Plasma Homocysteine Concentrations Research Articles

PSLBII-4 The effect of standardized ileal digestible sulfur amino acid intake during late gestation on gilt whole-body nitrogen retention and subsequent litter performance

Abstract Gestating gilts [n = 27; body weight (BW) = 158 ± 5.5 kg] were used to determine the effect of standardized ileal digestible (SID) sulfur amino acid (SAA) intake during late gestation on whole-body nitrogen (N) retention and subsequent litter performance. Gilts were assigned to one of two experimental diets that provided SAA at 60 or 200 % of estimated requirements during late gestation (0.29 and 0.92 % SID SAA, respectively; n = 15 and 12, respectively; Table 1 and 2). Each gilt received 2.53 kg of the assigned diet between gestation d 90 and farrowing; standard lactation and nursery diets were provided to gilts after farrowing and offspring after weaning, respectively. Gilt whole-body N balance was determined between d 107 and 109 of gestation using total urine collection and fecal grab-sampling. After farrowing, litters were standardized to 13 piglets and were not offered creep feed. Whole-body N retention was greater in gilts fed the diet containing 0.92 vs. 0.29 % SID SAA in late gestation (27.2 vs. 19.3 ± 1.8 g/d; P < 0.05; Table 3), but the number of piglets born alive, litter birth weight, subsequent piglet growth rates, and litter size at weaning were not different between treatment groups. The post-weaning growth performance of offspring was also not influenced by maternal dietary treatment in late gestation (Table 4). At farrowing, the post-absorptive plasma concentration of Cys tended to be less (P = 0.072) and taurine was greater (P < 0.01) for gilts fed 0.92 vs. 0.29 % SID SAA in late gestation; however, there were no differences in plasma SAA metabolites concentrations for gilts at weaning or offspring at birth (Table 5. At weaning, offspring from gilts fed 0.92 % SID SAA had greater plasma homocysteine (P < 0.05) and plasma Cys concentrations (tendency; P = 0.072) vs. offspring from gilts fed 0.29 % SID SAA in late gestation. Three weeks after weaning, plasma taurine concentration was less (P < 0.05) for offspring from gilts fed 0.92 vs. 0.29 % SID SAA in late gestation (Table 6). Six weeks after weaning, plasma glutathione concentration tended to be less (P = 0.057) for offspring from gilts fed 0.92 vs 0.29 % SID SAA in late gestation. When SAA were fed below estimated requirements during late gestation, whole-body N retention was reduced, but fetal growth appeared to be maintained, likely at the expense of maternal N retention. Such divergences in dietary SAA supply in late gestation had no effect on subsequent offspring growth performance, but it appeared that offspring SAA metabolism was impacted until at least 6 wk after weaning. The influence of differences in sulfur AA metabolites on offspring performance beyond the nursery phase remains unknown. Therefore, carry-over effects of maternal SAA supply in late gestation should be considered when developing feeding recommendations for gestating gilts.

Biochemical and histological changes in two nonalcoholic fatty liver disease models of different severity

Background. One of the priority areas of modern medicine, which unites the interests of various specialists (therapists, cardiologists, gastroenterologists, endocrinologists), is the study of the pathogenesis and clinical manifestations of nonalcoholic fatty liver disease (NAFLD), which is widespread and of unconditional social significance. The search for adequate experimental models of NAFLD that reflect the severity of liver damage is of paramount importance for studying its etiology and pathogenesis.The aim of the study. To compare biochemical and histological changes in experimental models of NAFLD of varying severity.Materials and methods. Two NAFLD model versions were used: a light one – nonalcoholic steatosis (NAS) and a severe variant – non-alcoholic steatohepatitis (NASH). The following biochemical parameters were measured: enzyme activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (AP), plasma glucose concentration, total protein (TP), total bilirubin (TBil) and its conjugate fraction (CB), plasma concentrations of homocysteine (HC), total cholesterol (TC), triacylglycerides (TG), catalase (Cat), superoxide dismutase (SOD) and malondialdehyde (MDA).Results. When used in a model of steatohepatitis, liver function was impaired to a significantly greater extent than in the model of steatosis; this difference was manifested in a statistically significant increase in ALT, AST, AP, TC, Tbil, MDA (p < 0.001) and a decrease in Cat, SOD (p < 0.05). This is confirmed by the development of more pronounced symptoms of disorders of pigment and lipid metabolism, cytolytic and cholestatic syndromes, significant activation of lipid peroxidation and depression of the antioxidant system when modeling non-alcoholic steatohepatitis. Various degrees of severity of morphological changes in the experimental groups were revealed.Conclusion. The study showed the priority of determining biochemical markers, including the levels of ALT, AST, OBIL, TG, MDA and SOD to optimize laboratory methods for diagnosing the severity of liver dystrophy.The practical originality of the results lies in the optimization of the methodology for laboratory diagnosis of the severity of the pathological process in NAFLD.

СООТНОШЕНИЕ H2S/ГОМОЦИСТЕИН КАК ПОТЕНЦИАЛЬНЫЙ БИОМАРКЕР ПРОГНОЗИРОВАНИЯ ПРОГРЕССИРОВАНИЯ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ У ДЕТЕЙ

Background. The H2S/homocysteine ratio is a potential biomarker for predicting the progression of cardiovascular diseases. The purpose. To establish the features of changes in the H2S/homocysteine ratio in children with arterial hypertension. Material and methods. A total of 111 children aged 14 to 18 years were examined. Based on the results of 24-hour blood pressure monitoring (n=81), two groups were formed: group 1 (n=51) – children with arterial hypertension (AH), group 2 (n=30) – children with high-normal blood pressure (HNBP). Group 3 included 30 healthy children. Plasma homocysteine level was determined by high-pressure liquid chromatography [Naumov A.V. et al., 2010]. The level of endogenous hydrogen sulfide was assessed by spectrophotometric method based on the reaction between sulfide anion and an acidic solution of the reagent N, N-dimethyl-p-phenylenediamine hydrochloride [Norris Eric J., 2011]. Results. A significant increase in plasma homocysteine concentration was revealed in patients with AH and HNBP compared with healthy children. The plasma levels of hydrogen sulfide in children with AH were significantly lower than in the comparison group. Hypertensive children in comparison to healthy children showed significantly lower plasma H2S/homocysteine ratio. Correlations have been established between the H2S/homocysteine ratio and plasma levels of homocysteine and hydrogen sulfide. Conclusions. Hypertensive children have a lower H2S/homocysteine ratio, which is due to the presence of hyperhomocysteinemia and reduced H2S levels. The H2S/homocysteine ratio can be used as a potential marker for predicting the progression of AH.

The Association of Plasma Homocysteine Concentrations with a 10-Year Risk of All-Cause and Cardiovascular Mortality in a Community-Based Chinese Population.

This study is aimed to examine the association of plasma homocysteine (Hcy) concentrations with a 10-year risk of all-cause and cardiovascular (CV) mortality and to explore the modification effect of methylenetetrahydrofolate reductase (MTHFR) C677T genetic polymorphism. This study included 5200 participants from a community-based Chinese population. Cox proportional hazard regression models were used to analyze the associations of Hcy and MTHFR C677T genotype with all-cause and CV mortality. The possible modification effect of the MTHFR C677T genotype on the Hcy-mortality relationship was assessed. The individuals with Hcy concentrations ≥ 10 μmol/L had a significantly higher risk of all-cause mortality compared to those with Hcy < 10 μmol/L (hazard ratio [HR]: 1.72, 95% confidence interval [CI]: 1.11-2.68, p = 0.015). The risk of CV mortality increased by 2% per 1 μmol/L Hcy increment (HR: 1.02, 95% CI: 1.00-1.03, p = 0.036). Despite the MTHFR genotype alone not being correlated with the mortality, the relationship between Hcy and all-cause mortality was significant in the CC genotype compared with CT/TT genotype (p for interaction = 0.036). Elevated plasma Hcy concentrations were associated with an increased 10-year risk of all-cause and CV mortality among the Chinese population. MTHFR C677T genetic polymorphism could modify the association between Hcy and all-cause mortality.

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study

BackgroundThe absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy. ObjectivesWe aimed to assess the efficacy of oral vitamin B12 supplementation in PA. MethodsWe enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid–to–creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 μg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration. ResultsWe included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297–485) compared with 148 (116–213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9–29.8) compared with 18.6 (13.7–46.8) μmol/L; P < 0.0001], and pMMA [0.24 (0.16–0.38) compared with 0.56 (0.28–1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms. ConclusionsOral supplementation with 1000 μg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

The effect of methionine and folic acid administered in ovo on the blood biochemical parameters of chickens (Gallus gallus domesticus)

Methionine is one of the most frequently supplemented amino acids in raising of poultry. However, an overdose of methionine can cause hyperhomocysteinemia. Folic acid, taking part in the process of homocysteine remethylation, is a factor affecting the reduction of the concentration of this amino acid. The study was carried out in 2 stages. The experiment of step I was to investigate the effect of methionine and/or folic acid administration in ovo in the early stage of embryogenesis (E4), and the experiment of the second stage - in the late stage of embryogenesis (E17) on the following biochemical parameters of chicken blood: glucose concentration in whole blood and concentration of homocysteine and uric acid in plasma of domestic chickens (Gallus gallus domesticus). Our results confirm that methionine supplementation may increase the concentration of uric acid and homocysteine. Moreover, we demonstrated that folic acid administered during embryogenesis decreased homocysteine concentration, also in groups simultaneously supplemented with methionine, especially in the initial stage of postnatal life of the bird.

Homozygous MTHFR C677T carriers develop idiopathic portal vein thrombosis 20 years earlier than wild type.

The aim of this study was to evaluate the impact of methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C→T667 transition) on age at first idiopathic portal vein thrombosis (PVT) and to identify clinical and/or laboratory variables influencing age at first PVT, including plasma homocysteine and the prothrombin rs1799963 PT (G→A transition at position 20210) (PT) mutation. A retrospective cross-sectional cohort, including 15 MTHFR TT, 32 MTHFR TC and 22 MTHFR CC idiopathic PVT participants contributing demographics, age at PVT, plasma concentrations of homocysteine and of natural anticoagulants. MTHFR TT carriers presented with a lower age at PVT than heterozygous or wild-type genotypes (31 ± 8 vs. 48 ± 15 vs. 52 ± 13 years, P = 0.001) and were more likely to have a plasma HC concentration above the cut-off (73.3 vs. 32 vs. 50%, P = 0.04). MTHFR TT and protein C predicted age at PVT ( P < 0.0001 and P = 0.06); MTHFR TT predicted plasma homocysteine ( P = 0.05). In the MTHFR TT group, plasma homocysteine inversely related to protein C ( P = 0.03). Plasma homocysteine predicted the extent of PVT ( P = 0.03). Compound MTHFR TT + PT GA did not lower age at first PVT compared to MTHFR TT alone (35 ± 9 vs. 30 ± 8 years). MTHFR TT is associated with a 20-year earlier PVT presentation than heterozygous and wild-type MTHFR genotypes. The inverse relation between plasma homocysteine and protein C contributes to the prematurity of PVT in the MTHFR TT group, whereas plasma homocysteine contributes to the extent of PVT. The recent exclusion of MTHFR genotyping from the thrombophilia screen needs revisiting in this setting.

Plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine

BackgroundOrthostatic intolerance, which includes vasovagal syncope and postural orthostatic tachycardia syndrome, is common in children and adolescents. Elevated plasma homocysteine levels might participate in the pathogenesis of orthostatic intolerance. This study was designed to analyze the plasma metabolomic profile in orthostatic intolerance children with high levels of plasma homocysteine.MethodsPlasma samples from 34 orthostatic intolerance children with a plasma homocysteine concentration > 9 µmol/L and 10 healthy children were subjected to ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry analysis.ResultsA total of 875 metabolites were identified, 105 of which were significantly differential metabolites. Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, 1-(1Z-octadecenyl)-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphocholine, histidine, isocitric acid, and DL-glutamic acid and its downstream metabolites were upregulated, whereas 1-palmitoyl-sn-glycero-3-phosphocholine, 1-stearoyl-sn-glycerol 3-phosphocholine, sphingomyelin (d18:1/18:0), betaine aldehyde, hydroxyproline, and gamma-aminobutyric acid were downregulated in the orthostatic intolerance group compared with the control group. All these metabolites were related to choline and glutamate. Heatmap analysis demonstrated a common metabolic pattern of higher choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid, and lower sphingomyelin (d18:1/18:0), 1-stearoyl-sn-glycerol 3-phosphocholine, and 1-palmitoyl-sn-glycero-3-phosphocholine in patients with certain notable metabolic changes (the special group) than in the other patients (the common group). The maximum upright heart rate, the change in heart rate from the supine to the upright position, and the rate of change in heart rate from the supine to the upright position of vasovagal syncope patients were significantly higher in the special group than in the common group (P < 0.05). Choline, 1-stearoyl-2-linoleoyl-sn-glycero-3-phosphocholine, and DL-glutamic acid were positively correlated with the rate of change in heart rate from the supine to the upright position in vasovagal syncope patients (P < 0.05).ConclusionsThe levels of choline-related metabolites and glutamate–related metabolites changed significantly in orthostatic intolerance children with high levels of plasma homocysteine, and these changes were associated with the severity of illness. These results provided new light on the pathogenesis of orthostatic intolerance.

Effect of feeding sows a combination of extra vitamin B2, vitamin B6, vitamin B12, and folic acid during the first 45 days of gestation on piglet birthweight

The objective of this study was to test whether a high inclusion rate of dietary vitamin B2, B6, B12, and folic acid during the first 45 d of gestation could decrease within-litter variation in piglet birth weight and increase the average birth weight of the litter. Two hundred forty-one multiparous sows (Landrace x Yorkshire) were allotted to either a control or a B vitamin diet from mating to d 45 of gestation. The experimental unit was the sow or the litter. Sows in the control group were fed a standard gestation diet complying with Danish recommendations: 5.11, 3.07, 0.02, and 1.53 mg/kg for vitamin B2, B6, B12, and folic acid, respectively. Sows fed the B vitamin diet were fed the same standard gestation diet including an extra premix providing 232, 210, 1000, and 668 % extra vitamin B2, B6, B12, and folic acid, respectively. From d 46 until farrowing, all sows were fed the standard diet. The backfat thickness of sows was measured at farrowing and weaning in the previous cycle and at d 14, 45, and 112 of gestation. From a subsample of 10 second parity sows per treatment, blood samples were taken using jugular venipuncture into 10 mL EDTA tubes at weaning and d 14, 45, and 112 of gestation. The plasma was analyzed for the concentration of homocysteine. At farrowing, the number of live and stillborn piglets were recorded, and for a subsample of 71 (control) and 66 (B vitamin) sows, the weight, crown-rump length and abdominal circumference of individual piglets in the litters were measured. The plasma concentration of homocysteine at weaning and during gestation was unaffected by dietary treatments. For the overall treatments, there was no difference in live born (Control: 19.5; B vitamin: 19.9) and stillborn (Control: 1.5; B vitamin: 1.6) piglets between treatments. The average birth weight of live born (Control: 1,270 g; B vitamin: 1,245 g) and stillborn (Control: 992 g; B vitamin: 870 g) piglets and the within-litter variation in birth weight (Control: 294 g; B vitamin: 307 g) were unaffected by dietary treatment. The abdominal circumference (Control: 23.3 cm; B vitamin: 22.7 cm) and the crown-rump length (Control: 31.6 cm; B vitamin: 31.0 cm) were greater for piglets born to sows fed the control diet compared to sows fed the B vitamin diet (P < 0.05). In conclusion, there was no positive effect of supplementing surplus B vitamins above recommended inclusion rates to sows in early gestation on piglet birth weight.

Protein intake affects erythrocyte glutathione synthesis in healthy adults aged ≥60 years in a repeated-measures trial

BackgroundProtein recommendations for older adults are based on nitrogen balance data from young adults. Physiological studies using the indicator amino acid oxidation method suggest they need 30% to 50% more protein than current recommendations. We herein present glutathione (GSH) as a physiological estimate of protein adequacy in older adults. ObjectivesThe objective was to measure GSH kinetics in response to varying protein intakes in a repeated-measures design in healthy adults aged ≥60 y using the precursor-product method. MethodsSixteen healthy older adults (n = 8 male and n = 8 female; body mass index ≤30 kg/m2) were studied. Each received 4 of 6 protein intakes in random order (0.66, 0.8, 0.9, 1.1, 1.3 and 1.5 g⋅kg−1⋅d−1). At each intake level, participants underwent isotope infusion studies of 7 h duration following a 3-d adaptation to the test level of protein. On the fourth day, GSH fractional (FSR) and absolute synthesis (ASR) rates were quantified by measuring the incorporation of U-[13C2-15N]glycine into GSH at isotopic steady state. A mixed-effect change-point regression model was used to determine a breakpoint in FSR and ASR. Secondary outcomes included plasma concentrations of oxidative stress markers, homocysteine, 5-L-oxoproline (5-OP), and urinary sulfate. The effect of secondary outcomes on GSH kinetics was analyzed using a joint linear mixed-effect model and Tukey’s post hoc test. ResultsA protein intake of 1.08 g⋅kg−1⋅d−1 (95% confidence interval [CI]: 0.83, 1.32; Rm2 = 0.207; Rc2 = 0.671; P < 0.001) maximized GSH FSR. There was no effect of protein intake on concentrations of erythrocyte GSH, plasma homocysteine, oxidative stress markers, or 5-OP (P > 0.05). Protein intake had a positive effect on urinary sulfate excretion (P < 0.0001). ConclusionA protein intake of 1.08 g⋅kg−1⋅d−1 from a high-quality protein maximized GSH synthesis in adults ≥60 y. This lends support to data suggesting a requirement higher than the current recommendation.This study was registered at clinicaltrials.gov as NCT02971046.

Vitamin B and One-Carbon Metabolite Profiles Show Divergent Associations with Cardiometabolic Risk Markers but not Cognitive Function in Older New Zealand Adults: A Secondary Analysis of the REACH Study

BackgroundVitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways. ObjectivesThe study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status. MethodsThree hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B12). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling. ResultsOver 90% of participants met dietary recommendations for riboflavin and vitamins B6 and B12, but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses. ConclusionsVitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults.

Functional vitamin B12 deficiency is a consistent feature in hospital admissions for neurological disorders due to the use of nitrous oxide

Introduction: Misuse of inhaled nitrous oxide is a growing concern in France. It is known to alter concentrations of vitamin B12, which is required as a cofactor for methionine synthase and methylmalonyl-CoA mutase activity. Hence, measurement of the concentrations of cobalamin metabolism biomarkers, including vitamin B12, homocysteine, and methylmalonic acid, could assist in the management of patients with a complex clinical presentation or in those who deny the consumption of nitrous oxide. Methods: We retrospectively collected clinical and biological data in patients hospitalized for nitrous oxide use in a university hospital in southern France between January 2020 and October 2022. Results: Thirty-one patients were identified during 34 months; 79% were men with a median age of 23.7 years. Most (97%) presented with peripheral polyneuropathy and/or myelopathy. The median vitamin B12 concentration was 134.6 pmol/L, with 17 of 31 patients having values less than 145 pmol/L (the lower limit of the normal range). The median plasma folate concentration was 20.1 nmol/L, which is within the normal range. The median plasma homocysteine concentration was 87.7 µmol/L (normal range >15 µmol/L), and the median plasma methylmalonic acid concentration was 3.8 µmol/L (normal range >0.5 µmol/L). Conclusion: Nitrous oxide use is an emerging public health problem in France, as shown by the number of patients admitted to our hospital. The presence of a functional vitamin B12 deficiency was a consistent feature that could be helpful in diagnosis in complex cases.

Fortified foods with methylated forms of B vitamin for the prevention of hyperhomocysteinemia

Aim. To study the relationship between blood homocysteine levels and genetic and epigenetic factors and assess the possibility of correcting homocysteine levels using products enriched with methylated forms of B vitamin.Material and methods. The study included 20 people (6 men and 14 women) aged 24-67 years (mean age — 41,5 years). Muscleto-fat ratio was determined by bioelectrical impedance analysis. The plasma concentration of homocysteine was measured using an immunochemistry analyser. Polymorphism analysis of folate cycle genes was performed using polymerase chain reaction. Statistical processing of the material, training and data prediction was performed using artificial neural networks (ANNs). Homocysteine levels before a 3-month consumption of fortified products are presented as Hc1, after — Hc2.Results. The blood level of homocysteine before taking fortified fruitberry bars varied from 6,5 to 24,2 µmol/l, averaging 12,45±2,9 µmol/l. After 3 months of use, the blood homocysteine level decreased to the range of 7,1-18 µmol/l and, on average, amounted to 10,87±2,6 µmol/l (p=0,028). Hyperhomocysteinemia was detected in two women (19,7 and 24,2 µmol/l) and one man (17,1 µmol/l). After consuming fruitberry bars, a significant decrease in blood homocysteine levels was observed from 19,7 to 14,3 µmol/l, from 24,2 to 14,1 µmol/l and from 17,1 to 15,5 µmol/l, respectively. A significant average correlation was revealed between Hc1 and Hc2 (r=0,579; p&lt;1×10-5). Correlations were noted between blood homocysteine levels and body mass index, as well as responses about elevated blood glucose levels and the frequency of desire to reduce body weight (p&lt;6,74×10-5).Conclusion. The results demonstrate a significant decrease in blood homocysteine in all participants when taking food products fortified with methylated forms of B vitamin (p=0,028). Individuals adhering to dietary restrictions showed a more pronounced decrease in homocysteine levels (p&lt;6,74×10-5).

Maternal hyperhomocysteinemia increases seizures susceptibility of neonatal rats

AimsNeonatal seizures are severe pathologies which may result in long-term neurological consequences. High plasma concentrations of homocysteine – hyperhomocysteinemia (hHCy) - are associated with epilepsy. In the present study, we evaluated susceptibility to seizure of neonatal rats with prenatal hHCy. Main methodsPrenatal hHCy was induced by feeding females with a high-methionine diet. Experiments were performed on pups during the first three postnatal weeks. Flurothyl-induced epileptic behavior was assessed according to Racine's scale. Epileptiform activity in the hippocampus was recorded using electrophysiological methods. The balance of excitation/inhibition, functional GABAergic inhibition and GABA reversal potential in hippocampal neurons were analyzed. Key findingsRats with hHCy developed more severe stages of behavioral patterns during flurothyl-induced epilepsy with shorter latency. Electrophysiological recordings demonstrated higher background neuronal activity in rats with hHCy. Seizure-like events triggered by flurothyl (in vivo) or 4-aminopyridine (in vitro) showed shorter latency, higher power and amplitude. An increased glutamate/GABA synaptic ratio was shown in the pyramidal neurons of rats with hHCy and more slices demonstrated excitation by isoguvacine, a selective GABA(A) receptor agonist, during the first and second postnatal weeks. The GABA driving force and the reversal potential of GABA(A) currents were more positive during the second postnatal week for hHCy rats. SignificanceThe higher susceptibility to seizures in rats with prenatal hHCy due to a shift in the balance of excitation/inhibition toward excitation may underlie the clinical evidence about the association of hHCy with an increased risk of epilepsy.

Homocysteine Modulates Social Isolation-Induced Depressive-Like Behaviors Through BDNF in Aged Mice.

Social isolation is an unpleasant experience associated with an increased risk of mental disorders. Exploring whether these experiences affect behaviors in aged people is particularly important, as the elderly is very likely to suffer from periods of social isolation during their late-life. In this study, we analyzed the depressive-like behaviors, plasma concentrations of homocysteine (Hcy), and brain-derived neurotropic factor (BDNF) levels in aged mice undergoing social isolation. Results showed that depressive-like behavioral performance and decreased BDNF level were correlated with increased Hcy levels that were detected in 2-month isolated mice. Elevated Hcy induced by high methionine diet mimicked the depressive-like behaviors and BDNF downregulation in the same manner as social isolation, while administration of vitamin B complex supplements to reduce Hcy alleviated the depressive-like behaviors and BDNF reduction in socially isolated mice. Altogether, our results indicated that Hcy played a critical role in social isolation-induced depressive-like behaviors and BDNF reduction, suggesting the possibility of Hcy as a potential therapeutic target and vitamin B intake as a potential value in the prevention of stress-induced depression.

СЕРОСОДЕРЖАЩИЕ АМИНОКИСЛОТЫ И РИСК РАЗВИТИЯ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ У ДЕТЕЙ

Introduction. Currently, sulfur-containing amino acids are potential candidates as risk factors for cardiovascular disease. The purpose: to establish the role of sulfur-containing amino acids and their derivatives in the risk of developing arterial hypertension in children. Matherial and methods. 111 children aged 14 to 18 years were examined. All patients were divided into 3 groups: the 1st group (n=51) consisted of children with arterial hypertension, the 2nd group (n=30) – with high normal blood pressure, the 3rd group – 30 healthy children. The content of sulfur-containing amino acids and their derivatives in blood plasma was determined by high-performance liquid chromatography. Result. The concentration of sulfur-containing amino acids methionine, homocysteine, cysteine and cysteinylglycine in the blood plasma of children with arterial hypertension tend to increase in comparison with the group of healthy children. Pathological decrease in endothelium-dependent vasodilation accompanied by an increase in the concentration of methionine, homocysteine, cysteine, cysteinylglycine, glutathione in blood plasma and a decrease – taurine. A prognostic model has been developed based on the determination of the concentration of homocysteine and cysteinylglycine in the blood plasma of children. With a calculated value of p≥0,44, makes it possible to predict a high probability of arterial hypertension with a sensitivity of 90,2%, a specificity of 66,7% and a diagnostic efficiency of 82,1%. Conclusions. The concentration of sulfur-containing amino acids methionine, homocysteine, cysteine and cysteinylglycine in the blood plasma of children with arterial hypertension tend to increase in comparison with the group of healthy children.

Plasma Homocysteine (Hcy) Concentration Functions as a Predictive Biomarker of SPECT-Evaluated Post-Ischemic Hyperperfusion in Acute Ischemic Stroke.

Homocysteine (Hcy) concentration has been reported to be associated with ischemic stroke. In this study, we aimed to investigate the potential of plasma Hcy in the prediction of post-ischemic hyperperfusion in AIS patients, which was diagnosed with the single-photon emission computed tomography (SPECT) method. A total of 112 ischemic stroke patients were recruited in this study. According to whether the patients were subjected to post-ischemic hyperperfusion, all recruited subjects were divided into a post-ischemic hyperperfusion (+) group (N=48) and post-ischemic hyperperfusion (-) group (N=64). The basic demographical data, clinicopathological data and laboratory biochemical data were collected and compared. Level of homocysteine (Hcy) and cystatin-C (Cys-C) and their potential as predictive biomarker are also investigated. No significant differences were spotted between the post-ischemic hyperperfusion group (+) and post-ischemic hyperperfusion (-) group in respect to the basic demographical and clinicopathological data. And the serum Hcy levels were lower in the post-ischemic hyperperfusion (+) group. Moreover, ROC analysis indicated significant relationships between Hcy levels and the onset of post-ischemic hyperperfusion. In conclusion, we validated that the plasma Hcy concentration can be used as a predictive biomarker of SPECT-evaluated post-ischemic hyperperfusion in patients suffering from acute ischemic stroke.

Changes in homocysteine and non-mercaptoalbumin levels after acute exercise: a crossover study

BackgroundAcute exercise is one factor that increases blood homocysteine levels, and elevated homocysteine levels cause oxidative stress. Albumin, which is abundant in blood, is an antioxidant, and the redox state of albumin is used as an index of oxidative stress in blood. This study aimed to assess the effect of acute exercise on plasma homocysteine levels and the blood non-mercaptoalbumin/mercaptoalbumin ratio as an oxidative stress marker.MethodsThis study used a crossover design with exercise and control conditions. Under exercise conditions, a bicycle ergometer was used to perform 40 min of transient constant-load exercise at 65% heart rate reserve. Under control conditions, participants rested for 40 min. Blood was collected before, 30 min after, and 90 min after exercise, and at the same time points under control conditions. Samples were analyzed for the homocysteine concentration and non-mercaptoalbumin/mercaptoalbumin ratio.ResultsThe results revealed that a 65% heart rate reserve and 40 min of acute exercise increased plasma homocysteine concentration and non-mercaptoalbumin ratio. In the intra-condition comparison, the plasma Hcy concentration was significantly increased at Post 30 min (+ 0.83 ± 0.70 µmol/L, P = 0.003) compared with that at Pre in the exercise condition. Furthermore, 90 min after exercise, the blood non-mercaptoalbumin ratio was significantly increased (+ 0.35 ± 0.71%, P = 0.030) compared to Pre.ConclusionThese results indicate that the plasma Hcy concentration first increased, and then the non-mercaptoalbumin/mercaptoalbumin ratio increased as the elevated state was maintained. This study revealed that 65% heart rate reserve, 40 min of acute exercise increased plasma Hcy concentration and non-mercaptoalbumin ratio.

Association between Micronutrients and Hyperhomocysteinemia: A Case-Control Study in Northeast China.

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular and cerebrovascular diseases where the plasma homocysteine (Hcy) concentration exceeds 15 µmol/L. HHcy is affected by vitamins B12, B6, and folic acid (fol); however, its relationship with other nutrients is not fully understood. We investigated the nutritional and genetic factors associated with HHcy and the possible dose-response relationships or threshold effects in patients in Northeast China. Genetic polymorphisms and micronutrients were tested with polymerase chain reaction and mass spectrometry, respectively. This trial was registered under trial number ChiCTR1900025136. The HHcy group had significantly more males and higher body mass index (BMI), methylenetetrahydrofolate reductase (MTHFR 677TT) polymorphism proportion, and uric acid, Zn, Fe, P, and vitamin A levels than the control group. After adjusting for age, sex, BMI, vitamin B12, fol, and MTHFR C677T, the lowest Zn quartile reduced the odds ratio of HHcy compared with the highest Zn quartile. The dose-response curves for the association between plasma Zn and HHcy were S-shaped. High plasma Zn concentrations were significantly correlated with high HHcy odds ratios, and the curve leveled off or slightly decreased. Most importantly, HHcy risk decreased with decreasing plasma Zn concentration; the threshold was 83.89 µmol/L. Conclusively, individuals residing in Northeast China, especially those with the MTHFR 677TT polymorphism, must pay attention to their plasma Zn and Hcy levels.

Homocysteine in chronic kidney disease: Clinical diagnostic aspects

Chronic kidney disease (CKD) is one of the most common pathologies worldwide. With CKD, cardiovascular risk increases and mortality rises. The article presents the role of homocysteine as a laboratory marker of renal failure and the development of cardiovascular disease. Homocysteine is a thiol-containing amino acid, which is an intermediate product of methionine metabolism, which is metabolized in two ways: due to the transfer of the sulfate group, which occurs in the presence of vitamin B 6, or remethylation, which occurs in the presence of vitamin B 12 and folic acid. Normally, in an adult, the concentration of total homocysteine in blood plasma does not exceed 15 μmol/L. It has been shown that with CKD, hyperhomocysteinemia is observed at the initial stages and its frequency increases at the pre- and dialysis stages of the disease. Hyperhomocysteinemia provokes endothelial dysfunction, accelerates systemic atherosclerosis, increases the risk of atherothrombotic complications. Evaluation of plasma homocysteine levels may be useful in stratifying nephrocardio- and cerebrovascular risk in CKD.