Blood Folate Research Articles

Maternal B vitamin status in pregnancy week 18 according to reported use of folic acid supplements.

Epidemiological studies on the association between pregnancy outcomes and use of periconceptional folic acid are often based on maternal reported intake. Use of folic acid during pregnancy is associated with a higher socioeconomic status known to have an impact on diet quality. We have studied plasma B vitamin status according to reported use of folic acid supplements during the periconceptional period in Norwegian women. Plasma levels of folate, cobalamin, pyridoxal 5'-phosphate (vitamin B6), riboflavin, and the metabolic markers total homocysteine, methylmalonic acid and 3-hydro-xykynurenine were measured in pregnancy week 18 and related to reported intake of folic acid from 4 weeks prior to conception throughout week 18 in 2911 women from the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Being a folic acid user during the periconceptional period was associated with a better socioeconomic status, and a higher intake of several micronutrients, including vitamins, trace-metals, and omega 3 fatty acids. Folic acid users had a significantly better plasma B vitamin status. Epidemiological data based on maternal reported intake of folic acid supplements during pregnancy, should take into account the numerous nutritional implications, in addition to higher blood folate levels, of being a folic acid user.

Homocysteine, folate and pregnancy outcomes

The purpose of this study is to evaluate the relationship between maternal and/or cord blood folate/homocysteine concentrations and adverse pregnancy outcomes. The study population included a random sample of singleton pregnant women in whom we measured total homocysteine and folic acid in maternal or cord blood at deliveries. A total of 227 pregnant women were enrolled. The concentration of folate in maternal blood tended to be significantly lower in pre-term birth than in full-term delivery group (median (95% CI), 14.4 (3.6–73) vs 25 (7.3–105.5) p < 0.01). The total homocysteine in maternal and cord blood was significantly higher in the pre-eclampsia than in the normotensive group (7.9 (1.7–28.2) vs 5.9 (1.8–14.6) μmol/ml, p < 0.05; and 5.8 (2.6–14.4) vs 4.2 (0.7–7.9) ng/ml, p < 0.05, respectively). Lower maternal serum folate concentration is associated with pre-term delivery and higher maternal plasma homocysteine concentration with pre-eclampsia.

Relative Distribution of Folate Species Is Associated with Global DNA Methylation in Human Colorectal Mucosa

Folate exists as functionally diverse species within cells. Although folate deficiency may contribute to DNA hypomethylation in colorectal cancer, findings on the association between total folate concentration and global DNA methylation have been inconsistent. This study determined global, LINE-1, and Alu DNA methylation in blood and colon of healthy and colorectal cancer patients and their relationship to folate distribution. Blood and normal mucosa from 112 colorectal cancer patients and 114 healthy people were analyzed for global DNA methylation and folate species distribution using liquid chromatography tandem mass spectrometry. Repeat element methylation was determined using end-specific PCR. Colorectal mucosa had lower global and repeat element DNA methylation compared with peripheral blood (P < 0.0001). After adjusting for age, sex and smoking history, global but not repeat element methylation was marginally higher in normal mucosa from colorectal cancer patients compared with healthy individuals. Colorectal mucosa from colorectal cancer subjects had lower 5-methyltetrahydrofolate and higher tetrahydrofolate and formyltetrahydrofolate levels than blood from the same individual. Blood folate levels should not be used as a surrogate for the levels in colorectal mucosa because there are marked differences in folate species distribution between the two tissues. Similarly, repeat element methylation is not a good surrogate measure of global DNA methylation in both blood and colonic mucosa. There was no evidence that mucosal global DNA methylation or folate distribution was related to the presence of cancer per se, suggesting that if abnormalities exist, they are confined to individual cells rather than the entire colon.

Comprehensive quantitative measurement of folate polyglutamates in human erythrocytes by ion pairing ultra‐performance liquid chromatography/tandem mass spectrometry

The erythrocyte folate pool is reflective of an individual's long-term folate status; however, comprehensive quantitative determination of the various folate isoforms including polyglutamation (Glu(n)) status has posed an analytical problem. Factors complicating such analysis are the absence of authentic (isotope-labeled) standards and the large number of potential analytes. The present work presents high-throughput analytical methodology for the indirect comprehensive quantitation of the erythrocyte folate pool with commercially available standards. The erythrocyte folate pool was determined comprehensively by utilizing a cascade of three complementary ultra-performance liquid chromatography (UPLC) tandem mass spectrometry (MS/MS) assays. In a first assay utilizing ion-pairing UPLC/MS/MS the relative (%) polyglutamation distribution (Glu(3-10)) of 5-methyltetrahydrofolate, tetrahydrofolate and 5-formyltetrahydrofolate is determined in a thermal extract obtained from packed erythrocytes, not requiring analytical standards. Quantitation of the erythrocyte folate pool was accomplished by performing two additional stable isotope dilution UPLC/MS/MS assays to determine whole blood and plasma folate content, utilizing commercially available [(13)C(5)]-labeled analogs of the Glu(1) analytes. Based on the values provided by each individual assay the comprehensive erythrocyte folate content could be calculated. The various assays have been validated for intra- and inter-run precision, accuracy, linearity and are robust. The method was sensitive enough to measure the comprehensive erythrocyte folate distribution in a Down's syndrome patient with extremely low folate, bearing the C677T mutation in the gene encoding for methylenetetrahydrofolate reductase. The erythrocyte folate pool can be comprehensively quantitated by running three complementary UPLC/MS/MS assays. The present assays are robust and allow for high-throughput analysis. The method can be utilized to support larger investigations that investigate the relationship between folate isoform and polyglutamation distribution and disease pathogenesis.

Serum Folate and Depressive Symptoms Among Japanese Men and Women: A Cross-Sectional and Prospective Study

Although several studies have reported an association between blood folate concentrations and depressive symptoms, few studies have prospectively examined the association. This study aimed to investigate the cross-sectional and prospective associations between serum folate concentrations and depressive symptoms among Japanese. We analysed data among 545 subjects who participated in a health survey at the time of periodic check-up in 2009 for a cross-sectional association and among 272 subjects without depressive symptoms at baseline (in 2006) who responded to both baseline (2006) and follow-up (2009) surveys for prospective association. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. In a cross-sectional analysis, serum folate concentrations were significantly associated with a decreased prevalence of depressive symptoms (CES-D scale of ≥16). Moreover, serum folate concentrations at baseline were significantly inversely associated with depressive symptoms after 3 years; the multivariate-adjusted odds ratios (95% confidence intervals) of depressive symptoms for the lowest through highest tertile categories of serum folate concentrations were 1.00 (reference), 0.66 (0.29–1.52) and 0.40 (0.16–0.99) (P for trend=0.047). Our findings suggest that a higher serum folate may be associated with decreased risk of depressive symptoms in Japanese.

The Good SHP2 Association

In this issue of the Journal, Goodship and colleagues report results from an association study for common genetic variants underlying tetralogy of Fallot (TOF).1 By studying a limited number of single-nucleotide polymorphisms (SNPs) tagging haplotypes at 22 candidate genes, they associated a single SNP at a chromosome 12 locus harboring PTPN11 , which encodes the protein tyrosine phosphatase SHP2, and other genes with TOF. This SNP was calculated to have a per-allele risk of 1.34 and a population-attributable risk of roughly 5%. If this study, undertaken with British white subjects, can be replicated in additional populations, it will represent a significant advance in our understanding of the genetics of congenital heart defects (CHD). Article see p 287 The genetic architecture of CHD has been the source of considerable debate and uncertainty. It has been known for some time that chromosomal defects and single-gene mutations can cause CHD, often in the context of a multisystem disease. For TOF, examples include trisomy 21 and TBX5 point mutations underlying Down and Holt-Oram syndromes, respectively.2 The discovery of 22q11 microdeletions, usually arising de novo, added significantly to our understanding of the genetic underpinnings of conotruncal forms of CHD, as these account for substantial percentages of some cardiac lesions (eg, 34% of truncus arteriosus and 16% of TOF).3 Nonetheless, these known genetic causes of CHD are estimated to account for less than 20% of cases overall. Epidemiological studies of CHD have strongly pointed to genetic factors as the predominant cause, although environmental exposures are also relevant. Parental consanguinity significantly increases the risk of CHD in offspring, probably as the result of the shared genetic background of unaffected parents.4 In countries where consanguineous marriages are customary, the rates of consanguinity are 2- to 3-fold higher among couples with offspring with CHD than …

Folate degradation due to ultraviolet radiation: possible implications for human health and nutrition

Folate is essential for human health in the prevention of megaloblastic anemia and neural tube birth defects and plays important roles in cardiovascular disease and cancer. Therefore, research into environmental factors that may impact folate status, such as solar ultraviolet (UV) radiation, is of great health significance. In vitro studies have shown that UV radiation can degrade folate and folic acid in human blood and this has been confirmed in several human studies. Despite these findings, there is a dearth of epidemiological research into investigating the relationship between folate status and the links to solar UV exposure.

Estimation of Trends in Serum and RBC Folate in the U.S. Population from Pre- to Postfortification Using Assay-Adjusted Data from the NHANES 1988–20101–3

The NHANES has monitored folate status of the U.S. population from prefortification (1988–1994) to postfortification (1999–2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999–2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.

Changes in Measurement Procedure from a Radioassay to a Microbiologic Assay Necessitate Adjustment of Serum and RBC Folate Concentrations in the U.S. Population from the NHANES 1988–2010 ,

AbstractThe NHANES measured serum and RBC folate concentrations by using a radioassay during prefortification (1988–1994) and postfortification (1999–2006) periods followed by the use of a microbiologic assay (MBA) from 2007–2010. The MBA produces higher concentrations than does the radioassay and is considered to be more accurate. To allow for accurate long-term trending (1988–2010), we evaluated different regression models (linear, piecewise linear, and fractional polynomial) to assay-adjust the radioassay results to be comparable to the MBA results. The data used to derive the regression models originated from 2 crossover studies in which the 2 assays were applied to a set of 325 serum and 171 whole-blood samples. Fractional polynomial regression of logarithmically transformed data provided the best fit for serum folate. Linear regression of logarithmically transformed whole-blood data provided an equally good fit compared with the other models and was the simplest to apply for RBC folate. Prefortification serum and RBC folate geometric mean concentrations increased after adjustment from 13.0 to 16.7 nmol/L and from 403 to 747 nmol/L, respectively. Postfortification serum folate concentrations increased from ~30 to ~43 nmol/L, and RBC folate concentrations increased from ~600 to ~1100 nmol/L after adjustment, with some variation across survey cycles. The presented regression equations allow the estimation of more accurate prevalence estimates and long-term trends in blood folate concentrations in the U.S. population by using results that are equivalent to the MBA. This information will be useful to public health officials in the United States who are dealing with folic acid fortification issues.

Folate-Binding Protein in Milk: A Review of Biochemistry, Physiology, and Analytical Methods

Folate-binding protein (FBP) was discovered in cow's milk around 40 years ago. Bovine FBP belongs to a family of several folate-binding proteins. In milk, it is a soluble whey protein with the ability to sequester folate from blood plasma. Bovine FBP is a well-characterized protein in terms of amino acid sequence and binding characteristics. Affinity and binding kinetics towards various folate forms have been intensively studied because they are crucial in using bovine FBP as an analytical tool. Shortly after the identification of bovine FBP, a competitive protein-binding assay for measuring serum and blood folate concentrations was introduced. Another analytical application of bovine FBP is in affinity chromatography, as a clean-up/concentration step for analysis of folates in foods and biological samples by liquid chromatographic methods. Concentrations of FBP in milk and dairy products have been determined by ELISA and Surface Plasmon Resonance-biosensor techniques. Since the initial reports of FBP in cow's milk, its physiological role has been discussed, especially regarding its effects on folate absorption from milk and dairy products. This review summarizes recent biochemical, analytical, food science, and nutritional advances regarding folate-binding protein in milk.

Abstract 5432: The effect of folic acid supplementation on chemosensitivity of colon cancer cells to 5-fluorouracil in a xenograft model

Abstract Background: As a mediator of one-carbon transfer reactions, folate is an essential cofactor in nucleotide biosynthesis. Interruption of intracellular folate metabolism and the consequent inhibition of tumor growth has been the basis for chemotherapy using antifolates and 5-fluorouracil (5FU). A growing body of evidence suggests that folic acid (FA; the synthetic form) may promote the progression of established colorectal (pre)neoplastic lesions. Folate blood levels in North America have dramatically increased over the past decade owing to FA fortification and widespread supplement use. Furthermore, over 50% of newly diagnosed colorectal cancer patients use vitamin supplements containing FA in addition to chemotherapeutic agents whose mechanisms of action are based on interruption of folate metabolism. This study therefore investigated whether FA supplementation can affect chemosensitivity of colon cancer cells to 5FU, the cornerstone of colorectal cancer treatment, in vivo. Methods: Male athymic nude mice were placed on the control diet containing 2 mg FA/kg diet and were inoculated with human HCT116 colon cancer cells. When xenografts were established, the animals were randomized to receive a diet containing 2, 8, or 25 mg FA/kg diet for eight weeks. Within each diet group, the animals were further randomized to receive saline vehicle or 5FU (20 mg/kg) + leucovorin (1 mg/kg) for five days. The primary endpoints were the rate of xenograft growth and the final volume. At necropsy, blood was collected and xenografts were harvested and evidence of metastasis was determined. Results: Plasma folate concentrations of animals on the 2 mg FA diet were significantly lower than those of animals fed the 8 and 25 mg FA diets (p&amp;lt;0.05). Xenograft folate concentrations significantly reflected the supplemental levels of FA in a dose-responsive manner (p=0.002). The effect of dietary levels of FA and 5FU alone were not significant, p=0.907 and p=0.193, respectively, but the interaction effect was significant (p&amp;lt;0.007). 5FU was beneficial only to animals fed the 2 mg FA diet (p&amp;lt;0.0001). In contrast, animals fed the 8 mg FA diet fared worse on 5FU (p=0.048) whereas animals fed the 25 mg FA diet demonstrated no effect of 5FU (p=0.31). All animals exhibited macroscopically evident lymph node involvement, but no distant metastases, irrespective of dietary levels of FA. Conclusion: Our data suggests that FA supplementation may adversely affect chemosensitivity to 5FU chemotherapy, although a dose-responsive relationship was not evident. Results of this study pose a legitimate public health concern given the drastically increased intake of FA from supplements, particularly among recently diagnosed colorectal cancer patients and from mandatory fortification. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5432. doi:1538-7445.AM2012-5432

Association between folate intake and melancholic depressive symptoms. A Finnish population-based study

An association between low blood folate levels and depressive symptoms (DS) has been reported in several epidemiological studies, but no studies have examined folate intake in melancholic or non-melancholic DS in population-based samples. The aim of the study was to evaluate folate intake in DS with or without melancholic characteristics as a part of the Finnish diabetes prevention program (FIN-D2D). Altogether, 4500 randomly selected subjects aged 45-74 years were selected from the National Population Register. The study population (N=2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out in 2007 according to the WHO MONICA project. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off≥10 points). A summary score of melancholic items in the BDI was used in dividing the participants with DS (N=429) into melancholic (N=138) and non-melancholic DS (N=291) subgroups. Folate intake was assessed using a validated food frequency questionnaire (FFQ). DS associated linearly with gender specific tertiles of folate intake (p for linearity=0.003). The OR for melancholic DS was 0.55 (95%CI 0.34 to 0.90) for the high tertile of folate intake versus the low (p for linearity=0.018), while the ORs for non-melancholic DS were nonsignificant. Assessment of DS was based on a self-rating scale, and the population was in advanced middle-aged. A low folate intake was associated with DS through its effect on melancholic DS.

Blood Folate is Associated with Asymptomatic or Partially Symptomatic Alzheimer's Disease in the Nun Study

Asymptomatic and partially symptomatic Alzheimer's disease (APSYMAD) are a series of cognitive states wherein subjects have substantial Alzheimer's disease (AD) pathology (classification B or C by the Consortium to Establish a Registry for AD criteria), but have normal or only partially impaired cognitive function; all of these subjects are non-demented. These cognitive states may arise from the prevention or delay of clinical symptom expression by exposure to certain nutritional factors. This study examined blood levels of folate and antioxidants (i.e., carotenoids) in relation to APSYMAD, nested in the Nun study, a longitudinal study of aging and AD. Sixty elderly female subjects, who had AD on the basis of neuropathology exams, were included. Following adjustment for APOE4 status, education level, and age at blood draw, subjects with the highest blood folate levels had a higher likelihood of being in the APSYMAD group as compared to the demented (AD) group (odds ratio = 1.09, 95% CI = 1.00-1.18. p < 0.06). This association was not significantly influenced by additional adjustment for blood concentrations of carotenoids. Restriction of the population to subjects with near normal cognition on the cognitive state score (score = 1-3) indicated an elevated association with blood folate (odds ratio = 1.12, 95% CI = 1.01-1.25, p < 0.04). Blood carotenoids were not associated with APSYMAD. Thus, folate status may influence the expression of clinical symptoms of AD disease and aid in the delay or prevention of dementia.

Examination of Circulating Folate Levels as a Reflection of Folate Intakes among Older Adult Supplement Users and Nonusers in the National Health and Nutrition Examination Survey 2003-2004

High intakes of folic acid and/or elevated blood folate concentrations have been associated with negative health outcomes; thus, it is critical to identify those at greatest risk of such exposures. The goal of this research was to describe folate intakes (folic acid [μg], folate [μg], and total folate [dietary folate equivalent] from food) and identify people 45 years or older in the National Health and Nutrition Examination Survey 2003-2004 at risk of exposure to elevated serum folate concentrations (≥21.8 ng/mL [49.4 nmol/L]) when stratified by race or ethnicity and supplement use within sex. Black men consumed a lower mean food folate and exhibited lower red blood cell folate concentrations when compared to those of white or Mexican-American men (P<0.01 and P<0.01 for both). Black women consumed a lower food folate than Mexican-American women (P<0.01), less total folate (dietary folate equivalent) than white women (P<0.01), and had lower red blood cell folate concentrations than white women (P<0.01). Multivariate odds of elevated serum folate levels increased with age in men (P<0.001) and women (P=0.01). All white subjects and all supplement users (all P<0.001) were more likely to have elevated folate concentrations, while smoking reduced the odds of such exposures in women (P<0.001) and men (P=0.04). These findings highlight the need to understand the impact of chronic exposure to elevated folate intakes, especially among white subjects with increasing age and who use supplements.

Community intervention trial promote healthy behaviors in farmers in Tianjin, China

Objectives: To assess a community intervention trial promoting healthier lifestyles in rural Chinese farmers using the stage of change health behavior model. Methods: A community intervention trial utilized an intervention and control village with farmers as study subjects. The intervention village (n= 549) participated in a stage-specific interventions while the control village (n=557) received general health education messages. Farmers in both villages were initially categorized using the stage of change model and observed for attitudinal and behavior changes over one year. Data collection included dietary habits, physical activity, anthropomorphic measures, and biomarkers at baseline, mid-point, and study termination. Results: The intervention group demonstrated greater progress in moving from awareness to the action stage in their adoption of healthier behaviors. Total cholesterol, homocysteine, blood pressure and urine sodium decreased while blood and urine folic acid increased in intervention subjects only. Conclusions: The first documented use of the stage of change model in rural Chinese farmers was successful at increasing healthier eating and physical activity in an infrequently studied population. Given China’s escalating burden of chronic diseases, the stage of change model should further be evaluated in promoting healthier behaviors and addressing lifestyle related illness in the world’s most populous nation. © 2012 GESDAV

Serum unmetabolized folic acid in a nationally representative sample of adults ≥60 years in the United States, 2001–2002

Folic acid is a compound that does not occur naturally in food but is added as a fortificant and dietary supplement. When it is ingested it is converted into forms of reduced folate that are identical to those arising from ingestion of naturally occurring folate in foods; however, some folic acid may appear unmetabolized in the serum (1, 2). Very little is known about its metabolism and biological effects. Folic acid fortification increased dietary intakes of folic acid (3) and blood folate levels in the United States (4). Some (5-9) but not all (10-12) research suggests that high folic acid intakes may promote the growth of pre-existing cancers or malignant lesions. Keywords: folic acid; folate; NHANES; folic acid fortification (Published: 2 April 2012) Citation: Food & Nutrition Research 2012. 56 5616 - DOI: 10.3402/fnr.v56i0.5616

Nutritional Consequences of Adhering to a Low Phenylalanine Diet for Late-Treated Adults with PKU : Low Phe Diet for Adults with PKU.

The main treatment for phenylketonuria (PKU) is a low phenylalanine (Phe) diet, phenylalanine-free protein substitute and low-protein special foods. This study describes dietary composition and nutritional status in late-diagnosed adult patients adhering to a PKU diet. Nineteen patients, followed at Oslo University Hospital in Norway, participated; median age was 48 years (range 26-66). Subjects were mild to severely mentally retarded. Food intake, clinical data and blood analyses relevant for nutritional status were assessed. Median energy intake was 2,091 kcal/day (range 1,537-3,277 kcal/day). Carbohydrates constituted 59% (range 53-70%) of the total energy, including 15% from added sugar; 26% was from fat. The total protein intake was 1.02 g/kg/day (range 0.32-1.36 g/kg/day), including 0.74 g/kg/day (range 0.13-1.07 g/kg/day) from protein substitutes. Median dietary Phe intake was 746 mg/day (range 370-1,370 mg/day). Median serum Phe was 542 μmol/L (range 146-1,310 mg/day). Fortified protein substitutes supplied the main source of micronutrients. Iron intake was 39.5 mg/day (range 24.6-57 mg/day), exceeding the upper safe intake level. Intake of folate and folic acid, calculated as dietary folate equivalents, was 1,370 μg/day (range 347-1744 μg/day), and resulted in high blood folate concentrations. Median intake of vitamin B(12) was 7.0 μg/day (range 0.9-15.1 μg/day). The diet supplied adequate protein and energy. Fortification of the protein substitutes resulted in excess intake of micronutrients. The protein substitutes may require adjustment to meet nutritional recommendations for adults with PKU.

Child's homocysteine concentration at 2 years is influenced by pregnancy vitamin B12 and folate status.

Longitudinal studies investigating vitamin B12 and folate status of mothers and their offspring will provide a better understanding of intergenerational nutrition. During pregnancy and 2 years (2y) after delivery, we measured plasma vitamin B12 and folate concentrations in 118 women [aged (mean ± s.d.) 22.9 ± 3.9y] who attended a rural (n = 68) or an urban (n = 50) antenatal clinic in Pune, India. Cord blood vitamin B12 and folate were measured, and when the child was 2y total homocysteine (tHcy) was also measured. Demographic and diet measurements were recorded using standard methods. Pregnancy plasma vitamin B12 concentration at 34 weeks was low [median (25th, 75th), 115 (95, 147) pm]; 75% had low status (<150 pm). Plasma folate was high (mean ± s.d., 33 ± 21 nm); one had a folate concentration <7 pm. Cord plasma vitamin B12 and folate concentrations were higher than and positively associated with maternal concentrations. In stepwise regression, higher child vitamin B12 at 2y was predicted (total R 2 15.7%) by pregnancy vitamin B12 (std β 0.201, R 2 7.7%), current consumption of cow's milk (std β 0.194, R 2 3.3%) and whether breast feeding was stopped before 2y (std β -0.234 R 2 7.2%). Child's 2y tHcy concentration was high (11.4 ± 3.6 μm) and predicted by lower pregnancy vitamin B12 (std β -0.206, R 2 4.1%), lack of vitamin supplementation (std β -0.256, R 2 5.6%) in pregnancy and whether currently breastfed (std β 0.268, R 2 8.4%). Low maternal vitamin B12 status in pregnancy and prolonged breast-feeding results in disturbed one-carbon metabolism in offspring at 2y. Supplementation of women of child-bearing age, particularly during pregnancy and lactation, may improve the homocysteine status of these children.

The relationship between maternal folate status in pregnancy, cord blood folate levels, and allergic outcomes in early childhood

Dietary changes may epigenetically modify fetal gene expression during critical periods of development to potentially influence disease susceptibility. This study examined whether maternal and/or fetal folate status in pregnancy is associated with infant allergic outcomes. Pregnant women (n=628) were recruited in the last trimester of pregnancy. Folate status determined by both food frequency questionnaires and folate levels in maternal and cord blood serum was examined in relation to infant allergic outcomes at 1 year of age (n=484). Infants who developed allergic disease (namely eczema) did not show any differences in cord blood or maternal folate levels compared with children without disease. Although maternal folate intake from foods was also not different, folate derived from supplements was higher (P=0.017) in children with subsequent eczema. Furthermore, infants exposed to >500 μg folic acid/day as a supplement in utero were more likely to develop eczema than those taking <200 μg/day (OR [odds ratio] =1.85; 95% CI 1.14-3.02; P=0.013), remaining significant after adjustment for maternal allergy and other confounders. There was a nonlinear relationship between cord blood folate and sensitization, with folate levels <50 nmol/l (OR=3.02; 95% CI 1.16-7.87; P=0.024) and >75 nmol/l (OR=3.59; 95% CI 1.40-9.20; P=0.008) associated with greater sensitization risk than levels between 50 and 75 nmol/l. Fetal levels between 50 and 75 nmol/l appeared optimal for minimizing sensitization. While folate taken as a supplement in higher doses during the third trimester was associated with eczema, there was no effect on other allergic outcomes including sensitization. Further studies are needed to determine the significance of this.

Folate and risk of coronary heart disease: A meta-analysis of prospective studies

Background and aimsEpidemiologic studies are inconsistent regarding the association between folate and coronary heart disease (CHD) risk. The aim was to perform a meta-analysis to determine whether an association exists between folate and total CHD endpoints in prospective studies. Methods and resultsWe searched the PUBMED and EMBASE databases for studies conducted from 1966 through August 2010. Data were independently abstracted by 2 investigators using a standardized protocol. Study-specific risk estimates were combined by using a random effects model.A total of 14 studies were included in the meta-analysis: 7 studies on dietary folate intake and 8 studies on blood folate levels. For dietary intake, the summary relative risk (RR) indicated a significant association between the highest folate intake and reduced risk of CHD (summary RR: 0.69; 95% CI: 0.60, 0.80). Furthermore, an increase in folate intake of 200 ug/day was associated with a 12% decrease in the risk of developing CHD (summary RR: 0.88; 95% CI: 0.82, 0.94). For blood folate levels, we also found a borderline inverse association of highest blood folate levels on CHD risk (summary RR: 0.74; 95% CI: 0.53, 1.02); our dose-response analysis indicated that an increment in blood folate levels of 5 mmol/l was associated with an 8% decrease in the risk of developing CHD (summary RR: 0.92; 95% CI: 0.84, 1.00). ConclusionThis meta-analysis suggests that dietary folate intake and blood folate level are inversely associated with CHD risk.