Nonisotopic binding assay for measuring vitamin B12 and folate in serum.

We evaluated a nonisotopic method (CEDIA; cloned enzyme donor immunoassay) for estimating vitamin B12 and folate in serum. The assays were performed with a Cobas-Mira analyzer. Intra-assay CVs were from 3.7% to 11.0% for vitamin B12 and from 1.2% to 10.7% for folate. Interassay CVs ranged from 9.5% to 11.9% for vitamin B12 and from 6.1% to 18.5% for folate. Linearity was satisfactory, with analytical recovery of 94% at 8.7 and 25.4 nmol/L for folate and 280 and 554 pmol/L for vitamin B12. The detection limit was 3.6 nmol/L for folate and 12.3 pmol/L for vitamin B12. Results of this assay correlated well with those of a conventional radioassay: r = 0.98 for vitamin B12 (n = 51) and r = 0.97 for folate (n = 57). The CEDIA was easy to perform but appeared to be unreliable for use with samples from myeloma patients.     

Long-term diuretic therapy in hypertensive patients: effects on serum homocysteine, vitamin B6, vitamin B12, and red blood cell folate concentrations.

BACKGROUND: The effects of chronic diuretic use on serum homocysteine and its metabolic cofactors vitamin B6, vitamin B12, and red blood cell (RBC) folate have not been well studied. METHODS: Blood samples from 17 hypertensive patients receiving long-term diuretic therapy and 17 hypertensive patients not taking diuretics were analyzed for serum homocysteine, vitamin B6, vitamin B12, and RBC folate. RESULTS: The mean serum homocysteine concentration for patients taking diuretics (17.87 +/- 1.72 micromol/L) was significantly higher than the mean serum homocysteine concentration for patients not taking diuretics (10.31 +/- 0.99 micromol/L). The mean RBC folate concentration for patients taking diuretics (281.01 +/- 17.56 ng/mL) was significantly lower than the mean RBC folate concentration for patients not taking diuretics (430.85 +/- 28.58 ng/mL). Serum vitamin B6 and vitamin B12 concentrations were not significantly different between the two groups. CONCLUSIONS: Chronic diuretic use is associated with a significant increase in serum homocysteine concentration, a significant decrease in RBC folate concentration, and no significant change in concentrations of vitamins B6 and B12.     

18周内孕妇血清同型半胱氨酸、叶酸及维生素B12水平对妊娠结局的影响

目的观察18周内孕妇血清同型半胱氨酸、叶酸及维生素B12水平对产后胎盘重量、胎儿体重、早产结局的影响。方法我院2006年6至2011年12月孕龄小于18周的孕妇806例,抽血检测血清标志物同型半胱氨酸、叶酸及维生素B12的含量,生产后记录妊娠结局,并使用线性回归和Logistic回归分析孕早期血清标志物与不良妊娠结局的关系。结果高血清同型半胱氨酸水平(>8.3μmol/L)孕妇的胎盘重量比低同型半胱氨酸水平(<8.3μmol/L)孕妇平均轻30 g(P<0.001),新生儿体重轻110 g(P<0.001);而低叶酸水平(<9.2 nmol/L)孕妇的胎盘重量比高叶酸水平(>9.2 nmol/L)孕妇平均轻26 g(P<0.001),新生儿体重轻125 g(P<0.001),早产风险升高(OR 2.2,P=0.002),子痫前期风险上升(OR 2.1,P=0.04)。维生素B12的血清含量对妊娠结局无显著影响。结论血清同型半胱氨酸的含量升高,血清叶酸的含量降低,胎盘重量和新生儿体重会降低,早产和前期子痫的发生风险增高。     

Biomarkers of folate and vitamin B12 are related in blood and cerebrospinal fluid

BACKGROUND: B-vitamins (folate, B(12)) are important micronutrients for brain function and essential cofactors for homocysteine (HCY) metabolism. Increased HCY has been related to neurological and psychiatric disorders. We studied the role of the B-vitamins in HCY metabolism in the brain. METHODS: We studied blood and cerebrospinal fluid (CSF) samples from 72 patients who underwent lumbar puncture. We measured HCY, methylmalonic acid (MMA), and cystathionine by gas chromatography-mass spectrometry; S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) by liquid chromatography-tandem mass spectrometry; and the B-vitamins by HPLC or immunoassays. RESULTS: Concentrations were lower in CSF than serum or plasma for HCY (0.09 vs 9.4 micromol/L), SAH (13.2 vs 16.8 nmol/L), cystathionine (54 vs 329 nmol/L), and holotranscobalamin (16 vs 63 pmol/L), whereas concentrations in CSF were higher for MMA (359 vs 186 nmol/L) and SAM (270 vs 113 nmol/L; all P <0.05). CSF concentrations of HCY correlated significantly with CSF folate (r = -0.46), CSF SAH (r = 0.48), CSF-albumin (r = 0.31), and age (r = 0.32). Aging was also associated with lower concentrations of CSF-folate and higher CSF-SAH. The relationship between serum and CSF folate depended on serum folate: the correlation (r) of serum and CSF-folate was 0.69 at serum folate <15.7 nmol/L. CSF concentrations of MMA and holotranscobalamin were not significantly correlated. CONCLUSIONS: CSF and serum/plasma concentrations of vitamin biomarkers are significantly correlated. Older age is associated with higher CSF-HCY and CSF-SAH and lower CSF-folate. These metabolic alterations may be important indicators of low folate status, hyperhomocysteinemia, and neurodegenerative diseases.     

An International Standard for whole blood folate: evaluation of a lyophilised haemolysate in an international collaborative study.

Folate measurements, particularly for whole blood, show wide inter-laboratory and inter-methodology variability. This variability appears to be due in part to the lack of internationally accepted reference materials. A whole blood haemolysate, lyophilised in ampoules and designated 95/528, was therefore evaluated by 15 laboratories in five countries for its suitability as an International Standard (IS) for whole blood folate. The preparation was assayed using a variety of microbiological and protein-binding methodologies against local standards and calibrators. A consensus folate content was assigned to 95/528. The inclusion of three whole blood samples in the study with widely differing folate levels demonstrated a considerable reduction in inter-laboratory variability when the folate content of the samples was determined relative to the proposed IS 95/528 rather than to laboratories' local standards and calibrators. Accelerated degradation studies indicated that the folate content of 95/528 is stable when stored at -20 degrees C. On the basis of the results presented here, the World Health Organization Expert Committee on Biological Standardization established 95/528 as an IS for whole blood folate.     

Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification

OBJECTIVE: To estimate the associated risk of folate and vitamin B12 (B12) insufficiency, as well as vitamin repletion, following folic acid food fortification. DESIGN: Retrospective cross-sectional study over a 5-year period. SETTING: Two large laboratory databases in the provinces of Ontario and British Columbia, Canada. PARTICIPANTS: Canadian women aged 65 years and over who underwent concomitant clinical testing of serum folate and B12 during the pre-fortification period of January 1996 to December 1997 in Ontario (n = 733) and British Columbia (n = 3839), and in the near-complete post-fortification period of January 1998 to December 2000 in Ontario (n = 4415) and British Columbia (n = 6677). MEASUREMENTS: Geometric mean concentrations of serum folate and B12 before and after folate fortification. Prevalence ratios (PR) were used to separately compare the post- and pre-fortification period rates of folate deficiency (below 6.0 nmol/L); B12 insufficiency (below 150 pmol/L); and B12 insufficiency in combination with supraphysiological concentrations of serum folate (above 45 nmol/L). RESULTS: The mean baseline folate and B12 concentrations were similar between provinces. Using the combined provincial data, the mean serum folate concentration increased by 64% after fortification, from 14.8 to 24.2 nmol/L (p < 0.001). The average B12 concentration increased from 280 to 300 pmol/L, which was more pronounced in BC (p < 0.001) than in Ontario (p = 0.16). The prevalence of folate deficiency declined from 6.3% to 0.88% after fortification (PR 0.14, 95% confidence interval [CI] 0.11-0.18), while the decline in B12 deficiency was less pronounced (PR 0.78, 95% CI 0.71-0.86). CONCLUSIONS: The prevalence of combined B12 insufficiency with supraphysiological concentrations of serum folate increased from 0.09% pre-fortification to 0.61% post (PR 7.0, 95% CI 2.6-19.2).The introduction of folic acid food fortification was associated with a substantial improvement in the folate status of Canadian women aged 65 years and older, paralleled by a large decline in the rate of folate deficiency. Improvement in the B12 status of these women was far less pronounced. Because the prevalence of combined B12 insufficiency and supraphysiological concentrations of serum folate may have increased with folic acid food fortification, consideration should be given to confirming this finding, and possibly, to the addition of B12 to folate fortified foods.     

Vitamin B(12) deficiency associated with histamine(2)-receptor antagonists and a proton-pump inhibitor

OBJECTIVE: To report a case of vitamin B(12) deficiency associated with long-term use (approximately 4 1/2 y) of histamine(2) (H(2))-receptor antagonists and a proton-pump inhibitor (PPI) in a patient with gastroesophageal reflux. CASE SUMMARY: A 78-year-old nonvegetarian white woman with symptomatic gastroesophageal reflux (GER) was started on cimetidine 300 mg 4 times daily in February 1990 and took various other antisecretory medications over the course of the next 4 1/2 years. She had a normal serum vitamin B(12) concentration of 413 pg/mL in August 1992. In June 1994, her serum vitamin B(12) concentration was found to be in the low normal range at 256 pg/mL. Biochemical markers of vitamin B(12)-dependent enzyme activity were measured at that time, and methylmalonic acid (MMA) and homocysteine (HCYS) were elevated at 757 nmol/L and 27.3 micromol/L, respectively. Serum folate was within the normal range at 4.9 ng/mL, and serum creatinine was slightly elevated at 1.4 mg/dL. MMA and HCYS concentrations decreased dramatically with oral replacement of vitamin B(12) 1000 microg/d, which confirmed vitamin B(12) deficiency. Oral replacement also demonstrated that the woman was able to adequately absorb nonprotein-bound vitamin B(12) from the gastrointestinal tract, suggesting that her deficiency was a result of food-cobalamin malabsorption. The accumulation of MMA and HCYS was not a consequence of renal dysfunction, since both metabolites dramatically decreased with vitamin B(12) replacement. DISCUSSION: Malabsorption of dietary protein-bound vitamin B(12) has been demonstrated with the use of H(2)-receptor antagonists and PPIs. One previous case report of vitamin B(12) deficiency resulting from long-term use of omeprazole has been published. The malabsorption of dietary vitamin B(12) is thought to be a result of its impaired release from food protein, which requires gastric acid and pepsin as the initial step in the absorption process. CONCLUSIONS: The use of H(2)-receptor antagonists and/or PPIs may impair the absorption of protein-bound dietary vitamin B(12) and could contribute to the development of vitamin B(12) deficiency with prolonged use. Patients taking these medications for extended periods of time, particularly >4 years, should be monitored for vitamin B(12) status.     

Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay

BACKGROUND: Current clinical methods for folate give different results and cannot measure the various forms of folate. We developed an isotope-dilution tandem mass spectrometric method coupled to liquid chromatography (LC/MS/MS) as a candidate reference method for 5-methyltetrahydrofolic acid (5MeTHF), 5-formyltetrahydrofolic acid (5FoTHF), and folic acid (FA) in human serum. METHODS: We quantitatively isolated folates from 275 microL of serum with a phenyl solid-phase extraction cartridge, then detected and quantified them in stabilized serum extracts by positive-ion electrospray ionization LC/MS/MS. We used an isocratic mobile phase of acetic acid in organic solvent on a C(8) analytical column. (13)C-labeled folates were used as internal standards. RESULTS: Limits of detection in serum were 0.13 (5MeTHF), 0.05 (5FoTHF), and 0.07 (FA) nmol/L. Within- and between-run imprecision (CV) was <7% for 5MeTHF and <10% for 5FoTHF at concentrations >0.5 nmol/L, and <10% for FA at concentrations >2.0 nmol/L. Total folate (TFOL) concentrations determined by competitive protein binding radioassay were approximately 9% lower than results obtained with LC/MS/MS. The microbiologic assay gave approximately 15% higher TFOL results with FA calibrator and no difference with 5MeTHF calibrator. The mean (SD) [range] TFOL in 42 sera was 35.5 (17.8) [6.5-75.6] nmol/L. Thirty-two samples with TFOL <50 nmol/L had, on average, 93.3% 5MeTHF, 2.3% FA, and 4.4% 5FoTHF. Ten samples with TFOL >50 nmol/L had, on average, 81.7% 5MeTHF, 15.7% FA, and 2.5% 5FoTHF. CONCLUSIONS: This stable-isotope-dilution LC/MS/MS method can quantify 5MeTHF, 5FoTHF, and FA in serum. Currently used clinical assays agree with this candidate reference method.     

Methionine synthetase activity of human lymphocytes both replete in and depleted of vitamin B12

The activity of the enzyme methionine synthetase (MS) (methyltetrahydrofolate:homocysteine methyltransferase) (EC 2.1.1.13) was measured in human lymphocytes of various types and cobalamin (vitamin B12) status. Total and holo MS activity was low in unstimulated peripheral blood lymphocytes from persons with tissue deficiency of cobalamin, but not in cells from those with low serum cobalamin levels for other reasons. The MS activity of the lymphocyte was increased by treatment of the patients with vitamin B12. The number of lymphocytes was often low or low normal in the circulation of those deficient in cobalamin. Holo MS activity was low in an established line of human B cells, RPMI 6410 cells, depleted of cobalamin. The total and holo MS activity of both RPMI 6410 cells, replete or depleted, and lymphocytes stimulated in culture was increased by cobalamin in vitro; 222 nmol/L free cobalamin was roughly the equivalent of 0.22 nmol/L cobalamin bound to transcobalamin II. Both lymphocytes and RPMI 6410 cells required folate for growth and could meet these needs via methylfolate, homocysteine, and the cobalamin-dependent MS reaction. Depleted RPMI 6410 cells, however, used cobalamin in some way in addition to the provision of available folate from methylfolate. The consequences of the reduced MS activity in deficient cells could include a reduction in available folate with diminished capacity for clonal expansion of lymphocytes in reaction to infection and impairment of essential methylations including those of protein synthesis. The prompt induction of MS activity by cobalamin, especially in the in vitro model, suggests an effect of therapeutic vitamin B12 well in advance of the numerical increase in cells of the blood.     

The effect of serum vitamin B12, folate,ferritin levels and transferrin saturation on stem cell mobilization in allogeneic donors

IntroductionPeripheric blood derived stem cells are used in 75 % of allogeneic stem cell transplantations. Iron, vitamin B12 and folate involve in hematopoiesis. Therefore serum levels of iron, vitamin B12 and folat may effect stem cell mobilization. We aimed to analyze the effects of iron status, vitamin B12 and folate levels on peripheric blood stem cell mobilization in healthy donors.MethodThe mobilization results of 218 allogeneic donors were analyzed retrospectively.ResultsIn 64 donors, serum ferritin level was <15 μg / L and transferrin saturation was <20 %. When we compared the donors with iron deficiency to the donors without iron deficiency, the number of collected CD34 + cell was significantly higher in donors without iron deficiency. We did not find any impact of serum vitamin B12 and folate level on CD34+ cells collected.ConclusionOur study shows that serum ferritin and transferrin saturation have a greater effect on the amount of CD34+ cells collected from donors than serum vitamin B12 and folate levels. Consequently, when compliance tests of allogeneic donors are performed, the evaluation of vitamin B12 and folate levels is not necessary; whereas iron deficiency must be assessed and –if possible– corrected before apheresis is performed.     

阿尔茨海默病与维生素 B12及同型半胱氨酸的相关性

背景维生素 B12缺乏会产生神经功能障碍,影响中枢神经系统及全身的代谢,补充维生素 B12对预防及延缓阿尔茨海默病( Alzheimer disease, AD)的发展作用机制尚不清楚. 目的 研究 AD与血清维生素 B12,叶酸及血浆同型半胱氨酸水平之间的关系,探讨导致痴呆的机制. 设计以诊断为依据的非随机对照研究. 地点和对象 2002-10/2003-05于华中科技大学同济医学院附属协和医院住院治疗的 AD患者 30例( AD组),均符合美国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)的很可能 AD标准.对照组为同期参加体检的健康正常人 30例. 方法 采用简易精神状态量表( MMSE)对两组患者进行评分,并用放免分析法测定血清维生素 B12及叶酸水平,荧光偏振免疫法( fluorescence polarization immunoassay, FPIA)测定血浆同型半胱氨酸水平. 主要观察指标 ① AD组及对照组之间维生素 B12水平差异.② AD组及对照组之间 Hcy的水平差异.③ MMSE得分与维生素 B12及 Hcy之间的相关性. 结果 AD组维生素 B12水平( 217.3± 134.2) pmol/L明显低于对照组( 313.6± 184.7) pmol/L,二者差异有极显著性 (t=3.93,P< 0.001). AD组血浆同型半胱氨酸 (18.9± 6.8) μ mol/L高于对照组 (9.4± 4.1) μ mol/L,差异有极显著性意义 (t=7.66,P< 0.001). AD组叶酸水平( 29.2 ± 12.7) nmol/L低于对照组( 37.2± 21.2) nmol/L,但差异无显著性 (P >0.05). AD患者维生素 B12水平与 MMSE得分呈正相关( r=0.87).结论 AD患者血清维生素 B12水平与智能障碍及其程度有关.     

Homocysteine, vitamin B12, and serum and erythrocyte folate in peritoneal dialysis and hemodialysis patients.

BACKGROUND: Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. High levels of plasma Hcy have been observed in end-stage renal disease patients. Few studies have compared peritoneal dialysis (PD) and hemodialysis (HD) patients and few data are available on erythrocyte folate (ery-F) levels in dialysis patients. OBJECTIVES: To evaluate plasma Hcy concentrations, vitamin B12 (B12), and folate status in dialysis patients; to analyze the possible causes of high Hcy levels; to follow up changes in folate and B12 concentrations after 6 months. DESIGN: A cross-sectional observational study. SETTING: Nephrology division and laboratory of hematology in a university and clinical research hospital. PATIENTS: The study included 82 patients treated with PD for 37 + 37 months and 70 patients treated with HD for 136 + 95 months. LABORATORY METHODS: Plasma Hcy was measured by the immunoenzymatic IMx Hcy FPIA method (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, U.S.A.), serum folate (s-F) and ery-F by the Stratus folate fluorometric enzyme-linked assay, and B12 by the Stratus vitamin B12 fluorometric enzyme-linked assay (DADE-Behring, Newark, DE, U.S.A.). RESULTS: Ninety-six percent of PD and 97% of HD patients had Hcy levels above the cutoff (13.5 micromol/L). Homocysteine level was higher in HD than in PD patients, while the prevalence of hyperhomocysteinemia was similar with the two techniques. Erythrocyte folate was significantly higher in PD (1333 +/- 519 pmol/L) than in HD (1049 +/-511 pmol/L, p < 0.01). Statistically significant correlations were observed between Hcy and B12, s-F, ery-F, and dialysis duration. Multivariate analysis showed a strong correlation between s-F and Hcy. After 6 months there were no differences in Hcy, B12, s-F, and ery-F levels. CONCLUSIONS: Plasma Hcy levels were high in more than 95% of our dialysis patients, with no relation to the type of dialysis. Vitamin B12 and folate were normal in the majority of our patients. However, serum folate was the major determinant of Hcy levels. Such a relation between Hcy and folate suggests that levels of folate within the reference interval are inadequate for dialysis patients.     

Stability of fat-soluble and water-soluble vitamins in artificially prepared, vitamin-enriched, lyophilized serum

Vitamin-enriched, lyophilized serum (VES) was prepared for an inter-laboratory study to compare vitamin assays. The VES contained water-soluble vitamins (vitamin B1, vitamin B12, vitamin C, and folate), fat-soluble vitamins (vitamin A and vitamin E), and cholesterol. We performed stability studies and determined vitamin concentrations and total cholesterol in VES stored at -20 degrees C for 12 months. Our recovery of the water-soluble vitamins in reconstituted VES was 70-142%, but we recovered only 33-45% of the fat-soluble vitamins. Physicochemical properties, such as specific gravity and viscosity of the reconstituted VES did not affect manual or automated measurements of these vitamins. Vial-to-vial differences found for the VES were the same as the within-day analytical variations. There was no evidence of degradation of vitamin A, vitamin B1, vitamin B12, vitamin C, folate, and cholesterol over 12 months in VES stored at -20 degrees C. Following deproteinization, vitamin C concentration was found to be lower than when not deproteinated. Vitamin E was less stable in VES, however, and the degradation during 12 months was lower than the between-day analytical variation of the assay. Our VES is the first preparation of lyophilized control serum that contains water-soluble and fat-soluble vitamins.     

Vitamin B12 deficiency is the dominant nutritional cause of hyperhomocysteinemia in a folic acid-fortified population.

Prevalence rates for folate deficiency and hyperhomocysteinemia have been markedly reduced following the introduction of folic acid fortification in the United States. We report the prevalence of hyperhomocysteinemia in a population of community-dwelling elderly Latinos in the post-folic acid fortification era. We measured homocysteine, total vitamin B12, holotranscobalamin, red blood cell folate, and serum creatinine in 1096 subjects aged > or =60 years. Hyperhomocysteinemia (>13 micromol/L) was observed in 16.5% of the subjects. The population attributable risk percentages for hyperhomocysteinemia were 29.7% for total B12 <148 pmol/L, 36.4% for holotranscobalamin <35 pmol/L, and 41.4% for creatinine >115 micromol/L. In contrast, the population attributable risk percentage for hyperhomocysteinemia was only 0.3% for red blood cell folate <365 nmol/L. We conclude that in the post-folic acid fortification era, low vitamin B12 status has become the dominant nutritional determinant of hyperhomocysteinemia. Steps to either reduce the prevalence of vitamin B12 deficiency or to identify and treat individuals with vitamin B12 deficiency could further reduce the prevalence of hyperhomocysteinemia.     

The influence of iron,vitamin B(12), and folate levels on soluble transferrin receptor concentration in pregnant women

BACKGROUND: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B(12), and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B(12), and folate status in pregnant women. METHODS: The concentration of the sTfR, hematocrit (Hct), hemoglobin (Hb), red blood cell (RBC) and white blood cell (WBC) counts, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation, serum ferritin, zinc protoporphyrin (ZPP), vitamin B(12), and serum and RBC folate were determined in 40 healthy pregnant women who delivered term babies. RESULTS: sTfR concentration was significantly higher when the women had iron deficiency (serum ferritin <10 microg/l, p<0.01), but there was no significant difference in sTfR concentration according to vitamin B(12), serum, and RBC folate concentrations. Women who had serum ferritin <10 microg/l also had lower vitamin B(12) values (p<0.01). There was no significant correlation between vitamin B(12) and serum folate with sTfR concentration. According to a regression analysis, sTfR concentration was associated with serum iron, serum ferritin, RBC count, and hemoglobin concentration. CONCLUSION: Iron was the only micronutrient that influenced the sTfR concentration. Vitamin B(12) and folate concentrations were probably not sufficiently low to have an impact on the sTfR concentration.     

Two radioassays for serum vitamin B12 and folate determination compared in a reference interval study

For 154 subjects, we verified that vitamin B12 and folate status was normal, using as criteria the average polymorphonuclear lobe count, mean corpuscular volume, and hemoglobin concentration. We then used blood from these subjects to compare values obtained with two radioassay kits, each designed for simultaneous vitamin B12 and folate determination. Although regression analysis showed reasonable correlation between the folate (r = 0.87) and vitamin B12 (r = 0.94) kits, we observed significant differences in the overall mean values for vitamin B12 (p less than 0.01) and folate (p less than 0.001) as measured with the kits in this population. Radioassay standard-curve data for the folate assays were similar, but these data indicated greater sensitivity at low concentrations for one vitamin B12 kit than the other. Using reference intervals recommended in the kit inserts, we found that the vitamin B12 status for 9% of these subjects would have been misclassified by one kit, 2% by the other.     

Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily.

BACKGROUND: Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine. METHODS: Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests. RESULTS: A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B(12) concentration (<100 pmol/L). The level of dependency, determined by the Barthel index, influenced homocysteine blood levels (p<0.0001), independent of age (p<0.0001), folate (p=0.0028) and vitamin B(12) (p=0.0165). Homocysteine was significantly associated with stroke (p=0.0027) and peripheral arterial vascular disease (p=0.0001), but not with myocardial infarction, angina pectoris, venous thrombosis or cancer. Vitamin B(12) was lower in myocardial infarction and higher in diabetes and venous thrombosis compared to the other diseases. CONCLUSIONS: The prevalence of deficits in folate and vitamin B(12) was paradoxically high in the mountainous northeastern area of Sicily. Our study also underlines the association of homocysteine with dependency of the elderly and with stroke and peripheral arteriopathy.     

Relations between homocysteine, folate and vitamin B12 in vascular dementia and in Alzheimer disease

OBJECTIVES: The aim of this study was to evaluate the relationship between homocysteine (Hcy), folate and vitamin B12 levels in vascular dementia (VaD) and Alzheimer Disease (AD) to elucidate if they had similar pathogenesis due to cerebrovascular injury. DESIGN AND METHODS: Plasma Hcy and serum folate, vitamin B12 levels were studied 67 VaD, 51 AD and 40 healthy control subjects. Vascular risk factors in these groups were also considered. RESULTS: The changes in the levels of Hcy, folate and vitamin B12 were found to be not related with vascular risk factors. In VaD, Hcy level was higher (p<0.001), folate and vitamin B12 levels were lower (p<0.05 for folate, p<0.001 for vitamin B12) than those in AD. Hcy level was negatively correlated with folate and vitamin B12 (p<0.05) in VaD but in AD. Hcy/folate and Hcy/vitamin B12 ratios were the highest in VaD. CONCLUSION: The increase of Hcy in AD were seemed to be not related to cerebrovascular injury. It is possibly related to biochemical damages as result of oxidative stress.     

Folate and vitamin B12-deficiency anemias in Vietnamese immigrants living in Southern California

BACKGROUND: Although the occurrence of iron deficiency anemia and hemoglobinopathies in Vietnamese immigrants has been reported, folate and vitamin B12 deficiencies have not. Proper diagnosis and effective treatment is necessary to achieve a complete correction of anemia. METHODS: We retrospectively analyzed the records of Vietnamese immigrants seen in our medical clinic from 1991 to 1993. Fifty-nine anemic patients (48 females and 11 males) had low levels of red blood cell (RBC) folate and/or serum vitamin B12. RESULTS: The patients' mean age was 37.7+/-17 years. Mean hemoglobin and hematocrit values were 11.4+/-0.7 g/dL and 34.4%+/-2.2%, respectively. Mean corpuscular volume (MCV) was normal in 40 patients (68%) (mean, 89.1+/-5 fL) and low in 19 patients (32%) (mean, 69.7+/-6 fL). Forty-four patients had low RBC folate levels (mean, 157.7+/-41.7 ng/mL). Twenty patients had low serum vitamin B12 levels (mean, 165.6+/-47 pg/mL). Fourteen patients had ferritin levels of <20%. CONCLUSIONS: Concomitant folate, vitamin B12, and iron deficiencies or hemoglobinopathies might have been responsible for either normal or low MCV in some of our anemic patients. In this ethnic group, RBC folate and serum vitamin B12 levels should be determined in all anemic patients.     

Low serum vitamin B12 is associated with recurrent pregnancy loss in Syrian women

Abstract Background: Hyperhomocysteinemia and B-vitamin deficiency are associated with recurrent abortion. Recent studies have not investigated functional markers of vitamin B12 deficiency, such as methylmalonic acid. Methods: A total of 43 consecutive Syrian women with unexplained recurrent abortion and 32 pregnant controls were enrolled in the study. Serum folate, vitamin B12, methylmalonic acid and plasma homocysteine were determined. Results: Vitamin B12 was significantly decreased in patients with recurrent abortion compared to controls (mean concentrations 197 vs. 300 pg/mL, p=0.004). The lowest mean serum vitamin B12 (172 pg/mL) was observed in primary aborters. Homocysteine was elevated in aborters in comparison to controls (8.3 vs. 7.1 mumol/L, p=0.093). Folate and methylmalonic acid did not differ significantly between the study groups. A highly significant correlation between homocysteine and methylmalonic acid and vitamin B12 was observed only in patients but not in controls (p<0.001 and p=0.002, respectively). In the logistic regression model, only serum vitamin B12 emerged with a significant odds ratio. Conclusions: The results confirm low serum vitamin B12 in recurrent abortion patients. However, methylmalonic acid did not support that functional vitamin B12 plays a role in this group. This unexpected result might be due to a decrease of the metabolically inert vitamin B12 fraction (holohaptocorrin) or confounding factors. Further studies are necessary to investigate the role of vitamin B12 deficiency in recurrent abortion. Clin Chem Lab Med 2008;46:1265-9.