Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 2666 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 5  |  Page : 779-788
Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients


1 Department of Human Nutrition, National Nutrition and Food Technology Research Institute, Tehran, Iran
2 Department of Nephrology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Research and Development, Hakim Pharmaceutical Company, Tehran, Iran
4 Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

Click here for correspondence address and email

Date of Web Publication2-Sep-2009
 

   Abstract 

To evaluate the efficacy of supplementation with high dose folic acid with and with­out vitamin B 12 in lowering plasma total homocysteine (tHcy) concentrations in hemodialysis (HD) patients, we studied 36 HD patients randomized into four groups according to the received thera­peutic regimen: group I (only folic acid (FA), 5 mg/day), group II (FA, 5 mg/day + vitamin B 12 , 1 mg/day) group III (only FA, 15 mg/day), group IV (FA, 15 mg/day, vitamin B 12 , 1 mg/day) for a period of 8 weeks. Plasma tHcy and serum FA and vitamin B 12 levels were measured at baseline and after the supplementation period. Dietary intakes were assessed during the study period. At baseline, 27.8% of the patients had normal levels of tHcy and 72.2% had hyperhomocysteinemia. After supplementation, plasma tHcy increased by 1.35% in group I and decreased by 6.99%, 14.54% and 30.09% in groups II, III and IV respectively, which was only significant in group IV (P= 0.014). The patients did not show any significant changes in serum folic acid, but a significant change in serum vitamin B 12 in group IV (P= 0.006). Percentage of patients reaching normal levels of plasma tHcy was 5.6 fold higher in group IV than in the reference group (group I). No corre­lations were found between changes of plasma tHcy levels and dietary intakes. We conclude that oral supplementation with 15 mg/day folic acid together with 1 mg/day of vitamin B 12 is effective in reducing tHcy levels in HD patients. These supplements also have a desirable effect on serum folic acid and vitamin B12.

How to cite this article:
Azadibakhsh N, Hosseini RS, Atabak S, Nateghiyan N, Golestan B, Rad AH. Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients. Saudi J Kidney Dis Transpl 2009;20:779-88

How to cite this URL:
Azadibakhsh N, Hosseini RS, Atabak S, Nateghiyan N, Golestan B, Rad AH. Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2019 Dec 7];20:779-88. Available from: http://www.sjkdt.org/text.asp?2009/20/5/779/55361

   Introduction Top


Hyperhomocysteinemia is present in 80 to 100 percent of hemodialysis (HD) patients. [1],[2] It is a common manifestation of chronic kidney di­sease (CKD) as the glomerular filtration rate declines, and dialysis does not usually normalize its levels. [3],[4]

Retrospective, observational studies have shown that hyperhomocysteinemia is an independent risk factor for CVD and especially atheroscle­rosis and atherotrombosis. [5],[6],[7],[8],[9],[10],[11],[12],[13] However, large prospective studies have been inconsistent and suggest that tHcy could be a marker of nutri­tional status and not a cause of vascular disea­ses. [14],[15],[16],[17] However, lowering tHcy concentrations in HD patients is desirable since tHcy levels may partially account for thrombotic disease in dialysis patients and the correlation is con­founded by malnutrition, inflammation, and athe­rosclerosis syndrome, [2] which may result in car­diovascular events. [18]

Homocysteine (Hcy) is metabolized by two pathways: remethylation and transsulfuration. Both pathways involve tetrahydrofolate, the active form of folic acid, and vitamin B 12 , as the cofactor. [19],[20],[21] Based on these metabolic path­ ways, different studies have been designed to normalize plasma tHcy levels in HD patients. Most of these studies supplemented HD pa­tients with different doses of folic acid (FA) in order to achieve a considerable reduction in plasma tHcy or even normalize its levels. [3],[22].[23],[24] .Some others evaluated the effect of supplemen­tation with vitamin B 12 , vitamin B 6 , folinic acid, betaine, serine, and taurine, alone or in combi­nation on tHcy concentrations in HD patients [12],[22],[23],[24],[25],[26],[27] and showed variable results. In none of these studies, the impact of dietary intake was considered on the outcome of the patients.

Most HD patients receive oral FA 5 mg/day by the time they are initiated on HD treatment; however, this strategy is inadequate to control hyperhomocysteinemia in them. [28],[29]

The aim of this study is to compare the effi­cacy of low and high doses of FA, with and without vitamin B 12 supplements in lowering tHcy concentrations in HD patients in addition to understanding of the impact of diet control on these levels.


   Patients and Methods Top


We studied 40 HD patients who had been re­ceiving 5 mg/d FA supplements for at least 3 months in a prospectively randomized double­blind clinical trial. We excluded from the study patients under 18 years of age, having dialysis duration less than 3 months, being dialyzed other than 12 hours/week (3 sessions each las­ting 4 hours, using bicarbonate based dialysate and polysulfone dialyzers), receiving supple­mentation history of more than 5 mg/d FA or any vitamin B, using Hcy interacting drugs, [30],[31] having indication or contraindication for any of the study supplements or study procedure, being malnourished (Alb < 2 mg/dL) or vitamin B12 deficient (serum vitamin B 12 < 100 pg/mL), ha­ving a history of graft rejection in the last 6 months, or having a history of liver disease.

Before the supplementation period, the study patients were interviewed to determine their baseline characteristics including age, sex, height, dialysis duration, cigarette smoking (defined as smoking minimum 1 cigarette/d), consumption of tea (as there was not any coffee consumer among subjects), use of oral contraceptives (OCPs) and antacids (as Hcy interacting drugs), menopausal status, and etiology of CKD.

Fasting pre-dialysis blood samples were ana­lyzed for plasma tHcy and serum FA, vitamin B 12 , albumin (Alb), creatinine (Cr) and blood urea nitrogen (BUN). Post-dialysis BUN was also determined to calculate urea reduction ratio (URR) as an indicator of dialysis efficiency, by dividing it to pre-dialysis BUN. [32] Baseline cha­racteristics of patients are shown in [Table 1].

The study patients were divided randomly into four equal groups according to the received the­rapeutic regimen: group I (only folic acid (FA), 5 mg/day), group II (FA, 5 mg/day + vitamin B 12 , 1 mg/day) group III (only FA, 15 mg/day), group IV (FA, 15 mg/day, vitamin B 12 , 1 mg/day) for a period of 8 weeks.

At the end of the supplementation period, plas­ma concentrations of tHcy and serum concen­trations of FA and vitamin B 12 were measured again. All patients were monitored for Kt/V (dia­lysis efficiency index) during the study proce­dure, with the goal of Kt/V > 1.2. [32]

The ethical committee of Shahid Beheshti Uni­versity of Medical Sciences approved the whole procedure.

Laboratory Analysis

For biochemical assessments, fasting blood samples were drawn in the beginning and at the end of the study period. Whole blood samples were immediately cooled on ice packs and se­parated for plasma and serum within one hour using a refrigerated centrifuge.

Plasma samples were analyzed for tHcy con­centrations by a rapid, isocratic, high perfor­mance liquid chromatography (HPLC) assay. [33] We adopted the described normal range for tHcy (5-12 µmol/L) and the borderline range (12-16 µmol/L) in our study. We also con­sidered tHcy levels above 16 µmol/L as hyper­homocysteinemia. [34]

The measurement of serum FA and vitamin B 12 were performed using competitive immuno­assay and an automated chemiluminescence sys­tem. [35] We adopted in our study the described normal ranges for serum FA and vitamin B 12 (3­16 ng/mL and 110-800 pg/mL, respectively). [36]

Alb, Cr and BUN concentrations were mea­sured by Brom cresol green chemical method, chemical method based on reaction with alkaline picrate and enzymatic method based on hydro­lysis of urea with urease relatively. [37],[38] We adop­ted in our study the described normal ranges for these parameters (3.5-5 g/dL, 10-15 mg/dL and < 100 mg/dL, respectively). [39]

All fasting blood samples were collected before the dialysis session. Patients always re­ceived the FA and vitamin B 12 supplements 23­-24 hours before the blood sampling.

Dietary Assessment

Dietary intakes of energy, macronutrients (car­bohydrate, protein and fat) and vitamins invol­ving Hcy metabolism (FA and vitamins B12, B6 and B 2 ) were assessed during the supplemen­tation period, using 24-hour recall method. The patients were interviewed, consecutively, for 3 days at the beginning, 2 days at week 4 and 3 days at the end of the supplementation period (8 days for each patient). 24-hour recall sheets were analyzed with the food processor (FP) software. To minimize measurement errors, the dietary assessment procedure (interviewing and analy­zing) was done by a trained dietitian.


   Statistical Analysis Top


All the statistical analysis was performed using the statistical software, SPSS (version 11.5). Descriptive statistics are reported in the form of mean values ± standard deviation (SD) together with 95% confidence intervals (CI). Since Kol­mogorov-Smirnov test [40] showed that all the va­riables were normally distributed, we used para­metric tests for the analysis. In order to com­pare the means of plasma tHcy and serum FA and vitamin B 12 levels within the groups before and after supplementation, the Student's "t" test [41] for paired samples was used. The effect of treatment and baseline measurements on post values of the main study variables was analyzed using linear regression. [42]

To determine the correlations between plasma tHcy concentrations and objective confounding factors, the Pearson's correlation coefficient [43] was used, while to compare the means of tHcy levels and subjective confounders, "t" test [44] for independent samples was used.

To monitor dietary intakes during the study period, we used ANOVA for repeated measure­ments. [45] In case of significant changes in these variables, linear regression [42] was used to assess the relationship between changes in tHcy concentrations and changes in dietary intakes. The significance level in this study was set at P= 0.05.


   Results Top


From the 40 study patients, 2 died and 2 were eliminated due to injection of blood and vita­min B 12 . Only 36 finished the study period (n=9 in group I, n= 9 in group II, n= 10 in group III, and n= 8 in group IV). [Table 1] shows the main characteristics of the study patients.

Pearson's test revealed a statistically signifi­cant correlation between the mean of the initial plasma tHcy levels and the mean of the initial serum FA levels (r = -0.331, P= 0.048), height (r = -0.35, P= 0.036), and creatinine (r = -0.351, P= 0.88).

The mean of the initial plasma tHcy levels was significantly higher in women than in men (26.08 ± 9.39 µmo/L vs 19.58 ± 7.74 µmol/L, P= 0.032).

Effect of supplementation on plasma tHcy levels

At baseline, 72.2% of our study patients re­vealed hyperhomocysteinemia. Percentage of reduction in mean plasma tHcy level was only significant in group IV (-30.09 ± 22.55 %, P= 0.014) in comparison to group I [Table 2]. The percentage of reduction has been increased from group I to group IV [Figure 1].

Calculating the odds ratio to compare the per­centage of patients with the normal range of plasma tHcy levels after the supplementation period, showed that the patients in group IV were 5.6 times more likely to enter the normal range than those in group I (OR= 5.6, 95% CI: 0.03 - 3.13). Compared to group I, reaching the normal range was 90% and 66% less likely in group II (OR= 0.1, 95%CI: 0 - 1.53) and group III (OR= 0.34, 95%CI: 0.03 - 3.13), respectively.

The linear regression analysis showed that in case of a constant initial mean of plasma tHcy levels, supplementation with 15 mg/day FA + vitamin B 12 might reduce plasma tHcy levels by 5.27 µmol/L ((3= -5.27, SE(R)= 2.28, P= 0.027) in comparison to group I.

Effect of supplementation on serum FA levels

The changes of serum FA levels were not significant in any of the 4 study groups [Table 2]. Supplementation with 5 mg/d FA + vitamin B12 did not result in a significant decrease in the mean serum FA levels [Table 2].

Changes of serum FA levels were the highest in the group receiving 15 mg/d FA + vitamin B 12 and negative in the group receiving 5 mg/d FA + vitamin B 12 [Figure 2].

Linear regression analysis showed that in case of a constant initial mean serum FA level, sup­plementation with 15 mg/day FA + vitamin B 12 might increase the mean serum FA levels by 130 ng/mL (R = 130, SE(13) = 50.9, P= 0.015) in comparison to group I.

Effect of supplementation on serum vitamin B 12 levels

The changes of serum vitamin B 12 levels were only significant in group IV (2150± 1539 pg/mL, P= 0.006) in comparison to group I [Table 2]. Supplementation with 5 mg/day FA + placebo for vitamin B 12 resulted in an insigni­ficant decrease in serum vitamin B 12 concen­tration [Table 2].

The changes of serum vitamin B 12 levels increased from group I to IV, which exhibited the greatest increase [Figure 3].

Linear regression analysis showed that supple­mentation with 15 mg/day FA + vitamin B 12 may increase serum vitamin B 12 level by 1642 pg/mL β= 1642, SEβ = 505, P= 0.003) in comparison to group I. This increase is independent of the initial mean of the serum vitamin B 12 levels.

Effect of changes in dietary intake on main study variables

The dietary intake of energy, macronutrients and vitamins related to Hcy metabolism, during the study period is shown in [Table 3]. Based on ANOVA for repeated measurements, the changes in dietary intake of energy (P= 0.05), protein (P= 0.001) and fat (P= 0.031) were significant during the study period. Linear regression ana­lysis showed no correlation between the changes of plasma tHcy levels and the changes in die­tary intake of energy including protein and fat. The changes in the dietary intake of other nut­rients assessed in the study were not significant.


   Discussion Top


The results of our study demonstrate that sup­plementation with 15 mg/day of FA + 1 mg/day of vitamin B 12 resulted in a 30 percent (sta­tistically significant) reduction in plasma tHcy concentrations. This finding supports the findings of the studies by Koyama et al and Manns et al, [22],[23] but is different from the results of studies conducted by Billion et al and Trimarchi et al. [1],[46]

Billion et al could normalize plasma tHcy levels by 15 mg/d FA FA and vitamin B 12 supp­lements for two months. [1] This and previous stu­dies have shown that the baseline plasma tHcy level is the major predictor of the response to therapy; the higher the tHcy level the better the response, and patients with normal levels of tHcy may show insignificant response. [47],[48] This finding has been confirmed by our study too.

Trimarchi et al supplemented 62 HD patients in 4 groups receiving 10 mg/day oral FA and 500 µg i.v. vitamin B 12 treatments twice per week, alone or together. The changes in plasma tHcy concentrations were not significantly di­fferent in the co-supplemented group in com­parison to the group that received only FA. [46] This result is probably due to the low dose of the FA supplements used, which is the same as the results obtained in group II of our study population (5 mg/day FA + 1 mg/day vitamin B12).

We evaluated the percentage of patients reaching the normal range in each group, as in some studies it was recommended to investigate the changes of this percentage in place of the changes of plasma tHcy levels, which is highly dependent on the baseline tHcy concentrations.

This evaluation showed that the greatest pro­portion of shifts to the normal range occurred in the group IV.

The dietary intakes of the patients revealed no change in dietary intakes of carbohydrates and vitamin B related to Hcy metabolism, during the study period. The changes in dietary intakes of energy, protein and fat were statistically sig­nificant in this period but these changes had no effects on the changes of plasma tHcy concen­trations in our study groups.

Comparing serum FA concentrations, before and after the supplementation period, showed no significant change, whereas the analysis bet­ween groups showed a statistically significant change in the group IV in comparison to the reference group. These findings are in accor­dance with those of the studies by Manns et al and Arnadottir et al, who suggested that sup­plementation with increased dose of FA increa­ses the amount of FA in cells and does not re­sult in significant increase in serum FA. [23],[49]

We also found out that supplementation with 5 mg/d FA + 1 mg/d vitamin B 12 leads to a de­crease in serum FA concentrations in compa­rison to the other groups that exhibited elevated levels of FA, and this is proportional to the amount of FA required within the cells. 5­methyltetrahydrofolate is essential for Hcy me­thylation using vitamin B 12 dependent methio­nine syntase. Supplementation with vitamin B12 increases the intracellular demand for 5-methyl­tetrahydrofolate, which results in a decrease in serum FA levels and an increase in 5 methyl­tetrahydrofolate in the serum. Because serum folate counts for only 1-2% of extracellular fo­late, the distribution of folate between the intra and extracellular compartments severely influen­ces the serum FA levels. The decrease in serum FA is highly dependent on the baseline FA; the higher the baseline levels, the lower are the eventual levels. [50],[51] This decrease was not ob­vious in the group IV in our study, maybe be­cause in these patients the intracellular FA le­vels were sufficient to satisfy the cell demands, which rendered the tHcy methylation pathway less dependent on the serum FA levels.

Comparing serum vitamin B 12 changes within and between groups revealed the significant changes in group IV, which was independent of the baseline levels of serum vitamin B 12 . This finding is in accordance with the results of Elian et al. [27]

The changes of serum vitamin B 12 concen­trations show a strong relationship between the metabolism of FA and vitamin B 12 ; increasing FA consumption results in an increase in serum vitamin B 12 levels. The low dose of FA supple­mentation results in substitution of vitamin B12 in some metabolic pathways, but increasing the dose decreases the utilization of vitamin B12 and thus inhibits the decrease of this vitamin levels in serum. [52] This mechanism explains why increasing the dose of FA in both groups re­ceiving placebo or 1 mg/day vitamin B 12 in­hibits the decline in the serum vitamin B12 levels.

We conclude that oral supplementation with 15 mg/d FA + 1 mg/d vitamin B 12 is effective in reducing tHcy levels in HD patients. The next step is to design randomized, prospective, inter­ventional studies to determine the effect of tHcy reduction on cardiovascular events.


   Acknowledgement Top


This work was financially supported by Shahid Beheshti University of Medical Sciences. We thank Massoud Laboratory ( www.massoudlab. com ) for biochemical assessments; staff of the dialysis ward in Imam Hossein hospital for their technical assistance; library and computer sec­tion in nutrition faculty of Shahid Beheshti Uni­versity of medical sciences and most of all, the dialysis patients who took part in this clinical trial, in spite of all their complications.

Nassim Azadibakhsh designed the study, col­lected and analyzed the data and wrote the ma­nuscript. Rahebeh Shaker Hosseini gave signi­ficant advice and supervised the study in nutri­tional aspects. Shahnaz Atabak advised and mo­nitored the study and analyzed the adverse events. Navid Nateghiyan formulated and ma­nufactured vitamin B 12 supplements. Banafsheh Golestan supervised the statistical analysis.Anahita Hooshyar Rad gave consultation in the dietary assessment.

 
   References Top

1.Billion S, Tribout B, Cadet E, et al. Hyper­homocysteinaemia, folate and vitamin B 12 in unsupplemented hemodialysis patients: effects of oral therapy with folic acid and vitamin B12. Nephrol Dial Transplant 2002;17:455-61.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Nair AP, Nemirovsky D, Kim M, et al. Elevated homocysteine levels in patients with end-stage renal disease. Mt Sinai J Med 2005;72(6):365­73.  Back to cited text no. 2    
3.Righetti M, Ferrario GM, Milani S, et al. effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients. Med Sci Monit 2003;9:137-42.  Back to cited text no. 3    
4.Wang HT, Peng YM, Liu H. Alteration of ho­mocysteine before and after hemodialysis in chronic hemodialysis patients. Hunan Yi Ke Da Xue Xue Bao 2003;28(3):266-8.  Back to cited text no. 4    
5.Friedman AN. Pharmacologic B-vitamin therapy for hyperhomocysteinemia in dialysis patients: has the time come? Nutr Clin Care 2002;5:20-4.  Back to cited text no. 5  [PUBMED]  
6.Arnesen E, Refsum H, Bonaa KH, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995;24:704-9.  Back to cited text no. 6    
7.Alfthan G, Pekkanen J, Jauhiainen M, et al. Relation of serum homocysteine and lipoprotein (a) concentrations to atherosclerotic disease in prospective Finnish population based study. Atherosclerosis 1994;106:9-19.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Verhoef P, Hennekens CH, Malinow MR, et al. A prospective study of plasma homocysteine and risk of ischemic stroke. Stroke 1994;25: 1924-30.  Back to cited text no. 8  [PUBMED]  
9.Taylor LM Jr, DeFrang RD, Harris EJ Jr, Porter JM. The association of elevated plasma homo­cysteine with progression of symptomatic peri­pheral arterial disease. J Vasc Surg 1991;13: 128-36.  Back to cited text no. 9  [PUBMED]  
10.Boushey CJ, Beresford SA, Omenn GS, Mo­tulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995;274:1049-57.  Back to cited text no. 10    
11.Matetzky S, Freimark D, Ben Ami S, et al. Association of elevated homocysteine levels with a higher risk of recurrent coronary events and mortality in patients with acute myocardial infarction. Arch Intern Med 2003;163:1933-7.  Back to cited text no. 11    
12.Gonin JM, Nguyen H, Gonin R, et al. Con­trolled trial of very high dose folic acid, vitamin B 12 and B 6 , intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD. J Nephrol 2003;16:522-34.  Back to cited text no. 12  [PUBMED]  
13.Goldman L, Ausiello D. Cecil textbook of medicine. In: Tolkoff-Rubin N, Goes N. Treat­ment of irreversible renal failure. Saunders; 2004. p. 719.  Back to cited text no. 13    
14.Evans RW, Shaten BJ, Hempel JD, et al. Homo­cysteine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial. Arterioscler Thromb Vasc Biol 1997;17:1947­-53.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.The Heart Outcome Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-77.  Back to cited text no. 15    
16.Bonaa KH, Njolstad I, Ueland PM, et al. Homo­cysteine lowering and cardiovascular events after myocardial infarction. N Engl J Med 2006; 354:1578-88.  Back to cited text no. 16    
17.Guttormsen AB, Ueland PM, Svarstad E, Refsum H. Kinetic basis of hyperhomocystei­nemia in patients with chronic renal failure. Kidney Int 1997;52:495-502.  Back to cited text no. 17  [PUBMED]  
18.Suliman ME, Stenvinkel P, Heimburger O, et al. Plasma sulfur amino acids in relation to cardiovascular disease, nutritional status, and diabetes mellitus in patients with chronic renal failure at start of dialysis therapy. Am J Kidney Dis 2002;40:480-8.  Back to cited text no. 18    
19.Skoupy S, Fodinger M, Veitl M, et al. Ribo­flavin is a determinant of homocysteine plasma concentrations in end stage renal disease pa­tients. J Am Soc Nephrol 2002;13:1331-7.  Back to cited text no. 19    
20.Finkelsteine JD. The metabolism of homo­cysteine: pathways and regulation. Eur J Pediatr 1998;157:s40-4.  Back to cited text no. 20    
21.Toborek M, Hennig B. Dietary methionine imbalance, endothelial cell dysfunction and atherosclerosis. Nut Res 1996;16:1251-66.  Back to cited text no. 21    
22.Koyama K, Usami T, Takeuchi O, Morozumi K, Kimura G. Efficacy of methylcobalamin on lowering total homocysteine plasma concen­trations in hemodialysis patients receiving high dose folic acid supplementation. Nephrol Dial Transplant 2002;17:916-22.  Back to cited text no. 22  [PUBMED]  [FULLTEXT]
23.Manns B, Hyndman E, Burgess E, et al. Oral vitamin B 12 and high dose folic acid in hemo­dialysis patients with hyper homocysteinemia. Kidney Int 2001;59:1103-9.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Bostom AG, Shemin D, Lapane KL, et al. High dose B-vitamin treatment of hyperhomocystei­nemia in dialysis patients. Kidney Int 1996;49: 147-52.  Back to cited text no. 24  [PUBMED]  
25.Pastore A, De Angelis S, Casciani S, et al. Effect of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotype. Clin Chem 2006;52:145-8.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.Hoffer LJ, Saboohi F, Golden M, Barre PE. Cobalamine dose regimen for maximum homo­cysteine reduction in end stage renal disease. Metabolism 2005;54:835-40.  Back to cited text no. 26    
27.Elian KM, Hoffer J. Hydroxocobalamin reduces hyperhomocysteinemia in end stage renal disease. Metabolism 2002;51:881-6.  Back to cited text no. 27    
28.Sombolos K, Fragia T, Natse T, et al. The effect of long-term intravenous high dose B-complex vitamins with or without folic acid on serum homocysteine in hemodialysis patients. J Nephrol 2002;15:671-5.  Back to cited text no. 28  [PUBMED]  
29.Spence D, Cordy P, Kortas C, Freeman D. Effect of usual doses of folate supplementation on elevated plasma homocysteine in hemodialysis patients: No difference between 1 and 5mg daily. Am J Nephrol 1999;19:405-10.  Back to cited text no. 29    
30.Eikelboom JW, Lonn E, Genest J, et al. Homo­cysteine and cardiovascular disease: A critical review of the epidemiologic evidence. Ann Intern Med 1999;131:363-75.  Back to cited text no. 30    
31.Schaefer EJ. Lipoproteines, nutrition and heart disease. Am J Clin Nutr 2002;75:191-212.  Back to cited text no. 31  [PUBMED]  [FULLTEXT]
32.Kasper DL, Braunwald E, Fauci AS, Hauser SL, Longo DL, Jameson JL. Harrison's principles of internal medicine. In: Singh AK, Brenner BM. Dialysis in the treatment of renal failure. USA: McGraw-Hill; 2005. p. 1564.  Back to cited text no. 32    
33.Pfeiffer CM, Twite D, Shih J, et al. Method comparison for total plasma homocysteine between the Abbott IMX analyzer and an HPLC assay with internal standardization. Clin Chem 1999;45:152-3.  Back to cited text no. 33  [PUBMED]  [FULLTEXT]
34.Kopple JD, Massry SG. Kopple and Massry's nutritional management of renal disease. In: Perna AF, Santo NG, (eds). End stage renal disease. Philadelphia: Lippincot Williams & Wilkins; 2004. p. 118.  Back to cited text no. 34    
35.Burtis CA, Ashwood ER. Tietz textbook of clinical Chemistry. In: Fairbanks VF, Klee GG. Biochemical aspects of hematology. USA: W.B. Saunders Company; 1999. p. 1696-7.  Back to cited text no. 35    
36.Anderson SC, Cockayne S. Clinical chemistry, concepts and applications. In: Miller SM, Mears E. Nutritional status assessments. USA: McGraw Hill Companies; 2003. p. 593-6.  Back to cited text no. 36    
37.Burtis CA, Ashwood ER. Tietz textbook of cli­nical Chemistry. In: Johnson AM, Rohlfs EM, Silverman LM. Proteins. USA: W.B. Saunders Company; 1999. p. 529-30.  Back to cited text no. 37    
38.Burtis CA, Ashwood ER. Tietz textbook of clinical Chemistry. In: Newman DJ, Price CP, (eds). Renal function and nitrogen metabolites. USA: W.B. Saunders Company; 1999. p. 1240-4.  Back to cited text no. 38    
39.Mahan LK, Escott-Stump S. Krause's food, nutrition and diet therapy. In: Wilkens KG (ed). Medical nutrition therapy for renal disorders. Philadelphia: Saunders Company; 2000. p. 851-3.  Back to cited text no. 39    
40.Hollander M, Wolfe DA. Non parametric statis­tical methods. In: The two-sample dispersion problem and other two-sample problems. USA: John Wiley and sons' Inc; 1999. p. 178-86.  Back to cited text no. 40    
41.Rosner B. Fundamentals of biostatistics. In: Hypothesis testing: two-sample inference. USA: Wadsworth Publishing Co; 1995. p. 253-6.  Back to cited text no. 41    
42.Mickey RM, Dunn OJ, Clark VA. Applied sta­tistics analysis of variance and regression. In: Linear regression random X model and corre­lation. USA: John Wiley and sons' Inc; 2004. p. 265-76.  Back to cited text no. 42    
43.Mickey RM, Dunn OJ, Clark VA. Applied sta­tistics analysis of variance and regression. In: Linear regression random X model and corre­lation. USA: John Wiley and sons' Inc; 2004. p. 278-84.  Back to cited text no. 43    
44.Rosner B. Fundamentals of biostatistics. In: Hypothesis testing: two-sample inference. USA: Wadsworth Publishing Co; 1995. p. 257-61.  Back to cited text no. 44    
45.Mickey RM, Dunn OJ, Clark VA. Applied sta­tistics analysis of variance and regression. In: Repeated measurement design. USA: John Wiley and sons' Inc; 2004. p. 203-9.  Back to cited text no. 45    
46.Trimarchi H, Schiel A, Freixas E, Diaz M. Randomized trial of methylocobalimin and folate effects on homocysteine in hemodialysis patients. Nephron 2002;91:58-63.  Back to cited text no. 46    
47.Sunder-Plassmann G, Fodinger M, Buchmayer H, et al. Effect of high dose folic acid therapy on hyperhomocysteinemia in hemodialysis patients: result of Vienna Multicenter Study. J Am Soc Nephrol 2000;11:1106-16.  Back to cited text no. 47    
48.Campo A, Goia F, Cottino R, Musso M, Viglino G. Homocysteine, folate therapy and outcome in hemodialysis: results from a prospective study. G Ital Nephrol 2003;20:484-9.  Back to cited text no. 48    
49.Arnadottir M, Gudnason V, Hultberg B. Trea­tment with different doses of folic acid in hemo­dialysis patients: effects on folate distribution and aminothiol concentrations. Nephrol Dial Transplant 2000;15:524-8.  Back to cited text no. 49  [PUBMED]  [FULLTEXT]
50.Loehrer FM, Haefeli WE, Angst CP, et al. Effect of methionine loading on 5 methyltetra­hydrofolate, S-adenosylmethionine and Sade­nosyl homocysteine in plasma of healthy humans. Clin Sci (Colch) 1996;91:79-86.  Back to cited text no. 50    
51.Mansoor MA, Kristensen O, Hervig T, et al. Low concentrations of folate in serum and ery­throcytes of smokers. Clin Chem 1997;43:2193-4.  Back to cited text no. 51    
52.Dierkes J, Domrose U, Ambrosch A, et al. Supplementation with vitamin B 12 decreases homocysteine and methylmolonic acid but also serum folate in patients with end-stage renal disease. Metabolism 1999;48:631-5.  Back to cited text no. 52    

Top
Correspondence Address:
Nassim Azadibakhsh
Postal Code 1965653453, Tehran
Iran
Login to access the Email id


PMID: 19736473

Rights and Permissions


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]

This article has been cited by
1 The application of HPLC for the detection of tHcy and the diagnosis of central retinal artery occlusion
Zhou, H. and Zhang, W. and Wang, L. and Hao, J. and Wang, S. and Zhang, H.
Applied Mechanics and Materials. 2013; 241-244: 805-808
[Pubmed]
2 Role of homocysteine in end-stage renal disease
Wu, C.-C. and Zheng, C.-M. and Lin, Y.-F. and Lo, L. and Liao, M.-T. and Lu, K.-C.
Clinical Biochemistry. 2012; 45(16-17): 1286-1294
[Pubmed]
3 Hyper-homocysteinemia: A novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical Buncertainties
Cacciapuoti, F.
Journal of Thrombosis and Thrombolysis. 2011; 32(1): 82-88
[Pubmed]
4 Comparison of oral folic acid and folinic acid on blood homocysteine level of patients on hemodialysis
Soleimani, A. and Usefzadeh, M. and Mianehsaz, E. and Foroozanfard, F. and Nikoueinejad, H. and Moraveji, S.A. and Nasiri, O. and Rajali, M.
Iranian Journal of Kidney Diseases. 2011; 5(1): 45-49
[Pubmed]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Introduction
    Patients and Methods
    Statistical Analysis
    Results
    Discussion
    Acknowledgement
    References
    Article Figures
    Article Tables
 

 Article Access Statistics
    Viewed4035    
    Printed91    
    Emailed0    
    PDF Downloaded989    
    Comments [Add]    
    Cited by others 4    

Recommend this journal