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Original Articlehttp://mjiri.iums.ac.ir Medical Journal of the Islamic Republic of Iran (MJIRI)
Iran University of Medical Sciences
____________________________________________________________________________________________________________________1. PhD in Nutrition, Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences,Tehran, Iran. [email protected]. (Corresponding author) PhD, MSPH in Nutrition, Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Teh-ran University of Medical Sciences, Tehran, Iran. [email protected]. MD, PhD. in Epidemiology, Associate Professor of Clinical Epidemiology, Endocrine Research Center (Firouzgar), Institute of Endocrinolo-gy & Metabolism, Iran University of Medical Sciences, Tehran, Iran. [email protected]. MSc. in Medical Library and Information Science, EBM Group, Endocrinology and Metabolism Research Center, Endocrinology and Metab-olism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. [email protected]
Vitamin B12 supplementation in end stage renal diseases: a sys-tematic review
Maryam Amini1, Maryam Khosravi2, Hamid Reza Baradaran3, Rasha Atlasi4
Received: 29 November 2013 Accepted: 3 May 2014 Published: 27 January 2015
AbstractBackground: Hyperhomocysteinemia is a risk factor for cardiovascular disease particularly in patients with
end stage renal disease (ESRD). Vitamin B12 supplementation on its own still remains as a controversial issuefor clinicians in decreasing the level of homcysteine in this group of patients.
Methods: Using all randomized controlled trials (RCTs), clinical trials and pre-post-trial studies found duringJanuary 1999 to March 2014, we conducted a systematic review which assessed the effects of vitamin B12 indecreasing homocysteine levels in patients with ESRD.
Results: The findings of this study revealed that, overall, the greatest effect of B12 supplementation on de-creasing homocysteine levels in patients with ESRDs occurred when it was combined with folate supplementa-tion. It was also demonstrated that injection treatments might be more beneficial than oral intake treatments.
Conclusion: More rigorous studies are needed to draw a firm conclusion about B12 therapy and the level ofhomocyteine in patients with ESRD.
Keywords: Homocysteine, Kidney Failure, Vitamin B12, Hemodialysis, Kidney, Amino Acids, Renal Failure,Review.
Cite this article as: Amini M, Khosravi M, Baradaran H.R, Atlasi R. Vitamin B12 supplementation in end stage renal diseases: a sys-tematic review. Med J Islam Repub Iran 2015 (27 January). Vol. 29:167.
IntroductionHyperhomocysteinemia is an important
risk factor for cardiovascular disease (1).Homocysteine is a nonessential amino acid,and a metabolite for methionine metabo-lism. It has two fates: remethylation to me-thionine which is catalyzed by the vitaminB12 dependent enzyme, methionine synthe-tase, and transsulphuration to cystathionine,and then into cysteine. The two essentialsubstances in the remethylation pathwayare vitamin B12, as a cofactor, and folate asa substrate. Vitamin B6 is another crucialcofactor for transsulphuration of homocys-teine to cystathionine (2). Many of hemodi-alysis patients are B12 depleted (3). Dialy-
sis patients usually have poor nutritionalintake, predisposing them to B12 deficien-cy (4). Moreover, food sources of vitaminB12 contain high concentrations of electro-lytes which are dangerous for dialysis pa-tients, and limit them to foods with low vit-amin B12 content. In addition, B12 is a typ-ical middle-sized chemical molecule to becleared with new high-flux dialyzers (3).Therefore, plasma total homocysteine(tHcy) concentration is noticeably in-creased in end-stage renal disease (ESRD)(5). Furthermore, comparing to patientswith normal renal function, the prevalenceof hyperhomocysteinemia and the resultingdeath caused by atherosclerotic vascular
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disease are substantially greater in ESRDpatients (6). Hcy-lowering therapy is aneffective approach for hyperhomocyste-inemia therapy of ESRD patients (7-9).However, it is controversial whether cobal-amin supplementation alone could be use-ful in lowering the tHcy concentration inthese patients (10). Focusing on this con-troversy, we conducted a systematic reviewto assess the effects of vitamin B12 sup-plementation alone on tHcy concentrationin ESRD patients.
MethodsSearch StrategyWe found no systematic review or meta-
analysis on this subject; therefore, wesearched all English and Persian medicalliterature published from January 1999 toMarch 2014 in PubMed, Google Scholar,Ovid, Cochrane Library, EMBASE, CI-NAHL, Springer, Proquest, Scopus, Web ofScience, Science Direct, SID, Iranmedexand Magiran databases.
The main search key words were as fol-lows: ‘‘vitamin B12’’ AND ‘‘homocyste-
ine’’ AND ‘‘End Stage Renal Disease’’with their synonyms, related words andMedical Subject Headings (MeSH) terms.The search strategy used in the PubMeddatabase can be found in Appendix 1.
A total of 1964 articles were collected, ofwhich 18 were duplicates. Titles of the re-maining articles were reviewed for theirrelevance to the homocysteine loweringeffect of vitamin B12 in end-stage renaldisease. If the articles were potentially rel-evant, then their full texts were retrieved. Afurther 1928 articles were excluded due tofailing to meet the eligibility criteria. Afterreading the full text of the articles, 12 wereexcluded because in those studies vitaminB12 was not administered alone. All thetitles and abstracts which were derivedfrom the searches were extracted by a re-viewer. In the event that the reviewer de-termined that an article did not meet theeligibility criteria, then the article wouldhave been rejected on initial screening. Anevaluation of the full texts was conductedby a review team. Two reviewers evaluatedthe full articles separately.
Fig.. 1. Flowchart of the Procedure used to Select the Relevant Articles
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Any disagreements between the reviewerswere resolved by discussion until consen-sus was reached.
Inclusion CriteriaRandomized controlled trials (RCTs),
clinical trials and pre-post-trials were se-lected for this systematic review. The focuswas on dialysis patients with end-stage re-nal disease. Figure 1 demonstrates the pro-cedure applied to select the relevant arti-cles.
ResultsOnly 6 out of the total of 1964 articles
were eligible for the systematic review.Most of these studies were trials (RCTs,cross over and prospective), and only onestudy was quasi-experimental (pre-post-treatment) (Table 1). These studies wereheterogeneous with respect to the followingfactors: type of administration (oral or in-travenous), chemical construction of B12(hydroxycobalamin, methycobalamin, cya-nocobalamin or not defined), duration ofintervention, period of outcome assessment,study design and quality (Table 1). There-
Table 1. Methodological Description of the Included StudiesAuthor/Year/Location
Samplesize
Type ofStudy
Intervention/Comparison(Study Arms)
Study Exclusion/InclusionCriteria
Comments
Chiu,Y.W.2009,Taiwan [11]
75 RCT I: Received vitamin B121mg/week intravenouslyfor 3 monthsC: Received folinic acid3mg/week intravenouslyfor 3 monthsCombination group:Received intravenoussupplementation withboth agents weekly for 3months
Inclusion criteria:-Hemodialysis patientswithout any acute illness
Masking wasNOT reported.Method of ran-dom allocationwas not men-tionedHemodialysisperiod was notsimilar in dif-ferent arms ofthe study.
Pastore, A. 2006,Italy [10]
200 RCT(crossover)
Group 1: Based on 3genotypes CC, CT andTT, Initially receivedcobalamin 1250 µg perweek for 2 months, oral-ly, then received 15 mgfolic acid daily for 8weeks, orally.Group 2: Initially re-ceived folic acid 2months, then B12 fornext 2 months.
Exclusion criteria:-Receiving folic acidand/or vitamin B12 beforethe studyInclusion criteria:-All patients had baselinetHcy concentrations >20µmol/L-All had been undergoingHD for at least 3 monthsand duration of 4 h eachtime.
Loss to follow-up was as highas 52% but notconsidered inthe analysis(Itention to treatanalysis).Study was sin-gle-blinded.
Polkinghorne,2003,Austrailia [2]
28 RCT I: Received hydroxyco-balamin 1 mg per monthfor 3 months, adminis-tered by intramascularinjection.C: Received placebo(saline) for 3 months
Exclusion criteria:-Current high dose folicacid supplementa-tion(>5mg/w)-Vitamin B12 deficiency-Past medical history ofcancer or inflammatorybowel disease- Recent return to dialysisafter transplantation, im-minent live donor trans-plant-Current use of antifolateor anti convulsant medica-tionInclusion criteria:-Age>18y- Hemodialysis at least 1month prior to recruitment
The participantsand the investi-gator wereblind; however,nurses whoinjected paceboor B12 were notblind.Power is notlarge enough toshow smallchanges (lessthan 30%).
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fore, it was not appropriate to synthesizethe results for a meta-analysis.
The findings of the trials and quasi-experimental studies are summarized inTables 2 and 3, respectively.
Six interventions administered B12 alone.All 5 selected trials applied B12 in at leastone study arm (2, 10-13).
There were four groups in Chiu’s study(Table 1) (11). In one group, B12 was in-jected alone while all other three groupshad taken folate in advance. In the final as-sessment, the blood levels of tHcy weredecreased significantly in all groups, in-cluding the group which received B12alone. However, the combination groupshowed an added effect, indicating the syn-ergistic role of folate and B12 in tHcy low-ering.
In Polkinghorne’s trial (2), one mg vita-min B12 was administered intramuscularlyin one group to determine whether B12,without the effect of folic acid, could lowerthe homocysteine (Table 1). However, intheir study, the tHcy concentration was notdifferent in the two groups at the end of the
intervention. Therefore, they concluded thatthere was no decrease in tHcy levels withinthe three months of intramuscular admin-istration of B12 alone.
Arnadottir (13) held a trial on folate-replete hemodialysis patients. The treat-ment group received vitamin B12 tablets(orally) at a dose of 2 mg 3 times a weekfor 6 weeks while the control group re-ceived no treatment. At the end of the studyperiod, plasma tHcy concentration de-creased significantly in both groups with nodifference between them.
There were four study arms in Tri-marchi’s study (12). One group receivedonly 500 µg Me-Cobalamin twice a week,but at the end of the study, no significantchanges of tHcy level was observed in thisgroup, indicating the minor role of B12 intHcy level correction.
The role of genotype in the reduction oftHcy was discussed in two different studies.In a cross-over design, Pastore et al. (10)compared the effect of folate and B12 sup-plementation on Hcy (homocysteine) re-duction. Consecutive vitamin therapy de-
Table 1. ContinuedArnadottir,M.,2003,Sweden [13]
28 RCT I: Received 2mg B12 tablets 3times a week for 6 weeksorallyC: Received no such treat-ment
Nothing men-tioned
Participants orthe researcherswere not blind;control groupdid not takeplacebo.
Trimarchi H.2002Argentina [12]
62 ProspectiveRandomized
trial
I: Group A receivedmethylcobalamin 500 microgram twice/week plus folicacid 10 mg/day; group B re-ceived folic acid 10 mg/dayalone; group C received novitamin supplementation, andgroup D was on Methylcobal-amin 500 micro gramtwice/week alone.C: folic acid 10 mg/day alone;no vitamin supplementationfor 4 months postdialysis
Exclusion crite-ria:-Previous vitaminsupplementationInclusion criteria:-Patients between19 and 86 y-Requiring HDfor at least 5months
Randomizationand blindnesswas not de-scribed in thestudy.The study wassingle-blinded.
Dierks, J.1999Norway [5]
14 Quasi-experimental
Before: Cyanocobalamin,1mg per week for 4 weekswas administered in B12 defi-cient participants Intravenous-ly.After: Changes of tHcy afterthe injection of vitaminB12was measured.
Inclusion criteria:-low serum co-balamin concen-trations
The sample sizewas too small.Inclusion orexclusion crite-ria was notdefined exactly.
I: Intervention, C: Comparison
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creased tHcy in both groups and the de-crease was genotype-dependant.
Only one study was conducted based on abefore/after design (5). In this study, theeffect of intravenous injection of cyanoco-balamin was investigated in ESRD patientswith low serum cobalamin concentration.
Because tHcy concentration was unequalamong these studies at baseline, plasmatHcy decreased significantly either withnormal or deficient levels of tHcy. In asemi-experimental study, Dierkes et al. (5)concluded that the tHcy lowering effect ofB12 may be due to the reduction of cellular
tHcy rather than renal clearance, and it isinfluenced by genotype.
DiscussionTo our knowledge, this was the first re-
view to focus on the role of B12 alone inlowering tHcy in patients with end-stagerenal disease. A significant proportion ofESRD patients have physiological vitaminB12 deficiency. These patients may have adefect in their ability to convert vitaminB12 into its active form, hydroxylcobala-min, which is needed for homocysteine me-tabolism (14-15). In addition, transcobala-
Table 2. Findings of the Included Studies (Randomized Controlled Trials)Author Control
mean dif-ference
% ofchangefor con-
trolgroup
P value forcontrol group
Interventionmean differ-
ence
% of changefor interven-tion group
P value forintervention
group
Differencebetweencontrol
and othergroups
P valueChiu 2009 3.3 ↓16.4 <0.05 5.9 ↓29.3 α <0.05 <0.005
7.8 ↓38.9 β <0.05 NSPastore2006
Group1 γ
CC 25.2 ↓35.39 0.021 5.3 ↓8.5 0.2 Not appli-cable
CT 81.4 ↓60.97 <0.05 16.7 ↓19.4 0.41 Not appli-cable
TT 221.7 ↓74.49 <0.01 101 ↓32.52 0.135 Not appli-cable
Group2 δ
CC 26 ↓45.61 0.2 17 ↓36.95 <0.05 Not appli-cable
CT 44.3 ↓63.92 <0.05 12.1 ↓23.22 0.169 Not appli-cable
TT 88.5 ↓42.24 0.237 -8.8 ↑11.62 0.497 Not appli-cable
Polkinghorne2003
-2 ↑8.22 - 2.01 ↓7.89 ε - 0.4
Arnadottir 2003 5 ↓23.15 <0.05 3.6 ↓17.3 κ <0.01 NSTrimarchi 2002 -1.4 ↑5.4 NS 12.3 ↓54.6 λ 0.003 <0.001
8.7 ↓43.7 μ 0.012 <0.0012.3 ↓8.6 ν NS NS
α: Vitamin B12 administered 1mg/week intravenously for 3 monthsβ: IV supplementation with folinic acid 3mg plus B12 1mg intravenously for 3 months/weekγ : Initially received cobalamin 1250 µg per week for 2 months, orally, then received 15 mg folic acid daily for 8 weeks, orally.δ : Initially received folic acid 2 months, then B12 for next 2 monthsε: Hydroxycobalamin 1 mg/month for 3 months admininstered by intramuscular injectionκ: B12 tablets 2mg, administered 3 times a week for 6 weeks orallyλ: Received methylcobalamin 500 micro gram twice/week plus folic acid 10 mg/dayμ: Received folic acid 10 mg/day aloneν: Received methylcobalamin 500 micro gram twice/week aloneNS: Not significantNA: Not Applicable
Table 3. Findings of the Included Quasi-Experimental StudyAuthor Defference between baseline
and final assessment (median)% of change Difference between before
and after(P value )Dierkes 1999 CC 13.2 ↓38.15 NS
CT,TT 12.2 ↓26.69 NSAll 11.4 ↓27.94 0.01
NS: Not significant
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min II, which is necessary for the entry ofvitamin B12 into tissues, may be impairedin ESRD (6, 14-15). Therefore, tHcy con-centration increases in patients with ESRD.It is debatable whether vitamin B12 sup-plementation alone could reduce tHcy con-centration in these patients. Moreover, it isreported that folate supplementation canlower the high levels of homocysteine inESRD patients (16-18). However, it is notclear whether vitamin B12 could reducehomocysteine without the high-dose of fo-lic acid. In the current review, all the in-cluded studies administered B12 alone, butwith different approaches.
In Chiu’s study, the reduction of tHcy inB12 group was significantly more than theFolinic acid group (Table 2). It is also not-ed that the combined supplementation wasthe most effective method (11). In thisstudy, there was no significant differencebetween the patients with respect to age,sex, MTHFR C667T genotype, plasma lev-els of folic acid, VitB12, or tHcy level atbaseline. However, the only differenceamong the patients was the period of he-modialysis at that time. Therefore, the tHcylevel of the vitamin B12 group might havebeen affected by the difference in hemodi-alysis duration (11).
In Polkinghorne’s trial (2), patients withcurrent high dose supplementation with fo-late were not included in the study. Thelevels of B12 and folate in serum werenormal in these patients, but the haemodi-alysis period was in a very wide range; andthis may cause mixed results and could beadjusted initially. Compared with anotherstudy (20), the supplemental dose of B12 inPolkinghorne’s study (2) appears to be toolow (1 mg/month vs. 2-3 mg/week) whichmay have led to such a result.
Arnadottir et al. held a trial on folate-replete hemodialysis patients (13). Thestudy samples were on hemodialysis for atleast 3 months and had all been receivingfolic acid in advance. However, the simul-taneous decrease of serum homocysteineconcentration was not consistent in the con-trol and intervention groups; this point was
not well described by the article (13). Thisresult may be due to the confounders whichwere not considered by the researcher inadvance, which makes the result rather un-reliable.
In Trimarchi’s study, the random alloca-tion, blindness of patients and having acontrol group were almost impeccable (12).
In Pastore’s study, the consecutive vita-min therapy lowered tHcy in both groups,and the decrease was genotype-dependant(10). In Fodinger’s study, despite the roleof genotype and folate in the tHcy concen-tration, B12 administration made no chang-es in ESRD patients (20). The results of thelast two studies indicated that the effect ofB12 on tHcy should be measured in pa-tients with normal serum folate. This find-ing is inconsistent with that of the Dierk’sstudy, in which the level of serum folatewas normal, but B12 level was low andB12 supplementation lowered tHcy by 35%(5). In a study by Trimarchi, the patientsreceived no supplementation in advance,and B12 supplementation resulted in nochanges in the tHcys level (12).
Only one study was performed based on aquasi-experimental design (5). In thisstudy, the intravenous injection of cyano-cobalamin lowered the tHcy level in ESRDpatients with low serum cobalamin concen-trations. The author suggested that the re-duction of cellular tHcy was the cause, ra-ther than the renal clearance, which is in-fluenced by genotype. With respect to theresult of the study, some points should beconsidered. First, the result was probablydue to the low baseline serum cobalamin inpatients. In other words, the correction ofB12 deficiency, rather than B12 supple-mentation, was effective. Furthermore, ac-cording to the article, sample size was toosmall to represent a significant difference.And finally, the study design could havebeen more improved by having a controlgroup. One strong point of the study wasthe inclusion of genotype. They indicatedthat the reduction of homocysteine levels inpatients with CC genotype is much morethan in those with T allele (CT, TT). It
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seems that the essential role of cobalaminin remethylation of tHcy was the reasonbehind the simultaneous reduction of ho-mocysteine and folate levels. They con-cluded that folate is used as substrate andthis cycle is influenced by genotype (5).
ConclusionIn all the included studies, the design,
dosage of supplements, method of applica-tion, status of other supplements and treat-ments were different, and this makes thefinal conclusion relatively difficult. Itseems that the maximum effect of B12supplementation in ESRD patients is yield-ed by injection, rather than oral intake. Fur-thermore, the administration of pharmaco-logic dosage of B12 in combination withfolate makes it more efficient. Conductingfuture studies with randomized controlleddesign, sufficient sample size and on pa-tients with normal level of folate and B12 ishighly recommended to clarify the effect ofB12 supplementation on tHcy concentra-tions in ESRD.
AcknowledgementsThe authors wish to thank Hossein Ansa-
ri, Javad Tarrahi, Dr. Sakineh Shabbidarand Dr. Hadi Tabibi for their technical andvaluable comments.
Appendix-1Search Strategy in PubMed:("Vitamin B 12"[Mesh] OR "Vitamin B
12 Deficiency"[Mesh] OR "factor III, vita-min B 12" [Supplementary Concept] OR"Vitamin B Complex"[Mesh] OR "VitaminB Complex" [Pharmacological Action] OR"Vitamin B Deficiency"[Mesh] OR (vita-min AND ("b12" OR "b 12")) OR Cyano-cobalamin OR Cobalamins OR CobalaminOR "HMQC" OR ("factor III" AND cor-rinoid) OR "5-hydroxybenzimidazolylcobamide" OR "5-hydroxybenzimidazolylcobamid" OR "5hydroxybenzimidazolylcobamide" OR "5hydroxybenzimidazolylcobamid")
AND("Hyperhomocysteinemia" [Mesh] OR
"Homocysteine"[Mesh] OR "Homocys-tine"[Mesh] OR "Homocystinuria"[Mesh]OR Hyperhomocysteinemias OR homo-cystinuria OR homocysteine OR homocys-tine OR "thcy" OR "hcy" OR "2-amino-4-mercaptobutyric acid" OR "2 amino 4 mer-captobutyric acid")
AND("Kidney Failure, Chronic"[Mesh] OR
"Renal Dialysis"[Mesh] OR "Ure-mia"[Mesh] OR "Renal Insufficien-cy"[Mesh] OR "Renal Replacement Thera-py"[Mesh] OR "Hemofiltration"[Mesh] OR"Hemodiafiltration"[Mesh] OR "Ultrafiltra-tion"[Mesh] OR "Kidneys, Artifi-cial"[Mesh] OR ((Kidney OR RENAL)AND (End-Stage OR End Stage OR failureOR Insufficiencies OR Insufficiency ORreplacement OR artificial)) OR (ChronicAND (Kidney OR RENAL) AND (FailureOR Insufficiencies OR Insufficiency )) ORESRD OR ((Dialyses OR Dialysis) AND(Renal OR Extracorporeal)) OR Hemodial-ysis OR Hemodialyses OR Uremias ORUremia OR Hemofiltration OR Ultrafiltra-tion OR Hemodiafiltration)
References1. Ross C, et al. Modern Nutrition in Health and
Diseases. 11th edition ed. 2012: LippincottWilliams & Wilkins.
2. Polkinghorne K.R, et al. Randomized, placebo-controlled trial of intramuscular vitamin B12 forthe treatment of hyperhomocysteinaemia in dialysispatients. Intern Med J, 2003. 33(11): p. 489-94.
3. Saifan C, et al. Treatment of confirmed B12deficiency in hemodialysis patients improvesEpogen (R) requirements. Int J Nephrol RenovascDis, 2013. 6: p. 89-93.
4. Iqbal N, et al. Serum methylmalonic acid andholotranscobalamin-II as markers for vitamin B12deficiency in end-stage renal disease patients. AnnClin Lab Sci, 2013. 43(3): p. 243-9.
5. Dierkes J, et al. Supplementation with vitaminB12 decreases homocysteine and methylmalonicacid but also serum folate in patients with end-stage renal disease. Metabolism, 1999. 48(5): p.631-5.
6. Hyndman M.E, et al. Vitamin B12 decreases,but does not normalize, homocysteine andmethylmalonic acid in end-stage renal disease: alink with glycine metabolism and possibleexplanation of hyperhomocysteinemia in end-stage
Dow
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mjir
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Vitamin B12 supplementation in end stage renal diseases…
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renal disease. Metabolism, 2003. 52(2): p. 168-72.7. Billion S, et al. Hyperhomocysteinaemia,
folate and vitamin B12 in unsupplementedhaemodialysis patients: effect of oral therapy withfolic acid and vitamin B12. Nephrol DialTransplant, 2002. 17(3): p. 455-61.
8. Elian K.M, and Hoffer L.J. Hydroxocobalaminreduces hyperhomocysteinemia in end-stage renaldisease. Metabolism, 2002. 51(7): p. 881-6.
9. Heinz J, et al. B vitamins and the risk of totalmortality and cardiovascular disease in end-stagerenal disease: results of a randomized controlledtrial. Circulation, 2010. 121(12): p. 1432-8.
10. Pastore A, et al. Effects of folic acid beforeand after vitamin B12 on plasma homocysteineconcentrations in hemodialysis patients withknown MTHFR genotypes. Clin Chem, 2006.52(1): p. 145-8.
11. Chiu Y.W, et al. Pharmacological dose ofvitamin B12 is as effective as low-dose folinic acidin correcting hyperhomocysteinemia ofhemodialysis patients. Ren Fail, 2009. 31(4): p.278-83.
12. Trimarchi H, et al. Randomized trial ofmethylcobalamin and folate effects onhomocysteine in hemodialysis patients. Nephron,2002. 91(1): p. 58-63.
13. Arnadottir M, and B Hultberg. The effect ofvitamin B12 on total plasma homocysteineconcentration in folate-replete hemodialysispatients. Clin Nephrol, 2003. 59(3): p. 186-9.
14. Vrentzos G.E, et al. Intravenousadministration of vitamin B12 in the treatment ofhyperhomocysteinemia associated with end-stagerenal disease. J Nephrol, 2003. 16(4): p. 535-9.
15. Manns B, et al. Oral vitamin B(12) and high-dose folic acid in hemodialysis patients with hyper-homocyst(e)inemia. Kidney Int, 2001. 59(3): p.1103-9.
16. Koyama K, et al. Efficacy ofmethylcobalamin on lowering total homocysteineplasma concentrations in haemodialysis patientsreceiving high-dose folic acid supplementation.Nephrol Dial Transplant, 2002. 17(5): p. 916-22.
17. Sunder-Plassmann G, et al. Effect of highdose folic acid therapy on hyperhomocysteinemiain hemodialysis patients: results of the Viennamulticenter study. J Am Soc Nephrol, 2000. 11(6):p. 1106-16.
18. Dierkes J, et al. Response ofhyperhomocysteinemia to folic acidsupplementation in patients with end-stage renaldisease. Clin Nephrol, 1999. 51(2): p. 108-15.
19. Henning B.F, et al. Homocyst(e)inemetabolism in hemodialysis patients treated withvitamins B6, B12 and folate. Res Exp Med (Berl),2001. 200(3): p. 155-68.
20. Fodinger M, et al. Effect of TCN2 776C>Gon vitamin B12 cellular availability in end-stagerenal disease patients. Kidney Int, 2003. 64(3): p.1095-100.
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