叶酸对孤独症谱系障碍儿童甲基化水平和氧化应激状态的影响

了解孤独症谱系障碍(autism spectrum disorders,ASD)儿童叶酸、同型半胱氨酸(Hcy)和谷胱甘肽(GSH)代谢状况,为探讨叶酸对ASD儿童甲基化水平和氧化应激状态的作用提供参考.方法 采用病例对照研究方法,收集哈尔滨医科大学儿童发育行为研究中心就诊的ASD儿童53例,选取53例性别年龄匹配的儿童为对照组,应用传统方法检测血清叶酸,Hcy,GSH和氧化型谷胱甘肽(GSSG)水平.招募参与结构化教学训练的ASD儿童83例,根据是否补充叶酸分为叶酸干预组和非叶酸干预组.采用自闭症儿童心理教育评核第3版(Psychoeducational Profile-third edition,PEP-3)对干预前后的ASD儿童进行发育水平评估,同时应用高效液相色谱检测叶酸干预组中29例ASD儿童干预前后的血浆叶酸,Hcy,GSH以及GSSG水平,并与对照儿童进行比较.结果 病例对照研究中,ASD组血清叶酸,GSH和GSH/GSSG比值明显低于对照组,Hcy和GSSG明显高于对照组,差异均有统计学意义(P值均<0.05).叶酸干预组的ASD儿童认知、语言理解和情感表达方面较非叶酸干预组提高.叶酸干预前,ASD儿童血浆叶酸,GSH,GSH/GSSG低于正常儿童,Hcy和GSSG高于正常儿童;叶酸干预后,ASD儿童叶酸,GSH,GSH-/GSSG明显升高,Hcy和GSSG明显降低,差异均有统计学意义(P值均<0.05);且与正常儿童相比,叶酸水平升高而Hcy降低.相关分析显示,Hcy的改变与行为特征—语言评分的改变呈负相关(r=-0.411,P=0.027).结论 ASD儿童体内叶酸水平低、Hcy水平高、氧化应激强.叶酸干预能够有效调节甲基化水平和氧化应激状态,对于参与结构化训练的ASD儿童具有良好的辅助治疗作用.     

孤独症谱系障碍儿童血清叶酸、维生素B12水平与肠道菌群的关联

目的 探讨孤独症谱系障碍(ASD)儿童血清叶酸、维生素B12水平与肠道菌群之间的关系。方法 2020年1月—2021年2月在重庆市妇幼保健院门诊调查79例2～7岁ASD儿童和79例年龄、性别相匹配健康儿童，采用化学发光法检测两组儿童血清叶酸、维生素B12水平，对两组儿童粪便样本中细菌16SrRNA基因的V3-V4高变区进行测序。结果 ASD组血清叶酸水平低于对照组[33.55(20.47,39.73)nmol/Lvs. 35.50(27.80,41.90)nmol/L](Z=-2.114,P=0.035);ASD组血清维生素B12水平低于对照组[539.0(422.50,702.75)pmol/L vs.632.0(519.0,859.0)pmol/L](Z=-3.114,P=0.002)。ASD组和对照组的肠道菌群Alpha多样性、Beta多样性差异无统计学意义(P>0.05)。在属水平，ASD组相比于对照组萨特菌属和脱硫弧菌属的丰度显著提高，双歧杆菌属和莱茵海默氏菌属的丰度显著降低(P<0.05)。Spearman相关性分析显示，血清叶酸水平与双歧杆菌属(r=0.203...     

孤独症谱系障碍儿童维生素B12及相关代谢产物MMA和转运蛋白TCN2的病例对照研究

探讨孤独症谱系障碍(ASD)儿童体内维生素B12水平,为ASD早期发现及药物治疗提供理论依据.方法 收集哈尔滨市ASD儿童和正常对照儿童各89人,应用酶联免疫吸附试验技术(ELISA)测定尿液甲基丙二酸(Methylmalonic acid,MMA)及血清维生素B12、转运蛋白转钴胺素蛋白Ⅱ(TranscobalaminⅡ,TCN2)的含量,应用SNaPshot对TCN2基因rs1801198位点进行基因分型.结果 ASD儿童的血清维生素B12和TCN2水平[(369.08±131.88)pmol/L,(1.56±0.16)ng/mL]均低于对照组儿童[(485.16±200.33)pmol/L,(1.71±0.17)ng/mL](t值分别为-5.47,-5.92,P值均<0.05),ASD儿童尿液中MMA水平[(758.97±106.96)ng/mL]高于对照组[(693.66±121.72)ng/mL](t=3.94,P<0.05);TCN2基因rs1801198位点基因多态性与ASD的患病风险的关联无统计学意义(P值均>0.05),与血清TCN2水平的关联无统计学意义(F=1.16,P>0.05).结论 ASD儿童维生素B12潜在缺乏,应在开展ASD干预的同时加强营养干预.     

不同叶酸、维生素B_6摄入水平对模拟失重大鼠同型半胱氨酸代谢的影响

目的观察模拟失重条件下大鼠血清叶酸、维生素B6以及同型半胱氨酸(Hcy)代谢变化情况和不同叶酸、维生素B6摄入水平对Hcy代谢的影响。方法本实验采用大鼠尾部悬吊模型,将SD雄性大鼠按体重随机分为地面对照组、尾吊对照组及尾吊营养素干预组(按正交设计的方法分为9组),总共11组,对照组和尾吊营养干预组经人工灌胃的方式分别给于对应剂量的纯净水和维生素混合溶液,饲养4w后断头取血分离血清,按试剂盒方法测定其相关各项生化指标。结果尾吊对照组的血清叶酸、维生素B6水平低于地面对照组,而Hcy水平有增高的趋势;尾吊营养干预组的血清Hcy水平均低于尾吊对照组,血清叶酸、维生素B6水平均高于尾吊对照组,并且随着叶酸、维生素B6摄入的增加,血清Hcy水平有递减的趋势,正交结果分析显示剂量水平在H1组(叶酸高剂量水平和维生素B6低剂量水平)时,降低血清Hcy水平效果最佳。尾吊对照组的血清超氧化物歧化酶(SOD)活力显著高于其他各组(P<0.05),谷胱甘肽过氧化物酶(GSH-Px)活力各组无显著性差异。尾吊对照组血清血栓素A2(TXA2)水平显著增加(P<0.05)以及血清前列环素(PGI2)水平显著降低(P<0.05)。结论在尾吊条件下,实验4 w后大鼠体内叶酸、维生素B6水平降低,Hcy水平有升高的趋势;补充叶酸、维生素B6可以有效增加大鼠血清叶酸、维生素B6水平,降低血清Hcy水平,并且采用H1组剂量时效果最佳;补充叶酸、维生素B6可以通过调节Hcy的代谢,减少体内过氧化产物的形成,调节了PGI2与TXA2的水平,从而减小Hcy升高带来的消极影响。     

25-羟维生素D 维生素B_(12)及叶酸对2～6岁孤独症谱系障碍儿童智力及核心症状的影响

目的分析25-羟维生素D[25(OH)D]、维生素B_(12)及叶酸对2～6岁孤独症谱系障碍(ASD)患儿智力及核心症状的影响。方法选取2019年1-12月湖北省妇幼保健院收治的2～6岁ASD患儿116例为观察组,另选取同期体检健康儿童116例为对照组,检测并比较两组儿童血清25(OH)D、维生素B_(12)及叶酸水平。观察组儿童采用中国韦氏幼儿智力量表第四版(WPPSI-Ⅳ)测定智力,采用孤独症评定量表(CARS)和孤独症行为量表(ABC)评估孤独症病情程度和症状;根据CARS评分将观察组分为轻中度组和重度组,比较不同组别儿童血清25(OH)D、维生素B_(12)及叶酸水平的差异;运用Pearson偏相关分析各指标与韦氏总智商和ABC评分的相关性。结果观察组患儿血清25(OH)D、维生素B_(12)及叶酸水平均明显低于对照组,且轻中度组高于重度组,差异均有统计学意义(均P0.01)。患儿血清25(OH)D、维生素B_(12)及叶酸水平与智力水平呈正相关关系(P0.01),与ABC量表评分均呈负相关关系(P0.05)。结论 ASD患儿的血清25(OH)D、维生素B_(12)及叶酸水平均下降,且与患儿的病情严重程度、智力及核心症状相关。     

同型半胱氨酸水平与胎儿神经管畸形的相关性研究

目的探讨同型半胱氨酸(Hcy)水平与胎儿神经管畸形的相关性,为预防胎儿神经管畸形的发生提供参考依据。方法选取2016年1月至2018年2月在本院经B超检查确诊为胎儿神经管畸形的孕妇62例作为研究组,选取同期于本院检查胎儿健康的孕妇60例作为对照组,检测两组血清叶酸、维生素B12及Hcy水平,经单因素及多因素Logistic回归分析孕妇血清叶酸、维生素B12、Hcy水平与胎儿神经管畸形的相关性。结果:研究组血清叶酸、维生素B12水平分别为(28.05±3.48) nmol/L、(319.56±90.26) pmol/L,对照组血清叶酸、维生素B12水平分别为(29.76±3.61) nmol/L、(302.56±87.43) pmol/L,组间比较差异均无统计学意义(均P0.05)。研究组血清Hcy水平为(10.86±0.92)μmol/L,高于对照组的(7.05±0.43)μmol/L,差异具有统计学意义(P0.05)。单因素分析显示,发生胎儿神经管畸形与血清Hcy水平相关(P0.05),而与年龄、孕次、孕周、体重、叶酸及维生素B12水平无关(P0.05)。多因素Logistic回归分析显示,Hcy10μmol/L是发生胎儿神经管畸形的独立危险因素(P0.05)。结论孕妇血清Hcy水平与胎儿神经管畸形相关,应加大产前筛查力度,通过降低孕妇Hcy水平来防控胎儿神经管畸形。     

不同剂量叶酸联合维生素B_(12)治疗老年高血压合并高同型半胱氨酸血症的临床疗效分析

目的探讨不同剂量叶酸联合维生素B_(12)治疗老年高血压合并高同型半胱氨酸(Hcy)血症(简称"H型高血压")对患者Hcy、叶酸和血压水平的影响。方法本研究选取2015年1-5月于重庆市九龙坡区西彭镇体检的140例H型高血压患者为研究对象。将患者分为3组:对照组(n=36)、叶酸A组(n=60)和叶酸B组(n=44)。对照组患者治疗方案:常规降压治疗;叶酸A组患者治疗方案:常规降压治疗+叶酸(0.4mg/次)+维生素B_(12)(500μg/次);叶酸B组患者治疗方案:常规降压治疗+叶酸(0.8mg/次)+维生素B_(12)(500μg/次)。结果治疗12周时,对照组、叶酸A组和叶酸B组患者Hcy水平分别为(26.73±8.99)μmol/L,(16.26±5.71)μmol/L,(16.59±6.12)μmol/L。3组患者Hcy水平比较,差异有统计学意义(P0.05)。叶酸A组、叶酸B组患者Hcy水平均低于治疗前,差异有统计学意义(P0.05)。同时,叶酸A组、叶酸B组患者Hcy水平均低于对照组,差异均有统计学意义(P 0.05)。治疗12周时,对照组、叶酸A组和叶酸B组患者叶酸水平分别为(3.88±1.37)μg/L,(10.72±3.39)μg/L,(12.78±4.73)μg/L。3组患者叶酸水平比较,差异有统计学意义(P0.05)。叶酸A组、叶酸B组患者叶酸水平均高于治疗前,差异有统计学意义(P0.05)。同时,叶酸A组、叶酸B组患者叶酸水平均高于对照组,差异均有统计学意义(P0.05)。叶酸B组患者叶酸水平高于叶酸A组,差异有统计学意义(P0.05)。治疗12周时,对照组、叶酸A组和叶酸B组患者收缩压(SBP)水平分别为(141.2±10.9)mmHg(1mmHg=0.133kPa),(133.8±10.6)mmHg,(129.3±7.8)mmHg。3组患者SBP水平比较,差异有统计学意义(P0.05)。叶酸A组和叶酸B组患者SBP水平均低于对照组,差异均有统计学意义(P0.05)。此外,治疗过程中,3组患者均未出现药物过敏、肝肾损伤等药品不良反应。结论适当补充叶酸和维生素B_(12)可显著降低Hcy水平,提高叶酸水平,改善血压水平,同时每天服用0.8mg叶酸在改善Hcy水平及SBP水平方面的效果优于每天服用0.4mg叶酸,值得在基层医疗机构中推广应用。     

血清维生素B12、叶酸和同型半胱氨酸水平与乳腺癌发病风险的关系

目的对乳腺癌患者血清维生素B12、叶酸(Folic acid,FA)和同型半胱氨酸(Homocysteine,Hcy)水平进行研究,探讨其与乳腺癌发病风险的关系。方法选择2013年1月-2015年1月衢州市人民医院乳腺癌患者52例作为乳腺癌组,同期体检中心健康体检的健康女性52例作为对照组。测定血清维生素B12、FA和Hcy水平,观察乳腺癌组和对照组血清维生素B12、FA和Hcy水平;乳腺癌组和对照组血清维生素B12、FA和Hcy的相关性;乳腺癌患者中血清维生素B12、FA、Hcy水平和发病风险的关系。结果乳腺癌组血清FA水平低于对照组(P0.05);乳腺癌组血清Hcy水平高于对照组(P0.05);乳腺癌组血清维生素B12水平和对照组比较,差异无统计学意义(P0.05)。乳腺癌组血清FA和Hcy呈负相关(P0.05),血清维生素B12和FA无相关性(P0.05),血清维生素B12和Hcy无相关性(P0.05);对照组血清FA和Hcy呈负相关(P0.05),血清维生素B12和FA无相关性(P0.05),血清维生素B12和Hcy无相关性(P0.05)。乳腺癌患者血清维生素B12和乳腺癌的发病风险之间没有相关性(P0.05)。乳腺癌患者血清FA和乳腺癌的发病风险之间有显著相关性(P0.05)。高血清FA人群是低血清FA人群患乳腺癌风险的0.364倍。乳腺癌患者血清Hcy和乳腺癌的发病风险之间有显著相关性(P0.05)。高血清Hcy人群是低血清Hcy人群患乳腺癌风险的17.231倍。结论乳腺癌患者血清FA水平降低,血清Hcy水平升高,乳腺癌患者的发病风险和血清FA水平负相关,和血清Hcy水平正相关,和血清维生素B12水平没有相关性。     

复合维生素片在辅助生殖患者中的应用及效果评价

目的探讨复合维生素片对体外受精-胚胎移植(IVF-ET)女性血清和卵泡液中微量元素以及叶酸含量的影响,以明确服用复合维生素片后是否对IVF-ET助孕结局有改善作用。方法选取2016年1-12月在该院进行IVF-ET助孕的患者390例,用随机数字表法分为试验组和对照组。试验组均口服多维元素片1片/d,共90 d,对照组患者未服用复合维生素片等相关药物。分别测定两组血清和卵泡液中铜、锌、钙、铁、镁、叶酸及同型半胱氨酸(Hcy)的含量。结果试验组锌与叶酸的含量均明显高于对照组(P0.05),Hcy水平明显低于对照组(P0.05)。试验组较对照组妊娠率略有增高,且流产率降低,但差异均无统计学意义(P0.05)。结论复合维生素的摄入可以平衡女性血清及卵泡液中微量元素的水平。     

脐血中同型半胱氨酸、叶酸、维生素B_(12)水平变化与宫内胎儿生长发育的相关性分析

目的探讨脐血中维生素B_(12)、叶酸、同型半胱氨酸(Hcy)水平变化与宫内胎儿生长发育的关联性。方法选取2017年1-12月于该院进行分娩的孕妇69例,分娩后依据胎龄和出生体质量百分位数间关系分为胎儿生长受限(FGR)组(24例)、适于胎龄儿(AGA)组(25例)及大于胎龄儿(LGA)组(20例)。分别抽取孕妇静脉血及分娩后脐静脉血4 ml,离心处理后检测血清维生素B_(12)、叶酸及Hcy水平,并统计对比3组新生儿生长参数[体质量指数(BMI)、胎盘质量、腹围、头围、身长、出生体质量],分析新生儿脐血血清维生素B_(12)、叶酸、Hcy水平与生长参数的相关性。结果新生儿生长参数:3组新生儿BMI、胎盘质量、腹围、头围、身长、出生体质量比较,差异均有统计学意义(均P0.05),且FGR组BMI、胎盘质量、腹围、头围、身长、出生体质量均小于AGA组与LGA组,差异均有统计学意义(均P0.05)。脐血血清维生素B_(12)、叶酸、Hcy水平:3组新生儿脐血血清维生素B_(12)、叶酸、Hcy水平比较,差异均有统计学意义(均P0.05),且FGR组血清Hcy水平高于AGA组与LGA组,血清维生素B_(12)、叶酸水平低于AGA组与LGA组(P0.05)。脐血血清指标水平与生长参数相关性:新生儿脐血血清维生素B_(12)、叶酸水平与新生儿生长参数无明显相关性(P0.05),血清Hcy水平与新生儿BMI、胎盘质量、腹围、头围、身长、出生体质量呈明显负相关(P0.05)。结论生长发育受限胎儿生长参数及脐血血清维生素B_(12)、叶酸、Hcy水平均与正常胎儿存在明显差异,妊娠期缺乏维生素B_(12)及叶酸可能会引发高同型半胱氨酸血症(HHcy),而胎儿宫内生长发育受限可能与血清Hcy水平增高具有一定相关性。     

缺血性脑卒中的发生与血清叶酸、血小板聚集率、同型半胱氨酸和维生素B12的关系研究

目的:探讨缺血性脑卒中患者血清叶酸(Folic Acid,FA)、血小板聚集率(Platelet Aggregation Rate,PAR)、同型半胱氨酸(Homocysteine,Hcy)和维生素B12(vitamin B12,VitB12)变化的原因及其关系。方法:选择缺血性脑卒中患者和健康对照组各60例,利用免疫法测其FA、PAR、Hcy和vitamin B12水平。结果:缺血性脑卒中患者体内FA水平偏低,PAR、VitB12和Hcy水平偏高,P<0.05;与缺血性脑卒中关系依次为FA>VitB12>PAR>Hcy,FA与PAR的相关关系r=0.006,P<0.01;HCY与PAR的相关关系r=0.03,P<0.05,FA与HCY的相关关系r=0.07。结论:缺血性脑卒中患者FA水平偏低,补充叶酸能降低PAR、改善HCY的氧化和VitB12的吸收,降低缺血性脑卒中的发生。     

Supplementation with [6S]-5-methyltetrahydrofolate or folic acid equally reduces serum homocysteine concentrations in older adults

Folic acid (FA) supplementation reduces the elevated serum homocysteine (Hcy) concentrations. [6?S]-5-methyltetrahydrofolate ([6?S]-5-MTHF) is an alternative to FA due to possible advantages, that is, no masking cobalamin deficiency. The study aim was to evaluate the effectiveness of [6?S]-5-MTHF in relations to FA supplementation in reducing the serum Hcy. Healthy volunteers, aged 50–65, had normal serum folate and did not use supplements with B-vitamins for 6?months. Forty subjects were divided into two groups: receiving 400?μg/d FA or the equimolar amount of [6?S]-5-MTHF. Blood was collected at baseline and after 4?weeks. In both groups, a significant decrease in the mean Hcy level after intervention period was observed. Supplementation with [6?S]-5-MTHF was slightly less effective, but not significantly, in Hcy lowering than FA (p?=?.243 between the groups), that is, by 7.8% and 13.4%, respectively. The [6?S]-5-MTHF was shown to be an adequate alternative to FA in reducing Hcy concentrations.     

老年冠心病与血浆同型半胱氨酸及其代谢相关因子

目的观察老年冠心病及糖尿病与血浆同型半胱氨酸及其代谢相关因子之间的关系。方法选择老年冠心病患者68例,其中伴发Ⅱ型糖尿病的16例为A组;无伴发Ⅱ型糖尿病52例为B组;选择22例健康老年人作为对照组C组。对受试者进行血浆同型半胱氨酸、叶酸和维生素B12定量测定。结果患病组老年血浆同型半胱氨酸值明显高于健康老年组,血浆Vit B12、叶酸值明显低于健康对照组,两组间比较有统计学意义(P<0.05),Ⅱ型糖尿病组(A组)血浆同型半胱氨酸值明显高于无糖尿病组(B组)(P<0.05),且A组VitB12和叶酸值明显低于B组(P<0.01),B组血浆同型半胱氨酸值高于C组,Vit B12明显低于C组(P<0.01),而叶酸两组间差别无统计学意义。患病组的同型半胱氨酸值和叶酸、VitB12呈明显的负相关,相关系数分别为-0.61和-0.49,P均<0.01。结论老年冠心病患者高同型半胱氨酸血症与动脉硬化、冠心病的发病及糖尿病胰岛素相对或绝对缺乏有密切关系,探讨老年人同型半胱氨酸的代谢规律对预防老年心脑血管疾病有重要意义。     

Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia

Background/Objectives: To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocols in subjects with “moderate” hyperhomocysteinemia, also taking into account C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. Subjects/Methods: We performed a 13 week open, randomized, double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia, with daily 200 μg from a natural folate-rich diet, 200 μg [6S]5-methyltetrahydrofolate (5-MTHF), 200 μg folic acid or placebo. Participants were stratified according to their MTHFR genotype. Results: Homocysteine (Hcy) levels were reduced after folate enriched diet, 5-MTHF or folic acid supplementation respectively by 20.1% (p < 0.002), 19.4% (p < 0.001) and 21.9% (p < 0.001), as compared to baseline levels and significantly as compared to placebo (p < 0.001, p < 0.002 and p < 0.001, respectively for enriched diet, 5-MTHF and folic acid). After this enriched diet and the folic acid supplementation, Hcy in both genotype groups decreased approximately to the same level, with higher percentage decreases observed for the TT group because of their higher pre-treatment value. Similar results were not seen by genotype for 5-MTHF. A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations, as compared to placebo. Conclusions: Supplementation with natural folate-rich foods, folic acid and 5-MTHF reached a similar reduction in Hcy concentrations.     

高同型半胱氨酸血症与颈动脉粥样硬化对老年急性脑梗死影响的研究

目的：探讨老年急性脑梗死患者血清同型半胱氨酸（Hcy）水平与颈动脉硬化（CAA）程度之间的关系。方法：对80例老年急性脑梗死患者进行空腹血浆Hcy、空腹血糖、胆固醇、甘油三酯、叶酸、维生素B12（VitB12）水平的测定,并且进行彩超检查颈动脉内膜-中层厚度（IMT）、斑块大小、狭窄程度及血流速度的检测,按照颈动脉狭窄程度及IMT值分为A、B、C、D四组;对Hcy水平与叶酸、VitB12及其他相关因素进行分析。结果：（1）随着CAA程度的加重,Hcy水平升高,A、B、C组和D组之间比较差异均有统计学意义（P〈0.05）;（2）叶酸与VitB12的水平随着CAA程度的加重而降低,仅在A组和D组之间比较差异有统计学意义（P〈0.05）;（3）统计学分析表明血清Hcy水平与血叶酸和VitB12水平负相关（r=-0.328、-0.442,P〈0.05）。结论：高Hcy血症与颈动脉粥样硬化程度密切相关,是脑梗死发生的独立危险因素。     

Folate: in vitro and in vivo effects on VLDL and LDL oxidation

Raised total homocysteine (tHcy) levels may be involved in the etiology of cardiovascular disease and can lead to damage of vascular endothelial cells and arterial wall matrix. Folic acid supplementation can help negate these detrimental effects by reducing tHcy. Recent evidence has suggested an additional anti-atherogenic property of folate in protecting lipoproteins against oxidation. This study utilized both an in vitro and in vivo approach. In vitro: Very-low-density lipoprotein (VLDL) and low density lipoprotein (LDL) were isolated by rapid ultracentrifugation and then oxidized in the presence of increasing concentrations (0-->10 micromol/L) of either folic acid or 5-methyltetrahydrofolate (5-MTHF). In vivo: Twelve female subjects were supplemented with folic acid (1 mg/day), and the pre- and post-VLDL and LDL isolates subjected to oxidation. In vitro: 5-MTHF, but not folic acid, significantly increased the resistance of VLDL and LDL to oxidation. In vivo: Following folic acid supplementation, tHcy decreased, serum folate increased, and both VLDL and LDL displayed a significant increase in their resistance to oxidation. These results indicated that in vitro, only the active form of folate, 5-MTHF, had antioxidant properties. In vivo results demonstrated that folic acid supplementation reduced tHcy and protected both VLDL and LDL against oxidation. These findings provide further support for the use of folic acid supplements to aid in the prevention of atherosclerosis.     

Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid

The natural diastereoisomer [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) may be a safer fortificant than folic acid for neural tube defect (NTD) prevention because it is unlikely to mask vitamin B-12 deficiency. An inverse relationship between NTD risk and blood folate concentrations has been reported. In this randomized, placebo-controlled, double-blind trial, we compared the effects of [6S]-5-MTHF and folic acid supplementation for 24 wk on plasma folate and red cell folate (RCF) in women of childbearing age (18-49 y). Women (n = 104) were randomly assigned to receive a supplement containing [6S]-5-MTHF (113 micro g/d), folic acid (100 micro g/d) or placebo. The mean estimated linear increase in plasma folate concentration was 0.3 [95% confidence interval (CI): 0.1, 0.5], and 0.4 (0.2, 0.6) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. The mean estimated linear increase in RCF was 7.4 (95% CI: 4.5, 10.3), and 8.3 (4.4, 12.3) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. There were no differences in the slopes between the [6S]-5-MTHF group and the folic acid group in either plasma folate (P = 0.48) or RCF (P = 0.70). At 24 wk, estimated mean increases in plasma folate concentrations were 6.9 (95% CI: 1.7, 12.2) and 9.2 (3.3, 15.1) nmol/L, and in RCF, 251 (143, 360) and 275 (148, 402) nmol/L, in the [6S]-5-MTHF and folic acid groups, respectively, relative to the placebo group. These data suggest that low dose [6S]-5-MTHF and folic acid supplementation increase blood folate indices to a similar extent. A steady state in the blood indices had not been reached by 24 wk.     

Red blood cell folate concentrations increase more after supplementation with [6S]-5-methyltetrahydrofolate than with folic acid in women of childbearing age

BACKGROUND: For the primary prevention of neural tube defects (NTDs), public health authorities recommend women of childbearing age to take 400 mug folic acid/d 4 wk before conception and during the first trimester. The biologically active derivate [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) could be an alternative to folic acid. OBJECTIVE: We investigated the effect of supplementation with [6S]-5-MTHF compared with that of folic acid on red blood cell folate concentration, an indicator of folate status. DESIGN: The study was designed as a double-blind, randomized, placebo-controlled intervention trial. Healthy women (n = 144) aged 19-33 y received 400 microg folic acid, the equimolar amount of [6S]-5-MTHF (416 microg), 208 microg [6S]-5-MTHF, or placebo as a daily supplement for 24 wk. Red blood cell and plasma folate concentrations were measured at baseline and at 4-wk intervals. RESULTS: The increase in red blood cell folate over time was significantly higher in the group receiving 416 microg [6S]-5-MTHF/d than in the groups receiving 400 microg folic acid/d or 208 microg [6S]-5-MTHF/d (P < 0.001). No plateau was reached in red blood cell folate concentration in the 3 treatment groups during 24 wk of intervention; however, plasma folate plateaued after 12 wk. CONCLUSIONS: We showed that administration of [6S]-5-MTHF is more effective than is folic acid supplementation at improving folate status. In addition, the study indicates that the recommended period for preconceptional folic acid supplementation should be extended to >4 wk for maximal prevention of NTDs based on folate concentrations. [6S]-5-MTHF might be an efficient and safe alternative to folic acid.     

MTHFR基因C677T位点多态性与胎儿生长受限的相关性

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T位点多态性与胎儿生长受限(FGR)的关系。方法:FGR患者62例,正常妊娠妇女65例。聚合酶链反应—限制性内切酶片段长度多肽性(PCR-RFLP)法检测MTHFR C677T基因多态性;荧光偏振免疫法测定血浆总同型半胱氨酸水平;微粒子酶免分析法测定血浆叶酸、VitB12浓度。结果:①FGR组MTHFR C677TC/T基因型频率显著高于正常对照组,C/C基因型频率显著低于对照组,总的突变T等位基因频率显著高于对照组(P<0.05)。②FGR组MTHFRT/T基因型Hcy水平较C/C、C/T基因型患者显著增高,而血清叶酸水平则明显降低(P<0.05)。血清VitB12水平在FGR3种基因型之间差异无显著性(P>0.05)。对照组MTHFR C677T3种基因型之间血清Hcy、叶酸、VitB12,水平差异无显著性(P>0.05)。结论:MTHFR基因C677T位点多态性与FGR有关,高同型半胱氨酸血症是FGR发病的危险因素。