Serum tHcy Levels Research Articles

Does the Available Literature about Hyperhomocysteinemia Cause Confusion to Clinicians?

Background—Aim: Hyperhomocysteinemia (HHcy) (typically defined as serum total homocysteine/tHcy levels >15 μmol/L) has been associated with more than 100 diseases, syndromes, or outcomes. However, the current literature about the testing for or the treatment of HHcy causes confusion to clinicians. The aim of this study was to present and comment on the main causes of this confusion. Discussion: The main causes of the above confusion are the important limitations of clinical trials related to the management of HHcy, the false impression that measurement of serum tHcy levels is not useful generally in clinical practice, the inability of modern diet (poor in folate and rich in methionine) to reduce the serum tHcy levels, and, finally, the consequent exclusion of identifying individuals with genetic causes of HHcy, as MTHFR C677T gene mutation. Conclusion: The recommendations about the testing for or the treatment of HHcy must be clarified.

The effects of folinic acid and l-methylfolate supplementation on serum total homocysteine levels in healthy adults

Hyperhomocysteinemia is recognized as a risk factor for several diseases and conditions. The aim of this study was to investigate and compare the efficacy of two total homocysteine (tHcy)-lowering treatments including folinic acid or l-methylfolate in healthy Greek adults. Two hundred and seventy-two healthy Greek adults (143 men, 129 women; mean age±SD: 43.0±15.3 years), with serum tHcy levels ≥10μmol/L received randomized folinic acid ("Folinic acid Group") or l-methylfolate ("l-methylfolate Group") orally for three months. All subjects with serum cobalamin (Cbl) levels <300pg/mL additionally received 1mg hydroxycobalamine intramuscularly twice a week for the first month only. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and MTHFR A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. At the end of the 3-month intervention period, the levels of serum folate and Cbl increased significantly, whereas the levels of serum tHcy decreased significantly in the two groups. The individuals with MTHFR 677TT genotype had a significantly higher reduction in serum tHcy levels than the individuals with the MTHFR 677CC or MTHFR 677CT genotypes. Although the "Folinic acid Group" had a considerably higher increase in their serum folate levels (but not Cbl) than the "l-methylfolate Group", the reduction of serum tHcy levels between the two groups was not substantially different. The individuals with MTHFR 677CT genotype had a statistically significant higher reduction in serum tHcy levels when supplemented with folinic acid rather than l-methylfolate. The administration of folinic acid compared to l-methylfolate caused a higher increase of serum folate levels but no difference in the reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not MTHFR A1298C gene polymorphisms. The individuals with MTHFR 677CT genotype appear to benefit more by folinic acid than l-methylfolate supplementation.

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

FOLINIC ACID OR L-METHYLFOLATE SUPPLEMENTATION FOR THE TREATMENT OF HYPERHOMOCYSTEINEMIA

Objective: Hyperhomocysteinemia (HHcy) is recognized as a risk factor for for cardiovascular disease. The aim of this study was to investigate and compare the efficacy of two tHcy-lowering treatments including FNA or L-methylfolate in healthy Greek adults. Design and method: Two hundred and seventy two (272) health Greek adults (143 men; mean age±SD: 43.0±15.3 years), with elevated serum tHcy levels (&gt;10 mmol/L) received randomized folinic acid (Group 1) or L-methylfolate (Group 2) orally both with hydroxycobalamine im for three months. Serum folate, Cbl and tHcy levels were determined using immunoassays methods at the beginning and the end of the study period. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Results: At the end of the 3-month intervention period the levels of serum folate and Cbl were significantly increased, whereas serum tHcy concentrations were significantly decreased in both groups. The individuals with 677TT genotype had significantly higher reduction of serum tHcy levels than individuals with the 677CC or 677CT genotypes. Although the individuals of Group 1 had significantly greater increase of their serum folate levels than those of Group 2, the reduction of serum tHcy concentrations between the two groups did not differ significantly. The individuals with 677CT genotype had statistically significant greater reduction of serum tHcy levels when received folinic acid than methylfolate supplementation. Conclusions: The tHcy-lowering treatment which included FNA supplementation compared to treatment which included L-methylfolate supplementation caused a greater increase of serum folate levels but no difference in reduction of serum tHcy levels. The reduction of serum tHcy levels was influenced by the existence of MTHFR C677T and not A1298C gene polymorphisms. The individuals with 677CT genotype appear to benefit more by the treatment which included FNA than L-methylfolate supplementation.

Vitamin B12, Folate, Homocysteine, Inflammatory Mediators (Interleukin-6, Tumor Necrosis Factor-α and C-Reactive Protein) Levels in Adolescents with Anxiety or Depressive Symptoms.

To evaluate the prevalence of abnormal vitamin B12, folate, total homocysteine (tHcy), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) levels, to analyze the relationship between these parameters and the severity of anxiety or depressive symptoms, and to explore the possible factors associated with abnormal levels of these parameters in adolescents with anxiety or depressive symptoms. Adolescent (aged 12-18 years) outpatients with anxiety or depressive symptoms were recruited. The patient health questionnaire-9 and generalized anxiety disorder scale-7 were used to measure the severity of depression and anxiety. Serum vitamin B12, folate, tHcy, IL-6, TNF-α, and CRP levels were determined. 128 subjects were recruited. The prevalence of vitamin B12 and folate deficiency, tHcy, TNF-α, IL-6, and CRP elevation was 8.6%, 10.2%, 25.8%, 14.8%, 21.9%, and 10.2%, respectively, in adolescents with anxiety or depressive symptoms. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety and depressive symptoms. The severity of some symptoms of anxiety or depression were weakly correlated with vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were not associated with inflammatory mediators. Vitamin B12 deficiency was associated with older age and higher tHcy levels. Folate deficiency was associated with elevatedtHcy. ElevatedtHcy was associated with lower vitamin B12 and folate levels. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking. Lower vitamin B12 levels were correlated with a higher risk of severe anxiety or depressive symptoms. Weak correlations were observed between the severity of some symptoms of anxiety or depression and vitamin B12, folate, tHcy, IL-6, and CRP levels. Vitamin B12, folate, and tHcy levels were related to each other. IL-6 elevation was associated with elevated CRP and TNF-α. CRP elevation was associated with older age, higher BMI, and current drinking.

Association of methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms with serum folate, cobalanin and homocysteine concentrations in Greek adults

Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men and 184 women) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The MTHFR C677T and not the A1298C gene polymorphism had a significantly influence on serum folate and tHcy levels. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Associations of Serum Total Homocysteine Levels with Various Demographic, Clinical and Genetic Characteristics in Healthy Greek Adults.

The aim of this study was to investigate the association of serum total Hcy (tHcy) levels with various demographic, clinical and genetic characteristics in healthy Greek adults. Anthropometric characteristics (height, weight), systolic and diastolic blood pressure, complete blood count and biochemical assessments, were recorded and measured among 383 Greek adults (199 men). Serum folate, Cobalamin (Cbl) and tHcy levels were determined using immunoassays methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. MTHFR C677T gene polymorphism, serum folate and Cbl levels were correlated with serum tHcy levels independently. The individuals with 677TT genotype had significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. Regarding the MTHFR C677T gene polymorphism, the existence of the T allele was associated with statistically significantly lower serum folate and higher serum tHcy levels than C allele. Regarding the MTHFR A1298C gene polymorphism, the existence of the C allele was associated with statistically significant lower serum tHcy levels than A allele. Furthermore, there was no significant correlation between the serum tHcy levels and demographic (except age) or clinical characteristics (sex, BMI, smoking status, SBP, DBP, HGB, HCT, TC, TG, HDL-C, LDL-C, TC/HDL-C). Serum tHcy levels are influenced by the existence of MTHFR C677T gene polymorphism (mainly 677TT genotype), serum folate and Cbl levels. Individuals with hyperhomocysteinemia should be further investigated for the existence of MTHFR C677T gene polymorphism, with the aim to determine the suitable treatment.

Relationship between MMP-9 serum levels and tHcy levels and total imaging load and cognitive dysfunction

ObjectivesTo investigate the correlation and predictive value of serum matrix metalloproteinase-9 (MMP-9) level with cognitive dysfunction and total imaging load in patients with cerebral small vessel disease (CSVD). MethodsA total of 80 patients with CSVD who were admitted to the First Affiliated Hospital of Xinxiang Medical University between April 2019 and April 2020 were enrolled. All subjects underwent T1-weighted imaging (T1WI), T2WI, fluid-attenuated inversion recovery (FLAIR), diffusion weighted imaging (DWI), serum sample collection, and assessment of cognitive function at a specific time-point after admission. According to the results of the neuropsychological test, subjects were divided into cognitive dysfunction group (n=40) and normal cognitive function group (n=40). The total imaging load was estimated according to the neuroimaging findings. Serum MMP-9 level was measured by an enzyme-linked immunosorbent assay (ELISA) kit. Beside, serum MMP-9 level and total imaging load were compared between the two groups. ResultsSerum levels of MMP-9 and plasma total homocysteine (tHcy) were negatively correlated with cognitive function (P<0.05). Serum MMP-9 level was found as a significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.756; sensitivity and specificity were 97.5% and 75.0%, respectively). THcy level was also found as significant factor for diagnosing cognitive impairment due to CSVD (area under the curve (AUC), 0.727; sensitivity and specificity were 97.5% and 75.0%, respectively). ConclusionSerum MMP-9 level and tHcy level were significantly correlated with cognitive function in patients with CSVD. Serum MMP-9 level has a specific correlation with the total imaging load in patients with CSVD. It plays an important role in diagnosing cognitive impairment in patients with CSVD.

Cerebral small vessel disease mediates the association between homocysteine and cognitive function.

ObjectiveTo investigate the relations of serum total homocysteine (tHcy) with cerebral small vessel disease (CSVD) and cognitive function and evaluate whether CSVD mediates the effect of serum tHcy on cognitive function.MethodsA total of 1,033 consecutive eligible participants who received serum tHcy, brain magnetic resonance imaging (MRI), and neuropsychological assessment were included in this retrospective study. White matter hyperintensity, lacune, cerebral microbleed, and enlarged perivascular space were evaluated based on brain MRI. We used multivariate binary logistic regression analysis, multivariate ordinal logistic regression analysis, and mediation analyses to assess the relations of serum tHcy with CSVD and cognitive function.ResultsSerum tHcy levels were higher in patients with cognitive impairment than those with no cognitive impairment. Logistic regression analyses showed elevated serum tHcy was associated with cognitive impairment [odds ratio (OR): 10.475; 95% confidence interval (CI): 4.522 to 24.264; p < 0.001] and a higher CSVD burden score (OR: 17.151; 95% CI: 8.785 to 33.921; p < 0.001) after adjusting potential confounders. Compared with the lowest tHcy quartile, the multivariable-adjusted OR of the highest quartile was 4.851 (95% CI: 3.152 to 7.466; p for the trend < 0.001) for cognitive impairment, 3.862 (95% CI: 2.467 to 6.047; p for the trend < 0.001) for a severe CSVD burden score. Mediation analyses showed significant moderating effects (9.3–23.6%) by different imaging markers of CSVD on the association between higher serum tHcy levels and cognitive impairment.ConclusionElevated serum tHcy is associated with cognitive impairment and the development of CSVD. A proportion of the association between elevated serum tHcy and cognitive impairment may be attributed to the presence of different imaging markers of CSVD, especially the severe CSVD burden score.

Relationship between carotid artery stiffness and total serum homocysteine in coronary slow flow phenomenon: a high-resolution echo-tracking study

Coronary slow flow phenomenon (CSFP) is not uncommon in conventional coronary angiography. A disorder of serum homocysteine (tHcy) metabolism may play a role in the pathogenesis of slow coronary flow. Moreover, elevated tHcy concentration is closely associated with atherosclerosis. We aimed to evaluate the relationship between carotid artery stiffness and serum tHcy levels in patients with CSFP. This was a case-control study. The study population comprised 146 patients with newly diagnosed stable angina, including 73 patients with CSFP and 73 patients with normal coronary flow. All participants underwent conventional coronary angiography, carotid ultrasonography, and biochemical examination. The carotid artery stiffness parameters of β index (β), pressure-strain elastic modulus (Ep), and local pulse wave velocity (PWV) in the CSFP group were significantly higher than those in the control group (β: 10.75±2.16 vs. 9.02±2.11, P=0.007; Ep: 147.41±41.22 vs. 116.21±39.21, P=0.004; PWV: 7.45±1.23 vs. 6.16±1.20, P=0.003), However, arterial compliance (AC) was lower in the CSFP group than the control group (0.52±0.11 vs. 0.69±0.24, P=0.008). The mean thrombolysis in myocardial infarction (TIMI) frame count and the tHcy concentration in the CSFP group were significantly higher than those in the control group (48.60±1.30 vs. 24.50±3.80, P=0.001; 19.95±4.00 vs. 9.12±2.72, P=0.009). The tHcy concentration was positively correlated with β (R value =0.494, P<0.0001), Ep (R value =0.469, P<0.0001), and PWV (R value =0.436, P<0.0001), but negatively correlated with AC (R value =-0.230, P=0.022). The predictors of CSFP were tHcy concentration, left PWV, right PWV, left β index, and right β index. Among them, the left β index and right β index were the best indictors for predicting CSFP. The cutoff values of left β index, right β index, left PWV, and right PWV were 9.3, 9.3, 6.7, and 6.6, respectively. Our data showed that serum tHcy levels were elevated in patients with CSFP compared with the control group. Carotid artery stiffness parameters were correlated with tHcy. The best predictors of CSFP were left β index and right β index. These findings may contribute to a better understanding of systemic vascular disorders in patients with coronary slow flow, rather than simply attributing such disorders to a single and isolated lesion of the epicardial coronary artery.

Serum homocysteine level in pediatric patients with COVID-19 and its correlation with the disease severity.

BackgroundThrombosis and embolism are possible complications in coronavirus disease 2019 (COVID)‐19‐positive pediatric patients. Although the risk is lesser in children than it is in adults, it does exist during acute infection and multi‐inflammatory syndrome in children. Biomarkers such asd‐dimer, prothrombin time, and fibrinogen degradation products are ineffective at detecting disease severity. Homocysteine (Hcy) is a prothrombotic factor that has been reported to be higher in adult COVID‐19 patients, leading to speculation that it could be used as a biomarker for disease severity.PurposeTo detect the correlation between serum total homocysteine (tHcy) level and the severity of COVID‐19 in pediatrics.MethodsA cross‐sectional study was conducted on 40 children with COVID‐19 and 40 healthy control subjects. Serum tHcy was measured by enzyme‐linked immunosorbent assay and correlated with the clinical, laboratory, and radiological parameters of the patients.ResultsThe median serum tHcy level in COVID‐19 patients was 27.5 (interquartile range [IQR]: 23–31.75) μmol/L, while that in the controls was 1.8 (IQR: 1.6–1.875) μmol/L. There was a statistically significant increase in the tHcy level in cases compared to controls (p < 0.001). There was a statistically significant positive correlation between serum tHcy and d‐dimer, ferritin, alanine transaminase, aspartate transaminase, blood urea nitrogen, and a highly significant positive correlation between tHcy and COVID‐19 reporting and data system score, pediatric intensive care unit admission, and the disease severity classification.ConclusionHcy could be a biomarker of importance in predicting the severity of COVID‐19 in pediatrics.

Combined homocysteine and apoE rs429358 and rs7412 polymorphism in association with serum lipid levels and cognition in Chinese community-dwelling older adults

BackgroundApoE gene polymorphism and serum total homocysteine (tHcy) has been reportedly associated with cognition. In this study, we assessed the association of combined ApoE gene polymorphism and tHcy with cognition in Chinese elder adults.MethodsA cross- sectional study was carried out by recruiting 1458 community-dwelling people aged 55+ and above in Beijing in 2009. All participants were interviewed using a standard questionnaire and underwent a physical examination. The mini-mental scale examination (MMSE) score was used in assessing cognitive function. Fasting venous blood samples were taken for ApoE rs429358, rs7412 genotyping, tHcy and other serum lipid measurements.ResultsParticipants with high serum tHcy level showed a relatively lower orientation, attention abilities as well as the total MMSE score than the group with normal tHcy after adjusting confounding factors. ApoE rs429358 and rs7412 variants were observed to have the highest serum TC and TG level in the subjects with high serum tHcy level (p < 0.05). Cognition of the subjects was found to be significantly associated with high serum tHcy level and ApoE genetic polymorphism (p < 0.05). Independent of age, BMI, education levels, smoking and alcohol drinking, the worst cognitive ability were detected in the high serum tHcy level subjects with ApoE rs429358C/T and rs7412 C/T as compare with other groups, especially orientation function, memory and delayed recall ability and attention ability.ConclusionHigh serum tHcy level in combination with ApoE rs429358 and rs7412 variants might be linked with serum lipid levels and cognition, particularly for orientation function and memory and delayed recall ability in old Chinese adults.

The association between serum total homocysteine and subacute combined degeneration of spinal cord

Objective: The research was aimed to investigate the association between serum total homocysteine (tHcy) and subacute combined degeneration of the spinal cord (SCD). Methods: A retrospective survey of 106 newly diagnosed patients with SCD were enrolled in this research who were treated in the department of neurology of Xijing Hospital from January 2008 to February 2019, meanwhile, 121 patients with spinal cord lesion (not SCD) and 104 neurology mild outpatients were selected as controls. Serum tHcy level was determined by using the chemiluminescent immunoassay assay. A multivariate logistic regression model was used to analyze the risk factors for SCD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, sensitivity, specificity and Youden index were used to evaluate the diagnostic efficacy of tHcy. Spearman correlation analysis was used to observe the correlation between tHcy and SCD severity. The SCD patients were categorized into normal or mild tHcy group, moderate tHcy group, and severe tHcy group based on tHcy levels. Clinical symptoms, nerve conduction velocity, magnetic resonance imaging (MRI) findings from the patients were studied. Results: The serum tHcy levels in SCD patients were 64.3(26.5, 98.8) μmol/L, while in patients with spinal cord lesion (not SCD) group were 13.7(10.8, 19.2) μmol/L, neurology mild outpatients were 10.6(8.2, 13.0) μmol/L, which was higher in SCD group (H=112.020,P<0.001), (H=165.525,P<0.001).The multivariate logistic regression model showed tHcy is the impact factor of SCD (OR=1.107, 95%CI:1.077-1.139, P<0.001). At ROC analysis, tHcy showed diagnostic value with an optimal cut-off value of 24.9 μmol/L (AUC 0.913, 95%CI: 0.875-0.951, sensitivity 79.2%, specificity 91.6%). Spearman correlation analysis showed that tHcy was positively correlated with functional disability rating scale (r=0.254, P=0.009). Conclusions: Serum tHcy is the risk factor for SCD and related to its disability. Focus on the increased level of tHcy plays a positive role in the diagnosis of SCD.

Hypohomocysteinemia may increases the risk of dementia and Alzheimer's disease: A nationwide population-based prospective cohort study

Hyperhomocysteinemia has been repeatedly found to increase the risk of dementia. However, the effects of hypohomocysteinemia on the risk of dementia have been barely investigated. If hypohomocysteinemia, like hyperhomocysteinemia, increases the risk of dementia, misuse or overuse of homocysteine-lowing agents such as vitamin supplements may increase the risk of dementia. To investigate whether hypohomocysteinemia, like hyperhomocysteinemia, could increase the risk of dementia and Alzheimer's disease (AD) in a large population-based cohort of older adults. This prospective cohort study followed 2655 randomly sampled, community-dwelling, non-demented individuals aged 60 years or older from 2010 to 2018. We measured baseline serum total homocysteine (tHcy) levels and examined the effect of serum tHcy on the risks of dementia and AD using Cox proportional hazards models. During the follow-up period (mean=5.4 years, SD=0.9), dementia and AD developed in 85 and 64 participants, respectively. Not only the participants with high serum tHcy (≥10.6μmol/L) but also those with low serum tHcy (≤8.9μmol/L) were 4-5 times more likely to develop dementia and AD compared to those with serum tHcy levels between 9.0 and 10.5μmol/L. With the increase in serum tHcy concentration, the use of vitamin supplements decreased, and 41.2% of the participants with low serum tHcy (≤8.9μmol/L) were taking vitamin supplements. Not only hyperhomocysteinemia but also hypohomocysteinemia considerably increased the risk of dementia and AD in older adults. The risk of dementia that results from overuse or misuse of vitamin supplements should be acknowledged and homocysteine-lowering health policies should be tailored to consider dementia risks that are associated with hypohomocysteinemia.

Analysis of differential neonatal lethality in cystathionine β-synthase deficient mouse models using metabolic profiling.

Cystathionine beta-synthase (CBS) is a key enzyme of the trans-sulfuration pathway that converts homocysteine to cystathionine. Loss of CBS activity due to mutation results in CBS deficiency, an inborn error of metabolism characterized by extreme elevation of plasma total homocysteine (tHcy). C57BL6 mice containing either a homozygous null mutation in the cystathionine β-synthase (Cbs-/- ) gene or an inactive human CBS protein (Tg-G307S Cbs-/- ) are born in mendelian numbers, but the vast majority die between 18 and 21 days of age due to liver failure. However, adult Cbs null mice that express a hypomorphic allele of human CBS as a transgene (Tg-I278T Cbs-/- ) show almost no neonatal lethality despite having serum tHcy levels similar to mice with no CBS activity. Here, we characterize liver and serum metabolites in neonatal Cbs+/- , Tg-G307S Cbs-/- , and Tg-I278T Cbs-/- mice at 6, 10, and 17 days of age to understand this difference. In serum, we observe similar elevations in tHcy in both Tg-G307S Cbs-/- and Tg-I278T Cbs-/- compared to control animals, but methionine is much more severely elevated in Tg-G307S Cbs-/- mice. Large scale metabolomic analysis of liver tissue confirms that both methionine and methionine-sulfoxide are significantly more elevated in Tg-G307S Cbs-/- animals, along with significant differences in several other metabolites including hexoses, amino acids, other amines, lipids, and carboxylic acids. Our data are consistent with a model that the neonatal lethality observed in CBS-null mice is driven by excess methionine resulting in increased stress on a variety of related pathways including the urea cycle, TCA cycle, gluconeogenesis, and phosphatidylcholine biosynthesis.

Homocysteine Associated With Low Cognitive Function Independent of Asymptomatic Intracranial and Carotid Arteries Stenoses in Chinese Elderly Patients: An Outpatient-Based Cross-Sectional Study.

A high homocysteine (Hcy) concentration is correlated with cognitive impairment; however, the exact underlying mechanism is still not fully elucidated. The present study aimed to investigate whether asymptomatic intracranial and carotid arteries stenoses are involved in Hcy-related low cognitive function. This was a cross-sectional study in outpatient clinics. Residents aged ≥60 years, who came to the Stroke and Rehabilitation Clinic of Shandong Provincial Third Hospital in Jinan, Shandong Province from December 2019 to May 2020 to seek consultation due to abnormal transcranial Doppler reports (eg., increased cerebral blood flow velocity) were eligible. Information including demographics, medical history, lifestyle habits were collected. Fasting blood was used to detect total serum homocysteine level (tHcy). Cerebrovascular magnetic resonance angiography and neck vascular ultrasound examination were used to confirm the diagnosis of intracranial and carotid artery stenoses. The Mini-Mental State Examination was used to assess the cognitive function of each participant. Logistic regression was used to evaluate the relationship between tHcy levels and cognitive function. This study included 236 participants (mean age: 64.0 (SD, 7.5) years, female: 58.1%). Multivariable analyses adjusted for several potential confounders, including creatinine and cardiovascular risk factors, showed that tHcy was associated with carotid artery stenosis (CAS). After adjusting for CAS, ICAS and several potential confounders, the association between tHcy level and low cognitive function remained significant (odds ratio: 1.09, 95% confidence interval: (1.03, 1.16), P = 0.032) . Increased serum tHcy level was associated with low cognitive function independent of asymptomatic intracranial and carotid arteries stenoses.

The Association between Hyperhomocysteinemia and Thoracoabdominal Aortic Aneurysms in Chinese Population.

Objective To shed light on the association between hyperhomocysteinemia (HHcy) and thoracoabdominal aortic aneurysms (TAAAs). Methods From July 2013 to March 2017, we conducted a matched case–control study involving individuals who presented to the Chinese People's Liberation Army General Hospital and underwent thoracoabdominal magnetic resonance angiography or computed tomography angiography. A total of 73 patients with TAAAs were enrolled in the case group, and 219 sex-matched subjects without TAAAs were included in the control group. We then examined the relationship between HHcy and TAAAs by logistic regression models and subgroup as well as interaction analyses. Results Serum total homocysteine (tHcy) concentrations and the proportion of HHcy were significantly higher in the patients with TAAAs than in those without TAAAs (P < 0.001). Furthermore, the multivariate logistic regression models indicated that participants with HHcy had a 2.14-fold higher risk of TAAAs than those with a normal serum tHcy level (adjusted odds ratio (OR), 2.14; 95% confidence interval, 1.00–4.56). Similarly, each 1 μmol/L increase in the serum tHcy concentration was associated with a 4% higher risk of TAAAs (adjusted OR, 1.04; 95% confidence interval, 1.00–1.07). Subgroup analyses indicated that HHcy tended to be associated with a greater risk of TAAAs in all stratified subgroups (adjusted ORs > 1). Furthermore, the interaction analyses revealed no interactive role in the association between HHcy and TAAAs. Conclusions The present case–control study suggests that HHcy is an independent risk factor for TAAAs. Larger prospective cohort studies are warranted to validate these findings.

Serum homocysteine and risk of dementia in Japan

ObjectiveTo examine the association between serum total homocysteine levels (tHcy) and dementia risk.MethodsA total of 1588 Japanese adults aged ≥60 years without dementia were prospectively followed from 2002 to 2012....

Association of Hyperhomocysteinemia with Acute Myocardial Infarction in Kurdish Patients

Cardiovascular disease (CVD) is the main cause of death worldwide. Among multiple cardiovascular risk factors, such as age, blood pressure, diabetes, smoking and hyperlipidemia, hyperhomocysteinemia has recently emerged to have an important role in increasing risk of CVD by impairing oxidative stress-induced endothelial dysfunction and inducing atherothrombosis. However, the association between high circulating level of homocysteine and increasing the risk of CVD in human remains controversial and has not been consistently observed. OBJECTIVES: The aim of this study is to evaluate the association between serum total homocysteine (tHcy) concentrations with increased risk of CAD in patients with acute myocardial infarction (MI) in Kurdish population. In addition, correlations of classical risk factors including hypertension, smoking, diabetes and hyperlipidemia with hyperhomocysteinemia in MI patients were studied. Its role in in development of CVD could be pivotal. METHODS: In a case-control study, a total of 74 patients (51 male; 23 female; aged 22-80 years) who had diagnosed with acute CAD on angiography were enrolled in this study and 74 gender and age matched non-CAD individuals were included as the control group. The serum tHcy level was measured by enzymatic immunoassay. Hyperhomocysteinemia (HHcy) was defined as Hcy>15 µmol/l. RESULTS: the mean ± standard deviation (SD) of serum total homocysteine (tHcy) level in acute myocardial infarction patients was 22.8 ± 1.30 µmol/l, which was significantly higher compared to that of control group being 15.1 ± 1.33 µmol/l (P < 0.001), indicating that a high homocysteine level may promote pathogenesis of atherosclerosis. 51 (68.9%) MI cases had hyperhomocysteinemia; of these 35 MI patients (47.3%) had mild hyperhomocysteinemia (15-30µmol/L), and 16 MI patients (21.6%) had moderate levels of hyperhomocysteinemia (30-100 µmol/L). No significant correlation between tHcy levels and MI risk factors such as hypertension, hyperlipidemia, and diabetes mellitus, was observed. The tHcy levels were significantly higher in smoker patients than in non-smokers. CONCLUSIONS: These findings confirm that in patients with acute myocardial infarction, elevated homocysteine levels are associated with development of MI independent of other risk factors. A strong association between elevated levels of serum tHcy in MI patients was observed in Kurdish population. This study concludes that Hcy is considered as a strong emerging cardiovascular risk factor for development of myocardial infarction. Moreover, the measurement of Homocysteine levels might act as a surrogate laboratory marker and as one of the effective ways to diagnose patients with myocardial infarction in hospitals.