Homocysteine Concentrations In Patients Research Articles

Homocysteine concentrations in patients with diabetes mellitus – relationship to microvascular and macrovascular disease

Diabetes, Obesity and MetabolismVolume 7, Issue 2 p. 117-121 Homocysteine concentrations in patients with diabetes mellitus – relationship to microvascular and macrovascular disease Alan N. Elias, Corresponding Author Alan N. Elias Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine Medical Center, Orange, CA, USA *Alan N. Elias, MD, UCI Medical Center, 101 City Drive South, Rt.81, Building 53, Room 218C, Orange, CA 92868, USA E-mail:anelias@uci.eduSearch for more papers by this authorSteven Eng, Steven Eng Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine Medical Center, Orange, CA, USASearch for more papers by this author Alan N. Elias, Corresponding Author Alan N. Elias Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine Medical Center, Orange, CA, USA *Alan N. Elias, MD, UCI Medical Center, 101 City Drive South, Rt.81, Building 53, Room 218C, Orange, CA 92868, USA E-mail:anelias@uci.eduSearch for more papers by this authorSteven Eng, Steven Eng Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine Medical Center, Orange, CA, USASearch for more papers by this author First published: 10 November 2004 https://doi.org/10.1111/j.1463-1326.2004.00376.xCitations: 18Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume7, Issue2March 2005Pages 117-121 RelatedInformation

Plasma Homocysteine and Immune Activation in Patients with Malignant Melanoma Undergoing Treatment with IFN-α

Immune activation and cell proliferation may contribute to the development of increased homocysteine concentrations in patients with malignant diseases. In this study, we investigated the effect of interferon-alpha (IFN-alpha) on plasma homocysteine concentrations in patients being treated for malignant melanoma. In parallel, neopterin formation and tryptophan degradation were monitored to assess the capacity of IFN-alpha to activate macrophages. Plasma concentrations of homocysteine, folate, and vitamin B(12) were determined in 15 patients with malignant melanoma during 12 weeks of high-dose IFN-alpha therapy. Concurrently, concentrations of neopterin, tryptophan, and kynurenine were measured, and the kynurenine/tryptophan ratio (kyn/trp) was calculated. Homocysteine and folate concentrations during treatment with IFN-alpha did not differ from baseline. In contrast, significant increases in neopterin formation and tryptophan degradation were apparent during IFN-alpha therapy. Plasma concentrations of vitamin B(12) and cysteine also increased. These results indicate that IFN-alpha directly activates macrophages to release neopterin and to degrade tryptophan, but obviously treatment with INF-alpha did not affect homocysteine metabolism.

B-group Vitamins Reduce Plasma Homocysteine Concentration in Patients with Type II Diabetes Mellitus and Normal Basal Homocysteine

Purpose: High total plasma homocysteine (tHcy) is an independent risk factor for premature cardiovascular disease/mortality in the general population. tHcy has not been well defined as a risk factor in patients with diabetes mellitus (DM) and, therefore, we sought to investigate tHcy and its response to B-group vitamins in patients with DM. Design: Randomized placebo-controlled intervention study. Patients and Methods: Thirty patients with type II DM, aged 60±10 years (range 42-77 years) were compared with 17 age-matched (range 45-69 years) normoglycaemic subjects. Thereafter, the patients were randomly assigned to either B vitamin (B6, folic acid and B12) (n=18) or placebo (n=12) groups for 4 weeks. tHcy was measured using an amino acid analyzer. Results: Compared with the normoglycaemic patients, there were no differences in respect to tHcy, B12, plasma and erythrocyte (RBC) folate in patients with DM. In the B vitamin treatment group, plasma and RBC folate increased from 9.3±4.1 and 395±188 ng ml−1 to ...

The Plasma Homocysteine Levels Are Increased in Polycystic Ovary Syndrome

Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease risk factors. Since hyperhomocysteinemia is associated with early atherosclerosis, it was postulated that the homocysteine levels are higher in PCOS patients than in control subjects which, therefore, may explain the cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects were studied. Endocrine assays, lipid profile, homocysteine and insulin level determinations, and ultrasound evaluation were performed in all subjects. We found significantly higher mean plasma homocysteine concentrations in patients with PCOS as compared with controls (10.4 ± 4.4 vs. 7.2 ± 1.5 ng/dl; p < 0.003). These data show that in PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile – PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk.

Effect of treatment with folic acid and vitamin B6 on lipid and homocysteine concentrations in patients with coronary artery disease

Effect of treatment with folic acid and vitamin B6 on lipid and homocysteine concentrations in patients with coronary artery disease

Renal function exerts only a minor influence on high plasma homocysteine concentrations in patients with acute coronary syndromes.

It has been suggested that hyperhomocysteinemia observed in patients with occlusive vascular disease is caused by reduced renal function secondary to renovascular disease. We have therefore used serum cystatin C, a new sensitive marker for glomerular filtration, in 59 patients with acute coronary syndromes and high plasma homocysteine (tHcy) concentration to measure renal function. Samples were also obtained from 34 patients with low-normal plasma tHcy and 50 control subjects. The patients with low-normal plasma tHcy concentration showed decreased concentrations of serum cystatin C and serum creatinine and increased concentrations of blood folate and serum cobalamin compared to the controls and to the patients with high plasma tHcy. There was a large overlap in cystatin C concentrations between patients with high and low-normal plasma tHcy. None of the parameters investigated except plasma tHcy were significantly different in the group of patients with high plasma tHcy concentration compared to the control group. In order to further demonstrate the importance of renal impairment, a subgroup of the patients with high plasma tHcy was supplemented daily with folic acid 5 mg, pyridoxine 40 mg and cyancobalamin 1 mg for 3 months. Vitamin therapy reduced plasma tHcy from 18.3+/-4.6 pmol/l to 9.6+/-2.2 pmol/l (p<0.0001). However, vitamin treatment did not strengthen the correlation between cystatin C and plasma tHcy concentrations. These findings do not support the hypothesis that subtle renal dysfunction is an important cause of high plasma tHcy concentration in patients with acute coronary syndromes.

Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease

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. 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. The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. 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. 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.

Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake?

Hyperhomocysteinemia is considered as a risk factor for cardiovascular diseases. Usually, an inverse relationship exists between homocysteine and folate levels, and supplementation with folate lowers homocysteine concentrations in patients. Therefore, hyperhomocysteinemia is mainly ascribed to the insufficient dietary intake of folate. Hyperhomocysteinemia has also been observed in infections and inflammatory diseases. Oxidative stress appears to be involved in the pathogenesis of these disorders, and associations have been found between homocysteine and e.g., neopterin concentration. Increased neopterin concentration indicates immune system activation and also allows an estimate of thus elicited oxidative stress. It may be relevant that the active cofactor, tetrahydrofolate, is very susceptible to oxidation. Immunologically induced oxidative stress could lead to folate depletion resulting in hyperhomocysteinemia. Thus, hyperhomocysteinemia in patients can be considered as an indirect consequence of hyperconsumption of antioxidant vitamins during prolonged states of immune activation.

Homocysteine and endogenous markers of renal function in type 2 diabetic patients without coronary heart disease

The aim of this study was to assess parameters of renal function and other determinants of plasma homocysteine in type 2 diabetic patients without coronary heart disease (CHD). Fasting plasma homocysteine, serum cystatin C and serum creatinine were determined in 183 (75 men, 108 women) Type 2 diabetic patients without clinical evidence of CHD. Creatinine clearance was calculated and parameters such as blood pressure, body mass index (BMI), and glycated haemoglobin (HbA 1c) were assessed. The urine albumin:creatinine ratio was used to classify patients as normo-, micro- or macroalbuminuric. One hundred and ten patients were normoalbuminuric, 67 patients were microalbuminuric and six patients were macroalbuminuric. There was no statistically significant difference in plasma homocysteine concentration between patients with normoalbuminuria and microalbuminuria. There was a trend towards increasing plasma homocysteine with decreasing glomerular filtration rate (GFR) ( r=−0.46; P<0.0001). There was statistically significant correlation between plasma homocysteine and age ( r=0.37), serum cystatin C ( r=0.47), and serum creatinine ( r=0.56). Plasma homocysteine concentration was significantly higher in patients with BMI<30 kg/m 2 and showed significant inverse correlation with weight ( r=−0.16; P=0.03) and body mass index ( r=−0.24; P=0.001). Homocysteine and serum creatinine were significantly higher in males than females and higher in smokers than non smokers but was not associated with glycemic control and duration of diabetes. In conclusion, elevated homocysteine concentration in patients with type 2 DM without CHD is related to age, gender, smoking, BMI and GFR. Follow up studies will provide further information on the association between hyperhomocysteinemia and the development of cardiovascular disease.

Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications?

Patients with inflammatory bowel disease (IBD) are at increased risk for thromboembolic events. Hyperhomocysteinemia, which is an established risk factor for arterial as well as venous thrombosis, may be more prevalent in IBD because of vitamin deficiencies. In this retrospective study, we studied the concentrations of total homocysteine (tHcy), cobalamin, folate, and pyridoxine in 231 consecutive patients with IBD, of whom 16 patients had a history of venous thrombosis, and nine a history of arterial thrombosis. Age- and gender-matched healthy volunteers served as controls (n = 102). Homocysteine concentrations in patients were higher (12.3 micromol/L [range 4.6-51.3] vs 11.1 micromol/L [range 3.9-27.6], p = 0.001) and hyperhomocysteinemia tended to be more prevalent in patients than in the controls (11.1% vs 5%, p = 0.07). Folate, cobalamin, creatinine, and pyridoxine concentrations were correlated with tHcy. Folate deficiency was infrequently encountered in IBD patients (4.3%). The tHcy concentration in patients with a history of venous or arterial thrombosis was not higher than in patients without a history of thrombosis (12.7 micromol/L [range 4.6-40.1] and 15.2 micromol/L (range 10.5-26.8) vs 12.3 micromol/L [range 10.5-26.8], not significant). Hyperhomocysteinemia was found in 18.8% of the patients with venous thrombosis, 11.1% of the patients with arterial thrombosis, and 10.5% of the patients without thrombosis (not significant). Hyperhomocysteinemia is a common phenomenon in IBD and correlates with serum folate, cobalamin, creatinine, and pyridoxine concentrations. No correlation between tHcy and a history of venous or arterial thromboembolic complications is found. Hyperhomocysteinemia does not seem to be a major contributory factor in the development of venous or arterial thrombosis in IBD patients.

Homocysteine in inflammatory bowel disease: a risk factor for thromboembolic complications?

OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk for thromboembolic events. Hyperhomocysteinemia, which is an established risk factor for arterial as well as venous thrombosis, may be more prevalent in IBD because of vitamin deficiencies. METHODS: In this retrospective study, we studied the concentrations of total homocysteine (tHcy), cobalamin, folate, and pyridoxine in 231 consecutive patients with IBD, of whom 16 patients had a history of venous thrombosis, and nine a history of arterial thrombosis. Age- and gender-matched healthy volunteers served as controls (n = 102). RESULTS: Homocysteine concentrations in patients were higher (12.3 μmol/L [range 4.6–51.3] vs 11.1 μmol/L [range 3.9–27.6], p = 0.001) and hyperhomocysteinemia tended to be more prevalent in patients than in the controls (11.1% vs 5%, p = 0.07). Folate, cobalamin, creatinine, and pyridoxine concentrations were correlated with tHcy. Folate deficiency was infrequently encountered in IBD patients (4.3%). The tHcy concentration in patients with a history of venous or arterial thrombosis was not higher than in patients without a history of thrombosis (12.7 μmol/L [range 4.6–40.1] and 15.2 μmol/L (range 10.5–26.8) vs 12.3 μmol/L [range 10.5–26.8], not significant). Hyperhomocysteinemia was found in 18.8% of the patients with venous thrombosis, 11.1% of the patients with arterial thrombosis, and 10.5% of the patients without thrombosis (not significant). CONCLUSIONS: Hyperhomocysteinemia is a common phenomenon in IBD and correlates with serum folate, cobalamin, creatinine, and pyridoxine concentrations. No correlation between tHcy and a history of venous or arterial thromboembolic complications is found. Hyperhomocysteinemia does not seem to be a major contributory factor in the development of venous or arterial thrombosis in IBD patients.

Redox status of plasma homocysteine and other plasma thiols in stroke patients

Despite the growing evidence that plasma homocysteine is a cardiovascular risk factor, the mechanism behind the vascular injuries is still unknown. Studies are difficult as a result of the fact that little is known about the formation of different homocysteine species in vivo. Since extracellular glutathione and cysteine may influence the formation of different homocysteine species, we have in the present study investigated the different fractions of homocysteine and their relation to the different fractions of glutathione and cysteine in stroke patients and control subjects. We found a ratio of about 32–33% between reduced and total plasma glutathione concentrations and 2.6–3.0% between reduced and total plasma cysteine concentrations both in patients and in healthy control subjects. We noted an elevated concentration of total plasma homocysteine in stroke patients, but no difference in the ratio between reduced and total plasma homocysteine concentrations in patients and control subjects (mean value 1.20 and 1.10%, respectively). However, in a subgroup of patients with higher concentrations of total plasma homocysteine, we observed a significantly lower ratio of reduced to total plasma homocysteine compared to a subgroup of patients with lower concentration of total plasma homocysteine. A low reduced/total ratio of plasma homocysteine in combination with elevated plasma homocysteine concentrations might reflect an increased pro-oxidant activity in plasma from these patients. Thus, increased pro-oxidant activity in plasma might be one factor, besides genetic and nutritional factors, that could explain hyperhomocysteinemia. Since substantial evidence indicates that progression of atherosclerosis is related to enhanced pro-oxidant activity, the premature vascular disease associated with increased plasma homocysteine concentration might be as a result of increased pro-oxidant activity and the elevated plasma homocysteine concentration may only reflect the increased oxidative stress.

Whole grain consumption reduces insulin demand, lipid peroxidation and plasma homocysteine concentrations in patients with coronary artery disease

Background:Although current dietary guidelines recommend to increase the consumption of whole grain, these recommendations are mainly derived from the belief that replacing fats with carbohydrate may reduce risk of coronary artery disease (CAD by improving serum lipids. Our objective was to evaluate whether the isocalorical replacement of refined rice with whole grain reduce CAD risk factors such as insulin demand and lipid peroxidation in CAD patients. Methods:Thirty-eight male patients with CAD were provided with 70 g powder of whole grain (220 kcal for 16 weeks, replacing cooked refined rice as a carbohydrate source of breakfast. An oral glucose tolerance test (OGTT was performed in all subjects to determine the effect of whole grain consumption on serum concentrations of insulin and glucose in CAD patients with different degree of glucose tolerance. Results:With the substitution of whole grain for refined rice, serum glucose concentrations decreased by 24% without altering body weight and energy intake. Estimates of daily fiber and vitamin E intakes increased by 24% and 50%, respectively. Whole grain consumption in CAD patients without diabetes decreased fasting glucose (22% and the area under the curve (AUC for insulin (26% and glucose (19% during an OGTT. CAD patients with diabetes also showed reductions in fasting glucose (27% and AUC for glucose (25% during the OGTT, compared with baseline values. Whole grain consumption reduced plasma malon- dialdehyde and homocysteine and urinary 8-epi-prostaglandin F2α concentrations by about 30%. Lipid-corrected concentrations of α-carotene, retinol, α- and γ-tocopherol and lycopene increased by 22-46%, compared with baseline values. Whole grain consumption decreased the percentage composition of ω6 fatty acids of serum phospholipid increased by 14%. Conclusion:The replacement of refined rice with whole grain as a carbohydrate source of a meal showed significant beneficial effects on glucose, insulin and homocysteine concentrations and lipid peroxidation in CAD patients. These effects are likely to substantially reduce the risk factors of CAD and diabetes in CAD patients. (Korean Circulation J 2000;30(6 :693-701

Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease1-3

Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Influence of 5,10-methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine concentration in patients with end-stage renal disease.

The purpose of this study is to observe the influence of the methylenetetrahydrofolate reductase (MTHFR) gene (677C-->T substitution) on plasma homocysteine levels in end-stage renal disease (ESRD) patients who received a relatively large amount of folate (2 mg/d) and are undergoing hemodialysis. A cross-sectional study of plasma homocysteine, vitamin B(12), and folate was performed in patients with ESRD. The study population for the MTHFR gene study included 312 healthy subjects and 106 patients with ESRD undergoing hemodialysis. The C677T transition in the MTHFR gene was detected by HinF 1 restriction enzyme analysis and subsequent electrophoresis in a 3% agarose gel. The genotype of the MTHFR gene in 106 patients with ESRD was homozygous C677T mutation (VV) in 17 patients (16.1%) and heterozygous (AV) in 63 patients (58.4%); 26 patients (24.5%) did not carry this mutation (AA). The mean levels of homocysteine, vitamin B(12), and folate in the patients with ESRD were 23.3 +/- 14.0 mmol/L, 620.2 +/- 98.5 pmol/L, and 138.6 +/- 55.6 nmol/L, respectively. There was no significant difference in homocysteine levels among the three genotypes: 28.2 +/- 19.4 mmol/L for VV, 22.7 +/- 14.9 mmol/L for AV, and 23.4 +/- 11.1 mmol/L for AA genotype (P > 0.05). There was no difference in genotype distribution between the patient groups of less than 25th and greater than 75th percentiles, classified according to plasma homocysteine levels (P = 0.47). In conclusion, with high-dose folate supplementation, the hyperhomocysteinemia in patients with ESRD does not seem to be caused by the 677C-->T mutation in the MTHFR gene.

Plasma homocysteine concentrations in patients with type 1 diabetes.

To determine the plasma concentration of total homocysteine (tHcy), a recognized risk factor for vascular disease, in patients with type 1 diabetes and to examine the relationships with age, sex, duration of diabetes, microvascular complications and neuropathy, and folic acid concentration. Plasma tHcy and folic acid concentrations were measured in a randomly selected cohort of type 1 diabetic patients (n = 119), well characterized as regards microvascular complications, and in a matched control group (n = 51). Plasma tHcy was higher in male than in female control subjects (geometric mean [95% CI]: 9.3 [8.0-10.9] vs. 6.1 [5.2-7.2] micromol/l, P < 0.001), as previously described, but there was no sex difference in diabetic patients. Plasma tHcy significantly correlated with age in patients (r = 0.348, P < 0.01) but not in control subjects (r = 0.007, P = 0.96). Male patients without microvascular complications had lower plasma tHcy concentrations than did male control subjects (6.2 [5.1-7.5] vs. 9.3 [8.0-10.9] micromol/l, P < 0.001), but values in female patients without complications were similar to those of female control subjects. Plasma folic acid concentration was higher in diabetic patients than in control subjects. The expected negative association between plasma tHcy and folic acid was stronger in control subjects than in patients. Subnormal tHcy concentrations in male patients, the absence of a sex difference, and the positive association with age indicate that homocysteine metabolism differs between type 1 diabetic patients and control subjects. Homocysteine is unlikely to be of pathogenic significance in patients, particularly male subjects, with early microvascular disease and/or neuropathy.

4.P.153 The effect of folic acid supplementation on homocysteine concentrations in patients on hemodialysis therapy

4.P.153 The effect of folic acid supplementation on homocysteine concentrations in patients on hemodialysis therapy

Vitamin therapy of hyperhomocysteinaemia in chronic renal failure

s 1933 Vitamin therapy of hyperhomocysteinaemia in chronic renal failure M. Hages, K. Pietrzik Institut fur Ernahrungswissenschaft, Abt. Pathophysiologie der Ernahrung des Menschen. Rheinische Friedrich-Wilhelms-Universitat. Bonn, Germany In patients with chronic renal failure, plasma homocysteine levels are already elevated significantly at an early stage and show a negative correlation with the glomerular filtration rate and serum creatinine concentration, respectively. End-stage renal disease patients on dialysis have homocysteine levels threeor fourfold above normal [1,2]. In several studies moderate hyperhomocysteinemia has been identified as a potential independent risk factor for premature cardiovascular disease, a frequent complication of advanced renal diseases. The mechanism of the atherogenic action of homocysteine is not clearly understood, but it is theorized that homocysteine is cytotoxic to the endothelial wall and promotes the oxidative modification of LDL cholesterol [3]. The elevated homocysteine concentration in patients with renal failure is mainly caused by the decreased catabolism of homocysteine in the proximal tubular cells due to reduced filtration and to tubular dysfunction. Additionally, the extrarenal homocysteine metabolism is decreased due to inhibition by retained metabolites [4]. Homocysteine is an amino acid, which is formed as an intermediate in the metabolism of methionine. Homocysteine can be remethylated to methionine with folic acid as methyl-donor and vitamin B12 as co-factor. Additionally, it can be converted to cystathionine by condensation with serin in an irreversible reaction. This metabolic step requires vitamin B6 as cofactor. The status of vitamin B6, B12, and folic acid is regarded as an important factor influencing the homocysteine level. However, many renal patients with elevated homocysteine concentrations have normal baseline serumand red cell folate levels, as well as normal serum B12 and B6 concentrations. Therefore, it is unlikely that manifest vitamin deficiencies contribute to the elevated homocysteine levels in patients with uraemia and end-stage renal disease. Nevertheless, the folic acid and vitamin B12 status in these patients is negatively correlated with their plasma homocysteine concentration [5,6]. Patients with renal failure, especially dialysis patients, frequently show vascular dysfunction as manifested by an elevated plasma level of von-Willebrand factor (vWF)-antigen, which is reported to be one of the specific markers of endothelial activation and inflammation. The elevated concentration of this indicCorrespondence and offprint requests to: M. Hages, Institut fur Ernahrungswissenschaft, Abt. Pathophysiologie der Ernahrung des Menschen, Rheinische Friedrich-Wilhelms-Universitat, Bonn, Germany. ator of endothelial damage is not only due to the reduced clearance in renal failure because there is no correlation between GFR and the blood level of this factor. Moreover, the level of von-Willebrand factor antigen in dialysis patients is negatively correlated with the duration (years) of hemodialysis [7]. These observations suggest the possibility of endothelial injury. There is in-vitro evidence that homocysteine promotes the release of von-Willebrand factor antigen [8]. However, in most studies, the fasting homocysteine plasma concentration and von-Willebrand factor don't correlate [9]. But after methionine loading test (0.1 g methionine/kg BW), the post-load homocysteine levels showed a significant relationship to the endothelial function parameter [9]. A methionine loading test stresses the pathway involved in homocysteine metabolism and is a valid diagnostic test for an abnormal homocysteine handling. Treatment with high doses of folic acid (5 mg/d) significantly lowers [10,11] the elevated homocysteine concentrations, both in non-dialyzed and in haemodialyzed patients, by the stimulation of the remethylation of homocysteine. This can be observed even in the absence of evident folate deficiency. In patients with mild hyperhomocysteinaemia and peripheral arterial occlusive disease, the vitamin is also able to reduce the elevated levels of von-Willebrand factor and appears to ameliorate the endothelial function [9]. Corresponding studies with renal failure patients are missing. Separate or additive effects of vitamin B6 and/or vitamin B12 on the homocysteine concentration in patients with renal failure have not been observed so far. Further research is needed to identify the optimal therapeutic dose and/or combination of vitamins in the therapy of hyperhomocysteinemia due to renal insufficiency.