tHcy Concentrations Research Articles

Protective effect of folic acid on osteoporosis in ovariectomized rats

Objective To investigate the protective effect of folic acid(FA) on osteoporosis in ovariectomized(OVX) rats.Methods Forty three-month-old female SD Rats were divided into 5 groups, sham operation group, OVX group, diethylstilbestrol group(0.03mg·kg-1·d-1),low dose FA Group (5 mg·kg-1·d-1),and high dose FA group (20 mg·kg-1·d-1).Gastric gavage in each group was started from one week after being ovariectomized and lasted 10 weeks. Sham operation group and OVX group were treated with solvent. The rats were sacrificed at the end of 10th week after treatment. The total homocysteine(tHcy) in plasma, alkaline phosphatase(ALP), and tartrate-resistant acid phosphatase(TRACP) activity of bone homogenates were measured. The bone mineral density(BMD) and bone biomechanics were determined using L5 vertebrae and right femur. The bone tissue slices were made with L6 vertebrae and left femur and HE stained, and then the histomorphology was observed. Results Compared with sham operation group, plasma tHcy level was significantly increased(P＜0.01), BMD of lumbar vertebrae and femur was remarkedly decreased in OVX group(all P＜0.01). Plasma tHcy concentration was negatively correlated with lumbar BMD(r=-0.359, P=0.040). Plasma tHcy level in both groups treated with folic acid was significantly reduced(all P＜0.01). The ALP concentration in bone homogenates was higher, the TRACP concentration in bone homogenates was lower, and BMD and bone biomechanics of lumbar vertebrae and femur were increased in high dose FA group than those in OVX group(all P ＜0.01). Conclusions In OVX rats hyperhomocysteinemia existed and was involved in the development of osteoporosis. Folic acid could protect OVX rats from osteoporosis, due probably to improved homocysteine metabolism. Key words: Folic acid; Homocysteine; Osteoporosis; Ovariectomized; Rat

Testing homocysteine-induced neurotransmitter deficiency, and depression of mood hypothesis in clinical practice

high total plasma homocysteine (tHcy) levels may cause neurotransmitter deficiency, and consequently depression of mood. We have recently shown that mixed oral nutritional supplements containing B-group vitamins led to a statistically significant benefit on depressive symptoms. The aim of this report was to examine the association between elevated plasma tHcy and symptoms of depression in older patients. two-hundred and thirty-six hospitalised acutely ill older patients, who were part of a randomised double-blind placebo-controlled trial, were assigned to receive daily mixed oral nutritional supplements containing B-group vitamins or a placebo for 6 weeks. Outcome measures included symptoms of depression measured using Geriatric Depression score and plasma tHcy levels. the mean tHcy concentration fell by 22% among patients given the supplements compared with the placebo group (mean difference 4.1 µmol/l (95% CI: 0.14-8.03), P = 0.043). tHcy concentrations was divided into four quartiles and analysed against depression scores. tHcy concentrations in the first relative to the fourth quartile of the distribution were associated with a lower depression symptoms at the end of the supplement period (Geriatric depression score r = -0.20, P = 0.042). lower plasma tHcy concentrations were associated with reduced depression symptoms in older patients recovering from acute illness.

Plasma homocysteine and MTHFRC677T polymorphism as risk factors for incident dementia

BackgroundElevated total plasma homocysteine (tHcy) has been associated with increased risk of dementia. The C677T polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) increases tHcy and provides a means of studying...

Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum

Oxidative stress is a hypothesis for the association of reactive oxygen species with cerebrovascular and neurodegenerative diseases. Thus, we examined whether oral betaine can act as a preventive agent in ethanol-induced oxidative stress on the cerebellum of rats. Thirty-two adult male Sprague-Dawley rats were divided into four equal groups (control, ethanol, betaine, and betaine plus ethanol) with different dietary regimens and were followed up for 1month. Total homocysteine (tHcy) of plasma and cerebellum homogenate was determined by an Axis(®) homocysteine EIA kit, and antioxidant enzyme (glutathione peroxidase (GPx), SOD, and CAT) activities of cerebellum homogenate were measured chemically by a spectrophotometer. Lipid peroxidation of cerebellum was shown by the measurement of thiobarbituric reactive substances (TBARS) via a spectrophotometer. Ethanol-induced hyperhomocysteinemia was manifested by an increase in the concentrations of tHcy in the plasma and cerebellum homogenates of the ethanol group, while ethanol-induced oxidative stress was indicated via an increase in lipid peroxidation marker (TBARS) in cerebellum homogenates of ethanol-treated rats. In contrast, betaine prevented hyperhomocysteinemia and oxidative stress in the betaine plus ethanol group as well as the betaine group. The results of the present investigation indicated that the protective effect of betaine is probably related to its ability to strengthen the cerebellum membrane cells by enhancement of antioxidant enzyme activity principally GPx, while the methyl donor effect of betaine to reduce hyperhomocysteinemia has been explained previously and confirmed in the present study.

Nitrous Oxide Anesthesia and Plasma Homocysteine in Adolescents

Nitrous oxide inactivates vitamin B(12), inhibits methionine synthase, and consequently increases plasma total homocysteine (tHcy). Prolonged exposure to nitrous oxide can lead to neuropathy, spinal cord degeneration, and even death in children. We tested the hypothesis that nitrous oxide anesthesia causes a significant increase in plasma tHcy in children. Twenty-seven children (aged 10-18 years) undergoing elective major spine surgery were enrolled, and serial plasma samples from 0 to 96 hours after induction were obtained. The anesthetic regimen, including the use of nitrous oxide, was at the discretion of the anesthesiologist. Plasma tHcy was measured using standard enzymatic assays. The median baseline plasma tHcy concentration was 5.1 μmol/L (3.9-8.0 μmol/L, interquartile range) and increased in all patients exposed to nitrous oxide (n = 26) by an average of +9.4 μmol/L (geometric mean; 95% confidence interval, 7.1-12.5 μmol/L) or +228% (mean; 95% confidence interval, 178%-279%). Plasma tHcy peaked between 6 and 8 hours after induction of anesthesia. One patient who did not receive nitrous oxide had no increase in plasma tHcy. Several patients experienced a severalfold increase in plasma tHcy (maximum +567%). The increase in plasma tHcy was strongly correlated with the duration and average concentration of nitrous oxide anesthesia (r = 0.80; P < 0.001). Pediatric patients undergoing nitrous oxide anesthesia develop significantly increased plasma tHcy concentrations. The magnitude of this effect seems to be greater compared with adults; however, the clinical relevance is unknown.

Cobalamin Status Modifies the Effect of Zinc Supplementation on the Incidence of Prolonged Diarrhea in 6- to 30-Month-Old North Indian Children

AbstractThe observed effect of zinc supplementation on diarrheal morbidity varies between trials and there is a need to identify subgroups most likely to benefit from improved zinc nutriture. In a randomized, double-blind trial in 2296 children in New Delhi, India, we assessed whether baseline cobalamin or folate status modified the effect of zinc supplementation on the incidence of prolonged (≥7 d duration) and acute diarrhea. Children aged 6–30 mo received zinc or placebo daily for 4 mo. We measured plasma concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA) at enrollment and assessed the efficacy of zinc supplementation in subgroups based on these variables. The efficacy of zinc on reducing the risk of prolonged diarrhea was higher in those with plasma cobalamin concentrations below the 25th percentile and in those with tHcy and MMA concentrations above the 75th percentile. The OR (95% CI) for children below and above the 25th percentile for cobalamin were 0.53 (0.35–0.78) and 0.90 (0.73–1.11), respectively (P-interaction = 0.015). There were similar differences for the OR when comparing efficacy in those above and below the 75th percentile for tHcy and MMA (P-interaction = 0.045 and 0.188, respectively). Baseline folate status did not modify the effect of zinc on prolonged diarrhea. Neither cobalamin nor folate status influenced the effect of zinc on acute diarrhea. Children with poor cobalamin status benefited more from zinc supplementation for the prevention of prolonged diarrhea.

Plasma homocysteine, brain imaging and cognition in older patients with mental illness

Total plasma homocysteine (tHcy) concentration is elevated in older patients with mental illness, and patients with vascular disease have higher plasma tHcy concentration than patients without vascular disease. Plasma tHcy has been reported to be associated with cognitive functions. The mechanism by which plasma tHcy may influence cognitive functions is not clear. We have investigated the relation between plasma tHcy, brain imaging findings (computer tomography scan [CT]) and cognition, measured as Mini mental state examination (MMSE), in 395 consecutively enrolled older patients with mental illness. Age and plasma tHcy were significant predictors of MMSE score, whereas pathological CT findings, indicating cerebrovascular disease, showed no prediction of MMSE score. The relation between plasma tHcy and cognition is not mediated by cerebrovascular disease as evaluated by pathological CT findings.

Vitamin B12 and folate deficiency and elevated plasma total homocysteine in workers with chronic exposure to chromate

ObjectivesChronic occupational exposure to chromium can result in a broad range of adverse effects including multiple organ damage, genotoxicity and carcinogenesis. However, the metabolic consequences of chromium exposure have not...

Abstract 115: Correlation between homocysteine concentration in serum and response to anti-hormonal treatment in breast tumor patients

Abstract Background: Breast tumors are today the most incident tumor in women. One of the widely used markers for breast cancer is the estrogen receptor (ER), which is member of the nuclear receptor superfamily of transcription factors. Almost 70% of the breast cancer patients are ER positive and can be beneficiated with hormonal therapy. Patients with ER+ tumors are candidates for anti-hormonal therapy, including tamoxifen and anastrozol. Many studies proposed that elevated levels of total homocysteine (tHcy) in the blood can be a risk factor for cancer. It is also known that estrogen status is associated with tHcy concentration. One important epigenetic mechanism which is a well-described for carcinogenesis, and seems to be related to homocysteine pathways, is the DNA methylation. In tumors, it is well documented a decrease in total DNA methylation and a hipermethylation of specific gene promoters. There are no studies showing the impact of anti-hormonal treatment in the tHcy concentration and in the DNA methylation pattern of the breast tumor patients. Objectives: In this study we aimed to verify which is the impact of the anti-hormonal treatment in the tHcy concentration and its correlation with the clinical data. Samples and Methods: To investigate the effect of anti-hormonal therapy on homocysteine metabolism, 50 breast tumor patients were randomly assigned to therapy with anastrozol or tamoxifen or placebo. Sera from the patients were obtained before and after the treatment with anti-hormonal drugs. Homocysteine levels were determined by HPLC. Total DNA methylation was evaluated in the tumor biopsies before the treatment by restriction enzyme method. Pearson's correlation test and t test were performed for statistical analysis. Results: We observed that the tHcy before the anti-hormonal treatment increase in the patients with a high agressive tumor (p=0,0401), and with positive lifonodes (p=0,0379). After the treatment with tamoxifen, the tHcy level decreases (p=0,0263). We could observe that the decrease was significant in the patients with positive linfonodes (p=0,0400). No significant correlations were observed when the patients were treated with anastrozol or placebo and also no correlation were observed in these patients when we correlated the tHcy variation with the clinical data set. We observed a total DNA hypomethylation in the tumors before treatment when compared with adjacent tissue (p=0,0157). Conclusions and perspectives: We could observe that the higher tHcy levels are related to aggressive tumors. Our results also show that the treatment with tamoxifen, mainly in aggressive tumors, decreases the tHcy levels showing that this treatment can have a role in the tHcy level. Other clinical data and new studies should be done to evaluate the tamoxifen impact in tHcy and also its relation with the tumor DNA methylation. Financial support: Fapesp, CAPES, CNPq. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 115. doi:10.1158/1538-7445.AM2011-115

Physiologic changes in homocysteine metabolism in pregnancy: A longitudinal study in Spain

Objective The aim was to investigate whether pregnancy-induced changes in total homocysteine (tHcy) are associated with folate and vitamin B12 nutritional status, genetic C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) enzyme, and gestation outcome at a time when folic acid supplementation started to be recommended in the Spanish health system. Methods In total 154 pregnant women were recruited from among gynecologic patients of the Alcorcón Public Hospital Outpatient Clinic (Madrid, Spain). Blood tests were performed at weeks 15, 24, and 32 of pregnancy. Total Hcy, folate, and vitamin B12 serum fasting concentrations were measured using an IMx system. Genotype analyses were done by polymerase chain reaction/restriction fragment/length polymorphism analysis. Results Folate and vitamin B12 serum concentrations decreased significantly ( P < 0.01) through pregnancy and reached the lowest values in the third trimester. Serum tHcy concentrations were significantly ( P < 0.01) lower in the second trimester but increased in the third trimester. Frequencies of MTHFR C667T genotype were CC (35.7%), CT (57.2%), and TT (7.1%). Total Hcy concentration was not statistically influenced by maternal genotype. Plasma folate was the single negative predictor of maternal tHcy in the first trimester of pregnancy; 11.1% of gestations resulted in intrauterine growth restriction, 7.9% in gestational diabetes mellitus, and 4.8% in gestational hypertension. No significant differences in serum folate, vitamin B12, or tHcy concentrations were found in complicated pregnancies and these were unrelated to MTHFR genotype. Conclusion Although tHcy seems to be physiologically low in this Spanish population and unrelated to folate and B12 nutritional status, C677T MTHFR genotype, and some pregnancy complications, we support the statement that appropriate folate concentration may be important throughout pregnancy to prevent abnormalities associated with altered status (e.g., neural tube defects). According to our study, supplementation with folic acid seems to achieve this purpose because diet alone may be insufficient. In addition, a poor vitamin B12 status, as measured by plasma levels, may indicate that supplementation of both vitamins is needed.

Relationship Between Genetic Polymorphisms of Methylenetetra hydrofolate Reductase (C677T, A1298C, and G1793A) as Risk Factors for Idiopathic Male Infertility

The human methylenetetrahydrofolate reductase (MTHFR) gene plays a crucial role in folate metabolism. Data regarding the influence of MTHFR gene polymorphisms on male fertility status are scarce and conflicting. We determined associations between 3 MTHFR gene polymorphisms (C677T, A1298C, and G1793A), serum folate, and total homocysteine (tHcy) levels, with male fertility status and semen parameters. MTHFR genotypes were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique and serum tHcy, folate, and vitamin B12 concentrations were measured in 164 men with idiopathic infertility and 328 healthy participants. There was a significant difference in genotype frequency distribution of MTHFR C677T polymorphism between infertile patients and controls (P = .004). The 677T allele carriers (TC or TT) had a significantly increased risk of infertility compared with the CC homozygotes (odds ratio [OR] 1.60, 95% confidence interval [CI] 1.21-2.75, and OR = 2.68, 95% CI = 1.84-3.44, respectively), in a logistic regression model after adjustment for confounding factors. Men with the 677T, 1298C, and 1793G alleles showed significantly higher serum tHcy and lower folate levels (all Ps < .01). We found a positive correlation between serum folate concentrations and sperm density (r = .74, P = .001), percentage of sperm with progressive motility (r = .68, P = .001), as well as percentage of sperm with normal morphology (r = .72, P = .001). MTHFR C677T polymorphism is associated with an increased risk of idiopathic male infertility. Further study on the biologic role that this polymorphism plays in the development of infertility may lead to better understanding of the etiology of impaired spermatogenesis.

Oral clefts and maternal biomarkers of folate‐dependent one‐carbon metabolism in utah

Maternal folate intake and related biomarkers have been inconsistently associated with a risk of oral clefts. Maternal concentrations of plasma folate (PF) and erythrocyte folate (EF), plasma pyridoxal-5'-phosphate (PLP; active vitamin B(6) ) and total plasma homocysteine (tHcy) were measured in a Utah study with 347 cases and 469 controls. Risk of all clefts combined, including cleft lip with or without cleft palate (CL/P) and cleft palate only (CP), was 65% lower in the highest versus lowest PF quartile (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.23-0.53; p-trend < 0.001). Results remained significant in the subgroups with isolated CL/P and CP (p-trend < 0.001 in each). EF results were similar. In the highest versus lowest PLP quartile, risk of CP with other malformations was lower (OR, 0.25; 95% CI, 0.07-0.95); however, no other associations were significant for PLP or tHcy. Differences in mean biomarker levels between cases and controls widened with an increasing interval between delivery and maternal blood collection. Decreased cleft risk with increasing quartiles of PF, EF, and PLP and decreasing tHcy was more apparent in mothers with a longer versus shorter interval between the index child delivery and blood collection. Low maternal blood folate concentration was associated with an increased risk of clefts, and the differences in mean case and control PF, EF, PLP, and tHcy concentrations widened over time. Additional mechanistic studies are warranted to elucidate whether an acquired or inherited disorder of folate metabolism plays a role in the etiology of clefts.

Essential Fatty Acid Intake and Coronary Heart Disease Risk Factors Among College Students of 3 Ethnic Groups

Few studies address gender and ethnic variations in essential fatty acid (EFA) intake and risk factors for coronary heart disease (CHD). The purpose of this study was to estimate EFA intake among college students of 3 ethnic groups and compare the relationship between EFA intake and CHD risk factors. Using a cross-sectional design, 300 subjects from 3 ethnic groups--one-third (n = 100) non-Hispanic white, one-third Hispanic, and one-third non-Hispanic black-completed the Cardiovascular Risk Assessment Instruments and a Food Frequency Questionnaire to determine fatty acid intake. Measured CHD risk factors were quantified as CHD Risk Point Standards (CHDRPS). Results showed that Hispanic females had a significantly higher mean percent intake of arachidonic acid and ratio of linoleic acid to alpha-linolenic acid than non-Hispanic white females, and Hispanic males had significantly higher mean percent intake of EPA and [EPA plus docosahexaenoic acid (DHA)] than non-Hispanic white males. An inverse correlation was found between CHDRPS and DHA among non-Hispanic blacks. A significant positive correlation was found between CHDRPS and linoleic acid among non-Hispanic white females, as well as serum homocysteine (tHcy) concentrations and the ratio of linoleic acid to alpha-linolenic acid intake among non-Hispanic black females. Gender and ethnic differences play a role in adherence to dietary guidelines, demonstrating relevance for future research in this area.

Relation of body mass index to blood folate and total homocysteine concentrations in Japanese adults

Plasma folate concentrations are suggested to be negatively associated with body mass index (BMI, kg/m(2)), although these findings are controversial. Our objective was to evaluate the association of BMI with blood folate and total homocysteine (tHcy) concentrations. We measured plasma and erythrocyte folate and plasma tHcy concentrations in 434 healthy adults (343 women and 91 men; mean age of 63.8 ± 10.7 [SD, range 23-88] years), who participated in a 2007 population-based survey in western Japan. The overall mean plasma and erythrocyte folate and tHcy were 21.6 (±11.0, SD) nmol/L, 844 (±291) nmol/L and 11.6 (±3.9) μmol/L, respectively. The mean BMI was 22.8 (±3.0; 15.6-33.3) kg/m(2), and only 72 subjects (17%) had BMI > 26.0 kg/m(2). Mean plasma folate decreased as BMI increased (p-trend < 0.01), whereas mean erythrocyte folate and plasma tHcy were similar regardless of BMI (p-trends = 0.49 and 0.28, respectively). Our data indicate that the interpretation of plasma folate concentrations to assess folate nutritional status is complicated by BMI, although the impact of BMI on plasma folate was relatively small. It is important to take this association into account for the selection of subjects for future large-scale studies. The mechanism of this inverse association between BMI and plasma folate concentrations should be investigated.

A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people

Whether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear. 140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18. Trial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 μmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 μmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 μmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003). Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.

Folate, vitamin B12 and total homocysteine levels in Arab adolescent subjects: Reference ranges and potential determinants

Background & AimsElevated circulating fasting total homocysteine (tHcy) concentration is associated with an increased risk of occlusive vascular disease in adults. Important determinants of tHcy levels are folate, vitamin B12 and vitamin B6. This study aimed to investigate age, gender, and body mass as determinants of folate, vitamin B12 and tHcy levels in Arab older children and adolescents and to propose population, gender and age-specific reference ranges for these biomarkers. Methods & Results774 (316 boys, 458 girls) healthy 10–19 yr olds attending secondary schools in Kuwait were assessed for anthropometry and fasting blood levels of Hcy, folate and vitamin B12. The mean (95% CI) serum levels of tHcy, folate and vitamin B12 were respectively 6.57 μmol/L (6.42–6.73), 16.0 ng/ml (15.6–16.3) and 354.3 pg/ml (343.0–365.7). Boys had significantly higher tHcy and folate concentrations than the girls, although vitamin B12 levels were greater in the latter. Folate and vitamin B12 levels decreased significantly with age, while correspondingly, tHcy levels increased, with mean values (μmol/L) for boys (6.71; 8.25) and girls (5.36; 6.67) aged 10–14 yr and 14–19 yr respectively. Bivariate and multivariate analyses with adjustment for confounders such as age, gender, need for dietary control and socio-demographic variables indicated that the independent determinants of levels of tHcy were age, gender and body mass. ConclusionThere is an age-related increase in tHcy in adolescents reflecting decreased levels of folate and vitamin B12, with the suggestion that age-related reference ranges for these biomarkers be used. These observations may have implications for prevention of future atherogenic disease.

Effect of an antioxidant drink on homocysteine levels in Alzheimer's patients

Background A large body of evidence supports a role of oxidative stress in Alzheimer disease (AD) and in cerebrovascular disease. Blood levels of homocysteine may be increased in AD and hyperhomocysteinemia may contribute to disease pathophysiology by vascular and direct neurotoxic mechanisms. Even in the absence of vitamin deficiency, plasma total homocysteine (tHcy) concentration may be influenced by administration of polyphenols. Objective To determine the effect of an antioxidant beverage rich in polyphenols on the plasmatic levels of tHcy in Alzheimer's patients. Design, setting, and patients A multicenter, randomized, double-blind controlled clinical trial of polyphenols supplementation in 100 subjects (52 of control group, 24 AD patients in initial phase and 24 AD patients in moderate phase) (Mini-Mental State Examination scores between 14 and 26, inclusive). Fasting plasma concentrations of tHcy, folate and vitamin B 12 were measured before (Ti) and after (Tf) the ingestion of the beverage. The study was conducted at clinical research places of the Catholic University San Antonio and University Hospital Virgen de la Arrixaca of Murcia (Spain). Intervention Participants of the three groups were randomly assigned to 2 groups of the same size: 50% treated with antioxidant beverage rich in polyphenols and 50% treated with an identical placebo beverage. Subjects consumed 1 brick (200 mL/day) of antioxidant drink or placebo drink for 8 months. Results Higher tHcy levels were observed in the AD moderate phase patients (Ti:12.65 ± 1.21 μmol/L) than in the AD initial phase patients (Ti:9.13 ± 1.24 μmol/L) and in the control group (Ti:9.86 ± 0.77 μmol/L). Lower folate levels were observed in the AD moderate phase patients (Ti:8.20 ± 1.29 ng/mL) than in the AD initial phase patients (Ti:9.41 ± 1.56 ng/mL) and in the control group (Ti:12.32 ± 0.67 ng/mL). Antioxidant drink vs placebo drink attenuated the tHcy increase in the control group (Tf values of 11.74 ± 0.45 vs 15.63 ± 1.79 μmol/L) and AD patients, especially in the moderate phase (Tf: 10.49 ± 0.73 vs 16.58 ± 2.73 μmol/L). Conclusions The regular ingestion of polyphenols contained in an antioxidant beverage may decrease tHcy plasmatic concentrations in Alzheimer's patients.

The effect of folinic acid supplementation on homocysteine concentrations in newborns

The incidence of cerebrovascular accidents (CVA) occurring perinatally is relatively high and aspects of the multifactorial pathophysiology remain unclear. Elevated homocysteine concentrations have been shown to be associated with an increased risk for CVA in children and even in newborns. We studied the possible homocysteine lowering effect of folinic acid in newborns. We included 37 newborns in our prospective randomized folinic acid (given as 5-formyltetrahydrofolate) intervention study from patients admitted to our neonatal intensive care unit (18 controls, 19 intervention group). We measured total homocysteine (tHcy) and plasma folate concentrations at three time points (baseline, 1 and 2 weeks after intervention). The intervention group was treated with folinic acid (70 μg/kg/day) for 2 weeks. We calculated median concentrations (25th and 75th percentiles). Median tHcy concentrations at the three time points did not differ from each other in the control group nor in the intervention group. We also could not observe different tHcy concentrations between both groups. Plasma folate concentrations increased in the intervention group (mean increase 167% (95% confidence interval (CI) -291, 625)) compared with control group (mean increase -12% (95% CI -132, 108)), P for treatment effect: 0.03. We could not demonstrate a homocysteine lowering effect of folinic acid administration in newborns. This indicates that one carbon metabolism in newborns differs form adults. Cobalamin might be a better strategy to lower tHcy concentrations in newborns.

The transcobalamin (TCN2) 776C&gt;G polymorphism affects homocysteine concentrations among subjects with low vitamin B12 status

Methionine synthase catalyzes the conversion of 5-methyltetrahydrofolate to tetrahydrofolate and homocysteine (Hcy) to methionine using vitamin B(12) as a cofactor. Transcobalamin is the main transporter of vitamin B(12) from blood into cells. This study was undertaken to assess the relationship between the transcobalamin P259R (TCN2 776C>G) polymorphism and both serum vitamin B(12) and total Hcy (tHcy) levels. The population comprised 613 men from Northern Ireland, aged 30-49 years, for whom tHcy, serum vitamin B(12) and serum folate concentrations were available. TCN2 776C>G genotypes were determined using a TaqMan 5' nuclease Real-Time PCR assay. Standard statistical tests of association were applied to assess the relationships between the polymorphism and phenotypic variables. The TCN2 776CC homozygous genotype was associated with lower serum vitamin B(12) concentrations compared with the 776CG (P(unadjusted)=0.01; P(adjusted)=0.03) and 776GG genotypes (P(unadjusted)=0.015; P(adjusted)=0.045). Among individuals with vitamin B(12) concentrations in the lower half of the distribution, tHcy concentrations were higher in TCN2 776GG homozygotes than in individuals with the other genotypes (P(unadjusted)=0.015; P(adjusted)=0.06). These data suggest that, relative to transcobalamin with arginine at position 259 (776G), transcobalamin with proline at this position (776C) is either more efficient at vitamin B(12) transport from blood to tissues or has higher affinity for vitamin B(12). Furthermore, vitamin B(12) status influences the relationship between TCN2 776C>G genotype and tHcy concentrations. Thus, the TCN2 776C>G polymorphism may contribute to the risk of pathologies associated with a low B(12), and high tHcy phenotype.

Plasma Homocysteine and Cognition in Elderly Patients with Dementia or Other Psychogeriatric Diseases

Background: Total plasma homocysteine (tHcy) concentration is elevated in elderly patients with mental illness, and patients with vascular disease have higher plasma tHcy concentrations than patients without vascular disease. Increasing evidence indicates that vascular risk factors play a role in the development of cognitive impairment. Method: We have investigated the relation between plasma tHcy, its determinants and cognition, measured as MMSE, in 448 consecutively enrolled patients with dementia or other psychogeriatric diseases. Results: Multiple regression analyses showed that plasma tHcy was related to cognitive function in all patients as well as in demented and non-demented patients. The apparent close relationship between plasma tHcy and cognition was mainly dependent on its determinant age, whereas the other determinants of plasma tHcy exhibited a limited influence on the relation between plasma tHcy and cognition. Plasma tHcy has its own, albeit modest, relationship to cognitive function (predictive value about 5%). Conclusion: Plasma tHcy itself seems to play a minor role in cognitive impairment in patients with dementia or other psychogeriatric diseases. When investigating the relation between plasma tHcy and cognition, it is important to consider the distribution of the main determinants of plasma tHcy and to correct plasma tHcy for these variables.