Red Blood Cell Folate Research Articles

Folate receptor alpha in human plasma: relationship to folate status and effect of supplementation in healthy reproductive aged females (827.17)

Little research has been conducted to determine the effect of chronic folic acid (FA) intake on folate receptors (FR). We aimed to determine if long‐term supplementation with FA (140 or 400 μg/d) changes expression of FRα in blood. Samples from a 40‐wk randomized placebo controlled trial in 144 reproductive aged females were used. Plasma FRα was determined by ELISA, plasma folate vitamer concentrations by LC‐MS/MS, and red blood cell (RBC) folate by microbiologic assay. The geometric mean (SD) FRα concentration was 12.4 (1.7) nmol/L at baseline and 13.2 (1.6) nmol/L at 40‐wks. There were no significant correlations between FRα and any blood folate indices at baseline, however, after 40‐wks, FRα was significantly correlated with RBC folate (Spearman’s r = 0.217, P = 0.021). In a multivariable model, FRα at baseline significantly predicted FRα at 40‐wks (Ratio 2.41, 95% CI 2.23 – 2.60, P < 0.001). While there was no overall effect of treatment (P = 0.124), exploratory subgroup analysis revealed a borderline association of 400 μg/d FA with FRα at 40‐wks (Ratio 1.10, 95% CI 1.00‐1.20, P = 0.043), yet no effect of 140 μg/d FA (Ratio 1.04, 95% CI 0.95‐1.13, P = 0.414). This suggests that FRα in plasma, which may reflect FRα from decomposed RBCs and neutrophils, may be slightly increased by long‐term FA supplementation. Larger studies are needed to determine effects of chronic FA exposure on FR expression, including in other tissues.Grant Funding Source: Supported by University of Otago Research Grant

Effects of folate deficiency with HPV16 infection on cervix cancerization

To investigate the relationship between folate in serum, red blood cell (RBC), cervix cancerization, as well as the interaction between folate deficiency and HPV16 infection in cervix cancerization. 254 samples were selected from the patients who were newly pathologically diagnosed of having cervix inflammation (CI), low-grade cervical intraepithelial neoplasia (CIN I), high-grade cervical intraepithelial neoplasia (CIN II/III) and cervical squamous cell carcinoma (SCC). PCR and microbiological assay were adopted to detect HPV infection and folate concentration. Rates of HPV16 infection increased with the severity of cervix cancerization (tend: χ² = 34.96, P < 0.001), while decreased with concentrations of serum and RBC folate (tend: χ² = 42.17, P < 0.001; tend: χ² = 31.39, P < 0.001). There was a positive correlation between serum and RBC folate (r = 0.405, P < 0.001). Data from grouping analysis showed that OR and aOR of serum and RBC folate appeared a rising trend, with statistical significance in CIN II/III and SCC, but did not show the same trend in CIN I. Results from interaction analysis showed that serum folate deficiency had an additive interaction with HPV16 infection in CIN II/III and SCC, while RBC folate having an additive interaction with HPV16 infection in the whole process of cervix cancerization. Both serum and RBC folate deficiency could increase the risk of cervix cancerization, and folate deficiency might have a synergic action with HPV16 in this procession.

Obesity is associated with increased red blood cell folate despite lower intake and serum levels of this vitamin among adults in the United States (LB411)

Background: Folates are essential cofactors in various metabolic pathways. Limited evidence has investigated how obesity affects folate metabolism. We investigated the association between body mass index (BMI) and obesity‐related metabolic factors with blood folate status.Methods: A representative study population of 3829 US adults was derived from the National Health and Nutrition Examination Survey (2003‐2006). Regression analyses were performed to examine the association between BMI and obesity‐related metabolic factors with serum folate and red blood cell (RBC) folate.Results: Serum folate levels were lowest in both the underweight and obese groups, closely paralleling with the lower dietary folate intakes in these two groups. In contrast, RBC folate incrementally increased with BMI. Regression analyses demonstrated a negative relationship between BMI and serum folate, but a positive relationship for RBC folate. These relationships were significant for 19‐50 year old individuals, but not for elders (蠅 51 yrs).Conclusion: Obesity is associated with decreased serum folate, and concurs with lower total intake among the obese. In contrast, obesity is positively associated with increased RBC folate. These relationships are significant for young and middle‐aged adults, but not for elders. RBC folate appears to be a better biomarker of cellular folate status in obese individuals.Grant Funding Source: Supported in part by the USDA/NIFA grant (2014‐67017‐21762, ZL), the USDA Hatch grant (MAS00454, ZL) and the funding from Rays of Hope Center of Breast Cancer Research, Baystate Medical Center (ZL)

Examining the folate status of Canadians: An analysis of the Canadian Health Measures Survey to assess and guide folate policies

Canada fortifies certain products with folic acid and has periconceptional supplementation guidelines [Formula: see text] policies designed to improve folate status and reduce the incidence of poor birth outcomes. Though optimal folate concentrations have been linked to health benefits, concerns have been raised regarding potential associations with adverse health outcomes. Direct biochemical assessment of the folate status of Canadians based on a nationally representative sample has not been done in more than 40 years. The overall purpose of this research was to investigate the folate status of the Canadian population. All analyses used the nationally representative 2007–2009 Canadian Health Measures Survey (CHMS). Red blood cell (RBC) folate was measured by Immulite 2000 immunoassay. Key findings indicate that folate deficiency (&lt;305 nmol/L) was virtually nonexistent in the Canadian population (6–79 years old). Still, one-fifth of women of childbearing age (WCBA; 15–45 years old) had suboptimal concentrations for the prevention of neural tube defects (&lt;906 nmol/L). Folic acid supplement intake was a primary determinant of WCBA, achieving a RBC folate concentration of ≥906 nmol/L. A distinct shift towards elevated RBC folate concentrations emerged. Three hypothetical cut-offs (1450 nmol/L, 1800 nmol/L and 2150 nmol/L) were examined to create a dialogue since a universal definition of high RBC folate concentration does not exist. Females, participants aged 60–79 years, and those who were overweight or obese had the greatest prevalence of having high RBC folate at each cut-off. We conducted the first national-level comparison of RBC folate concentrations between the United States and Canada. Two different folate assay methods [Formula: see text] microbiologic assay (NHANES) and Immulite 2000 immunoassay (CHMS) [Formula: see text] necessitated the application of a conversion equation. Median Canadian RBC folate concentrations (adjusted to microbiologic assay) were lower than those of Americans but unadjusted Canadian median RBC folate values were higher. Canadian WCBA were less likely than American WCBA to have RBC folate ≥906 nmol/L, though Canadian WCBA with unadjusted RBC folate values were more likely to achieve this cut-off. These results indicate a need for strategies targeting WCBA to improve compliance with folic acid supplement recommendations. The strength and necessity of supplements for the general population should be re-assessed. Further, harmonization of folate measurement procedures in future surveillance efforts would support comparisons and inform policy directions.

Fumonisin B1induced neural tube defects were not increased in LM/Bc mice fed folate-deficient diet

Fumonisin B1 (FB1 ) is found in corn-based foods and is a possible risk factor for neural tube defects (NTDs). The mechanism(s) underlying NTD induction by FB1 in LM/Bc mice is not understood; however, evidence suggests disrupted folate transport is involved. Female LM/Bc mice were fed folate-sufficient (control) or folate-deficient diet beginning 5 wk before mating, treated with 0 (vehicle), 2.5 or 10 mg/kg FB1 by intraperitoneal injection on embryonic days 7 (E7) and E8, and their fetuses examined on E16. Dose-dependent NTD induction was found in groups fed the control diet: 3 of 13 low-dose and 10 of 11 high-dose litters were affected. Among groups fed folate-deficient diet, NTDs were found only in 4 of 11 high-dose litters. In another trial, consumption of folate-deficient diet also resulted in fewer NTDs at a dose of 10 mg/kg FB1 and reduced maternal red blood cell folate levels by 80%. In utero death did not fully account for the differences in NTD rates. Folate deficiency does not exacerbate NTD induction by FB1 in LM/Bc mice. Interactions between folate, other nutritional factors, and FB1 in this mouse model for NTDs are complex and require further investigation.

An optimal periconception maternal folate status for embryonic size: the Rotterdam Predict study

To investigate the association between periconception maternal folate status and embryonic size. Prospective periconception cohort study. Erasmus University Medical Centre, Rotterdam, the Netherlands. Seventy-seven singleton pregnancies recruited in 2009 and 2010. We recruited women before 8 weeks of gestation and performed weekly three-dimensional ultrasound scans from enrolment up to 13 weeks of gestation. As a measure of embryonic growth, crown-rump length (CRL) measurements were performed using V-Scope software in the BARCO I-Space. Maternal blood was collected to determine first-trimester long-term red blood cell (RBC) folate status. Non-malformed live births were included in the analysis. We calculated quartiles of RBC folate, square root-transformed CRL data and performed multivariable linear mixed model analyses. Serial first-trimester CRL measurements. In total, 484 ultrasound scans were performed in 77 women, in 440 (90.7%) of which CRLs could be measured. RBC folate in the third quartile (1513-1812 nmol/l) was significantly associated with an increased CRL compared with the first two quartiles (814-1512 nmol/l) and the upper quartile (1813-2936 nmol/l; P(overall) = 0.03; adjusted for gestational age, smoking, body mass index and fetal sex). Compared with the third quartile, embryos in the upper quartile were 24.2% smaller at 6(+0) weeks [4.1 mm (95% confidence interval 3.5, 4.7) versus 5.4 mm (95% confidence interval 4.8, 6.1)] and 7.6% smaller at 12(+0) weeks [55.1 mm (95% confidence interval 52.9, 57.3) versus 59.6 mm (95% confidence interval 57.4, 62.0)] of gestation. This study suggests that a very high maternal periconception folate status is associated with reduced embryonic size. Whether these effects are beneficial or harmful requires further investigation.

Folate in der Depressionsbehandlung

Depression is an important and often recurrent illness. An initial antidepressant trial is effective at achieving remission for about 30 % of patients when prescribed as monotherapy, with the majority of patients returning as partial or non-responders. Suboptimal serum and red blood cell folate levels have been associated with a poorer response to antidepressant therapy, a greater severity of symptoms, later onset of clinical improvement, and overall treatment resistance. This article reviews the evidence for L-methylfolate and folic acid as antidepressive agents in depression and discusses their clinical use.

Serum and red blood cell folate testing for folate deficiency: new features?

Folate deficiency is assessed by serum and red blood cell folate measurements. Nevertheless, no consensus for the lower limit of serum folate reference values exists. We investigated the appropriate use of RBC folate to detect folate deficiency and the relationship between serum and RBC folate and with other parameters such as vitamin B12 and homocysteine in order to propose serum folate cut-off values. Retrospectively, 63,113 and 20,459 results of serum and RBC folate were collected. If present, the results of red cell indices, vitamin B12 and homocysteine were also collected. A significantly positive correlation between serum and RBC folate was demonstrated. A significant effect of serum folate levels under 6 μg/L (or 14 nm) was observed on RBC indices. A relation was found between vitamin B12 and folate, for serum and RBC. A significant rise in homocysteine concentrations was observed for serum folate levels under 8 μg/L (or 18 nm). To observe haematological abnormalities, folate deficiency should be profound. Serum folate levels under 8 μg/L (or 18 nm) should be considered as a decision limit for folate depletion because a positive effect on homocysteine was observed. Fasting serum folate concentration should be preferred for assessing folate status. Our results suggest that the need for RBC folate testing is less meaningful.

Socioeconomic factors are associated with folate and vitamin B12 intakes and related biomarkers concentrations in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study

Because socioeconomic factors (SEFs) may influence dietary quality and vitamin intakes, this study aimed to examine associations between socioeconomic factors and folate and vitamin B12 intakes as well as their related biomarkers in the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Vitamin intakes were obtained from two 24-hour recalls in 2253 participants (47% males). Vitamin B biomarkers were assessed in a subsample of 977 participants (46% males). Socioeconomic factors were assessed by questionnaire, and 1-way analysis of covariance and linear regression analysis were applied. For males and females, mean intakes of folate were 211.19 and 177.18μg/d, and for vitamin B12, 5.98 and 4.54μg/d, respectively. Levels of plasma folate, red blood cell folate, serum B12, and holotranscobalamin were 18.74, 807.19, 330.64, and 63.04nmol/L in males, respectively, and 19.13, 770.16, 377.9, and 65.63nmol/L in females, respectively. Lower folate intakes were associated with several SEFs, including maternal and paternal education in both sexes. Regarding folate biomarkers, lower plasma folate intakes were associated with single/shared care in males and with lower paternal occupation in females. Lower vitamin B12 intakes were associated with almost all the studied SEFs, except paternal occupation in both sexes. In females, when considering vitamin B12 biomarkers, lower plasma vitamin B12 was associated with lower maternal education and occupation, and lower holotranscobalamin was associated with lower maternal education and lower paternal occupation. In conclusion, from the set of socioeconomic determinants studied in a sample of European adolescents, maternal education and paternal occupation were more consistently associated with folate and vitamin B12 intakes and biomarkers concentrations.

Extremely high concentration of folates in premature newborns

Extremely high concentration of folates in premature newborns: case reports. Folates are a group of water soluble compounds, which are important for metabolic processes in human body. These are important during periods of rapid cell growth. The most accurate indicator of long-term folate level status in the body is the determination of red blood cell (RBC) folate concentrations. The optimal level of RBC folate is not known in neonatal period. Authors discuss the reasons for extremely high level of RBC folate concentrations. In our work we present the cases of two premature newborns with extremely high level of RBC folate concentrations, which were analyzed immunochemically on the first day of life and after six weeks of life. In both cases we measured RBC folate concentrations on the 1st day of life. After 6 weeks we found extremely high RBC folate concentration level (5516.67 ng/ml) in the first case after RBC transfusions. In second case after two months of life the RBC folate concentration level was doubled (2335.1 ng/ml) until 24 hours after RBC transfusion compared to levels after birth. The normal range of RBC folate values vary in newborns. The upper limit of daily dose of folic acid in pregnancy and neonatal period is not known. On the other hand it is an easily excreted water-soluble vitamin but in premature newborn it can lead to the disruption of metabolic balance and slow its degradation. Some factors can have an impact on RBC folate concentration. Blood transfusion can be one of the main influences on RBC folate concentration. To clarify these mechanisms further studies are required (Ref. 29).

Differential Behavior of Serum and Red Blood Cell Folate During a Treatment with Levofolinic Acid. Gender Differences

Folates are essential nutrients that maintain nucleotide synthesis and methylation reactions. Folate levels depend essentially on the diet. In the present work, the changes in the folate-homocysteine (Hcy) metabolic axis were studied in response to treatment with levofolinic acid. 49 college students (23 men and 26 women) underwent a treatment voluntarily with 5 mg/day levofolinic acid for one month. Serum and red blood cell folate, vitamin B12, and Hcy levels were determined on days 2, 5, 10, and 30 during treatment and 30 days after completion of treatment. Serum folate and Hcy levels showed a plateau beginning on day 10, while red blood cell folate increased towards treatment completion. Gender differences were found in basal levels of Hcy, these differences remaining until the 10th day of treatment and reappearing 30 days after the treatment was finished. Between gender differences in treatment evolution were found only in percentage changes in red blood cell folate in women and men at day 30 of treatment. There is a compartmentalization of folates in the body that presents a plateau in serum and an erythrocyte reservoir. Folate metabolism presents differential features between genders. The greater physiological need for folate in women of childbearing age could be the determining factor in this difference.

Biomarker responses to folic acid intervention in healthy adults: a meta-analysis of randomized controlled trials

The task of revising dietary folate recommendations for optimal health is complicated by a lack of data quantifying the biomarker response that reliably reflects a given folate intake. We conducted a dose-response meta-analysis in healthy adults to quantify the typical response of recognized folate biomarkers to a change in folic acid intake. Electronic and bibliographic searches identified 19 randomized controlled trials that supplemented with folic acid and measured folate biomarkers before and after the intervention in apparently healthy adults aged ≥18 y. For each biomarker response, the regression coefficient (β) for individual studies and the overall pooled β were calculated by using random-effects meta-analysis. Folate biomarkers (serum/plasma and red blood cell folate) increased in response to folic acid in a dose-response manner only up to an intake of 400 μg/d. Calculation of the overall pooled β for studies in the range of 50 to 400 μg/d indicated that a doubling of folic acid intake resulted in an increase in serum/plasma folate by 63% (71% for microbiological assay; 61% for nonmicrobiological assay) and red blood cell folate by 31% (irrespective of whether microbiological or other assay was used). Studies that used the microbiological assay indicated lower heterogeneity compared with studies using nonmicrobiological assays for determining serum/plasma (I(2) = 13.5% compared with I(2) = 77.2%) and red blood cell (I(2) = 45.9% compared with I(2) = 70.2%) folate. Studies administering >400 μg folic acid/d show no dose-response relation and thus will not yield meaningful results for consideration when generating dietary folate recommendations. The calculated folate biomarker response to a given folic acid intake may be more robust with the use of a microbiological assay rather than alternative methods for blood folate measurement.

Obesity during pregnancy alters maternal oxidant balance and micronutrient status

Little is known about the effect of obesity on inflammatory status in pregnant women. The objective of this study was to determine the effect of obesity on markers of inflammation, oxidative stress and micronutrient status in obese pregnant women and their infants compared with lean controls (Lc). This was a prospective case-control study. A total of 15 obese (Ob; body mass index (BMI) >30 kg m(-2)) and 15 lean (BMI 18-25 kg m(-2)) women were recruited based on prepregnancy BMI. Vitamins A, B6, C, E and 25-hydroxyvitamin D (25(OH)D), zinc, red blood cell (RBC) folate, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α and oxidized and reduced glutathione were measured from maternal blood between 24 and 28 weeks of gestation. Vitamins A, B6, C and E, 25(OH)D, zinc, red blood cell folate, CRP and IL-6 were measured from cord blood at delivery. Ob pregnant women have statistically significantly lower levels of vitamin B6, vitamin C, vitamin E, RBC folate, higher CRP and IL-6 levels and higher ratio of oxidized to reduced glutathione compared with Lc pregnant women. Infants born to Ob mothers did not have statistically significantly higher measures of inflammation or oxidative stress. There were no differences in micronutrient concentrations between Lc and Ob infants, but folate, vitamin B6 and zinc levels correlated strongly between mother and infant. There was no statistically significant difference in any parameter between Ob and Lc cord blood. Ob pregnant women have increased inflammation and oxidative stress, and lower levels of nutritional antioxidant defenses compared with Lc pregnant women. We speculate that lower antioxidant defenses combined with increased oxidative stress and inflammation may contribute to the adverse outcomes associated with pregnancy in Ob women.

Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort

DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994–1995), peri- (1996–1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.

The causal effect of red blood cell folate on genome-wide methylation in cord blood: a Mendelian randomization approach

BackgroundInvestigation of the biological mechanism by which folate acts to affect fetal development can inform appraisal of expected benefits and risk management. This research is ethically imperative given the ubiquity of folic acid fortified products in the US. Considering that folate is an essential component in the one-carbon metabolism pathway that provides methyl groups for DNA methylation, epigenetic modifications provide a putative molecular mechanism mediating the effect of folic acid supplementation on neonatal and pediatric outcomes.ResultsIn this study we use a Mendelian Randomization Unnecessary approach to assess the effect of red blood cell (RBC) folate on genome-wide DNA methylation in cord blood. Site-specific CpG methylation within the proximal promoter regions of approximately 14,500 genes was analyzed using the Illumina Infinium Human Methylation27 Bead Chip for 50 infants from the Epigenetic Birth Cohort at Brigham and Women’s Hospital in Boston. Using methylenetetrahydrofolate reductase genotype as the instrument, the Mendelian Randomization approach identified 7 CpG loci with a significant (mostly positive) association between RBC folate and methylation level. Among the genes in closest proximity to this significant subset of CpG loci, several enriched biologic processes were involved in nucleic acid transport and metabolic processing. Compared to the standard ordinary least squares regression method, our estimates were demonstrated to be more robust to unmeasured confounding.ConclusionsTo the authors’ knowledge, this is the largest genome-wide analysis of the effects of folate on methylation pattern, and the first to employ Mendelian Randomization to assess the effects of an exposure on epigenetic modifications. These results can help guide future analyses of the causal effects of periconceptional folate levels on candidate pathways.

Dietary Folate Intake and Blood Biomarkers Reveal High-Risk Groups in a Mediterranean Population of Healthy Women of Childbearing Potential

Background/Aims: An important public health issue is monitoring folate inadequacy in women of childbearing potential. The aim of the present study was to investigate associations between folate intake, red blood cell (RBC) folate, total homocysteine (tHcy) and the MTHFR 677T allele. Methods: A total of 204 women were enrolled in a cross-sectional study. Folate intake was assessed by a food frequency questionnaire, and RBC folate, tHcy and MTHFR C677T genotype were determined. Results: About half of the women had a decreased RBC folate level (<305 nmol/l) and all were <906 nmol/l, even though 51% of the subjects reported use of supplements. Overall 91.5% had a high Hcy concentration. Notably, younger women, and those with a low level of education, were shown to be at higher risk of inadequate RBC folate levels. Additionally, younger women were also at higher risk of carrying the TT genotype, particularly unfavorable in the setting of a low folate status. Conclusions: Our study revealed significant folate deficiency in our Mediterranean population and higher than ideal Hcy concentrations, thus emphasizing that in these groups an improvement in the folate status is needed via a food-based approach or supplement. Consequently, public health policy strategies aiming at improved supplementation are required.

Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of Folic Acid Supplementation in the Second and Third Trimesters

Supplementation with folic acid (FA) is recommended worldwide before and during early pregnancy because of its proven effect in preventing neural tube defects, but the role of FA after the 12th gestational week (GW) is much less clear. We investigated maternal folate and homocysteine responses and related effects in the newborn that resulted from continued FA supplementation after the first trimester of pregnancy. Pregnant women, aged 18-35 y, who were attending an antenatal clinic in Northern Ireland with singleton uncomplicated pregnancies and reported taking FA supplements in the first trimester, were randomly assigned at the start of trimester 2 to receive 400 μg FA/d or a placebo capsule. A total of 119 women (60 women in the placebo group; 59 women in the treatment group) completed the trial. From GWs 14-36, mean (±SD) serum folate decreased (from 45.7 ± 21.3 to 19.5 ± 16.5 nmol/L; P < 0.001) in unsupplemented women, whereas plasma homocysteine increased (6.6 ± 2.3 to 7.6 ± 2.3 μmol/L; P < 0.001). However, FA supplementation prevented these changes and resulted in a significant increase in red blood cell folate concentrations from 1203 ± 639 to 1746 ± 683 nmol/L (P < 0.001; GWs 14-36). Cord blood folate was significantly higher in the FA group than in the placebo group (red blood cell concentrations of 1993 ± 862 and 1418 ± 557 nmol/L, respectively; P = 0.001). Continued supplementation with 400 μg FA/d in trimesters 2 and 3 of pregnancy can increase maternal and cord blood folate status and prevent the increase in homocysteine concentration that otherwise occurs in late pregnancy. Whether these effects have benefits for pregnancy outcomes or early childhood requires additional study.

Maternal Phenylketonuria International Collaborative Study revisited: evaluation of maternal nutritional risk factors besides phenylalanine for fetal congenital heart defects

Maternal phenylketonuria (MPKU) is known to affect fetal outcome, often being associated with microcephaly and congenital heart defects (CHD) if the maternal diet is not appropriately managed. We hypothesized that other nutrients aside from phenylalanine (Phe) may have significant effects on fetal outcome in MPKU pregnancies. The 416 pregnancies that resulted in live births reported in the Maternal PKU Collaborative Study (MPKUCS) were grouped according to whether or not the offspring were diagnosed with CHD. The groups were compared on first-trimester values of maternal data, including weight gain, plasma amino acids, protein and Phe intake, and red blood cell (RBC) folate. Patients were also grouped by first-trimester average blood Phe (≤910 μmol/L and >910 μmol/L) and then divided by total natural protein and medical food intake. The CHD group of 28 offspring had significantly higher blood Phe and lower proline, valine, methionine, isoleucine, leucine, lysine, arginine, and RBC folate. A significantly higher risk for CHD was found in the groups with lower natural protein and medical food intake, regardless of blood Phe levels. Insufficient natural protein and medical food product intake appears to be a risk factor for CHD independent of first-trimester plasma Phe levels. Low RBC folate and plasma methionine levels in the CHD group may suggest involvement of global DNA hypomethylation.

Red blood cell folate levels in pregnant women with a history of mood disorders: A case series

Maternal folate supplementation reduces offspring risk for neural tube defects (NTDs) and other congenital abnormalities. Maternal red blood cell (RBC) folate concentrations of >906 nmol/L have been associated with the lowest risk of having a neural tube defect affected pregnancy. Mood disorders (e.g., depression, bipolar disorder) are common among women and can be associated with folate deficiency. Thus, pregnant women with histories of mood disorders may be prone to RBC folate levels insufficient to provide optimal protection against neural tube defects. Although previous studies have assessed RBC folate concentrations in pregnant women from the general population, none have looked specifically at a group of pregnant women who have a history of a mood disorder. We collected data about RBC folate concentrations and folic acid supplement intake during early pregnancy (<161 days gestation) from n = 24 women with histories of mood disorders. We also collected information about offspring congenital abnormalities and birth weight. Among women with histories of mood disorders, the mean RBC folate concentration was 674 nmol/L (range, 362-1105 nmol/L). Only 12.5% (n = 3) of the women had RBC folate concentrations >906 nmol/L, despite all participants reporting current daily use of folic acid supplements. Data regarding offspring were available for 22 women: birth weights ranged from 2296 g to 4819 g, and congenital abnormalities were identified in two (hypoplastic left heart, annular pancreas). Data from this exploratory case series suggest a need for future larger scale controlled studies investigating RBC folate concentrations in early pregnancy and offspring outcomes among women with and without histories of mood disorders.

A pilot study of folic acid supplementation for improving homocysteine levels, cognitive and depressive status in eating disorders.

Several authors have reported low folate intake in patients with eating disorders (ED). This vitamin plays an essential role in synthesis reactions for neurotransmitters and structural elements of neurons, and therefore its deficiency has been associated with the presence of different disorders linked to mental function. The aim of this study was to determine the effect of folic acid supplementation on homocysteine levels and the cognitive and depressive status of a group of patients with eating disorders with low folate intake. The study was designed as a randomised, prospective clinical trial, which included 24 participants assigned to two treatment groups for six months: supplemented group (SG) (10 mg/day of folic acid [ACFOL]) and a placebo group (PG). Both groups maintained their medical, dietary and psychological treatment. At baseline and end of the intervention, anthropometric, dietary and biochemical parameters (plasma homocysteine [Hcy], serum and red blood cell folate) were recorded. Cognitive and depressive status questionnaires were administered (Stroop Test, Trail Making Test and Beck Depression Inventory). Twenty-two patients completed the study (SG: 12, PG: 10, mean age: 24.2 ± 8.8 years, BMI 18.9 ± 3.5 kg/m2). The SG significantly increased their serum and red blood cell folate levels and lowered Hcy levels (9.4 ± 2.4 μmol/l vs. 7.5 ± 1.7 μmol/l, P < 0.01). The SG also significantly improved most of their test scores for cognitive and depressive status. The PG showed no significant changes in any of the evaluated variables. The results show that folic acid supplementation may be used as another tool within the comprehensive and multidisciplinary treatment applied to patients with ED.