Administration of B-group vitamins reduces circulating homocysteine in polycystic ovarian syndrome patients treated with metformin: a randomized trial. Effects of Metformin With or Without Supplementation With Folate on Homocysteine Levels and Vascular Endothelium of Women With Polycystic Ovary Syndrome Metformin increases total serum homocysteine levels in non-diabetic male patients with coronary heart disease. Vitamin B12 and homocysteine status during pregnancy in the metformin in gestational diabetes trial: responses to maternal metformin compared with insulin treatment. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. Efficacy of folate and vitamin B12 in lowering homocysteine concentrations in hemodialysis patients. Randomized Trial of Methylcobalamin and Folate Effects on Homocysteine in Hemodialysis Patients Homocysteine Lowering by Folate-Rich Diet or Pharmacological Supplementations in Subjects with Moderate Hyperhomocysteinemia Effect of multivitamins on plasma homocysteine and folate levels in patients on hemodialysis. Randomized, placebo-controlled trial of intramuscular vitamin B12 for the treatment of hyperhomocysteinaemia in dialysis patients. Hyperhomocysteinemia in Japanese patients with convalescent stage ischemic stroke: Effect of combined therapy with folic acid and mecobalamine The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study The effect of vitamin B12 on total plasma homocysteine concentration in folate-replete hemodialysis patients. Prospective, randomized trial of metformin and vitamins for the reduction of plasma homocysteine in insulin-resistant polycystic ovary syndrome. Effect of folate supplementation on serum homocysteine and plasma total antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a double-blind randomized controlled clinical trial. Comparative study of response to treatment with supraphysiologic doses of B-vitamins in hyperhomocysteinemic hemodialysis patients. Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.
BACKGROUND The aim of the current study was to assess the effects of B-group vitamins and folic acid administration on serum levels of homocysteine ( Hcy ) in patients with polycystic ovarian syndrome ( PCOS ) on short-term metformin treatment . METHODS Patients were r and omly assigned to one of three treatment groups . Group 1 patients ( n = 20 ) received metformin ( 850 mg twice daily ) ; group 2 patients ( n = 20 ) received metformin ( 850 mg twice daily ) and B-group vitamins ( vitamin B1 , 250 mg ; vitamin B6 , 250 mg ; vitamin B12 , 1000 microg twice daily ) ; and group 3 patients ( n = 20 ) received metformin ( 850 mg twice daily ) and folic acid ( 174 microg twice daily ) . In all groups , lipid profiles and plasma total Hcy , vitamin B12 , folic acid and glucose levels were recorded at baseline and at 3 months . RESULTS A 26.5 % increase in Hcy levels was seen after 12 weeks of metformin therapy , while 21.17 and 8.33 % decreases in Hcy levels were detected when B-group vitamins or folic acid plus metformin were given respectively . There were no statistically significant differences recorded in insulin sensitivity using homeostasis model assessment in the three groups . CONCLUSION These findings suggest that B-group vitamins and folic acid administration counteract the Hcy-increasing effect seen with metformin therapy OBJECTIVE To evaluate whether the administration of metformin exerts any effects on serum homocysteine ( Hcy ) levels in patients with polycystic ovary syndrome ( PCOS ) and whether supplementation with folate enhances the positive effects of metformin on the structure and function of the vascular endothelium . RESEARCH DESIGN AND METHODS A total of 50 patients affected by PCOS , without additional metabolic or cardiovascular diseases , were enrolled in a prospect i ve nonr and omized placebo-controlled double-blind clinical study . They were grouped into two treatment arms that were matched for age and BMI . Patients were treated with a 6-month course of metformin ( 1,700 mg daily ) plus folic acid ( 400 μg daily ; experimental group , n = 25 ) or placebo ( control group , n = 25 ) . Complete hormonal and metabolic patterns , serum Hcy , folate , vitamin B12 , endothelin-1 levels , brachial artery diameter at the baseline ( BAD-B ) and after reactive hyperemia ( BAD-RH ) , flow-mediated dilation , and intima-media thickness in both common carotid arteries were evaluated . RESULTS After treatment , a significant increase in serum Hcy levels was observed in the control group compared with the baseline values and the experimental group . A beneficial effect was observed in the concentrations of BAD-B , BAD-RH , flow-mediated dilation , intima-media thickness , and serum endothelin-1 in both groups . However , the results were improved more significantly in the experimental group than in the control subjects . CONCLUSIONS Metformin exerts a slight but significant deleterious effect on serum Hcy levels in patients with PCOS , and supplementation with folate is useful to increase the beneficial effect of metformin on the vascular endothelium It is known that the metabolism of homocysteine ( Hcy ) depends on the vitamins B6 , B12 and folate , and furthermore that metformin reduces serum vitamin B12 levels . In order to investigate whether metformin treatment affects serum total Hcy ( tHcy ) levels we performed an open , prospect i ve , r and omised study in 60 non-diabetic male patients with cardiovascular disease . After a 4-week run-in period with lovastatin 40 mg day-1 , and diet and lifestyle advice , patients were r and omised into two groups , both continuing the run-in treatment . One group received metformin up to 2000 mg day-1 , whereas the control group got no additional treatment . After 12 and 40 weeks of metformin treatment , tHcy levels increased moderately but significantly by 7.2 % ( p < 0.05 ) and 13.8 % ( p < 0.05 ) in the metformin group relative to the control group , whereas serum vitamin B12 levels decreased by 13.4 % ( p < 0.0005 ) and 17.7 % ( p < 0.0005 ) , respectively . Serum folate levels did not change after 12 weeks , but decreased by 8.0 % after 40 weeks ( p = 0.061 ) relative to the control group . Serum levels of total cysteine and methylmalonic acid ( MMA ) did not change . In conclusion , metformin treatment increased tHcy levels and decreased levels of vitamin B12 and folate . Since MMA levels were unchanged , it remains an open question whether the increase in tHcy levels is secondary to reduced vitamin B12 levels , folate levels or a combination of both AIM The aim of the study is to compare the effects of metformin and insulin treatment for gestational diabetes mellitus ( GDM ) on vitamin B12 and homocysteine ( Hcy ) status . METHODS Women with GDM , who met criteria for insulin treatment , were r and omly assigned to metformin ( n = 89 ) or insulin ( n = 91 ) in the Adelaide cohort of the metformin in gestational diabetes ( MiG ) trial .  Fasting serum total vitamin B12 ( TB12 ) , holotranscobalamin ( HoloTC ) , a marker of functional B12 status and plasma Hcy concentrations were measured at 20 - 34 weeks ( at r and omization ) and 36 weeks gestation , then at 6 - 8 weeks postpartum . RESULTS Circulating TB12 , HoloTC and Hcy were similar in both treatment groups at each time point . Women who were taking dietary folate supplements  at r and omization had higher serum TB12 and HoloTC at r and omization than those not taking folate . Overall , serum TB12 fell more between r and omization and 36 weeks gestation in the metformin group than in the insulin group ( metformin : -19.7 ± 4.7 pmol/l , insulin : -6.4 ± 3.6 pmol/l , p = 0.004 ) . The decrease in serum TB12 during treatment was greater with increasing treatment duration in metformin-treated ( p < 0.001 ) , but not in insulin-treated women . CONCLUSIONS Total , but not bioavailable , vitamin B12 stores were depleted during pregnancy to a greater extent in metformin-treated  than in insulin-treated women with GDM , but neither analyte differed between groups at any stage . This adds further evidence supporting metformin as a safe alternative treatment to insulin in GDM . Further investigation is needed to evaluate whether women treated with metformin for longer periods in pregnancy require additional B12 or other supplementation OBJECTIVE Metformin is a key treatment option in type 2 diabetes . However , metformin may decrease vitamin B12 levels and increase levels of homocysteine , a cardiovascular risk factor . We investigated whether 16 weeks of treatment with metformin affects serum concentrations of homocysteine , folate and vitamin B12 in subjects with type 2 diabetes treated with insulin . DESIGN Placebo-controlled , r and omized trial . MEASUREMENTS at baseline and 16 weeks later . SETTING This trial was conducted in the outpatient clinics of three general hospitals in The Netherl and s. SUBJECTS A total of 745 patients with type 2 diabetes , treated with insulin and not known with a contraindication for the use of metformin , were approached ; 390 gave informed consent and entered the study . Thirty-seven subjects dropped out ( 12 placebo and 25 metformin users ) . INTERVENTION Addition of metformin or placebo to insulin therapy . PRIMARY OUTCOME PARAMETERS : Serum homocysteine , folate , vitamin B12 , indices of glycaemic control and body weight . RESULTS Amongst those who completed 16 weeks of treatment , metformin use , as compared with placebo , was associated with an increase in homocysteine of 4 % ( 0.2 to 8 ; P=0.039 ) and with decreases in folate [ -7 % ( -1.4 to -13 ) ; P=0.024 ] and vitamin B12 [ -14 % ( -4.2 to -24 ) ; P<0.0001 ] . In addition , the increase in homocysteine could be explained by the decreases in folate and vitamin B12 . CONCLUSION In patients with type 2 diabetes , 16 weeks of treatment with metformin reduces levels of folate and vitamin B12 , which results in a modest increase in homocysteine . The clinical significance of these findings remains to be investigated 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 r and omized 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 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 prospect i ve r and omized 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 ( 24.3 ± 11.8 µmol/l , p < 0.001 ) and similar to group B ( 11.2 ± 1.9 µmol/l , p = n.s . ) . Mean tHcy levels showed a significant decrease in group A from 22.5 ± 15.6 to 10.2 ± 3.1 µmol/l ( p = 0.003 ) and in group B from 19.9 ± 4.0 to 11.2 ± 1.9 µmol/l ( p = 0.012 ) , while no significant changes were observed in groups C ( 25.9 ± 9.3 vs. 27.3 ± 9.7 µmol/l , p = n.s . ) and D ( 26.6 ± 14.3 vs. 24.3 ± 11.8 µmol/l , p = n.s . ) . Conclusion : Oral FA ( 10 mg/day ) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients ; the addition of i.v . Me-Cbl ( 500 µg twice/week ) to this regimen showed no benefit . Separately , FA corrected hyperhomocysteinemia ( HtHcy ) , while Me-Cbl showed no change Background / Objectives : To compare the efficacy of a diet rich in natural folate and of two different folic acid supplementation protocol s in subjects with “ moderate ” hyperhomocysteinemia , also taking into account C677 T polymorphism of 5,10-methylenetetrahydrofolate reductase ( MTHFR ) gene . Subjects/ Methods : We performed a 13 week open , r and omized , double blind clinical trial on 149 free living persons with mild hyperhomocyteinemia , with daily 200 μg from a natural folate-rich diet , 200 μg [6S]5-methyltetrahydrofolate ( 5-MTHF ) , 200 μg folic acid or placebo . Participants were stratified according to their MTHFR genotype . Results : Homocysteine ( Hcy ) levels were reduced after folate enriched diet , 5-MTHF or folic acid supplementation respectively by 20.1 % ( p < 0.002 ) , 19.4 % ( p < 0.001 ) and 21.9 % ( p < 0.001 ) , as compared to baseline levels and significantly as compared to placebo ( p < 0.001 , p < 0.002 and p < 0.001 , respectively for enriched diet , 5-MTHF and folic acid ) . After this enriched diet and the folic acid supplementation , Hcy in both genotype groups decreased approximately to the same level , with higher percentage decreases observed for the TT group because of their higher pre-treatment value . Similar results were not seen by genotype for 5-MTHF . A significant increase in RBC folate concentration was observed after folic acid and natural folate-rich food supplementations , as compared to placebo . Conclusions : Supplementation with natural folate-rich foods , folic acid and 5-MTHF reached a similar reduction in Hcy concentrations Hyperhomocysteinemia is a risk factor for cardiovascular disease in patients on hemodialysis . Causes include genetic enzyme deficiencies , chronic renal failure , and vitamin deficiencies . Homocysteine correlates negatively with folate status . In patients on hemodialysis , supraphysiologic doses of B vitamins and folate reduce homocysteine by 26 - 33 % . No study has examined the effect of a st and ard multivitamin ( Nephro-Vite Rx ) , containing B vitamins and 1 mg of folate , on erythrocyte-folate ( RBC-folate ) and homocysteine in patients on dialysis . We examined RBC-folate and homocysteine levels in 11 stable chronic patients on hemodialysis , mean duration of dialysis 9.8+/-4.1 months , who were not on vitamin or folate supplements  , and repeated these levels after 3 weeks of once daily Nephro-Vite Rx dosage . Plasma homocysteine levels fell by 23.7 % from 27.8+/-5.9 to 21.2+/-6.6 micromol/L ( p = 0.007 ) , whereas RBC-folate levels rose 60 % from 631.2+/-208.3 to 1007.5+/-423.7 nmol/L ( p = 0.001 ) . The optimum dose of B vitamins and folate remains to be established , and a clinical benefit from lowering homocysteine has not yet been demonstrated . In summary , a st and ard multivitamin such as Nephro-Vite Rx reduces plasma homocysteine levels and increases RBC-folate levels in patients on hemodialysis . Our results may have implication s for the modification of cardiovascular risk in these patients BACKGROUND Plasma homocysteine is elevated in patients with end-stage renal disease ( ESRD ) and is a risk factor for cardiovascular disease . Folic acid has been shown to partially reduce homocysteine levels in dialysis patients . It is not known whether vitamin B12 reduces homocysteine independent of folic acid in patients who are not vitamin B12 deficient . AIM To determine whether 1 mg vitamin B12 lowers homocysteine in stable , chronic , haemodialysis patients independent of folic acid . METHODS Twenty-eight haemodialysis patients were r and omized to receive three doses of 1 mg vitamin B12 or 1 mL saline placebo in a double-blind fashion at 1-month intervals . Fasting plasma total homocysteine , folic acid , red-cell folate , vitamin B12 and haemoglobin levels were determined prior to each dose and 4 weeks after the final injection . The study was powered to detect a 30 % reduction in homocysteine over the 3 months . RESULTS Both the two groups were well matched with respect to total homocysteine levels , folic acid , red-cell folate and vitamin B12 levels . Serum vitamin B12 levels were significantly higher in the treatment group compared to placebo ( 217.7 pmol/L ; 95 % confidence interval ( CI ) 103.0 - 332.5 ; P < 0.001 ) at the end of the trial but homocysteine levels were not significantly different ( 3.08 micromol/L ; 95 % CI -4.44 - 10.61 ; P= 0.406 ) . CONCLUSIONS The administration of intramuscular vitamin B12 over a 3-month period does not result in any reduction of plasma homocysteine levels in haemo-dialysis patients independent of folate status , however reductions of < 30 % can not be excluded by the present study . High-dose folic acid remains the treatment of choice in reducing homocysteine , but whether this results in a reduction in cardiovascular events remains to be determined Hyperhomocysteinemia is considered to be a risk factor for vascular diseases including ischemic stroke . It has been shown that plasma homocysteine level can be lowered by folic acid supplementation . Vitamin B(12 ) may be also beneficial when included in the supplement regimen with folic acid . We have examined in Japanese patients with ischemic stroke the homocysteine-lowering potential of a combination therapy with folic acid and vitamin B(12 ) .  Patients with ischemic stroke were r and omized into three groups and each group received vitamin B(12 ) ( 1500 microg/day , n = 63 ) , folic acid ( 5 mg/day , n = 64 ) , or both vitamin B(12 ) and folic acid ( n = 64 ) for 8 weeks . Plasma levels of homocysteine and these vitamins were followed . Significant reduction in plasma homocysteine was observed in all three groups , and the combination therapy yielded the most remarkable result , i.e. , plasma total homocysteine was reduced by 38.5 % and this was significantly larger than the reduction in other two groups ( 22.4 % and 10.9 % in the groups received folic acid and vitamin B(12 ) , respectively ) . Vitamin B(12 ) synergizes with folic acid in reducing plasma homocysteine in Japanese patients with ischemic stroke and the combined therapy may be particularly effective in the secondary prevention Objectives : To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine , an independent risk factor for occlusive vascular disease , in a general population . Design : A r and omized double-blind placebo-controlled intervention study .Subjects : One hundred and nineteen healthy volunteers , whose intake of fortified or supplemental folic acid was low , were recruited by letter from the patient register of a large inner-city group general practice . Methods : Volunteers were r and omized to receive unfortified cereals , or cereals fortified with 200 μg of folic acid per portion , with or without other vitamins . Blood sample s were taken presupplement and at 4 , 8 and 24 weeks on treatment and analysed for plasma homocysteine , cysteine and vitamin B12 and serum and red cell folate .  Ninety-four subjects completed the study providing blood sample s on all four occasions . Results : There were no significant changes in any measured parameter in those eating unfortified cereals . Overall , folic acid fortification of cereals led to significant increases ( P<0.001 ) in serum folate ( 66 % ) , and red cell folate ( 24 % ) , and a decrease in plasma homocysteine ( 10 % ; P<0.001 ) . There were no changes in vitamin B12 or cysteine . The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate . Conclusions : If homocysteine is found to be a causative risk factor in occlusive vascular disease , food fortification with physiological levels of folic acid should have a significant impact on the prevalence of the disease in the general population .Sponsorship : We acknowledge , with thanks , financial support from the Kellogg Company of Great Britain AIM Results from several studies indicate that the total homocysteine ( tHcy ) concentration in plasma is an independent risk factor for cardiovascular disease in hemodialysis patients .  Folic acid is the established mainstay of homocysteine-lowering treatment , but since such treatment does not normalize plasma tHcy concentration in hemodialysis patients , it is of importance to search for additional therapy . METHODS Twenty-eight folate-replete hemodialysis patients were r and omized to 2 equally sized groups , a treatment group and a control group . The treatment group received vitamin B12 tablets at a dose of 2 mg 3 times a week for 6 weeks ( after each dialysis session ) while the control group received no such treatment .  Blood sample s were collected before and at the end of the treatment period for analysis of tHcy in plasma and vitamin B12 , methylmalonic acid as well as folate in serum . RESULTS At the end of the study period , serum vitamin B12 concentrations were significantly higher in the treatment group than in the control group . Plasma tHcy concentrations decreased significantly in both groups during the study period . However , there was no difference between the responses of the 2 groups . CONCLUSION The results of this open , r and omized controlled study did not support the hypothesis that treatment with oral vitamin B12 has considerable homocysteine-lowering effect in folate-replete hemodialysis patients One hundred and two women with insulin-resistant polycystic ovary syndrome were r and omized to treatment with a vitamin B preparation , metformin , or both , in conjunction with st and ard infertility treatment . Plasma homocysteine levels were significantly reduced by both B vitamins and metformin , but to a greater degree by B vitamins , and higher pregnancy rates were associated with vitamin B treatment BACKGROUND AND AIMS Hypercholesterolemia is one of the predisposing factors of cardiovascular diseases . A positive correlation of homocysteine ( Hcy ) concentration with total cholesterol is described . Lovastatin , one of the most administered agents in hypercholesterolemia , is not effective in lowering the level of serum Hcy and increasing serum total antioxidant capacity ( TAC ) . This study was performed to evaluate the effects of folate supplementation on lowering Hcy level and changes of TAC in asymptomatic hypercholesterolemic adults under lovastatin treatment . METHODS This was a double-blind r and omized controlled clinical trial . Forty asymptomatic newly diagnosed hypercholesterolemic individuals were recruited . Patients were r and omized into two groups : group A--20 patients supplemented for 8 weeks with folate ( 5 mg daily ) and group B--20 patients receiving placebo . Lovastatin was administered to both groups . Laboratory lipid profiles , serum Hcy and folate concentration , and TAC were measured at the beginning and after the 8(th ) week of the study period . RESULTS After folate supplementation in group A subjects , serum Hcy was significantly decreased ( 13.35+/-5.01 micromol/L to 8.43+/-2.52 micromol/L , p=0.001 ) , whereas no significant changes occurred in group B ( p>0.05 ) . A significant increase in TAC was only observed in group A ( 1.54+/-0.24 micromol/L to 1.96+/-0.42 micromol/L , p<0.001 ) . CONCLUSIONS Folate supplementation decreases the serum level of Hcy and increases TAC . It seems that a pharmacological dose of folate supplementation could potentially decrease the risk of cardiovascular diseases by reducing serum level of Hcy in adults with hypercholesterolemia BACKGROUND Hyperhomocysteinemia is a well-recognized risk factor for accelerated atherosclerosis in hemodialysis patients . OBJECTIVES 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 . METHODS In a r and omized prospect i ve 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 weeks washout from all folic acid and B-vitamins that were given . MFTHR alleles were analyzed , as were activated protein C resistance , von Willebr and factor and lupus anticoagulant . RESULTS Basal plasma Hcy levels were significantly elevated in hemodialysis patients compared with normal subjects ( 33.8 + /- 4.3 vs. 4.5 to 14.0 micromol/L ) . Following treatment , Hcy levels were significantly reduced to 21.2 + /- 1.6 in group A and 18.6 + /- 1.4 micromol/L in group B ( P < 0.01 ) . There was no difference in Hcy reduction following the administration of either high or low dosage of vitamins B6 and B12 utilized in the present study . There was no correlation between Hcy levels or thrombophilia and high incidence of thrombotic episodes in hemodialysis patients . Genotypic evaluation of MTHFR revealed that the presence of homozygous thermolabile MTHFR ( n = 5 ) was associated with higher Hcy levels and better response to treatment ( Hcy levels decreased by 58 % , from 46.2 + /- 14.6 to 19.48 + 4.1 micromol/ L following treatment ) . In patients with heterozygous thermolabile MTHFR ( n = 25 ) , Hcy levels decreased by 34 % , from 31.2 + /- 3.7 to 18.1 + /- 1.1 micromol/L following treatment . The efficacy of high and low doses of B-vitamins on the reduction of homocysteine levels was comparable . CONCLUSIONS Treatment with B-vitamins in combination with folic acid significantly decreased homocysteine levels in hemodialysis patients , independently of the tested doses . In addition , mutations in MTHFR were associated with elevated plasma levels of Hcy . Neither vascular access nor the presence of diabetes was associated with higher pre- or post-treatment homocysteine level OBJECTIVE Hyperhomocysteinemia occurs in nearly 100 % of patients with end-stage renal disease ( ESRD ) and is associated with increased morbidity and mortality . Means to reduce elevated homocysteine concentrations is supplementation with folic acid , vitamin B6 , and vitamin B12 . However , doses of vitamins required for optimized treatment are subject of debate . Therefore , the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared . DESIGN Patients received 3 times per week either 2 tablets of preparation A ( 800 microg folic acid , 6 microg vitamin B12 , 10 mg vitamin B6 ) , 2 tablets of preparation B ( 160 microg folic acid , no vitamin B12 , 10 mg vitamin B6 ) , or placebo for a period of 12 weeks with control of total homocysteine ( tHcy ) levels at baseline , and at 4 , 8 , and 12 weeks . SETTING The study was performed at the University Hospital of Magdeburg , Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis . RESULTS Preparation A reduced the tHcy concentration significantly by nearly 50 % , whereas preparation B did not change the tHcy concentration in comparison with placebo . However , tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone . Nevertheless , hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation , in contrast with results obtained in healthy volunteers
Therefore , although the overall effect of metformin on the concentration of serum Hcy was neutral , our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given
The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine ( Hcy ) with and without simultaneous supplementation of B-group vitamins or folic acid .