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Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger–Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency. [ABSTRACT FROM AUTHOR]

Background and objectives: Prevalence estimates for classical homocystinuria (HCU) are variable and likely underestimated due to underdiagnosis. Claims data represent a strong but seldom used resource to analyze prevalence of HCU. The aim of this study was to estimate a prevalence range of HCU in the US utilizing a combination of diagnosis codes, total homocysteine levels, and clinical presentations indicative of HCU. Methods: This was a non-interventional retrospective cohort study, using Optum's de-identified Market Clarity Data, with a patient identification period from January 01, 2016, through September 30, 2021. An algorithm was developed to identify 2 cohorts of patients using broad and strict definitions of HCU. The index date was the date within the identification period on which the first criterion was met for the inclusion criteria. Baseline demographics, clinical characteristics, and complications were assessed and summarized using descriptive statistics. Crude and standardized prevalence estimates were calculated. Results: There were 3880 and 633 patients that met the relevant inclusion criteria for the broad and strict cohorts, respectively. The projected US prevalence of HCU was calculated to be 17,631 and 3466 based on the broad and strict definitions, respectively. The average annual standardized prevalence across 2016–2020 was 5.29 and 1.04 per 100,000 people for the broad and strict cohorts, respectively. Conclusions: Prevalence estimates of HCU vary depending on databases or datasets used and identification criteria. Many patients with clinical presentations suggesting a diagnosis of HCU did not have an associated diagnosis, potentially indicating underdiagnosis or underreporting. Future research should study alternative methods, such as the identification algorithm in our analysis, to better diagnose and understand the true prevalence of HCU.

Abstract Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P

Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin‐converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double‐blind, parallel‐controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine‐FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow‐up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8‐week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04‐24.78, P <.001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11‐16.47, P <.001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP‐lowering and occurrence of adverse events between the three groups. [ABSTRACT FROM AUTHOR]

The study was designed to evaluate the medical relevance of total homocysteine (tHcy), total antioxidant capacity (TAC), and malondialdehyde (MDA) before and after chemotherapy for women with breast cancer (BRCA). Blood samples were taken from Oncology Unit in Merjian Teaching hospital in Hilla city (Iraq). Sixty patients suffering from breast cancer (BRCA) were enrolled in this study, and twenty-one apparently healthy subjects were considered as a control group control. We found that significantly increased lipid peroxidation, measured as MDA, was demonstrated in the serum of BRCA patients who were not taken any medication was higher than in the control group (P<0.01) were (25±15) nmol/ml of MDA levels in BRCA patient and (14.5±7.9) nmol/ml of MDA levels in healthy controls. We found that treatment by chemotherapy resulted in a significant increase in MDA levels when compared with MDA levels in patients who were not taken any medication. The tHcy level in BRCA patients before and after treatment were changed. In addition, it is found that the mean serum TAC levels in BRCA patients were significantly less than in the control group. Moreover, a positive correlation was observed between the activity of chemotherapy and MDA levels in the patient and the same correlation between tHcy levels and TAC levels while a negative correlation was observed between TAC levels with MDA levels in the patient group. [ABSTRACT FROM AUTHOR]

The early diagnosis of and intervention in vitamin B12 deficiency in exclusively breastfed infants by mothers with low vitamin B12 is crucial in preventing possible irreversible neurologic damage, megaloblastic anemia, and failure to thrive. We assess the usefulness of the early detection of asymptomatic B12 deficiency related to acquired conditions and highlight the importance of monitoring serum vitamin B12 levels during pregnancy. We describe demographic, clinical, dietary, and biochemical data, including the evolution of a vitamin B12 deficiency's functional biomarkers. We enrolled 12 newborns (5 males) with an age range of 1–2 months old that were exclusively breastfed and asymptomatic. These cases were referred to our metabolic unit due to alterations in expanded newborn screening: high levels of methylmalonic acid and/or total homocysteine (tHcy). All mothers were under a vegetarian diet except three who had abnormal B12 absorption, and all presented low or borderline serum B12 level and high plasma levels of tHcy. Supplementation with oral vitB12 re-established the metabolic homeostasis of the mothers. In infants, therapy with an intramuscular injection of 1.0 mg hydroxocobalamin led to the rapid normalization of the metabolic pattern, and a healthy outcome was observed. Acquired B12 deficiency should be ruled out before proceeding in a differential diagnosis of cobalamin metabolism deficits, methylmalonic acidemia, and homocystinuria. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess whether raised baseline plasma tHcy concentrations increased the risks of major adverse cardiovascular events (MACE) and all-cause death outcomes in older patients with obstructive sleep apnea (OSA). Design: A multicenter, prospective, observational study. Setting: Beijing, Shandong Province, Gansu Province of China. Participants: A total of 1, 290 OSA patients aged 60 to 96 years from sleep centers of six hospitals in China consecutively recruited between January 2015 and October 2017. Measurements: Cox proportional models assessed the association between tHcy and the risk of new-onset all events among Chinese older OSA patients. Results: The final analysis (60.1% male; median age, 66 years) used data from 1, 100 subjects during a median follow-up of 42 months, a total of 105 (9.5%) patients developed MACE and 42 (3.8%) patients died. Multivariable Cox regression analysis showed higher adjusted hazard ratios (aHRs) of MACE, myocardial infarction (MI), hospitalization for unstable angina, and composite of all events with tHcy levels in the 4th quartile (HR=5.93, 95% CI: 2.79–12.59; HR=4.72, 95% CI:1.36–4.61; HR=4.26, 95% CI:1.62–5.71; HR=4.17, 95% CI:2.23–7.81) and the 3rd quartile (HR=3.79, 95% CI:1.76–8.20; HR=3.65, 95% CI:1.04–2.98; HR=2.75, 95% CI:1.08–3.76; HR=2.51, 95% CI:1.31–4.83) compared to reference tHcy levels in quartile 1, respectively, while the aHRs (95% CIs) of all-cause death showed significantly higher only in the highest tHcy level quartile than in the lowest quartile (HR=3.20, 95% CI=1.16–8.84, P=0.025) with no significant differences in risks of cardiovascular death and hospitalisation for heart failure among groups (P>0.05). Conclusions: tHcy, a marker of prognosis for older OSA patients, was significantly associated with the increased risk of MACE and all-cause death in this population independent of BMI, smoking status, and other potential risk factors, but not all clinical components events of MACE. New therapeutic approaches for older patients with OSA should mitigate tHcy-associated risks of MACE, and even all-cause death. [ABSTRACT FROM AUTHOR]

Background: Increased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China. Methods: A total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regressionmodels, two piecewise linear regressionmodels, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function. Results: This analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels andMMSE scores [beta coefficient (b) per standard deviation (SD) increase: -0.26, 95% confidence interval (CI) -0.35, -0.16, P < 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 µmol/L. The effect size [b (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was -0.93 (-1.24, -0.6) on the left side and -0.07 (-0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was <0.001). Moreover, subgroup analyses revealed that sex could influence the negative association between plasma tHcy levels and MMSE scores up to a specific threshold (P-value for interaction <0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels andMMSE scores in female patients with tHcy concentrations less than 26.9 µmol/L compared to male patients with tHcy concentrations less than 32.0 µmol/L. Conclusions: Plasma tHcy levels had a threshold effect on MMSE scores among hypertensive patients in China. Increased plasma tHcy levels were independently inversely associated with cognitive decline among hypertensive patients with tHcy concentrations <27.1 µmol/L. [ABSTRACT FROM AUTHOR]

• Four analytes are detected simultaneously in the DBSs by UPLC-MS/MS. • Only only 12 μL of whole blood are used for sample preparation. • The analysis intervals are only three minutes. Homocysteine, methionine, methylmalonic acid and 2-methylcitric acid are clinically relevant markers in the methionine, propionate, and cobalamin metabolism. This study aimed to develop and validate an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for simultaneously determining total homocysteine, methionine, methylmalonic acid and 2-methylcitric acid in dried blood spots. Three 3.2 mm discs were punched from each calibrator, quality control, and sample dried blood spot into a 96-well U-plate. Each sample was spiked with internal standards and extracted. Then the supernatant was transferred to another 96-well U-plate. After nitrogen drying, the dried residues were reconstituted, centrifuged, and the resulting supernatant was transferred to another 96-well plate for analysis. The method was performed using UPLC-MS/MS within 3 min, validated according to guidance documents, and applied to 72 samples from confirmed patients with methionine, propionate, and cobalamin metabolism disorders. The UPLC-MS/MS method provided satisfactory separation of the four analytes. The R2 values were ≥ 0.9937 for all analytes. The recoveries ranged from 94.17 to 114.29 %, and the coefficients of variation for intraday and interday precision were 0.19 % to 5.23 % and 1.02 % to 6.89 %, respectively. No significant carry-over was detected for the four analytes, and most of confirmed samples exhibited biomarker patterns characteristic of the relevant disorders. A simple and fast UPLC-MS/MS method was successfully developed, validated, and applied to clinical samples for the simultaneous determination of total homocysteine, methionine, methylmalonic acid, and 2-methylcitric acid in dried blood spots. [ABSTRACT FROM AUTHOR]

Abstract Background The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults. Methods A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG

Abstract Background Major depressive disorder is among main worldwide causes of disability. The low medication compliance rates in depressed patients as well as the high recurrence rate of the disease can bring up the nutrition-related factors as a potential preventive or treatment agent for depression. The aim of this study was to investigate the association between dietary patterns and depression via the intermediary role of the serum folate and vitamin B12, total homocysteine, tryptophan, and tryptophan/competing amino acids ratio. Methods This was an individually matched case-control study in which 110 patients with depression and 220 healthy individuals, who completed a semi-quantitative food frequency questionnaire were recruited. We selected the depressed patients from three districts in Tehran through non-probable convenience sampling from which healthy individuals were selected, as well. The samples selection and data collection were performed during October 2012 to June 2013. In addition, to measure the serum biomarkers 43 patients with depression and 43 healthy people were randomly selected from the study population. To diagnose depression the criteria of Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were utilized. Results The findings suggest that the healthy dietary pattern was significantly associated with a reduced odds of depression (OR: 0.75; 95% CI: 0.61–0.93) whereas the unhealthy dietary pattern increased it (OR: 1.382, CI: 1.116–1.71). The mediation analysis showed that the healthy dietary pattern was associated with a reduced risk of depression via increased serum levels of the folate and vitamin B12; however, the unhealthy dietary pattern was associated with increased risk of depression via decreased serum levels of folate and vitamin B12, based on tree adjusted logistic regression models. Conclusion Dietary patterns may be associated with depression by changing the serum levels of folate and vitamin B12. Further studies are required to confirm the mechanism.

Homocystineimia is an Inborn Errors of Metabolism (IEM) which can occur due to accumulation of homocysteine. Homocysteine is one of the sulfur-containing amino acid with thiol group that is formed by demethylation of methionine. Deficiency of enzymes involves in homocysteine metabolism can give rise to seven types of homocystinemia subject to total homocysteine level. Therefore reference ranges are needed to differentiate between normal and abnormal population as well as the type of homocystineimia depending on the enzymes defect in the pathway. Hence, homocysteine reference ranges in children for the Malaysian population were postulated. 3 mL of blood was collected from 86 normal individuals (52 boys and 34 girls) and then subsequently processed and analysed using High Performance Liquid Chromatogrphy -- Ion Exchange Chromatography (HPLC-IEC). The calculated mean total homocysteine for the population was 8.1 ± 3.89 µM (95% confidence interval, l 7.3-8.9 µM). Reference range was 2.5 -- 16.2 µM with lower and upper cut-off were 1.0 µM dan 21.0 µM, respectively. The newly developed reference range of total homocysteine for Malaysian children is able to reduce false negative cases in the laboratory. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prevalence estimates for classical homocystinuria (HCU) are variable and likely underestimated due to underdiagnosis. Claims data represent a strong but seldom used resource to analyze prevalence of HCU. The aim of this study was to estimate a prevalence range of HCU in the US utilizing a combination of diagnosis codes, total homocysteine levels, and clinical presentations indicative of HCU., Methods: This was a non-interventional retrospective cohort study, using Optum's de-identified Market Clarity Data, with a patient identification period from January 01, 2016, through September 30, 2021. An algorithm was developed to identify 2 cohorts of patients using broad and strict definitions of HCU. The index date was the date within the identification period on which the first criterion was met for the inclusion criteria. Baseline demographics, clinical characteristics, and complications were assessed and summarized using descriptive statistics. Crude and standardized prevalence estimates were calculated., Results: There were 3880 and 633 patients that met the relevant inclusion criteria for the broad and strict cohorts, respectively. The projected US prevalence of HCU was calculated to be 17,631 and 3466 based on the broad and strict definitions, respectively. The average annual standardized prevalence across 2016-2020 was 5.29 and 1.04 per 100,000 people for the broad and strict cohorts, respectively., Conclusions: Prevalence estimates of HCU vary depending on databases or datasets used and identification criteria. Many patients with clinical presentations suggesting a diagnosis of HCU did not have an associated diagnosis, potentially indicating underdiagnosis or underreporting. Future research should study alternative methods, such as the identification algorithm in our analysis, to better diagnose and understand the true prevalence of HCU., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mahim Jain reports financial support was provided by Travere Therapeutics Inc. Kamlesh M. Thakker reports financial support was provided by Travere Therapeutics Inc. Mehul Shah reports a relationship with Travere Therapeutics Inc. that includes: employment and equity or stocks. Agness Pelts Block reports a relationship with Travere Therapeutics Inc. that includes: employment and equity or stocks. Lionel Pinto reports a relationship with Travere Therapeutics Inc. that includes: employment and equity or stocks. Andrew Rava and Colette Ndiba-Markey are employees of Genesis Research Group, which receives consulting fees from Travere Therapeutics, Inc. for this study and other related studies. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. M.J. has received consultancy fees from Travere Therapeutics, Inc. M.S. is an employee and stock/options holder (vested and unvested) of Travere Therapeutics, Inc. K.M.T has a consulting contract with Travere Therapeutics, Inc. and does not have any equity interest in Travere Therapeutics, Inc. A.R. is an employee of Genesis Research Group, which receives consulting fees from Travere Therapeutics, Inc. for this study and other related studies. A.P.B. is an employee and stockholder of Travere Therapeutics Inc. C.N.M. is an employee of Genesis Research Group, which receives consulting fees from Travere Therapeutics, Inc. for this study and other related studies. L.P. is a former employee and stock/options holder (vested and unvested) of Travere Therapeutics, Inc., (© 2024 The Authors.)

Background: Homocystinuria is a rare autosomal recessive disease complicated by early and aggressive occlusive arterial disease. This may be related to the grossly increased homocysteine concentrations seen in this disease. More recently, milder hyperhomocysteinemia has been proposed as an independent risk factor for coronary artery disease. Cardiovascular disease (CVD) is among the diseases with multiple contributing factors, hence making it difficult to pinpoint a particular factor alone. The main factor that is of relevance to this study is homocysteine. Coronary artery disease is the narrowing or blockage of the arteries and vessels that supply oxygen and nutrients to the heart (1, 2). CVD is the major cause of morbidity and mortality worldwide. Obesity, HTA, Diabetes mellitus, hypercholesterolemia, and smoking have been recognized as major risk factors for CVD. Aim: Aim of this paper is to examine concentrations of Hcyt and lipid profiles in patients with CVD and positive personal history for CVD, comparing them with the control group composed of healthy individuals. Our study aimed to verify the role of Homocysteine as a new independent risk factor on the onset of early atherosclerosis and atheromatous processes in coronary arteries in patients with CVD. Materials and methods: The results obtained represent the average value earned once every three months in the 3 year period. 5ccm serum with a few heparin spots was sent to the Clinical Laboratory of the University Clinic of Skopje. Results: The results obtained from patients with CVD and control groups are presented in the following text, where a statistically significant difference was observed for p

Background: Major depressive disorder is among main worldwide causes of disability. The low medication compliance rates in depressed patients as well as the high recurrence rate of the disease can bring up the nutrition-related factors as a potential preventive or treatment agent for depression. The aim of this study was to investigate the association between dietary patterns and depression via the intermediary role of the serum folate and vitamin B12, total homocysteine, tryptophan, and tryptophan/competing amino acids ratio. Methods: This was an individually matched case-control study in which 110 patients with depression and 220 healthy individuals, who completed a semi-quantitative food frequency questionnaire were recruited. We selected the depressed patients from three districts in Tehran through non-probable convenience sampling from which healthy individuals were selected, as well. The samples selection and data collection were performed during October 2012 to June 2013. In addition, to measure the serum biomarkers 43 patients with depression and 43 healthy people were randomly selected from the study population. To diagnose depression the criteria of Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were utilized. Results: The findings suggest that the healthy dietary pattern was significantly associated with a reduced odds of depression (OR: 0.75; 95% CI: 0.61–0.93) whereas the unhealthy dietary pattern increased it (OR: 1.382, CI: 1.116–1.71). The mediation analysis showed that the healthy dietary pattern was associated with a reduced risk of depression via increased serum levels of the folate and vitamin B12; however, the unhealthy dietary pattern was associated with increased risk of depression via decreased serum levels of folate and vitamin B12, based on tree adjusted logistic regression models. Conclusion: Dietary patterns may be associated with depression by changing the serum levels of folate and vitamin B12. Further studies are required to confirm the mechanism. [ABSTRACT FROM AUTHOR]

Kuwait is a small Arabian Gulf country with a high rate of consanguinity and where a national newborn screening program was expanded in October 2014 to include a wide range of endocrine and metabolic disorders. A retrospective study conducted between January 2015 and December 2020 revealed a total of 304,086 newborns have been screened in Kuwait. Six newborns were diagnosed with classic homocystinuria with an incidence of 1:50,000, which is not as high as in Qatar but higher than the global incidence. Molecular testing for five of them has revealed three previously reported pathogenic variants in the CBS gene, c.969G>A, p.(Trp323Ter); c.982G>A, p.(Asp328Asn); and the Qatari founder variant c.1006C>T, p.(Arg336Cys). This is the first study to review the screening of newborns in Kuwait for classic homocystinuria, starting with the detection of elevated blood methionine and providing a follow-up strategy for positive results, including plasma total homocysteine and amino acid analyses. Further, we have demonstrated an increase in the specificity of the current newborn screening test for classic homocystinuria by including the methionine to phenylalanine ratio along with the elevated methionine blood levels in first-tier testing. Here, we provide evidence that the newborn screening in Kuwait has led to the early detection of classic homocystinuria cases and enabled the affected individuals to lead active and productive lives.

Background: As a methyl donor required in the folate-vitamin B-12 independent remethylation of total homocysteine (tHcy) to methionine, betaine is critical for fetal development. Pregnant South Asian women living in Canada had a higher reported prevalence of low vitamin B-12 status compared with Europeans; betaine concentrations in this population are unknown.Objectives: We aimed to compare serum betaine concentrations between South Asian and European pregnant women, and to determine the relation between betaine and tHcy concentrations in early pregnancy.Methods: A retrospective cohort study was conducted using biobanked serum samples of 723 apparently healthy pregnant women of South Asian (50%) and European ethnicity residing in British Columbia, Canada. Betaine, dimethylglycine (DMG), tHcy, and related metabolites were quantified in samples collected in the first (8-13 weeks of gestation) and second (14-20 weeks of gestation) trimesters. The relation between betaine and tHcy concentrations was assessed using a generalized regression model adjusted for weeks of gestation, ethnicity, prepregnancy BMI, maternal age, neonatal sex, parity, total vitamin B-12, folate, pyridoxal 5'-phosphate, and methionine concentrations.Results: Median serum concentrations of betaine and its metabolite DMG were higher in South Asian women in the first (19.8 [IQR: 16.3-25.0] and 1.55 [IQR: 1.30-1.96] $\mu {\rm mol/L} $, respectively) and second trimesters (16.1 [IQR: 12.9-19.8] and 1.42 [IQR: 1.14-1.81] $\mu {\rm mol/L} $, respectively) compared with European women (17.6 [IQR: 13.7-22.6] and 1.38 [IQR: 1.12-1.77] $\mu {\rm mol/L} $, respectively) and (12.9 [IQR: 10.6-16.7] and 1.19 [IQR: 0.97-1.52] $\mu {\rm mol/L} $, respectively; all P values < 0.0001). Betaine was inversely associated with tHcy concentration (β = -0.0208; 95% CI: -0.0341, -0.00742; P = 0.002). Additionally, total vitamin B-12 was associated with tHcy concentration (β = -0.0312; 95% CI: -0.0401, -0.0224), after adjusting for confounding factors.Conclusions: Pregnant South Asian women residing in Canada had higher betaine and DMG concentrations, compared with women of European ethnicity, while betaine and total vitamin B-12 predicted tHcy independent of ethnicity. Our results emphasize the role of betaine, as methyl donor, in the remethylation of tHcy in a folate-replete population. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the association between Glasgow Coma Scale (GCS) and total homocysteine (tHcy) levels and examine the possible effect modifiers in patients with hemorrhagic stroke. Methods: A total of 1,516 participants with hemorrhagic stroke and having the complete data on baseline GCS and tHcy measurements were included in the final analysis. Results: The mean (SD) of age, tHcy, and GCS levels were 61.5 (11.3) years, 17.0 (10.3) μmol/L, and 13.9 (2.2), respectively. Compared with participants with severe damage (GCS <9), those with mild damage (GCS ≥13) had significantly lower transformed tHcy levels (β = –2.46; 95% CI –4.80 to –0.12). Consistently, a significantly lower transformed tHcy levels were found in participants with mild damage (GCS ≥13; β = –1.37; 95% CI –2.66 to –0.08) compared with those with moderate to severe damage (GCS <13). In the stratified analysis, a stronger inverse association between GCS categories (≥13 vs. <13) and tHcy concentrations was observed in ever smokers (vs. never; p for interaction = 0.045), and in participants with systolic blood pressure (SBP) ≥160 mm Hg (vs. <160 mm Hg; p for interaction = 0.031), or total cholesterol (TC) ≥5.2 mmol/L (vs. <5.2 mmol/L; p for interaction = 0.025). Conclusion: There was an inverse association between GCS level and tHcy concentration among patients with hemorrhagic stroke, especially in ever smokers or in participants with higher SBP or TC levels. [ABSTRACT FROM AUTHOR]

Background: Identification of novel risk factors is needed to further lower stroke risk. Data concerning the association between plasma retinol concentrations and the risk of stroke are limited. Objectives: We aimed to evaluate the effect of plasma retinol on the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods: The study sample population was drawn from the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, including 620 cases with first stroke and 620 matched controls. In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The median treatment duration was 4.5 y. Results: There was a significant inverse association between plasma retinol and the risk of first stroke (per 10-μg/dL increment; OR: 0.92; 95% CI: 0.86, 0.97) and first ischemic stroke (OR: 0.92; 95% CI: 0.86, 0.98). When retinol was assessed as quartiles, significantly lower risks of first stroke (OR: 0.64; 95% CI: 0.46, 0.88) and first ischemic stroke (OR: 0.67; 95% CI: 0.46, 0.96) were found in participants in quartiles 2–4 compared with those in quartile 1. Furthermore, a stronger inverse association between plasma retinol and first stroke was observed in participants with baseline total homocysteine (<10 compared with ≥10 μmol/L; P-interaction = 0.049). However, plasma retinol had no significant effect on first hemorrhagic stroke (per 10-μg/dL increment; OR: 0.98; 95% CI: 0.79, 1.18). Conclusions: Our data showed a significant inverse association between plasma retinol and the risk of first stroke among Chinese hypertensive adults. [ABSTRACT FROM AUTHOR]

Small molecule-binding aptamers often suffer from high cross reactivity to structure analogues in biological samples, limiting their value for clinical diagnosis. Herein, we present a method to overcome this issue, by performing binding-inhibited organic reaction-based regioselective selection of aptamers against homocysteine (Hcy), which is a marker for diagnosing many disorders including stroke and Alzheimer's. This approach has led to isolation of a DNA aptamer that binds to the alkane thiol chain of Hcy with exceptional specificity against cysteine. It also binds with oxidized Hcy at weaker affinity. Using this new aptamer, we produced a reusable fluorescent optical fiber aptasensor for direct and validated detection of both free and total Hcy in nondeproteinized patient plasma in the diagnostic concentration range. The binding site-specific aptamer selection and optical-fiber-sensing strategy can expand the practical utility of aptamers in clinical diagnosis. [Display omitted] [ABSTRACT FROM AUTHOR]

We sought to examine the potential modifiers in the association between long-term low-dose folic acid supplementation and the reduction of serum total homocysteine (tHcy) among hypertensive patients, using data from the China Stroke Primary Prevention Trial (CSPPT). This analysis included 16 867 participants who had complete data on tHcy measurements at both the baseline and exit visit. After a median treatment period of 4·5 years, folic acid treatment significantly reduced the tHcy levels by 1·6 μmol/l (95 % CI 1·4, 1·8). More importantly, after adjustment for baseline tHcy and other important covariates, a greater degree of tHcy reduction was observed in certain subgroups: males, the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, higher baseline tHcy levels (≥12·5 (median) v. <12·5 μmol/l), lower folate levels (<8·0 (median) v. ≥8·0 ng/ml), estimated glomerular filtration rate (eGFR) <60 ml/min per 1·73 m2 (v. 60–<90 and ≥90 ml/min per 1·73 m2), ever smokers and concomitant use of diuretics (P for all interactions <0·05). The degree of tHcy reduction associated with long-term folic acid supplementation can be significantly affected by sex, MTHFR C677T genotypes, baseline folate, tHcy, eGFR levels and smoking status. [ABSTRACT FROM AUTHOR]

Summary Background & aims The debated vascular risk potential of total homocysteine (tHcy), due to failed clinical trials designed on B vitamin supplementation, raises many possible explanations like the higher risk potential of the deleterious, free form of homocysteine (fHcy) or, the unchecked confounding effects of B-vitamins in tHcy-based association studies. Additionally, the cardiovascular risk probability of altered status of the homocysteine precursor, methionine (tMet) could shed light on the causality of association between tHcy and cardiovascular diseases. Hence, we aimed to evaluate the risk associations of elevated plasma levels of tHcy, fHcy and low levels of tMet with premature, ischemic stroke. Methods We recruited 171 young, ischemic stroke patients (aged ≤45 years) and 249 age- and gender-matched healthy controls. Plasma levels of fHcy, tHcy, tMet and vitamin B6 were estimated using HPLC coupled with coulometric electrochemical detection. Plasma levels of vitamin B12 and folate were estimated by radioimmunoassay. Results Elevated fHcy (>2.9 μmol/L) was independently and strongly associated with the risk of premature, ischemic stroke (OR = 9.62, 95% CI = 3.51–26.40). On the contrary, association between premature ischemic stroke and elevated tHcy (>15.0 μmol/L) was found to attenuate when adjusted for vitamin B6 values (OR = 0.24, 95%, CI = 0.03–1.69). Interestingly, compromised B6-status (<59.2 nmol/l) was found to confer high risk of premature ischemic stroke (OR = 170.80, 95% CI = 58.22–501.06). We could not establish any significant correlation between fHcy and B-vitamin levels (P > 0.05). Low tMet (<13.86 μmol/L) was also not significantly associated with premature, ischemic stroke (OR = 2.53, 95% CI = 0.613–10.38). Conclusion Our results indicate significant but not-correlated, independent associations of fHcy and vitamin B6 with risk of premature, ischemic stroke. However, the causality of these associations need prospective and large scale validations. Further, our findings highlight the crucial confounding effects of B-vitamins on risk association between tHcy and premature ischemic stroke. [ABSTRACT FROM AUTHOR]

Clinical presentations of disorders of the nervous system manifest in young and middle-aged patients with congenital and acquired mitochondrial dysfunctions and cognitive disorders manifest in patients with mitochondrial diseases more often. Nowadays the effective methods of initial diagnosing of these conditions are neurological and neuropsychological examination of patients, using of biochemical markers of mitochondrial diseases: the indices of lactate, total homocysteine in plasma and liquor. Neuro-visual study (Magnetic resonance imaging of the brain, MR spectroscopy, tractography, diffusion-weighted magnetic resonance imaging of the brain, mitochondrial DNA typing) is actually used for the differential diagnosing of mitochondrial diseases with other disorders that are accompanied by demyelinating disorders.

Conflicting associations between total homocysteine (tHcy), body mass index (BMI) lean body mass, and fat mass in the general population have been reported. We investigated the hypothesis that elevated tHcy levels are associated with increased BMI, waist-to-hip ratio (WHR), and body fat mass percent. In Jordan, obesity and overweight are prevalent among reproductive women and hyperhomocysteinemia, along with obesity and overweight, are independent risk factors for cardiovascular diseases. The participants used in this cross-sectional study were 325 overweight Jordanian women aged between 18 and 49 years old. The main outcome measures were tHcy, BMI, WHR, fat mass, fat-free mass, and total body water. Serum tHcy was analyzed using a liquid chromatography tandem mass spectrophotometry (LC–MS/MS) complete kit. The body compositions were measured using a bioelectrical impedance analyzer. Study participants were stratified according to their tHcy level into two groups, ≤10 μ mol/L and >10 μ mol/L, and the difference between mean values of body compositions was evaluated. The tHcy was significantly and negatively correlated with age, fat-free mass, and total body water, and significantly and positively correlated with BMI, hip circumference, WHR, fat mass, and dry lean weight. The chi-square and the independent sample t-tests showed statistically significant ( P ≤ .05) differences between tHcy and BMI, WHR, fat and fat-free mass, and total body water percentages. In conclusion, BMI, WHR and body fat mass were found to be associated with elevated tHcy levels among overweight reproductive women, and they might be used as independent predictors of the tHcy level. [ABSTRACT FROM AUTHOR]

Background: The effect of folic acid supplementation on uric acid (UA) concentrations is still inconclusive. Objective: We aimed to test the efficacy of folic acid therapy in reducing serum UA in hypertensive patients. Design: A total of 15,364 hypertensive patients were randomly assigned to a double-blind daily treatment with a single tablet that contained 10 mg enalapril and 0.8 mg folic acid (n = 7685) or 10 mg enalapril alone (n = 7679). The main outcome was the change in serum UA, which was defined as UA at the exit visit minus that at baseline. Secondary outcomes were as follows: 1) controlled hyperuricemia (UA concentration <357 mmol/L after treatment) and 2) new-onset hyperuricemia in participants with normal UA concentrations (<357 mmol/L). Results: After a median of 4.4 y of treatment, the mean 6 SD UA concentration increased by 34.7 ± 72.5 μmol/L in the enalaprilalone group and by 30.7 ± 71.8 μmol/L in the enalapril-folic acid group, which resulted in a mean group difference of 24.0 μmol/L (95% CI: 26.5, 21.6 μmol/L; P = 0.001). Furthermore, compared with enalapril alone, enalapril-folic acid treatment showed an increase in controlled hyperuricemia (30.3% compared with 25.6%; OR: 1.31; 95% CI: 1.01, 1.70) and a decrease in new-onset hyperuricemia (15.0% compared with 16.3%; OR: 0.89; 95% CI: 0.79, 0.99). A greater beneficial effect was observed in subjects with hyperuricemia (P-interaction = 0.07) or higher concentrations of total homocysteine (tHcy) (P-interaction = 0.02) at baseline. Furthermore, there was a significant inverse relation (P < 0.001) between the reduction of tHcy and the change in UA concentrations. Conclusions: Enalapril-folic acid therapy, compared with enalapril alone, can significantly reduce the magnitude of the increase of UA concentrations in hypertensive adults. This trial was registered at clinicaltrials.gov as NCT00794885. [ABSTRACT FROM AUTHOR]