Higher Homocysteine Concentrations Research Articles

Activation of arginase II by asymmetric dimethylarginine and homocysteine in hypertensive rats induced by hypoxia: a new model of nitric oxide synthesis regulation in hypertensive processes?

In recent years, the increase in blood pressure at high altitudes has become an interesting topic among high-altitude researchers. In our animal studies using Wistar rats, we observed the existence of two rat populations that exhibit differential physiological responses during hypoxic exposure. These rats were classified as hypoxia-induced hypertensive rats and nonhypertensive rats. A decrease in nitric oxide levels was reported in different hypertension models associated with increased concentrations of asymmetric dimethylarginine (ADMA) and homocysteine, and we recently described an increase in arginase type II expression under hypoxia. ADMA and homocysteine decrease nitric oxide (NO) bioavailability; however, whether ADMA and homocysteine have a regulatory effect on arginase activity and therefore regulate another NO synthesis pathway is unknown. Therefore, the aim of this study was to measure basal ADMA and homocysteine levels in hypoxia-induced hypertensive rats and evaluate their effect on arginase II activity. Our results indicate that hypoxia-induced hypertensive rats presented lower nitric oxide concentrations than nonhypertensive rats, associated with higher concentrations of homocysteine and ADMA. Hypoxia-induced hypertensive rats also presented lower dimethylarginine dimethylaminohydrolase-2 and cystathionine β-synthase levels, which could explain the high ADMA and homocysteine levels. In addition, we observed that both homocysteine and ADMA had a significant effect on arginase II activation in the hypertensive rats. Therefore, we suggest that ADMA and homocysteine have dual regulatory effects on NO synthesis. The former has an inhibitory effect on eNOS, and the latter has a secondary activating effect on arginase II. We propose that arginase II is activated by AMDA and homocysteine in hypoxia-induced hypertensive rats.

Evaluation of serum homocysteine in young patients presenting with myocardial infarction: a study from rural Maharashtra

Background: It has been shown that elevated serum homocysteine levels are associated with an increased risk of ischemic heart disease (IHD) and stroke. Also, higher homocysteine concentrations in IHD or stroke patients than in controls have been reported. Some prospective and case-control studies with inconsistent results, some with highly significant results and others with no association have been observed. Objective of the study was to evaluate the serum homocysteine level in young myocardial infarction patients of rural hospital.Methods: The present hospital based cross sectional observational study was carried out in Department of Medicine, MIMER Medical College and Hospital, Talegaon Dabhade, Pune. The study population included 45 young patients having acute myocardial Infarction coming to our hospital. The data thus collected was entered in MS excel sheet and analysed by using SPSS 24.0 IBM USA.Results: Mean age of the study cohort was 36.7 years with 48.9% cases in between the age of 31-40 years and 33.3% were in the age range of 41-45 years. Male predominance was seen in the study cases with 68.9% males and 31.1% females. Prevalence of hyperhmocysteinemia was observed as 64.4% in present study. Mortality rate in our study was 6.67%. Serum homocysteine and all lipid parameters were in positive correlation except High-density lipoprotein which has negative correlation. Homocysteine levels were correlating significantly with level of atherosclerosis as measured by Gensini score.Conclusions: Coronary heart disease is related to high serum homocysteine concentration. Serum homocysteine levels also correlates well with the severity of MI.

Characteristics of clinical and anamnestic data and of condition of primary hemostasis in chronic diseases of liver in children

Aim. To perform a comparative analysis of clinical and anamnestic data and of the condition of primary hemostasis in chronic liver diseases in children and to identify additional informative diagnostic criteria that reflect severity of the course of autoimmune hepatitis (AIH) and chronic viral hepatitis C (CVHC) in children.
 Materials and Methods. 91 Patients from 3 to 7 years old were examined, of them: 60 children with AIH and 31 children with CVHC. The control group included 15 children of I and II health groups. In all the patients the clinic-anamnestic data and the condition of the primary hemostasis were evaluated. Concentrations of endothelin-1 and homocysteine, activity of Willebrand factor, amount of platelets and their aggregation activity were determined.
 Results. AIH is characterized by a more aggressive course as compared to CVHC manifested by clinical signs of a severe liver damage, significant biochemical changes and a high rate of fibrosis within the first two years. In all the children there were found disorders in the primary hemostasis interrelated with the main clinical and laboratory syndromes reflecting the severity of the liver damage. AIH is characterized by a higher concentration of homocysteine (р=0.007) and of the activity of Willebrand factor (р=0.037) in comparison with CVHC.
 Conclusions. Signs of a severe liver damage are not characteristic of children with CVHC in the first 10 years of the disease, however, disorders of the primary hemostasis are present characterized by hyperaggregation of platelets and by endothelial dysfunction. AIH in children is characterized by aggressive course and more pronounced deviations of the primary hemostasis in comparison with CVHC. In AIH and CVHC, the pathology of the primary hemostasis is closely related to some clinical-laboratory symptoms that reflect severity of the disease.

The importance of homocysteine in the development of cardiovascular complications in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) not only leads to disability due to joint changes, but also significantly shortens the life expectancy of patients, mainly due to more frequent occurrence of heart attacks and strokes. Accelerated atherosclerosis in these patients is caused, among other factors, by high homocysteine (HCY) concentration in blood. Numerous studies have shown that treatment with vitamin B significantly reduces the concentration of HCY in blood, but does not reduce the risk of heart diseases. Recent studies have shown, however, that folic acid (FA) administration reduces the risk of stroke by 10–20%. Due to the fact that in patients with RA strokes are more frequent than in the general population and hyperhomocysteinemia (HHCY) is often found, determination of HCY concentration in blood is advisable, and in persons with HHCY it is recommended to use FA in primary and secondary stroke prevention.

Vitamin D Provides Benefit Based on the Proinflammatory Effects of Homocysteine in Elderly Patients With Type 2 Diabetes Mellitus

PurposeIt is unclear whether vitamin D provides any benefit against the pro-inflammatory effects of homocysteine in elderly patients with type 2 diabetes mellitus (T2DM). MethodsWe compared lymphocyte counts for CD3, CD19, CD4, and CD8 subsets between elderly (age ≥65 years) T2DM patients (n = 5098) and nondiabetes control subjects (n = 20,590) based on the serum concentrations of homocysteine and total vitamin D (calcidiol + calcifediol [total vitamin D, TVD]; <20, 20-30, and >30 ng/mL). FindingsSignificant variation in CD19 (P = 0.019), CD4 (P = 0.015), and CD8 (P < 0.001) were associated with serum TVD in T2DM patients with homocysteine ≤15 μmol/L, whereas CD3 (P = 0.003) and CD8 (P = 0.019) varied in control subjects with homocysteine ≤15 μmol/L. In T2DM patients with high homocysteine (>15 μmol/L) levels, significant variation based on serum TVD occurred in CD19 only (P = 0.024), whereas CD3 (P = 0.016) and CD4 (P = 0.001) varied in control subjects with high homocysteine concentrations. ImplicationsSerum TVD influences variation in CD3, CD19, CD4, and CD8 lymphocyte subsets based on the serum homocysteine concentration in elderly T2DM patients and nondiabetic individuals with moderate to high homocysteine concentrations. The effect of TVD is partially attenuated in individuals with high homocysteine concentrations, with greater attenuation occurring in patients with T2DM. Differences in the variation of lymphocyte subsets between nondiabetes subjects with moderate homocysteine concentrations and those with high homocysteine concentrations constitute a shift from CD8-positive cells to CD4-positive cells, suggesting a change in TH1/TH2 balance based on TVD and homocysteine concentrations that is absent in diabetes cases with high homocysteine concentrations.

Obstructive sleep apnea syndrome: functional state of vascular endothelium and features of brain hemodynamics

The aim of the study is to identify the relationships between the functional state of vascular endothelium and regional cerebral blood flow in people of working age with moderate to severe obstructive sleep apnea syndrome. A transverse prospective observational study was conducted. It included 24 patients. Among them were 16 patients of working age with moderate to severe obstructive sleep apnea syndrome who were included in the main study group and 8 patients without sleep disorders in the control group according to polysomnography. The levels of biochemical markers of endothelial dysfunction, the indicators of endothelium-dependent vasodilation of the brachial artery were determined. Single-photon emission computed tomography of the brain was performed using 99mTc-hexamethylpropyleneaminoxime. In the patients of working age with moderate to severe obstructive sleep apnea syndrome, significantly lower average group values of the serum nitric oxide level of 11.7 (6.25‒18.30) μmol/l were detected versus 34.4 (25.33‒41.70) μmol/l in the control group, p &lt; 0.01), as well as higher homocysteine concentrations of 19.4 (15.13‒23.76) μmol/l versus 11.6 (6.40‒ 14.71) μmol/l in the control group, p &lt; 0.05, sP-selectin 176 (142.0‒189.0) ng/ml versus 122 (113.3‒168.5) ng/ml in the control group, p &lt; 0.05, and sE β-selectin 78 (69.0‒121.0) ng/ml versus 52 (43.1‒73.3) ng/ml in the control group, p &lt; 0.05. The data on the correlation of the level of neurohumoral markers of endothelial dysfunction of sP-selectin (p &lt; 0.01) and sE-selectin (p &lt; 0.05) with the degree of impaired regional cerebral blood flow were obtained. A direct relationship was found between the markers of endothelium-dependent vasodilation and regional cerebral blood flow in the frontal segments (p &lt; 0.05), the temporal segment on the right (p &lt; 0.05).

Long-term effects of folic acid and vitamin-B12 supplementation on fracture risk and cardiovascular disease: Extended follow-up of the B-PROOF trial

In the initial B-proof, we found inconsistent results of B vitamin supplementation. However, the debate regarding the effects of B vitamins on age-related diseases continues. Therefore, our aim was to investigate the long-term effects (5-7 years follow-up) of an intervention with folic acid and vitamin-B12 supplementation on fracture and cardiovascular disease risk. Extended follow-up of the B-PROOF trial, a multi-center, double-blind randomized placebo-controlled trial designed to assess the effect of 2-3 years daily supplementation with folic acid (400μg) and vitamin-B12 (500μg) versus placebo (n=2,919). Primary outcome was verified self-reported fracture incidence and secondary outcomes were self-reported cardiovascular endpoints, which were collected through a follow-up questionnaires Proportional hazard analyses was used for the effect of the intervention on risk of fracture(s) and logistic regression for the effect of the intervention on risk of cardiovascular disease. A total of 1,298 individuals (44.5%) participated in the second follow-up round with median of 54 months [51-58], (n=662 and n=636, treatment versus placebo group). Median age at baseline was 71.0 years [68.0-76.0] for both groups. No effect was observed of the intervention on osteoporotic fracture or any fracture risk after a follow-up (HR: 0.99, 95% CI: 0.62-1.59 and HR: 0.77; 95% CI: 0.50-1.19, respectively), nor on cardiovascular or cerebrovascular disease risk (OR: 1.05; 95%CI: 0.80-1.44 and OR: 0.85; 95%CI: 0.50-1.45, respectively). Potential interaction by baseline homocysteine concentration was observed for osteoporotic- and any fracture (p=0.10 and 0.06 respectively), which indicated a significantly lower risk of any fracture in the treatment group with higher total homocysteine concentrations (>15.1μmol/l). No age-dependent effects were present. This study supports and extends previous null-findings of the B-PROOF trial and shows that supplementation of folic acid and vitamin-B12 has no effect on fracture risk, nor on cardiovascular disease in older individuals over a longer follow-up period. However, B-vitamin supplementation may be beneficial in reducing fractures in individuals with high total homocysteine concentrations, a finding which needs to be replicated.

The combination of nutraceuticals and functional feeds as additives modulates gut microbiota and blood markers associated with immune response and health in weanling piglets.

This study aimed to evaluate the effects of a combination of feed additives with complementary functional properties on the intestinal microbiota, homocysteine, and vitamins E and B status as well as systemic immune response of weanling piglets. At weaning, 32 litters were assigned to one of the following dietary treatments (DT): 1) conventional diet (CTRL); 2) CTRL diet supplemented with antibiotics (ATB); 3) a cocktail of feed additives containing cranberry extract, encapsulated carvacrol, yeast-derived products, and extra vitamins A, D, E, and B complex (CKTL); or 4) CKTL diet with bovine colostrum in replacement of plasma proteins (CKTL + COL). Within each litter, the piglets with lowest and highest birth weights (LBW and HBW, respectively) and two piglets of medium birth weight (MBW) were identified. The MBW piglets were euthanized at 42 d of age in order to characterize the ileal and colonic microbiota. Blood samples were also collected at weaning and at 42 d of age from LBW and HBW piglets to measure insulin-like growth factor-1 (IGF-1), cysteine, homocysteine, and vitamins E, B6, and B12, and to characterize the leukocyte populations. At 42 d of age, cytokine production by stimulated peripheral blood mononuclear cells was also measured. In a second experiment, piglets were reared under commercial conditions to evaluate the effects of the DT on the growth performance. At the indicator species analysis, the highest indicator value (IV) for Succinivibrio dextrinosolvens was found in the CKTL group, whereas the highest IV for Lactobacillus reuteri and Faecalibacterium prausnitzii was evidenced in the CKTL + COL group (P < 0.05). Compared with the other DT, CTRL piglets had higher concentrations of homocysteine, whereas the CKTL and CKTL + COL supplementations increased the concentrations of vitamins E and B12 (P < 0.05). DT had no effect on IGF-1 concentration and on blood leukocytes populations; however, compared with HBW piglets, LBW animals had lower values of IGF-1, whereas the percentages of γδ T lymphocytes and T helper were decreased and increased, respectively (P < 0.05). CKTL + COL also improved the growth performance of piglets reared under commercial conditions (P < 0.05). This study highlights the impact of birth weight on piglet systemic immune defenses and the potential of weaning diet supplemented with feed additives and bovine colostrum to modulate the homocysteine metabolism and the intestinal microbiota.

3'-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.

As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3’-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426 C>T, TCN2 rs10418 C>T, SLC19A1 rs1051296 G>T, and SLC19A2 rs16862199 C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533–16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480–22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478–7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094–4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.

Plasma Homocysteine in Patients with Coronary and Carotid Artery Disease: A Case Control Study.

Homocystein (Hcy) is an amino acid and elevated plasma cause endothelial damage, followed with inflammation in the blood vessels and its progression in atherosclerosis. We aimed to evaluate the correlation between cardiovascular disease and serum homocysteine levels.. We performed a case control analysis of 212 patients, either for cardiovascular risk stratification or for invasive diagnostics and treatment of cardiovascular ischemic disease (CAD). Patients were divided into 4 groups: Group 1. Patients with low risk for CAD, with no symptoms of CAD and total of 10 years risk <10%. Group 2. High-risk patients with no symptoms of CAD, but 10 years total CAD risk of >20%. Group 3. Patients with symptomatic CAD, where angiography was performed and >50% occlusion of at least one coronary vessel was found. Group 4. Patients with carotid artery disease and documented CAD. Group 1 consists of 56 subjects, of whom 33 (60%) males and 22 (40%) females. Their mean age was 52.18±8.07 years and their average CAD risk was 5. Group 2 included 60 patients, with average CAD risk of 23.73. There was a statistically significant difference between plasma homocysteine levels between the control and high CAD risk group, as well as between those with CAD and both CAD and CARD (p=0.001). In the high-risk subjects group, the level of homocysteine correlates albeit weak with the total CAD risk (p=0.04). Homocysteine levels correlate with the WBC count (p=0.02). In the subgroup of smokers with high CAD risk, homocysteine correlates with age, total CAD risk, total cholesterol, BUN (define BUN) and creatinine. Group 3 consisted of 49 subjects with manifested and angiographically proven CAD, out of whom 80% were males and 20% females, mean age 56.06±9.7 years, with average 2 coronary vessels affected. There were significantly higher homocysteine plasma levels between the control group and the group with manifested CAD (p=0.008).There is no significant difference of homocysteine plasma levels between the high risk group and the group with manifested coronary artery disease (15.03□mol/l vs. 16.38□mol/l). In this group, plasma levels of homocysteine correlate only with the highest level of vessel stenosis (>95%) with (p=0.04). The study population in group 4 showed a mean of IMT 0.9 +..09 mm and mean Hcy plasma levels of 21 + 11 µmol/L. From the evaluated patients with CAD, 82.9% of patients had elevated level of Hcy. From those, one showed elevated Hcy, 79.4 % had hypertension, 58.9 % had hyperlipidemia, 28.2% had diabetes mellitus as additional risk factors for atherosclerosis. 76.9 % of the patients had increased intima-media thickness; in 58.9 % plaques were detected, while 23 % of the patients had significant stenosis: 10.2 % with intermediate-grade stenosis (50-69%) and 12.8 % with high-grade stenosis (70-99 %). 17.1 % of the patients had normal level of Hcy, and in those ones 62.5 % only had increased IMT. We found linear correlation between IMT and HCy levels (r 0.7, p 0.05). Case control analysis showed significant higher level of Hcy in the group with CAD and carotid artery disease vs. CAD group (p 0.001). High plasma homocysteine concentrations are associated with high risk for vascular disease and consequently CAD itself and carotid artery disease, as well, proving its likely role in the development of atherosclerosis on inflammatory and metabolic levels.

2151-PUB: Association of Homocysteine with Early Nephropathy in Patients with Type 2 Diabetes

Early predication and intervention of diabetic nephropathy is increasingly imperative. Hyperhomocysteinemia is common and chronically induces arteriolar thickening, and tubulointerstitial and podocyte injury, therefore, could play a causative role in early renal injury in the kidney in type 2 diabetes. In this study, we for the first time investigated the relation of plasma total homocysteine concentration to early nephropathy in type 2 diabetes. We enrolled 183 type 2 diabetic patients in a cross-sectional study. Early diabetic nephropathy status was diagnosed by presence of microalbuminuria. Plasma total homocysteine levels were measured using fluorescence polarization immunoassay. Variables for diabetic nephropathy were obtained from fasting blood samples and interviewer- questionnaire. We found that plasma total homocysteine concentrations were elevated in subjects with early diabetic nephropathy than without (13.3±2.9)µmol/l vs. (8.5 ± 1.4)μmol/l, p &amp;lt; 0.01). The association of homocysteine with the diabetic nephropathy was independent of major traditional risk factors for diabetic nephropathy (duration of diabetes, HbA1c, and blood pressure) and determinants of higher homocysteine concentration (age, sex, serum folate and vitamin B12, Biguanide use, and serum cystatin or creatinine levels,) (OR: 1.36 (1.08-1.74), p &amp;lt; 0.05). Furthermore, per increase of 5.0 μmol/l plasma homocysteine was related to early nephropathy (OR: 1.15 (1.04-1.29), p &amp;lt; 0.05), after controlling for per unit increase of other factors: per 5 year increase of duration of diabetes, per 1% increase of HbA1c, per 10 nmol/l increase of serum folate, per 100 pmol/l increase of serum B12, per 0.1 mg/L increase of serum cystatin or per 10 μmol/l increase of creatinine, and per 10 or 5 mmHg increase of systolic or diastolic blood pressure. We concluded that plasma total homocysteine concentration was independently associated with occurrence of early diabetic nephropathy. Future prospective studies are warranted. Disclosure J. Li: None. Q. Lv: None. H. Lu: None. H. Zhang: None. J. Zhou: None. Funding National Natural Science Foundation of China (81070655); Jiangsu Provincial Natural Science Foundation of China (BK2009441)

Postprandial One-Carbon Metabolite Responses Are Dependent on Meal Composition and Age: A Comparison Between Older and Younger Adults

Abstract Objectives Vitamin deficiencies are prevalent in the elderly. Common diseases of aging are characterized by alterations of one-carbon (1C) metabolites, namely homocysteine. Despite the importance of diet-derived nutrients and interconversion to active coenzymes for regulation of 1C metabolism, little is known about age-related alterations in 1C metabolism in response to meals. This study aimed to identify whether postprandial 1C metabolite regulation is impaired in older adults, and determine the influence of meal type. We hypothesized that older adults would have altered 1C metabolite responses, and that these would differ between energy dense and nutrient dense meals. Methods In a double-blinded randomized crossover design, healthy younger (n = 15) and older (n = 15) adults consumed mixed-meal breakfasts on separate occasions: an energy-dense (ED) meal (sausage and egg sandwich) and a nutrient-dense (ND) meal (oats, toast, cottage cheese and fruit). Plasma collected at fasting and hourly for 5 h was analysed for 12 1C metabolites using high-performance liquid chromatography with tandem mass spectrometry. Results Postprandial concentrations of five 1C metabolites differed between older and younger subjects, dependent on meal type. Unlike younger subjects, older subjects had similar meal responses for betaine, choline, taurine, and glycine concentrations (meal × age interactions P &amp;lt; 0.05 each, respectively; older ED vs. ND meal P &amp;gt; 0.05 each, respectively). Younger subjects had higher homocysteine concentrations than older after the ED meal (meal × age interaction P &amp;lt; 0.05; older vs. younger P &amp;lt; 0.05), but lower choline, glycine, and taurine concentrations than after the ND meal (P &amp;lt; 0.05 each, respectively). Conclusions Postprandial 1C metabolite responses are unaffected by meal type in older subjects, responding more similarly to divergent meals than in younger subjects. Although the implications to biological pathways and health outcomes relying on 1C metabolites are not clear, modification of these responses through acute dietary change may be less effective in the elderly. Funding Sources This research was funded by the Liggins Institute Trust, AgResearch Science Strategic Investment Fund Nutritional Strategies for an Aging Population, the Maurice and Phyllis Paykel Trust and a Faculty Research and Development Fund from the University of Auckland.

Maternal B12, Folate and Homocysteine Concentrations and Offspring Cortisol and Cardiovascular Responses to Stress.

ContextImbalances in maternal 1-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India.ObjectiveWe examined the hypothesis that low plasma vitamin B12 (B12) and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic–pituitary–adrenal axis (cortisol) and cardiovascular responses during the Trier Social Stress Test for Children (TSST-C) in an Indian birth cohort.MethodsAdolescents (n = 264; mean age: 13.6 years), whose mothers’ plasma B12, folate and total homocysteine concentrations had been measured during pregnancy, completed 5-minutes each of public speaking and mental arithmetic tasks in front of 2 unfamiliar “judges” (TSST-C). Baseline and poststress salivary cortisol concentrations were measured. Heart rate, blood pressure, stroke volume, cardiac output, and total peripheral resistance were measured continuously at baseline, during the TSST-C, and for 10 minutes after the TSST-C using a finger cuff; beat-to-beat values were averaged for these periods, respectively. ResultsMaternal low B12 status (plasma B12 < 150 pmol/L) was associated with greater cortisol responses to stress in the offspring (P < .001). Higher homocysteine concentrations were associated with greater offspring heart rate response (P < .001). After adjustment for multiple comparisons, there were nonsignificant associations between higher maternal folate concentrations and offspring total peripheral resistance response (P = .01).ConclusionOur findings suggest that maternal 1-carbon nutritional status may have long-term programming implications for offspring neuroendocrine stress responses.

The determinants of maternal homocysteine in pregnancy: findings from the Ottawa and Kingston Birth Cohort.

Observational studies have linked elevated homocysteine to vascular conditions. Folate intake has been associated with lower homocysteine concentration, although randomised controlled trials of folic acid supplementation to decrease the incidence of vascular conditions have been inconclusive. We investigated determinants of maternal homocysteine during pregnancy, particularly in a folic acid-fortified population. Data were from the Ottawa and Kingston Birth Cohort of 8085 participants. We used multivariable regression analyses to identify factors associated with maternal homocysteine, adjusted for gestational age at bloodwork. Continuous factors were modelled using restricted cubic splines. A subgroup analysis examined the modifying effect of MTHFR 677C>T genotype on folate, in determining homocysteine concentration. Participants were recruited in Ottawa and Kingston, Canada, from 2002 to 2009. Women were recruited when presenting for prenatal care in the early second trimester. In 7587 participants, factors significantly associated with higher homocysteine concentration were nulliparous, smoking and chronic hypertension, while factors significantly associated with lower homocysteine concentration were non-Caucasian race, history of a placenta-mediated complication and folic acid supplementation. Maternal age and BMI demonstrated U-shaped associations. Folic acid supplementation of >1 mg/d during pregnancy did not substantially increase folate concentration. In the subgroup analysis, MTHFR 677C>T modified the effect of folate status on homocysteine concentration. We identified determinants of maternal homocysteine relevant to the lowering of homocysteine in the post-folic acid fortification era, characterised by folate-replete populations. A focus on periconceptional folic acid supplementation and improving health status may form an effective approach to lower homocysteine.

Health outcomes associated with vegetarian diets: An umbrella review of systematic reviews and meta-analyses.

Several meta-analyses evaluated the association between vegetarian diets and health outcomes. To integrate the large amount of the available evidence, we performed an umbrella review of published meta-analyses that investigated the association between vegetarian diets and health outcomes. We performed an umbrella review of the evidence across meta-analyses of observational and interventional studies. PubMed, Embase, Cochrane Database of Systematic Reviews, and ISI Web of Knowledge. Additional articles were retrieved from primary search references. Meta-analyses of observational or interventional studies that assessed at least one health outcome in association with vegetarian diets. We estimated pooled effect sizes (ESs) using four different random-effect models: DerSimonian and Laird, maximum likelihood, empirical Bayes, and restricted maximum likelihood. We assessed heterogeneity using I2 statistics and publication bias using funnel plots, radial plots, normal Q-Q plots, and the Rosenthal's fail-safe N test. The umbrella review identified 20 meta-analyses of observational and interventional research with 34 health outcomes. The majority of the meta-analyses (80%) were classified as moderate or high-quality reviews, based on the AMSTAR2 criteria. By comparison with omnivorous diets, vegetarian diets were associated with a significantly lower concentration of blood total cholesterol (pooled ES=-0.549mmol/L; 95% CI:-0.773 to-0.325; P<0.001), LDL-cholesterol (pooled ES=-0.467mmol/L; 95% CI:-0.600 to-0.335); P<0.001), and HDL-cholesterol (pooled ES=-0.082mmol/L; 95% CI:-0.095 to-0.069; P<0.001). In comparison to omnivorous diets, vegetarian diets were associated with a reduced risk of negative health outcomes with a pooled ES of 0.886 (95% CI: 0.848 to 0.926; P<0.001). In comparison to omnivores, Seventh-day Adventists (SDA) vegetarians had a significantly reduced risk of negative health outcomes with a pooled ES of 0.721 (95% CI: 0.625 to 0.832; P<0.001). Non-SDA vegetarians had no significant reduction of negative health outcomes when compared to omnivores (pooled ES=0.973; 95% CI: 0.873 to 1.083; P=0.51). Vegetarian diets were associated with harmful outcomes on one-carbon metabolism markers (lower concentrations of vitamin B12 and higher concentrations of homocysteine), in comparison to omnivorous diets. Vegetarian diets are associated with beneficial effects on the blood lipid profile and a reduced risk of negative health outcomes, including diabetes, ischemic heart disease, and cancer risk. Among vegetarians, SDA vegetarians could represent a subgroup with a further reduced risk of negative health outcomes. Vegetarian diets have adverse outcomes on one-carbon metabolism. The effect of vegetarian diets among pregnant and lactating women requires specific attention. Well-designed prospective studies are warranted to evaluate the consequences of the prevalence of vitamin B12 deficiency during pregnancy and infancy on later life and of trace element deficits on cancer risks. CRD42018092470.

Homocisteína y trastornos neurocognitivos. ¿Una luz al final del túnel?

&#x0D; &#x0D; &#x0D; &#x0D; El deterioro cognitivo es uno de los procesos que acompañan al envejecimiento y puede depender de factores nutricionales, genéticos o ambientales. La identificación de factores de riesgo modificables proporciona un enfoque esencial para la prevención de dicho deterioro y de los trastornos neurocognitivos. Uno de los factores de riesgo involucrados es la elevada concentración de homocisteína plasmática, la cual se ha relacionado con hallazgos histopatológicos en demencia senil y enfermedad de Alzheimer. Los diferentes estudios sobre esta asociación revelan inconsistencia o contradicción en los resultados. El propósito de esta revisión es relacionar la posible interacción de tres factores en la instalación y progresión del deterioro neurocognitivo: a) factores de tipo nutricional (homocisteína, ácido fólico y vitamina B12), b) la utilización de pruebas para el diagnóstico de disfunción o deterioro cognitivo como el Mini Examen del Estado Mental, y c) la presencia de variantes genéticas polimórficas de la enzima metilentetrahidrofolato reductasa. Una consecuencia directa de esta triple relación es que el tratamiento con ácido fólico y vitamina B12 logra disminuir las elevadas concentraciones de homocisteína plasmática, asumiendo que una mejoría en los síntomas clínicos de deterioro cognitivo puede retrasar los cambios relacionados con progresión a estados demenciales. La intervención temprana mediante políticas de promoción y prevención de la salud mental puede ser efectiva si se comienza con la administración de ácido fólico y vitamina B12 en los estadios iniciales de la alteración cognitiva, logrando así reducir sus funestas consecuencias. Las políticas de salud pública centradas en la salud mental de ancianos pueden identificar a las personas con disfunción cognitiva inicial a través de la promoción de la salud y medidas preventivas; en esta etapa puede ser posible la administración de vitaminas B para reducir o minimizar la progresión del deterioro cognitivo, que podría conducir a trastornos neurocognitivos como la demencia y la enfermedad de Alzheimer.&#x0D; &#x0D; &#x0D; &#x0D;

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma.

α-Lipoic acid, glutathione, cysteine, and cysteinylglycine can be applied as therapeutic agents in civilization diseases such as diabetes mellitus, cardiovascular diseases, and cancers. On the other hand, a higher concentration of homocysteine can result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. Here, the first simplified HPLC-UV assay that enables simultaneous determination of α-lipoic acid and low-molecular-mass thiols in plasma, reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials is described. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearity in the detector responses for plasma samples were observed in ranges: 0.12–5.0 nmol mL−1 for α-lipoic acid; 2.0–20.0 nmol mL−1 for glutathione, cysteinylglycine, and homocysteine; and 40.0–400.0 for cysteine. The LODs for α-lipoic acid and low-molecular-mass thiols were 0.08 and 0.12 nmol mL−1, respectively, while LOQs were 0.12 and 0.16 nmol mL−1, respectively. The usefulness of the proposed method has been proven by its application to real samples.

Evaluation of Serum Folic Acid and Vitamin B12 in Children with Congenital Heart Defect

Congenital heart defects are the result of incomplete heart development and, like many diseases, have been associated with high homocysteine concentration, the aim of the study is to evaluate serum folate and cobalamin levels in children with CHD with correlation to maternal level, a prospective study (case-control) carried out from January 2018 to December 2019.The study was conducted on 60 children (males & females) and their mothers , from pediatric cardiology unit and outpatient clinic of Benha University Hospital, was subdivided into; Group (I): Which included 40 know youngsters diagnosed Concerning illustration inherent heart deformity What's more their moms Similarly as examine group,Group (II): Which incorporated 20 sound kids What's more their moms Similarly as control group, newborn child What's more maternal homocystiene ≥9. 65 Furthermore ≥11. 25 separately could fundamentally separate cyanotic starting with acyanotic CHD patients. Auc were 0. 964 Also 0. 808 for babies and maternal values separately. The affectability What's more specificity to newborn child homocystiene were 95. 2% Also 89. 5% respectively, same time maternal cutoff worth required a affectability and specificity for 90. 5% Also 63. 2% respectively, a helter skelter maternal tHcy centralization may be connected with an expanded hazard from claiming Hosting a tyke with CHD in a concentration‐dependent manner, incompletely because of low serum folate and vitamin B12. Those folate status of the tyke may make included and also blacks Furthermore ought to a chance to be investigated together with other pathways embroiled Previously, CHD.

Association between maternal serum homocysteine concentrations in early pregnancy and adverse pregnancy outcomes.

Background:There is still conflicting evidence on the extent to which maternal hyperhomocysteinemia is a risk factor for pregnancy complications.Aims:The study aimed to investigate the impact of elevated maternal homocysteine concentrations on adverse pregnancy outcomes among Nigerian women in Lagos.Materials and Methods:This was a prospective cohort study conducted at the Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria. Participants were enrolled during the first trimester of pregnancy following which relevant data were obtained by the interview. Fasting blood samples were collected for the measurement of maternal homocysteine concentration using the enzyme-linked immunosorbent assay method. Pregnancy outcomes and complications were obtained by abstracting the antenatal, delivery, and newborn medical records. Preterm births, low-birth weight (LBW), and antepartum fetal death were used as confirmatory outcome variables in the final analysis. Descriptive statistics for all data were computed using SPSS version 22.0. The associations between the variables were tested and multivariate analyses were used to study the effects of the major baseline characteristics on the pregnancy outcome. P < 0.05 was considered statistically significant.Results:Hyperhomocysteinemia was recorded in 41 (24.6%) patients. Women with a high homocysteine concentration and those with a normal homocysteine level did not differ significantly in terms of age (P = 0.684), level of education (P = 0.866), and parity (P = 0.647). Women with hyperhomocysteinemia had an approximately twelve-fold higher risk of preterm birth (P = 0.001) and a ten-fold higher risk of delivering a term neonate with LBW (P = 0.004), but had no risk of antepartum fetal death (P = 0.118) compared to women with a normal homocysteine concentration.Conclusions:The prevalence of hyperhomocysteinemia among mothers in Lagos was relatively low. The associations between hyperhomocysteinemia and adverse pregnancy outcomes could have implications in future for the prevention of these adverse outcomes.

Growth performance, blood parameters and metabolic-enzyme gene expression of finishing pigs as affected by dietary level of methionine + cystine supplemented with vitamin B6

Context Methionine (Met) is an essential amino acid in pig diets. However, high blood homocysteine concentration, a risk factor for cardiovascular disease, can arise from high dietary Met intake and may indicate an imbalance in the Met cycle. Vitamin B6 acts as a cofactor for enzymes associated with the trans-sulfuration pathway, considered the major elimination route of excess homocysteine. Aims We evaluated the effects of different levels of dietary Met and vitamin B6 supplementation and their interaction with respect to growth performance, blood parameters and metabolic-enzyme gene expression of finishing pigs. Methods Fifty-six crossbred barrows, averaging 75.11 ± 1.84 kg bodyweight (BW), were assigned in a completely randomised block design arranged in a 2 × 4 factorial with two levels of vitamin B6 supplementation (1.58 and 3.58 mg/kg) and four levels of standardised ileal digestible (SID) Met + cystine (Cys) (0.35%, 0.45%, 0.55 and 0.65%), with seven replicates and one animal per pen, for an average duration of 26 days. BW of each pig and quantity of experimental diets on-offer and consumed were recorded at the beginning and end of the experiment. Plasma concentrations of glucose, urea, total proteins, creatinine and triacylglycerol were determined by the colourimetric method, and serum homocysteine by chemiluminescence. Gene expression was measured by quantitative real-time polymerase chain reaction. Key results No interactions (P > 0.05) between vitamin B6 supplementation and SID Met + Cys levels were observed for growth performance, blood parameters or metabolic-enzyme gene expression. Higher vitamin B6 supplementation (3.58 mg/kg) improved (P = 0.05) the feed : growth ratio. Treatments did not affect (P > 0.05) expression of the enzymes methionine synthase or cystathionine γ-lyase, and there was a linear increase (P = 0.01) in serum homocysteine levels with increasing dietary Met + Cys. Increasing vitamin B6 supplementation (3.58 mg/kg) in finishing pig diets increased plasma glucose concentration (P = 0.05), but did not mitigate the increase in homocysteine concentration. Conclusions Overall, a dietary SID Met + Cys intake of 10.46 g/day (corresponding to 0.35%) was sufficient for the growth of finishing barrows from 75 to 100 kg BW. Vitamin B6 supplementation at 3.58 mg/kg improved the feed : growth ratio but was not effective for metabolising the increasing homocysteine concentration via the trans-sulfuration pathway. Implications This study provides much needed empirical data on the dietary SID Met + Cys requirements for finishing pigs, and the metabolism of these amino acids.