Effects of carbamazepine on serum levels of folic acid and homocysteine

Epilepsy is resistant to drug treatment in about one third of cases, but the mechanisms underlying this drug resistance are not understood. The aim of this study is to assess carbamazepine [CBZ] effect on homocysteine and folic acid occurrence in patients with epilepsy. A total of 45 epileptic outpatients treated by CBZ and 28 sex and age matched healthy controls. The mean of homocysteine and folic acid in epileptic patients were significantly higher 16.46 +/- 1.79 micro mol/L; 8.46 +/- 0.35 ng/ml compared with healthy controls 8.54 +/- 0.64; 10.61 +/- 0.63 [p = 0.0001; p = 0.006, respectively]. Epileptic patients were divided into two groups, therapy-response, and therapy-resistant. Homocysteine serum concentration was significantly higher in the first group of patients [therapy-resistant] compared with healthy controlled group 19.77 +/- 2.96 versus 8.54 +/- 0.64 [p = 0.0001], respectively. However, folic acid concentration was significantly lower in the first group of patients [therapy-resistant] compared with healthy controlled group 7.58 +/- 0.3 versus 10.61 +/- 0.63 [p = 0.001] respectively. In therapy-response group, homocysteine serum concentration was significantly different compared with healthy controlled group [12.3 +/- 1.11 versus 8.54 +/- 0.64], but it remained within the normal value. There was no significant difference in levels of folic acid between the therapy-response group and healthy controlled group 9.55 +/- 0.61 versus 10.61 +/- 0.63 [p = 0.21]. This study demonstrates that epileptic patients taking antiepileptic drug [CBZ] have increased serum levels of homocysteine. Serum homocysteine levels in patients treated with CBZ were higher - up to 50%. The elevated levels of homocysteine may occur due to deficiency of folic acid that is necessary for homocysteine metabolism

[ effect of isotretinoin on plasma homocysteine concentration of patients with acne vulgaris]

Isotretinoin [ISO] revolutionized the treatment of acne since 1980s and there after, severe forms of acne have been treated more effectively, with less residual cosmetic or psychological damage. The use of Isotretinoin is associated with significant side-effects such as mucocutaneous involvement, dyslipidemia and increased liver enzymes. The aim of study was the evaluation of homocysteine [Hey] levels and the responsible vitamins for its metabolism in patients with moderate to severe acne vulgaris undergone ISO treatment. Forty-seven [n=47] patients with acne, prepared with liver function tests, folate, vitamin B12, homocysteine and serum lipids evaluations. Hey was evaluated before [Value 1] and on the 2[nd] month [value 2] of treatment with Isotretinoin [0.5 mg/kg/day], by HPLC methods. Hey levels [value 1: 11.8 +/- 5.3 micro mol/L vs. value 2: 13.6 +/- 7.4 micro mol/L; P<0.001] were statically significantly increased in patients treated with ISO. In addition, lipids and liver enzymes increased in mentioned group. However, there was no significant correlation between Hey levels, vitamins and liver enzymes. Elevated Hey levels in patients after 2 months on ISO treatment might be resulted from liver function disturbances. Folate supplementation along with frequent evaluations of Hey serum levels are strongly reconnnened for the prevention of a premature occlusive disease

[Effects of omega 3 on serum level of malondialdehyde and homocysteine in type 2 diabetic patients]

Diabetes is regarded as a serious condition for both the individual and the society. One of the most important mortality reasons in diabetic patients is atherosclerosis. Many epidemiological studies have shown that the total homocysteine concentration is a risk indicator for cardiovascular disease. Malondialdehyde [MDA] also is a highly toxic by-product formed in part by lipid oxidation derived free radicals. Many studies have shown that its concentration increases considerably in diabetes mellitus. Epidemiological data indicate that the consumption of omega-3 unsaturated fatty acids [O3FA] leads to a reduction in cardiovascular disorders may protect against metabolic diseases. In recent years, numerous researches on omega-3 fatty acids have been done but it cannot be used as a confident additive. So in order to evaluate and compare the effects of omega 3 on malondialdehyde [as fat peroxidation indicator] and homocysteine on diabetic type 2 patients, this research was carried out in Tehran University. A randomized double blind placebo controlled clinical trial was conducted on 81 type 2 diabetic patients, 45-85 years old with diabetes for at least 2 years. Diabetic patients were randomly assigned to one of the case or control groups, each subject received 3 capsules per day of omega-3 or placebo for a period of 2 months. 10 ml blood was collected from each subject at the beginning and at the end of a 2-month trial. Serum MDA was determined with Tiobarbituric acid for more sensitivity and homosystein was measured by Hitachi autoanalyzer with Enzymatic Cycling method. Nutrients intakes were estimated using 24 h dietary recall questionnaire at the beginning and at the end of the 2-month trial for 2 days and analyzed by FPn. T-test also was used to compare groups. Comparing the meant +/- S.D of BMI and food intake in both groups showed no significant differences. MDA level degreased 0.72 nmol/ml in case group but the difference with the control group was not significant but the differences of homosystein level in case [3.10 micro mol/lit] and control [0.126 micro mol/lit] groups were significant. Consumption of omega-3 fatty acids supplementation [3 gr/per day] in capsul form can decrease the serum level of homocysteine in diabetic patients without inducing any changes in MDA level and lipid peroxidation

Avaliação dos níveis séricos de homocisteína em transplantados renais com e sem hipercolesterolemia / Serum homocysteine levels in renal transplant recipients with and without hypercholesterolemia

FUNDAMENTO: A ocorrência de hiper-homocisteinemia parece ser freqüente após o transplante renal. Nenhum estudo até o momento avaliou o papel da homocisteína (Hcy) associada à dislipidemia no Brasil. OBJETIVO: Determinar a prevalência de hiper-homocisteinemia (Hcy sérica >15 mmol/l) em pacientes estáveis submetidos a transplante renal e avaliar o papel dos lipídios séricos e da função do enxerto nos níveis de Hcy sérica. MÉTODOS: Cento e cinco pacientes estáveis submetidos a transplante renal foram avaliados, levando-se em consideração idade, tempo pós-transplante, níveis séricos de colesterol, função do enxerto, proteinúria e uso de ciclosporina (analisados por regressão linear múltipla). A prevalência de hiper-homocisteinemia foi de 74,3 por cento. Os pacientes foram divididos em dois grupos: hipercolesterolêmicos (colesterol total > 200 mg/dl, colesterol LDL > 130 mg/dl) e normocolesterolêmicos. RESULTADOS: Os pacientes hipercolesterolêmicos eram mais velhos, tinham menor tempo pós-transplante, menor depuração de creatinina endógena, maior proteinúria e níveis séricos mais elevados de Hcy. Os pacientes com hiper-homocisteinemia tinham níveis séricos de triglicérides significativamente mais elevados e função do enxerto significativamente pior; além disso, seus níveis de colesterol LDL apresentaram tendência a ser mais elevados. Houve uma correlação positiva entre os níveis séricos de creatinina e de Hcy (r = 0,32; p = 0,01). A análise de regressão linear múltipla revelou que tanto a dislipidemia quanto a função renal afetam de forma independente os valores de Hcy. CONCLUSÃO: Observamos uma alta prevalência de hiper-homocisteinemia em pacientes submetidos a transplante renal, especialmente em hipercolesterolêmicos, sugerindo que uma pior função do enxerto pode influenciar negativamente os níveis séricos de Hcy e colesterol. Estudos futuros deverão investigar se esse perfil metabólico adverso está associado com maior mortalidade cardiovascular...

BACKGROUND: Hyperhomocysteinemia seems to be frequent after renal transplantation. No study so far has assessed the role of homocysteine (Hcy) associated with dyslipidemia in Brazil. OBJECTIVE: To determine the prevalence of hyperhomocysteinemia (serum Hcy >15 mmol/l) in stable renal transplant recipients and to evaluate the role of serum lipids and graft function in serum Hcy levels. METHODS: One hundred and five stable renal transplant recipients were evaluated, considering age, post-transplant time, cholesterol levels, graft function, proteinuria, and cyclosporine (analyzed using multiple linear regression). The prevalence of hyperhomocysteinemia was 74.3 percent. Patients were further divided into two groups, hyper (total cholesterol >200mg/dl, LDL-cholesterol >130mg/dl) and normocholesterolemic. RESULTS: Hypercholesterolemic recipients were older, had shorter post-transplant time, lower endogenous creatinine clearance, and higher proteinuria and Hcy serum levels. Patients with hyperhomocysteinemia had statistically significantly higher serum triglycerides and poorer graft function, and their LDL-cholesterol also tended to be higher. A positive correlation was found between serum creatinine and Hcy levels (r = 0.32, P = 0.01). Multiple regression analysis revealed that both dyslipidemia and renal function independently affect Hcy values. CONCLUSION: We observed a high prevalence of hyperhomocysteinemia in renal transplant recipients, especially in hypercholesterolemic, suggesting that worse graft function may influence serum Hcy and cholesterol levels negatively. Further studies should investigate if this adverse metabolic profile is associated with higher cardiovascular mortality in the long term.

Effect of folic acid supplementation on homocysteine level in postmenopausal women

Hyperhomocysteinemia is an independent risk factor for atherosclerotic diseases including Ischaemic heart disease, stroke and peripheral vascular disease. Homocysteine [Hcy] is an intermediate formed during the catabolism of essential sulphur containing amino acid methionine, increased Hcy is associated with endothelial dysfunctions in healthy human. Plasma Hcy is significantly lower in premenopausal women than young men but after menopause basal homocysteinemia increases significantly in women approaching those in men. Several studies showed that hyperhomocysteinemia to be stronger risk factor for CHD [Coronary Heart Disease] in women than men. It seems likely that altered hormonal status and age related low folate intake are responsible for this. The present study was designed to evaluate the effect of folic acid supplements for six months, on Hcy level in postmenopausal women. Hcy was estimated by Flourescence Polarization Immunoassay [FPIA]. There was a significant [p < 0.001] decrease in Hcy level after six months of folic acid supplements. Hcy is an independent risk factor for atherosclerotic disease, this study favours the view that after menopause Hcy level increases significantly and a simple non Toxic and relatively inexpensive vitamin [folic acid] intervention might be useful in primary cardiovascular prevention in this high risk group because Hcy is a stronger risk factor for CHD in postmenopausal women than men

Disminución de homocisteína plasmática con vitaminas B6, B12 y ácido fólico. Su efecto en la concentración de los lípidos en pacientes con hiperlipoproteinemia secundaria tipo IV, con y sin tratamiento con Lovastatina / Lowering plasma homocysteine with vitamins B6, B12 and folic acid. Effect on lipids concentration in patients with secondary hyperlipoproteinemia type IV, with and without Lovastatina treatment

Se disminuyó la concentración de homocisteina plasmática mediante el uso oral de vitaminas B6 (300 mg/día), B12 (250μg/dνa) y ácido fólico (10 mg/día), y se estudió su efecto en los lípidos de pacientes con hiperlipoproteinemia secundaria tipo IV, durante 120 días, en 30 pacientes, de 45 a 70 años de edad, con infarto al miocardio. Se dividieron en grupo A (n=15) sin tratamiento con Lovastatina y grupo B (n=15) con el hipolipemiante. La homocisteina basal fue de 17,4±1,0 μmol/L y 16,7±1,0 µmol/L para los grupos A y B respectivamente, disminuyendo un 24% al final del tiempo experimental, en ambos grupos. El colesterol total se redujo por debajo de 220 mg/dl, mientras que los triglicéridos disminuyeron 25,4 mg/dl y 27,0 mg/dl en los grupos A y B respectivamente, por cada µmol/L de homocisteina catabolizada. Las lipoproteínas de baja densidad (LDL) y de muy baja densidad (VLDL) disminuyeron significativamente (p<0,005), mientras que las de alta densidad (HDL) se incrementaron en 1,0 mg/dl para el grupo A y 1,15 mg/dl para el grupo B, por cada μmol/L de homocisteina metabolizada, disminuyendo el riesgo coronario en un 28,5% grupo A y 35,9% grupo B. Se concluye que estas vitaminas disminuyen la concentración de homocisteína plasmática, promoviendo la disminución de la concentración de lípidos y lipoproteínas en este tipo de pacientes; mientras que la Lovastatina no reduce la concentración plasmática del aminoácido; pero si ejerce un efecto sinérgico con las vitaminas en la disminución de la concentración de los lípidos, en el grupo B.

The concentration of plasma homocysteine was diminished by the oral use of vitamins B6 (300 mg/day), B12 (250μg/day) and folic acid (10 mg/day), and the effect was studied in the lipids of patient with hiperlipoproteinemia secondary type IV, during 120 days, in 30 patients, 45 to 70 years old, with myocardial heart attack. They were divided in group A (n=15) without treatment with Lovastatin and group B (n=15) with Lovastatin. Basal homocysteine concentration was 17,4±1,0 µmol/L and 16,7±1,0 µmol/L for the groups A and B respectively, diminishing 24% at the end of the experimental time, in both groups. Total cholesterol decreased below 220 mg/dl, while the triglycerides diminished 25,4 mg/dl and 27,0 mg/dl in groups A and B respectively, by each µmol/L of homocysteine catabolissed. Low density lipoproteins (LDL) and very low density (VLDL) diminished significantly (p<0,005), while the high-density (HDL) increased 1,0 mg/dl in group A and 1,15 mg/dl in group B, for each μmol/L of homocysteine metabolized, lowering the coronary risk factor in 28,5% group A and 35,9% group B. We concluded that these vitamins decreased plasma homocysteine concentration, promoting the lowering of lipids and lipoprotein concentratation in this type of patients; while Lovastatin doesn't reduce homocysteine, but it had a synergic effect with the vitamins, dincreasing the lipid concentration, in group B.

Effect of folic acid supplementation on plasma homocysteine levels in patients with coronary artery disease

Our objective was to asses the effect of folic acid supplementation on homocysteine levels in patients with established coronary artery disease. This quasi experimental study was carried out at department of Cardiology, KRL Hospital, Islamabad during the period of May 2002 to December 2003. The patients with raised fasting homocysteine levels were supplemented with 5mg of folic acid and were followed up for a period of six months. The primary end point was the change in homocysteine level and secondary end point was untoward cardiac events. In primary end point, folic acid supplementations decreased mean plasma homocysteine concentration in 17 [56.7%] of the patients with mean change in homocysteine concentration of up to 7.7 +/- 9.3 micro mol/l. There was evidence of substantial interindividual variation in the homocysteine response including an increase in homocysteine in 13 [43.3%] subjects [mean increase 5.5 +/- 10.7 pmol/l]. In secondary end point, three patients were admitted with exacerbation of chronic stable angina; they were ruled out for any myocardial damage. Twenty seven patients had uneventful follow up. The variability of response to folic acid replacement with paradoxical rise in homocysteine levels in certain individuals mandate that we retest the homocysteine level in patients undergoing folic acid replacement to establish its continued salutary response

La hiperhomocisteinemia como factor de riesgo vascular en hemodializados crónicos / Hyperhomocysteinemia as a vascular risk factor in chronic hemodialysis patients

La homocisteína es un factor de riesgo independiente de enfermedad cardiovascular en la población general, y juega un rol protagónico en el desarrollo de la aterogénesis y las trombosis vasculares, sobre todo en pacientes con insuficiencia renal. Así pues, los pacientes en hemodiálisis están bajo los efectos tóxicos de la hiperhomocisteinemia, presente en cerca del 90% de estos pacientes. En nuestra experiencia hemos encontrado que el ácido fólico es un tratamiento eficaz para disminuir los niveles de homocisteína, y el agregado de metilcobalamina intravenosa potencia este efecto; sin embargo, la metilcobalamina por sí sola fue insuficiente para normalizar la homocisteinemia. A lo largo del tiempo, un grupo de pacientes requirió dosis más elevadas de ácido fólico para corregir la hiperhomocisteinemia. Los pacientes homocigotas y, en menor medida hete-rocigotas para la variante termolábil C677T de la enzima metilentetrahidrofolato reductasa (MTHFR), presentaron una actividad catalítica reducida reflejada en la necesidad de una mayor dosis de ácido fólico para normalizar los niveles de homocisteína. Los efectos trombóticos vasculares fueron similares en todos los pacientes respecto a las variantes genéticas de la enzima metilentetrahidrofolato reductasa, sugiriendo que el tratamiento de la hiperhomocisteinemia es importante para disminuir el riesgo de trombosis. Sin embargo, también la hipoho-mocisteinemia, asociada generalmente a estados de desnutrición, se asocia a mayor mortalidad. Si bien se considera a la hiperhomocisteinemia como un factor de riesgo vascular en los pacientes con insuficiencia renal, aún no se determinó en esta población si su corrección se asocia a una disminución de la tasa de enfermedad vascular y de trombosis. No obstante...

Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.