Plasma Homocysteine Concentrations Research Articles

Homocysteine in chronic kidney disease: Clinical diagnostic aspects

Chronic kidney disease (CKD) is one of the most common pathologies worldwide. With CKD, cardiovascular risk increases and mortality rises. The article presents the role of homocysteine as a laboratory marker of renal failure and the development of cardiovascular disease. Homocysteine is a thiol-containing amino acid, which is an intermediate product of methionine metabolism, which is metabolized in two ways: due to the transfer of the sulfate group, which occurs in the presence of vitamin B 6, or remethylation, which occurs in the presence of vitamin B 12 and folic acid. Normally, in an adult, the concentration of total homocysteine in blood plasma does not exceed 15 μmol/L. It has been shown that with CKD, hyperhomocysteinemia is observed at the initial stages and its frequency increases at the pre- and dialysis stages of the disease. Hyperhomocysteinemia provokes endothelial dysfunction, accelerates systemic atherosclerosis, increases the risk of atherothrombotic complications. Evaluation of plasma homocysteine levels may be useful in stratifying nephrocardio- and cerebrovascular risk in CKD.

Controlled Dietary Folate Affects Folate Status in Nonpregnant Women

In a study designed to estimate the requirement for dietary folate in nonpregnant women, 17 women (21–27 y) consumed 200, 300, or 400 µg/d of total folate for 70 d which was provided by low folate conventional foods (30 µg) plus supplemental folic acid. Group means for initial serum and erythrocyte folate and plasma homocysteine concentrations were not significantly different. Serum and erythrocyte folate decreased relative to the initial value in the 200 µg/d group (43.4 ± 12.1%, 13.6 ± 16.6%, respectively; mean ± SD), in contrast to an increase in the 400 µg/d group (16.8 ± 52.0%, 10.2 ± 18.5%, respectively). The final serum folate in the 200 and 300 µg/d groups (6.4 ± 0.8 nmol/L, 7.3 ± 1.1 nmol/L, respectively) was significantly lower than that of the 400 µg/d group (14.3 ± 2.0 nmol/L), with evidence in the 200 µg/d and 300 µg/d groups of low (<6.8 nmol/L) serum folate concentrations. Differences in final erythrocyte folate did not reach statistical significance, although low values (<362 nmol/L) were frequent in subjects with 200 µg/d intake. In the 200 µg/d group, plasma homocysteine was negatively correlated with serum and erythrocyte folate, and final mean plasma homocysteine (12.6 ± 1.7 µmol/L) was significantly higher than that of the 300 or 400 µg/d groups. Elevated plasma homocysteine levels (>16 µmol/L) were observed in the 200 µg/d group only. Data from this study indicate that 200 µg/d of folate was not sufficient to maintain folate status of these women and suggest that the current RDA of 180 µg/d may not be adequate to meet the dietary folate intake needs of nonpregnant women.

ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ ЭНДОТЕЛИЯ СОСУДОВ ПРИ ГИПЕРГОМОЦИСТЕИНЕМИИ У ДЕТЕЙ С АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИЕЙ

Background. Homocysteine is a sulfur-containing amino acid that can have a damaging effect on the vascular endothelium, being an independent risk factor for the development of cardiovascular pathology. The purpose. To evaluate the functional state of the vascular endothelium in hyperhomocysteinemia in children with arterial hypertension. Material and methods. 111 children aged 14 to 18 years were examined. All patients were divided into 3 groups:group I (n=51) consisted of children with arterial hypertension, group II (n=30) included those with high normal blood pressure, group III was composed of 30 healthy children. Plasma homocysteine was determined by high-pressure liquid chromatography. Results. Plasma homocysteine concentration increases in patients with high normal blood pressure and arterial hypertension compared with healthy children. Pathological decrease in endothelium-dependent vasodilation is accompanied by an increase in the concentration of homocysteine in the blood plasma.

Factors Related to Plasma Homocysteine Concentration in Young Adults: A Retrospective Study Based on Checkup Populations

The distribution profile of plasma homocysteine (Hcy) in young adults and its related factors are not well understood. We performed a generalized estimating equations (GEE) analysis for plasma-Hcy-correlated factors in 2436 young adults, aged 20-39 years, from a health checkup population. We observed that the mean Hcy concentration in males (16.7 ± 10.3 μmol/L) was significantly higher than that in females (10.3 ± 4.0 μmol/L), and hyperhomocysteinemia (HHcy) prevalence in males was 5.37 times than that in females (33.3% vs. 6.2%). A GEE analysis stratified by sex indicated that age (B = -0.398, p < 0.001) and LDL-C (B = -1.602, p = 0.043) were negatively correlated, while BMI (B = 0.400, p = 0.042) was positively correlated, with the Hcy level in young males. ALT (B = -0.021, p = 0.033), LDL-C (B = -1.198, p < 0.001) and Glu (B = -0.446, p = 0.006) were negatively correlated, while AST (B = 0.022, p = 0.048), CREA (B = 0.035, p < 0.001), UA (B = 0.004, p = 0.003) and TG (B = 1.042, p < 0.001) were positively correlated, with the Hcy level in young females. These results suggest that young males have a significantly higher plasma Hcy level and HHcy prevalence than young females; therefore, more attention should be paid to the reason for and effect of the higher HHcy prevalence in young males.

High prevalence of vitamin B-12 deficiency before and early after gastrectomy in patients with gastric cancer.

Gastrectomy causes vitamin B-12 deficiency since vitamin B-12 requires gastric acid and intrinsic factor for its absorption. Vitamin B-12 deficiency is considered to develop years after gastrectomy because of large hepatic storage. However, most gastric cancer develops after long-standing atrophic gastritis with vitamin B-12 malabsorption. We have investigated vita-min B-12 status in 22 patients before gastrectomy and 53 patients after gastrectomy due to gastric cancer, also with consideration on post-gastrectomy anemia. Blood vitamin B-12, folic acid, homocysteine concentrations, parameters of anemia, and dietary intake were evaluated. Percentage of patients with severe vitamin B-12 deficiency (serum vitamin B-12 < 150 pmol/L), vitamin B-12 deficiency (150 pmol/L to < 258 pmol/L) was 19.0 %, and 52.4 % respectively in patients gastrectomized within three years. Before gastrectomy, three and seven patients exhibited severe deficiency and deficiency, respectively. In gastrectomized patients, plasma homocysteine concentration was inversely associated with serum vitamin B-12 concentration, and vitamin B-12 deficiency- and iron deficiency- anemia coexisted with their mean corpuscular volume within the reference range. Vitamin B-12 deficiency is prevalent in patients early after and before gastrectomy. Coexistence of vitamin B-12 and iron deficiency obscures the diagnosis of post-gastrectomy anemia, and necessitates the blood vitamin B-12 measurement.

Evaluation of Plasma Homocysteine Levels in Type II Diabetes and Hypertensive Patients Attending University of Port Harcourt Teaching Hospital, Nigeria

Background: Homocysteine is an important non-protein amino acid, very useful in all methylation reactions occurring in the body as the precursor of the sole methyl group donor S-Adenosyl-methionine (SAM). However, elevated plasma homocysteine levels have been reported to contribute to epithelial damage leading to coronary artery disease and other metabolic syndromes. This study was aimed at evaluating the concentration of plasma homocysteine in diabetics and hypertensive patients in Port Harcourt, Nigeria. Methods: The study population included 60 Type II diabetes mellitus and Hypertensivesubjectsas group (I), 60 Type II diabetes mellitus and Normotensive subjects as group (II), 60 Hypertensive subjects as group (III), and 60 healthy subjects as control group within the age range of 30 - 70 years. An enzyme-linked immunosorbent assay (ELISA) method was used to quantitatively measure homocysteine in the serum sample, glycated haemoglobin were determined quantitatively using sandwich immunodetection and blood pressure was determined using mercury sphygnanometer. Statistics: The statistical analysis was done using GraphPad Prism version 9.4.1, and statistical significance was determined by a P < 0.05. Results: The results showed significantly higher plasma homocysteine levels in diabetics and hypertensive comorbidity patients when compared to healthy controls, P < 0.013. There was also a significant increase in plasma homocysteine levels in the comorbidity and hypertensives single morbidity, P < 0.0001 and also diabetes single morbidity, but there was no significant difference from the levels in the diabetics and hypertensives single morbidity. Furthermore, there was no significant difference between groups in terms of age range or duration of diagnosis. Conclusion: Our result shows an increase in plasma homocysteine levels in diabetics and hypertensives when compared to controls, and comorbidity instigates a higher increase in plasma levels when compared with the single morbidity.

Hyperhomocysteinemia as an Independent Risk Factor for Coronary Heart Disease. Comparison with Conventional Risk Factors.

The present study was designed to evaluate the strength of association of raised plasma homocysteine concentration as a risk factor for coronary heart disease independent of conventional risk factor. It was a case control study conducted at Punjab Institute of Cardiology Lahore. A total of 210 subjects aged 25 to 60 years comprising of 105 newly admitted patients of CHD as cases and 105 age and sex matched healthy individuals with no history of CHD as control were recruited for the study. Fasting blood samples were obtained from cases and controls. Plasma homocysteine was analyzed by fluorescence polarization immunoassay (FPIA) method on automated immunoassay analyzer (Abbott IMX). Total cholesterol, triglyceride and HDL cholesterol were analyzed using calorimetric kit methods. The concentration of LDL cholesterol was calculated using Friedewald formula. The patients were also assessed for traditional risk factors such as age, sex, family history of CVD, hypertension, smoking and physical activity, and were compared with control subjects. The collected data was entered in SPSS version 24 for analysis and interpretation.The mean age in controls and experimental groups were 43.00± 8.42 years and 44.72± 8.59 years with statistically same distribution (p- value= 0.144). The mean plasma homocysteine for cases was 22.33± 9.22 µmol/L where as it was 12.59±3.73 µmol/L in control group. Highly significant difference was seen between the mean plasma level of homocysteine in cases and controls (p˂0.001).Simple logistic regression indicates a strong association of coronary heart disease with hyperhomocysteinemia (OR 7.45), which remained significantly associated with coronary heart disease by multivariate logistic regression (OR 7.10, 95%C1 3.12-12.83, p=0.000). The present study concludes that elevated levels of Plasma homocysteine is an independent risk factor for coronary heart disease independent of conventional risk factors and can be used as an indicator for predicting the future possibility for the onset of CVD.

Association Between Plasma Homocysteine Level and Mortality: A Mendelian Randomization Study.

In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on all-cause and cardiovascular mortality using Mendelian randomization (MR) analysis. This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26-1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28-2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62-1.57) and 1.76 (95% CI, 0.54-5.77), respectively. This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.

694 DRUG INDUCED KIDNEY INFARCTION: A CASE REPORT

Abstract Isotretinoin (ISO) is a synthetic analog of vitamin A. Notwithstanding the well-known long-term efficacy in the treatment of severe resistant cystic acne, ISO induces several side effects too. Dyslipidemia, increased liver enzymes, as well as reduction of biotidinase have been already reported [1]. Homocysteine (HCY), a sulfur-containing amino acid, is recycled into methionine by a transmethylation reaction requiring folate and vitamin B12. Given that during ISO treatment elevated liver enzymes (SGOT, SGPT) are often observed, it has been hypothesized that iatrogenic liver dysfunction could affect cystathionine-b-synthase, an enzyme involved in HCY metabolism, [2]. Several studies have highlighted that elevated plasma HCY concentrations are associated with an increased risk of premature occlusive vascular disease. We hereby report a case of drug-induced kidney infarction after ISO therapy. A previously healthy 18-year-old male, on therapy with 40 mg/die isotretinoin for acne, was admitted to the Emergency Unit for abdominal pain, nausea and vomiting and dyspnea. A trans-thoracic echocardiogram showed dilated and hypocontractile left ventricle. During the hospitalization he had a total body CT that showed the presence of an ischemic lesion on left kidney without other pathological findings. He started therapy with 12 IU/kg UFH as soon as a surgical emergency was excluded. Subsequently, he underwent a coronary angiogram that resulted unremarkable. Cardiac MRI showed extensive delayed gadolinium late enhancement with intramural linear pattern. In the hypothesis of drug-induced vasculitis, an extensive serological testing was performed. Elevation of serum liver enzymes (SGOT, SGPT), CRP, LDH was found. Mutations on MTHFR gene and Leiden Factor were not detected, neither alteration in coagulation parameters. Finally the dosage of plasmatic HCY resulted over the range of normality and ISO was discontinued. The patient was discharged on optimized medical therapy for heart failure. He is currently managed as outpatient. HCY levels could be found elevated in patients with ischemic events during ISO treatment. Given the widespread use of this drug for acne, it could be reasonable to dose HCY in patients with suspected liver dysfunction. Physicians should be aware of this scenario and should act swiftly to avoid uneventful outcomes. [1] Schulpis KH et al. Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne. Int J Dermatol. 2001 Jan;40(1):33-6. [2] Polat M, et al. Plasma homocysteine level is elevated in patients on isotretinoin therapy for cystic acne: a prospective controlled study. J Dermatolog Treat. 2008;19(4):229-32.

Recent therapeutic approaches to cystathionine beta-synthase-deficient homocystinuria.

Cystathionine beta-synthase (CBS)-deficient homocystinuria (HCU) is the most common inborn error of sulfur amino acid metabolism. The pyridoxine non-responsive form of the disease manifests itself by massively increasing plasma and tissue concentrations of homocysteine, a toxic intermediate of methionine metabolism that is thought to be the major cause of clinical complications including skeletal deformities, connective tissue defects, thromboembolism and cognitive impairment. The current standard of care involves significant dietary interventions that, despite being effective, often adversely affect quality of life of HCU patients, leading to poor adherence to therapy and inadequate biochemical control with clinical complications. In recent years, the unmet need for better therapeutic options has resulted in development of novel enzyme and gene therapies and exploration of pharmacological approaches to rescue CBS folding defects caused by missense pathogenic mutations. Here, we review scientific evidence and current state of affairs in development of recent approaches to treat HCU.

Applying the indicator amino acid oxidation technique in the domestic cat: results of a pilot study and development of a non-steady state prediction model.

The aim of this study was to evaluate whether the indicator amino acid oxidation (IAAO) method could be applied in the domestic cat. Six adult male cats were used in a replicated 3 × 3 Latin square design. Three semi-synthetic diets were developed: a methionine (Met) and total sulfur AA (TSAA) deficient diet (T-BASAL; 0.24% Met+Cys - DM basis) and two Met and TSAA-sufficient diets in which either dl-Met (T-DLM) or 2-hydroxy-4-(methylthio)-butanoic acid (T-MHA) were supplemented, respectively, on an equimolar basis to meet the TSAA requirement (0.34%). After a 2-d diet adaptation, IAAO studies were performed. Cats were offered 13 small meals. The sixth meal contained a priming dose (4.8 mg/kg-BW) of l-[1-13C]-Phe and the remaining meals a constant dose (1.04 mg/kg-BW). Breath samples were collected every 25 min to measure 13CO2 enrichment. The following morning, fasted blood samples were collected. Cats returned to the T-BASAL top dressed with a dl-Met solution for 4 d prior to being fed a new dietary treatment. Isotopic steady state was evaluated through visual inspection. Data were analyzed using PROC GLIMMIX procedure in SAS 9.4. While 13CO2 enrichment was successfully captured in breath samples, cats failed to reach 13CO2 steady state. Thus, a non-steady state isotope model was developed and coded in ACSLX (V3.1.4.2) individually for each cat on each study day to predict 13CO2 enrichment, and then, calculate oxidation of l-[1-13C]-Phe (F13CO2). A higher predicted F13CO2 was observed for cats fed T-BASAL compared to the others (P < 0.05), while no differences were observed between T-DLM and T-MHA (P > 0.05). Cats fed T-DLM tended to have higher plasma Met concentrations compared to those fed T-BASAL with cats fed T-MHA intermediate (P = 0.0867). Plasma homocysteine concentrations were higher in cats fed T-BASAL compared to the others (P < 0.05), while threonine concentrations tended to be higher in cats fed T-BASAL compared to those fed T-MHA (P = 0.0750). In conclusion, short-term provision of a semi-synthetic diet deficient in Met may elicit a metabolic response aiming to conserve Met. The successful quantification of 13CO2 enrichment in breath and the higher predicted F13CO2 in cats fed a Met deficient diet suggest that the IAAO technique may be used in cats. Adaptations in the isotope protocol should be made to achieve 13CO2 steady state in breath and avoid mathematical modeling to predict F13CO2.

Short-Term Combined Intake of Vitamin B2 and Vitamin E Decreases Plasma Homocysteine Concentrations in Female Track Athletes

Female athletes who endure physical strain on the same bone area are prone to stress fractures. Preventing these improves their quality of life. Blood vitamin B2 (V.B2) and E (V.E) levels influence blood homocysteine (Hcy) levels, which, when elevated, increase the risk of stress fractures. We aimed to determine the effects of V.B2 and V.E supplementation on plasma Hcy concentrations in these athletes carrying the C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR). This study is a before–after study in 16 female athletes. It was divided into three intervention periods of V.B2 (28 mg/day), V.E (60 mg/day), and V.B2 + V.E intake, and each period was 14 days. Blood samples were collected before and after each period, and plasma Hcy concentration and each blood vitamin concentration were measured. Plasma Hcy concentration significantly decreased in all periods, but the maximum lowering effect was obtained when V.B2 and V.E were used in combination. The administration of V.B2 might have lowered the plasma Hcy level by maximizing the catalytic activity of MTHFR; V.E might have suppressed cell oxidation, increasing the efficiency of folate in lowering the plasma Hcy level. We propose the combined intake of V.B2 and V.E as effective nutrients to reduce plasma Hcy concentrations in female athletes with MTHFR polymorphisms.

Efficacy and pharmacokinetics of betaine in CBS and cblC deficiencies: a cross-over randomized controlled trial

BackgroundBetaine is an “alternate” methyl donor for homocysteine remethylation catalyzed by betaine homocysteine methyltransferase (BHMT), an enzyme mainly expressed in the liver and kidney. Betaine has been used for more than 30 years in pyridoxine non-responsive cystathionine beta-synthase (pnrCBS) and cobalamin C (cblC) deficiencies to lower the hyperhomocysteinemia, although little is known about the optimal therapeutic dosage and its pharmacokinetic in these patients.AimsWe compared 2 betaine doses (100 mg/kg/day vs. 250 mg/kg/day) in children affected by pnrCBS or cblC deficiencies. We also measured the pharmacokinetics parameters after a single dose of betaine (100 or 250 mg/kg) in these patients.MethodsWe conducted a prospective, randomized, crossover clinical trial with blinded evaluation. The primary outcome was the equivalence of total plasma homocysteine (tHcy) concentrations upon one-month oral treatment with betaine at 100 versus 250 mg/kg/day.ResultsEleven patients completed the study (5 pnrCBS and 6 cblC). tHcy concentrations were equivalent after a one-month treatment period for the two betaine dosages. Multivariate analysis showed a significant effect of betaine dose on methionine (Met) (p = 0.01) and S-adenosylmethionine (SAM) concentrations (p = 0.006).ConclusionsOur analysis shows that there is no overt benefit to increasing betaine dosage higher than 100 mg/kg/day to lower tHcy concentrations in pnrCBS and cblC deficiencies. However, increasing betaine up to 250 mg/kg/d could benefit cblC patients through the increase of methionine and SAM concentrations, as low Met and SAM concentrations are involved in the pathophysiology of this disease. In contrast, in pnrCBS deficiency, betaine doses higher than 100 mg/kg/day could be harmful to these patients with pre-existing hypermethioninemia.Trial registration: Clinical Trials, NCT02404337. Registered 23 May 2015—prospectively registered, https://clinicaltrials.gov.

Does Risk of Hyperhomocysteinemia Depend on Thiol-Disulfide Exchange Reactions of Albumin and Homocysteine?

Significance: Increased plasma concentrations of total homocysteine (tHcy; mild-moderate hyperhomocysteinemia: 15-50 μM tHcy) are considered an independent risk factor for the onset/progression of various diseases, but it is not known about how the increase in tHcy causes pathological conditions. Recent Advances: Reduced homocysteine (HSH ∼1% of tHcy) is presumed to be toxic, unlike homocystine (∼9%) and mixed disulfide between homocysteine and albumin (HSS-ALB; homocysteine [Hcy]-albumin mixed disulfide, ∼90%). This and other notions make it difficult to explain the pathogenicity of Hcy because: (i) lowering tHcy does not improve pathological outcomes; (ii) damage due to HSH usually emerges at supraphysiological doses; and (iii) it is not known why tiny increments in plasma concentrations of HSH can be pathological. Critical Issues: Albumin may have a role in Hcy toxicity, because HSS-ALB could release toxic HSH via thiol-disulfide (SH/SS) exchange reactions in cells. Similarly, thiol-disulfide exchange processes of reduced albumin (albumin with free SH group of Cys34 [HS-ALB]) or N-homocysteinylated albumin are plausible alternatives for initiating Hcy pathological events. Adverse effects of albumin and other data reviewed here suggest the hypothesis of a role of albumin in Hcy toxicity. Future Directions: HSS-ALB might be involved in disruption of the antioxidant/oxidant balance in critical tissues (brain, liver, kidney). Since homocysteine-albumin mixed disulfide is a possible intermediate of thiol-disulfide exchange reactions, we suggest that homocysteinylated albumin could be a new pathological factor, and that studies on the redox role of albumin and mixed disulfide production via thiol-disulfide exchange reactions could offer new therapeutic insights for reducing Hcy toxicity.

The effect of vitamin B supplementation on neuronal injury in people living with HIV: a randomized controlled trial.

Effective antiretroviral therapy has radically changed the course of the HIV pandemic. However, despite efficient therapy, milder forms of neurocognitive symptoms are still present in people living with HIV. Plasma homocysteine is a marker of vitamin B deficiency and has been associated with cognitive impairment. People living with HIV have higher homocysteine concentrations than HIV-negative controls, and we have previously found an association between plasma homocysteine concentration and CSF concentration of neurofilament light protein, a sensitive marker for ongoing neuronal injury in HIV. This prompted us to perform this randomized controlled trial, to evaluate the effect of vitamin B supplementation on neuronal injury in a cohort of people living with HIV on stable antiretroviral therapy. At the Department of Infectious Diseases at Sahlgrenska University Hospital in Gothenburg, Sweden, 124 virally suppressed people living with HIV were screened to determine eligibility for this study. Sixty-one fulfilled the inclusion criteria by having plasma homocysteine levels at or above 12 μmol/l. They were randomized (1:1) to either active treatment (with cyanocobalamin 0.5 mg, folic acid 0.8 mg and pyridoxine 3.0 mg) q.d. or to a control arm with a cross over to active treatment after 12 months. Cognitive function was measured repeatedly during the trial, which ran for 24 months. We found a significant correlation between plasma neurofilament light protein and plasma homocysteine at screening (n = 124, r = 0.35, P < 0.0001). Plasma homocysteine levels decreased by 35% from a geometric mean of 15.7 μmol/l (95% confidence interval 14.7-16.7) to 10.3 μmol/l (95% confidence interval 9.3-11.3) in the active treatment arm between baseline and Month 12. No significant change was detected in the control arm during the same time period [geometric mean 15.2 (95% confidence interval 14.3-16.2) versus geometric mean 16.5 μmol/l (95% confidence interval 14.7-18.6)]. A significant difference in change in plasma homocysteine levels was seen between arms at 12 months [-40% (95% confidence interval -48 to -30%), P < 0.001]. However, no difference between arms was seen in either plasma neurofilament light protein levels [-6.5% (-20 to 9%), P = 0.39], or cognitive measures [-0.08 (-0.33 to 0.17), P = 0.53]. Our results do not support a vitamin B-dependent cause of the correlation between neurofilament light protein and homocysteine. Additional studies are needed to further elucidate this matter.

Preoperative homocysteine modifies the association between postoperative C-reactive protein and postoperative delirium.

BackgroundHomocysteine and C-reactive protein (CRP) may serve as biomarkers of postoperative delirium. We set out to compare the role of blood concentration of homocysteine versus CRP in predicting postoperative delirium in patients.Materials and methodsIn this prospective observational cohort study, the plasma concentration of preoperative homocysteine and postoperative CRP was measured. Delirium incidence and severity within 3 days postoperatively were determined using the Confusion Assessment Method and Confusion Assessment Method-Severity algorithm.ResultsOf 143 participants [69% female, median (interquartile range, 25th–75th) age of 71 (67–76) years] who had knee or hip surgery under general anesthesia, 44 (31%) participants developed postoperative delirium. Postoperative plasma concentration of CRP was associated with postoperative delirium incidence [adjusted odds ratio (OR) per one standard deviation change in CRP: 1.51; 95% Confidence Interval (CI): 1.05, 2.16; P = 0.026], and severity [in which each one standard deviation increase in postoperative CRP was associated with a 0.47 point (95% CI: 0.18–0.76) increase in the severity of delirium, P = 0.002] after adjusting age, sex, preoperative Mini-Mental State Examination score and the days when postoperative CRP was measured. A statistically significant interaction (adjusted P = 0.044) was also observed, in which the association between postoperative plasma concentration of CRP and postoperative delirium incidence was stronger in the participants with lower preoperative plasma concentrations of homocysteine compared to those with higher preoperative levels.ConclusionPending validation studies, these data suggest that preoperative plasma concentration of homocysteine modifies the established association between postoperative plasma concentration of CRP and postoperative delirium incidence.

High plasma homocysteine level is associated with increased prevalence of the non-remission state in rheumatoid arthritis: Findings from the KURAMA cohort.

We aimed to determine the clinical impact of plasma homocysteine levels on disease activity and clinical remission in patients with rheumatoid arthritis (RA). A cross-sectional study was conducted using KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. We enrolled 291 female patients, who were treated in a treat-to-target manner. We measured plasma total homocysteine using a liquid chromatography-tandem mass spectrometry system and collected clinical data including a 28-joint RA disease activity score-erythrocyte sedimentation rate (DAS28-ESR). Clinical remission of disease activity was defined as a DAS28-ESR < 2.6. In a univariable analysis, the plasma homocysteine concentration was significantly and positively associated with DAS-28-ESR and was higher in the non-remission group than in the remission group. The cutoff value of the plasma homocysteine level was calculated to be 7.9 nmol/mL by the test of the receiver operating characteristic curve analysis. In a multivariable analysis, after adjusting for clinically relevant variables, the high homocysteine level remained a significant positive association for DAS28-ESR (estimate 0.27, P = .0019) and a positive factor for the presence of RA non-remission (odds ratio 2.39, P = .0071). Increased plasma homocysteine levels showed a significant positive association with current disease activity and the non-remission state in female patients with RA under treat-to-target treatment. The findings suggest the potential utility of plasma homocysteine as a disease state marker reflecting conditions that are treatment failure and difficult to remission and may provide clinical evidence on the interplay between homocysteine and inflammatory activation in RA.

Differential expression of cystathionine beta synthase in adolescents with Down syndrome: impact on adiposity.

Obesity is more prevalent among people with Down Syndrome (DS) compared to general population. In this pilot study, we investigated the effect of cystathionine beta-synthase (CBS) overdosage on the regulation of transsulfuration pathway and the obesity phenotype in fifty adolescents (25 obese/overweight and 25 lean) with trisomy 21. The transcriptional levels of CBS in leukocytes and its translational levels in plasma were quantified using real time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Meanwhile, ultra performance liquid chromatography tandem mass spectrometry was used to determine the plasma concentrations of methionine, homocysteine, cystathionine and cysteine. Fasting plasma lipid profiles were assessed by colorimetric assays. The anthropometric measurements and indices of all subjects were recorded. Both DS groups had comparable levels of CBS transcripts (p = 0.2734). The plasma levels of the enzyme were significantly higher in the lean DS cases (p = 0.0174) compared to the obese/overweight participants. Total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, methionine, homocysteine, cystathionine and cysteine showed similar plasma levels in both groups. However, the plasma cysteine levels exceeded the normal range in all DS cases. We reported a statistically significant inverse association between CBS enzyme levels and weight (r= - 0.3498, p = 0.0128), hip circumference (r= - 0.3584, p = 0.0106), body mass index (r= - 0.3719, p = 0.0078) and body adiposity index (r= - 0.3183, p = 0.0243). Our data suggests that the high concentrations of CBS enzyme together with cysteine modulate the DS obesity presumably through increased hydrogen sulfide production which has recently showed anti-adiposity effects.

The Effect of 3-Week Betaine Supplementation on Blood Biomarkers of Cardiometabolic Health in Young Physically Active Males.

Betaine (BET) supplementation decreases homocysteine concentration in plasma, but it may also have an adverse effect on health by increasing blood lipid concentrations, at least in overweight and obese individuals. The aim of this study was to evaluate the effect of BET supplementation on the lipid profile and concentrations of homocysteine, inflammatory cytokines, and liver enzymes in physically active, healthy males. This was a randomized, placebo (PL)-controlled, double-blinded, crossover trial. BET (2.5 or 5.0 g/d) was administered for 21 days. Before and after supplementation with BET or PL, anthropometric measurements and blood were collected in a fasted state. Our results show that BET supplementation significantly decreased homocysteine concentration (from 17.1 ± 4.0 μmol/L before BET to 15.6 ± 3.5 μmol/L after BET, p = 0.009, η2 = 0.164). However, the intervention had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerol, interleukins 1β and 6, and tumour necrosis factor α concentrations, or alanine and aspartate activities. In addition, there were no interactions between the MTHFR genotype and BET dose. In conclusion, BET supplementation may be beneficial for homocysteine concentration in healthy, physically active males, with no detrimental effect on lipid profile.

Vitamin B12 and/or folic acid supplementation on linear growth; a 6 years follow-up study of a randomised controlled trial in early childhood in North India.

Folate and vitamin B12 are essential for growth. Our objective was to estimate their long-term effects on linear growth in North Indian children. This is a follow-up study of a factorial designed, double-blind, randomized placebo-controlled trial in 1,000 young children. Starting at 6-30 months of age, we gave folic acid (∼2 RDAs), vitamin B12 (∼2 RDAs), both vitamins, or a placebo daily for six months. Six years after the end of supplementation, we measured height in 791 children. We used the plasma concentrations of cobalamin, folate, and total homocysteine to estimate vitamin status. The effect of the interventions, the association between height-for-age z-scores (HAZ) and baseline vitamin status, and the interactions between supplementation and baseline status were estimated in multiple regression models. Mean (SD) age at follow-up was 7.4 (0.7) years (range 6 to 9 years). There was a small, non-significant effect of vitamin B12 on linear growth and no effect of folic acid. We observed a subgroup-effect of vitamin B12 supplementation in those with plasma cobalamin concentration < 200 pmol/L (P interaction = 0.01). The effect of vitamin B12 supplementation in this group was 0.34 HAZ (95% CI: 0.11-0.58). We found an association between cobalamin status and HAZ in children not given vitamin B12 (P interaction = 0.001). In this group, each doubling of the cobalamin concentration was associated with 0.26 (95% CI: 0.15 to 0.38) higher HAZ. Suboptimal B12 status in early childhood seemingly limits linear growth in North Indian Children.