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Abstract Plasma homocysteine (Hcy) has been globally recognized as an independent risk factor for various neurovascular diseases. In this study, the authors investigated the relationship between critical Hcy concentration and the risk of rupture in intracranial aneurysms (IAs). This study collected data from 423 patients with both ruptured and unruptured IAs. We compared demographic data, vascular rupture risk factors, and laboratory test results between the two groups. Multivariable logistic regression analysis was employed to determine the correlation between critical plasma Hcy levels and the risk of rupture in small to medium-sized IAs. A total of 330 cases of ruptured intracranial aneurysms (RIA) and 93 cases of unruptured intracranial aneurysms (UIA) were included. Univariate analysis revealed statistically significant differences between the ruptured and unruptured groups in terms of hypertension, hyperlipidemia, plasma Hcy levels, and IA morphology (all P

In previous studies, decreased vitamin B12 and increased plasma homocysteine levels were reported as risk factors for dementia. The aim of this study was to clarify this relationship in earlier ages. Twenty-one healthy middle-aged adults (9 females, 12 males) with a mean age of 46.21 ± 7.99 were retrospectively included in the study. A voxel-based morphometry analysis was performed to measure brain volume. Plasma homocysteine, vitamin B12 levels, verbal and non-verbal memory test performances were recorded. Correlation analyses showed that increased plasma homocysteine was associated with lower memory score. Decreased vitamin B12 level was found to be associated with smaller brain volume in temporal regions. These results suggest that vitamin B12 and plasma homocysteine levels are associated with brain and cognition as early as middle adulthood. Future studies are needed to clarify whether they might be utilized as early hematological biomarkers to predict cognitive decline and neural loss. [ABSTRACT FROM AUTHOR]

• High plasma concentrations of homocysteine could have a negative impact on embryo and placental development. • Extra B vitamins had a negative effect on piglet birth weight, but no effect on within-litter variation. • In the control group piglets had greater abdominal circumference and crown-rump length. • Extra B vitamins did not affect sow plasma concentration of homocysteine and back fat thickness. • There is no beneficial effect of supplementing B vitamins above requirement for gestating sows. The objective of this study was to test whether a high inclusion rate of dietary vitamin B 2 , B 6 , B 12 , and folic acid during the first 45 d of gestation could decrease within-litter variation in piglet birth weight and increase the average birth weight of the litter. Two hundred forty-one multiparous sows (Landrace x Yorkshire) were allotted to either a control or a B vitamin diet from mating to d 45 of gestation. The experimental unit was the sow or the litter. Sows in the control group were fed a standard gestation diet complying with Danish recommendations: 5.11, 3.07, 0.02, and 1.53 mg/kg for vitamin B 2 , B 6 , B 12 , and folic acid, respectively. Sows fed the B vitamin diet were fed the same standard gestation diet including an extra premix providing 232, 210, 1000, and 668 % extra vitamin B 2 , B 6 , B 12 , and folic acid, respectively. From d 46 until farrowing, all sows were fed the standard diet. The backfat thickness of sows was measured at farrowing and weaning in the previous cycle and at d 14, 45, and 112 of gestation. From a subsample of 10 second parity sows per treatment, blood samples were taken using jugular venipuncture into 10 mL EDTA tubes at weaning and d 14, 45, and 112 of gestation. The plasma was analyzed for the concentration of homocysteine. At farrowing, the number of live and stillborn piglets were recorded, and for a subsample of 71 (control) and 66 (B vitamin) sows, the weight, crown-rump length and abdominal circumference of individual piglets in the litters were measured. The plasma concentration of homocysteine at weaning and during gestation was unaffected by dietary treatments. For the overall treatments, there was no difference in live born (Control: 19.5; B vitamin: 19.9) and stillborn (Control: 1.5; B vitamin: 1.6) piglets between treatments. The average birth weight of live born (Control: 1,270 g; B vitamin: 1,245 g) and stillborn (Control: 992 g; B vitamin: 870 g) piglets and the within-litter variation in birth weight (Control: 294 g; B vitamin: 307 g) were unaffected by dietary treatment. The abdominal circumference (Control: 23.3 cm; B vitamin: 22.7 cm) and the crown-rump length (Control: 31.6 cm; B vitamin: 31.0 cm) were greater for piglets born to sows fed the control diet compared to sows fed the B vitamin diet (P < 0.05). In conclusion, there was no positive effect of supplementing surplus B vitamins above recommended inclusion rates to sows in early gestation on piglet birth weight. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of N , N -dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine β-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration. [ABSTRACT FROM AUTHOR]

Age-related decreases in executive function and an increase in arterial stiffness and plasma homocysteine levels are related to the risk of dementia. However, the association between executive function, arterial stiffness, and homocysteine levels remains unclear. This study aimed to investigate the relationship between executive function, arterial stiffness, and plasma homocysteine in 82 middle-aged and older women. The Stroop interference time, Brachial-ankle Pulse Wave Velocity (baPWV), and plasma homocysteine concentration were collected. The correlation analyses revealed that the Stroop interference time was significantly correlated with plasma homocysteine (r = 0.40, p < 0.001) and baPWV (r = 0.38, p = 0.001). In addition, plasma homocysteine levels were significantly correlated with baPWV (r = 0.48, p < 0.001). In the mediated analyses, the plasma homocysteine level directly (β = 0.24; p = 0.037) and indirectly (β = 0.12, 95% confidence interval [0.007, 0.238]) affected the Stroop interference time. These results suggest that higher plasma homocysteine levels are associated with a decline in executive function mediated by higher artery stiffness in middle-aged and older women. [ABSTRACT FROM AUTHOR]

Age-related decreases in executive function and an increase in arterial stiffness and plasma homocysteine levels are related to the risk of dementia. However, the association between executive function, arterial stiffness, and homocysteine levels remains unclear. This study aimed to investigate the relationship between executive function, arterial stiffness, and plasma homocysteine in 82 middle-aged and older women. The Stroop interference time, Brachial-ankle Pulse Wave Velocity (baPWV), and plasma homocysteine concentration were collected. The correlation analyses revealed that the Stroop interference time was significantly correlated with plasma homocysteine (r = 0.40, p < 0.001) and baPWV (r = 0.38, p = 0.001). In addition, plasma homocysteine levels were significantly correlated with baPWV (r = 0.48, p < 0.001). In the mediated analyses, the plasma homocysteine level directly (β = 0.24; p = 0.037) and indirectly (β = 0.12, 95% confidence interval [0.007, 0.238]) affected the Stroop interference time. These results suggest that higher plasma homocysteine levels are associated with a decline in executive function mediated by higher artery stiffness in middle-aged and older women.

Introduction: The present study was designed to assess the validity and efficacy of urinary markers (NAG, RBP, transferrin, α1-microglobulin, and plasma homocysteine) as early predictors of microalbuminuria in diabetic nephropathy in children and adolescents with type-1 diabetes, and its relation with haemoglobin glycated (HbA1c), serum lipid profile, and blood pressure. Material and methods: This study is a follow-up study to the 2002 study by Salem et al. The present study included 35 type 1 diabetes mellitus (T1DM) children and adolescents recruited from regular attendees of the specialised Diabetology Clinic, Children's hospital, Ain Shams University, with previously measured urinary N-acetyl-β-glucosaminidase (13) or homocysteine (11) or transferrin (28) or α1-microglobulin (27) or retinol binding protein (13) as an early predictor of diabetic nephropathy in T1DM. Thirty-five patients with type 1 diabetes mellitus were enrolled, and 24 patients were normoalbuminuric at baseline. The patients were tested for markers other than urinary microalbumin, to predict diabetic nephropathy and early renal impairment in children and adolescents with type 1 diabetes mellitus. Results: Regarding the metabolic control between the studied groups, we found that there is significant difference in HbA1c between the microalbuminuric patients and the normoalbuminuric patients. According to the number of positive markers of diabetic nephropathy, the only parameter that was higher in patients with more than one elevated marker was mean systolic blood pressure. Although mean diabetic blood pressure was higher, it was not statistically significant. Regarding to the predictability of urinary markers, urinary N-acetyl-β-glucosaminidase is the most predictable marker with high sensitivity and specificity. The least sensitivity noticed was urinary RBP and the least specificity noticed was urinary α1-microglobulin. Conclusions: Regarding the predictability of urinary markers, urinary NAG is the most predictable marker with both high sensitivity and specificity, with a sensitivity of 60%, specificity 75%, positive predictive value 60%, negative predictive value 75%, and a diagnostic accuracy of 0.58%. Urinary RBP is another marker with low sensitivity but high specificity. Urinary α1-microglobulin is a valid marker with high sensitivity but low specificity. Contrary to previous markers, plasma homocysteine has high specificity but low sensitivity. [ABSTRACT FROM AUTHOR]

Dementia is prevalent among elderly people, and projections show that the number of affected might triple over the next 50 years, because of a large increase in the oldest segment of the population. The objective of this study was to investigate the relationship between cognitive function and serum homocysteine level. This study was a cross-sectional study carried out in Mampang district, South Jakarta. A total of 94 elderly people was recruited for this study consisting of 44 females and 50 males. In this study serum homocysteine level was assessed by fluorescent polarization immunoassay and cognitive function with the mini mental state examination (MMSE). In elderly women MMSE scores for plasma homocysteine concentrations of 14.9 mmol/L were 24.00 ± 3.68, 23.80 ± 6.51, and 20.80 ± 9.00 respectively, with p=0.000. In elderly men the MMSE scores for plasma homocysteine concentrations of 14.9 mmol/L were respectively 27.66 ± 2.06, 26.33 ± 3.79 and 24.03 ± 5.52 with p=0.008. Homocysteine concentrations of >14.9 mmol/L were more commonly found in males (66%) than in females (22.70%). The results of a regression analysis indicated that the factors influencing cognitive function were level of education (p=0.001) and age (p=0.035), whereas gender and homocysteine concentration did not affect cognitive function (p=0.554 and p=0.714, respectively). Plasma homocysteine concentration was inversely related to cognitive function. The most important factors affecting cognitive function were level of education and age.

Plasma homocysteine (Hcy) levels are associated with elevated blood pressure. However, the causal association between Hcy levels and the risk of hypertension remains ambiguous. Taking the study design effect into consideration, this study aimed to investigate this issue through a cross-sectional and longitudinal analysis. Data were obtained from the Beijing Health Management Cohort study, which conducted routine health check-ups from 2012 to 2017. Multivariate logistic regression was used for the cross-sectional analysis, and a quadratic inference function approach was performed for the longitudinal analysis. A total of 30 376 subjects (mean age = 50.0 years) were included in the cross-sectional analysis, and a subgroup of 3913 subjects without hypertension at baseline was included in the longitudinal analysis. After adjusting for potential confounders, the risk of hypertension increased with Hcy levels in the cross-sectional analysis using the traditional definition of hypertension (OR = 1.262, 95% CI: 1.155-1.378, Q2 vs Q1; OR = 1.458, 95% CI: 1.335-1.593, Q3 vs Q1; OR = 1.520, 95% CI: 1.388-1.664, Q4 vs Q1) and the 2017 hypertension definition (OR = 1.159, 95% CI: 1.067-1.259, Q2 vs Q1; OR = 1.328, 95% CI: 1.221-1.445, Q3 vs Q1; OR = 1.328, 95% CI: 1.217-1.449, Q4 vs Q1). The longitudinal analysis showed that hypertension risk increased in the third quartile of Hcy (OR = 1.268, 95% CI: 1.030-1.560, Q3 vs Q1). Elevated total plasma Hcy may be used as a predictive biomarker for hypertension. Attention should be paid to gender-specific mechanisms when issuing precise precautions. [ABSTRACT FROM AUTHOR]

Background: Monotony resulting due to the wilderness, sparse population and isolation from society could adversely affect human physiology and cause mood alterations. Thus, observations need to be conducted in order to elucidate the possible role of circulating biomarkers in inducing altered mood and cognitive performance following prolonged exposure to high altitude (HA) with persistent monotonous environment.Objective: The present study aimed towards investigating the impact of monotonous environment in remote HA on mood and cognitive performance of human volunteers and its correlation with serum brain derived neurotrophic factor (BDNF) and plasma homocysteine level.Methods: The present study was conducted on male lowlander participants who had normal social life prior to induction in HA environment. Baseline data was acquired at altitude ≤240 m mean sea level (MSL). Thereafter, the participants were inducted to an altitude of 4500-4800 m MSL. After acclimatization to HA, the participants were assigned as acclimatized low landers (ALL). Longitudinal follow up was conducted after 8 months of high altitude induction on acclimatized low landers (8ALL). Further, to study the effect of monotony, the participants were randomly assigned into different group sizes during their further stay of 4 months in HA viz. ≤5 (12ALL ≤ 5) and ≥10 (12ALL ≥ 10). Mood and cognitive performance of the participants were assessed by standard self-administered questionnaires. Serum BDNF and plasma homocysteine were estimated and their correlation with mood and cognition were determined.Results: The findings showed significantly low serum BDNF in 12ALL ≤ 5 group when compared to baseline, 8ALL and 12AL ≥ 10 groups. Alleviated serum BDNF was associated with increased prevalence of mood alterations in HA with persistent monotonous environment. Participants of 12ALL ≥ 10 group showed significantly higher cognitive performance as compared to 12ALL ≤ 5 group which was associated with reduced plasma homocysteine level.Limitations: Total registered volunteers during baseline study were not available during the entire period of this study. The second limitation was exclusion of participants with medical history of severe head injuries, chronic diseases in family and extreme baseline serum profile. Third limitation of the study was to exclude the participants detected with MCI after 8 months of HA induction for negating the role of hypobaric hypoxia on mood and cognition.Conclusion: The study advocated that ALLs of 12ALL ≤ 5 group have increased prevalence of depressive trait and cognitive impairment which was correlated with reduced serum BDNF and augmented plasma homocysteine level as compared to participants of 12ALL ≥ 10 group having better social interaction with improved cognition and mood. The basic findings of the present study revealed that prolonged HA stay after physiological acclimatization should be regulated by proper social interaction involving normal group size to avoid detrimental effect of monotony and its significant impact on circulatory biomarkers. [ABSTRACT FROM AUTHOR]

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We examined whether soybean (SB) and soy protein isolate (SPI) can prevent the betaine-induced elevation of plasma cholesterol as well as maintain the betaine-induced reduction of plasma Hcy concentration. Rats were fed casein-, SB-, or SPI-based diet with or without betaine; SPI-based diet with betaine containing soybean fiber (SF) or soy lecithin (SL) or the combination of SF and SL. Plasma Hcy concentration was decreased by feeding betaine to rats fed the casein-, SB-, and SPI-based diets. Betaine-induced elevation of plasma cholesterol was decreased by feeding the SB-based diet compared with the casein-based diet, but was not decreased by feeding the SPI-based diet. In rats fed the SPI-based diet, the increased concentration of plasma cholesterol by betaine feeding was not prevented by independent addition of SL or SF, but was prevented by a combination of SL and SF, and was associated with increased fecal excretion of bile acids. [ABSTRACT FROM AUTHOR]

Background Methionine synthase deficiency is a rare inborn error of intracellular cobalamin metabolism caused by mutations in the MTR (5-methyltetrahydrofolatehomocysteine S-methyltransferase) gene, resulting in megaloblastic anemia and neurologic symptoms. Methods and Results We describe for the first time a homozygous MTR gene c.3518C > T (p.P1173L) mutation in a patient with severe megaloblastic anemia, developmental delay, and drug-resistant seizures associated with hyperhomocysteinemia and hypomethioninemia. Methionine synthase activity was only 9% of the reference value, and MTR protein expression was decreased in the fibroblasts of the patient. The clinical features of our patient are similar to previously published patients with the complementation type G disorder of methionine synthase deficiency with the exception of drug-resistant seizures. However, intramuscular injections of hydroxocobalamin (OHCbl) in conjunction with betaine and folic acid provided verified clinical and electrophysiological treatment response. Conclusion This study emphasizes the importance of early diagnosis of patients having neurologic symptoms due to methionine synthase deficiency where early treatment has significant effects on the clinical outcome of the patients. Elevated level of plasma homocysteine together with low methionine in plasma amino acid analysis should raise a suspicion of remethylation disorder. [ABSTRACT FROM AUTHOR]

Objectives: Hyperhomocysteinemia (Hhcy) is a known cardiovascular disease (CVD) risk factor. Observational studies had supported the role of lifestyle factors such as physical activity, diet and alcohol consumption in CVD prevention. Our study aimed to determine the relationship between Hhcy and lifestyle factors in general Chinese population.Methods: In this cross-sectional study, a total of 7135 adults (3320 men and 3815 women) aged 35 years or older were recruited from the rural Northeast China. Data on lifestyle factors, such as physical activities, sleep duration, current smoking and drinking status, dietary habits and familial factors were collected in interviews and laboratory examinations were performed by well-trained personnel.Results: Plasma total homocysteine (tHcy) level was higher in men than in women, and greater in the elderly than in other age groups. Subjects with Hhcy were more likely to be current smokers (men: OR 1.328, 95% CI 1.143-1.543, p<0.001; women: OR 1.465, 95% CI 1.214-1.767, p<0.001). Separately, men with Hhcy were more likely to have an education of primary school or below (OR 1.251, 95% CI 1.068-1.465, p=0.006) and less likely to eat more vegetables (OR 0.927, 95% CI 0.863-0.996, p=0.037) than the normal-tHcy participants. In women, participants with Hhcy were more likely to have longer sleeping time (>9h/d) (OR 1.677, 95% CI 1.292-2.177, p<0.001), low physical activity (OR 1.721, 95% CI 1.197-2.475, p=0.044) and increased diet score (OR 1.126, 95% CI 1.007-1.259, p=0.037) and less likely to be current drinkers (OR 0.488, 95% CI 0.297-0.802, p=0.005) than the normal-tHcy participants.Conclusion: Our study revealed that physical activity and current drinking status were not significantly associated with Hhcy in males, but inversely associated in females. In both genders, current smoking status and dietary habits were significantly associated with Hhcy. Our study supports existing recommendations for Chinese to maintain a physically active behaviors and healthy lifestyle habits. [ABSTRACT FROM AUTHOR]