***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The aim of this study was to assess the relationship between total plasma homocysteine ( tHC ) and several markers of endothelial function , coagulation , and pro-inflammatory status in renal transplant recipients . Our own previous study demonstrated the efficacy of folic acid ( FA ) and vitamin B(12 ) ( B(12 ) ) treatment to reduce tHC . Using 70 stable recipients , 56 of whom showed hyperhomocisteinemia ( HHC ) ( tHC > or = 14 micromol/L ) and a control group ( n = 14 , tHC < 14 micromol/L ) , we treated 29 patients in the HHC group ( 10 mg FA and 500 mg B(12 ) daily ) and determined their endothelial function , inflammatory activity , and coagulation status . We assessed plasma levels of von Willebr and Factor and fibrinogen as the prothrombotic profile and C-reactive protein and plasma albumin as inflammation markers . We performed Doppler sonography of the brachial artery to assess endothelial function . The mean value of plasma tHC of 19.05 + /- 3.70 micromol/L before treatment decreased to 13.45 + /- 3.25 micromol/L after 3 months of treatment ( P < .001 ) . The vWF was significantly correlated with tHC ( P < .05 ) and was higher in the HHC patients ( P < .05 ) . The fibrinogen mean level was also significantly higher in HHC patients ( P < .05 ) . The C-reactive protein level was significantly higher and the albumin level was lower among patients with HHC . The endothelium-dependent dilation ( EDD ) correlated with baseline tHC ( P < .05 ) . In preliminary data we observed that homocysteine-lowering therapy may provide cardiovascular protection by enhancing endothelial function , limiting oxidative stress , and reducing procoagulation status BACKGROUND The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid . We evaluated whether a high-dose L-5-methyltetrahydrofolate-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients . METHODS AND RESULTS We block-r and omized 50 chronic , stable hemodialysis patients on the basis of their screening predialysis tHcy levels , sex , and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d ( FA group ) or an equimolar amount ( 17 mg/d ) of oral L-5-methyltetrahydrofolate ( MTHF group ) . All 50 subjects also received 50 mg/d of oral vitamin B(6 ) and 1.0 mg/d of oral vitamin B(12 ) . The mean percent reductions ( + /-95 % CIs ) in predialysis tHcy were not significantly different : MTHF , 17.0 % ( 12.0 % to 22.0 % ) ; FA , 14.8 % ( 9.6 % to 20.1 % ) ; P=0.444 by matched ANCOVA adjusted for pretreatment tHcy . Final on-treatment values ( mean with 95 % CI ) were MTHF , 20.0 micromol/L ( 18.8 to 21.2 micromol/L ) ; FA , 19.5 micromol/L ( 18.3 to 20.7 micromol/L ) . Moreover , neither treatment result ed in " normalization " of tHcy levels ( ie , final on-treatment values < 12 micromol/L ) among a significantly different or clinical ly meaningful number of patients : MTHF , 2 of 25 ( 8 % ) ; FA , 0 of 25 ( 0 % ) ; Fisher 's exact test of between-groups difference , P=0.490 . CONCLUSIONS Relative to high-dose folic acid , high-dose oral L-5-methyltetrahydrofolate-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients . The preponderance of hemodialysis patients ( ie , > 90 % ) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen . This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution The mild fasting hyperhomocysteinemia commonly observed in chronic ( ie , > /=6 months posttransplantation ) renal transplant recipients ( RTRs ) can be effectively treated with combined B-vitamin supplementation featuring supraphysiological doses of folic acid . There are no controlled data evaluating the comparative efficacy of supraphysiological versus st and ard multivitamin dose folic acid supplementation in reducing fasting total homocysteine ( tHcy ) levels among RTRs . We block-r and omized 60 chronic , stable RTRs on the basis of their screening fasting tHcy level to 3 groups of 20 subjects treated for 12 weeks with folic acid  at either 2.4 ( group 1 ) , 0.4 ( ie , st and ard multivitamin dose ) ( group 2 ) , or 0.0 ( group 3 ) mg/d . All 60 study participants also received 50 mg/d vitamin B(6 ) and 0.4 mg/d vitamin B(12 ) . The mean percent reductions ( + /-SEM ) in fasting tHcy were as follows : group 1 , 32.3+/-2.4 % ; group 2 , 23.4+/-2.3 % ; and group 3 , 19.1+/-2.3 % . ANCOVA accounting for the pretreatment matching and adjusted for pretreatment levels of fasting tHcy , folate , and albumin ; change in creatinine during the study ; and  cyclosporine A use revealed significant overall group differences ( P=0.005 ) and significant differences between groups 1 and 2 ( P=0 . 038 ) and groups 1 and 3 ( P=0.001 ) , but not between groups 2 and 3 ( P=0.153 ) . Moreover , a chi(2 ) analysis of participants with pretreatment tHcy levels > /=15 micromol/L ( n=29 ) indicated that a significantly greater proportion of those in group 1 achieved posttreatment levels < 12 micromol/L : group 1 , 5 of 10 ( 50 % ) ; group 2 , 1 of 11 ( 9 % ) ; and group 3 , 0 of 8 ( 0 % ) ( P=0.016 ; test of trend P=0 . 007 ) . We conclude that a supraphysiological dose of folic acid is superior to st and ard multivitamin dosing for the reduction of fasting tHcy levels in chronic RTRs BACKGROUND Mild hyperhomocysteinemia is common among maintenance hemodialysis ( HD ) patients and renal transplant recipients ( RTR ) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups . Relative to their RTR counterparts , the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens , although controlled comparison data are lacking . METHODS We compared the relative responsiveness of ( n=10 ) RTR and ( n=39 ) HD patients with equivalent baseline total homocysteine ( tHcy ) levels ( i.e. , RTR range=14.2 - 23.6 micromol/L ; HD range=14.4 - 24.9 micromol/L ) to 12 weeks of tHcy-lowering treatment . The RTR received 2.4 mg/day of FA , 50.0 mg/day of vitamin B6 , and 0.4 mg/day of vitamin B12 , while the HD patients received 15 mg/day of FA or an equimolar amount ( 17 mg/day ) of the reduced folate , L-5-methyltetrahydrofolate , in addition to 50.0 mg/day of vitamin B6 , and 1.0 mg/day of vitamin B12 . RESULTS The mean percent ( % ) reductions ( + /-95 % confidence interval ) in tHcy were : RTR=28.1 % ( 16.2 - 40.0 % ) ; HD=12.1 % ( 6.6 - 17.7 % ) , P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels . Moreover , ( 50.0 % ) of 10 of the RTR versus only ( 5.1 % ) of 39 of the HD patients had final on-treatment tHcy levels < 12 micromol/L ; P=0.002 for comparison of between-groups differences by Fisher 's exact test . CONCLUSION Relative to RTR with comparable baseline tHcy levels , the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate , L-5-methyltetrahydrofolate . Accordingly , RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic  renal disease BACKGROUND Homocysteine is a risk factor for cardiovascular disease . We evaluated the efficacy of homocysteine-lowering treatment with B vitamins for secondary prevention in patients who had had an acute myocardial infa rct ion . METHODS The trial included 3749 men and women who had had an acute myocardial infa rct ion within seven days before r and omization . Patients were r and omly assigned , in a two-by-two factorial design , to receive one of the following four daily treatments : 0.8 mg of folic acid , 0.4 mg of vitamin B12 , and 40 mg of vitamin B6 ; 0.8 mg of folic acid and 0.4 mg of vitamin B12 ; 40 mg of vitamin B6 ; or placebo . The primary end point during a median follow-up of 40 months was a composite of recurrent myocardial infa rct ion , stroke , and sudden death attributed to coronary artery disease . RESULTS The mean total homocysteine level was lowered by 27 percent among patients given folic acid plus vitamin B12 , but such treatment had no significant effect on the primary end point ( risk ratio , 1.08 ; 95 percent confidence interval , 0.93 to 1.25 ; P=0.31 ) . Also , treatment with vitamin B6 was not associated with any significant benefit with regard to the primary end point ( relative risk of the primary end point , 1.14 ; 95 percent confidence interval , 0.98 to 1.32 ; P=0.09 ) . In the group given folic acid , vitamin B12 , and vitamin B6 , there was a trend toward an increased risk ( relative risk , 1.22 ; 95 percent confidence interval , 1.00 to 1.50 ; P=0.05 ) . CONCLUSIONS Treatment with B vitamins did not lower the risk of recurrent cardiovascular disease after acute myocardial infa rct ion . A harmful effect from combined B vitamin treatment was suggested . Such treatment should therefore not be recommended . ( Clinical Trials.gov number , NCT00266487 . ) OBJECTIVE To study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients . METHODS Thirty-six stable hyperhomocysteinemic renal-transplant recipients were r and omly assigned to vitamin treatment ( group A , n = 18 , folic acid 5 mg/d , vitamin B(6 ) 50 mg/d , B(12 ) 1000 microg/d ) or controlled group ( group B , n = 18 ) for 6 months . All subjects underwent assessment of levels for creatinine , creatinine clearance , average pressure , total cholesterol , triglyceride and fasting homocysteine . Endothelial function was evaluated using high-resolution vascular ultrasound . RESULTS The levels of homocysteine markedly decreased in group A [ ( 13 + /- 4 ) micromol/L vs ( 20 + /- 5 ) micromol/L , t = 5.3 , P < 0.01 ] after treatment , whereas no significant changes were observed in group B. In group A , endothelium dependent [ ( 12 + /- 5)% vs ( 9 + /- 5)% , t = 2.9 , P < 0.01 ] and independent [ ( 18 + /- 4)% vs ( 12 + /- 5)% , t = 3.4 , P < 0.01 ] vasodilatation responses significantly increased after treatment , no significant changes were observed in group B. Endothelium dependent [ ( 9 + /- 6)% , t = 2.8 , P < 0.01 ] and independent [ ( 12 + /- 5)% , t = 3.5 , P < 0.01 ] vasodilatation responses of group A were significantly lower than that of group B after treatment . CONCLUSIONS Vitamin B supplementation can reduce the 
    Output:
    
There is no current evidence to support the use of homocysteine lowering therapy for cardiovascular disease prevention in kidney transplant recipients