Decreased Plasma Homocysteine Research Articles

Short-Term Folate Supplementation in Physiological Doses Has No Effect on ESR1 and MLH1 Methylation in Colonic Mucosa of Individuals with Adenoma

Background/Aims: Low folate intake may increase risk of colorectal cancer by altering gene-specific methylation in the colon. We determined whether supplementation with physiological doses of folate could alter methylation in the oestrogen receptor 1 (ESR1) and mutL homolog 1 (MLH1) genes in colonic mucosa of subjects with colorectal adenoma. Methods: This was a randomised, double-blind, placebo-controlled trial. Subjects received either 400 µg/day folic acid (n = 15) or placebo (n = 14) for 10 weeks. Blood and colonic tissue samples were collected at baseline and after intervention to determine biomarkers of folate and vitamin B₁₂ status, MTHFR C677T and MS A2756G genotypes, and ESR1 and MLH1 methylation. Results: Although serum and red cell folate increased (p < 0.001 vs. placebo) and plasma homocysteine decreased (p = 0018 vs. placebo) in the folic acid group, there were no significant changes in ESR1 (p = 0.649 vs. placebo) or MLH1 (p = 0.211 vs. placebo) methylation. There was a significant effect of gender on ESR1 methylation (p = 0.004) and significant gender and genotype (MTHFR C677T and MS A2756G) interactions (p = 0.04 and p = 0.014, respectively) that were independent of treatment group allocation. Conclusions: Short-term folate supplementation in physiological doses decreases plasma homocysteine but has no effect on ESR1 and MLH1 methylation in colonic mucosa of individuals with adenoma. Further studies to investigate the interactions between gender, genotype and DNA methylation suggested in this study are warranted.

MAT1A variants modulate the effect of dietary fatty acids on plasma homocysteine concentrations

Background and AimDietary n-3 polyunsaturated fatty acids (PUFAs) are associated with decreased plasma homocysteine (Hcy), an important biomarker for cardiovascular disease. The S-adenosylmethionine synthetase type-1 (MAT1A), an essential enzyme in the conversion of methionine to S-adenosylmethionine, plays a key role in homocysteine metabolism. This study investigated the interaction between dietary fatty acids and MAT1A genotypes on plasma Hcy concentrations among Boston Puerto Ricans. Methods and ResultsPlasma Hcy and MAT1A genotypes were determined in 994 subjects of the Boston Puerto Rican Health Study. Dietary fatty acid intakes were assessed by interviews using a questionnaire adapted from the NCI/Block food frequency form. ResultIn the cross-sectional analysis, genetic variant MAT1A 3U1510 displayed a significant interaction with dietary n-3:n-6 PUFA ratio in determining plasma Hcy (p-value for interaction = 0.025). 3U1510G homozygotes had significantly lower plasma Hcy concentration than major allele homozygotes and heterozygotes (AA + AG) (p-value for trend = 0.019) when the n-3:n-6 ratio was >0.09. Two other MAT1A variants, d18777 and i15752, also showed significant interactions with different constituents of dietary fat influencing Hcy concentrations. Furthermore, haplotypes consisting of three variants displayed a strong interaction with n3:n6 ratio influencing Hcy concentrations. ConclusionsOur results suggest that MAT1A genotypes appear to modulate effects of dietary fat on plasma Hcy.

Association Between Adherence to Folic Acid Supplements and Serum Folate, and Plasma Homocysteine Among Hemodialysis Patients

To examine the relationship between adherence to prescribed folic acid supplements and folic acid intake, serum folate and plasma homocysteine in hemodialysis patients. The effects of change in adherence patterns from enrollment to 1 year later on changes in these same measures were also assessed. Secondary data analysis. Eighty-six hemodialysis patients who participated in the Hemodialysis (HEMO) Study's Homocysteine ancillary study. Folic acid supplement intake, serum folate, and plasma homocysteine. Eighty-eight percent of patients at enrollment and 91% 1 year later were adherent to prescribed folic acid supplements. Nonadherers had lower intakes of folic acid at both enrollment and 1 year later and lower serum folate levels at enrollment. Percent change was significantly different between the 3 adherence change groups for folic acid intake (P = .001) and plasma homocysteine (P < .001) from enrollment to 1 year later. The nonadherent group at enrollment had the lowest intakes and serum folate levels, and the highest plasma homocysteine levels. When they became adherent 1 year later, they had the greatest change in folic acid intake (5,461%; P = .03), coupled with a 69% increase in serum folate (P = .04) and a 29% decrease in plasma homocysteine (P = .03). Hemodialysis patients who were nonadherent to folic acid supplement prescriptions had low folic acid intakes, low serum folates, and high homocysteine levels. When their adherence improved, folic acid intakes rose, serum folates increased, and plasma homocysteine levels decreased, although mild hyperhomocysteinemia persisted.

Dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and risk of Parkinson's disease: a case–control study in Japan

Increased homocysteine levels might accelerate dopaminergic cell death in Parkinson's disease (PD) through neurotoxic effects; thus, increasing intake of B vitamins involved in the regulation of homocysteine metabolism might decrease the risk of PD through decreasing plasma homocysteine. However, epidemiological evidence for the association of dietary B vitamins with PD is sparse, particularly in non-Western populations. We conducted a hospital-based case-control study in Japan to examine associations between dietary intake of folate, vitamin B6, vitamin B12 and riboflavin and the risk of PD. Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n 249) and controls without neurodegenerative diseases (n 368) were recruited. Dietary intake during the preceding month was assessed at the time of study recruitment using a validated, self-administered, semi-quantitative, comprehensive diet history questionnaire. After adjustment for potential dietary and non-dietary confounding factors, intake of folate, vitamin B12 and riboflavin was not associated with the risk of PD (P for trend = 0.87, 0.70 and 0.11, respectively). However, low intake of vitamin B6 was associated with an increased risk of PD, independent of potential dietary and non-dietary confounders. Multivariate OR (95 % CI) for PD in the first, second, third and fourth quartiles of vitamin B6 were 1 (reference), 0.56 (0.33, 0.94), 0.69 (0.38, 1.25) and 0.48 (0.23, 0.99), respectively (P for trend = 0.10). In conclusion, in the present case-control study in Japan, low intake of vitamin B6, but not of folate, vitamin B12 or riboflavin, was independently associated with an increased risk of PD.

Docosahexaenoic acid decreases plasma homocysteine via regulating enzyme activity and mRNA expression involved in methionine metabolism

Objective The objective of this study was to investigate the regulatory effect of fish oil rich in ω-3 polyunsaturated fatty acids (PUFAs) on critical enzyme activity and mRNA expression involved in homocysteine (Hcy) metabolism. Methods Thirty-six male Sprague-Dawley rats aged 3 wk, weighing 120 ± 10 g, were randomly divided into three groups: the olive oil (OO) group, the tuna oil (TO) group, and the salmon oil (SO) group. The oil was orally administered every day using a stomach tube. Eight weeks later, plasma Hcy, phospholipids, ω-3 PUFAs, enzyme activity, and mRNA expression in tissues were determined. Results Compared with the control group, phospholipids, total ω-3 PUFAs, and ω-3/ω-6 PUFAs in the liver and lung were significantly elevated in the TO and SO groups; 22:6ω-3 in the liver and lung was significantly increased in the TO group; and 20:5ω-3 in the two tissues was significantly elevated in the SO group. The level of plasma Hcy was significantly decreased with TO; methionine adenosyl transferase (MAT) activity was significantly increased and MAT mRNA expression was significantly upregulated with TO; cystathionine-γ-lyase mRNA expression in TO was significantly upregulated; however, cystathionine β-synthase and S-adenosylhomocysteine hydrolases were not significantly changed when compared with control. Conclusion TO rich in 22:6ω-3 decreases the concentration of Hcy despite increasing MAT activity and upregulating MAT mRNA expression through compensatory cystathionine-γ-lyase mRNA expression, both of which are involved in Hcy metabolism.

Folic Acid Supplementation in Early Second Trimester and the Risk of Preeclampsia

Objective The objective of the study was to evaluate the association between folic acid supplementation in early second trimester and the risk of developing preeclampsia. Study Design We carried out a prospective cohort study between October 2002-December 2005. We recruited women who had their prenatal care visit (12-20 weeks’ gestation) at the Ottawa Hospital and Kingston General Hospital. All charts for participants with a diagnosis of preeclampsia were audited and blindly adjudicated by 4 study investigators to validate the diagnosis. Results A total of 2951 pregnant women were included in the final analysis. Supplementation of multivitamins containing folic acid was associated with increased serum folate (on average 10.51 μmol/L), decreased plasma homocysteine (on average 0.39 μmol/L), and reduced risk of preeclampsia (adjusted odds ratio, 0.37; 95% confidence interval, 0.18-0.75). Conclusion Supplementation of multivitamins containing folic acid in the second trimester is associated with reduced risk of preeclampsia.

Acute benzodiazepine administration induces changes in homocysteine metabolism in young healthy volunteers

Purpose High cortisol plasma concentrations have been shown to be associated with increases in homocysteine levels. Here we studied whether decreases in cortisol concentration, induced by an acute oral dose of a benzodiazepine, could decrease homocysteine, and if changes were similar in both genders. Methods This was a double-blind, cross-over design study of acute oral flunitrazepam (1.2 mg) and placebo in young, healthy, male and female ( n = 21) volunteers. Blood samples were collected 3 h after ingestion (after peak-plasma concentration of flunitrazepam was reached). Various biochemical parameters were analysed, such as plasma homocysteine, cysteine, folate, vitamins B6, B12, and sexual hormones. Results Flunitrazepam reduced cortisol ( p = 0.0011), cysteine ( p = 0.014) and homocysteine ( p = 0.028) concentrations, irrespective of gender. No correlations were found between cortisol and other biochemical markers (all r's < 0.03). Concentration of cysteine and homocysteine were negatively correlated with plasma flunitrazepam concentration, suggesting that changes in these amino acids might be related to the metabolism of this benzodiazepine. Conclusion Acute administration of flunitrazepam decreases plasma homocysteine and cysteine by mechanisms that seem unrelated to changes in cortisol. Given the importance of homocysteine as a marker of life-threatening disorders, the mechanisms involved in the decrease of these amino acids are potential targets for clinical application.

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

BackgroundCystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.Methodology and Principal FindingsA single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K+ content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.Conclusion and Significance5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.Trial RegistrationClinicalTrials.gov NCT00730509

Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes

Objective. Type 1 diabetes has a bad prognosis concerning the pathogenesis of cardiovascular diseases (CVD). The purpose of this study was to evaluate different possible new risk indices for CVD in children with type 1 diabetes. Material and methods. The present study included 30 children with diabetes (mean HbA1C 9.8%), aged between 4.7 and 18.6 years and with no clinical evidence of vascular complications, and 30 healthy subjects matched by sex, age and body mass index. Blood pressure was measured and blood samples were obtained for lipid profile, creatinine, glucose, high sensitive C‐reactive protein (hsCRP), intercellular adhesion molecule‐1 (ICAM‐1), asymmetric dimethylarginine (ADMA), adiponectin and homocysteine. Results. Children with diabetes had significantly higher blood pressure, plasma hsCRP, ICAM‐1, adiponectin levels and lower homocysteine, ADMA concentrations than their control subjects. In multivariate regression analysis, the best predictors for systolic blood pressure were diabetes group, plasma homocysteine concentration and BMI (Adj R2 = 0.38, p<0.0001), and for diastolic blood pressure diabetes group and triglycerides level (Adj R2 = 0.27, p<0.0001). Conclusions. Children with diabetes, in view of their higher future risk of CVD, are characterized by a higher concentration of protective adiponectin and paradoxically lower blood concentrations of some other possible risk markers of atherosclerosis, i.e. ADMA and homocysteine compared to healthy children.

Hepatic Cystathionine β-Synthase Activity Does Not Increase in Response to Methionine Supplementation in Rats Fed a Low Casein Diet: Association with Plasma Homocysteine Concentrations

To elucidate the mechanism by which moderate and high protein diets fail to increase plasma homocysteine concentration despite dietary methionine levels being higher, rats were fed diets with graded levels (10, 30, and 50%) of casein or low casein diets supplemented with methionine at levels of 0.5 and 1.0% together with or without glycine+serine, which corresponded to moderate and high casein diets with respect to these amino acids, for 14 d. The plasma homocysteine concentration significantly decreased with an increase in dietary casein level, whereas it significantly increased with an increase in dietary methionine level when the low casein diet was supplemented with methionine. Supplementation with glycine+serine significantly suppressed the elevation of plasma homocysteine concentration due to methionine supplementation, but it could not decrease plasma homocysteine concentration to the levels in rats fed corresponding casein diets. Increased concentrations of hepatic S-adenosylhomocysteine and homocysteine due to methionine supplementation were also significantly suppressed by glycine+serine. The activity of hepatic cystathionine beta-synthase (CBS) did not increase in response to methionine supplementation, while it significantly increased with an increase in dietary casein level. In contrast, the activity of hepatic betaine-homocysteine S-methyltransferase (BHMT) significantly increased with increase in both dietary casein level and dietary methionine level. Hepatic levels of mRNA for CBS and BHMT were parallel to the enzyme activities. The results suggest that, in contrast to methionine-supplemented low casein diets, moderate and high casein diets avoid increasing plasma homocysteine concentration through dual mechanisms, greater supply of glycine+serine and an increase in CBS activity.

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Rats were fed diets with and without 0.5% L-cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C+0.65% methionine or 25C+0.4% guanidinoacetic acid. Hepatic S-adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine beta-synthase and betaine-homocysteine S-methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine.

High Casein Diet Decreases Plasma Homocysteine Concentration in Rats

Experiments were conducted to clarify the relationship between dietary protein level and plasma homocysteine concentration in rats. Male Wistar rats were fed diets differing in casein level from 5 to 50% for 14 d (Expt. 1). Plasma total homocysteine concentration was positively correlated with dietary casein level in the range of 5 to 10% but inversely correlated with dietary casein level in the range of 10 to 50%. Hepatic cystathionine beta-synthase (CBS) and betaine-homocysteine S-methyltransferase (BHMT) activities and renal CBS activity increased in response to dietary casein level in the range of 10 to 50%, whereas hepatic serine and betaine concentrations decreased with increasing dietary casein levels. When rats were fed the 10% casein diet or 10% casein+17.2% amino acid mixture diet for 14 d, plasma homocysteine concentration was significantly lower in rats fed the amino acid mixture-added diet than in rats fed the 10% casein diet (Expt. 2), indicating that the hypohomocysteinemic effect of high casein diets was elicited by amino acids, not by casein contaminants. The degree of increase in plasma homocysteine concentration caused by dietary supplementation with 0.75% L-methionine was significantly lower in rats fed the 40% casein diet than in rats fed the 10% casein diet (Expt. 3). These results indicate that high casein diets do not increase but rather decrease plasma homocysteine concentration and cause resistance to hyperhomocysteinemic treatment, and suggest that such effects of high casein diets are mediated at least by increased activities of CBS and BHMT.

Dietary Selenium (Se) and Copper (Cu) Interact to Affect Homocysteine Metabolism in Rats

Previously, we reported that both Se deficiency and Cu deficiency decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which catalyzes the rate-limiting step in glutathione biosynthesis, was upregulated in Se and Cu deficiencies. We suggested that in both deficiencies, Hcys was being shunted through the trans-sulfuration pathway as a result of this up-regulation. Because both Se and Cu deficiencies have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further up-regulating Gclc. In a 2 x 2 experiment, male weanling Sprague-Dawley rats (n = 8-20/group) were fed an amino-acid-based diet containing either 0 or 0.2 microg Se (as selenite)/g and <1 or 6 microg Cu (as Cu carbonate)/g for 5 weeks. Our findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH. However, the up-regulation of liver Gclc alone cannot explain why rats fed with the doubly deficient diet have the lowest pHcys and the highest pGSH.

High-Casein Diet Suppresses Guanidinoacetic Acid-Induced Hyperhomocysteinemia and Potentiates the Hypohomocysteinemic Effect of Serine in Rats

To determine the effect of dietary protein level on experimental hyperhomocysteinemia, rats were fed 10% casein (10C) and 40% casein (40C) diets with or without 0.5% guanidinoacetic acid (GAA) for 14 d. In addition, rats were fed 10C + 0.75% methionine (10CM) and 40C + 0.75% methionine (40CM) diets with or without 2.5% serine for 14 d to determine the relationship between the dietary protein level and intensity of the hypohomocysteinemic effect of serine. GAA supplementation markedly increased the plasma homocysteine concentration in rats fed with the 10C diet, whereas it did not increase the plasma homocysteine concentration in rats fed with the 40C diet. Although serine supplementation significantly suppressed the methionine-induced enhancement of plasma homocysteine concentration, the decreased plasma homocysteine concentration was significantly lower in rats fed with the 40CM diet than in rats fed with the 10CM diet. The hepatic cystathionine beta-synthase and betaine-homocysteine S-methyltransferase activities were significantly higher in rats fed with the 40C or 40CM diet than in rats fed with the 10C or 10CM diet, irrespective of supplementation with GAA and serine. These results indicate that the high-casein diet was effective for both suppressing GAA-induced hyperhomocysteinemia and potentiating the hypohomocysteinemic effect of serine, probably through the enhanced activity of homocysteine-metabolizing enzymes.

Strontium ranelate decreases plasma homocysteine levels in postmenopausal osteoporotic women

We analyzed the effect of strontium ranelate treatment on plasma homocysteine (Hcy) levels in postmenopausal osteoporotic women. Forty-nine postmenopausal women diagnosed with osteoporosis with a mean age of 54.07 +/- 7.5 years (range 40-70) who visited our menopause clinic were participated in this prospective study. Patients with bone mineral density (BMD) at least 2.5 SD below the average value in young adults (T score < -2.5) were considered to have osteoporosis. Patients received strontium ranelate 2 g/day (Servier) orally with additional calcium supplements. Fasting plasma Hcy levels were assessed at baseline, 3, 6 and 12 months of the therapy with strontium ranelate. The mean plasma Hcy level (10.45 micromol/l) after 3 months of therapy was significantly lower compared to the basal plasma Hcy level (12.61 micromol/l) (P = 0.002). The plasma homocysteine level (10.54 micromol/l) of the 43 patients that were present at the 6 months of the therapy was also significantly lower compared to the basal plasma Hcy level (P = 0.005). At the end of the 12 months of the study, there were 42 patients. The plasma homocysteine level (10.107 micromol/l) at 12 months of therapy was also significantly lower compared to the basal Hcy level (P < 0.001). Strontium ranelate 2 g/day treatment for 1 year significantly decreases plasma Hcy levels in postmenopausal women with osteoporosis. Since the increased Hcy levels could lead to an increase risk of osteoporosis and fracture risk, this effect of strontium ranelate on Hcy level may cause additional benefit in terms of reducing the risk of fracture.

Pharmacogenetics of Nitrous Oxide

Pharmacogenetics of Nitrous Oxide

Methionine, folic acid and vitamin B12 in growing-finishing pigs: Impact on growth performance and meat quality

Growth performance, metabolic variables, and meat quality were measured in 78 growing-finishing pigs using supplements of 0 (C), or 0.2% of DL-methionine (M), and three combinations of folic acid [mg/kg] and cyanocobalamin [μg/kg], respectively 0 and 0 (V0), 10 and 25 (V1), and 10 and 150 (V2) in a 2 × 3 factorial arrangement. Feed conversion was lower (p = 0.05) in M than in C pigs during the growing period (0–4 weeks). Both V1 and V2 treatments increased plasma vitamin B12 (p < 0.01) and decreased plasma homocysteine (p < 0.01). Plasma 5-methyl-tetrahydrofolates were the lowest, highest and intermediate in V0, V1 and V2 pigs (p < 0.04), respectively. In V2 meat, folates were 32% higher, vitamin B12, 55% higher and homocysteine, 28% lower than in V0 (p < 0.01). Oxidative stability of the fresh meat was similar among treatments during a storage period of 42 days. Therefore, methionine supplements improved growth performance during the growing period. Vitamin supplements interacted with the methionine cycle pathway, increased vitamin content of pork meat but did not improve oxidative stability of the fresh meat during storage.

Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats

Previously we reported that both Se deficiency (SeD) and Cu deficiency (CuD) decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate‐cysteine ligase (Gclc), which catalyzes the rate limiting step in glutathione biosynthesis, was upregulated in SeD as well as in CuD. We suggested that in both deficiencies, that Hcys was being shunted through the transsulfuration pathway as a result of this upregulation. Because both SeD and CuD have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further upregulating Gclc. In a 2 × 2 experiment, male weanling Sprague‐Dawley rats (N=8–10/group) were fed an amino acid‐based diet containing either 0 or 0.2 μg Se (as selenite)/g and &lt;1 or 6 μg Cu (as Cu carbonate)/g for 5 wk. Values in the table are means±SD. Both SeD and CuD resulted in decreased pHcys; however, CuD in rats fed 0.2 μg Se/g resulted in a greater decrease in pHcys than did CuD in the SeD rats. SeD and CuD resulted in increased pGSH and the combined deficiencies further exacerbated the increase. Plasma cysteine (pCys) was decreased by SeD and increased by CuD.The findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH most likely as a result of increased GSH biosynthesis subsequent to upregulation of Gclc.

Is the Deficiency of Vitamin B12 Related to Oxidative Stress and Neurotoxicity in Parkinsons Patients?

This review deals with the results showing the relation between vitamin B(12) deficiency and neurotoxicity of homocysteine and nitrite (a metabolite of nitric oxide) in Parkinson's patients treated with levodopa (L-Dopa). We have already reported a linear relationship between the CSF levels of nitrite with glutamic acid and homocysteine suggesting that the production of nitrite is interrelated with the neurotoxic level of homocysteine. The levels of nitrite and homocysteine resulting in the deficiency of vitamin B(12) are some of the factors promoting degeneration in Parkinson's disease. This review emphasizes the importance of these parameters in designing suitable drug therapy for Parkinson disease. Additionally, there is evidence that increased homocysteine levels might accelerate dopaminergic cell death in Parkinson disease (PD), through neurotoxic effects. Furthermore, levodopa (L-Dopa) treatment of PD results in hyperhomocysteinemia as a consequence of L-Dopa methylation by catechol-O-methyltransferase (COMT). Therefore, higher dietary intakes of folate, vitamin B12, and vitamin B6 might decrease the risk of PD through decreasing plasma homocysteine.

Folic acid supplementation in early second trimester and the risk of preeclampsia

The objective of the study was to evaluate the association between folic acid supplementation in early second trimester and the risk of developing preeclampsia. We carried out a prospective cohort study between October 2002-December 2005. We recruited women who had their prenatal care visit (12-20 weeks' gestation) at the Ottawa Hospital and Kingston General Hospital. All charts for participants with a diagnosis of preeclampsia were audited and blindly adjudicated by 4 study investigators to validate the diagnosis. A total of 2951 pregnant women were included in the final analysis. Supplementation of multivitamins containing folic acid was associated with increased serum folate (on average 10.51 micromol/L), decreased plasma homocysteine (on average 0.39 micromol/L), and reduced risk of preeclampsia (adjusted odds ratio, 0.37; 95% confidence interval, 0.18-0.75). Supplementation of multivitamins containing folic acid in the second trimester is associated with reduced risk of preeclampsia.