Increased Plasma Hcy Research Articles

Vitamin B12 deficiency in newborns: impact on individual's health status and healthcare costs.

The identification of vitamin B12 (B12) deficiency in the newborn may prevent neurological damage and a delay in the normal growth. In this study we characterized the incidence of B12 deficiency in newborns, the costs associated to the clinical diagnosis and management, and the relevance to optimize the use of cobalamin biomarkers during treatment follow-up. Starting from a continuous case series of 146,470 screened newborns (November, 1st 2021- December, 3rd 2023), the Regional Reference Laboratory for Neonatal Screening identified 87 newborns having altered levels of biomarkers of cobalamin metabolism measured by Newborn Screening. These subjects were confirmed with a nutritional B12 deficiency of maternal origin by performing the serum B12 measurements and plasma homocysteine (Hcy) both on the newborns and respective mothers. A cost analysis was performed to characterize the costs/year of identifying and managing B12 deficiency cases. At baseline, median (interquartile range) serum B12 levels of 185.0 (142.3-246.0) ng/L and threefold increased plasma Hcy concentrations above the normal level confirmed a severe condition of deficiency in the newborns. After intramuscular B12 supplementation, serum B12 measured at the first follow up visit showed a fivefold increase, and the levels of Hcy returned to normal. From the healthcare perspective, the costs for diagnosing and managing all newborns with B12 deficiency is 188,480 €/year. Preventing B12 depletion in newborns lowers healthcare costs and likely improves their health outcomes. Further studies are however required to address the clinical pathway to identify, treat and monitor pregnant women with marginal and low B12 status, in order to achieve these goals.

Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. Involving 1042 volunteers aged 20 to 80years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] β = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10µmol/L. In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

Changes in homocysteine and non-mercaptoalbumin levels after acute exercise: a crossover study

BackgroundAcute exercise is one factor that increases blood homocysteine levels, and elevated homocysteine levels cause oxidative stress. Albumin, which is abundant in blood, is an antioxidant, and the redox state of albumin is used as an index of oxidative stress in blood. This study aimed to assess the effect of acute exercise on plasma homocysteine levels and the blood non-mercaptoalbumin/mercaptoalbumin ratio as an oxidative stress marker.MethodsThis study used a crossover design with exercise and control conditions. Under exercise conditions, a bicycle ergometer was used to perform 40 min of transient constant-load exercise at 65% heart rate reserve. Under control conditions, participants rested for 40 min. Blood was collected before, 30 min after, and 90 min after exercise, and at the same time points under control conditions. Samples were analyzed for the homocysteine concentration and non-mercaptoalbumin/mercaptoalbumin ratio.ResultsThe results revealed that a 65% heart rate reserve and 40 min of acute exercise increased plasma homocysteine concentration and non-mercaptoalbumin ratio. In the intra-condition comparison, the plasma Hcy concentration was significantly increased at Post 30 min (+ 0.83 ± 0.70 µmol/L, P = 0.003) compared with that at Pre in the exercise condition. Furthermore, 90 min after exercise, the blood non-mercaptoalbumin ratio was significantly increased (+ 0.35 ± 0.71%, P = 0.030) compared to Pre.ConclusionThese results indicate that the plasma Hcy concentration first increased, and then the non-mercaptoalbumin/mercaptoalbumin ratio increased as the elevated state was maintained. This study revealed that 65% heart rate reserve, 40 min of acute exercise increased plasma Hcy concentration and non-mercaptoalbumin ratio.

Causal effects of homocysteine levels on the components of sarcopenia: A two-sample mendelian randomization study.

Background: Currently, it is unclear whether there is a causal association between genetically predicted plasma homocysteine (Hcy) levels and the risk of sarcopenia. We performed a Mendelian randomization (MR) study to assess the association between circulating Hcy levels and the components [grip strength, walking pace, and appendicular lean mass (ALM)] of sarcopenia. Methods: Independent single nucleotide polymorphisms (SNPs) significantly associated with plasma Hcy levels served as instrumental variables. Summary-level data regarding the components of sarcopenia. Were obtained from the UK Biobank. Inverse variance weighted (IVW) as the primary method was used for Mendelian randomization (MR) analysis. We also use four models, weighted median, MR-Egger regression, Maximum likelihood, and Penalised weighted median, as supplementary methods to IVW. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of the causal association between Hcy levels and the components of sarcopenia. Results: The IVW-MR analysis suggested significant negative associations of increased plasma Hcy levels with grip strength (right: effect = -0.036, SE = 0.032, p = 5.53E-4; left: effect = -0.045, SE = 0.010, p = 1.45E-5), walking pace (effect = -0.038, SE = 0.011, p = 3.18E-4), and ALM (effect = -0.058, 0.013, p = 1.03E-5). However, there were no significant associations of decreased plasma Hcy levels with grip strength (right: effect = 0.005, SE = 0.021, p = 0.82; left: effect = -0.006, SE = 0.014, p = 0.64), walking pace (effect = 0.01, 0.020, p = 0.61), or ALM (effect = -0.034, SE = 0.018, p = 0.06).The accuracy and robustness of these findings were confirmed by sensitivity tests. Conclusion: Increased circulating Hcy levels were associated with lower grip strength, slower walking pace, and decreased ALM.

A compound reflects the level of homocysteine based on Rhodamine B and its ability to respond to homocysteine in the plasma of diabetic patients.

BackgroundThe level of homocysteine (Hcy) is significantly elevated in the plasma of patients with diabetes. The increased plasma Hcy level is positively correlated with the severity of the disease and is one of the important causes of diabetic complications.MethodsWe designed and synthesized a compound could reflect the level of Hcy based on rhodamine B, and the structure was verified by 1H‐NMR and EI‐HRMS. Then, the linearity, repeatability, selectivity, and cellar toxicity, the effects of the fluid viscosity and pH of compound on Hcy were measured; meanwhile, the response of Hcy level in the plasma of diabetic patients was detected.ResultsThis is a novel compound that has never been reported. The compound showed a satisfactory linear range and repeatability at the viscosity and pH of physiological fluid. In addition, the compound was capable of evading the interference from other amino acids and metal ions, and it exhibited high selectivity toward Hcy.ConclusionThe compound showed increased responsiveness to plasma Hcy in patients with diabetes in comparison with healthy individuals and effectively reflected plasma Hcy levels in healthy individuals and diabetic patients. Therefore, the compound is expected to be used in the diagnosis of diabetes mellitus.

Correlations of plasma homocysteine with cerebral white matter lesion severity and cognitive impairment in elderly patients with hypertension

Objective To investigate the correlations of plasma homocysteine(Hcy)levels with cerebral white matter lesion(WML)severity and cognitive impairment in elderly hypertension patients. Methods A retrospective case-control study was conducted.Ninty-eight elderly patients with hypertension were enrolled.Based on the presence or absence of hyperhomocysteinemia(hypertension with plasma Hcy levels ≥10 μmol/L was defined as H-type hypertension), patients were divided into two groups: a control group(n=48)and an H-type hypertension group(n=50). The degree of WML was rated by the Fazekas scale using magnetic resonance imaging(MRI)analysis.Neuropsychological examinations including mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)were taken to assess cognitive function.The degree of WML and cognitive impairment were compared between the two groups.Correlations of plasma Hcy levels with the degree of WML and cognitive impairment were analyzed. Results Compared with the control group, scores of the Fazekas scale(3.2±1.0 vs.2.5±1.0, P<0.05)and deep white matter hyperintensity on MRI(1.7±0.8 vs.1.3±0.7, P<0.05)increased, and scores of MMSE(24.9±3.3 vs.27.7±1.8, P<0.05)and MoCA(18.6±3.9 vs.25.0±3.0, P<0.05)decreased in the H-type hypertension group.Plasma Hcy levels were positively correlated with the degree of WML(r=0.430, P<0.01)and negatively correlated with cognitive function(r=-0.406 in MMSE and-0.663 in MoCA, P<0.01). Multivariate logistic regression showed that Hcy, fasting blood-glucose, deep WML, low-density lipoprotein cholesterolin, age and systolic pressure were influencing factors for cognitive impairment(P<0.01). Conclusions WML and cognitive function are worse in elderly H-type hypertension patients than in hypertension patients with normal Hcy levels.WML and cognitive impairment are aggravated with increased plasma Hcy levels.The plasma Hcy level may be an effective clinical indicator of cognitive function in elderly people with hypertension. Key words: Hypertension; Cysteine; Leukoencephalopathies; Cognitive disorders

Link between Homocysteine and Cardiovascular Diseases

Purpose of Review Numerous studies have shown a positive correlation between serum Hcy level and various pathological conditions such as coronary, carotid, and peripheral vascular disease. Increased plasma Hcy levels are associated not only with an increased risk of arteriosclerosis but also with atherosclerosis and thrombosis. The aim of this review is to review biochemical mechanisms responsible for development and progression of cardiovascular diseases (CVD).

Mesenchymal Stem Cells Derived Exosomes Promotes Bone Regeneration through Cystathionine‐β‐synthase Enhanced Angiogenesis and Osteogenesis during Bone Development

It is critical that bone formation and angiogenesis are tightly coordinated during bone development and fracture healing, but the molecular regulator of such intercellular communication in bone microenvironment are not well studied. Cystathionine‐β‐synthase (CBS), an enzyme in homocysteine (Hcy) metabolic pathway play crucial role in osteoblast differentiation. Therefore, we hypothesize that CBS as a novel molecular regulator in osteoblasts, which regulates vascularization during bone development in osteoblast derived exosome. To test this hypothesis, we have used 7–10 weeks old male mice in our study; wild type mice (C57BL/6, WT) and CBS+/− mice. Blocking the CBS function was done by either inhibitor hydroxylamine (HA) or SiRNA prevented osteoblast differentiation and mineralization. This was supported by studies using osteoblasts cultured from bone marrow of CBS deficient (CBS+/−) mice. Exosomes of mesenchymal stem cell derived osteoblasts cultured stimulated endothelial migration and angiogenesis, which was prevented by blocking CBS in osteoblasts using HA or SiRNA. Mass spectrometry analysis and ELISA assay identified among others vascular endothelial growth factor (VEGF)‐A and VEGF homolog placental growth factor (PIGF) to be present in control osteoblasts culture medium and CBS(+/+) mice osteoblasts but not in osteoblasts treated with HA and CBS+/− osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of CBS+/− mice. However, osteopenia phenotype was confirmed in CBS+/− mice by microCT analysis. CBS+/− mice showed significantly reduced bone mineral density (BMD) and bone volume/tissue volume (BV/TV) and showed increased plasma Hcy levels compared to CBC+/+ mice (WT). However, CBS+/− mice exhibited a more significant increase in the number of TRAP‐positive osteoclasts and higher levels of RANKL than CBS+/+ mice. This suggests that Hcy levels may be associated with osteoclast activity. Furthermore, real‐time PCR and western blot analyses revealed significant decreases Alkaline phosphatase (ALP) and Runt‐related transcription factor 2 (RUNX2) expression in CBS‐deficient (CBS+/−) mouse bone marrow cells. In conclusion, we demonstrate that CBS in osteoblasts is at the crossroad of osteoblast differentiation/mineralization and angiogenesis. These findings uncover the previously undefined molecular understanding of CBS that promote angiogenesis and osteogenesis in bone development and fracture repair.Support or Funding InformationThis work is financial supported from National Institute of health grant AR‐067667 and HL‐107640‐NT are greatly acknowledged.

Hyperhomocysteinemia, insulin resistance and body mass index in Iranian young women with polycystic ovary syndrome

Abstract Objectives Polycystic ovary syndrome (PCOS) is a common disease among young women that causes hyperinsulinemia. Hyperhomocysteinemia is shown to be correlated positively with the hyperinsulinemia. This study aimed to evaluate serum homocysteine (Hcy) level and its correlation with other serum metabolic amongst over weight, obese and non-obese PCOS women. Methods Sixty women with PCOS and 20 healthy subjects were studied. Hormonal assays, lipid profile, Hcy and fasting insulin levels, insulin resistance (IR) indices (HOMA and QUICKI) determinations and ultrasound evaluation were performed. Results Mean of BMI was significantly higher in PCOS subjects as compared with the controls (29.95 ± 4.91 vs 26.09 ± 4.80 kg/m 2 ; p = 0.005). The mean fasting insulin levels were also significantly higher (17.80 ± 8.02 vs 11.55 ± 6.81 μU/dl; p = 0.003) where we found no difference in fasting glucose concentrations between groups. IR indices in PCOS women were significantly higher than control group (p Conclusions Our study shows the tendency toward hyperhomocysteinaemia, hyperinsulinemia and higher BMI in PCOS patients. These factors are critical predictors of PCOS; however, BMI and IR are an independent risk factor to increase plasma Hcy levels in PCOS women.

Hyperhomocysteinemia is associated with decreased apolipoprotein AI levels in normal healthy people.

BackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for various cardiovascular diseases. Animal studies have shown that homocysteine (Hcy) inhibits hepatic expression of apolipoprotein AI (apoAI). Our recent clinical study showed that increased plasma Hcy levels were associated with decreased apoAI levels in patients with impaired glucose tolerance. In this study, we assessed a potential association between Hcy and apoAI levels in normal healthy people.MethodsA total of 1768 normal healthy individuals were divided into two groups: the control group (subjects without HHcy) and the HHcy group (subjects with HHcy).ResultsHHcy subjects exhibited significantly lower high-density lipoprotein cholesterol (HDL-C) and apoAI levels than the control group (HDL-C: 1.18 ± 0.25 vs. 1.29 ± 0.32 mmol/L; apoAI: 1.38 ± 0.19 vs. 1.47 ± 0.25 g/L; all P < 0.01). Plasma Hcy levels were negatively associated with HDL-C and apoAI levels after adjustments for age, BMI and TG (HDL-C: r = –0.10; apoAI: r = –0.11; all P < 0.05). Multivariate regression analysis showed that the plasma Hcy levels were an independent influencing factor for apoAI (β = –0.065, P < 0.05).ConclusionsIncreased plasma Hcy levels were associated with decreased apoAI levels in normal healthy people, and the inhibition of apoAI synthesis might be a mechanism through which Hcy is linked with the development of atherosclerosis in HHcy subjects.

Long-term methionine-diet induced mild hyperhomocysteinemia associated cardiac metabolic dysfunction in multiparous rats.

Mild hyperhomocysteinemia (HHcy, clinically defined as less than 30 μmol/L) is an independent cardiovascular disease (CVD) risk factor, and is associated with many complications during pregnancy, such as preeclampsia (PE). The aim of this study was to assess the effect of long-term mild HHcy on cardiac metabolic function of multiparous rats. Female rats were mated 3 to 4 times and were fed with methionine in drinking water to increase plasma Hcy (2.9 ± 0.3 to 10.5 ± 2.3 μmol/L) until termination. This caused significant increase of heart weight/body weight (0.24 ± 0.01 to 0.27 ± 0.01 g/100 g) and left ventricle weight (0.69 ± 0.03 to 0.78 ± 0.01 g). Superoxide production was increased by 2.5-fold in HHcy hearts using lucigenin chemiluminescence. The ability of bradykinin and carbachol to regulate myocardial oxygen consumption (MVO2) in vitro was impaired by 59% and 66% in HHcy heart, and it was restored by ascorbic acid (AA), tempol, or apocynin (Apo). Protein expression of p22phox subunit of NAD(P)H oxidase was increased by 2.6-fold, but there were no changes in other NAD(P)H oxidase subunits, NOSs or SODs. Microarray revealed 1518 genes to be differentially regulated (P < 0.05). The mRNA level of NAD(P)H oxidase subunits, NOSs or SODs remained unchanged. In conclusion, long-term mild HHcy increases cardiac superoxide mainly through regulation of p22phox component of the NAD(P)H oxidase and impairs the ability of NO to regulate MVO2 in heart of multiparous mothers.

Folic Acid Mitigates Angiotensin-II-Induced Blood Pressure and Renal Remodeling

Clinical data suggests an association between systolic hypertension, renal function and hyperhomocysteinemia (HHcy). HHcy is a state of elevated plasma homocysteine (Hcy) levels and is known to cause vascular complications. In this study, we tested the hypothesis whether Ang II-induced hypertension increases plasma Hcy levels and contributes to renovascular remodeling. We also tested whether folic acid (FA) treatment reduces plasma Hcy levels by enhancing Hcy remethylation and thus mitigating renal remodeling. Hypertension was induced in WT mice by infusing Ang II using Alzet mini osmotic pumps. Blood pressure, Hcy level, renal vascular density, oxidative stress, inflammation and fibrosis markers, and angiogenic- and anti-angiogenic factors were measured. Ang II hypertension increased plasma Hcy levels and reduced renal cortical blood flow and microvascular density. Elevated Hcy in Ang II hypertension was associated with decreased 4, 5-Diaminofluorescein (DAF-2DA) staining suggesting impaired endothelial function. Increased expression of Nox-2, -4 and dihydroethidium stain revealed oxidative stress. Excess collagen IV deposition in the peri-glomerular area and increased MMP-2, and -9 expression and activity indicated renal remodeling. The mRNA and protein expression of asymmetric dimethylarginine (ADMA) was increased and eNOS protein was decreased suggesting the involvement of this pathway in Hcy mediated hypertension. Decreased expressions of VEGF and increased anti-angiogenic factors, angiostatin and endostatin indicated impaired vasculogenesis. FA treatment partially reduced hypertension by mitigating HHcy in Ang II-treated animals and alleviated pro-inflammatory, pro-fibrotic and anti-angiogenic factors. These results suggest that renovascular remodeling in Ang II-induced hypertension is, in part, due to HHcy.

Short-term creatine supplementation does not reduce increased homocysteine concentration induced by acute exercise in humans

The purpose of the study is to evaluate the effects of creatine supplementation on homocysteine (Hcy) plasma levels after acute exercise in humans. Twenty-three young (under-20) soccer players were divided into 2 groups: creatine (Cr)- and placebo (Pla)-supplemented groups. The supplementation was performed in double-blind controlled manner using creatine or placebo tablets with 0.3 g/kg during 7 days. Before and after 7 days of supplementation, the athletes performed an acute high-intensity sprint exercise (two consecutive running-based anaerobic sprint test protocol consisted in 6 × 35 m sprint with 10 s between them). Blood samples were collected before and after 7 days of supplementation as well as 0 and 1 h after exercise protocol. Homocysteine concentration significant increased (P < 0.05) 1 h after acute exercise (18%). Acute exercise also decreased red blood cell S-adenosylmethionine (SAM) 30% with no changes in SAM/SAH ratio. Seven days of creatine supplementation were able to increase (P < 0.05) plasma creatine concentration (Pla 130.1 ± 21.7 vs Cr 1,557.2 ± 220.3 μmol/L) as well as decrease (P < 0.05) plasma guanidinoacetic acid (33%). Controversially, creatine supplementation did not change Hcy plasma level after 7-day supplementation (Pla 6.9 ± 0.2 vs Cr 7.2 ± 0.2 μmol/L) or after acute exercise (Pla 8.2 ± 0.3 vs Cr 8.4 ± 0.3 μmol/L). No changes in plasma vitamin B12 and folate as well as cysteine and methionine were found. Seven days of creatine supplementation does not avoid increased plasma Hcy induced by acute sprint exercise in humans.

Formate metabolism is altered in riboflavin‐deficient rats

Riboflavin can play an important role in one‐carbon metabolism, particularly as its active forms, FAD and FMN, are used as cofactors in both the production and utilization of formate.Rats were fed either a riboflavin‐replete or a riboflavin‐deficient diet for 13 days at which point blood and tissue samples were taken. Riboflavin deficiency was assessed by the Erythrocyte Glutathione Reductase activation coefficient (EGRac). Total plasma homocysteine (Hcy), hepatic S‐adenosylmethionine (SAM), and S‐adenosylhomocysteine (SAH) concentrations were analyzed by HPLC. Hepatic methylenetetrahydrofolate reductase (MTHFR) was assessed by means of enzyme activity and immunoblot. Plasma formate was analyzed by GC‐MS.EGRac confirmed riboflavin deficiency. Plasma Hcy was elevated in the deficient animals. Hepatic SAM was lower in the deficient animals; there was no difference in SAH. MTHFR was found to be markedly reduced in the deficient group; plasma formate concentration was decreased by about 20%.The increased plasma Hcy and reduced hepatic SAM indicate an impairment in re‐methylation. The decreased plasma formate levels coupled with the defective remethylation suggest that the flavin‐dependent formate production may be decreased. This will be further examined by means of isotopic experiments to measure the endogenous rates of formate production.Grant Funding Source: Canadian Institutes of Health Research &amp; Research Development Corporation of Newfoundland and Labrador

C677T Methylenetetrahydrofolate Reductase and Plasma Homocysteine Levels among Thai Vegans and Omnivores

Hyperhomocysteinemia among vegetarians and vegans is caused mostly by vitamin B12 deficiency. A C-to-T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene results in a thermolabile MTHFR, which may affect homocysteine (Hcy) levels. The importance of this gene mutation among populations depends on the T allele frequency. Blood Hcy, vitamin B12, folate, vitamin B6, and MTHFR C677T mutation status were determined in 109 vegans and 86 omnivores aged 30 - 50 years. The vegans had significantly higher Hcy levels than the omnivores, geometric means (95 % CI) 19.2 (17.0 - 21.7) µmol/L vs. 8.53 (8.12 - 8.95) µmol/L, p < 0.001. A C-to-T mutation in the vegans increased plasma Hcy, albeit insignificantly; geometric means 18.2 µmol/L, 20.4 µmol/L, and 30.0 µmol/L respectively in CC, CT, and TT MTHFR genotypes. There was also a significant decrease in serum folate; geometric means 12.1 ng/mL, 9.33 ng/mL, and 7.20 ng/mL respectively, in the CC, CT, and TT mutants, p = 0.006, and particularly, in the TT mutant compared with the CC wild type, 7.20 ng/mL vs. 12.1 ng/mL, p = 0.023. These findings were not seen in the omnivores. It was concluded that hyperhomocysteinemia is prevalent among Thai vegans due to vitamin B12 deficiency. C-to-T MTHFR mutation contributes only modestly to the hyperhomocysteinemia.

Study on correlation between plasma homocysteine levels and TCM syndromes of dementia

Objective To investigate the relationship between plasma homocysteine (Hcy) levels and TCM syndromes of dementia.Methods 250 cases were divided into a dementia group (120 cases) and non-dementia group (130 cases).120 cases in the dementia group include 36 Alzheimer dementia(AD) patients and 84 vascular dementia (VaD) patients.The plasma levels of Hcy were measured in all 250 cases.The relationship between Hcy levels,TCM syndromes and dementia was analyzed.Results The level of plasma Hcy was significantly higher in the dementia group (17.13 ± 9.01) nmol/ml than that in the non-dementia group (12.81 ± 7.94) nmol/ml,and it was highest in the VaD patients (P＜0.01).The mean of Hcy concentration in obstruction of phlem-turbid syndrome was higher(18.43±7.81)nmol/ml than syndromes [Tanyuzuluo (5.38 ± 8.91)nmol/ml,Shenxusuikui (16.44 ± 9.05)nmol/ml,Shenyinkuixu(16.19 ± 9.24)nmol/ml,Ganjinghuowang (15.92 ± 7.28)nmol/m1,Pishen-Yangxu(12.26 ± 5.17) nmol/ml (P ＜ 0.01)].Conclusion Increased plasma Hcy levels may be one of the risk factors leading to AD or VaD. Key words: Dementia; Homocysteine; TCM syndromes

Akut İskemik İnmeli Hastalarda Plazma Homosistein Seviyeleri: Kesitsel Bir Çalışma

Objective: In this study, we aimed to investigate plasma homocysteine (Hcy) changes in patients within the acute period of ischemic stroke. Material and Methods: In this cross-sectional study, a total of 110 patients with acute ischemic stroke presenting within 48 hours of onset and 45 age and gender-matched healthy subjects were evaluated. Hcy was measured on 2nd, 4th, 7th, 10th and 14th days of the hospitalization. Control samples were also collected after a 12-hour fasting period. Results: Statistically significantly lower Hcy levels were found in acute ischemic stroke patients on the 2nd day compared to the control group (p<0.001). No significant difference was found in the 4th day between the groups (p=0.478). In all other days on which test was performed, Hcy levels were statistically significantly higher in acute ischemic stroke group compared to the control group (p<0.001 for all). Conclusion: This study suggests that Hcy levels are not significantly elevated after recent ischemic stroke, but rise in the 2nd week of admission, and our findings do not support the hypothesis that raised plasma Hcy levels predate ischemic stroke. Therefore, increased plasma Hcy level is a consequence of disease process, and has no value as a predictor of ischemic stroke.

Homocysteinemia in Mice with Genetic Betaine HomocysteineS -Methyltransferase Deficiency Is Independent of Dietary Folate Intake1–3

Elevated homocysteine (Hcy) concentrations are associated with increased risk of several chronic diseases. Hcy can be removed by methylating it to form methionine via either the betaine homocysteine S-methyltransferase (BHMT) or the methionine synthase (MS) pathway. BHMT uses betaine as the methyl donor, whereas MS uses 5-methyltetrahydrofolate. We previously found that mice with the gene encodingBhmt deleted ( Bhmt -/- ) had altered Hcy metabolites in tissues. This study aimed to determine whether folate supplementation of Bhmt -/- mice reverses, and folate deficiency exacerbates, these metabolic changes. Bhmt -/- mice and their littermates ( Bhmt +/+ mice) were fed a folate-deficient (FD; 0 mg/kg diet), a folate control (FC; 2 mg/kg diet), or a folate-supplemented (FS; 20 mg/kg diet) diet for 4 wk. Bhmt -/- mice had higher plasma Hcy and hepatic S -adenosylhomocysteine (AdoHcy) concentrations and had lower hepatic S -adenosylmethionine (AdoMet) concentrations compared with Bhmt +/+ mice for all diets. Although the FD diet increased plasma Hcy ( P < 0.05) and hepatic AdoHcy ( P < 0.001) concentrations in Bhmt +/+ mice compared with FC and FS mice, the FD diet had no effect on the metabolites measured in Bhmt -/- mice. The FS diet did not ameliorate elevated plasma Hcy and elevated hepatic AdoHcy concentrations but did increase hepatic AdoMet concentrations in Bhmt -/- mice ( P < 0.001) compared with FD and FC mice. We conclude that the BHMT pathway is a major route for the elimination of Hcy in mice and that the MS pathway has little excess capacity to methylate the Hcy that accumulates when the BHMT pathway is blocked.

Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients.

The main aim of the present study was to investigate the plasma phospholipids (PL) fatty acids status and its association with plasma Hcy in patients with type 2 diabetes mellitus (T2DM). One hundred and four T2DM (aged 57.3±13.4 y) and 150 healthy subjects (aged 48.4±8.7 y) were recruited. Plasma Hcy and PL fatty acids were determined by standard methods. Plasma Hcy concentration in T2DM was significantly higher than that in healthy subjects (p<0.001). The prevalence of hyperhomocysteinemia was significantly higher in T2DM (36.54%) than that in healthy subjects (17.32%) (p=0.012). Plasma PL 20:4n-6 (r=0.303, p=0.012), 22:5n-3 (r=0.312, p=0.01), total PUFA (r=0.303, p=0.012), n-6 PUFA (r=0.261, p=0.032) were significantly positively associated with plasma Hcy concentration in T2DM. While, plasma PL n-3:n-6 PUFA (r=-0.400, p=0.046) was negatively associated with plasma Hcy in T2DM. In healthy subjects, plasma PL 22:6n-3 (r=-0.201, p=0.042) was negatively associated with plasma Hcy. In addition, plasma PL 22:6n-3 (r=0.193, p=0.044) and 22:5n-6 (r=0.234, p=0.038) were significantly negatively associated with plasma vitamin B-12 in healthy subjects. Our results suggested that increased plasma Hcy levels in T2DM associated with low n-3:n-6 ratio intake. We suggest that T2DM increase their long chain n-3 PUFA intake from fish or fish oil while decrease n-6 PUFA intake.

Role of NO and Superoxide in Hyperhomocysteinemia Induced Cardiac Metabolic Dysfunction in Pregnant Cystathionine Beta‐synthase Heterozygote Mice

Genetic defects in cystathionine beta‐synthase (CBS) can cause severe hyperhomocysteinemia (HHcy). HHcy causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. This study assessed the mechanisms of HHcy on the NO‐dependent control of cardiac O2 consumption in pregnant CBS heterozygote (HET) mice. Pregnant CBS HET mice (n=8) were fed low‐folate diet for 20 days to increase plasma Hcy (8.2±0.5 of WT to 17.9±2.2 uM of HET). As compared to wild type (WT) (n=10), while heart weight/body weight increased by 18.2%, ejection fraction decreased from 85.7±0.8% to 80.3±1.8% in HET. Systolic blood pressure was significantly increased from 92.5±3.6 mmHg of WT to 114.5±4.0 mmHg in HET, and MBP from 66.8±9.2 mmHg to 82.9±5.5 mmHg, without hypertension. The total peripheral resistance significantly increased by 42.1%. The ability of bradykinin to reduce myocardial O2 consumption in vitro was impaired by 56% in heart. The response was restored by ascorbic acid, tempol and apocynin. O2− production was increased by 2.7 folds in Hcy heart using lucigenin chemiluminescence.ConclusionCBS deficiency caused HHcy during pregnancy, impairs cardiac function, increases O2− production and reduces the ability of NO to regulate myocardial O2 consumption probably through NADPH oxidase stimulation.