16.870、-22.181、-11.871,P0.05),且观察组患者治疗后的NIHSS评分、ADL评分均显著优于对照组(t=-7.798、10.516,P0.05)。结论应用叶酸和维生素B12治疗ACI,能够降低血浆Hcy水平,改善血管内皮功能,促进神经功能的恢复,增强日常生活能力,有助于改善患者的生存质量和预后。     

Higher vitamin B12 level at Parkinson's disease diagnosis is associated with lower risk of future dementia

IntroductionTo determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia.MethodsWe utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models.ResultsPD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44–0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60–0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05).ConclusionHigher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.     

Use of rCBF in diagnosis and follow-up of cerebral vitamin B12 deficiency

Evidence for cerebral B12 deficiency was searched for in 16 patients (age range 54–94 years) with subnormal serum B12 values (<110 pmol/l) with or without anaemia using sequential regional cerebral blood flow measurement (rCBF). Three patterns of responses followed B12 substitution in 11/16 cases: marked increase of the cerebral blood flow after one week (1); complete or partial normalization of regional decreases after one week (2) or after 1–3 months (3). Mental disturbances were observed in 14/16 patients and abnormally slow EEG activity in 11/12 patients before B12 substitution. During substitution a parallel clinical improvement was observed in 5/7 cases, who could cooperate in a follow-up study, and normalization or marked improvement of the abnormal EEG activity was observed in three cases. We propose that rCBF is a valuable tool for diagnosis and follow-up of this deficiency state. In addition, our results indicate that prophylactic B12 substitution should be considered at serum B12 serum values above the lower normal value especially in aged patients with coexisting organic brain disease.     

叶酸、Vit B_(12)干预对高Hcy的急性脑梗死近期预后的影响

目的观察叶酸、维生素B12干预治疗是否能降低高同型半胱氨酸血症的急性脑梗死患者的Hcy水平以及对患者近期预后的影响。方法根据血浆Hcy水平将急性脑梗死患者分为正常组(92例),干预组(39例)及对照组(37例),干预组除常规治疗外给予叶酸5mg.d-1和维生素B12500ug.d-1,其他两组仅予常规治疗。随访患者1年,观察血浆Hcy水平以及患者预后(NIHSS以及不良预后事件)。结果干预组Hcy水平显著降低(P=0.008),但是NIHSS评分较对照组无显著改善,不良预后事件发生率无差异。结论叶酸及维生素B12治疗能显著降低患者血浆Hcy水平,但是不能改善患者预后,考虑可能与维生素治疗不能改善炎症反应有关。维生素治疗能否降低心脑血管病的发生及复发需要进一步研究。     

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.     

Orthostatic tolerance in older patients with vitamin B12 deficiency before and after vitamin B12 replacement

Abstract. Orthostatic hypotension (OH) and vitamin B12 deficiency are common disorders in older people. Several case series have reported an association between vitamin B12 deficiency and OH. The effect of vitamin B12 replacement on this dysfunction has not been studied. We prospectively studied responses to head up tilt in patients over 70 years with vitamin B12 deficiency (intervention group) and compared their responses after replacement to those of matched patients with idiopathic OH and normal serum vitamin B12 concentrations (control group). Blood pressure (BP), heart rate (HR) and systemic vascular resistance (SVR) changes during orthostatic stress were evaluated using digital artery photoplethysmography. Eight patients and eight controls were studied. Initial head up tilt produced a mean BP decrease of 44/29 mmHg (s. e. m. 4/4 mmHg) in the intervention group and 33/12 mmHg (s. e. m. 3/2 mmHg) in the control group. Repeat head up tilt 6 months after vitamin B12 replacement produced a mean BP decrease of 15/9 mmHg (s. e. m. 5/2 mmHg) in the intervention group. The mean decrease in the control group was 30/12 mmHg (s. e. m. 2/2 mmHg). The difference in BP decreases between groups was statistically significant for both systolic and diastolic BP (p < 0.001 for both systolic BP and diastolic BP). Mean SVR in the intervention group decreased by 658 dynes/cm⁵/ sec (s. e. m. 74 dynes/cm⁵/sec) during initial head up tilt. Mean SVR during repeat head up tilt decreased by 79 dynes/cm⁵/sec (s. e. m. 12 dynes/cm⁵/sec). Mean SVR in the control group decreased by 158 dynes/cm⁵/sec (s. e. m. 10 dynes/cm⁵/sec) during initial head up tilt and by 258 dynes/cm⁵/sec (s. e. m. 31 dynes/cm⁵/sec). The difference in SVR changes between groups was statistically significant (p = 0.02). We conclude that replacing vitamin B12 in older patients with vitamin B12 deficiency is associated with improved orthostatic tolerance to head up tilt.