Effects of Folic Acid Before and After Vitamin B12 on Plasma Homocysteine Concentrations in Hemodialysis Patients with Known MTHFR Genotypes (original) (raw)
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Journal of pediatric nephrology, 2014
Introduction: Deficiencies of water soluble vitamins such as folate and vitamin B12 has been reported as etiologic factors of hyperhomocysteinemia. This study was conducted to find whether there is a correlation between serum levels of these vitamins and plasma total homocysteine (tHcy) levels. Material and Methods : 19 hemodialysis subjects were enrolled. The study group comprised 52.6% girls and 47.4% boys aged 80-324 (204.7±78.4) months who were on dialysis from 1.5-153 (42.1±43.3) months ago . All patients were supplemented by folate and 15 cases were received oral vitamin B12. Folate serum levels 15 µmol/L were defined as normal and hyperhomocysteinemia, respectively. The correlation between the serum levels of vitamins and plasma Hcy levels was checked by the Pearson correlation test and P-values 0.7 indicated a good (significant) correlation. Results: 13 patients (68.4%) had hyperhomocysteinemia whereas plasma tHcy levels were normal in 6 (31.6%). No patient had folate or vit...
Journal of Nephrology, 2015
Background Hyperhomocysteinaemia, an independent risk factor for cardiovascular diseases, is common in hemodialysis patients (HD) and particularly in those homozygous for polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. B vitamins supplementation has been shown to lower plasma total homocysteine (tHcy), but this has been contreversed in several groups. The aim of our study was to explore the response of tHcy in hemodialysis (HD) patients to individual supplementation with folic acid (B9) and/or vitamin B12, based on carrier status for the (MTHFR) polymorphism. Methods 132HD were randomized according to C677TMTHFR genotypes into 2 groups (AandB). The group (A) was treated initially with B9 (10mg/day orally) for 2 months (t1) and then with B12 vitamin (cyanocobalamin ampoule of 1000 lg) for the following 2 months (t2), then association of B9 and B12 for 2 months (t3). The group (B) was supplemented initially with vitamin B12 (t1), then with folic acid (t2) and then B9 ? B12 for 2 months (t3). A wash-out period of 2 months followed the treatment in both groups (t4). We determined tHcy, B9 and B12 concentrations at each time. Results In group A, we noted that the decrease in tHcy becomes significant for CC when patients were supplemented with vit B12 only (p = 0.009). While, B9 ? vit B12 supplementation did not seem to improve a significant effect compared with B12 alone. For genotypes (CT) and (TT) we noticed a significant decrease in tHcy at t1 (p = 0.038; 0.005 respectively) and at (t3; CT p = 0.024; TT p = 0.017). In group B, for genotypes CC, the decrease in tHcy became significant at t3 (vit B12 ? B9; p = 0.031). For genotypes (CT) and (TT), at the replacement of vit B12 by B9, tHcy was significantly decreased (p = 0.036; 0.012, respectively). The combination of the 2 vitamins (t3) showed no difference compared to folate alone. In the 2 groups (t4), there was an significant increase of tHcy again for 3 genotypes. Conclusion Supplementation with B vitamins correlated to the MTHFR genotypes has been shown to lower significantly tHcy in HD patients. Keywords MTHFR genotypes Á B9 and B12 vitamins Á plasma total Homocysteine Á (tHCy) Á Hemodialysis patients (HD)
Nephrology Dialysis Transplantation, 2002
Background. Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B-complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine-lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR. Methods. Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention. Results. At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1"15 mmolul). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2"7 mmolul (P-0.001) and no significant differences were observed between the different genotype subgroups (19.4"6 for CC, 21.3"8 for CT, 18.5"4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (rs 0.615, P-0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8"7 mmolul, NS ) or in any subgroup (19.1"5 for CC, 20.3"9 for CT and 20"7 mmolul for TT). Conclusions. (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups.
Randomized Trial of Methylcobalamin and Folate Effects on Homocysteine in Hemodialysis Patients
Nephron, 2002
Background: There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients. Methods: We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 µg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 µg twice/week alone. Fasting tHcy, vitamin B12, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy. Results: Final tHcy levels were significantly lower in group A (10.2 ± 3.1 µmol/l) compared to groups C (27.3 ± 9.7 µmol/l, p < 0.001) and group D ...
International Urology and Nephrology, 2006
Background: Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. Patients-methods: In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0±40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B 1 (250 mg), vitamin B 6 (250 mg) and vitamin B 12 (1.5 mg) was administered at the end of hemodialysis. Results: Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8±23 lmol/L vs. 22.0±17.6 and 15.0±4.5 lmol/L, respectively; p < 0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p < 0.000001). Mean serum tHcy levels were lowest at the end of period C (p < 0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 lmol/L. Conclusions: In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.
2010
Introduction. Hyperhomocysteinemia is common in patients with chronic kidney disease. There is a direct relationship between cardiovascular mortality and increase of blood homocysteine. Folic acid is used as common treatment in such patients. Folinic acid, a shortened form of folic acid, is not affected by inhibitors of dihydrofolate reductase enzyme such as methoterxate. This study was performed to evaluate the effect of oral folinic acid on the blood homocysteine level of hemodialysis patients, in comparison with folic acid. Materials and Methods. This clinical trial was performed on 60 hemodialysis patients. The participants were divided into 2 groups to receive either 15 mg of oral folic acid or 15 mg of oral folinic acid, daily. Blood homocysteine levels were measured before dialysis and after the study period. Results. Folic acid and folinic acid decreased the blood homocysteine levels by 33.0% and 28.7%, respectively (P < .001). However, only 3 patients (6.5%) enjoyed a no...
Iranian Journal of Kidney …, 2011
Introduction. Hyperhomocysteinemia is common in patients with chronic kidney disease. There is a direct relationship between cardiovascular mortality and increase of blood homocysteine. Folic acid is used as common treatment in such patients. Folinic acid, a shortened form of folic acid, is not affected by inhibitors of dihydrofolate reductase enzyme such as methoterxate. This study was performed to evaluate the effect of oral folinic acid on the blood homocysteine level of hemodialysis patients, in comparison with folic acid. Materials and Methods. This clinical trial was performed on 60 hemodialysis patients. The participants were divided into 2 groups to receive either 15 mg of oral folic acid or 15 mg of oral folinic acid, daily. Blood homocysteine levels were measured before dialysis and after the study period. Results. Folic acid and folinic acid decreased the blood homocysteine levels by 33.0% and 28.7%, respectively (P < .001). However, only 3 patients (6.5%) enjoyed a normalized homocysteine level. Conclusions. Our study showed that both folic and folinic acid decreased the blood homocysteine level and no meaningful difference was observed between them; therefore, we suggest they can be used interchangeably.
Metabolism, 1999
concentrations may be reduced by supplementation with folic acid or combinations of folic acid, vitamin B12, and vitamin Be. Supplementation studies with vitamin B12 alone in patients with ESRD have not yet been published. In this study, we investigated the effects of intravenous injection of cyanocobalamin (1 mg/wk for 4 weeks) in ESRD patients (N = 14) with low serum cobalamin concentrations (< 180 pmol/L). All patients had elevated levels of plasma tHcy, methylmalonic acid (MMA), and cystathionine before supplementation. After supplementation, plasma tHcy and MMA decreased 35% and 48%, respectively; however, cystathionine levels were unchanged. The extent of the plasma tHcy reduction tended to be influenced by the C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR). Serum cobalamin increased significantly upon supplementation, whereas serum folate levels were substantially reduced by 47%. In contrast, red blood cell (RBC) folate was unchanged. This study shows that vitamin B12 supplementation effectively decreases both MMA and plasma tHcy in ESRD patients with low B~2 levels. Furthermore, it illustrates the close interrelation between vitamin B12 and folate metabolism.
Nutrition, 2007
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.
The Israel Medical Association journal: IMAJ
Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients. To examine the effects of two doses of vitamins B6 and B12 and folic acid on homocysteine levels in hemodialysis patients and assess the functional impact of the methylenetetrahydrofolate reductase genotype on the response to treatment. In a randomized prospective study, we assessed the effects of folic acid and two doses of B-vitamins in 50 hemodialysis patients with hyperhomocysteinemia. Patients were divided into two groups: 26 patients (group A) who received 25 mg of vitamin B6 daily and one monthly injection of 200 microg vitamin B12, and 24 patients (group B) who received 100 mg of vitamin B6 daily and one monthly injection of 1,000 microg vitamin B12. In addition, both groups received 15 mg folic acid daily. Patients were evaluated for homocysteine levels as well as for coagulation and a thorough lipid profile. Baseline Hcy levels were determined after at least 4 we...