Do iron and vitamin C co-supplementation influence platelet function or LDL oxidizability in healthy volunteers?

OBJECTIVE: To examine the effect of co-supplementation with iron and vitamin C on antioxidant status, platelet function and low density lipoprotein oxidation in normal healthy volunteers. DESIGN: The study was carried out with two groups of 20 subjects each acting as their own control, comparing presupplemention with postsupplemention. One group was supplemented with iron and the RDA level of vitamin C and the second group with iron and 260 mg/d vitamin C. SETTING: The International Antioxidant Research Centre, The Guy's, King's College and St Thomas's School of Biomedical Science, Guy's Campus, London. SUBJECTS: Forty normal healthy volunteers, recruited from the staff of the Medical School and Hospital in which two volunteers withdrew during the study. INTERVENTIONS: Subjects in both studies were randomly assigned to one of two groups (5 males and 5 females group) and received supplements containing iron (14 mg/d) and either 60 mg/d (Group A) or 260 mg/d (Group B) vitamin C for 12 wk. Blood samples were taken at 6 wk and 12 wk, and prior to supplementation and analysed for iron and antioxidant status (transferrin bound iron, vitamin C and E, and beta-carotene levels) in both studies. Samples from the first study were analysed for the susceptibility of LDL isolated from plasma to Cu2+-induced oxidation and samples from the second for platelet function. RESULTS: Transferrin-bound iron was significantly increased (P < 0.05) at 12 wk, in Group A subjects (from 14.9+/-5.3 micromol/1 to 19.5+/-2.3 micromol/l; mean+/-s.d.; n=19), whereas those in Group B showed a significant increase (P < 0.05) after 6 wk (from 15.8+/-4.5 micromol/l to 20.4+/-6.6 micromol/l; n = 19) which decreased at 12 wk (16.3+/-5.0 micromol/l). Plasma total ascorbate significantly increased from an initial level of 59.3+/-21.3 micromol/l to 87.6+/-29.0 micromol/l after 6 wk and 81.7+/-11.4 micromol/l after 12 wk following the Group B supplementation, but only after 12 wk in Group A (from 64.0+/-24.8 micromol/l to 77.2+/-13.2 micromol/l). Plasma alpha-tocopherol concentrations were significantly increased after 6 wk and 12 wk with both levels of supplementation (from 24.2+/-5.71 micromol/l Group A and 23.4+/-5.3 micromol/l Group B to 26.3+/-5.5 micromol/l and 25.71+/-4.7 micromol/1 respectively at 12wk). The mean lag phase to oxidation of low density lipoprotein (LDL) was significantly increased in subjects in Group B after 12 wk ingestion of iron and 260 mg vitamin C (from 80.0+/-14.8 min to 97.2+/-16.9 min; n = 9). Platelet sensitivity to ADP-induced aggregation was significantly decreased (P < 0.05) by 12 wk in Group A (from EC50 2.3 < or = 1.3 microM to 3.7+/-2.2 microM; n = 10), whereas those receiving higher vitamin C showed a significant decrease (P < 0.05; from EC50 1.9+/-0.6 microM to 3.1+/-1.8 microM) after 6wk which subsequently increased towards presupplemental levels (2.6+/-1.6 microM). Platelets from the latter subjects showed a significant reduction in ADP-induced ATP secretion at both 6wk and 12 wk. CONCLUSION: The results show modest beneficial effects on LDL oxidation and platelet function following supplementation with iron and vitamin C. No evidence for pro-oxidant effects was observed.     

Effects of supplementation with folic acid and antioxidant vitamins on homocysteine levels and LDL oxidation in coronary patients

Hyperhomocysteinemia is an important cardiovascular risk factor. Serum homocysteine levels are specially dependent on folate nutritional status. In addition, the oxidative modification of low-density lipoproteins (LDLs) in the endothelial microenvironment is a damaging factor that can be modified with fat-soluble antioxidant vitamins. The present study was done to assess the effect of a supplementation of folic acid and antioxidant vitamins on homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease. Twenty-three patients with angiographically proven coronary artery disease were given supplements for 15 d consisting of one capsule twice a day of a multivitamin preparation containing 0.65 mg folic acid, 150 mg alpha-tocopherol, 150 mg ascorbic acid, 12.5 mg beta-carotene, and 0.4 microgram vitamin B12. Serum lipids, vitamin and homocysteine levels, and in vitro LDL oxidation were measured before and after the supplementation period. During the supplementation period, serum folate levels increased from 5.0 +/- 1.5 to 10.8 +/- 3.8 ng/mL (P < 0.001), vitamin B12 increased from 317.4 +/- 130.4 to 334.5 +/- 123.8 pg/mL (P < 0.05), and alpha-tocopherol increased from 8.2 +/- 5.1 to 13.7 +/- 7.9 mg/L (P < 0.001). Serum homocysteine levels decreased from 8.7 +/- 4.3 to 6.3 +/- 2.2 mumol/L (P < 0.001). In vitro LDL oxidation decreased from 2.6 +/- 1.1 to 1.6 +/- 1.1 nmol malondialdehyde/mg protein (P < 0.001). In comparing patients with healthy controls, basal levels of folate were lower in the patients, whereas vitamin B12, alpha-tocopherol, and homocysteine levels were similar. No changes in serum lipid levels or body weight were observed. In conclusion, a short-term supplementation with folic acid and antioxidant vitamins can reduce serum homocysteine levels and in vitro LDL oxidation in patients with coronary artery disease.     

叶酸、维生素B6、B12对脑缺血大鼠学习记忆的影响

目的研究叶酸、维生素B6（VB6）和B12（VB12）对局灶性脑缺血大鼠血浆同型半胱氨酸（homocysteine,Hcy）水平和学习记忆能力的影响。方法sD大鼠按体重随机分为假手术组（Sham OP）、大脑中动脉闭塞模型组（MCAO）、大脑中动脉闭塞＋叶酸组（MCAO＋FA）和MCAO＋复合维生素（叶酸、VB6和VB12）组（MCAO＋CV）,补充前、后和缺血后分别检测大鼠血浆Hcy浓度,缺血后进行神经功能评分,测定学习记忆能力。结果大鼠脑缺血后血浆Hcy浓度MCAO＋FA组（6．92±1．04）μmol／L和MCAO＋CV组（5．49±1．00）μmol／L低于Sham OP组（9．33±1．11）μmol／L和MCAO组（10．90±2．03）μmol／L（P〈0．05）,且MCAO＋CV组低于MCAO＋FA组（P〈0．05）;神经功能缺失评分MCAO＋FA组（1．75±0．46）和MCAO＋CV组（1．38±0．52）以及Y型迷宫中受电击次数MCAO＋FA组（123．50±39．77）和MCAO＋CV组（86．25±21．39）低于MCAO组神经功能缺失评分（2．62±0．52）和电击次数（173．25±46．32）（P〈0．05）,而记忆正确次数MCAO＋CV组（3．75±0．42）高于MCAO组（2．12±0．45）（P〈0．05）。结论叶酸能降低脑缺血大鼠血浆Hcy浓度,增强脑缺血大鼠学习记忆能力,改善神经功能,且联合补充VB6和VB12优于单独补充叶酸。     

Plasma homocysteine levels in patients with ischemic heart disease

In the latest years it became clear that beside traditional cardiovascular risk factors the high plasma homocysteine level increases the risk of atherosclerotic diseases too. Metaanalysis of 27 papers found that 10% of population's coronary risk is attributable to homocysteine and a 5 mumol/l increase in its plasma level elevates the coronary risk by as much as 0.5 mumol/l cholesterol increase. Recent studies have shown an inverse relation between the levels of plasma homocysteine and that of folic acid, vitamin B6, vitamin B12. The latters are cofactors and substrates of the homocysteine and methionin metabolism. The plasma total cholesterol, HDL-cholesterol, triglyceride, lipoprotein(a), Apo A1, Apo B and homocysteine concentrations were examined in 39 patients suffering from coronary artery disease treated in the Cardiac Rehabilitation Department of our hospital. Twenty of them were treated by folic acid and vitamin B6 for a three week period. The mean (+/- SD) plasma homocysteine concentration was 15.60 +/- 6.14 mumol/l. In the treated subgroup the mean (+/- SD) plasma homocysteine concentration was 17.3 +/- 7.00 mumol/l, the mean (+/- SD) plasma folic acid level was 8.58 +/- 4.6 mumol/l. After the three week treatment period (folic acid and vitamin B6) the plasma homocysteine level decreased by 26.5% (p = 0.012), that of folic acid increased by 68.7% (p = 0.002). From the plasma lipids the level of total- and LDL-cholesterol decreased significantly (6.7% and 10.4%, P < 0.05), caused by the strict diet during hospital treatment. As for the genetic polymorphism of the V677 gen of the metylenetetrahydrofolate-reductase (MTHFR) enzyme there was a significant correlation with homocysteine level (r = 0.436, p = 0.010), and a negative, but not significant correlation with the folic acid level (r = -0.354).     

Cardiovascular effects of milk enriched with omega-3 polyunsaturated fatty acids, oleic acid, folic acid, and vitamins E and B6 in volunteers with mild hyperlipidemia

OBJECTIVE: Results from epidemiologic studies and clinical trials have indicated that consumption of omega-3 fatty acids, oleic acid, and folic acid have beneficial effects on health, including decreased risk of cardiovascular disease. We evaluated the combined effects of these nutrients through the consumption of milk enriched with omega-3 polyunsaturated fatty acids, oleic acid, vitamins E and B6, and folic acid on risk factors for cardiovascular disease in volunteers with mild hyperlipidemia. METHODS: Thirty subjects ages 45 to 65 y (51.3 +/- 5.3 y) were given 500 mL/d of semi-skimmed milk for 4 wk and then 500 mL/d of the enriched milk for 8 wk. Plasma and low-density lipoproteins were obtained at the beginning of the study and at 4, 8, and 12 wk. RESULTS: Consumption of enriched milk for 8 wk increased plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid and significantly (P < 0.05) decreased plasma concentrations of triacylglycerol (24%), total cholesterol (9%), and low-density lipoprotein cholesterol (13%). Plasma and low-density lipoprotein oxidation and vitamin E concentration remained unchanged throughout the study. Significant decreases in plasma concentrations of vascular cell adhesion molecule-1 (9%) and homocysteine (17%) were found, accompanied by a 98% increase in plasma concentration of folic acid. CONCLUSIONS: Dairy supplementation strategies with omega-3 polyunsaturated fatty acids, oleic acid, and vitamins may be useful for decreasing risk factors for cardiovascular disease.     

A mixed fruit and vegetable concentrate increases plasma antioxidant vitamins and folate and lowers plasma homocysteine in men

Fruit and vegetable consumption is inversely associated with coronary heart disease (CHD) risk. The aim of the present study was to determine the effect of supplementation with dehydrated juice concentrates from mixed fruit and vegetables on selected plasma vitamins and antioxidant status. We assessed CHD risk by measuring the concentrations of homocysteine, lipids, lipoproteins, glucose and insulin. Men were recruited to participate in a randomized double-blind, crossover trial with 2 periods of 6 wk, separated by a 3-wk wash-out period. Supplementation with the encapsulated mixed extract (Juice Plus) was compared with physically similar placebo capsules. Thirty-two men (13 smokers, 19 nonsmokers) completed the study with a mean compliance of 88%. Compared with placebo, supplementation increased the concentrations of plasma beta-carotene (0.24 +/- 0.15 vs. 1.12 +/- 0.70 micro mol/L; mean +/- SD; P < 0.0001), retinol (1.87 +/- 0.33 vs. 2.00 +/- 0.43 micro mol/L; P < 0.05), alpha-tocopherol (16.8 +/- 7.3 vs. 19.3 +/- 6.8 micro mol/L; P < 0.01), ascorbic acid (72.1 +/- 19.4 vs. 84.1 +/- 13.5 micro mol/L; P < 0.002) and folic acid (24.5 +/- 10.0 vs. 44.9 +/- 16.9 nmol/L; P < 0.0001). Plasma homocysteine was reduced (8.2 +/- 1.5 vs. 7.6 +/- 1.1; P < 0.05) and inversely related (r = -0.40, P < 0.001) with serum folate concentrations. Plasma vitamin C was positively correlated with the resistance of LDL to oxidation (r = 0.26, P < 0.05) and the plasma ferric reducing/antioxidant power (FRAP) tended to be greater after supplementation than after the placebo period (1125.5 +/- 144.1 vs. 1180.3 +/- 158.1 micro mol/L; P < 0.065). Plasma glucose, insulin and lipid concentrations were unaffected. Responses of smokers and nonsmokers did not differ. In the absence of dietary modification, supplementation with a fruit and vegetable concentrate produced responses consistent with a reduction in CHD risk.     

Complex multivitamin supplementation improves homocysteine and resistance to LDL-C oxidation

OBJECTIVE: We previously reported in an open-label pilot trial that a 24-ingredient multivitamin formula favorably influenced homocysteine concentration and LDL-C oxidation indices following 24 weeks of supplementation. Our current aim was to more thoroughly examine this same formula in a randomized, placebo-controlled, clinical study. METHODS: We examined 182 participants for selected plasma vitamin concentrations and clinically relevant variables including homocysteine, lipids and LDL-C oxidation indices at baseline and six months. RESULTS: We found no significant differences between groups for any parameter at baseline. Following six months of vitamin supplementation, we observed elevations in plasma concentrations of vitamin B6 (as pyridoxal 5'-phosphate; PLP), vitamin B12, folate, vitamin C, vitamin E and beta-carotene (p < 0.0001), all of which were significantly greater than respective placebo group changes (p < 0.0001). Homocysteine decreased in the treatment (8.38 +/- 2.9 vs. 6.93 +/- 2.5 micro mol/L; p < 0.0001) and placebo group (8.17 +/- 3.0 vs. 7.42 +/- 2.2 micro mol/L; p < 0.0001) from baseline to six months, respectively, with reductions in the treatment group being greater than placebo (p < 0.008). LDL-C oxidation indices were also improved as LDL-C oxidation rate was decreased (-0.39 micro mol/min/g protein; p < 0.0003) and LDL-C lag time increased (11.3 min; p < 0.003) in supplemented participants. Further analysis also showed that LDL-C oxidation rate was lower (p < 0.0007) and LDL-C lag time longer (p < 0.0001) for the vitamin group than placebo treatment after six months. CONCLUSION: We conclude that a multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL-C oxidation indices.     

Effect of fortified spread on homocysteine concentration in apparently healthy volunteers

OBJECTIVE: To determine the effect of folic acid, vitamin B(6) and B(12) fortified spreads on the blood concentrations of these vitamins and homocysteine. DESIGN AND SETTING: A 6-week randomized, double-blinded, placebo-controlled, parallel trial carried out in a clinical research center. SUBJECTS: One hundred and fifty healthy volunteers (50% males). INTERVENTIONS: For 6 weeks, the subjects consumed the test spreads (20 g/day): containing per 20 g (1) 200 microg folic acid, 2 microg vitamin B(12) and 1 mg vitamin B(6), or (2) 400 microg folic acid, 2 microg vitamin B(12) and 1 mg vitamin B(6) or (3) no B-vitamins (control spread). RESULTS: The B-vitamin status increased on using the test spreads, with the largest effect on the serum folate concentration: 48% in men and 58% in women on spread 1 and 92 and 146%, respectively, on spread 2 (P-values all <0.05). The plasma homocysteine decreased in the groups treated with the fortified spreads as compared to the control group. Average decreases were for males: 0.7+/-1.5 micromol/l (6.8%) on spread 1 and 1.7+/-1.7 micromol/l (17.6%) on spread 2 and for females: 1.4+/-1.2 micromol/l (14.2%) and 2.4+/-2.0 micromol/l (23.3%), respectively (P-values all <0.05). CONCLUSIONS: Consumption of a spread fortified with folic acid, vitamin B(6) and vitamin B(12) for 6 weeks significantly increases the blood concentrations of these vitamins and significantly decreases the plasma concentration of homocysteine. Fortified staple foods like spreads can contribute to the lowering of homocysteine concentrations.     

Folic acid and vitamin B12 are more effective than vitamin B6 in lowering fasting plasma homocysteine concentration in patients with coronary artery disease

OBJECTIVE: To investigate whether vitamin B(6) supplementation had a beneficial effect on lowering fasting plasma homocysteine concentrations in coronary artery disease (CAD) patients. DESIGN: A single-blind intervention study. SETTING: The study was performed at the Taichung Veterans General Hospital, the central part of Taiwan. SUBJECTS: A total of 50 subjects were identified by cardiac catheterization to have at least 70% stenosis of one major coronary artery. In all, 42 patients successfully completed this study. INTERVENTIONS: Patients were randomly assigned to one of five groups and treated with a daily dose of placebo (n=8), 5 mg vitamin B(6) (n=8), 10 mg vitamin B(6) (n=8), 50 mg vitamin B(6) (n=9), or 5 mg folic acid combined with 0.25 mg vitamin B(12) (n=9) for 12 weeks. MAIN OUTCOME MEASURES: Nutrient intakes were recorded by using 24-h diet recalls when patients returned to the cardiology clinic before the intervention (week 0) and at week 12. Vitamin B(6) status was assessed by direct measures (plasma pyridoxal 5'-phosphate) and indirect measures (erythrocyte alanine and aspartate aminotransaminase activity coefficient). Fasting plasma homocysteine, serum folic acid, and vitamin B(12) were measured. RESULTS: Fasting plasma homocysteine concentration did not respond to high or low doses of vitamin B(6) when compared with a placebo treatment after 12 weeks of supplementation. The mean fasting plasma homocysteine concentration, however, decreased significantly after 12 weeks of folic acid combined with vitamin B(12) supplementation (P=0.047). Further, within group, mean fasting plasma homocysteine concentration was nonsignificantly increased by 25.5, 16.2, and 18.3% in placebo, 10 mg/day and 50 mg/day vitamin B(6) supplemented groups, respectively; whereas folic acid combined with vitamin B(12) supplementation significantly reduced fasting plasma homocysteine concentration by 32% (P<0.001). CONCLUSIONS: Our results indicate that vitamin B(6) supplementation alone is less effective than folic acid combined with vitamin B(12) in lowering plasma homocysteine concentrations in CAD patients. SPONSORSHIP: This study was supported by the National Science Council, Taiwan, Republic of China (NSC-91-2320-B-040-023).     

Low-dose folic acid supplementation does not influence plasma methionine concentrations in young non-pregnant women

An elevated plasma total homocysteine (tHcy) concentration is a risk factor for cardiovascular disease and for having offspring with a neural-tube defect. Folate is a methyl donor in the remethylation of homocysteine into methionine. Although folic acid supplementation decreases tHcy concentrations, effects of folic acid supplementation on plasma methionine concentrations are unclear. There is also concern that folic acid supplementation negatively affects vitamin B12 status. We studied effects of low-dose folic acid supplementation on methionine and vitamin B12 concentrations in plasma. We also investigated whether baseline plasma methionine and tHcy concentrations correlated with the baseline folate and vitamin B12 status. For a period of 4 weeks, 144 young women received either 500 micrograms folic acid each day, or 500 micrograms folic acid and placebo tablets on alternate days, or a placebo tablet each day. Plasma methionine, tHcy and plasma vitamin B12 concentrations were measured at start and end of the intervention period. Folic acid supplementation had no effect on plasma methionine or plasma vitamin B12 concentrations although it significantly decreased tHcy concentrations. Plasma methionine concentrations showed no correlation with either tHcy concentrations (Spearman rs-0.01, P = 0.89), or any of the blood vitamin variables at baseline. Baseline tHcy concentrations showed a slight inverse correlation with baseline concentrations of plasma vitamin B12 (rs-0.25, P < 0.001), plasma folate (rs-0.24, P < 0.01) and erythrocyte folate (rs-0.19, P < 0.05). In conclusion, low-dose folic acid supplementation did not influence plasma methionine or plasma vitamin B12 concentrations. Furthermore, no correlation between plasma methionine concentrations and the blood folate and vitamin B12 status was shown.     

Hyperhomocysteinemic subjects have enhanced expression of lectin-like oxidized LDL receptor-1 in mononuclear cells

An elevated plasma concentration of homocysteine is an independent risk factor for cardiovascular disease. However, the mechanisms are still unclear. Lectin-like oxidized LDL receptor-1 (LOX-1) has ligand specificity for oxidized LDL (oxLDL). We hypothesized that homocysteine's atherogenic effects may involve LOX-1-mediated mechanisms. We examined the effect of folic acid supplementation for 6 wk and 12 mo (5 mg/d for 1 wk, 1 mg/d for 37 wk and 0.4 mg/d for the remaining 14 wk) on LOX-1 mRNA levels and on oxLDL-induced release of tumor necrosis factor alpha from peripheral blood mononuclear cells in hyperhomocysteinemic individuals. Compared with healthy controls, hyperhomocysteinemic subjects had elevated mRNA levels of LOX-1 in mononuclear cells (P < 0.001), and their mononuclear cells released more tumor necrosis factor alpha (TNFalpha) upon oxLDL stimulation (P = 0.01). This oxLDL-stimulated release of TNFalpha correlated with LOX-1 expression (r = 0.57, P = 0.026). Folic acid treatment led to a normalization of homocysteine levels accompanied by a reduction in LOX-1 gene expression (P < 0.02) and in oxLDL-stimulated release of TNFalpha (P < 0.05). These novel findings suggest both that homocysteine exerts its atherogenic effect in part by elevating levels of LOX-1, thereby enhancing oxLDL-induced inflammatory responses, and most important, that folic acid supplementation may downregulate these responses.     

Plasma homocysteine levels in hyperinsulinemic patients

In order to evaluate the clinical characteristics of metabolic syndrome, a screening procedure was performed and in a cohort of middle-aged (40-60 years) hyperinsulinaemic (fasting plasma insulin > 15 microU/ml) and/or postprandial [120 min after 75 g glucose load] insulin > 45 microU/ml) subjects (n = 91; men/women: 38/53; age mean +/- SD 47.6 +/- 4.3 years; body mass index: 34.6 +/- 4.9 kg/m2; waist-hip ratio: 0.92 +/- 0.07; actual blood pressure 146 +/- 16/87 +/- 9 mmHg; fasting insulin: 24.2 +/- 11.3 microU/ml; postprandial insulin 125.5 +/- 103.8 microU/ml; serum LDL-cholesterol: 3.73 +/- 1.09 mmol/l; HDL-cholesterol: 1.12 +/- 0.30 mmol/l; triglycerides: 2.97 +/- 2.38 mmol/l; uric acid 279 +/- 79 mumol/l) plasma fasting homocysteine, vitamin B12 and folic acid levels were simultaneously determined. The values were separately evaluated according to the stages of glucose tolerance (normal glucose tolerance [n = 47]; impaired glucose tolerance [n = 24] and diabetes mellitus [n = 20]). Laboratory normal values were determined in 47 healthy subjects (control group, age: 45.0 +/- 7.8 years, men/women: 19/28). There was no significant difference between hyperinsulinaemic and control subjects regarding plasma homocysteine (9.28 +/- 3.81 mumol/l vs. 9.63 +/- 2.70 mumol/l), folic acid (8.5 +/- 5.9 ng/ml vs. 7.5 +/- 2.1 ng/ml) and vitamin B12 levels (423 +/- 141 pg/ml vs. 356 +/- 121 pg/ml). Plasma homocysteine levels were significantly (p < 0.001) higher in hyperinsulinaemic men than women (11.34 +/- 4.72 mumol/l [n = 38] vs. 7.86 +/- 2.13 mumol/l [n = 53]). There was no significant difference between subgroups classified according to the stages of glucose tolerance in hyperinsulinaemic groups. Plasma homocysteine values exceeding the upper limit of normal range (> 12.45 mumol/l) were detected at a similar prevalence rate in control (4/47 = 8.5%) and in hyperinsulinaemic subjects (10/91 = 10.9%). A weak but statistically significant correlation was found between plasma homocysteine values and age of subjects (r = 0.222; p < 0.05) whereas a stronger correlation was documented between plasma homocysteine and serum creatinine values (r = 0.658; p < 0.001) in hyperinsulinaemic groups (n = 91). Plasma homocysteine values independently from the stages of glucose tolerance are not elevated in hyperinsulinaemic subjects. Hyperhomocysteinaemia is not a characteristic feature of hyperinsulinism suggesting that plasma homocysteine levels are of no considerable importance in the complex pathomechanism of atherosclerosis at early stages of metabolic syndrome.     

Preconception homocysteine and B vitamin status and birth outcomes in Chinese women

BACKGROUND: The associations between homocysteine, B vitamin status, and pregnancy outcomes have not been examined prospectively. OBJECTIVE: We assessed the associations of preconception homocysteine and B vitamin status with preterm birth and birth of low-birth-weight (LBW) and small-for-gestational-age (SGA) infants in Chinese women. DESIGN: This was a case-control study of women aged 21-34 y. Preterm cases (n = 29) delivered living infants at <37 wk gestation; term controls (n = 405) delivered infants at > or =37 wk. LBW cases (n = 33) had infants weighing <2500 g; normal-birth-weight controls (n = 390) had infants weighing > or =2500 g. SGA cases (n = 65) had infants below the 10th percentile of weight-for-gestational-age; appropriate-for-gestational-age controls (n = 358) had infants above this cutoff. Nonfasting plasma concentrations of homocysteine, folate, and vitamins B-6 and B-12 were measured before conception. RESULTS: Elevated homocysteine (> or =12.4 micro mol/L) was associated with a nearly 4-fold higher risk of preterm birth (OR: 3.6; 95% CI: 1.3, 10.0; P < 0.05). The risk of preterm birth was 60% lower among women with vitamin B-12 > or =258 pmol/L than among vitamin B-12-deficient women (OR: 0.4; 95% CI: 0.2, 0.9; P < 0.05) and was 50% lower among women with vitamin B-6 > or =30 nmol/L than among vitamin B-6-deficient women (OR: 0.5; 95% CI: 0.2, 1.2; NS). Folate status was not associated with preterm birth, and homocysteine and B vitamin status were not associated with LBW or SGA status. CONCLUSIONS: Elevated homocysteine and suboptimal vitamin B-12 and B-6 status may increase the risk of preterm birth. These results need to be confirmed in larger prospective studies.     

同型半胱氨酸、叶酸和维生素B12水平与不良妊娠结局的相关性分析

目的:探讨同型半胱氨酸、叶酸和维生素B12与不良妊娠结局的相关性。方法:选取2016年10月-2017年3月发生不良妊娠结局的孕妇70例为观察组,未发生不良妊娠事件的孕妇627例为对照组,健康未孕育龄期妇女60例为未孕组。对比3组血清同型半胱氨酸、叶酸和维生素B12血清水平;通过Pearson相关性分析检验同型半胱氨酸和叶酸、维生素B12的相关性;通过非条件logistic多元逐步回归分析统计发生不良妊娠事件的相关危险因素。结果:观察组的同型半胱氨酸水平(11.2±2.8μmol/L)高于另外两组,而叶酸水平(645.9±281.4nmol/L)、维生素B12水平(247.2±102.3pmol/L)均低于另外两组(均P0.05);Pearson相关性分析结果显示,血清同型半胱氨酸水平与叶酸、维生素B12水平呈负相关关系(r=-0.089,-0.108,均P0.05);非条件logistic多元逐步回归分析结果显示,同型半胱氨酸升高、维生素B12降低以及年龄增大是不良妊娠发生的相关危险因素(均P0.05)。结论:同型半胱氨酸升高、维生素B12降低以及年龄增大是不良妊娠发生的相关危险因素,临床应加强孕期保健,对年龄较大的孕妇应加强同型半胱氨酸及维生素B12的监测,预防不良妊娠的发生。     

Breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 increases vitamin concentrations and reduces homocysteine concentrations: a randomized trial

BACKGROUND: High homocysteine and low B vitamin concentrations have been linked to the risk of vascular disease, stroke, and dementia and are relatively common in older adults. OBJECTIVE: We assessed the effect of breakfast cereal fortified with folic acid, vitamin B-6, and vitamin B-12 on vitamin and homocysteine status. DESIGN: A randomized, double-blind trial was conducted in 189 volunteers aged 50-85 y. The subjects had no history of hypertension, anemia, asthma, cancer, or cardiovascular or digestive disease and did not regularly consume multiple or B vitamin supplements or highly fortified breakfast cereal. Subjects were randomly assigned to consume 1 cup (0.24 L) breakfast cereal fortified with 440 microg folic acid, 1.8 mg vitamin B-6, and 4.8 microg vitamin B-12 or placebo cereal for 12 wk. Blood was drawn at 0, 2, 12, and 14 wk. Methionine-loading tests were conducted at baseline and week 14. RESULTS: Final baseline-adjusted plasma homocysteine concentrations were significantly lower and B vitamin concentrations were significantly higher in the treatment group than in the placebo group (P < 0.001). The percentage of subjects with plasma folate concentrations < 11 nmol/L decreased from 2% to 0%, with vitamin B-12 concentrations < 185 pmol/L from 9% to 3%, with vitamin B-6 concentrations < 20 nmol/L from 6% to 2%, and with homocysteine concentrations > 10.4 micromol/L (women) or > 11.4 micromol/L (men) from 6.4% to 1.6%. The percentage of control subjects with values beyond these cutoff points remained nearly constant or increased. CONCLUSIONS: In this relatively healthy group of volunteers, consumption of 1 cup fortified breakfast cereal daily significantly increased B vitamin and decreased homocysteine concentrations, including post-methionine-load homocysteine concentrations.     

Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses

One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.     

The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people

Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B-12 lowers homocysteine levels. In January 2000, the Chilean government initiated a flour folic acid fortification program to decrease the occurrence of neural tube defects. The aim of this study was to evaluate the effect of this program on serum homocysteine and folate levels in elderly subjects after 6 mo. A total of 108 elderly people were studied. We measured serum folate, homocysteine and vitamin B-12 levels before the fortification started and 6 mo later. At baseline, folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7 +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to 11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged. Flour fortification with folic acid had a moderate lowering effect on homocysteine levels. Given that vitamin B-12 deficiency was more common than folate deficiency, it may be more appropriate to add vitamin B-12 to food, at least in foods for this age group.     

Hyperhomocysteinemia and oxidative stress in hemodialysis: effects of supplementation with folic acid

This study was undertaken to evaluate two different doses of folic acid and their effects on the control of hyperhomocysteinemia, and on pro-oxidant and antioxidant changes in a group of 32 hemodialysis (HD) patients. Blood samples were collected in a group of patients at three different times: before (basal; B), after the first (S1), and after the second (S2) three-month supplementation periods, and compared to samples from a group of healthy individuals. Analysis of vitamins (C, E, folate, and B12), oxidant parameters (lipid and protein oxidation), and homocysteine were performed. Hyperhomocysteinemia of different degrees was observed in all patients on HD (45.30 +/- 24.89 microM). Oxidative stress was also detected, with lipoperoxidation and protein oxidation being associated with lower concentrations of antioxidant substances (vitamins E and C). The first folate dose (2.5 mg after each dialysis session) reduced by half the initial concentrations of homocysteine (44.92 +/- 22.05 to 20.56 +/- 6.79 microM; p < 0.05) but did not normalize its values. The second dose (15 mg) did not show an additional effect, but it was at this time that lipoperoxidation was significantly reduced, although the protein oxidation showed no change. It was concluded that the first dose of folic acid was efficient in reducing homocysteine concentrations, without normalization of values. The participation of hyperhomocysteinemia in oxidative stress appeared to be partial, but in combination with dialysis treatment, may contribute to the induction of an oxidative environment in this group. The possible antioxidant action of folate must also be considered in this case, acting directly against lipoperoxidation or through hyperhomocysteinemia control. Routine supplementations of folic acid and other antioxidant vitamins should be considered in hemodialysis in order to reduce homocysteine levels to lower values, that although not normal, may be more beneficial in minimizing the cardiovascular risk in this group.     

Randomized controlled trial of homocysteine-lowering vitamin treatment in elderly patients with vascular disease

BACKGROUND: Homocysteine is an independent risk factor for vascular disease and is associated with dementia in older people. Potential mechanisms include altered endothelial and hemostatic function. OBJECTIVE: We aimed to determine the effects of folic acid plus vitamin B-12, riboflavin, and vitamin B-6 on homocysteine and cognitive function. DESIGN: This was a factorial 2 x 2 x 2, randomized, placebo-controlled, double-blind study with 3 active treatments: folic acid (2.5 mg) plus vitamin B-12 (500 microg), vitamin B-6 (25 mg), and riboflavin (25 mg). We studied 185 patients aged >or=65 y with ischemic vascular disease. Outcome measures included plasma homocysteine, fibrinogen, and von Willebrand factor at 3 mo and cognitive change (determined with the use of the Letter Digit Coding Test and on the basis of the Telephone Interview of Cognitive Status) after 1 y. RESULTS: The mean (+/-SD) baseline plasma homocysteine concentration was 16.5 +/- 6.4 micromol/L. This value was 5.0 (95% CI: 3.8, 6.2) micromol/L lower in patients given folic acid plus vitamin B-12 than in patients not given folic acid plus vitamin B-12 but did not change significantly with vitamin B-6 or riboflavin treatment. Homocysteine lowering with folic acid plus vitamin B-12 had no significant effect, relative to the 2 other treatments, on fibrinogen, von Willebrand factor, or cognitive performance as measured by the Letter Digit Coding Test (mean change: -1; 95% CI: -2.3, 1.4) and the Telephone Interview of Cognitive Status (-0.7; 95% CI: -1.7, 0.4). CONCLUSION: Oral folic acid plus vitamin B-12 decreased homocysteine concentrations in elderly patients with vascular disease but was not associated with statistically significant beneficial effects on cognitive function over the short or medium term.     

High frequency of maternal vitamin B12 deficiency as an important cause of infantile vitamin B12 deficiency in Sanliurfa province of Turkey

Summary Background Vitamin B₁₂ deficiency in infancy may cause failure to thrive, severe neurological disorders and megaloblastic pancytopenia. It is well known that infants born with deficient vitamin B₁₂ storage have increased the risk of vitamin B₁₂ deficiency. Vitamin B₁₂ deficiency is more prevalent in infancy in Sanliurfa province (at the southeast region of Turkey). Aim of the study The aim of this study was to determine the frequencies of vitamin B₁₂, folic acid and iron deficiencies in pregnants and their babies at birth and to what extend the mothers’ deficiency becomes effective on babies’ deficiencies. Methods The study groups were constituted by 180 pregnant women and their single and term babies. Venous blood samples of pregnants were obtained 1–3 h before delivery and babies’ cord bloods were collected at birth. Vitamin B₁₂ and folic acid levels were measured with electro chemiluminiscence method; serum iron and iron binding capacities were measured by colorimetric method and complete blood counts were performed by automatic blood counter. Results Mean vitamin B₁₂ levels in maternal and cord blood serum were 130 ± 61.7 pg/ml and 207 ± 141 pg/ml; mean folic acid levels were 8.91 ± 6.46 ng/ml and 17.8 ± 11.8 ng/ml; mean serum iron levels were 56.9 ± 37.5 μg/dl and 147 ± 43.2 μg/dl; and mean transferrin saturations were 11.8 ± 8% and 65.6 ± 24%, respectively. There were vitamin B₁₂ deficiency (<160 pg/ml) in 72% of the mothers and 41% of the babies, and severe deficiency (<120 pg/ml) in 48% of the mothers and 23% of the babies. Folic acid deficiency was found in 12% of the mothers, but was not found in the babies. There were iron deficiency in 62% of the mothers and 1% of the babies. There were statistically significant correlation between maternal and cord blood serum vitamin B₁₂ levels (r = 0.395, P < 0.001) and folic acid levels (r = 0.227, P = 0.017), while there were no correlation between maternal and cord blood iron levels and transferrin saturations. Conclusion The study results showed that vitamin B₁₂ deficiency is prevalent in pregnants in this region and that 41% of infants have born with deficient vitamin B₁₂ storages. Therefore, prophylactic use of vitamin B₁₂ by pregnant women in Sanliurfa and other poor communities could have considerable benefits to prevent vitamin B₁₂ deficiency and its complications in infants.