Plasma tHcy Concentrations Research Articles

The Associations of Habitual Intake of Sulfur Amino Acids, Proteins and Diet Quality with Plasma Sulfur Amino Acid Concentrations: The Maastricht Study

BackgroundPlasma sulfur amino acids (SAAs), i.e., methionine, total cysteine (tCys), total homocysteine (tHcy), cystathionine, total glutathione (tGSH), and taurine, are potential risk factors for obesity and cardiometabolic disorders. However, except for plasma tHcy, little is known about how dietary intake modifies plasma SAA concentrations. ObjectiveTo investigate whether the intake of SAAs and proteins or diet quality is associated with plasma SAAs. MethodsData from a cross-sectional subset of The Maastricht Study (n = 1145, 50.5% men, 61 interquartile range: [55, 66] y, 22.5% with prediabetes and 34.3% with type 2 diabetes) were investigated. Dietary intake was assessed using a validated food frequency questionnaire. The intake of SAAs (total, methionine, and cysteine) and proteins (total, animal, and plant) was estimated from the Dutch and Danish food composition tables. Diet quality was assessed using the Dutch Healthy Diet Index, the Mediterranean Diet Score, and the Dietary Approaches to Stop Hypertension score. Fasting plasma SAAs were measured by liquid chromatography (LC) tandem mass spectrometry (MS) (LC/MS-MS). Associations were investigated with multiple linear regressions with tertiles of dietary intake measures (main exposures) and z-standardized plasma SAAs (outcomes). ResultsIntake of total SAAs and total proteins was positively associated with plasma tCys and cystathionine. Associations were stronger in women and in those with normal body weight. Higher intake of cysteine and plant proteins was associated with lower plasma tHcy and higher cystathionine. Higher methionine intake was associated with lower plasma tGSH, whereas cysteine intake was positively associated with tGSH. Higher intake of methionine and animal proteins was associated with higher plasma taurine. Better diet quality was consistently related to lower plasma tHcy concentrations, but it was not associated with the other SAAs. ConclusionTargeted dietary modifications might be effective in modifying plasma concentrations of tCys, tHcy, and cystathionine, which have been associated with obesity and cardiometabolic disorders.

Daily Folic Acid and/or Vitamin B12 Supplementation Between 6 and 30 Months of Age and Cardiometabolic Risk Markers After 6–7 Years: A Follow-Up of a Randomized Controlled Trial

BackgroundDeficiencies of vitamin B12 and folate are associated with elevated concentrations of metabolic markers related to CVDs. ObjectivesWe investigated the effect of supplementation of vitamin B12 with or without folic acid for 6 mo in early childhood on cardiometabolic risk markers after 6–7 y. MethodsThis is a follow-up study of a 2 × 2 factorial, double-blind, randomized controlled trial of vitamin B12 and/or folic acid supplementation in 6–30-mo-old children. The supplement contained 1.8 μg of vitamin B12, 150 μg of folic acid, or both, constituting >1 AI or recommended daily allowances for a period of 6 mo. Enrolled children were contacted again after 6 y (September 2016–November 2017), and plasma concentrations of tHcy, leptin, high molecular weight adiponectin, and total adiponectin were measured (N = 791). ResultsAt baseline, 32% of children had a deficiency of either vitamin B12 (<200 pmol/L) or folate (<7.5 nmol/L). Combined supplementation of vitamin B12 and folic acid resulted in 1.19 μmol/L (95% CI: 0.09; 2.30 μmol/L) lower tHcy concentration 6 y later compared to placebo. We also found that vitamin B12 supplementation was associated with a lower leptin–adiponectin ratio in subgroups based on their nutritional status. ConclusionsSupplementation with vitamin B12 and folic acid in early childhood was associated with a decrease in plasma tHcy concentrations after 6 y. The results of our study provide some evidence of persistent beneficial metabolic effects of vitamin B12 and folic acid supplementation in impoverished populations.The original trial was registered at www.clinicaltrials.gov as NCT00717730, and the follow-up study at www.ctri.nic.in as CTRI/2016/11/007494.

Association of Homocysteine and Risks of Long-Term Cardiovascular Events and All-Cause Death among Older Patients with Obstructive Sleep Apnea: A Prospective Study.

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). A multicenter, prospective, observational study. Beijing, Shandong Province, Gansu Province of China. 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. Cox proportional models assessed the association between tHcy and the risk of new-onset all events among Chinese older OSA patients. 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). 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.

Threshold effect of plasma total homocysteine levels on cognitive function among hypertensive patients in China: A cross-sectional study

BackgroundIncreased 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.MethodsA 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 regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function.ResultsThis analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (β) per standard deviation (SD) increase: −0.26, 95% confidence interval (CI) −0.35, −0.16, P &amp;lt; 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 [β (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 &amp;lt;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 &amp;lt;0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels and MMSE 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.ConclusionsPlasma 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 &amp;lt;27.1 μmol/L.

Serum Total Homocysteine Level in Association with Folate and Vitamin B12 Status Among Algerian Prostate Cancer Patients

Background: Folate, vitamin B12 and homocysteine are essential for methyl group metabolism and thus also for DNA methylation and metabolic disorders may lead to carcinogenesis&nbsp;metabolic disorders, which may lead to carcinogenesis. In the present study, we proposed to evaluate the associations between folate and vitamin B12, with fasting plasma tHcy concentration in prostate cancer (PCa) patients. Methods: A case –control study was conducted with 40 newly patients with prostate cancer diagnosed with prostate cancer and 50 age matched healthy controls. Serum level of total homocysteine, folate and vitamin B12 were measured by enzyme conversion immunoassay and radioassay, respectively using the ARCHITECT system (both Abbott–Diagnostics Division). Results: The average rate of total PSA was 20.97 ng / ml (ranged between 8- 60 ng / ml). 53% of patients had a PSA≥20ng/ml. Histology confirmed that all patients accounted for prostatic adenocarcinoma with prognostic Gleason score that ranged between 7 and 8 . There are no significant differences between cases and controls about serum Hcy levels (adjusted OR&nbsp;=&nbsp;0.160% CI =&nbsp;0.832-1.031), folate levels (adjusted OR&nbsp;=&nbsp;0.428% CI &nbsp;=&nbsp;0.977-1.008) and vitamin B12 (adjusted OR&nbsp;=&nbsp;0.103% CI &nbsp;=&nbsp;0.992-1.001). Conclusion: In this study, the results show that homocysteine is not involved in prostate cancer. However, this study shows that the sporadic form is much more prevalent than familial one. The diagnosis is often made too late in advanced stage with a high PSA levels and biopsy showing high levels of Gleason

Association between Decreased Plasma Folate Levels and MTHFR C677T, and MTRR A66G Gene Polymorphisms as Determinants for Elevated Total Homocysteine Concentrations in Pregnant Women

Aims: The aims of this paper were to examine the association between gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G with levels of plasma folate and tHcy. Methods: Peripheral venous blood samples were obtained from 143 pregnant women, who had been fasted for more than 10 hours. Plasma tHcy and folate concentrations were measured in plasma specimens. The genotypes for polymorphisms were identified by the PCR-restriction fragment length polymorphism (RFLP). Results: Our results demonstrated that MTHFR 677T allele was the predictors of plasma folate levels in pregnant women. While MTHFR 677TT genotype and MTRR 66G allele were the predictors of plasma tHcy concentrations. Plasma folate levels were negatively correlated with tHcy concentrations (Pearson’s correlation coefficient r=-0.358, p=0.000012). With the increase of gestational weeks, the levels of plasma folate was first risen and then fall, whereas, there was a downtrend between gestational weeks and tHcy levels. Conclusion: Plasma folate status and total homocysteine level associated with MTHFR C677T and MTRR A66G gene polymorphisms in pregnant women. According to our study, the pregnant women of homozygous mutation of MTHFR 677TT and/or MTRR 66GG genes generally have lower levels of folate. Therefore, we recommend that pregnant women with 677TT and 66GG genotypes should supplement the appropriate dosage of folic acid based on their genotypes.

Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration.

Methionine demethylation during metabolism generates homocysteine (Hcy) and its remethylation requires folate and cobalamin. Elevated Hcy concentrations are associated with vascular-related complications of pregnancy, including increased vascular stiffness, predictive of clinical vascular disease. Maternal and fetal total Hcy (tHcy) concentrations are positively related, yet the influence of Hcy on fetoplacental vascular function in normal pregnancy has not been examined. We hypothesized that Hcy alters fetoplacental vascular characteristics with influences on fetal growth outcomes. We investigated (1) placental chorionic plate artery distensibility and neonatal blood pressure in relation to umbilical plasma tHcy; (2) relationships between cord venous (CV) and cord arterial (CA) plasma tHcy, folate, and cobalamin concentrations; and (3) tHcy associations with birth weight and anthropometric measurements of body size as indices of fetal growth in normal pregnancies with appropriate weight-for-gestational age newborns. Maternal plasma tHcy, folate, and cobalamin concentrations were consistent with published data. Placental chorionic plate artery distensibility index (β; measure of vessel stiffness) was inversely related to CA tHcy, yet neonatal blood pressure was not significantly affected. CV and CA tHcy concentrations were positively related and CV tHcy negatively related to CV cobalamin but not folate. CV tHcy concentration positively related to birth weight, corrected birth weight percentile, length, head circumference, and mid-arm circumference of newborns. CV cobalamin was inversely related to fetal growth indices but not to folate concentration. Our study demonstrates a potential relationship between fetal tHcy and placental artery distensibility, placing clinical relevance to cobalamin in influencing Hcy concentration and maintaining low vascular resistance to facilitate nutrient exchange favorable to fetal growth.

REL@X: SENSORY AND VIRTUAL IMMERSION TO REDUCE THE ANXIETY OF PATIENTS CONSULTING FOR THE FIRST TIME IN NICE MEMORY CENTER

Background: Neuropsychiatric symptoms (NS) such as agitation, physical aggression, shadowing and vocalizations are common in individuals with dementia compromising their quality of life and safety. NS have been associated with more time spent care-giving, high level of distress among caregivers and greater mortality among people with dementia. Although pharmacological interventions are frequently used to manage such symptoms, they can lead to adverse effects or even add to mortality. Some non-pharmacological approaches have been shown to be safe and to reduce NS. In the present investigation we describe a ran-domized clinical trial, using the Tailored Activity Program Outpatient version (TAP-O) in a Brazilian sample, to test the efficacy of an activity program to reduce NS in patients with dementia and their caregivers burden. TAP-O version was adapted from original TAP (home intervention). Methods: Patients with dementia and their caregivers were randomized to intervention (TAP-O method) or control group (psychoeducative method). TAP-O is a method involving eight sessions in an outpatient service conducted by occupational therapists who train caregivers in using meaningful activities at home, as part of their daily care routines. Outcome measures were obtained by Neuropsychiatric Inventory – Clinician Rating Scale (NPI-C) and Zarit Scale to measure NS in patients and caregiver burden, respectively. Results:A total of 21 dyads (individuals with dementia and their caregivers) were included. Most of patients were female (76.2%) with mean age of 78.7 (SD ¼ 5.8), and most of caregivers were family members (71.4%). Eleven patients were randomized to experimental intervention (TAP-O) and ten to control group. Patients from experimental group presented significant decrease in symptoms of hallucination (p¼0.008), anxiety (p¼0.03), and sleep disorder (p¼0.04) compared to the control group. Regarding the caregiver burden, measured by Zarit, it was possible to detect a statistically significant decrease in the experimental group (p¼0.003). Conclusions: These preliminary findings suggest that TAP-O may be clinically relevant, such as original TAP (home version) for the NS in patients with demen-tia and burden of their caregivers. Background: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and de-mentia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. A high prevalence of hyperhomocysteinemia and of cognitive impairment in kidney transplant recipients makes them a convenient population in which to evaluate this question. Methods: We evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients. The study was a longitudinal ancillary of the FAVORIT trial-a randomized, placebo controlled trial of high-dose B vitamins to reduce cardio-and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy. 584 subjects from 18 sites across North America were assessed annually for up to 5 years (mean 3.3 years) using a standardized neuropsychological test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations. Results: At baseline, cognitive impairment was prevalent with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, psychomotor speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes. Conclusions: High-dose B-vitamin supplementation provided modest benefit for cognitive function in our cohort of kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined. Background: Rel@x project aims at reducing the level of anxiety and to improve positive emotions in patients coming for the first time in consultation at Nice Memory Center. This is supposed to reduce errors due to stress in neuropsychological tests, and also allows to study emotion regulation capabilities of patients with and without cognitive impairment. To these aims, Rel@x project developed a multisensorial relaxing environment including virtual reality, music and odors. Methods: In the present study, we included 50 participants with (N¼25) and without (N¼25) mild cognitive impairment. Patients were immersed in a realistic universe then in a fantasy world on an island, and during this

B-Vitamin Therapy for Kidney Transplant Recipients Lowers Homocysteine and Improves Selective Cognitive Outcomes in the Randomized FAVORIT Ancillary Cognitive Trial.

Objectives: Elevated plasma total homocysteine (tHcy) is associated with increased risk of cardiovascular disease, stroke and dementia. Results of clinical trials using B-vitamins to reduce the cognitive risks attributed to tHcy have been inconsistent. The high prevalence of both hyperhomocysteinemia and cognitive impairment among kidney transplant recipients makes them an important population in which to evaluate the effect of lowering homocysteine on cognitive function. We therefore evaluated whether B-vitamin therapy to lower tHcy would prevent cognitive-decline in a cohort of stable kidney transplant recipients. The study was a longitudinal ancillary of the FAVORIT trial, a randomized, placebo-controlled multi-site trial of high-dose B vitamins to reduce cardiovascular and cerebrovascular events in clinically stable kidney transplant recipients with elevated tHcy. 584 participants from 18 sites across North America. The intervention consisted of a daily multivitamin containing high-doses of folate (5.0 mg), vitamin B12 (1.0 mg) and vitamin B6 (50 mg). The placebo consisted of a daily multi-vitamin containing no folate and recommended daily allowances of vitamins B12 and B6 (0 mg folate; 2.0 µg vitamin B12; 1.4 mg vitamin B6). Annual neuropsychological assessment for up to 5 years (mean 3.3 years) using a standardized test battery. Efficacy was analyzed on an intention-to-treat basis using end-of-trial data. Subgroup analyses included stratification for baseline plasma B-vitamin and tHcy concentrations. At baseline, cognitive impairment was common with 61% of participants falling more than one standard deviation below published norms for at least one cognitive test. Fewer than 1% of participants had insufficient plasma folate < 5 ng/ml or vitamin B12 < 148 pmol/L. However, 44.6% had plasma B6 concentrations < 30 nmol/L. At follow-up, processing speed and memory scores were modestly but significantly better in the B-vitamin supplement group than in controls (p≤0.05). There was no interaction between baseline tHcy, B-vitamin status and treatment on the cognitive outcomes. High-dose B-vitamin supplementation provided modest cognitive benefit for kidney transplant recipients with elevated baseline tHcy. Since nearly all participants were folate and vitamin B12 sufficient at baseline, the potential cognitive benefits of folate and B12 supplementation in individuals with poor B-vitamin status remains to be determined.

Dietary, anthropometric, and biochemical factors influencing plasma choline, carnitine, trimethylamine, and trimethylamine-N-oxide concentrations

The objective of the study was to evaluate the nutritional, anthropometric, and biochemical factors that influence choline, l-carnitine, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO) metabolism in elderly women. The volunteers’ diet was assessed using a food frequency questionnaire. Dietary patterns were estimated using a self-established score method. Body mass index (BMI), serum glucose, total, HDL, LDL cholesterol, triacylglycerol, homocysteine (tHcy), free choline (fchol), L-carnitine, TMA, and TMAO were assessed. Higher concentrations of l-carnitine, fchol, and TMAO were found in those women who had more western-style dietary patterns. Nor choline or betaine intake affected plasma fchol, TMA, or TMAO. BMI was positively correlated with fchol and TMA. tHcy was positively correlated with fchol, TMA, and TMAO, while fchol was also positively correlated with TMA and TMAO. Dietary patterns and plasma tHcy concentration influence fchol, TMA, and TMAO plasma concentration. Plasma TMA and fchol may be associated with BMI.

Methionine Metabolites in Patients With Sepsis.

Sepsis is characterized by microvascular dysfunction and thrombophilia. Several methionine metabolites may be relevant to this sepsis pathophysiology. S-adenosylmethionine (SAM) serves as the methyl donor for trans-methylation reactions. S-adenosylhomocysteine (SAH) is the by-product of these reactions and serves as the precursor to homocysteine. Relationships between plasma total homocysteine concentrations (tHcy) and vascular disease and thrombosis are firmly established. We hypothesized that SAM, SAH, and tHcy levels are elevated in patients with sepsis and associated with mortality. This was a combined case-control and prospective cohort study consisting of 109 patients with sepsis and 50 control participants without acute illness. The study was conducted in the medical and surgical intensive care units of the University of Rochester Medical Center. Methionine, SAM, SAH, and tHcy concentrations were compared in patients with sepsis versus control participants and in sepsis survivors versus nonsurvivors. Patients with sepsis had significantly higher plasma SAM and SAH concentrations than control participants (SAM: 164 [107-227] vs73 [59-87 nM], P < .001; SAH: 99 [60-165] vs 35 [28-45] nM, P < .001). In contrast, plasma tHcy concentrations were lower in sepsis patients compared to healthy control participants (4 [2-6]) vs 7 [5-9] μM; P = .04). In multivariable analysis, quartiles of SAM, SAH, and tHcy were independently associated with sepsis ( P = .006, P = .05, and P < .001, respectively). Sepsis nonsurvivors had significantly higher plasma SAM and SAH concentrations than survivors (SAM: 223 [125-260] vs 136 [96-187] nM; P = .01; SAH: 139 [81-197] vs 86 [55-130] nM, P = .006). Plasma tHcy levels were similar in survivors vs nonsurvivors. The associations between SAM or SAH and hospital mortality were no longer significant after adjusting for renal dysfunction. Methionine metabolite concentrations are abnormal in sepsis and linked with clinical outcomes. Further study is required to determine whether these abnormalities have pathophysiologic significance.

Plasma Homocysteine and Prognosis of Acute Ischemic Stroke: a Gender-Specific Analysis From CATIS Randomized Clinical Trial.

Elevated total homocysteine level (tHcy) has been hypothesized to be associated with morbidity and mortality of stroke; however, results regarding the association between plasma tHcy status and prognosis of acute ischemic stroke are inconsistent. Moreover, the gender effect on this association has yet to be explored. We thus prospectively investigated whether higher tHcy concentrations predicted poor stroke prognosis in Chinese adults. A total of 3309 acute ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Baseline tHcy concentrations were quantitatively determined via enzymatic cycling assay. The primary outcome was a combination of death and major disability at 3months (modified Rankin scale scores 3-6) after hospitalization. Multivariate logistic regression models with restricted cubic splines were used to determine the association between baseline plasma tHcy and the subsequent outcome. Higher plasma tHcy concentrations were associated with increased risks of the primary outcome in women but not in men (P interaction = 0.016). Adjusted odds ratios comparing two extreme tHcy quartiles were 1.83 (95% confidence interval 1.12-2.98; P trend = 0.02) in women and 0.87 (95% confidence interval 0.61-1.25; P trend = 0.37) in men. The significant association between baseline tHcy status and stroke prognosis in women, but not in men, persisted in further subgroup analyses, stratified by age, baseline systolic blood pressure, and other pre-specified factors. Elevated tHcy is positively associated with poor prognosis of acute ischemic stroke in women, but not in men. Further studies are needed to replicate our findings and to clarify the potential sex-specific mechanisms.

The Effect of Folic Acid Supplementation on Hyperhomocysteinemia and Pulmonary Function Parameters in Chronic Obstructive Pulmonary Disease: A Pilot Study.

Preliminary studies have established the elevated plasma total Homocysteine (tHcy) levels as a risk factor for Chronic Obstructive Pulmonary Disease (COPD). However, studies describing plasma tHcy levels and their relationship to folic acid supplementation and Forced Expiratory Volume in 1 Second (FEV1) status in COPD patients are still lacking. We investigated the role of hyperhomocysteinemia in COPD and then prospectively examined the relationship between plasma tHcy concentration and effect of folic acid supplementation on FEV1 status in COPD patients. This was a prospective case-control study with 50 clinically stable patients of COPD attending the chest clinic of the hospital and 30 healthy controls. The study was done at Maulana Azad Medical College and associated Lok Nayak Hospital, New Delhi, India, from August 2011 to February 2013. Plasma levels of Hcy were measured by Enzyme Linked Immuno-Sorbent Assay (ELISA) method. All the subjects were given folic acid therapy (5mg daily) for six weeks duration and were followed up. Repeat plasma Hcy and FEV1 were measured after six weeks. COPD patients had higher baseline plasma tHcy concentration than controls (Mean: 27.42±23.89μmol/L, versus 15.21±15.71μmol/L, p<0.001) and COPD was associated with higher tHcy concentrations also after adjusting for smoking, and age. The mean BMI of the patients was 21.36±4.26kg/m2. The mean Hcy values decreased from 27.42±23.89μmol/L to 15.2±15.71μmol/L (p-value=0.001) after six weeks of folic acid supplementation. However, no significant change was observed in FEV1 upon folic acid supplementation (FEV1=1.14±0.60 and 1.08±0.56 respectively; p-value=0.654). A significant correlation was observed between BMI and Hcy and also between plasma Hcy levels at the baseline and after six weeks of folic acid supplementation (r=0.283, p=0.04 and r=0.340, p=0.02, respectively) and (r=0.840, p=0.001). COPD patients seem to have a poor folic acid status and as a consequence high tHcy. Also, folic acid supplementation has shown decreased plasma tHcy concentrations, but not necessarily significant change in FEV1.

Hyperhomocysteinemia Is Associated with Vitamin B-12 Deficiency: A Cross-sectional Study in a Rural, Elderly Population of Shanxi China.

To report the association of lifestyle factors and plasma vitamin B-12 with hyperhomocysteinemia in a large sample of men and women living in a region of China where there is an increased risk of NTDs. Community-based, cross-sectional study of Lvliang City, Shanxi Province, China. Hyperhomocysteinemia is an independent risk factor for cardiovascular disease (CVD) and a sensitive marker of vitamin B-12 and folate deficiency. A total of 2355 (1044 men and 1311 women) participants born before 1 January 1958 (≥55 years of age) and living in Lvliang City for at least 2 months a year were included. The participants were assessed regarding demographic characteristics, height, weight, as well as having a physical examination and blood sampling for serum cholesterol, total homocysteine (tHcy), folate, and vitamin B12 levels. The median (25th-75th percentile) tHcy concentration was 21.5 (15.8-33.6) µmol/L in men and 18.0 (13.4-24.8) µmol/L in women. The overall prevalence of hyperhomocysteinemia (tHcy ≥15 µmol/L) was 72.6% (84.3% in men and 63.2% in women), inversely correlated with folate (r=-0.230, P=0.006) and vitamin B-12 (r=-0.540, P<0.001), and positively correlated with uric acid (r=0.054, P<0.001). Vitamin B-12 and folate deficiency, older age, and male gender were associated with elevated tHcy; with vitamin B-12 deficiency being the strongest. Plasma tHcy concentration and hyperhomocysteinemia were significantly higher in this population than in previously studied populations. Vitamin B-12 and folate supplementation, concomitant lifestyle changes such as smoking cessation, and lipid-lowering treatments may help to decrease plasma tHcy concentrations and reduce the CVD risk in this population.

Vitamin B12 Status in a Cohort of Canadian Pregnant Women and Newborn Infants

Low maternal concentrations of vitamin B12 (B12) adversely affect fetal development. In Canada, low serum B12 concentrations (&lt;148 pmol/L) are prevalent among women of reproductive age. We measured concentrations of serum B12 and its functional biomarkers, plasma total homocysteine (tHcy) and methylmalonic acid (MMA), in 368 pregnant women at 12‐16 wk gestation, at delivery and in cord blood. We also determined the effect of major fetal genetic variants of B12 metabolism on cord plasma concentrations of B12, tHcy and MMA. The prevalence of low serum B12 concentrations at recruitment and delivery was 17% and 37%, respectively. Elevated plasma MMA concentrations (&gt;270 nmol/L) were only observed in 2% and 5% of women at recruitment and delivery, respectively, and no women had plasma tHcy concentrations &gt;13 μmol/L. During pregnancy, mean serum B12 concentrations decreased by 23%, while plasma tHcy and MMA increased by 20% and 24%, respectively (p&lt;0.0001). Mean cord blood concentrations of B12, tHcy and MMA were 1.9, 0.8 and 2.3 times maternal concentrations at delivery (p&lt;0.0001). Cord plasma MMA concentrations were significantly altered by the MTR rs1805087, MUT rs1141321 and MMAA rs2270655 genotypes (p&lt;0.04), while cord serum B12 and plasma tHcy concentrations were altered by the TCN1 rs34324219 genotype (p=0.04). Our data suggest that although “suboptimal” serum B12 levels are prevalent in Canadian pregnant women, they are unlikely functionally significant as evidenced by MMA and tHcy status. Fetal genetic variants appear to influence cord blood concentrations of B12, MMA and tHcy. Funded by CIHR MOP#106446

Impact of physical activity and cardiovascular fitness on total homocysteine concentrations in European adolescents: The HELENA study.

We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8 ± 1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.05) with CVF in females (measured both by stages: r=-0.118 and by VO2max: r=-0.102) and positively with body mass index (r=0.100). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.05). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.

Plasma Total Homocysteine Level in Association With Folate, Pyridoxine, and Cobalamin Status Among Iranian Primary Breast Cancer Patients

Recently the elevated plasma total homocysteine (tHcy) concentration has been concerned as the secondary feature of tumoral proliferation and enhances the likelihood of thrombogenesis in cancer patients. The objective of this study was to determine the associations between folate, cobalamin, and pyridoxine with fasting plasma tHcy concentration in breast cancer (BC) patients. The intake levels of nutrients were assessed using a validated food frequency questionnaire in 141 newly diagnosed BC patients. The plasma tHcy and pyridoxal-5-phosphate were measured using high performance liquid chromatography with fluorescence detector. Plasma tHcy levels were observed to be significantly higher among BC participants with Stage III where the plasma concentrations of folate was also comparatively less (P < 0.05) than other stages. Dietary pyridoxine was even being consumed less at this stage (P < 0.05). The plasma, dietary, and residual variables of folate were inversely correlated with plasma tHcy concentration (P < 0.05). Dietary cobalamin was also associated negatively with tHcy (P < 0.05). The odds ratio of comparing the highest tertile of plasma cobalamin (>394 pmol/l) and folate (>11.4 ng/ml) vs. the lowest categories were associated with reduced odds of high tHcy occurrence with 0.20 (95% confidence interval: 0.04–0.98) and 0.14 (95% confidence interval: 0.03–0.64), respectively. In conclusion, nutrition-related methyl-group insufficiency could lead to imbalance in tHcy metabolism, as a possible cancer marker.

Folic acid supplementation on homocysteine levels in children taking antiepileptic drugs: A randomized controlled trial.

Objectives:To assess the level of homocysteine (tHcy) in children taking AEDs and to study whether daily oral supplementation of folic acid for 1 month will reduce the tHcy level.Materials and Methods:This was a double-blinded, randomized control trial conducted in Institute of Maternal and Child Health, Kozhikode, India. Totally 60 children were recruited and of them, 48 were enrolled. Of these children, 32 were assigned to the experimental group and 16 to the control group. Baseline data collection and tHcy estimation were done. One mg folic acid tablets were given to the experimental group and placebo tablets to the control group for 30 days. tHcy levels were re-estimated after 1 month follow-up. Statistical significance was tested by χ2 test, and paired and unpaired t-tests, as appropriate. Correlation was tested by Pearson correlation test and P value less than 0.05 was taken as the cut-off for statistical significance.Results:Baseline plasma tHcy concentrations in both groups were comparable [11.90 (6.3) and 13.02 (2.4) μmol/l, respectively]. During the follow-up period, no increase in seizure episodes or no serious adverse reactions were noticed in either group. The reduction of tHcy in the experimental group was 1.92 μmol/l (P = 0.04) and in the control group, there was an increase of 1.05 μmol/l (P = 0.16).Conclusions:In children on AED treatment, folic acid supplementation may reduce tHcy level and thus reduce CVD risk.

Methylenetetrahydrofolate reductase 677 genotype-specific reference values for plasma homocysteine and serum folate concentrations in korean population aged 45 to 74 years: the Namwon study.

The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (µM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea.

Effectiveness of Apricots (&amp;lt;i&amp;gt;Prunus armeniaca&amp;lt;/i&amp;gt;), Pomegranate (&amp;lt;i&amp;gt;Punica granatum&amp;lt;/i&amp;gt;) Juice and Lactic Acid Fermented Sobya on Plasma Levels of Lipid Profile Parameters and Total Homocysteine among Egyptian Adults

Objectives: The aim of this study was to investigate the effectiveness of dietary intervention with apricots, pomegranate juice or lactic acid fermented sobya on improving the plasma levels of lipid profile parameters and total plasma homocysteine (tHcy) among healthy adults. Design of the study: Thirty-five men and women (28.9 ± 3.0 years) with mean body mass index of 23.5 ± 1.2 kg/m2 were randomly assigned to a dietary intervention study. During the pre-feeding study records of 24-hour food intake, anthropometric measurements and blood sampling were collected for biochemical investigations. Thereafter the volunteers were divided into five groups: a control group (C); the other four groups received daily one of the following supplements: 200 g of deep yellow apricots (Prunus armeniaca) (AF); 250 g pomegranate (Punica granatum) juice (PJ); mixture of 100 g (PJ) and 150 g of fermented sobya (FS), (PJ-FS) or 165 g (FS). After completing the three-week dietary intervention, blood samples were collected and blood indices were again evaluated. Biochemical analysis of total lipids (TL), total glycerides (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) and tHcy were completed. The low density lipoprotein-cholesterol level and three indices of risk factors were calculated using the appropriate equations. Results: Three-week dietary intervention improved the levels of lipid profile parameters TG, TC, HDL-C and LDL-C as compared to the respective baseline levels and the response of the control group that did not receive any supplement. Consuming (PJ-FS) had a synergistic beneficially added value on some of the above mentioned lipid profile parameters. The mean plasma tHcy concentrations; a marker for occlusive vascular disease was reduced significantly following the three week consumption of (PJ) or (FS), compared with the respective pre-feeding levels. Conclusion: Pomegranate juice (PJ) or lactic acid fermented sobya (FS) or mixture of both are potential natural agents in lowering the plasma levels of lipid profile parameters and tHcy among apparently healthy young women and men, without dyslipidemic symptoms.