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Serum levels of Homocysteine, Vitamin B12 and Folate in Patients with Multiple Sclerosis: an Updated Meta-Analysis.
Li, X, Yuan, J, Han, J, Hu, W
International journal of medical sciences. 2020;(6):751-761
Abstract
Background: Multiple sclerosis (MS) is a demyelinating and disabling inflammatory disease of the central nervous system. MS is triggered by complex environmental factors which mostly affect genetically the susceptible young people. Emerging data has suggested that changes of homocysteine (Hcy), Vitamin B12 and folate serum levels may be associated with MS. However, previous findings are not always consistent. Methods: In this study, we aimed to investigate the relationships between MS and Hcy, Vitamin B12 and folate with updated available data (until September, 2019). The diagnosis of MS was performed based on international criteria for the diagnosis of MS, including magnetic resonance imaging and cerebrospinal fluid tests. We searched the databases including PubMed, EMBASE, Cochrane Library and ScienceDirect. After data collection, separate analyses based on random-effect models were used to test for relationships between MS and Hcy, Vitamin B12 or folate blood levels. The effective sizes were estimated by the combined standardized mean difference (SMD) and associated 95% confidence interval (CI). Results: Based on the inclusion criteria, a total of 21 original studies with 1738 MS patients and 1424 controls were included in this study. There were 17 studies for measuring Hcy, 16 studies for measuring Vitamin B12 and 13 studies for measuring folate in patients with MS, respectively. Specifically, patients with MS had higher serum levels of Hcy (SMD: 0.64; 95% CI:0.33, 0.95; P <0.0001) compared with control groups. There were no significant differences of SMD for Vitamin B12 (SMD: -0.08; 95% CI: -0.35, 0.20; P=0.58) or folate (SMD: 0.07; 95% CI: -0.14, 0.28; P=0.52) between MS and controls. Subgroup analysis demonstrated that there was statistically significant difference for Hcy between relapsing-remitting MS (RRMS) patients and controls with a SMD of 0.67 (95% CI: 0.21, 1.13; P=0.004). However, no significant difference of Hcy serum levels between secondary progressive MS patients or primary progressive MS patients and controls was noted in this study. In addition, there was no significant difference of Hcy levels in females (SMD: 0.22; 95% CI: -0.16, 0.60; P=0.25) or males (SMD: 0.56; 95% CI: -0.13, 1.26; P=0.11) between MS patients and controls. Conclusions: Higher serum levels of Hcy were noted in patients with MS when compared with control groups. And the difference was especially significant between RRMS patients and controls. Hcy may play an important role in the pathogenesis of MS. Functional studies are required to assess the effects of Hcy on patients with MS at the molecular level.
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A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects.
Xu, A, Cao, X, Lu, Y, Li, H, Zhu, Q, Chen, X, Jiang, H, Li, X
International heart journal. 2016;(6):725-728
Abstract
Controversial opinions exist with respect to the relationship between maternal folic acid (FA) supplementation and birth prevalence of congenital heart defects (CHDs).Eligible articles were retrieved by searching databases, including PubMed, Cochrane library, EMBASE, CNKI, and WanFang up to September 2015. A meta-analysis was performed to evaluate the effects of FA on CHDs. Odds ratios (ORs) and 95% confidence interval (CIs) were merged using STATA 12.0. Meta-regression analysis was used to explore the possible sources of heterogeneity. Subgroup analysis according to the selected sources was also performed. Publication bias was assessed by Egger's test.Twenty studies were included in the meta-analysis. The overall analysis showed that FA supplementation was significantly associated with decreased risk of CHDs. The meta-regression analysis showed that geographical area could be an important source of heterogeneity. The subgroup analysis based on the geographical area revealed that FA supplementation during pregnancy was a protective factor against CHDs in Chinese and European patients, but not in American patients. Subgroup analysis according to literature quality also displayed positive associations between FA supplementation and the decreased risk of CHDs of China.FA supplementation during pregnancy significantly decreases the risk of CHDs in newborns in China and Europe.
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Higher dietary folate intake reduces the breast cancer risk: a systematic review and meta-analysis.
Chen, P, Li, C, Li, X, Li, J, Chu, R, Wang, H
British journal of cancer. 2014;(9):2327-38
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Abstract
BACKGROUND Many epidemiological studies have investigated the association between folate intake, circulating folate level and risk of breast cancer; however, the findings were inconsistent between the studies. METHODS We searched the PubMed and MEDLINE databases updated to January, 2014 and performed the systematic review and meta-analysis of the published epidemiological studies to assess the associations between folate intake level, circulating folate level and the overall risk of breast cancer. RESULTS In all, 16 eligible prospective studies with a total of 744 068 participants and 26 205 breast cancer patients and 26 case-control studies with a total of 16 826 cases and 21 820 controls that have evaluated the association between folate intake and breast cancer risk were identified. Pooled analysis of the prospective studies and case-control studies suggested a potential nonlinearity relationship for dietary folate intake and breast cancer risk. Prospective studies indicated a U-shaped relationship for the dietary folate intake and breast cancer risk. Women with daily dietary folate intake between 153 and 400 μg showed a significant reduced breast cancer risk compared with those <153 μg, but not for those >400 μg. The case-control studies also suggested a significantly negative correlation between the dietary folate intake level and the breast cancer risk. Increased dietary folate intake reduced breast cancer risk for women with higher alcohol intake level, but not for those with lower alcohol intake. No significant association between circulating folate level and breast cancer risk was found when the results of 8 identified studies with 5924 participants were pooled. CONCLUSIONS Our studies suggested that folate may have preventive effects against breast cancer risk, especially for those with higher alcohol consumption level; however, the dose and timing are critical and more studies are warranted to further elucidate the questions.
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Supplementation of folic acid and vitamin B₁₂ reduces plasma levels of asymmetric dimethylarginine in patients with acute ischemic stroke.
Xia, XS, Li, X, Wang, L, Wang, JZ, Ma, JP, Wu, CJ
Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2014;(9):1586-90
Abstract
Increased levels of asymmetric dimethylarginine (ADMA) have been observed in patients with acute ischemic stroke. We aimed to investigate the correlation between ADMA and ischemic stroke, and evaluate the effect of supplementation of folic acid and vitamin B12 on concentrations of ADMA. Patients were randomized into intervention and non-intervention groups within 3 days after symptom onset. Intervention group patients were treated with folic acid (5mg daily) and vitamin B12 (500 μg twice daily) for 12 weeks. ADMA and homocysteine (Hcy) concentrations were measured before treatment (baseline) and 2 and 12 weeks after treatment. The laboratory measures were also collected from healthy controls. Eighty five subjects were enrolled in this study, from whom 72 with complete baseline and follow-up laboratory data were included in the present analysis. Thirty four patients were assigned to the intervention group and 38 patients to the non-intervention group. Sixty people were enrolled as healthy controls. Levels of ADMA and Hcy were raised (p<0.05) in patients with acute ischemic stroke. With supplementation of both folic acid and vitamin B12, the levels of ADMA and Hcy decreased significantly at 2 and 12 weeks (p<0.05). The present study reconfirmed that ADMA can be regarded as a risk biomarker for acute ischemic stroke. We observed that with supplementation of folic acid and vitamin B12, levels of ADMA were decreased in patients with acute ischemic stroke.
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Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis.
Li, C, Chen, P, Hu, P, Li, M, Li, X, Guo, H, Li, J, Chu, R, Zhang, W, Wang, H
Molecular biology reports. 2013;(12):6547-60
Abstract
Folate is essential for DNA synthesis and methylation and implicated in the process of carcinogenesis. Several studies inconclusively suggested increased folate intake may reduce ovarian cancer risk. Studies concerning the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, and ovarian cancer risk also resulted in no agreement. The meta-analysis was conducted based on current studies to assess the association between folate intake, the MTHFR C667T polymorphism and ovarian cancer risk. 1,158 cases out of 217,309 participants from four cohort studies, 4,519 cases and 6,031 controls from four case-control studies about folate intake along with 5,617 cases and 9,808 controls from 10 publications concerning the polymorphism were pooled, respectively. We detected no significant association between total folate (RR = 1.04, 95 % confidence interval (CI) = 0.87-1.23) or dietary folate (RR = 0.88, 95 % CI = 0.75-1.05) intake and ovarian cancer risk, and also no significant relationship was found between MTHFR C677T polymorphism and ovarian cancer risk (TT vs. CC: odds ratio (OR) = 1.15, 95 % CI = 0.90-1.46; CT vs. CC: OR = 1.04, 95 % CI = 0.94-1.16). Our analysis indicated neither folate intake nor MTHFR C677T polymorphism is related to altered susceptibility of ovarian cancer.
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[Impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine and asymmetric dimethylarginine levels of essential hypertension patients].
Wu, CJ, Wang, L, Li, X, Wang, CX, Ma, JP, Xia, XS
Zhonghua xin xue guan bing za zhi. 2012;(12):1003-8
Abstract
OBJECTIVE To investigate the impact of adding folic acid, vitamin B(12) and probucol to standard antihypertensive medication on plasma homocysteine (Hcy) and asymmetric dimethylarginine (ADMA), serum NO and eNOS of essential hypertensive patients. METHOD A total of 120 patients with hypertension were randomly divided to three groups (n = 40 each): group 1 (standard medication), group 2 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily) and group 3 (adding folic acid 5 mg/day and vitamin B(12) 500 µg twice daily and probucol 500 mg twice daily). Plasma Hcy and ADMA, serum NO and eNOS levels were observed at baseline, 2 and 12 weeks after various therapy. RESULTS In group 1, concentrations of plasma Hcy [(23.06 ± 14.15) µmol/L, (23.67 ± 12.31) µmol/L, (23.25 ± 11.64) µmol/L], ADMA [(0.21 ± 0.12) µmol/L, (0.23 ± 0.13) µmol/L, (0.21 ± 0.09) µmol/L] and serum NO [(64.14 ± 15.07) µmol/L, (65.29 ± 15.04) µmol/L, (65.32 ± 13.58) µmol/L], eNOS [(20.02 ± 4.50) µg/L, (20.79 ± 4.03) µg/L, (19.82 ± 5.70) µg/L] remained unchanged during the 12 weeks therapy (all P > 0.05). In group 2, concentrations of plasma Hcy [(12.54 ± 6.49) µmol/L] and ADMA[(0.18 ± 0.07) µmol/L] were significantly decreased after the treatment of 12 weeks than the treatment baseline value [(21.51 ± 7.82) µmol/L, (0.20 ± 0.12) µmol/L] and 2 weeks value[(19.38 ± 8.14) µmol/L, (0.21 ± 0.12) µmol/L], however the concentrations of serum NO and eNOS showed contrary results of the Hcy and ADMA's. (all P < 0.05). In group 3, similar changes occurred at 2 weeks after therapy (P < 0.05 2 weeks vs. baseline and 12 weeks vs. 2 weeks). Plasma ADMA level was positively correlated with Hcy at baseline (r = 0.546, P < 0.05). CONCLUSIONS Supplementation of folic acid, VitB(12) and/or probucol helps to improve endothelial function and reduce plasma Hcy and ADMA levels in patients with hypertension.