The effects of homocysteine and homocysteic acid on the metabotropic glutamate receptors of cerebellar neurons

Incubation of cerebellar neurons with homocysteine or homocysteic acid at a concentration of 500 μM for 30 min increases the intracellular level of free radicals. Specific antagonists of metabotropic glutamate receptors of the groups I (AIDA) and III (MSOP) decreased the accumulation of reactive oxygen species in cells, which suggests that homocysteine and homocysteic acid can interact with these receptors. Inhibition of NO-synthase does not affect the level of free radicals, which indicates that NO^• did not contribute to an increase in the level of free radicals in neurons under our conditions. Neither homocysteine nor homocysteic acid induced neuronal death; however, both compounds inhibited neuronal Na/K-ATPase. Inhibition of Na/K-ATPase was stronger in the case of activation of ionotropic glutamate receptors by NMDA as compared to simultaneous activation of both ionotropic and metabotropic glutamate receptors by homocysteine or homocysteic acid.     

缺血性脑卒中患者颈动脉斑块性质与同型半胱氨酸、血脂水平的相关性分析

目的研究缺血性脑卒中与同型半胱氨酸（HCY）及血脂水平的关系,并探讨不同斑块性质与同型半胱氨酸和血脂代谢的相关性。方法选择湖北省十堰市太和医院通过彩色多普勒技术检测出伴有颈动脉斑块的脑卒中患者162例,根据斑块分型,易损斑块73例,稳定斑块89例,并选择健康体检者70例,检测其血脂及同型半胱氨酸水平。结果脑卒中患者胆固醇（TC）、低密度脂蛋白（LDL_C）及同型半胱氨酸（t-HCY）水平较对照组明显升高（P〈0．05）;与稳定斑块组比较,易损斑块组血浆胆固醇（TC）、低密度脂蛋白（LDL-C）及同型半胱氨酸（t-HCY）水平升高（P〈0．05）。结论颈动脉粥样硬化斑块的形成与血脂水平异常密切相关,而高水平的同型半胱氨酸可影响血脂代谢并且是脑卒中发病的一个重要危险因素,个体优化调脂及逆转同型半胱氨酸水平治疗在脑卒中的二级预防中具有重要意义。     

Homocysteine and its derivatives as possible modulators of neuronal and non-neuronal cell glutamate receptors in Alzheimer's disease

Homocysteine (HC) and its derivatives may be involved in the etiology of Alzheimer's Disease (AD), although the precise mechanisms by which these compounds could cause cellular pathology are still unclear. Because interactions of HC with glutamate receptors have been implicated in AD, receptor-mediated effects of HC and homocysteic acid (HCA) on neurons and lymphocytes have been analyzed. Activation of glutamate receptors by these compounds has been shown to increase intracellular calcium and free radical levels in both types of cells, which may serve as a signal for development of apoptosis. Activation of group III metabotropic glutamate receptors stimulates, whereas activation of group I and group II metabotropic glutamate receptors prevent, the excitotoxic action of HC and HCA. These effects may contribute to the neuronal pathology and immunosenescence that occur in AD. It is proposed that selective agonists of metabotropic glutamate receptors that counter the effects of HC and its derivatives may be used for correction of neuronal and immune cell metabolism in vivo under the conditions of hyperhomocysteinemia, which can occur in AD.     

Plasma homocysteine is a predictor of alcohol withdrawal seizures

An adaptive consequence of prolonged ethanol consumption is a compensatory up-regulation of NMDA receptors in certain brain areas. Taking into account that homocysteine and its breakdown products (i.e. homocysteic acid) are putative neurotransmitters and agonists at the NMDA receptor, the aim of this study was to assess the influence of levels of homocysteine on alcohol withdrawal seizures. Six patients with chronic alcoholism who suffered from withdrawal seizures had significantly higher levels of homocysteine on admission (84.7 +/- 29.8 micromol/l) than patients (n = 26) who did not develop seizures (30.2 +/- 23.2 micromol/l; U = 8.0, p = 0.0007). Furthermore, seizure patients had significantly lower levels of folate and significantly higher blood alcohol concentrations. Using a logistic regression analysis, withdrawal seizures were best predicted by a high homocysteine level on admission (p < 0.01; odds ratio = 1.05). Homocysteine levels on admission may be a useful screening method to identify patients at risk for withdrawal seizures.     

Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: implications for the pathogenesis of Alzheimer's disease

The causes of neuronal dysfunction and degeneration in Alzheimer's disease (AD) are not fully understood, but increased production of neurotoxic forms of amyloid beta-peptide-42 (Abeta42) seems of major importance. Large extracellular deposits of aggregated Abeta42 (plaques) is a diagnostic feature of AD, but Abeta42 may be particularly cytotoxic when it accumulates inside neurons. The factors that may promote the intracellular accumulation of Abeta42 in AD are unknown, but recent findings suggest that individuals with elevated homocysteine levels are at increased risk for AD. We show that homocysteic acid (HA), an oxidized metabolite of homocysteine, induces intraneuronal accumulation of a Abeta42 that is associated with cytotoxicity. The neurotoxicity of HA can be attenuated by an inhibitor of gamma-secretase, the enzyme activity that generates Abeta42, suggesting a key role for intracellular Abeta42 accumulation in the neurotoxic action of HA. Concentrations of HA in cerebrospinal fluid (CSF) were similar in AD and control subjects. CSF homocysteine levels were elevated significantly in AD patients, however, and homocysteine exacerbated HA-induced neurotoxicity, suggesting a role for HA in the pathogenic action of elevated homocysteine levels in AD. These findings suggest that the intracellular accumulation of Abeta42 plays a role in the neurotoxic action of HA, and suggest a potential therapeutic benefit of agents that modify the production and neurotoxic actions of HA and homocysteine.     

Implications for hyperhomocysteinemia: not homocysteine but its oxidized forms strongly inhibit neuronal network activity

Severe hyperhomocysteinemia (50-200 microM) often presents itself with acute neuronal dysfunction including seizures and psychosis. Its moderate form (15-50 microM) is associated with cognitive impairment and dementia. We investigated the neuropharmacological effects of homocysteine and its oxidized forms, homocysteinesulfinic acid (HCSA) and homocysteic acid (HCA), on neuronal network function utilizing dissociated cortical neurons from embryonic Wistar rats on microelectrode arrays. All substances inhibited dose-dependently and reversibly spontaneous neuronal network activity within seconds: L-HCSA and L-HCA blocked spontaneous spike rate (SSR) significantly at very low concentrations, with an IC50 of 1.9 and 1.3 microM, respectively; whereas the dose-response curve of D,L-homocysteine revealed an IC50 of 401 microM. These effects were antagonized by 2-amino-5-phosphonovaleric acid (APV) pointing to the NMDA receptor as mediator of this fast and reversible inhibition of network activity. We conclude that a neuronal dysfunction observed in hyperhomocysteinemia is likely due to HCSA and HCA since effective concentrations of homocysteine are not reached in patients.     

Effect of central administration of phencyclidine on plasma concentrations of luteinizing hormone

Previous research has demonstrated that excitatory amino acids acting at N-methyl-D-aspartate (NMDA) receptors stimulate the release of luteinizing hormone (LH). Castration also elevates LH, an effect that may also involve NMDA receptors since the specific NMDA antagonist, DL-2-amino-5-phosphonopentanoic acid (AP5), antagonizes this action. Since PCP antagonizes a variety of actions of NMDA agonists, we hypothesized that it would diminish the ability of glutamate, homocysteic acid and castration to elevate LH. Our data support this hypothesis.     

Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people.

Depression among elderly people with reversible cognitive loss often manifests with concomitant vascular disease and can also precede the development of nonvascular degenerative dementia. Little is known about etiological factors for reversible or irreversible dementias in older depressed people. The amino acid homocysteine (HC), which is both a vascular disease risk factor and a precursor of the excitotoxic amino acids cysteine and homocysteic acid, could play a role in the pathophysiology of such individuals. Twenty-seven depressed elderly acute inpatients by DSM-III-R criteria had significantly higher plasma homocysteine levels and lower cognitive screening test scores than did 15 depressed young adult inpatients. HC was highest in the older patients who had concomitant vascular diseases (n = 14). HC was lowest in the older depressives who had neither vascular illnesses nor dementia (n = 8), comparable to the young adult depressives. Higher HC correlated significantly with poorer cognition only in the nonvascular geriatric patients (rs = -0.53). The findings extend earlier work showing higher HC in vascular patients from general medical populations, and also suggest a possible metabolic factor in certain dementias associated with late-life depression.     

Studies on the pharmacology of neurones in the nucleus accumbens of the rat.

A study was made of the effects of iontophoretically applied drugs on single neurones in the nucleus accumgens and caudate nucleus of rats anaesthetized with urethane. Neurones in the caudate nucleus were inhibited by dopamine, dibutyryl cyclic AMP, ADTN and ergometrine. Acetylcholine and homocysteic acid caused excitation of striatal neurones. In the nucleus accumbens neurones were inhibited by dopamine, ADTN, ergometrine, dibutyryl cyclic AMP, glycine and gamma-aminobutyric acid. The responses of glycine and gamma-aminobutyric acid were antagonised by strychnine and picrotoxin, respectively. Acetylcholine and homocysteic acid caused excitation of neurones in the nucleus acumbens; the effects of acetylcholine were blocked by atropine. The results are consistent with the suggestion that dopamine is an inhibitory transmitter in the nucleus accumbens and in the caudate nucleus and support the hypothesis that the effects of dopamine are mediated by cyclic AMP. The locomotor stimulants ADTN and ergometrine mimicked the inhibitory actions of dopamine in both the striatum and in the nucleus accumbens. These results support the suggestion that dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs.     

Effects of common anti-epileptic drug monotherapy on serum levels of homocysteine, vitamin B12, folic acid and vitamin B6.

There is emerging evidence to support the unfavorable effects of some anti-epileptic drugs on the plasma homocysteine concentrations. Elevated homocysteine levels induced by anti-epileptic drug administration can theoretically increase not only the risk of vascular occlusive diseases, but also the risk of resistance to anti-epileptics and development of refractory epilepsy. To investigate the effect of common anti-epileptic drugs on the homocysteine metabolism, a total of 75 epileptic patients receiving phenytoin (n=16), carbamazepine (n=19), or valproic acid (n=22) and no anti-epileptic drug (n=18) were enrolled. Eleven age- and sex-matched healthy subjects served as the control group. Blood concentrations of homocysteine, folic acid, Vitamin B12 and pyridoxal 5'-phosphate (active circulating form of Vitamin B6) were measured. Compared to the control group, epileptic patients on anti-epileptic drug had higher blood levels of homocysteine. No difference in homocysteine concentrations was observed among epileptic patients in terms of the anti-epileptic drug used. Patients receiving phenytoin had significantly lower folic acid levels and those receiving carbamazepine had marginally lower pyridoxal 5'-phosphate levels in comparison with those using other anti-epileptic drugs. A negative correlation between homocysteine and folic acid concentrations was detected in epileptic patients on anti-epileptic drug. The duration of anti-epileptic drug use was correlated to the decrease of folic acid levels, but not with changes observed in homocysteine, Vitamin B12 and pyridoxal 5'-phosphate levels. No relationship between seizure frequency and homocysteine levels was observed in epileptic patients. Our results confirm that common anti-epileptic drugs has disadvantageous effects on homocysteine status. Because there was no significant change in homocysteine concentrations in epileptic patients who were not receiving an anti-epileptic drug, and no positive correlation between seizure frequency and homocysteine levels, we suggest that increase of homocysteine levels may be due to anti-epileptic drug use, rather than being epileptic in origin. Additionally, the underlying mechanism for homocysteine increase seems to be a decrease of cofactor molecules in patients using carbamazepine and phenytoin (pyridoxal 5'-phosphate and folic acid, respectively). However, changes observed are not related to the alteration in the levels of cofactors and remain unclear in the patients using valproic acid.     

No effect of folic acid supplementation in the course of 1 year on haemostasis markers and C-reactive protein in older adults

Elevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (von Willebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers.     

Mechanisms of homocysteic acid neurotoxicity

Homocysteine (HC) and a product of its spontaneous oxidation, homocysteic acid (HCA), are neurotoxic compounds; however, the mechanism of their neurotoxicity is unknown. We found that application of HCA to neurons results in an increase in the intracellular level of reactive oxygen species (ROS), activation of MAP kinase (MAPK) and, finally, in cell death. We found that HCA increases both cellular apoptosis and necrosis, whereas preliminary incubation of cells with carnosine protects cells from these types of cell death.     

Neurochemical characterization of excitotoxin lesions in the cerebral cortex.

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.     

Cytotoxic actions and effects on intracellular Ca2+ and cGMP concentrations of sulphur-containing excitatory amino acids in cultured cerebral cortical neurons

Effects of the sulphur-containing acidic amino acids (SAAs) cysteic acid (CA), homocysteic acid (HCA), cysteine sulphinic acid (CSA), homocysteine sulphinic acid (HCSA), and S-sulphocysteine (SC) on intracellular concentrations of Ca²⁺ ([Ca²⁺]_i) and cGMP ([cGMP]_i) as well as their cytotoxic actions were investigated in cultured cerebral cortical neurons. The glutamate receptor subtype selective antagonists APV (D-(?)-2-amino-5-phosphonopentanoate) acting on N-methyl-D-aspartate (NMDA) receptors and DNQX (6,7-dinitroquinoxaline-2,3-dione) acting on non-NMDA receptors were employed to obtain information about the involvement of glutamate receptor subtypes in these actions of the SAAs. It was found that all SAAs exerted a cytotoxic action on the neurons. The ED₅₀ values for CSA, CA, HCSA, and HCA were around 30 to 50 μM and that for SC was about 150 μM. The glutamate transport blocker L-aspartate-β-hydroxamate increased the efficacy of CSA and CA but had no effect on the cytotoxic actions of the remaining SAAs. In case of CA, HCA, and SC the cytotoxicity could be prevented by APV alone and for HCSA, DNQX could block the toxic action. DNQX reduced the toxicity of HCA somewhat but the presence of APV was required for complete protection. CSA toxicity could only be blocked by the combination of APV and DNQX. All SAAs induced an increase in [cGMP]_i and [Ca²⁺]_i and with regard to [Ca²⁺]_i SC was the most potent and CA the least potent SAA. The effect of all SAAs on [cGMP]_i could be blocked by APV alone whereas DNQX had no effect except in the case of HCSA where the response was blocked completely and HCA where the response was inhibited by 75%. The SAA-induced increase in [Ca²⁺]_i could in all cases be significantly reduced by 0.6 mM Mg²⁺ and in the presence of Mg²⁺, APV dose dependently blocked the remaining SAA induced increase in [Ca²⁺]_i completely. Under these conditions DNQX was also found to block the SAA-induced increase in [Ca²⁺]_i dose dependently. In the absence of Mg²⁺, DNQX (25 μM) inhibited the response of the SAAs only by 65–75%. Under these conditions all SAA responses except that to SC could be fully antagonized by 300 μM APV. The SC-induced increase in [Ca²⁺]_i was inhibited by 60% by APV. The results show that no simple correlation exists between SAA-induced cytotoxicity and their ability to increase intracellular levels of Ca²⁺ and cGMP. However, when both NMDA and non-NMDA receptors were antagonized no toxicity or changes in calcium or cGMP were observed. © 1993 Wiley-Liss, Inc.     

进展性缺血性卒中相关危险因素分析

目的对进展性缺血性卒中(SIP)相关危险因素进行探讨。方法对我院41例SIP患者的入院时血压、血糖、体温、同型半胱氨酸、周围血白细胞、血脂、血沉、高敏C反应蛋白、梗死部位、动脉狭窄及既往病史等因素进行回顾性分析。结果SIP患者与对照组比较,入院时体温、白细胞计数、同型半胱氨酸及脑梗死部位等差异有统计学意义(P<0.05)。结论SIP多与入院时体温升高、高同型半胱氨酸及分水岭区脑梗死相关。     

Effects of excitatory sulfur amino acids on glutamate transport in synaptosomes isolated from the rat cerebral cortex]

Transport of glutamate, the disturbance of which has been implicated in amyotrophic lateral sclerosis (ALS), may be influenced by various substances. Excitatory sulfur amino acids (SAAs) could be increased in ALS, because the elevation of taurine, the final product of the metabolic pathway of SAAs, has been reported in this intractable disease. I examined effects of excitatory SAAs on the transport of glutamate in synaptosomes. Synaptosome fractions were prepared by discontinuous density-gradient centrifugation from the rat cerebral cortex, and were incubated at 35 degrees C with varying concentrations of L-[3H] glutamate in the absence or presence of excitatory SAAs; cysteine sulfinic acid (CSA), cysteic acid (CA), homocysteine sulfinic acid (HCSA), homocysteic acid (HCA) and S-sulfocysteine (SC). Kinetic characterization of uptake confirmed the high-affinity nature of the transport system, the Michaelis constant (Km) for glutamate uptake being 10 microM. The nature of inhibition was competitive. Potent inhibition of transport was exhibited by CSA and CA, whereas substantially weaker inhibitory effects were exhibited by HCSA, and almost no effects by HCA or SC. Inhibition by excitatory SAAs, especially CSA and CA of the high-affinity glutamate transporter may be involved in the pathogenesis of ALS.     

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。     

Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist

For patients with acute lymphoblastic leukemia or non-Hodgkin lymphoma, intrathecal (IT) methotrexate (MTX) significantly reduces the risk of relapse within the central nervous system, but is associated with neurotoxic sequelae. We established a rat model of MTX-induced cognitive deficits to further investigate the underlying pathophysiology and to develop protective therapeutic interventions. IT MTX 0.5 mg/kg was administered to 10-week old male Long Evans rats. Cerebrospinal fluid (CSF) was collected for measurement of folate, homocysteine, and excitotoxic glutamate analogs. Recognition and spatial memory were tested in the novel object recognition (NOR) task and the object placement (OP) task, respectively.Four doses of IT MTX in a two-week period induced cognitive deficits persisting at least three months after the final injection. CSF concentrations of the excitotoxic glutamate analogs homocysteic acid and homocysteine sulfinic acid were increased relative to baseline for the same three-month period. Dextromethorphan, a noncompetitive antagonist at the N-methyl-d-aspartate receptor, administered at a dose of 2 mg/kg intraperitoneally twice daily for a total of four doses, improved cognitive function among the MTX-treated rats, with no effect on control rats. Although this improvement was transient, each repeated treatment with dextromethorphan was followed by normalization of cognitive function.In conclusion, IT MTX induces persistent alterations in glutaminergic tone that may contribute to persistent cognitive deficits. Treatment with a glutamate receptor antagonist such as dextromethorphan may ameliorate the negative cognitive outcomes observed among patients with leukemia or lymphoma treated with repeated doses of prophylactic IT MTX.     

Brain amino acid concentrations and Ca-dependent release in intractable depression assessed antemortem

The concentrations of 3 putative neurotransmitters (glutamate, aspartate and γ-aminobutyrate), 4 related amino acids and 5 non-transmitter-related amino acids have been measured in neurosurgical samples (frontal cortex) from patients with intractable depression and controls. In addition, the glutamate receptor agonist 2-amino-4-sulpho-butanoic acid (homocysteic acid) has been identified in human brain and measured in these samples. There were no changes in the concentrations of amino acids in depressed patients compared to control with the exception of aspartic and homocysteic acids which were elevated in a sub-group of patients with depression compared to control. The Ca²⁺-dependent release (K⁺-stimulated) of putative neurotransmitters has been demonstrated for the first time from brain tissue of depressed patients. Glutamate release was unaltered from the control value. Aspartate values showed unexplained variability but it's release and that of γ-aminobutyrate were elevated in some depressed subjects. These results do not support the hypothesis of reduced amino acid function in depressive illness.     

药源性肥胖患者血清同型半胱氨酸水平研究

目的：了解抗精神病药所致药源性肥胖患者的血清同型半胱氨酸（Hcy）水平及其可能的影响因素。方法：调查60例药源性肥胖住院患者,用酶免疫法测定其血清Hcy水平,用化学发光法测定其血清叶酸、VitB12水平。以28名健康者为对照。结果1患者组血清Hey水平明显高于对照组（P〈0．001）,而血清叶酸、VitB12水平则显著低于对照组（P〈0．001及〈0．005）。单因素相关分析显示其血清Hcy与叶酸、VitB12呈负相关（r＝-0．520,P〈0．01;r：-0．372,P〈0．01）,多元逐步回归示叶酸是影响血清Hcv水平的因子（标准回归系数-0．490,t＝-5．16,P〈0．01）。结论：药源性肥胖患者多存在高同型半胱氨酸血症（HHcy）,其血清Hcy水平主要受叶酸的影响。