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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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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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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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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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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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Comparison of oral folic acid and folinic acid on blood homocysteine level of patients on hemodialysis.
Soleimani, A, Usefzadeh, M, Mianehsaz, E, Foroozanfard, F, Nikoueinejad, H, Moraveji, SA, Nasiri, O, Rajali, M
Iranian journal of kidney diseases. 2011;(1):45-9
Abstract
INTRODUCTION. Hyperhomocysteinemia is common in patients with chronic kidney disease. There is a direct relationship between cardiovascular mortality and increase of blood homocysteine. Folic acid is used as common treatment in such patients. Folinic acid, a shortened form of folic acid, is not affected by inhibitors of dihydrofolate reductase enzyme such as methoterxate. This study was performed to evaluate the effect of oral folinic acid on the blood homocysteine level of hemodialysis patients, in comparison with folic acid. MATERIALS AND METHODS. This clinical trial was performed on 60 hemodialysis patients. The participants were divided into 2 groups to receive either 15 mg of oral folic acid or 15 mg of oral folinic acid, daily. Blood homocysteine levels were measured before dialysis and after the study period. RESULTS. Folic acid and folinic acid decreased the blood homocysteine levels by 33.0% and 28.7%, respectively (P < .001). However, only 3 patients (6.5%) enjoyed a normalized homocysteine level. CONCLUSIONS. Our study showed that both folic and folinic acid decreased the blood homocysteine level and no meaningful difference was observed between them; therefore, we suggest they can be used interchangeably.
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Effect of moderate and high-dose simvastatin on asymmetric dimethylarginine-homocysteine metabolic pathways in patients with newly detected severe hypercholesterolemia.
Vladimirova-Kitova, LG, Deneva, TI, Marinov, B
Cardiovascular therapeutics. 2011;(5):340-8
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The assumption that statin therapy can decrease asymmetric dimethylarginine through lowering low-density lipoprotein cholesterol levels seems logical and yet arises some controversy. The aim of the present study is to compare the effects of moderate (40 mg) to high (80 mg) simvastatin doses on asymmetric dimethylarginine and total homocysteine levels in patients with newly detected severe hypercholesterolemia (after target LDL-C levels, ≤2.6 mmol/L, are reached). The study included 120 adult patients with newly detected severe hypercholesterolemia (total cholesterol ≥7.5 mmol/L and low-density lipoprotein cholesterol ≥4.9 mmol/L). Asymmetric dimethylarginine levels were determined by enzyme-linked immunosorbent assay, total homocysteine-by a high-performance liquid chromatographic method. There was a statistically significant decrease in total cholesterol, triglycerides, low-density lipoprotein cholesterol, and apolipoprotein-B levels as well as in the apolipoprotein-B/apolipoprotein-A1 index after a 1-month therapy with 40 mg simvastatin (P <0.001). Asymmetric dimethylarginine and total homocysteine levels were also decreased but the difference did not reach statistical significance (P= 0.571; P= 0.569). A dose-dependent effect was established, comparing the influence of moderate (40 mg) to high (80 mg) simvastatin doses on the tested atherogenic biomarkers (lipid profile, apolipoprotein-A1, and apolipoprotein-B). Asymmetric dimethylarginine and total homocysteine levels were lowered significantly with 80 mg simvastatin (P <0.001; P= 0.038). In conclusion, optimizing the target values of low-density lipoprotein cholesterol, a moderate dose (40 mg) of simvastatin has no effect on asymmetric dimethylarginine and total homocysteine in contrast to a high dose (80 mg) after target LDL-C levels are reached (≤2.6 mmol/L) in patients with newly detected severe hypercholesterolemia.
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Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the hordaland homocysteine study.
Gjesdal, CG, Vollset, SE, Ueland, PM, Refsum, H, Meyer, HE, Tell, GS
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2007;(5):747-56
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UNLABELLED Homocysteine and related factors were evaluated as risk factors for subsequent hip fractures among 4766 elderly men and women. High levels of homocysteine and low levels of folate predicted fracture, whereas vitamin B12 and genotypes were not related to fracture risk. High homocysteine may be a modifiable risk factor for hip fracture. INTRODUCTION Elevated plasma total homocysteine (tHcy) and deficiencies of folate and vitamin B12 are associated with risk of osteoporosis and fracture. We examined whether plasma levels of tHcy, folate, and vitamin B12 and the methylenetetrahydrofolate reductase (MTHFR) 677C-->T and 1298C-->T polymorphisms predicted hip fracture. MATERIALS AND METHODS This was a population-based prospective study of 2639 women and 2127 men who were 65-67 yr at enrollment in 1992-1993. Information on hip fracture was obtained from computerized records of discharge diagnoses from all hospitalizations in the region in the period between enrollment and November 30, 2005. Cox proportional hazard regression was used to estimate fracture risk according to levels of plasma tHcy, folate, and vitamin B12 and for different genotypes. RESULTS Over a median follow-up period of 12.6 yr, hip fracture was recorded in 184 (7.0%) women and 90 (4.2%) men. The adjusted hazard ratio (95% CI) for fracture in subjects with high (>or=15 microM) compared with low levels (<9.0 microM) of tHcy was 2.42 (1.43-4.09) among women and 1.37 (0.63-2.98) among men. Dose-response analyses indicated a positive association between plasma tHcy and risk of fracture in both sexes and a negative association between plasma folate and risk of fracture among women only. Plasma vitamin B12 level or MTHFR genotype was not significantly related to risk of fracture after adjustments for confounding factors. The association between tHcy and risk of hip fracture was only slightly weakened by adjustments for plasma levels of vitamin B12 and folate. CONCLUSIONS tHcy seems to be a predictor for hip fracture among elderly men and women. Folate was a predictor among women only, whereas vitamin B12 and MTHFR genotype did not predict hip fracture. Our data corroborate the hypothesis that homocysteine may play a role in the pathogenesis of osteoporotic fractures.