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1.
Periodontal Inflamed Surface Area Mediates the Link between Homocysteine and Blood Pressure.
Botelho, J, Machado, V, Leira, Y, Proença, L, Mendes, JJ
Biomolecules. 2021;(6)
Abstract
Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001-2002 and 2003-2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood pressure (BP) and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and BP. Mediation analysis was performed to understand the effect of PISA and PESA in the link between Hcy and BP. 4021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models (p < 0.01), but not PISA (p > 0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%. In conclusion, Hcy and periodontitis are associated. Further, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which Hcy levels increase in a clinical situation of periodontitis.
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2.
Leonurine affected homocysteine-methionine metabolism based on metabolomics and gut microbiota studies of clinical trial samples.
Liao, J, Suguro, R, Zhao, X, Yu, Y, Cui, Y, Zhu, YZ
Clinical and translational medicine. 2021;(10):e535
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3.
Hyperhomocysteinaemia and the risk of recurrent venous thrombosis: results from the MEGA follow-up study.
Hensen, ADO, Lijfering, WM, Cannegieter, SC, Rosendaal, FR, van Hylckama Vlieg, A
British journal of haematology. 2019;(2):219-226
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Abstract
The measurement of homocysteine is still part of routine thrombosis or thrombophilia work-up in many thrombosis centres in the world. Previous observational studies have shown that hyperhomocysteinaemia is associated with an increased risk of first and recurrent venous thrombosis (VT). Randomised trials, however, showed no benefit of homocysteine-lowering therapy on the risk of first or recurrent VT. This discrepancy could be explained by incomplete adjustment for confounders in the observational studies. We investigated in a large population-based follow-up study whether if the levels of homocysteine and its metabolites, methionine and cysteine, were associated with recurrent VT. Approximately three months after discontinuation of anticoagulant treatment, homocysteine, methionine and cysteine concentrations were measured in 2210 patients with VT. During a median follow-up of 6·9 years, 340 patients developed a recurrence (incidence rate, 2·8/100 patient-years). We found that elevated homocysteine concentrations were not associated with an increased risk of recurrent VT, neither as a continuous variable per 5 μmol/l increase (hazard ratio [HR] 0·98 (95% confidence interval [CI], 0·90-1·04)) nor when levels were >95th (>23·0 μmol/l) percentile (HR 1·03 (95% CI, 0·65-1·64)). Similar results were obtained for cysteine and methionine values. We conclude that hyperhomocysteinaemia is not associated with an increased risk of recurrent VT.
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Assessment of Serum Folic Acid and Homocysteine in Thalassemia Major Patients Before and After Folic Acid Supplement Cessation.
Baghersalimi, A, Hemmati Kolachahi, H, Darbandi, B, Kamran Mavardiani, Z, Alizadeh Alinodehi, M, Dalili, S, Hassanzadeh Rad, A
Journal of pediatric hematology/oncology. 2018;(7):504-507
Abstract
BACKGROUND Thalassemic patients have ineffective erythropoiesis. In recent treatment protocols, there are little data on folic acid supplementation for patients with thalassemia because it is supposed that regular blood transfusions prevent bone marrow hyperfunctioning. OBJECTIVE Investigators aimed to assess serum folic acid and homocysteine (Hcy) in thalassemia major patients before and after folic acid supplement cessation. PATIENTS AND METHODS This study was a before-after controlled clinical trial conducted in 17th Shahrivar Hospital, Rasht, North of Iran, during May to October 2016. The patients enrolled in this study had thalassemia major on regular blood transfusion and older than 2 years of age. They had at least a 6-month history of folic acid supplement consumption before enrollment in the study (1 mg/daily). Complete blood count, serum folic acid, and serum Hcy were measured before discontinuation of folic acid supplement. Then, patients did not receive folic acid for a month and after 1 month of folic acid cessation, the measurements were repeated. All data were entered in SPSS version 20.0 and analyzed. RESULTS Among the 40 patients in this study, 25 (62.5%) were female. The mean age of the participants was 21.39±11.17 years old. The mean of body mass index was 21.38±3.32 kg/m. Most of the participants had used folic acid supplement >5 years (29, 72.5%). The serum Hcy level was significantly increased (5.24±2.35 vs. 5.93±2.56; P=0.008) and serum folic acid level was decreased significantly (14.74±4.20 vs. 8.80±4.16; P<0.0001) from baseline. CONCLUSIONS Cessation of folic acid supplementations in beta thalassemia major patients can lead to a significant decrease in serum folic acid and increase in Hcy levels. According to our findings and efficacy of folic acid in patients with beta thalassemia major, it is recommended to use the supplementation in all patients.
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Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism.
Xu, B, Kong, X, Xu, R, Song, Y, Liu, L, Zhou, Z, Gu, R, Shi, X, Zhao, M, Huang, X, et al
Medicine. 2017;(8):e5862
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Abstract
BACKGROUND Previous studies support an association between elevated total homocysteine (tHcy) levels and increased all-cause mortality. However, few prospective studies have examined this association in hypertensive patients, and/or tested any effect modification by the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. METHODS This was a post hoc analysis of the China Stroke Primary Prevention Trial. Serum tHcy and folate were measured at baseline. Individual MTHFR C677T genotype (CC, CT, and TT) was determined. Evidence for death included death certificates or home visits. Cumulative hazards of all-cause mortality by tHcy quartiles were estimated using the Kaplan-Meier method, and group differences were compared by log-rank tests. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox proportional-hazard regression models, adjusting for age, sex, baseline folate, vitamin B12, blood pressure, body mass index, smoking and alcohol drinking status, study center, total cholesterol, triglycerides, high-density lipoprotein cholesterol, fasting glucose, creatinine, and treatment group. Potential effect modification by the MTHFR genotype on the relationship between tHcy and all-cause mortality was tested. RESULTS The analyses included 20,424 hypertensive patients (41% males) without a history of myocardial infarction or stroke. Baseline mean age (SD) was 60 ± 7.5 years and mean (SD) serum tHcy was 14.5 ± 8.4 μmol/L. After a mean follow-up period of 4.5 years, there were 612 (3%) all-cause deaths. Kaplan-Meier survival curves revealed a graded relationship between tHcy quartiles and all-cause mortality. The HRs, using the lowest quartile as the reference, were 1.2, 1.2, and 1.5 in Q2, Q3, and Q4, respectively. A linear trend test, using natural log-transformed tHcy, resulted in an HR of 1.5 (95% confidence interval 1.2-1.9, P < .001) after adjustment for lifestyle and health-related variables. Whereas the MTHFR genotype alone had little effect on mortality, it significantly modified the tHcy-mortality association, which was much stronger in the CC/CT genotype than in the TT genotype (P for interaction < 0.05). CONCLUSIONS Among Chinese hypertensive patients without cardiovascular comorbidities, elevated tHcy was a significant risk marker for death from all causes, and the association was subject to effect modification by MTHFR genotypes. If confirmed that tHcy and MTHFR genotypes may serve as useful biomarkers for mortality risk assessment and targeted intervention.
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Homocysteinemia control by cysteine in cerebral vascular patients after methionine loading test: evidences in physiological and pathological conditions in cerebro-vascular and multiple sclerosis patients.
Ulivelli, M, Priora, R, Di Giuseppe, D, Coppo, L, Summa, D, Margaritis, A, Frosali, S, Bartalini, S, Martini, G, Cerase, A, et al
Amino acids. 2016;(6):1477-89
Abstract
The toxicity risk of hyperhomocysteinemia is prevented through thiol drug administration which reduces plasma total homocysteine (tHcy) concentrations by activating thiol exchange reactions. Assuming that cysteine (Cys) is a homocysteinemia regulator, the hypothesis was verified in healthy and pathological individuals after the methionine loading test (MLT). The plasma variations of redox species of Cys, Hcy, cysteinylglycine, glutathione and albumin (reduced, HS-ALB, and at mixed disulfide, XSS-ALB) were compared in patients with cerebral small vessels disease (CSVD) (n = 11), multiple sclerosis (MS) (n = 12) and healthy controls (n = 11) at 2-4-6 h after MLT. In MLT-treated subjects, the activation of thiol exchange reactions provoked significant changes over time in redox species concentrations of Cys, Hcy, and albumin. Significant differences between controls and pathological groups were also observed. In non-methionine-treated subjects, total Cys concentrations, tHcy and thiol-protein mixed disulfides (CSS-ALB, HSS-ALB) of CSVD patients were higher than controls. After MLT, all groups displayed significant cystine (CSSC) increases and CSS-ALB decreases, that in pathological groups were significantly higher than controls. These data would confirm the Cys regulatory role on the homocysteinemia; they also explain that the Cys-Hcy mixed disulfide excretion is an important point of hyperhomocysteinemia control. Moreover, in all groups after MLT, significant increases in albumin concentrations, named total albumin (tALB) and measured as sum of HS-ALB (spectrophometric), and XSS-ALB (assayed at HPLC) were observed. tALB increases, more pronounced in healthy than in the pathological subjects, could indicate alterations of albumin equilibria between plasma and other extracellular spaces, whose toxicological consequences deserve further studies.
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Homocysteine Levels in Parkinson's Disease: Is Entacapone Effective?
Kocer, B, Guven, H, Comoglu, SS
BioMed research international. 2016;:7563705
Abstract
Plasma homocysteine (Hcy) levels may increase in levodopa-treated patients with Parkinson's disease (PD) as a consequence of levodopa methylation via catechol-O-methyltransferase (COMT). Results from previous studies that assessed the effect of COMT inhibitors on levodopa-induced hyperhomocysteinemia are conflicting. We aimed to evaluate the effects of levodopa and entacapone on plasma Hcy levels. A hundred PD patients were enrolled to the study and divided into three treatment groups (group I: levodopa and/or dopamine agonists; group II: levodopa, entacapone, and/or a dopamine agonist; and group III: dopamine agonist alone). We measured the serum B12, folic acid, and Hcy levels in all patients. There were no statistically significant differences between groups in terms of modified Hoehn and Yahr stages, Unified Parkinson's Disease Rating Scale II/III, Standardized Mini-Mental Test scores, and serum vitamin B12 and folic acid levels. Plasma median Hcy levels were found above the normal laboratory values in groups I and II, but they were normal in group III. However, there was no statistically significant difference in plasma Hcy levels between groups. Our results showed that levodopa treatment may cause a slight increase in the Hcy levels in PD compared with dopamine agonists and that COMT inhibitors may not have a significant effect on preventing hyperhomocysteinemia.
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Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism.
Poloni, S, Leistner-Segal, S, Bandeira, IC, D'Almeida, V, de Souza, CF, Spritzer, PM, Castro, K, Tonon, T, Nalin, T, Imbard, A, et al
Gene. 2014;(2):443-7
Abstract
INTRODUCTION Classical homocystinuria is a rare genetic disease caused by cystathionine β-synthase deficiency, resulting in homocysteine accumulation. Growing evidence suggests that reduced fat mass in patients with classical homocystinuria may be associated with alterations in choline and homocysteine pathways. This study aimed to evaluate the body composition of patients with classical homocystinuria, identifying changes in body fat percentage and correlating findings with biochemical markers of homocysteine and choline pathways, lipoprotein levels and bone mineral density (BMD) T-scores. METHODS Nine patients with classical homocystinuria were included in the study. Levels of homocysteine, methionine, cysteine, choline, betaine, dimethylglycine and ethanolamine were determined. Body composition was assessed by bioelectrical impedance analysis (BIA) in patients and in 18 controls. Data on the last BMD measurement and lipoprotein profile were obtained from medical records. RESULTS Of 9 patients, 4 (44%) had a low body fat percentage, but no statistically significant differences were found between patients and controls. Homocysteine and methionine levels were negatively correlated with body mass index (BMI), while cysteine showed a positive correlation with BMI (p<0.05). There was a trend between total choline levels and body fat percentage (r=0.439, p=0.07). HDL cholesterol correlated with choline and ethanolamine levels (r=0.757, p=0.049; r=0.847, p=0.016, respectively), and total cholesterol also correlated with choline levels (r=0.775, p=0.041). There was no association between BMD T-scores and body composition. CONCLUSIONS These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism.
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The importance of the one carbon cycle nutritional support in human male fertility: a preliminary clinical report.
Dattilo, M, Cornet, D, Amar, E, Cohen, M, Menezo, Y
Reproductive biology and endocrinology : RB&E. 2014;:71
Abstract
BACKGROUND Sperm chromatin structure is often impaired; mainly due to oxidative damage. Antioxidant treatments do not consistently produce fertility improvements and, when given at high doses, they might block essential oxidative processes such as chromatin compaction. This study was intended to assess the effect on male sub-fertility of a pure one carbon cycle nutritional support without strong antioxidants. METHODS Male partners of couples resistant to at least 2 assisted reproductive technology (ART) attempts, with no evidence of organic causes of infertility and with either DNA fragmentation index (DFI) measured by Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) or nuclear decondensation index (SDI) measured by aniline blue staining exceeding 20%, were invited to take part in a trial of a nutritional support in preparation for a further ART attempt. The treatment consisted of a combination of B vitamins, zinc, a proprietary opuntia fig extract and small amounts of N-acetyl-cysteine and Vitamin E (Condensyl™), all effectors of the one carbon cycle. RESULTS 84 patients were enrolled, they took 1 or 2 Condensyl™ tablets per day for 2 to 12 months. Positive response rates were 64.3% for SDI, 71.4% for DFI and 47.6% for both SDI and DFI. Eighteen couples (21%) experienced a spontaneous pregnancy before the planned ART cycle, all ended with a live birth. The remaining 66 couples underwent a new ART attempt (4 IUI; 18 IVF; 44 ICSI) resulting in 22 further clinical pregnancies and 15 live births. The clinical pregnancy rate (CPR) and the live birth rate (LBR) were 47.6% and 39.3% respectively. The full responders, i.e. the 40 patients achieving an improvement of both SDI and DFI, reported a CPR of 70% and a LBR of 57.5% (p<0.001). CONCLUSIONS Nutritional support of the one carbon cycle without strong antioxidants improves both the SDI and the DFI in ART resistant male partners and results in high pregnancy rates suggesting a positive effect on their fertility potential.
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10.
[Homocysteine after a methionine load in healthy subjects with adequate B-vitamin status].
López-Alarcón, M, Chávez-Negrete, A, Montalvo-Velarde, I, Maldonado-Hernández, J, Vital-Reyes, VS
Cirugia y cirujanos. 2011;(5):432-8
Abstract
BACKGROUND Plasma homocysteine (Hcy) determination at 6-8 h after an oral methionine load (OML) allows for identification of some, but not all, individuals at risk to develop cardiovascular disease. It is probable that in some cases the Hcy increases occur later, or it elevates between normal ranges but in a sustained manner. However, the entire Hcy response curve has not been described. We undertook this study to determine Hcy concentrations from baseline to 24- and 48-h after an OML in non-B-vitamin deficient adult subjects with other risk factors for high levels of Hcy such as smoking and overweight. METHODS In a cross-over, clinical design, Hcy concentrations were determined at 2-h intervals throughout 12 h and at 24 h and 48 h after an OML (0.1 g/kg). Hcy and vitamin B6 (VB6) concentrations were measured by high-performance liquid chromatography (HPLC). Folic acid (FA) and vitamin B12 (VB12) were measured by radioimmunoassay (RIA). Statistical analysis included delta values and areas under the curve. Student t-test and repeated measurement analyses were conducted to control for confounders. RESULTS Twenty-nine subjects with adequate Hcy, FA, VB6 and VB12 status were included. The maximum Hcy concentration occurred 8 h after the load and returned to baseline concentrations after 24 h. All subjects presented Hcy after the load within normal ranges, but smoking and overweight synergistically influenced the response to the challenge, producing a sustained elevation after the dose. CONCLUSIONS Hcy concentrations after an OML remained above baseline for at least 24 h. Smoking and overweight affected the response to the methionine challenge.