Increased Homocysteine Concentrations Research Articles

Evaluation of sensomotor development, behavioral reactions and cognitive functions of the second generation of rats with hyperhomocysteinemia

The adverse maternal exposure during pregnancy leads to developmental disorders in the offspring that can be passed on to later generations. Epigenetic regulation of DNA transcription may mediate inherited metabolic diseases. An increase in homocysteine concentration in the blood is associated with epigenetic modifications of the genome, which can alter the fetal brain’s development program and cause cognitive impairment. The aim of our work was to identify changes in sensomotor development, behavioral reactions and cognitive functions of offspring of second generation rats (HcyF2) of hyperhomocysteinemia. Our results indicate that unconditioned reflexes and physical parameters are delayed in HcyF2 rats. In “open field”, HcyF2 rats showed higher levels of anxiety and decreased exploratory and motor activity, while coordination of movements studied in “rotarod” test was not impaired. Decreased limb muscle strength was shown in the “grip strength” test. Additionally, HcyF2 rats demonstrated an impaired learning and longterm memory in the Morris water maze. Biochemical analysis revealed an imbalance in the antioxidant systems, which was attributed to decreased activity of glutathione peroxidases and H2S synthesis enzymes. It was suggested that elevated homocysteine levels during pregnancy may result in epigenetic modifications of the genome, which can impact the metabolism of offspring and be inherited by future generations.

The Relationship of Cobalamin and/or Folate to the Patient-Centred Outcomes in Multiple Sclerosis: A Systematic Review and Meta-analysis.

Background: To examine the relationship of vitamin B12 and folate concentrations to cognitive function, fatigue measures, physical function, quality of life (patient-centred outcomes) and homocysteine plasma concentrations (intermediate marker of cobalamin and folate deficiency) for patients with Multiple Sclerosis (MS). Methods: Systematic searches for eligible articles of MEDLINE, CINAHL, EMBASE, Scopus, Web of Science and OpenGray databases were conducted from 1983 in March 2021. Heterogeneity, Weighted Mean Difference (WMD) and Confidence Intervals (CI) calculated using Random Effects Model. Results: Sixteen studies were included involving; 616 MS patients and 655 healthy controls. 14 of these had acceptable or better quality but there was high heterogeneity. No difference was found between MS, healthy controls for folate and cobalamin concentrations; WMD 0.00ug/L (95% CI: -0.01, 0.01) and WMD 7.01pmol/L (95% CI: -25.54, 39.55) respectively. MS group showed mild-to-moderate disability WMD was 2.78 (95% CI: 2.00, 3.56). MS may be associated with elevated plasma homocysteine concentrations on average 2.47µmol/L more than healthy controls. Discussion: Physical ability of MS group was worse than healthy controls, but there was no difference in folate and cobalamin concentrations. This suggests folate and cobalamin are not influential factors in worsening physical function. There may be an association between worse cognitive function, and increased homocysteine concentrations. Results were inconclusive due to high heterogeneity and limited number of studies. A core outcome set would enable easier synthesis of future results.

Addition of dietary methionine but not dietary taurine or methyl donors/receivers to a grain-free diet increases postprandial homocysteine concentrations in adult dogs.

Grain-based ingredients are replaced in part by pulse ingredients in grain-free pet foods. Pulse ingredients are lower in methionine and cysteine, amino acid (AA) precursors to taurine synthesis in dogs. Although recent work has investigated plasma and whole blood taurine concentrations when feeding grain-free diets, supplementation of a grain-free diet with various nutrients involved in the biosynthesis of taurine has not been evaluated. This study aimed to investigate the effects of supplementing a complete grain-free dry dog food with either methionine (MET), taurine (TAU), or methyl donors (choline) and methyl receivers (creatine and carnitine; CCC) on postprandial AA concentrations. Eight healthy Beagle dogs were fed one of the three treatments or the control grain-free diet (CON) for 7 d in a 4 × 4 Latin square design. On day 7, cephalic catheters were placed and one fasted sample (0 min) and a series of nine post-meal blood samples were collected at 15, 30, 60, 90, 120, 180, 240, 300, and 360 min. Data were analyzed as repeated measures using the PROC GLIMMIX function in SAS (Version 9.4). Dogs fed MET had greater plasma and whole blood methionine concentrations from 30 to 360 min after a meal (P < 0.0001) and greater plasma homocysteine concentrations from 60 to 360 min after a meal (P < 0.0001) compared with dogs fed CON, TAU, and CCC. Dogs fed TAU had greater plasma taurine concentrations over time compared with dogs fed CON (P = 0.02) but were not different than dogs fed MET and CCC (P > 0.05). In addition, most AAs remained significantly elevated at 6 h post-meal compared with fasted samples across all treatments. Supplementation of creatine, carnitine, and choline in grain-free diets may play a role in sparing the methionine requirement without increasing homocysteine concentrations. Supplementing these nutrients could also aid in the treatment of disease that causes metabolic or oxidative stress, including cardiac disease in dogs, but future research is required.

Frequency of Elevated Homocysteine Level in Patients Presented with Ischemic Stroke

Background: A stroke is the rapidly developing focal or global neurological deficit due to disturbance in the blood vessels supplying to the brain. There is increasing proof that increased homocysteine concentration may act as independent risk factor for ischemic stroke. So, this study was done to find the elevated homocysteine in stroke patients. Objective: To determine the frequency of elevated homocysteine levels in patients presenting with ischemic stroke. Study Design: Cross sectional study. Settings: Department of Neurology, Mayo Hospital, Lahore, Pakistan. Duration: Six months from March to August 2011. Methodology: Patients detailed medical history, physical examination and demographics were stored electronically, moreover the blood samples were drawn under aseptic measures within 24 hours of stroke. For each patient, homocysteine level was assessed through standard procedures from the blood. Data was analyzed through SPSS version 20 and entered in Proforma. Results: Mean age of patients was 45.09 ± 5.36 years. Majority of the patients were male. 8(8.0%) patients were 20-30 years of age, 7(7.0%) patients were between 31-40 years old and 85(85%) patients were 41-50 years of age. Elevated homocysteine level was confirmed in 56 patients (56.0%). Conclusion: Homocysteine level was found to be frequently elevated in patients with ischemic stroke.

Methylenetetrahydrofolate reductase gene polymorphism, global DNA methylation and blood pressure: a population based study from North India

BackgroundHypertension is a complex disorder affected by gene-environment interactions. Methylenetetrahydrofolate reductase (MTHFR) gene is one of the genes in One Carbon Metabolic (OCM) pathway that affects both blood pressure and epigenetic phenomenon. MTHFR C677T gene polymorphism leads to reduced methylation capacity via increased homocysteine concentrations. Global DNA methylation (5mC%) also gets affected in conditions such as hypertension. However, no study is found to understand hypertension in terms of both genetics and epigenetics. The present study aims to understand the relation between methylation, MTHFR C677T gene polymorphism and hypertension. It also tries to understand relation (if any) between methylation and anti-hypertensive drugs.MethodsThis is a cross-sectional study where data were collected from a total of 1634 individuals of either sex in age group 35–65 years. Hypertensives (SBP ≥ 140 mm Hg and DBP ≥ 90 mm Hg) (on treatment/not on treatment) and absolute controls were 236 (cases) and 307 (controls), respectively. All the samples were subjected to MTHFR C677T gene polymorphism screening (PCR–RFLP) and global DNA methylation assay (ELISA based colorimetric assay). Results of both the analyses were obtained on 218 cases, 263 controls.ResultsMedian 5mC% was relatively lower among cases (p > 0.05) compared to controls, despite controlling for confounders (age, sex, smoking, alcohol, diet) (r2-0.92, p-0.08). Cases not on medication had significantly reduced 5mC% compared to controls (p < 0.05), despite adjusting for confounders (r2-0.857, p-0.01). Among cases (irrespective of treatment), there was a significant variation in 5mC% across the three genotypes i.e. CC, CT and TT, with no such variation among controls. Cases (not on medication) with TT genotype had significantly lower methylation levels compared to the TT genotype controls and cases (on medication) (p < 0.01).ConclusionGlobal DNA hypomethylation seems to be associated with hypertension and antihypertensive drugs seem to improve methylation. Hypertensive individuals with TT genotype but not on medication are more likely to be prone to global DNA hypomethylation. Important precursors in OCM pathway include micronutrients such as vitamin B-12, B-9 and B-6; their nutritional interventions (either dietary or supplement) may serve as strategies to prevent hypertension at population level. However, more epidemiological-longitudinal studies are needed for further validation.

Plasma homocysteine concentrations and depression: A twin study.

Homocysteine is an amino acid formed during metabolism of the essential amino acid methionine that plays an important role in energy metabolism and neurotransmitter synthesis. High levels of homocysteine have been linked to both depression and cardiovascular disease, however studies of depression have not always been consistent, possibly related to differences in methodology among studies. The study of twins in clinical research can be useful in controlling for confounding factors. The purpose of this study was to assess the relationship between depression and plasma homocysteine in a study of twins. Homocysteine concentration was assessed in twins (N = 202) from the Vietnam Era Twin Registry, including twin pairs discordant for the diagnosis of Major Depressive Disorder (MDD) and twin pairs without MDD. Self reported depressive symptom levels were also measured as a continous variable using the Beck Depression Inventory (BDI). The average homocysteine concentration was 7.9 μmol/L (2.1 μmol/L SD, range of 2.0-17.1 μmol/L). There were no within twin pair differences in homocysteine concentration within twin pairs discordant for MDD and within twin pairs that differed for BDI score. There was a significant pair-level relationship between depressive symptoms as measured by mean BDI score and homocysteine concentration, such that the higher the mean BDI score of the twin pair, the higher the mean homocystein of the pair (p < .001). Every 10 point increase in BDI score was associated with an 0.8 μmol/L increase in homocysteine concentration at the pair level. These findings are not consistent with a causal role for elevated homocysteine in the development of depression, but rather point to familial confounding or other factors that are shared by twin brothers and that contribute to both depression and homocysteine levels.

Особливості метаболічних перетворень гомоцистеїну та цистеїну в гепатоцитах щурів за умов нутрітивного дисбалансу

The work is devoted to the study of the homocysteine concentration in blood plasma and the activity of the enzymes of cysteine catabolic transformations γ-glutamate-cysteine ligase and cysteine dioxygenase in rats’ hepatocytes under the conditions of consumption of excessive sucrose content on the background of alimentary protein deprivation. It was found, that the consumption of a high-sucrose diet in animals is accompanied by the increase of homocysteine concentration in plasma by 57% compared to control, whereas the excess of sucrose under the conditions of protein deficiency leads to hypohomocysteinemia (the content of homocysteine decreased by 43% compared to control). The increased plasma homocysteine levels in excess-consuming sucrose can be considered as a prognostic marker of functional disorders of the transsulfuration pathway in the liver and used in the diagnosis of hepatopathologies. Since, the cysteine content in liver cells increased under the conditions of high-sucrose diet consumption, the increasing γ-GCS, a key enzyme of glutathione synthesis, is probably associated with the maintenance of intercellular glutathione stores. Our data of the occurrence hypohomocysteinemia under the conditions of the consumption of excessive amounts of sucrose on the background of dietary protein deficiency highlight gaps in the understanding of the correlation between the metabolic processes of methionine, homocysteine and cysteine in the liver. Under the excessive consumption of sucrose on the background of protein deficiency, the exogenous protein deficiency can be considered as a key factor in reducing the γ-GCS activity (36%) and the cysteine content, because not only the amount of this amino acid is reduced but also its synthesis is disrupted. At the same time, the maximum increase in cysteine dioxygenase activity in rats’ hepatocytes under the conditions of high-sucrose/low-protein diet consumption on the background of decreased γ-GCS activity indicates the utilization of excess cysteine with the formation of taurine and sulfates.

Polymorphism of folate cycle genes as a risk factor of hyperhomocysteinemia

Hyperhomocysteinemia (HHc) is a new factor being considered at the moment that can cause damage to vessel walls. Its occurrence depends on genetic peculiarities of a body. Our research goal was to estimate frequency of genetic polymorphisms (SNP) in folate cycle genes among people living in Perm region and its influence on homocysteine (Hc) concentration in blood serum. We examined 189 women (32.2±5.25). Hc concentration in blood serum was determined with immune chemiluminescent procedure. We examined frequency of SNP in folate cycle genes with pyrosequencing. Homozygote state as per minor alleles in methylene tetrahydrofolate reductase (MTHFR) gene (rs 1801133 и rs 1801131) and MTR gene (rs 1805087) was registered 7.5, 5.4, and 13.75 times less frequently than homozygote state as per neutral alleles. Heterozygote state prevailed for genes of methionine synthase reductase and folate transport protein among examined SNP. Homozygotes as per minor allele SNP in MTHFR gene (Ala222Val; rs 1801133) had higher Hc concentration in blood serum that amounted to 8.476 ± 3.193 mmol/L and was 1.276 times higher than the same parameter in homozygotes as per neutral allele (р=0.0036). We didn’t establish any influence on Hc contents in blood serum for the remaining 4 SNP in folate cycle genes (р&gt; 0.1). Examined SNP in MTHFR and MTR genes tended to have neutral alleles more frequently than minor ones. SNP in genes of other examined proteins belonging to folate cycle didn’t have any differences in frequency of examined alleles. We didn’t detect a combination of homozygote state as per two SNP in MTHFR gene or homozygote state as per one SNP and heterozygote state as per another one in a genome. Only SNP in MTHFR gene (Ala222Val, rs 1801133) authentically causes increase in homocysteine concentration out of all the examined SNP in genes of folate cycle enzymes and proteins

Полиморфизм генов фолатного цикла как фактор риска формирования гипергомоцистеинемии

Hyperhomocysteinemia (HHc) is a new factor being considered at the moment that can cause damage to vessel walls. Its occurrence depends on genetic peculiarities of a body. Our research goal was to estimate frequency of genetic polymorphisms (SNP) in folate cycle genes among people living in Perm region and its influence on homocysteine (Hc) concentration in blood serum. We examined 189 women (32.2±5.25). Hc concentration in blood serum was determined with immune chemiluminescent procedure. We examined frequency of SNP in folate cycle genes with pyrosequencing. Homozygote state as per minor alleles in methylene tetrahydrofolate reductase (MTHFR) gene (rs 1801133 и rs 1801131) and MTR gene (rs 1805087) was registered 7.5, 5.4, and 13.75 times less frequently than homozygote state as per neutral alleles. Heterozygote state prevailed for genes of methionine synthase reductase and folate transport protein among examined SNP. Homozygotes as per minor allele SNP in MTHFR gene (Ala222Val; rs 1801133) had higher Hc concentration in blood serum that amounted to 8.476 ± 3.193 mmol/L and was 1.276 times higher than the same parameter in homozygotes as per neutral allele (р=0.0036). We didn’t establish any influence on Hc contents in blood serum for the remaining 4 SNP in folate cycle genes (р&gt; 0.1). Examined SNP in MTHFR and MTR genes tended to have neutral alleles more frequently than minor ones. SNP in genes of other examined proteins belonging to folate cycle didn’t have any differences in frequency of examined alleles. We didn’t detect a combination of homozygote state as per two SNP in MTHFR gene or homozygote state as per one SNP and heterozygote state as per another one in a genome. Only SNP in MTHFR gene (Ala222Val, rs 1801133) authentically causes increase in homocysteine concentration out of all the examined SNP in genes of folate cycle enzymes and proteins.

Gender- and age-related differences in homocysteine concentration: a cross-sectional study of the general population of China

The primary goals of this study were to evaluate the gender- and age-related differences in homocysteine concentration in the general population of China and possible influencing factors. A total of 7872 subjects, divided into male and female groups, participated in this retrospective study. The average homocysteine level, prevalence of hyperhomocysteinemia, and independent factors affecting homocysteine concentration were analyzed. The homocysteine level was significantly higher in males than in females in each age range (aged 20–30, aged 30–40, aged 40–50, aged 50–60, aged 60–80, aged over 80) (P < 0.0001), and the trend did not abate with age. The homocysteine concentration first decreased and then increased, being lowest at 30–50 years of age and significantly increased after 50 years of age. Factors associated with homocysteine concentration in males were smoking status (current smokers versus ex-smokers: β: 0.112), estimated glomerular filtration rate (β = − 0.192), blood urea nitrogen (β = − 0.14), diastolic blood pressure (β = − 0.113), free triiodothyronine (β = − 0.091), serum potassium (β = − 0.107) and cystatin C (β = 0.173). In females, independent factors associated with homocysteine concentration were cystatin C (β = 0.319), albumin (β = 0.227), free thyroxine (β = 0.179), age (β = 0.148), free triiodothyronine (β = − 0.217) and serum potassium (β = − 0.153). The homocysteine level was significantly higher in males than in females and increased markedly after 50 years of age in both groups. The independent factors associated with increased homocysteine concentration differed between males and females.

Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype

DNA methylation is important in regulating gene expression and genomic stability while aberrant DNA methylation is associated with disease. Riboflavin (FAD) is a cofactor for methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate recycling, which generates methyl groups for homocysteine remethylation to methionine, the pre-cursor to the universal methyl donor S-adenosylmethionine (SAM). A polymorphism (C677T) in MTHFR results in decreased MTHFR activity and increased homocysteine concentration. Previous studies demonstrated that riboflavin modulates this phenotype in homozygous adults (MTHFR 677 TT genotype), however, DNA methylation was not considered. This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p < 0.001) were significantly hypermethylated in individuals with the MTHFR 677 TT compared to CC genotype. Riboflavin supplementation resulted in decreased global methylation, albeit only significant at one CpG. A significant reduction in DNA methylation at the MTHFR north shore (−1.2%, p < 0.001) was also observed in TT adults following intervention with riboflavin. This provides the first RCT evidence that DNA methylation may be modulated by riboflavin in adults with the MTHFR 677 TT genotype.

Blood total antioxidant status is associated with cortical glucose uptake and factors related to accelerated aging.

Identifying cerebral vulnerability in late life is of paramount importance to prevent pathological trajectories of aging before the onset of symptoms. Considerable evidence suggests that impaired antioxidant mechanisms are a fingerprint of aging-related conditions, but there is a lack of human research linking total antioxidant capacity (TAC) measured in peripheral blood to in vivo brain changes and other factors featuring accelerated aging. To address this issue, we have assessed in cognitively normal elderly subjects (N = 100) correlations between serum TAC, using the oxygen radical absorbance capacity assay, surface-based cortical thickness, surface-based 18F-fluorodeoxyglucose positron emission tomography cortical uptake, and different factors associated with accelerated aging [i.e., serum homocysteine (HCY), self-reported memory problems, and self-reported patterns of physical activity]. While no relationship was observed between serum TAC and variations in cortical thickness, decreased TAC level was significantly associated with lower FDG uptake in temporal lobes bilaterally. Remarkably, decreased TAC level was linked to increased HCY concentrations, moresubjective memorycomplaints, and lower frequency of physical activity. Overall, our results suggest that decreased serum TAC level may be helpful to detect vulnerable trajectories of aging.

Growth performance, blood parameters and metabolic-enzyme gene expression of finishing pigs as affected by dietary level of methionine + cystine supplemented with vitamin B6

Context Methionine (Met) is an essential amino acid in pig diets. However, high blood homocysteine concentration, a risk factor for cardiovascular disease, can arise from high dietary Met intake and may indicate an imbalance in the Met cycle. Vitamin B6 acts as a cofactor for enzymes associated with the trans-sulfuration pathway, considered the major elimination route of excess homocysteine. Aims We evaluated the effects of different levels of dietary Met and vitamin B6 supplementation and their interaction with respect to growth performance, blood parameters and metabolic-enzyme gene expression of finishing pigs. Methods Fifty-six crossbred barrows, averaging 75.11 ± 1.84 kg bodyweight (BW), were assigned in a completely randomised block design arranged in a 2 × 4 factorial with two levels of vitamin B6 supplementation (1.58 and 3.58 mg/kg) and four levels of standardised ileal digestible (SID) Met + cystine (Cys) (0.35%, 0.45%, 0.55 and 0.65%), with seven replicates and one animal per pen, for an average duration of 26 days. BW of each pig and quantity of experimental diets on-offer and consumed were recorded at the beginning and end of the experiment. Plasma concentrations of glucose, urea, total proteins, creatinine and triacylglycerol were determined by the colourimetric method, and serum homocysteine by chemiluminescence. Gene expression was measured by quantitative real-time polymerase chain reaction. Key results No interactions (P > 0.05) between vitamin B6 supplementation and SID Met + Cys levels were observed for growth performance, blood parameters or metabolic-enzyme gene expression. Higher vitamin B6 supplementation (3.58 mg/kg) improved (P = 0.05) the feed : growth ratio. Treatments did not affect (P > 0.05) expression of the enzymes methionine synthase or cystathionine γ-lyase, and there was a linear increase (P = 0.01) in serum homocysteine levels with increasing dietary Met + Cys. Increasing vitamin B6 supplementation (3.58 mg/kg) in finishing pig diets increased plasma glucose concentration (P = 0.05), but did not mitigate the increase in homocysteine concentration. Conclusions Overall, a dietary SID Met + Cys intake of 10.46 g/day (corresponding to 0.35%) was sufficient for the growth of finishing barrows from 75 to 100 kg BW. Vitamin B6 supplementation at 3.58 mg/kg improved the feed : growth ratio but was not effective for metabolising the increasing homocysteine concentration via the trans-sulfuration pathway. Implications This study provides much needed empirical data on the dietary SID Met + Cys requirements for finishing pigs, and the metabolism of these amino acids.

The role of maternal homocysteine concentration in placenta-mediated complications: findings from the Ottawa and Kingston birth cohort

BackgroundHomocysteine is an intermediate metabolite implicated in the risk of placenta-mediated complications, including preeclampsia, placental abruption, fetal growth restriction, and pregnancy loss. Large cohort and case-control studies have reported inconsistent associations between homocysteine and these complications. The purpose of this study was to investigate whether elevated maternal plasma homocysteine concentration in the early to mid-second trimester is associated with an increased risk of placenta-mediated complications. We examined the following potential moderating factors that may explain discrepancies among previous studies: high-risk pregnancy and the MTHFR 677C>T polymorphism.MethodsWe analyzed data from participants recruited to the Ottawa and Kingston (OaK) Birth Cohort from 2002 to 2009 in Ottawa and Kingston, Canada. The primary outcome was a composite of any placenta-mediated complication, defined as a composite of small for gestational age (SGA) infant, preeclampsia, placental abruption, and pregnancy loss. Secondary outcomes were, individually: SGA infant, preeclampsia, placental abruption, and pregnancy loss. We conducted multivariable logistic regression analyses with homocysteine as the primary continuous exposure, adjusting for gestational age at the time of bloodwork and explanatory maternal characteristics. The functional form, i.e., the shape of the homocysteine association with the outcome was examined using restricted cubic splines and information criteria (Akaike’s/Bayesian Information Criterion statistics). Missing data were handled with multiple imputation.Results7587 cohort participants were included in the study. Maternal plasma homocysteine concentration was significantly associated (linearly) with an increased risk of both the composite outcome of any placenta-mediated complication (p = 0.0007), SGA (p = 0.0010), severe SGA, and marginally with severe preeclampsia, but not preeclampsia, placental abruption and pregnancy loss. An increase in homocysteine concentration significantly increased the odds of any placenta-mediated complication (odds ratio (OR) for a 5 μmol/L increase: 1.63, 95% Confidence Interval (CI) 1.23–2.16) and SGA (OR 1.76, 95% CI 1.25–2.46). Subgroup analyses indicated some potential for modifying effects of the MTHFR 677C>T genotype and high-risk pregnancy, although the interaction was not statistically significant (high-risk subgroup OR 2.37, 95% CI 1.24–4.53, p-value for interaction =0.14).ConclusionsOur results suggest an independent effect of early to mid-pregnancy elevated maternal homocysteine on placenta-mediated pregnancy complications.

Vitamin B12 and Folate Status in Patients with Epilepsy Under Levetiracetam Monotherapy.

Background:Antiepileptic drugs (AEDs) may lead to an increase in the plasma concentration of homocysteine. There is limited information, especially from Iran, regarding the risk in patients who are treated with levetiracetam as a new type of AED. The aim of the present study was to investigate the effect of levetiracetam on plasma homocysteine, vitamin B12, and folate levels in adult patients with epilepsy.Methods:We conducted a case-control study and enrolled adult patients with epilepsy who had received monotherapy with levetiracetam for at least 6 months at some time prior to the study. homocysteine serum, vitamin B12, and folate were measured, and folate and vitamin B12 intake was determined by the food frequency questionnaire (FFQ).Results:Thirty-three patients on levetiracetam and 35 control subjects aged between 18 and 60 years were enrolled. No statistically significant differences in the means of the serum markers of vitamin B12, FA, and homocysteine levels were found between the two groups. In the first model, i.e., the crude model, no significant differences were observed in the serum concentrations of homocysteine, vitamin B12, and folate. In the second model, education was considered, and body mass index and folate intake was controlled with no significant difference being observed in the mean homocysteine serum level.Conclusions:Treatment with levetiracetam in patients with epilepsy has no effect on the serum levels concentrations of homocysteine, vitamin B12, and folate. This medication is suggested for patients who use AEDs on a long-term basis and at high dosages.

Rehydration during exercise prevents the increase of homocysteine concentrations.

This study aimed to assess the effect of rehydration during and after acute aerobic submaximal exercise on total homocysteine (tHcy) concentrations and related parameters in physically active adult males. Twenty trained males (29.4 ± 7.9years old) completed four exercise tests: two without rehydration during exercise (NH1 and NH2), one with rehydration during exercise using water (H1) and one with rehydration during exercise using an isotonic sports drink (H2). After finishing the exercise tests, subjects followed a rehydration protocol for 2h. Serum tHcy, vitamin B12, folate, creatine and creatinine were analysed before, after and at 2, 6 and 24h after exercise. Data were analysed with and without correcting for haemoconcentration to assess the changes in tHcy related. The methylenetetrahydrofolate reductase (MTHFR) 677TT genotype was also analysed. THcy (uncorrected by haemoconcentration) increased significantly after exercise (P < 0.05) in the NH1 and NH2 tests [mean increase ± SD: 1.55 ± 0.33 (15.18%) and 1.76 ± 0.25 (17.69%) µmol/L, respectively], while no significant differences were found in the H1 and H2 tests [mean increase: 0.65 (6.29%) and 0.90 (8.69%) μmol/L, respectively]. The increase was partly due to haemoconcentration and partly due to the metabolism underlying acute exercise. THcy concentrations recovered to baseline after 24h in all tests. In conclusion, adequate rehydration during acute aerobic exercise using either water or a sports drink maintains tHcy concentrations at baseline and for up to 2h after exercise in physically active male adults and prevents further increases when compared to no rehydration.

Homocysteine and Risk of Premature Coronary Heart Disease

Background: Homocystinuria is a rare autosomal recessive disease complicated by early and aggressive occlusive arterial disease. This may be related to the grossly increased homocysteine concentrations seen in this disease. More recently, milder hyperhomocysteinemia has been proposed as an independent risk factor for coronary artery disease. Cardiovascular disease (CVD) is among the diseases with multiple contributing factors, hence making it difficult to pinpoint a particular factor alone. The main factor that is of relevance to this study is homocysteine. Coronary artery disease is the narrowing or blockage of the arteries and vessels that supply oxygen and nutrients to the heart (1, 2). CVD is the major cause of morbidity and mortality worldwide. Obesity, HTA, Diabetes mellitus, hypercholesterolemia, and smoking have been recognized as major risk factors for CVD.&#x0D; Aim: Aim of this paper is to examine concentrations of Hcyt and lipid profiles in patients with CVD and positive personal history for CVD, comparing them with the control group composed of healthy individuals. Our study aimed to verify the role of Homocysteine as a new independent risk factor on the onset of early atherosclerosis and atheromatous processes in coronary arteries in patients with CVD.&#x0D; Materials and methods: The results obtained represent the average value earned once every three months in the 3 year period. 5ccm serum with a few heparin spots was sent to the Clinical Laboratory of the University Clinic of Skopje.&#x0D; Results: The results obtained from patients with CVD and control groups are presented in the following text, where a statistically significant difference was observed for p &lt;0.0001 between the parameters obtained by patients with CVD compared to the control group. Concentrations of homocysteine and lipids in patients with CVD compared to the control group showed statistically significant difference with p&lt;0.0001, expected results, and verified in many other multicentric studies. These facts show that raised Hcyt has more impact on the onset of CVD. When Hcy levels are in the blood, the activity of the cystathionine-synthetase enzyme is raised. It is believed that this enzyme plays a vital role in the metabolism of Hcyt. In recent years a lot of studies have been made on the effect of hyperhomocysteinemia and its impact on the onset of coronary and all have verified that hyperhomocysteinemia is a significant parameter for the onset of early atherosclerosis of coronary and CVD(6,7,8).&#x0D; Conclusions: In the above-mentioned cases, it is recommended substitutive therapy with folic acid, pyridoxine, vitamin B12, vitamin E and other antioxidants which are found that have an effect on the prevention of premature atherosclerosis in patients with CVD and raised Hcyt: acute myocardial infarction, CARB, angina pectoris. PTCA, Stenting, and prevention of stroke.

Inverse association between plasma homocysteine concentrations and type 2 diabetes mellitus among a middle-aged and elderly Chinese population

Background and aimsPlasma homocysteine concentrations have been reported to be associated with type 2 diabetes mellitus (T2DM) with controversial findings. The aim of the present study was to investigate the association between plasma homocysteine concentrations and T2DM. Methods and resultsA cross-sectional study including 19,085 eligible participants derived from the Dongfeng-Tongji cohort was conducted. Plasma homocysteine concentrations were measured by Abbott Architect i2000 Automatic analyzer and T2DM was defined according to American Diabetes Association criteria. Logistic regression model was used to explore the association between plasma homocysteine concentrations and T2DM. The prevalence of T2DM was 19.0% in the whole population (mean age 62.9 years), 21.8% in males, and 17.1% in females. In the multivariable logistic regression analyses, compared with those in the lowest quintile, the OR (95% CI) of T2DM was 1.05 (0.92–1.21), 0.99 (0.86–1.14), 0.90 (0.78–1.05), and 0.77 (0.66–0.90) for quintile 2 to quintile 5 of homocysteine concentrations after adjustment for potential confounders (P for trend < 0.0001). Homocysteine concentrations were associated with decreased T2DM prevalence risk (OR = 0.88 per SD increase of homocysteine concentration; 95% CI: 0.84–0.93). A significant interaction between homocysteine concentrations and drinking status on T2DM prevalence risk was observed (P for interaction = 0.03). The inverse association of plasma homocysteine concentrations with T2DM prevalence risk was observed in non-drinkers but not in current drinkers. ConclusionPlasma homocysteine concentrations were inversely correlated with T2DM among a middle-aged and elderly Chinese population.

EFFECT OF A COMBINED HIGH-FATTY DIET AND THIOLACTONE HYPERHOMOCYSTEINEMIA ON MASS, GROWTH AND ON BIOCHEMICAL MARKERS OF THE LIVER IN RATS

The impact of high fat diet (HFD) and thiolactone hyperhomocysteinemia combination on mass-growth parameters and biochemical markers of liver state in rats has been studied. It was proved that using HFD (54 % of kilocalories from fat) combined with the administration of homocysteine thiolactone (100 mg/kg intragastrically) for 60 days in rats lead to a significant increase of homocysteine concentration in the serum (by 55,0 %), BMI increase (by 8,9 %), total fat weight (by 39,8 %) and obesity index (by 18,5 %). In addition, the functional state of the liver was disturbed significantly and the processes of hepatic steatogenesis and fibrogenesis were accelerated, in comparison with single HFD use.

Homocysteine concentrations in the cognitive progression of Alzheimer's disease

ObjectivesHyperhomocysteinemia in Alzheimer's disease (AD) is widely reported and appears to worsen as the disease progresses. While active dietary intervention with vitamins B12 and folate decreases homocysteine blood levels, with promising clinical outcomes in Mild Cognitive Impairment (MCI), this so far has not been replicated in established AD populations. The aim of the study is to explore the relationship between hyperhomocystenemia and relevant vitamins as the disease progresses. MethodsIn this longitudinal cohort study, 38 participants with mild to moderate AD were followed for an average period of 13months. Plasma folate, vitamin B12 and homocysteine concentrations were measured at baseline and at follow-up. Dietary intake of B vitamins was also measured. Spearman's correlations were conducted by homocysteine and B vitamin status. ResultsAs expected, cognitive status significantly declined over the follow-up period and this was paralleled by a significant increase in homocysteine concentrations (p=0.006). However, during this follow-up period there was no significant decline in neither dietary intake, nor the corresponding blood concentrations of vitamin B12/folate, with both remaining within normal values. Changes in blood concentrations of B vitamins were not associated with changes in homocysteine levels (p>0.05). ConclusionIn this study, the increase in homocysteine observed in AD patients as the disease progresses cannot be solely explained by dietary and blood levels of folate and vitamin B12. Other dietary and non-dietary factors may contribute to hyperhomocysteinemia and its toxic effect in AD, which needs to be explored to optimise timely intervention strategies.