Homocysteine Concentrations Research Articles

Classical homocystinuria presenting with transient basal ganglia pathology and dystonia.

Classical homocystinuria is caused by pathogenic variants in the CBS gene leading to a deficiency of the vitamin B6-dependent enzyme cystathionine beta synthase. The disease is typically associated with high blood homocysteine concentrations. Clinical features include developmental delay/intellectual disability, psychiatric problems, thromboembolism, lens dislocation, and marfanoid habitus. We report on a child with classical homocystinuria presenting with acute episodes of dystonia and symmetrical basal ganglia abnormalities mimicking a mitochondrial disease. After starting treatment with vitamin B6, homocysteine levels rapidly normalized and dystonic episodes did not re-occur. Moreover, brain-imaging findings almost completely disappeared. The case illustrates that homocystinuria should be considered as a treatable differential diagnosis of dystonia.

The role of folate in the management of insulin resistance in adults : a systematic review

Insulin resistance (IR) is one of the main risk factors for type 2 diabetes. IR employs a heavy economic burden, and the prevalence rate of IR in Indonesia is high. Homeostasis model of assessment-insulin resistance (HOMA-IR) is proven to be a great clinical tool to assess IR. Nutrition intervention should be the primary focus in treating IR. Folate is proven to be effective in lowering homocysteine concentrations, which is one of the risk factors for IR. This study aimed to summarize the role of folate in the management of IR in adults.

Study of the state of th vascular endothelium in various forms of coronary heart disease

Purpose of the study: to investigate changes in markers of endothelial dysfunction and hemostasis system in patients with different forms of CHD on the background of treatment and before it.Materials and methods of the study. In order to fulfill the set tasks, 60 patients with different forms of CHD: stenocardia and myocardial infarction (according to the classification of the Canadian Association of Cardiology (L. Cam-peau, 1976)), 60 patients with different forms of CHD were examined during the study. Campeau, 1976), VNOC (2004), recommendations of the European Society of Cardiology (2007)), aged from 50 to 75 years (mean age 62.6 ± 3.5 and 65.1 ± 3.6 years, respectively) and 20 practically healthy individuals (without signs of CHD), comparable in age (mean age 62.7 ± 3.7 years), who constituted the control group. For comparative analysis of the results before and after treatment the subjects were divided into three groups: Group I - control group, respondents without CHD; Group II - patients with stable angina II and III functional classes (FC); Group III - patients with postinfarction cardiosclerosis, i.e. those who had undergone Ml.Results and their discussion Several risk factors were identified in the majority of hospitalized patients. CHD of II and III FC was more often registered in women (60%); men who had undergone myocardial infarction accounted for 63.3%, the indices were statistically insignificant (p >0.05). The main cardiovascular risk factors (obesity, arterial hypertension, body mass index and total cholesterol) were significantly higher (in % ratio) in patients of groups ll-lll compared to group I (p<0.001), but the cholesterol content and body mass index were on average higher in group II (4.5 ± 1.0 and 33.0 ± 1.3, respectively) than in group III (4.2 ±1.1 and 30.6 ± 2.6, respectively). As for the duration of the disease, group III patients were characterized by a longer history and a higher frequency of heart failure, i.e. patients in this group had a more severe clinical status (p > 0.05). It should be noted that of the total number of patients (n = 80), rural residents accounted for 46.25% and city dwellers for 53.75%.ConclusionsThe presence of a higher degree of endothelial dysfunction is observed in patients who underwent myocardial infarction, in contrast to the stable form of angina pectoris without myocardial infarction in the anamnesis. The progression and deterioration of vascular endothelium is mostly associated with the presence of hyperhomocysteinemia, and the most pronounced changes in endothelial function are determined in patients with a combination of cardiovascular risk factors. In different forms of CHD the increased content of DEK and homocysteine in blood serum, increasing in parallel with the severity of clinical course, their level correlates with the degree of endothelial dysfunction. A direct correlation between hemostasis markers (von-Willebrand factor, fibrinogen and platelets) and DEK was revealed. The greatest changes in vascular-thrombocytic and coagulation hemostasis are observed in patients with IMI than in patients with stenocardia.

Homocysteine, cancer and oncothrombosis

Introduction. Hyperhomocysteinemia (HHC) is one of the arms in the pathogenesis of thrombotic complications in female cancer patients.Aim: to assess an HHC-related impact to developing thrombotic complications in patients with malignant neoplasms of the female genital organs and breast cancer.Materials and Methods. There were retrospectively evaluated the data collected from 236 patients: with ovarian tumors (n = 63), cervical cancer (n = 51), breast tumors (n = 64), malignant neoplasms of the uterine body (n = 58). The control group consisted of 50 women without malignant neoplasms. The analysis of homocysteine (HC) concentration, the frequency of polymorphisms of the genes encoding folate cycle enzymes MTHFR C677T, MTHFR A1298C, MTRR A66G, MTR A2756G as well as the rate of thrombotic complications was carried out. A risk of blood HC level-related thrombotic complications was assessed.Results. Plasma HC concentration comprised ≥ 22 μmol/l in 30.5 % of patients. Thrombotic complications within one year after discharge from the hospital were developed in 15.3 % cases. The risk of thrombotic complications turned out to be higher in patients with elevated plasma HC level (≥ 22 μmol/l) (odds ratio = 2.99; 95 % confidence interval = 1.11–8.08). No significantly increased prevalence of polymorphisms in the genes encoding folate cycle enzymes among female cancer patients was detected.Conclusion. Monitoring HC level in female cancer patients contributes separately to predict a likelihood of thrombotic complications. Prescribing drugs that reduce HC level (folic acid) and monitoring its concentration in female cancer patients during therapy, including chemotherapy, can potentially lower an incidence of thrombotic complications.

Functional vitamin B12 deficiency is a consistent feature in hospital admissions for neurological disorders due to the use of nitrous oxide

Introduction: Misuse of inhaled nitrous oxide is a growing concern in France. It is known to alter concentrations of vitamin B12, which is required as a cofactor for methionine synthase and methylmalonyl-CoA mutase activity. Hence, measurement of the concentrations of cobalamin metabolism biomarkers, including vitamin B12, homocysteine, and methylmalonic acid, could assist in the management of patients with a complex clinical presentation or in those who deny the consumption of nitrous oxide. Methods: We retrospectively collected clinical and biological data in patients hospitalized for nitrous oxide use in a university hospital in southern France between January 2020 and October 2022. Results: Thirty-one patients were identified during 34 months; 79% were men with a median age of 23.7 years. Most (97%) presented with peripheral polyneuropathy and/or myelopathy. The median vitamin B12 concentration was 134.6 pmol/L, with 17 of 31 patients having values less than 145 pmol/L (the lower limit of the normal range). The median plasma folate concentration was 20.1 nmol/L, which is within the normal range. The median plasma homocysteine concentration was 87.7 µmol/L (normal range >15 µmol/L), and the median plasma methylmalonic acid concentration was 3.8 µmol/L (normal range >0.5 µmol/L). Conclusion: Nitrous oxide use is an emerging public health problem in France, as shown by the number of patients admitted to our hospital. The presence of a functional vitamin B12 deficiency was a consistent feature that could be helpful in diagnosis in complex cases.

Fortified foods with methylated forms of B vitamin for the prevention of hyperhomocysteinemia

Aim. To study the relationship between blood homocysteine levels and genetic and epigenetic factors and assess the possibility of correcting homocysteine levels using products enriched with methylated forms of B vitamin.Material and methods. The study included 20 people (6 men and 14 women) aged 24-67 years (mean age — 41,5 years). Muscleto-fat ratio was determined by bioelectrical impedance analysis. The plasma concentration of homocysteine was measured using an immunochemistry analyser. Polymorphism analysis of folate cycle genes was performed using polymerase chain reaction. Statistical processing of the material, training and data prediction was performed using artificial neural networks (ANNs). Homocysteine levels before a 3-month consumption of fortified products are presented as Hc1, after — Hc2.Results. The blood level of homocysteine before taking fortified fruitberry bars varied from 6,5 to 24,2 µmol/l, averaging 12,45±2,9 µmol/l. After 3 months of use, the blood homocysteine level decreased to the range of 7,1-18 µmol/l and, on average, amounted to 10,87±2,6 µmol/l (p=0,028). Hyperhomocysteinemia was detected in two women (19,7 and 24,2 µmol/l) and one man (17,1 µmol/l). After consuming fruitberry bars, a significant decrease in blood homocysteine levels was observed from 19,7 to 14,3 µmol/l, from 24,2 to 14,1 µmol/l and from 17,1 to 15,5 µmol/l, respectively. A significant average correlation was revealed between Hc1 and Hc2 (r=0,579; p<1×10-5). Correlations were noted between blood homocysteine levels and body mass index, as well as responses about elevated blood glucose levels and the frequency of desire to reduce body weight (p<6,74×10-5).Conclusion. The results demonstrate a significant decrease in blood homocysteine in all participants when taking food products fortified with methylated forms of B vitamin (p=0,028). Individuals adhering to dietary restrictions showed a more pronounced decrease in homocysteine levels (p<6,74×10-5).

Arginine, Transsulfuration, and Folic Acid Pathway Metabolomics in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD = -0.50, 95% CI -0.95 to -0.05, p = 0.029) and folic acid (SMD = -0.37, 95% CI -0.65 to -0.09, p = 0.009), and higher homocysteine (SMD = 0.78, 95% CI 0.48 to 1.07, p < 0.001) and cysteine concentrations (SMD = 0.34, 95% CI 0.02 to 0.66, p = 0.038). Additionally, COPD was associated with significantly higher ADMA (SMD = 1.27, 95% CI 0.08 to 2.46, p = 0.037), SDMA (SMD = 3.94, 95% CI 0.79 to 7.08, p = 0.014), and ornithine concentrations (SMD = 0.67, 95% CI 0.13 to 1.22, p = 0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests that the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036.).

Monitoring physiological processes of fast-growing broilers during the whole life cycle: Changes of redox-homeostasis effected to trassulfuration pathway predicting the development of non-alcoholic fatty liver disease.

In the broiler industry, the average daily gain and feed conversion ratio are extremely favorable, but the birds are beginning to approach the maximum of their genetic capacity. However, as a consequence of strong genetic selection, the occurrence of certain metabolic diseases, such as myopathies, ascites, sudden cardiac death and tibial dyschondroplasia, is increasing. These metabolic diseases can greatly affect the health status and welfare of birds, as well as the quality of meat. The main goal of this study was to investigate the changes in the main parameters of redox homeostasis during the rearing (1-42 days of age) of broilers with high genetic capacity, such as the concentrations of malondialdehyde, vitamin C, vitamin E, and reduced glutathione, the activities of glutathione peroxidase and glutathione reductase, and the inhibition rate of superoxide dismutase. Damage to the transsulfuration pathway during growth and the reason for changes in the level of homocysteine were investigated. Further, the parameters that can characterize the biochemical changes occurring in the birds were examined. Our study is the first characterize plasma albumin saturation. A method was developed to measure the levels of other small molecule thiol components of plasma. Changes in redox homeostasis induce increases in the concentrations of tumor necrosis factor alpha and inflammatory interleukins interleukin 2, interleukin 6 and interleukin 8 in broilers reared according to current large-scale husbandry technology and feeding protocols. A significant difference in all parameters tested was observed on the 21st day. The concentrations of cytokines and homocysteine increased, while the concentrations of glutathione and cysteine in the plasma decreased. Our findings suggest that observed changes in the abovementioned biochemical indices have a negative effect on poultry health.

Reference intervals for total serum homocysteine concentration in shenzhen adults investigated with the aid of nanomaterials

Hyperhomocysteinemia is a risk factor for cardiovascular disease. Therefore, assessing the reference intervals of total serum homocysteine concentration is a critical step in the process of preventing cardiovascular disease. The primary goals of this study were to evaluate gender- and age-related differences in homocysteine concentration in the general population of Shenzhen and possible influencing factors. This retrospective study enrolled 2665 healthy subjects aged 18 to 89 years (mean age, 46.68 years). Blood samples were collected and serum indexes were detected with the aid of magnetic nanoparticles, and serum homocysteine concentration was evaluated by the circulating enzymatic method. The reference intervals (5th and 95th percentiles) of total serum homocysteine concentrations were analyzed by the Hoffmann approach. This approach has been widely used to evaluate reference intervals for various analytical parameters. There were significant differences between males and females in some anthropometric and laboratory indexes in the Shenzhen general population. Men had higher levels of creatinine, uric acid, blood urea nitrogen, and homocysteine, whereas women had higher levels of estimated glomerular filtration rate and thyroid-stimulating hormone. Further studies showed that the reference intervals of total serum homocysteine showed significant differences between males and females and among subjects of different ages. These concentrations were higher in males (mean, 12.74 μmol/L) than in females, and the reference intervals increased with age. Men aged 18 to 40 years had a higher risk of hyperhomocysteinemia than women of the same age. Age- and gender-specific reference ranges of serum homocysteine were defined.

Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats

AimsNeonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine – hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy. Main methodsPrenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed. Key findingsRats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats. SignificanceThe higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.

A Cell-Free Biosensor for Assessment of Hyperhomocysteinemia.

Hyperhomocysteinemia─a condition characterized by elevated levels of homocysteine in the blood─is associated with multiple health conditions including folate deficiency and birth defects, but there are no convenient, low-cost methods to measure homocysteine in plasma. A cell-free biosensor that harnesses the native homocysteine sensing machinery of Escherichia coli bacteria could satisfy the need for a detection platform with these characteristics. Here, we describe our efforts to engineer a cell-free biosensor for point-of-care, low-cost assessment of homocysteine status. This biosensor can detect physiologically relevant concentrations of homocysteine in plasma with a colorimetric output visible to the naked eye in under 1.5 h, making it a fast, convenient tool for point-of-use diagnosis and monitoring of hyperhomocysteinemia and related health conditions.

Association of plasma folic acid, vitamin-B12 and homocysteine with recurrent pregnancy loss. "A case control study".

To investigate the relationship of serum homocysteine, folic acid, and vitamin-B12 levels with recurrent pregnancy loss (RPL). A case-control study was conducted in the Department of Gynecology and Obstetrics, Dr. Ruth Pfau Civil Hospital, Karachi from July 2021 to June 2022. Total 124 participants were recruited from gynecology outpatient department after taking informed consent. The participants included 62 non-pregnant females with two or more consecutive unexplained RPLs and 62 healthy women having at least two successful deliveries without any pregnancy loss. Serum folic acid and vitamin-B12 levels were measured by chemiluminescent method and serum homocysteine was measured by enzyme-linked immunosorbent assay (ELISA). Comparison of quantitative variables with RPL cases and control was done by Mann-Whitney U-test (for non-normally distributed data) and independent sample t-test (for normally distributed data), while Pearson's chi-square test was used for the association of qualitative variables with RPL cases and control. Correlation of homocysteine with vitamin-B12 and folic acid was assessed in RPL cases. The median age of the study population was 27 (IQR 25-32) years. The median body mass index (BMI) was 26.25 (IQR 22-29) kg/m2. Cases had significantly lower serum folic acid (p-value=0.022), while vitamin-B12 was decreased in cases as compared to controls (p-value=0.295). Mean concentration of serum homocysteine was higher in RPL cases as compared to controls (p-value=0.094). There was significant association of serum vitamin B12 (p-value=0.001) and folic acid levels (p-value=0.004) with RPL. The homocysteine was not significantly correlated with vitamin-B12 (r=0.124, p=0.338) and folic acid (r=0.067, p=0.606) in the RPL group. Reduced level of serum folic acid and vitamin B12 was significantly associated with RPL cases, while homocysteine was marginally raised however the difference was not significant. Folic acid and vitamin B12 supplementation before next pregnancy in RPL patients is likely to be beneficial in improving pregnancy outcomes.

Electrode surfaces based on multiwall carbon nanotubes-chitosan composites validated in the detection of homocysteine biomarkers for cardiovascular disease risk monitoring

Abstract This study aimed to modify screen-printed carbon micro-electrode surfaces by coating them with multiwall carbon-based nanotubes conjugated with chitosan and then validated the formed multiwall carbon-based nanotubes-chitosan coated screen printed carbon micro-electrode for the detection of homocysteine, a biomarker analyte known as a risk indicator in cardiovascular disease. The microstructure surface and crystallographic structure stability of the formed multiwall carbon-based nanotubes-chitosan obtained at formed multiwall carbon-based nanotubes per chitosan ratios of 1:1, 2:1, 3:1, and 4:1 were examined via field emission scanning electron microscopy, X-ray radiation, Raman spectroscopy, surface area and pore size, and thermogravimetric analyses. Homocysteine solutions at 30–100 µM were measured by cyclic voltammetry using the different formed multiwall carbon-based nanotubes-chitosan compositions as sensor electrodes. That with an optimal formed multiwall carbon-based nanotubes per chitosan ratio of 4:1 showed the highest crystallinity and electrical conductivity and gave a high coefficient of determination (R2 = 0.9036) between the homocysteine concentration and the oxidation current detection over an operating range of 30–100 µM. This new composite microelectrode for detecting homocysteine concentration makes it a promising candidate for clinical applications.

REVERSED PHASE HPLC DETERMINATION OF TOTAL HOMOCYSTEINE, CYSTEINE, CYSTEINYL GLYCINE, GLUTATHIONE IN PLASMA OF EPILEPTIC PATIENTS

The fast and accurate reversed-phase HPLC method was predicated on qualitative and quantitative estimation of the total concentrations of the essential thiols in the plasma of adults volunteers compared with epileptic patients, which is l-cysteine (Cys) total homocysteine (tHys), cysteinyl glycine (Cys-Gly), glutathione (GSH) and cysteamine (Cstm), respectively. The plasma samples of (50) epileptic patients were classified into three groups; the non-anti-epileptic drug consisted of 20 patients (12 male, eight female) who were mainly diagnosed with idiopathic generalized epilepsy. The mean age was 34 ± 13 (range 19–48) years. The second group consisted of 30 patients receiving two types of anti-epileptic drugs, 18 patients (12 male and six female) receiving Carbamazepine, and 12 patients (7 males and five female) receiving phenytoin. The mean age of the patients was 32 ± 11 Compared with 31 healthy volunteers (20 male and 11 female). The mean age of the controls was 31 ± 9 (range 26–49 years). The mean duration of treatment of patients receiving the anti-epileptic drug was six months). All measurement was done using pre-column derivatization with bromobimane, and the derivative of each standard mixture were baseline separated on C18-DB (50 x 4.6 mm ID) column, 3μm particle size. The regression coefficients for the separated and standard deviation SD within-run ranged from 0.09 to 8.40 μmol/L, and between-run ranged from 0.15to 9.16 μmol/L; the analytical procedure gave good linearity in the range between 1.25 to 20 µmole/ l, the detection limit was 0.1 µmole /L for all the thiol groups. Analytical recovery was 96.9–107.4 %; the mean concentration of plasma cysteine and total homocysteine was slightly higher in males than females; it was 221± 75 for adult males and 190± 44 μmol/L for adult females, while t-homocysteine was (10.55 ±2.45 vs. 9.79 ± 1.88 μmol/L, the results observed that the value of cysteine and homocysteine were significantly higher in epileptic patients using Carbamazepine and phenytoin than in healthy volunteers. Mean values for glutathione were lower, while cysteinyl glycine showed no significant difference in healthy and epileptic patients and no sex- and age-dependent.

Serum 5-Methyltetrahydrofolate Status Is Associated with One-Carbon Metabolism-Related Metabolite Concentrations and Enzyme Activity Indicators in Young Women.

Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18-25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman's rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

Raised Maternal Homocysteine Levels in Antenatal Women at 10 to 14 Weeks of Gestation and Placenta-Mediated Complications: A Cohort Study.

Background Placenta-mediated complications, such as preeclampsia, placental abruption, and fetal growth restriction, can indeed lead to significant maternal and perinatal morbidity and mortality. Early detection and management of these conditions are crucial to ensuring optimal outcomes for both the mother and baby.However, there have been inconsistent correlations found between maternal homocysteine levels and placenta-related problems in various studies. Therefore, prospective research based on data pointing to a role for hyperhomocysteinemia in placenta-mediated complications will open doors for early detection and management of these complications. Thus, this study aims to determine if a higher risk of placenta-mediated problems is connected with a higher maternal plasma homocysteine content between 10 and 14 weeks of gestation. Methodology An observational prospective cohort study was conducted in the Department of Obstetrics and Gynecology, consisting of all the antenatal women between 10 and 14 weeks of gestation attending outpatient departments or inpatients admitted in labor rooms or wards having singleton pregnancies. Along with socio-demographic information and detailed history, a clinical examination was performed, and blood samples were collected to determine plasma homocysteine levels. Results As per thereceiver operating characteristic curve (ROC curve), the cut-off value taken was <5 for the low level of serum homocysteine, 5 to 15 micromol/L for the normal value, and >15 micromol/L for a raised serum homocysteine level. The cutoff value for our study was 45 micromol/L with a sensitivity of 78.33%, a specificity of 91.67%, a positive predictive value of 90.38%, and a negative predictive value of 80.88% with a diagnostic accuracy of 85%. This means that, for most of the women included in the present study, those who developed placenta-mediated complications had serum blood homocysteine levels of 45 micromol/L or more at 10-14 weeks of gestation. Conclusion Women with high homocysteine levels in the late first trimester had more placenta-mediated complications, such as abruption, pre-eclampsia, restricted fetal growth, and recurrent pregnancy losses, compared to women with a normal level of homocysteine in the late first trimester. Therefore, measuring blood homocysteine levels in pregnancy may be helpful as a diagnostic test for the early detection of high-risk individuals for placenta-mediated complications.

Follicular homocysteine as a marker of oocyte quality in PCOS and the role of micronutrients

PurposeDoes follicular homocysteine predict the reproductive potential of oocytes following FSH stimulation in PCOS women? Can it be modulated by dietary interventions?MethodsThis was a prospective, randomized, interventional clinical study. Forty-eight PCOS women undergoing in vitro fertilization at a private fertility clinic were randomized for a dietary supplementation providing micronutrients involved in homocysteine clearance or no treatment. The supplement was assumed 2 months before stimulation until pick-up day. Monofollicular fluids were collected and frozen. After embryo transfer, the fluids from the follicles generating the transferred embryos were thawed and analyzed.ResultsFollicular homocysteine showed a negative correlation with clinical pregnancy both in the whole population (r = − 0.298; p = 0.041) and in controls (r = − 0.447, p = 0.053). The support achieved a non-significantly lower concentration of follicular homocysteine (median [IQR]–7.6 [13.2] vs 24.3 [22.9]). Supplemented patients required far less FSH for stimulation (1650 [325] vs 2250 [337], p = 0.00002) with no differences in the number of oocytes collected, MII rate, and fertilization rate. Supplemented patients enjoyed higher blastocyst rate (55% [20.5] vs 32% [16.5]; p = 0.0009) and a trend for improved implantation rate (64% vs 32%; p = 0.0606). Clinical pregnancy rates were 58% vs 33% in controls (p = ns).ConclusionFollicular homocysteine is a suitable reporter that might be investigated as a tool for oocyte-embryo selection. A diet enriched with methyl donors may be useful in PCOS and supplements may also help. These findings may be also true for non-PCOS women, which warrants investigation.The study was approved by the Acibadem University Research Ethics Committee (2017–3-42). Clinical trial retrospective registration number ISRCTN55983518.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Serum homocysteine concentration as a marker for advanced diabetic nephropathy in a cohort of elderly patients

BackgroundHyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN).MethodsClinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed.ResultsDN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration (P < 0.010) and urinary protein/creatinine ratio (P < 0.001) were risk factors, while the VD2 + VD3 serum concentration (P < 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN.ConclusionHcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.