Biochemical indices of vitamin B12 nutrition in pregnant patients with subnormal serum vitamin B12 levels

To determine the significance of the commonly observed fall in serum vitamin B₁₂ levels during pregnancy, serum levels of the B₁₂ metabolites methylmalonic acid (MMA) and homocysteine (Hcy) were measured in a group of 50 pregnant patients with subnormal serum B₁₂ (range 45-199 pg/ml) and the results compared with those of 25 pregnant controls (serum B₁₂208-580 pg/ml). Mean values for serum MMA and total Hcy in the subnormal B₁₂ group were 445.4 nmol/L and 7.03 μmol/L, respectively, which were not significantly different from the mean MMA of 440.5 nmol/L and Hcy of 6.88 nmol/L in the controls. For the total group of patients, neither serum MMA nor serum Hcy levels correlated with serum B₁₂. One-third of pregnant patients showed elevated serum MMA values, independent of B₁₂ status. Significant elevation of serum Hcy was detected in only two patients, both with subnormal serum B₁₂ and hematological evidence of B₁₂ deficiency. We conclude that the usual fall in serum B₁₂ concentration in pregnancy does not reflect B₁₂ deficiency at the biochemical level. In establishing true B₁₂ deficiency in pregnancy, the serum Hcy level (in the absence of folate deficiency) but not serum MMA, is of value. © 1995 Wiley-Liss, Inc.     

Hyper-homocysteinemia is not a main feature of juvenile uncomplicated type 1 diabetes

Total plasma homocysteine (tHcy) was measured by high pressure liquid chromatography (HPLC) method in 28 patients (12 females and 16 males) at the onset of type 1 diabetes mellitus (T1DM), 4 females during diabetes ketoacidosis (DKA) and 154 (68 females and 86 males) during follow-up. Serum folate, pyridoxal 5' phosphate (PLP) and Vitamin B12 (Vit B12) were also measured. Plasma tHcy levels were not found significantly different in T1DM patients known to have diabetes (males 9.2 +/- 7.7 and females 7.0 +/- 2.8 micromol/l) and in those who were newly diagnosed (males 9.7 +/- 4.8 and females 7.16 +/- 2.8 micromol/l) than in healthy controls (males 8.7 +/- 3.5 and females 7.8 +/- 2.55 micromol/l). Only a significant difference for sex was observed in known diabetes (p = 0.0281). Serum folate, PLP and Vit B12 were normal (12.6 +/- 3.6 ng/ml, 20.11 +/- 0.8 ng/ml and 416.7 +/- 41.9 pg/ml) in all T1DM patients. Age significantly correlated with plasma tHcy. Only in 4 patients, studied during DKA, plasma tHcy was significantly lower (2.76 +/- 1.33 micromol/l, p < 0.001) than the healthy controls.     

Relation of Helicobacter pylori infection to plasma vitamin B12, folic acid,and homocysteine levels in patients who underwent diagnostic coronary arteriography

OBJECTIVE: The aim of this study was to test the hypothesis that chronic atrophic gastritis induced by Helicobacter pylori (H. pylori) causes malabsorption of vitamin B12 and folate in food, leading ultimately to an increase in circulating homocysteine levels. METHODS: We performed endoscopy with stomach biopsy and measured fasting plasma homocysteine, vitamin B12, and folate levels in 93 patients who underwent diagnostic coronary arteriography. The patients were divided into two groups according to the presence (n = 57) or absence (n = 36) of H. pylori infection. Positive H. pylori infection was defined as positive H. pylori histology of biopsy specimens from the stomach. The extent of atrophic gastritis was endoscopically graded from 0 to 6. RESULTS: There were no differences in age, sex, or traditional coronary risk factors between the two groups. Atrophy scores of the stomach were greater in patients with H. pylori infection than in patients without (3.9 +/- 1.4 vs 2.2 +/- 1.8, p < 0.0001). Patients with H. pylori infection had lower levels of vitamin B12 (630 +/- 222 vs 747 +/- 259 pg/ml, p = 0.02) and folate (6.2 +/- 2.1 vs 7.4 +/- 2.8, p = 0.046), as well as higher levels of homocysteine (11 +/- 4.9 vs 8.3 +/- 2.1 nmol/ml, p = 0.01), than did patients without H. pylori infection. Plasma homocysteine levels correlated inversely with plasma vitamin B12 and folate levels and positively with atrophic scores. CONCLUSIONS: This study suggests that H. pylori-induced chronic atrophic gastritis decreases plasma vitamin B12 and folic acid levels, thereby increasing homocysteine levels. However, this effect does not seem to be strong.     

Gonadotropin treatment increases homocysteine levels in idiopathic hypogonadotropic hypogonadism: an indirect effect mediated by changes in body composition

The main objective of the present study was to examine the alterations in plasma total homocysteine (tHcy) concentrations during a testosterone-deficient state and after gonadotropin treatment for 6 Months in patients with idiopathic hypogonadotropic hypogonadism (IHH). Thirty-five newly diagnosed male patients with IHH (mean age 21.34+/-1.53 years) and 29 age- and body mass index-matched healthy males (mean age 21.52+/-1.77 years) were recruited into the study. Pretreatment levels of free testosterone (1.51+/-0.66 pg/ml), estradiol (21.37+/- 4.37 pg/ml), FSH (0.91+/-0.24 IU/l) and LH (1.25+/- 0.53 IU/l) were lower than controls (25.17+/-3.06 pg/ml, 31.00+/-4.96 pg/ml, 3.14+/-1.62 IU/l and 4.83+/-1.65 IU/l respectively) (P<0.001). They increased significantly after treatment (18.18+/-1.59 pg/ml, 27.97+/- 4.25 pg/ml, 2.41+/-0.27 IU/l and 2.79+/-0.19 IU/l respectively) (P<0.001). Patients with IHH had lower tHcy levels than controls (10.14+/-1.34 and 12.58+/- 2.29 micro mol/l respectively) (P<0.001). Plasma tHcy concentrations increased significantly (12.63+/-1.44 micromol/l) after 6 months of treatment (P<0.001). As compared with the controls, pretreatment levels of serum creatinine (63.54+/-13.01 vs 82.84+/-16.69 micromol/l), hemoglobin (12.98+/-0.56 vs 13.83+/-0.71 g/dl) and hematocrit (39.29+/-2.01 vs 41.38+/-1.95%) were significantly lower (P<0.001), and they increased significantly following treatment (80.24+/-11.93 micromol/l, 13.75+/-0.49 g/dl and 41.26+/-1.78% respectively) (P<0.001). The pretreatment folic acid and vitamin B(12) levels were significantly higher in patients when compared with controls (14.87+/-5.68 vs 12.52+/-4.98 nmol/l, P=0.034 and 289.75+/-92.34 vs 237.59+/-108.17 pmol/l, P=0.002 respectively). They decreased significantly after treatment (11.29+/-3.31 nmol/l and 228.51+/-54.33 pmol/l respectively) (P<0.001). The univariate and multivariate regression analysis results showed that only changes in creatinine, creatinine clearance, vitamin B12 and folic acid were independently associated with changes in tHcy levels in patients with IHH. In conclusion, the increase in plasma tHcy concentrations following gonadotropin treatment seems to be largely independent of changes in androgen levels.     

血浆同型半胱氨酸及其代谢酶基因多态性与溃疡性结肠炎的相关性研究

目的 探讨血浆同型半胱氨酸(Hcy)、叶酸和维生素B12水平及Hcy代谢酶基因多态性与溃疡性结肠炎(UC)的关系.方法 收集310例UC患者和936名正常对照者,采用聚合酶链反应-限制性片断长度多态性(PCR-RELP)法检测亚甲基四氢叶酸还原酶(MTHFR)C677T、A1298C、甲硫氨酸合成酶(MTR) A2756G和甲硫氨酸合成还原酶(MTRR) A66G基因多态性;并从中随机选取88例UC患者和100名正常对照者,采用循环酶法检测血浆Hcy水平,微粒子免疫化学发光法检测叶酸和维生素B12浓度.结果 UC患者MTHFR A1298C、MTR A2756G和MTRRA66G突变的等位基因及基因型频率均明显增高(P值均<0.01).UC患者Hcy平均水平为(21.73±6.59)mmol/L,较正常对照组显著增高[(12.47±5.01)mmol/L,P<0.01],而叶酸和维生素B12平均水平分别为(11.25±6.19)nmol/L和(322.81±128.47)pmol/L,明显较正常对照组降低[(15.28±7.72)nmol/L和(422.59±129.36)pmol/L,P值均<0.01].Logistic回归分析提示血浆Hcy、叶酸和维生素B12浓度是UC的独立危险因素(P值均<0.01).结论 Hcy代谢酶基因多态性及血浆Hcy、叶酸和维生素B12水平异常与UC明显相关,为临床采用叶酸、维生素B12补充疗法治疗UC提供了理论依据.     

Homocysteine, folate and vitamin b12 in patients with coronary heart disease

BACKGROUND/AIMS: Homocysteine and possibly also folate and vitamin B(12) are involved in the pathogenesis of cardiovascular disease. We investigated the prevalence of hyperhomocysteinemia in patients with coronary heart disease (CHD), as well as folate and vitamin B(12), the main nutritional factors determining the level of homocysteine. METHODS: Patients with angiographically documented CHD were prospectively investigated (n = 315, 70% male, mean age 61 [range 36-81] years). Fasting total serum homocysteine was determined by high-performance liquid chromatography and fluorescence detection. Folic acid and vitamin B12 were measured with AxSYMR Systems. RESULTS: Median homocysteine concentrations for homocysteine, folate and vitamin B12 were 12.8 micromol/l, 6.8 ng/ml and 345 pg/ml, respectively. Homocysteine levels >10 micromol/l were found in 82% of men and 73% of women. In 19% of the patients serum folate was <3 ng/ml and 22% of the patients had serum vitamin B12 values <250 pg/ml. In a multivariate linear regression model, folate and vitamin B(12) showed significant negative correlations to homocysteine, explaining 5 and 3% of its variability. Age and creatinine were the most important determinants for serum homocysteine, contributing 12 and 7%, respectively. DISCUSSION: The main determinants of total homocysteine in patients with CHD are higher age and increased creatinine. The association of lower levels of folate and vitamin B12 with higher levels of homocysteine may indicate poor dietary habits in these patients.     

Elevated homocysteine levels with weight loss after Lap-Band surgery: higher folate and vitamin B12 levels required to maintain homocysteine level.

OBJECTIVE: To investigate homocysteine levels and their relationship with serum folate and vitamin B12 concentrations with weight loss after the Lap-Band form of gastric restrictive surgery, with the view to minimizing risk. METHODS: We measured levels of fasting plasma homocysteine (tHcy), folate (serum and RBC) and vitamin B12 in two groups. The study group was 293 consecutive patients at 12 (n=192) or 24 (n=101) months review after surgery. The controls were 244 consecutive patients presenting for this surgery. RESULTS: The group losing weight had higher geometric mean tHcy levels: 10.4 (95% CI, 9.8-10.8) micromol/l compared with 9.2 (95% CI, 8.9-9.7) in controls (P<0.001). This occurred with higher folate levels and unchanged vitamin B12 levels. Levels of folate and B12 together explained 35% (r (2)) of the homocysteine variance in the weight loss group compared with only 9% (r (2)) in controls (P<0.001). Those taking regular multivitamin supplements had lower tHcy levels: 9.6 (9.1-10.0) micromol/l vs 12.3 (11.4-13.3) in those not taking supplements (P<0.001). A low normal plateau of tHcy levels occurred at levels of folate >15 ng/l and B12)600 ng/ml. A curvilinear relationship exists between these cofactors and tHcy levels, with the dose-response relationship shifted to the right in the weight loss group. CONCLUSION: This study shows elevated tHcy levels with weight loss, without lower serum folate or vitamin B(12) levels. There is an altered dose-response relationship with higher serum B(12) and folate levels required to maintain recommended tHcy levels. Patients losing weight have significant health benefits; however, they may be at greater risk of vascular events or fetal abnormality in association with raised tHcy levels. Multivitamin supplementation is effective in lowering tHcy levels.     

溃疡性结肠炎中血浆同型半胱氨酸和褪黑素水平的关联研究

目的 探讨血浆同型半胱氨酸(HCY)和褪黑素(MLT)水平改变与溃疡性结肠炎(UC)的临床关联.方法 收集112例UC患者临床资料,以110名健康体检者为对照.采用高效液相荧光检测法(HPLC-FD)检测血浆HCY、MLT水平,酶联免疫吸附分析(ELISA)法检测血浆叶酸(FA)、维生素B12水平,并分析该四项指标与UC患者临床特征的相关性.结果 UC患者血浆HCY水平高于健康对照[(11.27±7.26)μmol/L比(8.19±4.81)μmol/L,P=0.000],血浆MLT水平低于健康对照[(49.06±31.40)pg/ml比(64.28±41.16)pg/ml,P=0.008],血浆FA水平低于健康对照[(7.64±1.95)nmol/L比(9.14±1.23)nmol/L,P=0.005]、血浆维生素B12水平低于健康对照[(108.64±32.22)pmol/L比(112.64±33.33)pmol/L,P=0.004].UC患者血浆HCY、MLT水平与UC病情分度、病变范围、病程、红细胞沉降率(ESR)、C反应蛋白(CRP)水平无关.UC患者血浆HCY与MLT水平间无明显相关性.结论 UC患者血浆HCY水平高于健康对照,MLT水平低于健康对照,但二者间无明显相关性.

Abstract：

Objective To explore the clinical correlation of the variation of plasma homocysteine (HCY), melatonin (MLT) and ulceative colitis (UC). Methods The clinical data of 112 UC patients was collected, and 110 normal healthy persons as control. The level of plasma HCY and MLT was detected by high pressure liquid chromatography-fluorescence detection (HPLC-FD) method. The level of plasma folate ( FA) and vitamin B12 was detected by enzyme-linked immunosorbent assay (ELISA) method. The correlation of these four indexes and UC was analyzed. Results The serum level of HCY in UC patients was significantly higher than that in normal healthy persons [(11. 27± 7.26) μmol/L vs (8. 19±4. 81) μmol/L, P = 0. 000]. The serum level of MLT in UC patients was significantly lower than that in normal healthy persons [(49. 06 + 31. 40) pg/ml vs (64. 28±41. 16) pg/ml,P=0. 008]. The serum level of FA in UC patients was significantly lower than that in normal healthy persons [(7. 64 + 1.95) nmol/L vs (9. 14 + 1.23) nmol/L, P = 0. 005]. The serum level of vitamin B12 in UC patients was significantly lower than that in normal healthy persons [(108. 64 ±32. 22) pmol/L vs (112. 64±33. 33) pmol/L, P = 0. 004]. There was no correlation between plasma HCY, MLT and UC disease activity degree, range, disease duration, erythrocyte sedimentation rate (ESR), or C reactive protein (CRP) in UC patients. There was no significant correlation between MLT and HCY in UC patients. Conclusions The serum level of HCY is higher in UC patients than that in normal control, and MLT is lower than that in normal control. However there is no significant correlation between them.     

Helicobacter pylori eradication lowers serum homocysteine level in patients without gastric atrophy

AIM: To determine whether Helicobacter pylori (H pylori) infection caused hyperhomocysteinemia by altering serum vitamin B_(12), serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level. METHODS: The study involved 73 dyspeptic H pylork positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of H pylori 4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B_(12) folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after H pylori eradication therapy were compared. RESULTS: The group with a successful eradication of H pylori had significantly higher serum vitamin B_(12) and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210±97 pg/mL vs 237±94 pg/mL,P＜0.001 and 442±212 ng/mL vs 539±304 ng/mL, P=0.024, respectively), but showed no significant change in serum folate levels (5.6±2.6 ng/mL vs 6.0+2.4 ng/mL, P=0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1±5.2 μmol/L vs 11.9±6.2 μmol/L, P=0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P=0.01) and negatively with serum folate level before therapy (P=0.003). CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B_(12), serum folate and erythrocyte folate levels.     

Folate, Vitamin B12, Homocysteine, and Depressive Symptoms in a Population Sample of Older Chinese Adults

OBJECTIVES: To investigate the independent associations between folate, B12, and homocysteine levels and depressive symptoms in older adults.
DESIGN: Cross-sectional study.
SETTING: Resident population in southeast Singapore.
PARTICIPANTS: Six hundred sixty-nine community-living noninstitutionalized Chinese adults aged 55 and older.
MEASUREMENTS: Laboratory values of folate, vitamin B12, and homocysteine were examined for their independent relationships with depressive symptoms (Geriatric Depression Scale (GDS) score ≥5).
RESULTS: Respondents with depression (n=178) had lower mean serum folate concentrations (21.5 nmol/L) than those without (n=491, 24.0 nmol/L, P =.04). There was a linear relationship between descending quartiles of folate concentrations and increasing odds of association with depressive symptoms, independent of other risk factors (demographic, psychosocial, alcohol and smoking, chronic morbidity, functional status, nutritional risk, albumin, anemia, depression-inducing medications, use of antidepressants and vitamin supplements), including B12 and homocysteine ( P for trend=.02). The odds ratio (OR) of association between low folate (lowest quartile: <14.6 nmol/L) and depressive symptoms independent of other risk factors, including homocysteine and B12, was 1.72 (95% confidence interval (CI)=1.11–2.66). Vitamin B12 across a range of values did not show a linear association, but B12 deficiency (<180 pmol/L) appeared to be significantly associated with depressive symptoms (OR=2.68, 95% CI=1.20–6.00), independent of folate and homocysteine.
CONCLUSION: Decreasing and low levels of serum folate and deficient levels of B12 were associated with greater risk of depressive symptoms in older Chinese adults.     

Hyperhomocysteinemia in ulcerative colitis is related to folate levels

AIM: To study the prevalence and clinical significance of hyperhomocysteinemia (hHcys), an independent factor for arterial and venous thrombosis, in a group of patients with ulcerative colitis (DC). METHODS: Fasting homocysteine (Hcys), folate, and vitamin B12 serum levels were measured in 40 DC patients and 50 healthy controls. Clinical data regarding DC were gathered. RESULTS: Median serum Hcys levels in DC patients were similar to those in controls (12.26 umol/L vs 12.32 μmol/ L), but the prevalence of hHcys was higher in UC patients than in controls (30% vs 10%, P= 0.028).UC significantly increased the risk of hHcys (adjusted odds ratio: 4.125; 95%CI: 1.26-13.44). Multivariate regression analysis showed that male sex, folate and vitamin B12 deficiency or lower serum values were significant independent predictors of higher Hcys levels in UC patients (r2=0.4;P<0.001). CONCLUSION: hHcys is common in UC patients and it is related to folate and vitamin B12 deficiency or lower serum values. It would be reasonable for patients with UC to receive folate and vitamin B complex supplements as a prophylactic measure.     

Vitamin B12 and folate deficiency in later life

OBJECTIVES: to examine the prevalence of vitamin B12 deficiency and folate deficiency in later life in representative samples of the elderly population in the United Kingdom. DESIGN: a population-based cross-sectional analysis of 3,511 people aged 65 years or older from three studies was used to estimate the age-specific prevalence of vitamin B12 deficiency and of folate deficiency. Vitamin B12 deficiency is conventionally diagnosed if serum vitamin B12 < 150 pmol/l ('low vitamin B12'). We defined 'metabolically significant vitamin B12 deficiency' as vitamin B12 < 200 pmol/l and blood total homocysteine >20 micro mol/l. Folate deficiency, which usually refers to serum folate <5 nmol/l, was defined as 'metabolically significant' if serum folate was <7 nmol/l and homocysteine >20 micro mol/l. RESULTS: the prevalence of vitamin B12 deficiency, whether defined as low vitamin B12 or metabolically significant vitamin B12 deficiency increased with age in all three studies, from about 1 in 20 among people aged 65-74 years to 1 in 10 or even greater among people aged 75 years or greater. The prevalence of folate deficiency also increased with age, and was similar to that for vitamin B12 deficiencies, but only about 10% of people with low vitamin B12 levels also had low folate levels. CONCLUSION: the high prevalence of vitamin B12 and folate deficiency observed in older people indicates a particular need for vigilance for deficiency of these vitamins. Reliable detection and treatment of vitamin deficiency could reduce the risk of deficiency-related disability in old age.     

Plasma homocysteine after insulin infusion in type II diabetic patients with and without methionine intolerance.

BACKGROUND: A high prevalence of hyperhomocysteinemia has been reported in type II diabetic patients with documented vascular disease; hence the hypothesis that hyperhomocysteinemia may contribute to overall mortality in diabetic patients. The link between insulin and homocysteine metabolism has not been completely clarified yet; in particular, only few data are available on the effects of insulin in vivo on homocysteine metabolism in the presence of abnormalities of sulphur amino acid metabolism (methionine intolerance). MATERIALS AND METHODS: To establish whether methionine intolerance and which of its determinants could influence total plasma homocysteine in response to insulin infusion in vivo in type II diabetic patients, we submitted 18 patients (Group A) with normal and 18 patients with abnormal (hyperhomocysteinemia) (Group B) response to oral methionine load to a glucose/clamp study. At time 0, and 30, 60 and 120 minutes after hyperinsulinemia, homocysteine and methionine plasma levels were assessed. In order to evaluate the cause of methionine intolerance, all patients were assayed for fasting homocysteine-cysteine ratio (as a marker of suspected heterozygosis for cystathionine-beta-synthase deficit), MTHFR C (677)T status and homocysteine-related vitamin status (serum vitamin B (6) [PLP], vitamin B (12) and folate). RESULTS: After hyperinsulinemia, plasma methionine was reduced (by about - 30 % at 120 minutes vs. basal values) within both groups, whereas tHcy tend to decrease in group A following insulin administration (up to - 6.6 +/- 3.6 % vs. basal values at 120 minutes) with a significantly higher variability, while in patients with "methionine intolerance" (group B) tHcy tended to increase (up to + 29.05 +/- 8.3 % vs. basal values at 120 min from the clamp). Serum folic acid (7.45 +/- 2.8 vs. 4.82 +/- 2.5 nmol/L, p < 0.05), Vit. B (12) (348 +/- 78 vs. 242 +/- 65 pmol/L, p < 0.05) and PLP (84.1 +/- 23.6 vs. 50.6 +/- 32.4 nmol/L; p < 0.01) were significantly higher in group A than in group B; PLP levels significantly correlated with homocysteine after 4 h methionine load (n = 36; r = - 0.327, p < 0.05); group A showed also a significantly lower prevalence of suspected heterozygosis for cystathionine-beta-synthase deficit (1/18 [11.1 %] vs. 5/18 [33.3 %], p < 0.05) and MTHFR T allele presence (4/18 [22.2 %] vs. 11/18 [61.1 %], p < 0.01). A stepwise regression analysis with tHcy plasma level variations (event A = reduction; event B = increase) as the dependent variable showed that low serum folate and PLP levels and presence of MTHFR T allele were the variables associated with insulin-induced tHcy increase. CONCLUSIONS: Methionine intolerance may influence the effect of insulin administration on plasma homocysteine in patients affected by type 2 diabetes. To prevent a possible acute (and repeated) hyperhomocysteinemia due to insulin administration in cases of methionine intolerance, it may be useful to assess the presence of methionine intolerance (tHcy after oral methionine loading) and Hcy-related vitamin status in all patients due to be subjected to insulin therapy.     

Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.     

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.     

Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.     

Helicobacter pylori eradication lowers serum homocysteine level in patients without gastric atrophy

AIM: To determine whether Helicobacter pylori ( H pylori)infection caused hyperhomocysteinemia by altering serum vitamin B12, serum folate and erythrocyte folate levels and whether eradication of this organism decreased serum homocysteine level.METHODS: The study involved 73 dyspeptic H pylori-positive patients, none of them had gastric mucosal atrophy based on rapid urease test and histology. Out of 73 patients, 41 (56.2%) showed a successful eradication of Hpylori4 wk after the end of treatment. In these 41 patients, fasting serum vitamin B12, folate and homocysteine levels, and erythrocyte folate levels before and 4 wk after Hpylorieradication therapy were compared.RESULTS: The group with a successful eradication of Hpylori had significantly higher serum vitamin B12 and erythrocyte folate levels in the post-treatment period compared to those in pre-treatment period (210&#177;97 pg/mL vs237&#177;94pg/mL, P&lt;0.O01 and 442&#177;212 ng/mL vs 539&#177;304 ng/mL,P = 0.024, respectively), but showed no significant change in serum folate levels (5.6&#177;2.6 ng/mL vs 6.0&#177;2.4 ng/mL,P= 0.341). Also, the serum homocysteine levels in this group were significantly lower after therapy (13.1&#177;5.2 μmol/L vs 11.9&#177;6.2 μmol/L, P = 0.002). Regression analysis showed that serum homocysteine level was positively correlated with age (P = 0.01) and negatively with serum folate level before therapy (P = 0.003).CONCLUSION: Eradication of H pylori decreases serum homocysteine even in patients who do not exhibit gastric mucosal atrophy. It appears that the level of homocysteine in serum is related to a complex interaction among serum vitamin B12, serum folate and erythrocyte folate levels.     

No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis

OBJECTIVE: Elevated plasma total homocysteine (tHcy) concentrations are associated with premature cardiovascular disease. We assessed tHcy, folate, vitamin B12 (Vit B12), vitamin B6 (Vit B6), and genetic polymorphisms potentially enhancing tHcy in patients with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: Open study of 56 consecutive patients with JIA and 62 controls. RESULTS: tHcy concentrations were normal in JIA patients (mean 6.5 +/- 2 micromol/l) and controls (mean 7.5 +/- 2.2 micromol/l). Folate concentrations were significantly higher in JIA patients (40.2 +/- 67.9 ng/ml) compared to controls (13.6 +/- 8.2 ng/ml). The prevalence of genetic polymorphisms coding for key enzymes in the homocysteine pathway did not differ between patients and controls. Erythrocyte sedimentation rate (ESR) showed significant inverse correlations with circulating Vit B6 and tHcy concentrations. CONCLUSION: No evidence for hyperhomocysteinemia or evidence for a specific genetic predisposition for hyperhomocysteinemia was present in patients with JIA. Elevated ESR is not associated with hyperhomocysteinemia.     

Association of low red blood cell folate concentrations with coronary artery disease in Iranians: a matched case-control study

BACKGROUND: It is not fully established whether the increasing risk of coronary artery disease (CAD) is associated with high plasma homocysteine levels or components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5-methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this study, we tested the hypothesis that 5-MTHF in RBC, which represents the long-term folate status of individuals, may be a more reliable marker of homocysteine remethylation pathway disturbances, and its deficiency may be associated with CAD in Iranians. METHODS: Plasma total homocysteine (tHcy), vitamin B(12), and plasma and RBC 5-MTHF were measured in 200 angiographically documented patients and 200 controls matched for sex and age. RESULTS: In the plasma, tHcy levels were significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5 vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs. 461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2 +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients. RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a 2.5-fold increased prevalence of CAD compared to subjects in the highest quartile. The association of CAD in the first quartile with red-cell 5-MTHF remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p = 0.01). However, the association between CAD in the highest quartile and plasma tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF, vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence interval: 0.96-1.69, p = 0.11). CONCLUSION: In this study, the association between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study disturbances in the homocysteine remethylation pathway in Iranians.     

Regular vitamin B12 supplementation among older Chinese men in a veterans care home in Taiwan

Vitamin B(12) deficiency is common in older adults, and may be associated with cognitive impairment and depression. The main purpose of this study is to explore clinical effectiveness of regular vitamin B(12) supplementation on cognitive function and depressive symptoms among oldest old men living in a Taiwanese veterans care home. All residents of Banchiao Veterans Care Home were invited for study. Status of regular vitamin B(12) supplementation was determined. Cognitive function and depressive symptoms were evaluated by mini-mental state examination (MMSE) and geriatric depression scale (GDS). Subjects with renal insufficiency or established diagnosis of vitamin B(12) deficiency were excluded. Comparisons of demographic data, MMSE, GDS, and serum vitamin B(12) between subjects with and without regular supplementation were done. In total, 419 residents (mean age=80.8+/-5.5 years, all males) were enrolled. The mean serum level of vitamin B(12) was 1294.1+/-189.1 pg/ml (range: 50-30,000 pg/ml). Forty-five subjects (10.7%) reported regular vitamin B(12) supplementation, and their mean serum levels of vitamin B(12) were significantly higher than the non-supplementation subjects (8057.4+/-1408.3 pg/ml vs. 480.4+/-14.5 pg/ml, p<0.001). The mean MMSE (26.7+/-4.6 vs. 26.7+/-3.7, p=0.965), GDS (1.8+/-1.7 vs. 1.9+/-2.3, p=0.595), prevalence of cognitive impairment (13.6% vs. 19.3%, p=0.420) and depressive symptoms (4.5% vs. 8.4%, p=0.375) were similar between subjects with and without regular vitamin B(12) supplementation. In conclusion, regular vitamin B(12) supplementation and high serum level of vitamin B(12) are not associated with better cognitive function or depressive symptoms among asymptomatic oldest old men in a Taiwanese veterans care home.