Oral vitamin B12 supplementation reduces plasma total homocysteine concentration in women in India

People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations. In a proof of principle trial, we studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6-week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were randomly allocated to four study groups. Clinical measurements were made at the beginning and at the end of the study, and blood samples were collected before, and 2 and 6 weeks after commencement of intervention. Forty women completed the trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12 concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0 to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change in those who did not receive vitamin B12, and there was no change in plasma folate concentration in any of the groups. Blood haemoglobin concentration increased marginally within first two weeks in those women who received vitamin B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from 2 to zero. There was no change in vibration sensory threshold during the period of the study. High-dose per oral vitamin B12 supplementation significantly reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy concentration even after 6 weeks. People in India have a high prevalence of low vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.     

Folic acid and vitamin B12 determination in fetal liver.

The folate and vitamin B12 content of 61 fetal livers divided into 3 groups immature (13 cases); premature (27 cases); at terminus (21 cases) were determined microbiologically. The average concentration (mug/g) and the reserve (mug) of hepatic folate for the immature group were 2 and 43.2 (net weight); for the premature group were 3.05 and 163.6; for the third group were 2.54 and 225.3, respectively. The average concentration (mug/g) and the reserve (mug) of hepatic vitamin B12 for the immature group were 0.173 and 4.1; for the premature group were 0.207 and 10.7; for the third group were 0.300 and 27.3 respectively.     

Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete

BACKGROUND: Current data suggest that physiologic doses of vitamin B-6 have no significant homocysteine-lowering effect. It is possible that an effect of vitamin B-6 was missed in previous trials because of a much greater effect of folic acid, vitamin B-12, or both. OBJECTIVE: The aim of this study was to investigate the effect of low-dose vitamin B-6 supplementation on fasting total homocysteine (tHcy) concentrations in healthy elderly persons who were made replete with folate and riboflavin. DESIGN: Twenty-two healthy elderly persons aged 63-80 y were supplemented with a low dose of vitamin B-6 (1.6 mg/d) for 12 wk in a randomized, double-blind, placebo-controlled trial after repletion with folic acid (400 microg/d for 6 wk) and riboflavin (1.6 mg/d for 18 wk); none of the subjects had a vitamin B-12 deficiency. RESULTS: Folic acid supplementation lowered fasting tHcy by 19.6% (P < 0.001). After folic acid supplementation, baseline tHcy concentrations ranged from 6.22 to 23.52 micromol/L and 10 subjects had suboptimal vitamin B-6 status (plasma pyridoxal-P < 20 nmol/L). Two-way analysis of variance showed that the significant improvement in vitamin B-6 status in response to vitamin B-6 supplementation (on the basis of both pyridoxal-P: and the erythrocyte aspartate aminotransferase activation coefficient) was reflected in a significant reduction in plasma tHcy of 7.5%. CONCLUSIONS: Low-dose vitamin B-6 effectively lowers fasting plasma tHcy in healthy subjects who are both folate and riboflavin replete. This suggests that any program aimed at the treatment or prevention of hyperhomocysteinemia should include vitamin B-6 supplementation.     

Prudent dietary pattern influences homocysteine level more than folate,vitamin B12, and docosahexaenoic acid: a structural equation model approach

European Journal of Nutrition - A structural equation model (SEM) was used to test multiple and simultaneous relationships between socio-demographic factors, dietary patterns, biochemical levels of...     

Folic acid therapy reduces plasma homocysteine levels and improves plasma antioxidant capacity in hemodialysis patients

OBJECTIVE: We evaluated the effects of folic acid on homocysteine levels and oxidative stress in 46 stable patients on hemodialysis. METHODS: This double-blind, placebo-controlled, randomized trial assessed the effects of 6 mo of 10 mg of folic acid (26 patients) or placebo (20 patients) given three times weekly after each dialysis under nurse supervision on homocysteine levels, total plasma antioxidant capacity, and hydroperoxide plasma levels. RESULTS: Folic acid treatment normalized plasma homocysteine levels in most patients, significantly increased total plasma antioxidant capacity levels, but had no significant effect on hydroperoxide levels. Placebo treatment had no statistically significant effect on the three parameters. CONCLUSION: The folic acid therapy protocol effectively lowered plasma homocysteine levels and improved the total plasma antioxidant capacity in hemodialysis patients. Further studies are required to assess the usefulness of folic acid for decreasing cardiovascular mortality in patients with chronic kidney disease.     

Low plasma vitamin B-6 concentrations and modulation of coronary artery disease risk

BACKGROUND: Low concentrations of pyridoxal-5'-phosphate (PLP), the active metabolite of vitamin B-6, are associated with high C-reactive protein (CRP) concentrations. Both low PLP and elevated inflammatory markers, such as high-sensitivity CRP (hs-CRP) and fibrinogen, are related to higher risk of coronary artery disease (CAD). OBJECTIVES: The objectives were to evaluate the relation between PLP and acute-phase reactants in affecting CAD risk and to estimate the risk of CAD related to low plasma PLP, either alone or in combination with high concentrations of acute-phase reactants and other classic risk factors for CAD. DESIGN: A case-control study was conducted with 742 participants: 475 with severe multivessel CAD and 267 free from coronary atherosclerosis (CAD-free). We measured plasma PLP, fibrinogen, hs-CRP, and serum lipid concentrations and all major biochemical CAD risk factors, including total homocysteine. RESULTS: A significant, inverse, graded relation was observed between PLP and both hs-CRP and fibrinogen (P < 0.001). The prevalence of PLP concentrations in the lower half of the population (<50th percentile: 36.3 nmol/L) was significantly higher among CAD patients than among CAD-free subjects (P < 0.001). The odds ratio for CAD risk related to low PLP concentrations after adjustments for the major classic CAD risk factors, including hs-CRP and fibrinogen, was 1.89 (95% CI: 1.18, 3.03; P = 0.008). The CAD risk as a result of low PLP was additive when considered in combination with elevated hs-CRP concentrations or with an increased ratio of LDL to HDL. CONCLUSION: Low plasma PLP concentrations are inversely related to major markers of inflammation and independently associated with increased CAD risk.     

Reduction of plasma homocysteine and serum methylmalonate concentrations in apparently healthy elderly subjects after treatment with folic acid, vitamin B12 and vitamin B6: a randomised trial

OBJECTIVES: To investigate, in an elderly population: (1) the effects of oral B-vitamin therapy on P-tHcys, S-MMA and Hb/MCV, (2) the appropriate decision limit for 'high' metabolite concentrations and (3) the estimated prevalence of vitamin B(12)/folate deficiency on the basis of different decision limits. DESIGN: Double-blind placebo-controlled intervention study. SETTING: Outpatient clinic. SUBJECTS: A total of 209 community-dwelling subjects, median age 76 y (range 70-93) y. INTERVENTION: Four months of oral daily supplementation with 0.5 mg cyanocobalamin, 0.8 mg folic acid and 3 mg vitamin B(6). RESULTS: High P- tHcys was found in 64% of men and 45% of women, high S-MMA in 11% of both. Vitamin B(12) deficiency was observed in 7.2% and folate deficiency in 11% of all subjects. Health-related upper reference limits for the metabolites at the start were higher than the laboratory's upper reference limits. The latter were, however, similar to those of the vitamin replete group. There was a significant decrease in P-tHcys (P<0.001) and S-MMA (P=0.009) after 4 months of vitamin treatment. In a multivariate analysis, the P-Hcys change correlated positively with baseline P-tHcys and inversely with baseline P-folate and transferrin saturation (Fe/TIBC ratio). The S-MMA change correlated with baseline S-MMA and inversely with baseline vitamin B(12) and age. CONCLUSIONS: Suboptimal vitamin status is an important cause of elevated P-tHcys and S-MMA in apparently healthy elderly subjects. Oral B-vitamin therapy is an effective and convenient way to normalise P-tHcys and S-MMA.     

Homocysteine and risk of coronary artery disease: Folate is the important determinant of plasma homocysteine concentration

OBJECTIVES: The purposes of this study were to study the effects of folate and vitamins B6 and B12 on plasma homocysteine concentration and to estimate the risks for coronary artery disease (CAD) according to quartiles of plasma homocysteine concentration. METHODS: The study was designed as a case-reference observational study. Case subjects (CAD group, n = 60) were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery; otherwise, patients were considered for a reference group (n = 60). Risk factors of cardiovascular disease were recorded, including age, sex, blood lipid profile, hypertension, smoking habits, and drinking habits. Plasma homocysteine, folate, pyridoxal 5'-phosphate, and vitamin B12 were measured. RESULTS: CAD subjects had significantly higher mean plasma homocysteine concentrations than did the reference subjects (13.9 +/- 4.9 versus 9.1 +/- 3.3 micromol/L). There were no significant differences between groups with regard to the three B vitamins; however, mean serum folate concentrations for subjects in the highest two quartiles of plasma homocysteine concentration (10.8-13.8 and >/=13.9 micromol/L) were significantly lower than those for subjects in the lowest two quartiles (相似文献   

Inverse correlation between plasma Beta-carotene and interleukin-6 in patients with advanced coronary artery disease

The interrelationships between plasma beta-carotene, alpha-tocopherol, and the level of systemic inflammation and oxidative stress were investigated in patients with advanced coronary artery disease (CAD). Plasma beta-carotene, alpha-tocopherol, malondialdehyde, free radicals, interleukin-6, high sensitive C-reactive protein levels, and other risk factors of CAD were determined in a group of patients with advanced CAD [significant stenosis according to coronarographic examination (n=91) and a control group of examined patients with coronary arteries with no stenosis (n=49)]. Between-group differences in continuous variables were analyzed with the Hotelling T2-test (software NCSS2000), analyses of correlation matrix with the software STATISTICA. Advanced CAD coincided with significantly lower plasma concentrations of high-density lipoprotein (HDL)-cholesterol and beta-carotene as well as with elevated levels of all inflammatory markers, but only with mild increase of oxidative stress. Beta-carotene significantly inversely correlated with interleukin-6. This inverse correlation could suggest potential protective effect of beta-carotene on atherosclerosis due to the inhibition of inflammatory processes.     

Mineral water fortified with folic acid, vitamins B6, B12, D and calcium improves folate status and decreases plasma homocysteine concentration in men and women

OBJECTIVE: We investigated the effects of mineral water fortified with folic acid, vitamins B(6), B(12), D and calcium on folate concentrations in serum and erythrocytes, serum vitamin B(12) and plasma homocysteine concentrations in free-living subjects. In addition, we investigated the bioavailability of calcium added to mineral water by measuring urinary calcium excretion and serum alkaline phosphatase activity. DESIGN: Randomized, controlled, double-blinded, parallel design. SETTING: Outpatient dietary intervention with free-living subjects in Eastern Finland. SUBJECTS: Altogether, 66 subjects were recruited for the study. In all, 60 subjects completed the study. INTERVENTIONS: The study began with a 2-week run-in period followed by an 8-week intervention period. During the intervention study, subjects consumed mineral water fortified with folic acid (563 microg/day), vitamins B(6) (1 mg/day), B(12) (7.5 microg/day), cholecalciferol (0.6 microg/day) and calcium (563 mg/day) or placebo mineral water. RESULTS: The fortified mineral water increased serum and erythrocyte folate concentrations by 16.1+/-5.6 nmol/l (P<0.001) and 199+/-76 nmol/l (P<0.001), respectively, and decreased plasma homocysteine concentration by 1.6 micromol/l (P<0.001). Urinary calcium excretion and serum alkaline phosphatase activity for 24 h increased significantly (P<0.001 and P=0.01 respectively) in the intervention group. CONCLUSIONS: Mineral water fortified with folic acid, vitamins B(6), B(12) and D and calcium enhanced folate status and reduced plasma homocysteine concentration in normohomocysteinemic subjects without folate deficiency. Indirect measures of calcium and bone metabolism indicated that the calcium used in the fortification of the mineral water was bioavailable.     

Combined dietary folate, vitamin B-12, and vitamin B-6 intake influences plasma docosahexaenoic acid concentration in rats

Background

Folate, vitamin B-12, and vitamin B-6 are essential nutritional components in one-carbon metabolism and are required for methylation capacity. The availability of these vitamins may therefore modify methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) by PE-N-methyltransferase (PEMT) in the liver. It has been suggested that PC synthesis by PEMT plays an important role in the transport of polyunsaturated fatty acids (PUFAs) like docosahexaenoic acid (DHA) from the liver to plasma and possibly other tissues. We hypothesized that if B-vitamin supplementation enhances PEMT activity, then supplementation could also increase the concentration of plasma levels of PUFAs such as DHA. To test this hypothesis, we determined the effect of varying the combined dietary intake of these three B-vitamins on plasma DHA concentration in rats.

Methods

In a first experiment, plasma DHA and plasma homocysteine concentrations were measured in rats that had consumed a B-vitamin-poor diet for 4?weeks after which they were either continued on the B-vitamin-poor diet or switched to a B-vitamin-enriched diet for another 4?weeks. In a second experiment, plasma DHA and plasma homocysteine concentrations were measured in rats after feeding them one of four diets with varying levels of B-vitamins for 4?weeks. The diets provided 0% (poor), 100% (normal), 400% (enriched), and 1600% (high) of the laboratory rodent requirements for each of the three B-vitamins.

Results

Plasma DHA concentration was higher in rats fed the B-vitamin-enriched diet than in rats that were continued on the B-vitamin-poor diet (P?=?0.005; experiment A). Varying dietary B-vitamin intake from deficient to supra-physiologic resulted in a non-linear dose-dependent trend for increasing plasma DHA (P?=?0.027; experiment B). Plasma DHA was lowest in rats consuming the B-vitamin-poor diet (P?>?0.05 vs. normal, P?. enriched and high) and highest in rats consuming the B-vitamin-high diet (P?. poor and normal, P?>?0.05 vs. enriched). B-vitamin deficiency significantly increased plasma total homocysteine but increasing intake above normal did not significantly reduce it. Nevertheless, in both experiments plasma DHA was inversely correlated with plasma total homocysteine.

Conclusion

These data demonstrate that dietary folate, vitamin B-12, and vitamin B-6 intake can influence plasma concentration of DHA.     

肝病患者血清叶酸与维生素B12含量的临床意义

目的 探讨肝病患者血清叶酸(FA)与维生素B12(VitB12)含量的变化及其临床意义.方法 应用微粒子化学发光免疫分析技术(CLIA)检测315例肝病患者及84例健康对照者的血清FA和VitB12含量,并对检测数据进行统计学分析.结果 急性肝炎组血清FA含量与对照组比较,差异无统计学意义(P>0.05),但其VitB12含量明显高于对照组(P<0.05).慢性肝炎轻度组血清FA、VitB12含量与对照组相比,差异无统计学意义(P>0.05).慢性肝炎中度组血清FA、VitB12含量与对照组相比,差异有统计学意义(P<0.05).慢性肝炎重度组、肝炎后肝硬化组、原发性肝癌组的FA含量均低于对照组(P<0.01),VitB12含量均高于对照组(P<0.01).结论 血清FA、VitB12含量变化与肝细胞病损程度密切相关,其检测结果对肝脏疾病的诊断、治疗及预后判断具有重要的临床价值.     

Cost of lipid lowering in patients with coronary artery disease by case method learning

OBJECTIVES: This investigation was undertaken to study the costs of a Case Method Learning (CML)-supported lipid-lowering strategy in secondary prevention of coronary artery disease (CAD) in primary care. METHODS: This prospective randomized controlled trial in primary care with an additional external specialist control group in S?dert?lje, Stockholm County, Sweden, included 255 consecutive patients with CAD. Guidelines were mailed to all general practitioners (GPs; n=54) and presented at a common lecture. GPs who were randomized to the intervention group participated in recurrent CML dialogues at their primary health-care centers during a 2-year period. A locally well-known cardiologist served as a facilitator. Assessment of low-density lipoprotein (LDL) cholesterol was performed at baseline and after 2 years. Analysis according to intention-to-treat-intervention and control groups (n=88)--was based on group affiliation at baseline. The marginal cost of lipid lowering comprised increased cost of lipid-lowering drugs in the intervention group compared with the primary care control group, cost of attendance of the GP's in the intervention group, and cost of time for preparation, travel, and seminars of the facilitator. Costs are as of 2002 with an exchange rate 1 U.S. dollar = 9.5 SEK (Swedish Crowns). RESULTS: Patients in the primary care intervention group had their LDL cholesterol reduced by 0.5 (confidence interval [CI], 0.1-0.9) mmol/L compared with the primary care control group (p < .05). No change occurred in controls. LDL cholesterol in the external specialist control group decreased by 0.6 (CI, 0.4-0.8) mmol/L. The cost of the educational intervention represented only 2 percent of the drug cost. The cost of lipid lowering in the intervention group, including the cost of the educational intervention, was actually lower than that of patients treated at the specialist clinic--106 U.S. dollar per mmol decrease in LDL cholesterol in the intervention group and 153 U.S. dollar per mmol decrease in LDL cholesterol in the specialist group. EuroQol 5D Index, which gives an estimate of global health-related quality of life, was 0.80 (CI, 0.75-0.85) in the present cohort. CONCLUSIONS: The additional cost of CML was only 2 percent of the drug cost. Assuming the same gain in life expectancy per millimole decrease in LDL cholesterol as in the 4S-study gives a cost per gained quality-adjusted life year of U.S. dollar 24,000. This finding indicates that the CML-supported lipid-lowering strategy is cost-effective. The low cost of CML in primary care should probably warrant its use in the improvement of the quality of care in other major chronic diseases.     

Alendronate more effective than alfacalcidol in the prevention of osteoporosis in patients with rheumatic disease who are starting glucocorticoid therapy

OBJECTIVE: To compare the effects of alendronate and alfacalcidol in the prevention ofglucocorticoid-related osteoporosis in patients with a rheumatic disease. DESIGN: Randomised, double-blind, double-placebo clinical trial (www. clinicaltrials.gov; number: NCT00138983). METHODS: A total of 201 patients with rheumatic disease who were starting glucocorticoid treatment at a daily dose that was equivalent to at least 7.5 mg of prednisone were randomised to alendronate (10 mg) and a placebo capsule ofalfacalcidol daily (n = 100) or alfacalcidol (1 microg) and a placebo tablet ofalendronate daily (n = 101) for 18 months. Primary outcome was change in lumbar spine bone mineral density at 18 months. The main secondary outcome was the incidence of morphometrically confirmed vertebral deformities. RESULTS: Overall, 163 patients completed the study. The bone mineral density of the lumbar spine increased by 2.1% (95% CI: 1.1-3.1) in the alendronate group and decreased by 1.9% (95% CI: -3.I--0.7) in the alfacalcidol group. At 18 months the mean difference in change in bone mineral density between the two groups was 4.0% (95% CI: 2.4-5-5). Three patients in the alendronate group had a new vertebral deformity, compared with 8 patients in the alfacalcidol group, including 5 symptomatic vertebral fractures in 3 patients; the hazard ratio was 0.4 (95% CI: 0.1-1.4). CONCLUSION: Alendronate was more effective than alfacalcidol in preventing glucocorticoid-induced bone loss during this 18-month trial in patients with rheumatic diseases who were starting glucocorticoid treatment.     

Serum homocysteine,B12 and folic acid concentration in Thai overweight and obese subjects

This study investigated levels of serum homocysteine, vitamin B12, folic acid, vitamin B6 and vitamin C, in 37 male and 112 female overweight and obese Thai volunteers (body mass index; BMI > or = 25.00), and 23 male and 90 female normal-weight Thai volunteers, who came for a physical check-up at the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok from March to October of 2000. Data included anthropometric measurements and waist/hip ratios. All anthropometric variables, except height, were significantly higher for the overweight subjects than for the normal subjects. Statistically significantly higher levels of serum homocysteine were found in the overweight subjects. Serum homocysteine concentrations in overweight and obese males were significantly higher than in overweight and obese females. Serum folic acid and vitamin C in the overweight and obese were found to be statistically significantly lower than in the control subjects. No statistically significant difference in vitamin B12 was found in the overweight and obese subjects compared with the normal control subjects. The medians of serum folic acid and vitamin C concentrations for the overweight and obese males were significantly lower than those of the overweight and obese females. A negative correlation was found between serum folic acid and homocysteine concentrations in all overweight and obese subjects. A significant negative correlation between serum folic acid and vitamin B6 was observed in both male and female overweight and obese subjects. The results of the investigation suggest that homocysteine levels in overweight and obese subjects seem to be caused by insufficient dietary folic acid intake and probably not by B12 deficiency.     

血浆同型半胱氨酸与叶酸,维生素B12及还原酶的关系

目的 探讨叶酸、维生素Ｂ１２（ＶＢ１２）、血浆总同型半胱氨酸、５、１０－亚甲基四氢叶酸还原酶（ＭＴＨＦＲ）活性及其热敏感性基因型间的相互关系。方法 研究为３４例生育神经管畸形ＮＴＤＳ）儿的母亲及４２例生育正常儿的母亲,检测指标包括ｔＨｃｙ、红细胞叶酸、血清叶酸和ＶＢ１２、ＭＴＨＦＲ酶活性及热敏感性。ｔＨｃｙ、红细胞叶酸、血清叶酸在病例组与对照组间差异无统计学意义;ＮＴＤＳ患儿母亲ＶＢ１２显低于正