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Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire , adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. Results Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. Conclusions An inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Prenatal smoke exposure (PSE) is a risk factor for adverse outcomes in the offspring, including those affecting psychological development. However, it is uncertain whether these associations are the direct result of PSE or other confounding factors. The aim of this study was to examine the possible relationship between PSE and behavioral development in children at 7.5 years of age, considering several prenatal, neonatal and postnatal covariates. A cohort of 266 mother-child pairs was followed from the first trimester of pregnancy until the children reached 7.5 years of age. PSE was assessed using a questionnaire from prenatal clinical records and corroborated by plasma cotinine determinations in the first and second trimesters and in the cord. Mother-child pairs were classified into one of four groups: unexposed, exposed to passive smoking, first trimester active smoking only and active smoking throughout pregnancy. Child behavior was assessed using the Child Behavior Checklist for ages 6–18 and the Childhood Autism Spectrum Test. In multiple linear regression models, smoking during pregnancy was associated with higher scores in affective problems (β = 0.298; p = 0.004). No significant associations were found between smoking during pregnancy and externalizing problems. Findings indicate that PSE is negatively associated with behavioral development in childhood.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18–75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism–tHcy association (β standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype–hypertension association was confined to adults aged ≤50 years.

Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce.Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads.Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys.Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight.Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Objectives: To evaluate the impact of a pharmacy-technician centered medication reconciliation (PTMR) program by identifying and quantifying medication discrepancies and outcomes of pharmacist medication reconciliation recommendations. Methods: A retrospective chart review was performed on two-hundred patients admitted to the internal medicine teaching services at Cooper University Hospital in Camden, NJ. Patients were selected using a stratified systematic sample approach and were included if they received a pharmacy technician medication history and a pharmacist medication reconciliation at any point during their hospital admission. Pharmacist identified medication discrepancies were analyzed using descriptive statistics, bivariate analyses. Potential risk factors were identified using multivariate analyses, such as logistic regression and CART. The priority level of significance was set at 0.05. Results: Three-hundred and sixty-five medication discrepancies were identified out of the 200 included patients. The four most common discrepancies were omission (64.7%), non-formulary omission (16.2%), dose discrepancy (10.1%), and frequency discrepancy (4.1%). Twenty-two percent of pharmacist recommendations were implemented by the prescriber within 72 hours. Conclusion: A PTMR program with dedicated pharmacy technicians and pharmacists identifies many medication discrepancies at admission and provides opportunities for pharmacist reconciliation recommendations.

Compromised cobalamin status during pregnancy may put both mother and child at risk of deficiency during lactation and subsequent development. We investigated whether changes in cobalamin status during pregnancy are associated with impaired status in the mother and the cord. Plasma cobalamin, methylmalonic acid (MMA), and holotranscobalamin (holoTC) concentrations were determined in 92 women at preconception, 8, 20, and 32 wk of pregnancy, at labor, and in the cord. All variables [geometric mean percentiles 10, 90 (P(10), P(90))] were significantly reduced from preconception [cobalamin: 293 (155, 535) pmol/L; holoTC: 63 (38,98) pmol/L; MMA: 0.12 (0.09, 0.17) micromol/L] by 20 wk of pregnancy [cobalamin: 230 (123, 432) pmol/L; holoTC: 48 (34,78) pmol/L; MMA: 0.11 (0.08, 0.15) micromol/L P < 0.001]. Plasma cobalamin and holoTC remained lower throughout the remainder of pregnancy [32 wk: 198 (107, 339); labor: 224 (117, 444); P < 0.001] and [32 wk: 45 (26,82); labor: 40 (23,79); P < 0.05], respectively. By 32 wk, MMA was greater than preconception [0.14 (0.09, 0.20) micromol/L; P < 0.01]. Plasma holoTC at 32 wk and at labor was negatively correlated with cord MMA (r = -0.51, P < 0.001 and r = -0.40, P < 0.01, respectively). Women with lower holoTC at preconception had greater increases in MMA at 32 wk and at labor. Maternal MMA at 32 wk and at labor was significantly and independently associated with cord MMA only in women with lower holoTC at preconception (regression models: R(2) = 0.707, 0.682, respectively; P < 0.01). The moderate increases observed in the cobalamin biomarker, MMA, during pregnancy may indicate a functional depletion in intracellular cobalamin status.

Total fasting plasma homocysteine (tHcy) is significantly reduced during early–mid normal pregnancy. Elevated tHcy during or outside of pregnancy has been associated with adverse pregnancy outcomes, affecting either the fetus or the evolution of the pregnancy. Examples of direct adverse effects on the fetus are neural tube defects, Down’s syndrome, congenital heart defects and intrauterine growth retardation. Both fetal and maternal wellbeing can be affected by other adverse outcomes reported to be associated with elevated tHcy, such as recurrent spontaneous abortion, pre-eclampsia or placental vasculopathy. To date, endothelial activation of the placental vascularization system, apoptosis, toxicity and stimulation of uterine contractions have been proposed as possible modes of adverse action of homocysteine. The strength of the clinical evidence for a pathological role of elevated homocysteine in the evolution of pregnancy is examined in this review.

This cross-sectional study evaluated the association between daily calcium intake and body mass index (BMI) in 647 subjects from Reus, Spain. 261 men and 313 women, aged 18 to 70 years, were randomly selected from the population census. Food intake was quantified by the 24-hour recall method, for three non-consecutive days including one holiday. Weight and height were measured. The study sample was divided into quartiles of calcium intake adjusted for age, energy, and total fat and fiber intake in both men and women. Average calcium intake was low (557.6 ± 234.0 mg/day). Calcium intake was significantly (p < 0.0001) and positively associated with energy intake (r = 0.50 for men; r = 0.49 for women; p < 0.0001) and dietary fiber consumption (r = 0.27 for men; r = 0.25 for women; p < 0.0001). After adjusting for age, energy intake, fat intake, and dietary fiber, the odds ratio of being in the highest quartile of BMI was significantly reduced in the highest quartile of calcium intake [men: 0.63 (0.30–1.29); women: 0.36 (0.17–0.79)] compared to the lowest quartile in both sexes. We conclude that our study showed a negative relationship between calcium intake and BMI in a Mediterranean community.

Periconception supplementation with folic acid is recommended until 12 gestational weeks to prevent neural tube defects. Doses of folic acid contained in supplements and timing and length of use during pregnancy vary. The effects of status in periconception and pregnancy folate, cobalamin, betaine and their interactions on one carbon metabolism (1C), as well as the global effect of 1C on foetal growth and pregnancy outcome, are reviewed. Results from prospective studies are reviewed. Cessation of folic acid supplement use after the first trimester is associated with a sharp drop in plasma folate status and enhanced conversion of betaine to dimethylglycine. Dimethylglycine production is also higher in mothers with low folate status than in those with normal-high folate status. The effects of high doses of folic acid on one carbon metabolism in mothers with low early pregnancy cobalamin status and on foetal growth are also reviewed. Several studies report that moderately elevated early pregnancy fasting plasma total homocysteine (tHcy) is inversely associated with birth weight and a predictor of intrauterine growth retardation. There is also evidence for increased risk of preterm birth when maternal folate status is low.

BACKGROUND Although combinations of biologically relevant polymorphic variants affect folate status, most studies have focused on the effects of individual polymorphisms; however, these effects may be altered by interactions between polymorphisms. OBJECTIVE We investigated the individual and combined effects of polymorphisms that affect folate transport or metabolism on folate status. METHODS The associations between the methylenetetrahydrofolate reductase (MTHFR) 677C > T, methionine transferase reductase (MTRR) 66A > G, MTRR 524C > T, 5,10-methylenetetrahydrofolate dehydrogenase-5,10-methylenetetrahydrofolate cyclohydrolase-10-formyltetrahydrofolate synthetase (MTHFD1) 1958G > A, MTHFD1 -105C > T, dihydrofolate reductase (DHFR) 19-bp insertion/deletion, and solute carrier family 19A, member 1 (SLC19A1) 80G > A polymorphisms and fasting plasma folate (PF), red cell folate (RCF), and plasma total homocysteine (tHcy) were tested by ANCOVA and Cox regression analysis in 781 Spanish adults. RESULTS Folate deficiency (PF

Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother–child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2–10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected. Psychomotor and mental development were assessed at 4 months using the Bayley Scale of Infant Development (BSID) and cognitive development at 6 years using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Highest tertile preconception tHcy (≥9.04 µmol/L) was categorized as moderately elevated and low‐mid tertile tHcy as normal. Children, born to mothers with moderately elevated compared to normal preconception tHcy, scored lower [mean (95% CI)] in the BSID psychomotor [115 (105, 124) vs. 126 (121, 130), p = 0.03] and mental [101 (93, 109) vs. 113 (107, 119), p = 0.03] development tests. Multiple logistic regression analysis showed that moderately elevated compared to normal preconception tHcy was associated with greater probability, OR (95%CI), of scoring in the lowest tertile for BSID psychomotor development (≤120): 4.0 (1.1, 14.3) and lowest tertiles for WPPSI full (≤111), verbal (≤104) and performance (≤111), intellectual quotient: 6.0 (1.5, 23.7), 3.5 (1.1, 11.2) and 4.1 (1.1, 15.7), respectively. We conclude that moderately elevated preconception tHcy is inversely associated with psychomotor and cognitive development scores in infants and children.

It has been suggested that total plasma homocysteine (tHcy) concentrations and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms are risk factors for schizophrenia. We conducted a case-control study to investigate whether tHcy levels and MTHFR C677T and A1298C variants are associated with schizophrenia, giving special consideration to confounding factors. Logistic regression analysis showed that neither tHcy nor MTHFR polymorphisms were associated with schizophrenia. Homozygosity for MTHFR C677T was associated with higher tHcy concentrations in control and schizophrenia groups (P

C-reactive protein (CRP) has been proposed as an independent risk factor for cardiovascular disease. In this study we sought to investigate the association between several nutritional and lifestyle factors and serum CRP concentration in a population-based study. We studied 359 individuals (172 women, 187 men; age range 18-75 years) randomly selected from the town hall's registers and assessed their daily dietary intake using a 3-day estimated-food record. The median serum CRP concentration was 1.40 mg/L (range0.10-47.48 mg/L; geometric mean 1.20 mg/L). We noted significant and independent direct associations between CRP and age, body-mass index, female sex, and serum triglyceride concentration. Bivariate analysis showed a significant inverse association between CRP and many nutrients (e.g., carbohydrates, proteins, lipids, thiamine, pyridoxine, tocopherol, and folate), but multiple-regression analysis indicated that only the effect of dietary folate intake was not dependent on other factors. Differences in folate intake did not produce changes in plasma homocysteine concentration, and we detected no negative correlation between dietary folate intake and log homocysteine (r = .02, P = .711). Strong positive correlations between the intake of folate and numerous other nutrients were found. This population-based study shows that a higher folate intake, in addition to other known constitutive and lifestyle factors, is significantly associated with a lower serum CRP concentration.

One carbon metabolism is fundamental in providing sufficient methionine for optimal foetal development and pregnancy outcome. The methionine synthase (MS) and betaine:homocysteine methyltransferase (BHMT) pathways intersect in the methionine cycle and are key determinants of methionine synthesis. Folate and cobalamin drive the MS pathway and betaine, dietary or as a result of choline oxidation, drives the BHMT pathway. Cell, animal and human studies consistently show that these pathways interact. Globally, methionine synthesis depends initially on the MS pathway, but growing evidence shows that the BHMT pathway is stimulated or at least enhanced when the MS pathway is performing suboptimally or is metabolically stressed. This has been observed in developing embryos, in adults subjected to a methionine load test, in adults with suboptimal status in folate or other B vitamins and during pregnancy. BHMT activity, both in the mother and in the fetus, increases as pregnancy progresses and is greater when folate status is low. The converse applies when folate status is replete and betaine is spared. The phosphatidylethanolamine N-methyltransferase pathway for phosphatidylcholine synthesis is preferred over choline usage by the choline oxidation pathway during pregnancy.

Background: Fasting plasma total homocysteine (tHcy) decreases during pregnancy. Previous reports suggested that this is due to folic acid supplementation, hemodilution, or a decrease in albumin. However, these hypotheses have not been tested in a longitudinal study. Objective: We investigated the relation between pregnancyrelated physiologic changes and tHcy in a group of healthy women who were either unsupplemented or supplemented with folic acid. Design: In a longitudinal study from preconception throughout pregnancy, we studied 54 unsupplemented women and 39 women who were supplemented with folic acid during the second or third trimester of pregnancy. tHcy, hematocrit, and serum albumin were determined preconceptionally and at 8, 20, and 32 wk of pregnancy. Results: For the entire group, geometric mean tHcy concentrations at preconception (8.2 � mol/L) were significantly greater (P < 0.001) than those at 8 wk of pregnancy (6.4 � mol/ L). When the unsupplemented and supplemented groups were regarded separately, geometric mean tHcy concentrations at preconception were significantly greater than those at 20 (5.22 and 4.18 � mol/L, respectively) and 32 (5.16 and 4.42 � mol/L, respectively) wk of pregnancy (P < 0.001 for both). Mean reductions from preconception concentrations at 8, 20, and 32 wk of pregnancy were significantly greater (P < 0.001) for tHcy (� 11.5%, � 25.5%, and � 24.5%, respectively) than for hematocrit (� 1.9%, � 4.2%, and � 4.3%, respectively) or serum albumin (� 1.1%, � 9.8%, and � 13.4%, respectively). There was no correlation between changes in either hematocrit or serum albumin and changes in tHcy. Conclusions: This study refutes the previous explanations for the reduction in plasma tHcy known to occur in pregnancy, namely, folic acid supplementation, hemodilution, and a decrease in serum albumin. We suggest that the changes may be endocrine-based. Am J Clin Nutr 2002;76:614‐9.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), riboflavin-dependent enzymes, participate in homocysteine metabolism. Reported effects of riboflavin status on the association between the MTHFR 677C>T polymorphism and homocysteine vary, and the effects of the MTRR 66A>G or MTRR 524C>T polymorphisms on homocysteine are unclear. We tested the hypothesis that the effects of the MTHFR 677C>T, MTRR 66A>G and MTRR 524C>T polymorphisms on fasting plasma total homocysteine (tHcy) depend on riboflavin status (erythrocyte glutathionine reductase activation coefficient, optimum: G polymorphism and tHcy (p for interaction: 0.034). tHcy was 6.6 % higher in MTRR 66G allele carriers compared to the 66AA genotype with marginally deficient or optimal riboflavin status, but there was no difference when riboflavin status was deficient (p for interaction: 0.059). tHcy was 13.7 % higher in MTRR 524T allele carriers compared to the 524CC genotype when cobalamin status was low (p T polymorphism on tHcy depends on riboflavin status, that of the MTRR 66A>G polymorphism on cobalamin and riboflavin status and that of the MTRR 524C>T polymorphism on cobalamin status.

BACKGROUND Folate, choline, and betaine participate in homocysteine metabolism. It is not known whether they interact during pregnancy. OBJECTIVE The objective was to investigate how folate status affects choline, betaine, and dimethylglycine during pregnancy. DESIGN Fasting plasma folate, cobalamin, free choline, betaine, dimethylglycine, and total homocysteine (tHcy) were measured longitudinally at

Background DNA methylation is an epigenetic phenomenon that can modulate gene function by up or downregulation of gene expression. Vitamin B12 and folate pathways are involved in the production of S-Adenosylmethionine, the universal methyl donor. Findings Brain vitamin B12 concentration and global DNA methylation was determined in transcobalamin receptor (TCblR/CD320) knock out (KO) (n = 4) and control mice (n = 4) at 20–24 weeks of age. Median [IQR] brain vitamin B12 concentrations (pg/mg) in TCblR/CD320 KO mice compared with control mice was 8.59 [0.52] vs 112.42 [33.12]; p CD320 KO compared with control mice (Median [IQR]: 0.31[0.16] % vs 0.55[0.15] %; p Conclusions In TCblR/CD320 KO mice, brain vitamin B12 drops precipitously by as much as 90% during a 20 week period. This decrease is associated with a 40% decrease in global DNA methylation in the brain. Future research will reveal whether the disruption in gene expression profiles due to changes in DNA hypomethylation contribute to central nervous system pathologies that are frequently seen in vitamin B12 deficiency.

The objective of this research was to study whether positive and negative maternal emotional states were related to obstetrical outcomes in 205 women who participated in a study conducted between 2004 and 2007 in the Sant Joan University Hospital of Reus, Spain. Maternal anxiety and positive emotional states were assessed using the State Trait Anxiety Inventory. The obstetrical outcomes of interest were gestational age at birth, birth weight, and mode of delivery. More women with lower anxiety levels and a more positive state of mind had normal deliveries. Anxiety was related to lower birth weight and to difficult delivery. A positive state of mind and emotional stability were associated with having a normal delivery. Therefore, moderate levels of anxiety were associated with complications during delivery and poorer fetal outcomes, whereas a positive state of mind was associated with better childbirth experiences.

The aim of this review is to evaluate the evidence for and against fasting plasma total homocysteine (tHcy) as a biomarker/risk factor of impaired reproductive function before and during pregnancy. Apart from nutritional and lifestyle factors, tHcy is also influenced by physiological factors specific to pregnancy such as hemodilution, increased glomerular filtration rate, and endocrinological changes. These lead to a considerable reduction under normal circumstances in tHcy by midpregnancy. Stimulating excess endogenous homocysteine production before and during pregnancy in animal experiments and adding exogenous homocysteine to cell cultures result in the impairment of reproductive and developmental processes from preconception throughout pregnancy and during subsequent development of the offspring. Different studies have confirmed that elevated tHcy is a risk factor for subfertility, congenital developmental defects, preeclampsia, and intrauterine growth retardation. There is conflicting evidence that elevated tHcy is a risk factor for miscarriage, gestational diabetes, premature rupture of the membranes, placental abruption, and offspring with Down syndrome. Prospective, sufficiently powered, studies from preconception/early pregnancy are required to determine whether tHcy is a risk factor for these pregnancy complications.

Cobalamin deficiency can lead to several adverse health consequences: folate trapping in the methylation cycle and subsequent impaired DNA biosynthesis; pernicious anemia hematologically, similar to that caused by folate deficiency; elevated blood homocysteine (tHcy) (risk factor for cardiovascular disease and adverse pregnancy outcomes); and neural tube defects (NTDs). Population-wide folate status is expected to improve where folic acid fortification policies for reducing NTD occurrence are established. However, there is concern that cobalamin deficiency and its characteristic neuropathy could be masked when hematological abnormalities in risk groups such as the elderly and vegetarians are reversed through folic acid supplementation. Folate-cobalamin interactions and their impact on health are reviewed here.

Folate receptor (FR)-blocking autoantibodies (FR-autoantibodies) have been reported in women with neural tube defect-affected pregnancies and subfertility and in children with progressive neurodevelopment disorders. We investigated their prevalence and association with folate status and milk intake in adults unexposed to folic acid fortification. A cross-sectional study of a randomly selected representative sample of a Spanish population (aged 18-75 y) stratified by age and gender was performed. Plasma and red cell folate, plasma cobalamin, fasting plasma total homocysteine (tHcy) concentration, methylenetetrahydrofolate reductase C677T polymorphism, and FR-autoantibody titer were determined in blood samples from 787 fasting participants. Lifestyle data were collected and milk intake estimated from a 3-d dietary record. FR-autoantibody prevalence was 7.2% [0.30 +/- 0.27 nmol (mean +/- SD) FR blocked/L], equally affecting men and women of all ages. Plasma and red cell folate and tHcy did not differ between carriers and noncarriers of FR-autoantibodies. Milk intake was higher in carriers (225 +/- 199 g/d) than in noncarriers (199 +/- 147 g/d) (P0.01). The risk of having FR-autoantibodies increased progressively with increasing quintile of milk intake and was significant in the highest quintile (or =307 g/d) compared with the lowest (or =67 g/d) [odds ratio (OR), 2.41 [95% CI: 1.02, 5.69]; P0.05; linear trend, P = 0.02]. We concluded that FR-autoantibodies occur in men and women of all ages and do not affect indicators of folate status such as plasma and red cell folate and tHcy. Higher milk intake is associated with increased risk of having FR-autoantibodies.

The association between blocking folate receptor (FR) autoantibodies and subfertility was investigated in a longitudinal study of women attempting to become pregnant. Seventeen women with subfertility (failure to conceive during 12 menstrual cycles) and 25 control women (women who conceived and went on to have normal pregnancy outcomes) were studied. Subfertility risk was 12 times higher in women with blocking FR autoantibodies compared with those without (odds ratio, 12; 95% confidence interval, 1.9-129.6).

Inflammation is one of the recognised mechanisms involved in the development of atherosclerotic plaque and insulin resistance. Inflammatory or endothelial markers such as C-Reactive Protein (CRP), Interleukin-6 (IL-6), fibrinogen, Vascular Cell Adhesion Molecule-1 (VCAM-1) and Intracellular Adhesion Molecule-1 (ICAM-1) have been identified as independent predictors of cardiovascular disease (CVD) or diabetes in human prospective studies. Epidemiological and clinical studies suggest that some dietary factors, such as n-3 polyunsaturated fatty acids, antioxidant vitamins, dietary fiber, L-arginine and magnesium may play an important role in modulating inflammation. The relationship observed between frequent nut consumption and the reduced risk of cardiovascular mortality and type 2 diabetes in some prospective studies could be explained by the fact that nuts are rich in all of these modulator nutrients. In fact, frequent nut consumption has been associated with lower concentrations of some peripheral inflammation markers in cross-sectional studies. Nut consumption has also been shown to decrease the plasma concentration of CRP, IL-6 and some endothelial markers in recent clinical trials.

Prenatal methyl donor deficiency leads to homocysteine accumulation in the brain and impaired neurodevelopment in rats. We investigated the effect of moderately elevated preconception fasting total plasma homocysteine (tHcy) on child neurodevelopment in a prospective study of 67 and 76 mother-child pairs at 4 months and 6 years of age, respectively. Fasting blood samples at 2-10 weeks preconception, from the cord (nonfasting) and the mother and child 6 years after birth, were collected. Psychomotor and mental development were assessed at 4 months using the Bayley Scale of Infant Development (BSID) and cognitive development at 6 years using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI). Highest tertile preconception tHcy (≥9.04 µmol/L) was categorized as moderately elevated and low-mid tertile tHcy as normal. Children, born to mothers with moderately elevated compared to normal preconception tHcy, scored lower [mean (95% CI)] in the BSID psychomotor [115 (105, 124) vs. 126 (121, 130), p = 0.03] and mental [101 (93, 109) vs. 113 (107, 119), p = 0.03] development tests. Multiple logistic regression analysis showed that moderately elevated compared to normal preconception tHcy was associated with greater probability, OR (95%CI), of scoring in the lowest tertile for BSID psychomotor development (≤120): 4.0 (1.1, 14.3) and lowest tertiles for WPPSI full (≤111), verbal (≤104) and performance (≤111), intellectual quotient: 6.0 (1.5, 23.7), 3.5 (1.1, 11.2) and 4.1 (1.1, 15.7), respectively. We conclude that moderately elevated preconception tHcy is inversely associated with psychomotor and cognitive development scores in infants and children.

The aim of this study was to investigate the longitudinal changes in serum paraoxonase-1 (PON1) activity from preconception throughout normal pregnancy and their relationships with maternal dietary vitamin C and E intake. The study was performed in 35 women (studied at preconception, at 8, 20 and 32weeks of pregnancy, and at labour). PON1 activity decreased significantly from 145.8 (109.8–198.8) U/L at preconception to 111.1 (85.3–179.9) U/L (pClin Chem Lab Med 2006;44:880–2.

C-Reactive protein has been associated with several complications of pregnancy. The aims of the present study were: (1) to evaluate a turbidimetric immunoassay for the measurement of C-reactive protein; and (2) to investigate the chronological changes of the levels of this protein from preconception throughout normal pregnancy and its relationship with variables associated with preconception and pregnancy outcome. Inter-assay imprecision was 1mg/L and 18% at a mean value of 0.33mg/L. The limit of detection was 0.10mg/L. The method was linear between 0.10 and 30mg/L. There were no observed interferences from jaundice, hemolysis, lipemia or paraproteinemia at the levels studied. There was good agreement with the nephelometric method. A total of 39 women were studied at preconception, at 8, 20 and 32weeks of pregnancy, and in labor. Preconception C-reactive protein concentration was 1.17±0.18mg/L and increased (p

PUBLISHED, BACKGROUND: Increased homocysteine has been associated with pregnancy complications. METHODS: We investigated prospectively the effect of maternal homocysteine on normal pregnancy outcome. The study included 93 women and their offspring; 39 of the women took folic acid during the second and/or third trimesters of pregnancy. We measured homocysteine at preconception; at weeks 8, 20, and 32 of pregnancy; during labor; and in the fetal cord; we also recorded birth weight. RESULTS: Geometric mean (SE) maternal total homocysteine (tHcy) increased between 32 weeks of pregnancy and labor [7.98 (1.05) micromol/L in unsupplemented women and 6.26 (1.07) micromol/L in supplemented women; P, This study was supported financially by the Comision Interministerial de Ciencia y Tecnologia (Grant CICYT:ALI 89-0388), Fondo de Investigacion Sanitaria (Grant FIS:00/0954), Instituto de Salud Carlos III, RCMN (Grant C03/08; Madrid, Spain), EU Demonstration Project BMH 4983549, and Abbott GmbH (Weisbaden-Delkenheim, Germany).

This study measured the response of deoxypyridinoline, a biomarker of bone resorption, during 11 weeks of Marine recruit training.Urine samples were obtained from 155 female and 58 male Marine recruits from the first morning void every 3 days during training. Training miles of weight-bearing exercise were recorded daily, and injury data were obtained from the medical clinic staff.Deoxypyridinoline was significantly (p0.001) increased at week 2 and weeks 9 through 11 for women and at weeks 10 and 11 for men. The increase in bone resorption corresponded to an increase in miles of weight-bearing exercise performed throughout training. The incidence of stress fracture and reaction was 3.9% and 14.8%, respectively, for women and 1.7% and 3.4%, respectively, for men.Significant bone resorption took place at the end of Marine recruit training due to accumulation of weight-bearing exercise throughout training and the increase in marching toward the end.

Background: Paraoxonase may protect lipoproteins and cell membranes from peroxidation, and alterations in the activity of this enzyme have been associated with some chronic diseases. Serum paraoxonase appears to be mainly under genetic control, but some studies suggest that environmental factors may also modulate its activity. The aim of the present study was to investigate whether diet and lifestyle affect serum paraoxonase activity.Methods: We studied a population-based sample of 388 individuals (194 women and 194 men; age range, 18–75 years) and assessed their daily dietary intake using a 3-day estimated food record. The variables studied included serum paraoxonase activity, paraoxonase polymorphisms at positions 55 and 192, age, gender, smoking status, physical exercise, body mass index, energy consumption, nutrient intake (total lipids, saturated fatty acids, β-carotenes, vitamins C and E), and serum lipid concentrations.Results: Multiple linear regression analysis showed that only genetic polymorphisms, serum cholesterol, HDL-cholesterol concentrations, and cigarette smoking were significant predictors of serum paraoxonase activity. HDL-cholesterol concentrations were also related to body mass index, daily energy consumption, and saturated fatty acid intake.Conclusions: The between-individual variability of serum paraoxonase activity is regulated mainly by genetic determinants. Although HDL-cholesterol and tobacco smoking may contribute to the modulation of this enzyme, the other nutritional and lifestyle factors do not seem to play a significant role.

Homocysteine (Hcy)-induced vascular impairment may be partially mediated by the production of Hcy thiolactone (HTL). This compound acylates side-chain lysine groups in proteins and alters protein structure and function. HTL is formed under conditions of high Hcy resulting from insufficient remethylation of Hcy to methionine; however, HTL is not a reliable marker of plasma total Hcy (tHcy). In healthy volunteers, it contributes only 0.14%–0.28% of tHcy, has a half-life of 1 h, and is below the detection limit in approximately one half of volunteers (1). Paraoxonase 1 (PON1) is a hydrolase associated with HDL that is thought to degrade lipid peroxides and HTL (2). Decreased PON1 activity has been associated with atherosclerosis (3). Hepatic expression of the PON1 gene is down-regulated in hyperhomocysteinemic mice (4); it is plausible, therefore, that the proatherogenic effects of Hcy may involve diminished serum PON1 activity, leading to impaired antioxidant function and …

Plasma homocysteine (tHcy) is a marker of folate or cobalamin deficiency states (1) and a risk factor for cardiovascular diseases (2), and is altered by renal insufficiency (3). Increased tHcy in liver diseases may also play a role in hepatic disorders (4)(5). Chronic treatment of experimental animals with ethanol or CCl4 is associated with hyperhomocysteinemia, and the hepatoprotective effect of S -adenosylmethionine on experimental cirrhosis is accompanied by a normalization of methionine metabolism and a decrease in tHcy concentration (4)(5). Studies in cultured hepatocytes suggest a role of the liver in metabolism of Hcy (6). However, the presence and degree of hyperhomocysteinemia in patients with liver disease and its modulation by chronic alcohol intake are, as yet, not well defined. We studied 76 patients with liver cirrhosis (55 men and 21 women; age range, 57 ± 11 years) who were being treated in the outpatient clinic of Hospital Universitari de Sant Joan. The diagnosis of cirrhosis was based on liver biopsy or on clinical evidence, including echography to evaluate splenomegaly and portal vein dilation and fiber-optic gastroscopy to detect the presence of gastroesophageal varices. The etiology of cirrhosis was alcoholic in 48 patients (63%) and nonalcoholic in 28 (37%). Twenty-nine …