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Effects of individualized administration of folic acid on prothrombotic state and vascular endothelial function with H-type hypertension: A double-blinded, randomized clinical cohort study.
Zhang, S, Wang, T, Wang, H, Tang, J, Hou, A, Yan, X, Yu, B, Ran, S, Luo, M, Tang, Y, et al
Medicine. 2022;(3):e28628
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Abstract
BACKGROUND Hypertension and hyperhomocysteinemia (HHcy) have long been associated with adverse cardiovascular and cerebrovascular health outcomes. This study evaluated the effect of individualized administration of folic acid (FA) on homocysteine (Hcy) levels, prothrombotic state, and blood pressure (BP) in patients with H-type hypertension (combination of HHcy and hypertension). METHODS In this double-blinded, randomized clinical cohort study, 126 patients with H-type hypertension who were treated at our hospital were randomly divided into treatment and control groups (n = 55 each). The control group was treated with oral levamlodipine besylate tablets 2.5 mg and placebo, once a day (in the morning). The treatment group was first treated with oral levamlodipine besylate 2.5 mg and FA tablets 0.8 mg, once a day (in the morning), for 12 weeks. Then, in a second 12-week phase, the FA dose was adjusted using the methylene tetrahydrofolate reductase C677 polymorphism genotype. The levels of Hcy and coagulation factors, prothrombotic state parameters, BP, and adverse drug reactions were compared between the 2 groups. RESULTS Pretreatment general patient characteristics, including Hcy levels, were similar between the 2 groups (P > .05). BP and prothrombotic status did not differ before and after the first phase of treatment (P > .05). However, Hcy and endothelin-1 (ET-1) levels decreased, while nitric oxide levels increased significantly in the intervention group (P < .05). In the second phase, after 3 months' treatment with an FA dose adjusted according to methylene tetrahydrofolate reductase C677T genotype, the Hcy and ET-1/NO levels were significantly decreased in the intervention group and were lower than those after the first treatment phase and lower than in the control group (P < .01). BP, D-dimer levels, and fibrinogen scores were significantly lower after the second treatment phase (P < .01). There was no significant difference in the incidence of adverse drug reactions between the 2 groups (P > .05). CONCLUSIONS Individualized administration of FA tablets can effectively reduce BP, and Hcy and coagulation factor levels, and significantly improve prothrombotic status in patients with H-type hypertension.
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The association between serum homocysteine and depression: A systematic review and meta-analysis of observational studies.
Moradi, F, Lotfi, K, Armin, M, Clark, CCT, Askari, G, Rouhani, MH
European journal of clinical investigation. 2021;(5):e13486
Abstract
BACKGROUND Hyperhomocysteinaemia is known to interfere with neurological functions; however, there is a controversy regarding the relationship between homocysteine and depression. MATERIALS AND METHODS Science Direct, MEDLINE and ISI Web of Science were searched to find relevant articles, published up to August 2020. Studies were included if they compared homocysteine levels in healthy subjects with subjects with depression. Also, articles that reported the association between hyperhomocysteinaemia and risk of depression were included. Odds ratios of depression and means of homocysteine were used to ascertain the overall effect size. RESULTS Homocysteine level was higher in subjects with depression in comparison with healthy controls (weight mean difference = 2.53 µmol/L, 95% confidence interval: 1.77, 3.30), and the depression diagnostic tool was a source of heterogeneity. Homocysteine level was significantly higher in subjects with depression in studies that used Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), Geriatric Depression Scale (GDS), Zung Self-Rating Depression Scale (ZDRS) and Beck Depression Index II (BDI-II) as depression diagnostic tools. Also, participants with hyperhomocysteinaemia had a higher chance of depression (Pooled risk = 1.34, 95% confidence interval: 1.19, 1.52), where the depression diagnostic tool was a source of heterogeneity. In contrast to ZDRS and Patient Health Questionnaire (PHQ) subgroups, hyperhomocysteinaemia yielded a significantly higher risk of depression in DSM-IV, GDS and 'other' subgroups. CONCLUSION Homocysteinemia level is higher in individuals with depression. However, the depression diagnostic tool used is instrumental in influencing their association, and thus, future studies should focus on the tools for depression assessment.
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Homocysteine - from disease biomarker to disease prevention.
Smith, AD, Refsum, H
Journal of internal medicine. 2021;(4):826-854
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Abstract
We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The commonest associations are with cardiovascular diseases and diseases of the central nervous system, but a large number of developmental and age-related conditions are also associated. Few other disease biomarkers have so many associations. The clinical importance of these associations becomes especially relevant if lowering plasma total homocysteine by B vitamin treatment can prevent disease and so improve health. Five diseases can at least in part be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 μmol/L or below are probably safe, but that values of 11 μmol/L or above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease.
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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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Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses.
Bala, R, Verma, R, Verma, P, Singh, V, Yadav, N, Rajender, S, Agrawal, NR, Singh, K
Nutrition research (New York, N.Y.). 2021;:57-66
Abstract
One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.
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Vitamin D3 reduces risk of cardiovascular and liver diseases by lowering homocysteine levels: double-blinded, randomised, placebo-controlled trial.
Al-Bayyari, N, Hailat, R, Subih, H, Alkhalidy, H, Eaton, A
The British journal of nutrition. 2021;(2):139-146
Abstract
The objective of this study was to evaluate the effect of vitamin D3 on total homocysteine (tHcy) and C-reactive protein (CRP) levels and liver and kidney function tests in overweight women with vitamin D deficiency. Therefore, a randomised, double-blind placebo, controlled clinical trial was conducted on 100 eligible women. Subjects were randomly divided into two groups: the placebo (n 50) and the vitamin D (n 50) which received 1250 µg vitamin D3 per week for 2 months. The participants' 25-hydroxyvitamin D (25(OH)D), tHcy, CRP, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and estimated glomerular filtration rate (eGFR) were measured and compared before and after treatment. Results showed that the tHcy, CRP, AST, ALT and eGFR levels after the 2nd month of vitamin D3 intervention were significantly (P < 0·001) decreased and the 25(OH)D, urea and creatinine levels were significantly (P < 0·001) increased in the treatment group. In the placebo group, no significant changes were identified throughout the follow-up period. In conclusion, vitamin D3 intervention with a treatment dose of 1250 µg/week for at least 2 months may help in lowering Hcy and CRP levels and may improve liver function tests, which in turn might help in minimising the risk of CVD and liver diseases among overweight women but negatively affect kidney function.
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Association Between Homocysteine and Vitamin Levels in Demented Patients.
Hoffmann, J, Busse, S, von Hoff, F, Borucki, K, Frodl, T, Busse, M
Journal of Alzheimer's disease : JAD. 2021;(4):1781-1792
Abstract
BACKGROUND Although it is known that the nutritional status among elderly persons and, in particular, patients with dementia, is compromised, malnutrition that results in insufficient uptake of several vitamins is often not diagnosed. OBJECTIVE An elevated homocysteine level is a known strong risk factor for vascular dementia (VaD) and Alzheimer's disease (AD). Several B vitamins are involved in the metabolism of homocysteine. Therefore, we investigated the serum levels of vitamin B1, vitamin B6, folate, and vitamin B12 in 97 patients with mild cognitive impairment (MCI) or different forms of dementia and 54 elderly control persons without dementia. RESULTS Compared to aged non-demented people, vitamins B1, B6, B12, and folate were decreased in serum of patients with AD, and patients with Lewy body dementia had reduced vitamin B12 level. Vitamin B6 was diminished in VaD. Patients with frontotemporal dementia showed no alterations in vitamin levels. Age was identified as an important factor contributing to the concentrations of vitamin B1 and B6 in serum, but not vitamin B12 and folate. Increased levels of total homocysteine were detected especially in MCI and AD. Homocysteine correlated negatively with levels of vitamins B6, B12, and folate and positively with Q Albumin. CONCLUSION Our data suggest that despite increased homocysteine already present in MCI, vitamin levels are decreased only in dementia. We propose to determine the vitamin levels in patients with cognitive decline, but also elderly people in general, and recommend supplementing these nutrients if needed.
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Epigenetic memory: gene writer, eraser and homocysteine.
Tyagi, SC, Stanisic, D, Singh, M
Molecular and cellular biochemistry. 2021;(2):507-512
Abstract
Naturally chromatin remodeling is highly organized, consisting of histone acetylation (opening/relaxation of the compact chromatin structure), DNA methylation (inhibition of the gene expression activity) and sequence rearrangement by shifting. All this is essentially required for proper "in-printing and off-printing" of genes thus ensuring the epigenetic memory process. Any imbalance in ratios of DNA methyltransferase (DNMT, gene writer), fat-mass obesity-associated protein (FTO, gene eraser) and product (function) homocysteine (Hcy) could lead to numerous diseases. Interestingly, a similar process also happens in stem cells during embryogenesis and development. Despite gigantic unsuccessful efforts undertaken thus far toward the conversion of a stem cell into a functional cardiomyocyte, there has been hardly any study that shows successful conversion of a stem cell into a multinucleated cardiomyocyte. We have shown nuclear hypertrophy during heart failure, however; the mechanism(s) of epigenetic memory, regulation of genes during fertilization, embryogenesis, development and during adulthood remain far from understanding. In addition, there may be a connection of aging, loosing of the memory leading to death, and presumably to reincarnation. This review highlights some of these pertinent issues facing the discipline of biology as a whole today.
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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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Elevated Blood Homocysteine and Risk of Alzheimer's Dementia: An Updated Systematic Review and Meta-Analysis Based on Prospective Studies.
Zuin, M, Cervellati, C, Brombo, G, Trentini, A, Roncon, L, Zuliani, G
The journal of prevention of Alzheimer's disease. 2021;(3):329-334
Abstract
OBJECTIVE To investigate whether high serum homocysteine (Hcy) levels is associated with the risk of developing Alzheimer's disease (AD) by performing a meta-analysis based on updated published data. METHODS We conducted a comprehensive research using Medline (Pubmed), Scopus, Web of Science and EMBASE databases to identify all prospective studies published any time to July 7, 2020 evaluating the association between elevated Hcy levels and AD risk. RESULTS From an initial screening of 269 published papers, 9 prospective investigations conducted on a total of 7474 subjects with mean follow-up of 9.5 years (range: 3.7-10) were included in the meta-analysis. Eight seventy-five of these subjects converted to AD. Hcy was significantly higher in these individuals (HRadjusted:1.48, 95% CI:1.23-1.76, I2=65.6%, p<0.0001) compared with who did not convert to AD. There was a significant publication bias (Egger's test, t=6.39, p=0.0003) and this was overcome by the trim and fill method, which allowed to calculate a bias-corrected imputed risk estimate of HRadjusted:1.20, 95% CI:1.01-1.44, Q value=41.92. CONCLUSIONS The present meta-analysis found that having higher Hcy increases the risk of AD in the elderly and this finding is consistent with the widely suggested role of this non-proteinogenic α-amino acid in AD neurodegeneration.