Concentrations of B vitamins and homocysteine in children with sickle cell anemia

BACKGROUND: Elevated concentration of serum homocysteine contributes to thrombosis, a frequent event in patients with sickle cell anemia. We aimed to test whether children with sickle cell anemia have elevated concentrations of serum homocysteine with diminished levels of folate or B vitamins from accelerated blood cell turnover. METHODS: We conducted a case-control study of children with homozygous sickle cell anemia (n = 17) and unaffected children (n = 11). We measured serum and red blood cell folate, vitamin B6, vitamin B12, and homocysteine concentrations, and assessed micronutrient intake. RESULTS: Children with sickle cell anemia had concentrations of homocysteine slightly higher than those of unaffected children. They had lower vitamin B6 concentrations and comparable concentrations of folate and vitamin B12. Homocysteine concentration was inversely related to vitamin B12 concentration and was not independently associated with levels of vitamin B6 or folate. CONCLUSION: Despite comparable intake, children with sickle cell anemia had lower concentrations of vitamin B6 than unaffected children. Larger studies are needed to determine if chronically low serum vitamin B6 concentration contributes to hyperhomocysteinemia in this population.     

Screening for serum total homocysteine in newborn children

BACKGROUND: Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B12 (B12) deficiency or homocystinuria, but data on the causes of increased tHcy in screening samples are sparse. METHODS: Serum concentrations of tHcy, cystathionine, methionine, folate, and B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism were determined in 4992 capillary blood samples collected as part of the routine screening program in newborn children. Methylmalonic acid (MMA), gender (SRY genotyping), and the frequency of six cystathionine beta-synthase (CBS) mutations were determined in 20-27% of the samples, including all samples with tHcy > 15 micromol/L (n = 127), B12 < 100 pmol/L (n = 159), or methionine > 40 micromol/L (n = 154). RESULTS: The median (5th-95th percentile) tHcy concentration was 6.8 (4.2-12.8) micromol/L. B12 status, as determined by serum concentrations of B12, tHcy, and MMA, was moderately better in boys than in girls. tHcy concentrations between 10 and 20 micromol/L were often associated with low B12, whereas tHcy > 20 micromol/L (n = 43) was nearly always explained by increased methionine. tHcy did not differ according to folate concentrations or MTHFR 677C > T genotypes. None of the babies had definite CBS deficiencies, but heterozygosity led to low cystathionine, increased methionine, but normal tHcy concentrations. CONCLUSION: Increased tHcy is a common but not specific finding in newborns. The metabolite and vitamin profiles will point to the cause of hyperhomocysteinemia. Screening for tHcy and related factors should be further evaluated in regions with high prevalence of homocystinuria and in babies at high risk of B12 deficiency.     

Distribution of plasma total homocysteine concentrations in the healthy Iranians

OBJECTIVE: The distribution of plasma total homocysteine concentrations in a population of South West of Iran Shiraz is described to test for differences in homocysteine concentrations among gender and age groups and those levels reported in other populations. DESIGN AND METHODS: Two hundred one healthy males and 201 healthy females aged >15 years from Shiraz, Iran, were randomly selected. Plasma total homocysteine concentrations were measured using high-performance liquid chromatography. RESULTS: The mean plasma homocysteine level was significantly higher in men (geometric mean, 7.3 micromol/l) than in women (geometric mean, 6.3 micromol/l, P < 0.001). The geometric mean levels for ages 15-25, 26-36, 37-47, and 48-58, 59-69, and 70-80 years, were 5.9, 5.4, 5.2, 6.7, 7.3, and 7.6 micromol/l in women and 7.5, 8.7, 5.9, 5.9,7.2, and 9.1 micromol/l in men, respectively. CONCLUSIONS: The homocysteine distribution in a representative sample of people of southwest of Iran indicates age and gender differences, as is found in other populations.     

老年性白内障与MTHFR基因、同型半胱氨酸及B族维生素的相关性

目的 探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性及其酶代谢物与老年性白内障的相关性.方法 选取2019年1月至2020年6月绵阳市中心医院就诊的老年性白内障患者663例为疾病组,同期体检健康者646例为健康人对照组;分别检测各组MTHFR基因多态性(CC、CT或TT基因型)以及血清同型半胱氨酸(HCY)、叶酸(F...     

H型高血压患者吸烟与血清同型半胱氨酸的相关性研究

目的 分析H型高血压患者吸烟、戒烟对血清同型半胱氨酸(Hcy)水平的影响,分析吸烟指数、戒烟时间与Hcy水平的相关性.方法 对2018年10月至2019年10月在北京老年医院就诊的高血压患者进行Hcy检测,高血压合并Hcy≥10μmol/L者为H型高血压患者,筛选出H型高血压人群587例.对该人群全部进行调查问卷.分析...     

Stability of plasma total homocysteine concentrations in EDTA-whole blood kept on ice.

In recent years there has been increasing interest in monitoring plasma total homocysteine concentration (tHcy), as a risk factor for thrombotic disorders. One of the significant preanalytical factors that can affect the reliability of tHcy measurements is the generation of homocysteine by erythrocytes in vitro, prior to the separation of plasma from cells. We measured changes in tHcy from EDTA-whole blood kept on ice and at room temperature for three hours. Compared to the tHcy in plasma from EDTA-whole blood that was processed immediately after collection, there was no significant change in tHcy in samples kept on ice for up to three hours prior to processing (mean change = -0.1 +/- 0.24 umol/L, p = 0.2). In contrast, tHcy in samples kept at room temperature increased by 0.7 +/- 0.2 mumol/L per hour, p < 0.001. We conclude that tHcy is stable in EDTA-whole blood for at lest three hours, provided that the tubes are kept on ice until they are processed.     

正常妊娠妇女血清同型半胱氨酸水平调查

目的观察正常妊娠妇女血清同型半胱氨酸(Hcy)水平,为确定妊娠妇女Hcy水平的参考区间提供临床依据。方法采用循环酶法测定942例正常妊娠妇女血清Hcy水平,并收集其产检资料,追踪其分娩结局。根据测定Hcy时妊娠妇女的妊娠周期分为早、中和晚孕3组,各组例数分别为98例、202例和642例。结果正常妊娠妇女血清Hcy水平为(7.25±2.90)μmol/L,95%参考区间为1.57~12.93μmol/L。早孕组Hcy水平为(6.87±2.78)μmol/L,第75百分位数(P75)为7.53μmol/L;中孕组为(6.43±2.90)μmol/L,P75为7.21μmol/L;晚孕组为(7.54±2.86)μmol/L,P75为8.32μmol/L;3组之间差异有统计学意义(F=12.03,P=0.000)。两两比较显示早孕组与中孕组之间差异无统计学意义(t=0.99,P=0.321),中孕组与晚孕组之间差异有统计学意义(t=4.77,P=0.000)。晚孕组Hcy水平较中孕组平均升高(1.11±0.23)μmol/L[P=0.000;95%可信区间(CI)为0.65~1.56μmol/L]。线性相关分析显示Hcy水平与妊娠妇女年龄、检测孕周呈正相关(r值分别为0.14、0.15,P=0.000);将早、中和晚孕3组分别进行线性相关分析,仅晚孕组Hcy水平与检测孕周呈正相关(r=0.10,P=0.009)。多因素分析显示年龄、服用叶酸和Hcy检测孕周是影响孕妇Hcy水平的因素(F=16.59,P=0.000)。结论正常妊娠妇女血清Hcy水平妊娠早期为6.87μmol/L、中期为6.43μmol/L、晚期为7.54μmol/L;如妊娠早期Hcy水平7.53μmol/L(P75)、中期7.21μmol/L(P75)、晚期8.32μmol/L(P75)可能提示高Hcy血症。     

冠心病患者同型半胱氨酸水平测定及其临床应用

目的　测定 6 0例冠状动脉造影患者血清总同型半胱氨酸水平 ,探讨其对冠心病的临床意义。方法　将 6 0例冠脉造影患者分为冠心病组 (狭窄程度≥ 5 0 % ) 31例 ,与非冠心病组 (狭窄程度 <5 0 % ) 2 9例 ,其中冠心病组统计病变累及支数 ,并按冠脉狭窄程度分级得出冠脉狭窄程度记分 (CSS)。用酶免分析法分别测定两组的血清总同型半胱氨酸 (tHcy)浓度并进行比较。将tHcy水平与性别、年龄、收缩压、冠心病病变累及支数及冠脉狭窄程度记分等采用多元回归进行分析。结果　冠心病组患者血清tHcy浓度 (17 8± 7 1μmol/L)显著高于非冠心病组 (10 0± 5 8μmol/L)。多元回归分析表明 :非冠心病组tHcy增高与收缩压的相关性最强 ;冠心病组tHcy增高与病变累及支数及冠脉狭窄程度记分成正相关。结论　高同型半胱氨酸血症是冠状动脉粥样硬化性心脏病的危险因子 ,且其升高水平冠脉病变累及支数及狭窄程度呈正相关     

Routine determination of serum methylmalonic acid and plasma total homocysteine in Norway

Objective: To study the total number of combined analyses of methylmalonic acid (MMA) and total plasma homocysteine (tHcy) carried out during February 1998 at the Central Laboratory of Haukeland University Hospital. Methods: Laboratory data and requester comments of 2917 subjects in whom MMA was requested during February 1998, were retrieved from the laboratory information system (LIS). In 2520 cases, the results from the combined analyses of MMA and tHcy were available. Requester comments were registered in the LIS in 1084 cases. Results from additional laboratory analyses were accessible in about 10% of cases. Results: General practitioners requested MMA and tHcy on three main indications, i.e. low cobalamin, “control” and neurological symptoms. Metabolites were requested in twice as many women than men. Furthermore, MMA was requested in younger age groups of women compared with men. Plasma tHcy and MMA showed positive correlations with age and serum creatinine, and tHcy was generally 1–2?μmol/L higher in men than in premenopausal women. In cobalamin‐ (serum cobalamin>300?pmol/L) and/or folate‐ (serum folate >10?nmol/L) replete subjects, the average difference in MMA or tHcy according to the highest and lowest creatinine quartiles was 0.08 and 5–6?μmol/L, respectively. Different combinations of MMA and tHcy were evaluated by using a 5×5 matrix of predefined concentration intervals. Based on this matrix, cobalamin and folate deficiency could be excluded or the likely diagnoses proposed in 76% of cases. Cobalamin deficiency or folate deficiency was likely in about 7% and 12% of the subjects investigated, respectively. Conclusions: A combined analysis of MMA and tHcy provides complementary diagnostic information. When interpreting MMA and tHcy values, age, gender and renal function in particular must be taken into account. Typical combinations of MMA and tHcy concentration intervals could be proposed, which could either exclude deficiency or indicate likely diagnoses and/or influence of confounders.     

Routine determination of serum methylmalonic acid and plasma total homocysteine in Norway

OBJECTIVE: To study the total number of combined analyses of methylmalonic acid (MMA) and total plasma homocysteine (tHcy) carried out during February 1998 at the Central Laboratory of Haukeland University Hospital. METHODS: Laboratory data and requester comments of 2917 subjects in whom MMA was requested during February 1998, were retrieved from the laboratory information system (LIS). In 2520 cases, the results from the combined analyses of MMA and tHcy were available. Requester comments were registered in the LIS in 1084 cases. Results from additional laboratory analyses were accessible in about 10%, of cases. RESULTS: General practitioners requested MMA and tHcy on three main indications, i.e. low cobalamin, "control" and neurological symptoms. Metabolites were requested in twice as many women than men. Furthermore, MMA was requested in younger age groups of women compared with men. Plasma tHcy and MMA showed positive correlations with age and serum creatinine, and tHcy was generally 1-2 micromol/L higher in men than in premenopausal women. In cobalamin- (serum cobalamin > 300 pmol/L) and/or folate- (serum folate > 10 nmol/L) replete subjects, the average difference in MMA or tHcy according to the highest and lowest creatinine quartiles was 0.08 and 5-6 micromol/L, respectively. Different combinations of MMA and tHcy were evaluated by using a 5 x 5 matrix of predefined concentration intervals. Based on this matrix, cobalamin and folate deficiency could be excluded or the likely diagnoses proposed in 76% of cases. Cobalamin deficiency or folate deficiency was likely in about 7% and 12% of the subjects investigated, respectively. CONCLUSIONS: A combined analysis of MMA and tHcy provides complementary diagnostic information. When interpreting MMA and tHcy values, age, gender and renal function in particular must be taken into account. Typical combinations of MMA and tHcy concentration intervals could be proposed, which could either exclude deficiency or indicate likely diagnoses and/or influence of confounders.     

联合补充叶酸、维生素B6和B12对冠心病患者高同型半胱氨酸血症的影响

目的观察联合补充叶酸、维生索珑和维生素B12对冠心病合并高同型半胱氨酸血症患者降低血浆同型半胱氨酸（Hey）水平的影响。方法采用高压液相色谱法测定空腹血浆Hcy水平，应用放免分析法测定基础血浆叶酸及维生素B12浓度。冠心病患者中Hcy水平高于15μmol／L者为高I司型半胱氨酸血症，随机分为治疗组（55例）和对照组（43例），治疗组予以每日补充叶酸5mg，维生素B6 20mg 3次，维生素B12 0．5mg，对照组不予此三种药物治疗，4周后患者复查血浆Hcy水平。结果治疗组4周后Hcy水平平均降低了37．7％，治疗前后Hcy水平比较有显著差异（P〈0．01），治疗组中，治疗前后差值即经治疗后Hcy水平降低的幅度与基础叶酸浓度呈负相关（r=-0．386，P〈0．05）。结论联合补充叶酸、维生素B6和维生素B12可明显降低冠心病合并高同型半胱氨酸血症患者的血浆Hey水平，而且治疗前血浆叶酸浓度越低，Hcy水平降低的幅度越大，补充治疗的效果越好。     

Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes

OBJECTIVE: The purposes of this study were to compare plasma total homocysteine (tHcy) levels, a recognized cardiovascular risk factor, in nondiabetic subjects and type 1 diabetic patients, and to evaluate whether chronic cigarette smoking had a deleterious effect on plasma tHcy levels in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Plasma tHcy concentrations were measured in 60 young type 1 diabetic patients without clinical evidence of macroangiopathy and in 30 healthy control subjects who were matched for age, sex, BMI, and smoking habit. RESULTS: Plasma tHcy levels were significantly higher in type 1 diabetic patients than in control subjects (12.5 +/- 4.8 vs. 10.3 +/- 2.2 micromol/l, P = 0.01). After stratification by smoking status, diabetic smokers had values for age, sex, BMI, lipids, creatinine, blood pressure, glycometabolic control, diabetes duration, and microvascular complications that were superimposable on their nonsmoking counterparts. Nevertheless, plasma tHcy levels were markedly elevated in diabetic smokers versus nonsmokers (15.5 +/- 5.7 vs. 10.6 +/- 3 pmol/l, P < 0.0001) in a dose-dependent fashion (P < 0.0001, by analysis of variance when subjects were categorized for the number of cigarettes smoked daily). CONCLUSIONS: Chronic cigarette smoking seems to adversely affect plasma tHcy levels in young adults with type 1 diabetes.     

Effect of fish oil on LDL oxidation and plasma homocysteine concentrations in health

Oxidation of low-density lipoprotein (LDL) and hyperhomocysteinemia are believed to play a role in therogenesis. Whether n-3 polyunsaturated fatty acids increase LDL susceptibility to oxidation or influence homocysteine (Hcy) metabolism has long been a subject of controversy. In this study, we evaluated the effect of 8 weeks of dietary supplementation with 6 g/day of fish oil (FO; 3 g of n-3 fatty acids) on plasma lipoproteins, in vitro LDL peroxidation, antioxidant status, and plasma Hcy concentrations in 16 normolipidemic subjects. FO rapidly and significantly (P < .01) decreased plasma total and very low density lipoprotein triglyceride concentrations and had no effect on LDL or high-density-lipoprotein cholesterol. The mean lag time before onset of Cu(2+)-induced LDL oxidation, as well as plasma and LDL alpha-tocopherol and beta-carotene concentrations, was unchanged. However, changes in plasma aminothiol concentrations occurred during the study. Specifically, a progressive and significant increase in total Hcy plasma concentrations was observed (13.4% and 20% after 4 and 8 weeks, respectively; P < .01). Total glutathione concentrations were significantly higher after 8 weeks (P < .05). The tHcy increase was not associated with changes in plasma folate or vitamin B(12) concentrations. However, concentrations of plasma nitric oxide metabolites (NO(x) = NO(2) + NO(3)) were significantly higher than at baseline after 8 weeks of FO intake (74%; P < .01). Further, the changes in total Hcy and NO(x) plasma concentrations observed after 8 weeks of FO were found to be significantly correlated (r = .78, P < .001). With this study, we report for the first time the apparent interaction of n-3 fatty acids and nitric oxide on Hcy metabolism.     

The effects of adrenocorticotrophic hormone and cortisol on homocysteine and vitamin B concentrations.

BACKGROUND: Homocysteine metabolism is mainly governed by serum concentrations of folate and vitamin B(12), renal function and genetic factors. It is also well documented that endocrinological disturbances influence homocysteine metabolism. However, studies on the hormones of the hypothalamic-pituitary-adrenal axis have given conflicting results. METHODS: A total of 30 healthy young males were randomised into three groups of equal size; one group received adrenocorticotrophic hormone (ACTH)(1-24) 1 mg i.m. daily for 4 days, another group was treated with cortisol 50 mg i.m. t.i.d. for 4 days, while a control group was observed for 4 days. Fasting blood samples were collected before and after treatment or observation. RESULTS: The pattern of changes was the same for the ACTH and cortisol groups; there were significant decreases in serum concentrations of folate (23% and 24%) and cobalamines (13% and 19%) and decreases in plasma total homocysteine concentrations that did not reach significance. There were no changes in the control group. CONCLUSIONS: The virtually identical pattern of changes in both treatment groups suggests that the effects were mediated by cortisol. The reductions in serum concentrations of folate and cobalamines call for further research.     

Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.

Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.