Folate Concentrations Research Articles

Nonlinear Relationship Between Maternal and Cord Blood Vitamin B12 and Folate from a Chinese Population-Based Study.

There remains a data gap on vitamin B12 and folate level in maternal and child populations. This study aimed to assess the status of vitamin B12 and folate in maternal serum (MS) and umbilical cord serum (UCS). This was a planned secondary analysis of a case-control study. A total of 858 pregnant women during late pregnancy and their newborns in the hospitals of China were included. Maternal peripheral venous blood and neonatal umbilical cord blood were collected to determine serum vitamin B12 and folate concentration. Relationship of vitamin B12 or folate concentration between MS and UCS was assessed by a quantile regression model and the non-linear relationship between them was examined. Nutritional status of serum folate was better than that of vitamin B12. Prevalence of deficiency in MS vitamin B12 and folate was 73.4% and 14.2%, respectively and these figures were about 17.8% and 0.1% in UCS. Both vitamin B12 and folate levels in UCS were significantly higher than those in MS (vitamin B12: 321.0 pg/mL vs 158.3 pg/mL, folate: 16.5 ng/mL vs 7.0 ng/mL, P <0.001). The median UCS-MS ratio of vitamin B12 and folate was 2.0 (95% CI: 1.94-2.06) and 2.4 (95% CI: 2.30-2.53), respectively. The levels of folate and vitamin B12 in UCS increased nonlinearly with their increase in MS which presented an inverted U-shaped curve. Deficiency in vitamin B12 and folate in the women during late pregnancy in China is prevalent. Nutritional status of the two vitamins in umbilical cord serum is correlated nonlinearly with that in maternal serum. Folic acid supplementation may be accompanied with vitamin B12 to improve status of vitamin B12 and folate during pregnancy.

Ceruloplasmin and some biochemical parameters as a marker for acute myeloid leukemic patients

Acute myeloid leukemia is a second type of leukemia and has more effect on elder patients than adult. This research's objective was to measure the serum levels of ceruloplasmin (CP), ferritin (FR), vitamin B12 (VitB12), folic acid (FA), zinc (Zn), copper (Cu), and iron (Fe) in acute myeloid leukemic patients (AML) (before and after taking chemotherapy) and healthy control groups. In this study, about (160) blood samples (males and females) were collected from acute myeloid leukemic patients in Erbil’s Nanakali hospital and they were separated into four groups: Group 1 (G1) including (40) Apparently healthy control group, Group 2 (G2) include (40) acute myeloid leukemic patients before taking chemotherapy (new cases), Group 3 (G3) include (40) acute myeloid leukemia patients taking chemotherapy for one cycle, and Group 4 (G4) include (40) acute myeloid leukemic patients with taking chemotherapy for more than one cycle. The outcomes display a significant increase in serum concentration of ceruloplasmin, ferritin, vitamin B12, and iron in all patient groups when compared with control groups. While the serum concentration of folic acid, zinc, and copper decreased in all patient groups when compared with the healthy control group. In addition, the correlation analysis displays that there was a significant positive correlation between ceruloplasmin with ferritin, vitamin B12, and iron, on another hand have a non-significant negative correlation between ceruloplasmin with folic acid, zinc, and copper. According to the present study, there was a direct correlation between AML patients with the serum levels of CP, FR, VitB12, FA, Zn, Cu, and Fe. A high area under the curve of our data suggests that testing for (CP, FR, VitB12, FA, Cu, and Fe) could be helpful to detect AML. However, zinc is not a good biomarker for detecting AML patients.

Purine Nucleotide Alterations in Tumoral Cell Lines Maintained with Physiological Levels of Folic Acid.

Most cancer cells have an increased synthesis of purine nucleotides to fulfil their enhanced division rate. The de novo synthesis of purines requires folic acid in the form of N10-formyltetrahydrofolate (10-formyl-THF). However, regular cell culture media contain very high, non-physiological concentrations of folic acid, which may have an impact on cell metabolism. Using cell culture media with physiological levels of folic acid (25 nM), we uncover purine alterations in several human cell lines. HEK293T, Jurkat, and A549 cells accumulate 5'-aminoimidazole-4-carboxamide ribonucleotide (ZMP), an intermediary of the de novo biosynthetic pathway, at physiological levels of folic acid, but not with the artificially high levels (2200 nM) present in regular media. Interestingly, HEK293T and Jurkat cells do not accumulate high levels of ZMP when AICAr, the precursor of ZMP, is added to medium containing 2200 nM folate; instead, ATP levels are increased, suggesting an enhanced de novo synthesis. On the other hand, HeLa and EHEB cells do not accumulate ZMP at physiological levels of folic acid, but they do accumulate in medium containing AICAr plus 2200 nM folate. Expression of SLC19A1, which encodes the reduced folate carrier (RFC), is increased in HEK293T and Jurkat cells compared with HeLa and EHEB, and it is correlated with the total purine nucleotide content at high levels of folic acid or with ZMP accumulation at physiological levels of folic acid. In conclusion, tumoral cell lines show a heterogenous response to folate changes in the media, some of them accumulating ZMP at physiological levels of folic acid. Further research is needed to clarify the ZMP downstream targets and their impact on cell function.

One-pot synthesis of environmentally-friendly carbon quantum dots for “on-off” rapid fluorescent sensing of folic acid, Fe3+, and Ca2+

Detecting abnormal levels of folic acid (FA), Fe3+, and Ca2+ in the human body is crucial due to their association with various diseases. Orange peel carbon quantum dots (OP-CQDs) with blue fluorescence (λex = 370 nm, λem = 440 nm) were synthesized using a one-step hydrothermal method when waste biomass orange peel was utilized as the carbon source. An “on-off” fluorescence sensor, referred to as OP-CQDs-FA-Fe3+/Ca2+, was developed for quantitative analysis of the drug FA, as well as the metal ions Fe3+ and Ca2+. Additionally, the sensor was utilized for fluorescence imaging of HepG2 liver cancer cells, demonstrating its exceptional biocompatibility. The concentration of FA displayed a linear relationship in the range of 5.00–90.00 μmol L−1 and 0.30–2.50 mmol L−1, with a limit of detection (LOD) of 0.15 μmol L−1. The spiked recovery in folic acid tablets ranged from 95.70% to 104.50%. The addition of Fe3+ or Ca2+ leads to a reduction or restoration of the fluorescence intensity in the OP-CQDs-FA system, resulting in an “on-off” sensor mode. The spiked recoveries in human serum samples were 100.15%–100.48% for Fe3+ and 98.05%–98.18% for Ca2+. This study highlights the considerable potential of OP-CQDs for ion detection, drug analysis, and cell imaging.

Development of a highly sensitive voltammetric sensor for the detection of folic acid by using MoS2 and ionic liquid-modified carbon paste electrode.

Sensitive analytical determination of folic acid is important in clinical laboratories due to its versatile biological functions. A simple folic acid sensor was successfully fabricated based on two-dimensional transition metal dichalcogenide MoS2 modified carbon ionic liquid paste electrode (MoS2-CILPE). The electrochemical properties of the fabricated electrode were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry. The fabricated sensor displayed excellent electroactivity towards folic acid using CV. Under optimal conditions (0.1 M PBS (pH 7.0)), the DPV oxidation peak current was proportional to folic acid concentration in the range from 5.0 μM to 100.0 μM with an estimated limit of detection of 1.0 μM and limit of quantification of 5.0 μM. The ability of the sensor for routine analyses was demonstrated by the detection of folic acid present in folic acid tablets and urine samples with appreciable recovery values.

Prevalence and predictors of low folate levels among stroke survivors in a country without mandatory folate food fortification: Analysis of a Ghanaian sample

BackgroundWhile additional folic acid (FA) treatment has a neutral effect on lowering overall vascular risk in countries that mandate FA fortification of food, meta-analytic data suggest that folate supplementation reduces stroke risk in certain patient subgroups, and among people living in countries without mandatory folate food fortification. However, the burden of folate deficiency among adults with stroke in the world's poorest continent is unknown. PurposeTo assess the prevalence and predictors of folate deficiency among recent ischemic stroke survivors. MethodsWe analyzed data among consecutively encountered ischemic stroke patients aged ≥18 years at a tertiary medical center in Kumasi, Ghana between 10/2020 – 08/2021. We identified a modest sample of stroke free adults to serve as a comparator group. Fasting serum folate was measured using a radioimmunoassay and a cut-off of 4ng/mL used to define folate deficiency. Factors associated with serum folate concentration were assessed using a multilinear regression model. ResultsComparing stroke cases (n = 116) with stroke-free comparators (n = 20), mean folate concentration was lower among stroke cases (7 ng/ml vs. 10.2 ng/ml, p = 0.004). Frequency of folate deficiency was higher among stroke cases vs. stroke-free controls (31% vs 5%, p = 0.02). Male sex (beta coefficient of -2.6 (95% CI: -4.2, -0.9) and LDL (β: -0.76; -1.4, -0.07) were significantly associated with serum folate concentration. ConclusionAlmost one in three ischemic stroke survivors have folate deficiency potentially accentuating their risk for further adverse atherosclerotic events in a setting without folate fortification. A clinical trial of folate supplementation among stroke survivors is warranted.

Micronutrients and socio-demographic factors were major predictors of anaemia among the Ethiopian population.

Anaemia is characterised by low hemoglobin (Hb) concentration. Despite being a public health concern in Ethiopia, the role of micronutrients and non-nutritional factors as a determinant of Hb concentrations has been inadequately explored. This study focused on the assessment of serum micronutrient and Hb concentrations and a range of non-nutritional factors, to evaluate their associations with the risk of anaemia among the Ethiopian population (n 2046). It also explored the mediation effect of Zn on the relation between se and Hb. Bivariate and multivariate regression analyses were performed to identify the relationship between serum micronutrients concentration, inflammation biomarkers, nutritional status, presence of parasitic infection and socio-demographic factors with Hb concentration (n 2046). Sobel-Goodman test was applied to investigate the mediation of Zn on relations between serum se and Hb. In total, 18·6 % of participants were anaemic, 5·8 % had iron deficiency (ID), 2·6 % had ID anaemia and 0·6 % had tissue ID. Younger age, household head illiteracy and low serum concentrations of ferritin, Co, Cu and folate were associated with anaemia. Serum se had an indirect effect that was mediated by Zn, with a significant effect of se on Zn (P < 0·001) and Zn on Hb (P < 0·001). The findings of this study suggest the need for designing a multi-sectorial intervention to address anaemia based on demographic group.

Pregnancy, folic acid, and antiseizure medication

Abstract Background Although some antiseizure medications (ASMs) are teratogenic, most people with epilepsy need treatment in pregnancy. The risk of ASM fetotoxicity may be mitigated with folic acid. High-dose folic acid supplementation has traditionally been recommended before and during gestation despite little evidence of efficacy and safety for this patient group. Several studies have investigated the potential benefits and risks of folic acid supplements. Objective To provide an updated overview of the risks, benefits, and rationale for use of folic acid supplementation in relation to pregnant people of childbearing age using ASM. Materials and methods This is a narrative review based on an unstructured literature search of PubMed. We also scrutinized neurological and obstetrical guidelines. Results Antiseizure medication can decrease folate concentrations. In children exposed to ASM prenatally, those born to persons using folic acid supplements periconceptionally had lower risk of adverse neurodevelopment and preterm birth. It remains unclear whether the risk for congenital malformations can be equally alleviated. In studies of the general population, high plasma folate concentrations and/or high-dose folic acid supplements were associated with adverse neurodevelopmental outcomes. This has not been seen in children of mothers with epilepsy. However, an increased cancer risk has been found in children of mothers with epilepsy using high-dose folic acid supplements in pregnancy. Conclusion The optimal folic acid dose is not clear for persons of childbearing potential with epilepsy using ASM. Both low and excess folate status during pregnancy have been associated with adverse neurodevelopment. We propose an individual folic acid supplement dose that should be titrated based on maternal plasma folate concentrations during pregnancy.

Higher concentrations of folic acid reduced the dietary requirements of supplemental methionine for commercial broilers.

An experiment was conducted to study the effect of supplementing DL methionine (DL Met) at graded concentrations on performance, carcass variables, immune responses and antioxidant variables in broiler chicken fed folic acid (FA) fortified (4 mg/kg) lowmethionine diet. A basal diet (BD) without supplemental DL Met, but with higher level (4 mg/kg) of FA and a control diet (CD) with the recommended concentration of methionine (Met) were prepared. The BD was supplemented with DL Met at graded concentrations (0%, 10%, 20%, 30%, 40%, and 50% supplemental DL Met of CD). Each diet was fed ad libitum to 10 replicates of 5 broiler male chicks in each from 1 to 42 d of age. Body weight gain (BWG) reduced, and feed conversion ratio (FCR) increased in broilers fed low-Met BD. At 30% and 20% inclusion of DL met, the BWG and FCR, respectively were similar to those fed the CD. Similarly, supplementation of 10% DL Met to the BD significantly increased ready to cook meat yield and breast meat weight, which were similar to those of the CD fed broilers. Lipid peroxidation reduced, the activity of antioxidant enzymes (GSHPx and GSHRx) in serum increased and lymphocyte proliferation increased with increased supplemental DL Met level in the BD. The concentrations of total protein and albumin in serum increased with DL Met supplementation to the BD. Based on the data, it can be concluded that supplemental Met can be reduced to less than 50% in broiler chicken diets (4.40, 3.94, and 3.39 g/kg, respectively in pre-starter, starter and finisher phases) containing 4 mg/kg FA.

P-299 Influence of one carbon metabolism supplements over developmental dynamics and gene expression of genes related to DNA methylation machinery in mice

Abstract Study question Does betaine and the active metabolite 5-MTHF influence cleavage dynamics and expression of genes related to methylation during preimplantation embryos? Summary answer Supplementation of betaine and 5-MTHF had no influence over morphokinetics of mice preimplantation embryos but induced transcriptional variations over methylation activity related-genes. What is known already After fertilization, the emerging genome is reprogrammed to enable the control of cellular differentiation all over downstream events and lead further developmental progression. One of the most determining processes defining these new genomic states in cell daughter is mediated by methylation. S-adenosylmethionine (SAM) is the main donor of methyl groups to DNA and its availability during highly active conditions can be sensitive to external conditions and dependent on one carbon metabolism (OCM). DNA methyltransferases (DNMT1, DNMT3a and DNTM3b) and methionine adenosyltransferase (MAT2a and MAT2b) are influenced by OCM and key components of DNA methylation machinery. Study design, size, duration This is a prospective experimental study conducted from November 2022 to January 2023. F1 hybrid (B6/CBA) fresh mice embryos were exposed to different culture conditions. A primary analysis consisted of the morphokinetics assessment of embryo development through time-lapse system up to expanded blastocyst (105 hours), including a score assessment based on blastocyst appearance. Subsequently functional analysis based on gene expression of selected genes was carried out over individual embryos. Participants/materials, setting, methods The zygotes were collected from the oviduct, washed and culture in KSOM supplemented with 5-MTHF and betaine at respectively concentrations of 50μM and 50μg/mL (THF/bet(50)), 10μM and 10μg/mL (THF/bet(10)) and no supplements for control. Geri incubator was used for culture at 37 °C, 6%CO2 and 5%O2. In a new assay, 4cells and 8cells embryos exposed to THF/bet(50) and control conditions were individually collected for pre-amplification and subsequent RT-qPCR quantification using GADPH as housekeeping gene. Main results and the role of chance A total of 54 mice embryos were used for the present study. The timings required for embryos to reach different developmental stages (t2, t4, t8 and tB) were manually selected and their comparison did not show any overall differences. A slightly faster trend could be observed for the THF/bet(50) group during the 3 first cleavage events (t2, t4 and t8), this group showed proportionally better morphology of blastocysts. Expression analysis showed no variation for DNMT1; by contrast, greatest changes were observed for DNMT3a and DNMT3b whose relative expressions were downregulated at 4 cells ∼0.5 fold-changes (p &amp;lt; 0.01) and highly increased for more than 2 fold-change in 8 cells in THF/bet(50) group. In addition, early downregulation at 4 cells was observed for either MAT2a and MAT2b with ∼0.5 fold-changes (p &amp;lt; 0.01); however, at 8 cells levels were reestablished in both similar levels than control. One carbon metabolism induced changes in gene expression of enzymes involved in de novo methylation of DNA DNMT3a and DNMT3a. In addition, Methyl adenyl transferases MAT2a and MAT2b were also influenced, particularly MAT2a which has a pivotal role relevant for genome activation in the embryo. Limitations, reasons for caution The translational approach is still limited due to known differences between kinetics of mice and human embryo. Intracellular concentration of folates and betaine in embryos are still unknown and the range of dosage used has been decided accordingly to previous studies showing a response in mice embryos under similar conditions. Wider implications of the findings Folate supplements are widely accepted for pregnant and women attempting to become pregnant, these are also recently incorporated in some IVF mediums. The influence of OCM in surrounding environment during highly active methylation activities of early embryo is still unknown, benefits or risks of these supplies require further assessment. Trial registration number not applicable

Associations of serum 25-hydroxyvitamin D with serum folate, cobalanin, and homocysteine concentrations and methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in healthy adults.

The aim of this study was to investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] with various demographic, anthropometric, and genetic characteristics and biochemical parameters in healthy Greek adults. Demographic (age and sex), anthropometric (body mass index/BMI), and genetic (MTHFR gene polymorphisms) characteristics and biochemical parameters (serum folate, cobalamin/Cbl, and total homocysteine/tHcy concentrations), which had been recorded and measured, among others, in the framework of periodic medical examination (military personnel) or check-up (non-military personnel) of 383 healthy Greek adults (199 men and 184 women) were analyzed. Serum 25(OH)D, tHcy, folate, and Cbl levels were determined using immunoassay methods. The MTHFR C677T and A1298C gene polymorphisms were genotyped using polymerase chain reaction and reverse hybridization. Serum 25(OH)D concentrations were correlated with Cbl levels and MTHFR C677T gene polymorphism, while they had a reverse correlation with serum tHcy levels, age, and BMI. There was no significant correlation between serum 25(OH)D concentrations and sex, serum folate levels, and smoking status. Individuals with the 677TT genotype had statistically significantly lower serum 25(OH)D levels than those with the 677CC or 677CT genotype, while individuals with the 1298CC genotype had statistically significantly higher serum 25(OH)D levels than those with 1298AA or 1298AC genotype. Moreover, the reverse correlation between the serum 25(OH)D and tHcy levels was statistically significant in all six MTHFR genotypes. Serum 25(OH)D levels are associated with age, BMI, serum tHcy, and Cbl levels and MTHFR C677T gene polymorphism. The most significant finding of our study is the observed reverse correlation of serum 25(OH)D levels with serum tHcy levels. Considering that vitamin D deficiency and hyperhomocysteinemia (HHcy) are associated with an increased risk for cardiovascular diseases (CVDs), we suggest that individuals with high serum tHcy levels should be further investigated for, inter alia, their serum 25(OH)D levels.

Mitochondrial folate pathway regulates myofibroblast differentiation and silica-induced pulmonary fibrosis

BackgroundSilica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment.MethodsThe experiments were conducted in TGF-β treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo.ResultsBy quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-β stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice.ConclusionOur study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

Folate concentrations and serum perfluoroalkyl and polyfluoroalkyl substance concentrations in adolescents and adults in the USA (National Health and Nutrition Examination Study 2003–16): an observational study

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are a family of highly fluorinated aliphatic compounds, which are widely used in commercial applications, including food packaging, textiles, and non-stick cookware. Folate might counteract the effects of environmental chemical exposures. We aimed to explore the relationship between blood folate biomarker concentrations and PFAS concentrations. This observational study pooled cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2003 to 2016 cycles. NHANES is a population-based national survey that measures the health and nutritional status of the US general population every 2 years by means of questionnaires, physical examination, and biospecimen collection. Folate concentrations in red blood cells and in serum, and perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) concentrations in serum were examined. We used multivariable regression models to assess the percentage change in serum PFAS concentrations in relation to changes in folate biomarker concentrations. We additionally used models with restricted cubic splines to investigate the shape of these associations. This study included 2802 adolescents and 9159 adults who had complete data on PFAS concentrations, folate biomarkers, and covariates, were not pregnant, and had never had a cancer diagnosis at the time of the survey. The mean age was 15·4 years (SD 2·3) for adolescents and 45·5 years (17·5) for adults. The proportion of male participants was slightly higher in adolescents (1508 [54%] of 2802 participants) than in adults (3940 [49%] of 9159 participants). We found negative associations between red blood cell folate concentrations and serum concentrations of PFOS (percentage change for a 2·7 fold-increase in folate level -24·36%, 95% CI -33·21 to -14·34) and PFNA (-13·00%, -21·87 to -3·12) in adolescents, and PFOA (-12·45%, -17·28 to -7·35), PFOS (-25·30%, -29·67 to -20·65), PFNA (-21·65%, -26·19 to -16·82), and PFHxS (-11·70%, -17·32 to 5·70) in adults. Associations for serum folate concentrations and PFAS were in line with those found for red blood cell folate levels, although the magnitude of the effects was lower. Restricted cubic spline models suggested linearity of the observed associations, particularly for associations in adults. In this large-scale, nationally representative study, we found consistent inverse associations for most examined serum PFAS compounds in relation to folate concentrations measured in either red blood cells or serum among both adolescents and adults. These findings are supported by mechanistic in-vitro studies that show the potential of PFAS to compete with folate for several transporters implicated in PFAS toxicokinetics. If confirmed in experimental settings, these findings could have important implications for interventions to reduce the accumulated PFAS body burden and mitigate the related adverse health effects. United States National Institute of Environmental Health Sciences.

INFLUENCE OF THE METHYLENE TETRAHYDROFOLATE REDUCTASE (MTHFR) GENE POLYMORPHISMS ON SERUM FOLATE, COBALANIN AND HOMOCYSTEINE LEVELS IN HEALTHY GREEK ADULTS

Objective: Methylene tetrahydrofolate reductase (MTHFR) is a key enzyme of homocysteine metabolism participating in the folate cycle. It is well known that hyperhomocysteinemia is associated with an increased risk for cardiovascular disease. The aim of this study was to investigate the association of MTHFR C677T and MTHFR A1298C gene polymorphisms with serum folate, cobalamin (Cbl) and homocysteine (Hcy) concentrations in healthy Greek adults. Design and method: The MTHFR C677T and A1298C gene polymorphisms were genotyped in 383 healthy Greek adults (199 men; mean age±SD: 37.3±8.2 years) using polymerase chain reaction and reverse hybridization. Serum folate, Cbl and total Hcy (tHcy) levels were determined using immunoassays methods. Results: Among the 383 individuals, 73 (19.1%) were normal (CC), 202 (52.7%) were heterozygous (CT) and 108 (28.2%) were homozygous (TT) regarding the MTHFR C677T gene polymorphism, while 263 (68.7%) were normal (AA), 105 (27.4%) were heterozygous (AC) and 15 (3.9%) were homozygous (CC) regarding the MTHFR A1298C gene polymorphism. The overall C and T allele frequency for the MTHFR C677T gene polymorphism was 45.4% and 54.6%, respectively, while the overall A and C allele frequency for the MTHFR A1298C gene polymorphism was 82.3% and 17.6%, respectively. The individuals with 677TT genotype had significantly lower serum folate and significantly higher serum tHcy levels than individuals with 677 CC or CT genotypes. On the contrary, the A1298C gene polymorphism had no significantly influence on serum folate and tHcy levels. Conclusions: Serum folate and tHcy levels are influenced by the existence of the MTHFR C677T gene polymorphism (mainly 677TT genotype). Individuals with low serum folate levels and/or high serum tHcy levels should be further investigated for a possible existence of MTHFR C677T and not A1298C gene polymorphisms, with aim to determine the suitable treatment.

Association between serum folate and vitamin B12 and cervical high-risk human papillomavirus (HPV) infection.

5541 Background: Serum concentration of folate (vitamin B9) and vitamin B12 were inversely associated with cervical intraepithelial neoplasia and cervical cancer in some studies. The association between folate and vitamin B12, and human papillomavirus (HPV) infection has not been well elucidated. We evaluated whether low serum level of folate and vitamin B12 was associated with high-risk HPV (hrHPV) infection. Methods: The study population was 6,452 women, aged 18-59 years old, enrolled in the National Health and Nutrition Examination Survey (NHANES), from 2003 to 2016, in the United States. In this cross-sectional study, odds ratios (ORs) of hrHPV were calculated, by quintiles of low folate and vitamin B12 combined, using logistic regression models. Results: The mean age (standard deviation) of the women was 36.98 (12.19) years. Women in the lowest quintile had less than 20.6 nmol/L of folate and less than 248 pmol/L of vitamin B12. Some of the women, 23% (1,509/6,452), were hrHPV positive. In age-adjusted models, low folate and vitamin B12 was significantly associated with hrHPV infection. The ORs and 95% confidence intervals (CI) was (OR: 0.704, 95% CI: 0.509 - 0.975, p = 0.034) for the second, (OR: 0.671, 95% CI: 0.479 - 0.940, p = 0.020) third, (OR: 0.534, 95% CI: 0.370 - 0.770, p = 0.0008) fourth and (OR: 0.476, 95% CI: 0.33 - 0.679, p &lt; 0.0001) fifth quintiles, compared to women in the lowest quintile. The association remained statistically significant after the models were further adjusted for smoking status and income level; women in the highest quintile were less likely to have hrHPV infection compared to those in the lowest quintile (OR: 0.541, 95% CI: 0.343 - 0.855, p = 0.008). Conclusions: This study supports an association between low serum levels of folate and vitamin B12, and hrHPV infection, among women in the United States.

Anti- SARS-CoV-2 IgG and IgM Levels in Iraqi General Population.

Acquired immunity plays an important role in the prevention of viral infections. SARS-CoV-2 is an infection that leads to a pandemic. The development of specific anti-SARSCoV- 2 antibodies may play a vital role in disease prevention and control. Thus IgG antibody screening in the general population provides information on the immunological status of the community. To clarify the SARS-CoV-2 immune status in the general population. A cross-sectional study was conducted in Kirkuk province during the period from 15 May 2022 to 11 September 2022. The samples were collected from voluntary subjects and informed consent was taken from each participant before their enrolment in the study. SARS-CoV-2 IgG, SARSCoV- 2 IgM, 25-OH Vitamin D, Vitamin B12, and Folate were determined using the Electrochemiluminescence Immunoassay (eCLIA) technique with the instrument NIPIGON-Robot R1Automated ECL Analyzer (Canada). The overall IgG mean concentration was 37.75 ± 23.18 COI, with a median of 39.99 COI and a range of 0.25 - 87.23 COI. Additionally, 93% of tested samples were with concentrations of more than 1 COI. The highest frequency (18.2%) was for the IgG concentration of 51 to 60 COI, while the lowest frequency (1.3%) was for the concentration of 81 - 90 COI. The IgG was significantly higher (P = 0.046) in males (39.87 ± 24.04 COI) than that in females (35.12 ± 21.89 COI). The IgM overall concentration was 0.569 ± 0.456 COI, with a median of 0.489 COI and a range of 0.17 - 6.40 COI. The mean serum level of folic acid concentration was 9.03 ± 5.72 ng/ml, with a median of 7.476 ng/ml and a range of 0.60 - 20.00 ng/ml. The mean serum concentration of vitamin B12 was 462.65 ± 349.18 pg/ml, with a median of 353 pg/ml and a range of 13.05 - 2000 pg/ml. The mean serum concentration of vitamin D was 18.29 ± 18.42 ng/ml with a median of 12.44 ng/ml and a range of 3 - 100 ng/ml. IgG and IgM serum levels did not show a significant correlation with serum levels of folic acid, vitamin D, and vitamin B12. However, there was a significant correlation between folic acid and vitamin D (r = 0.197; P = 0.012); vitamin B12 and vitamin D (r = 0.253, P = 0.001). While there was a non-significant correlation between folic acid and vitamin D serum levels (r = 0.129, P = 0.10). General population IgG antibody concentration reflects a high rate of herd immunity. Folic acid was with a mean value of about half of the upper normal limit and only 17.7% were with low values. Vitamin B12, only 6.3% of the population had values lower than normal. However, the range of vitamin B12 was wide. While vitamin D values were lower than the normal limit at 82.6%. However, a large scale well designed was warranted to evaluate COVID-19 national immune response.

Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes

Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes. To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort. In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022. Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy. Birth weight and gestational age, abstracted from delivery records; birth weight z score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks. The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight z score only among mothers whose dietary folate intake (birth weight: β, -89.13 g; 95% CI, -166.84 to -11.42 g; birth weight z score: -0.13; 95% CI, -0.26 to -0.003) or plasma folate concentration (birth weight: -87.03 g; 95% CI, -180.11 to 6.05 g; birth weight z score: -0.14; 95% CI, -0.30 to 0.02) were below the 25th percentile (dietary: 660 μg/d, plasma: 14 ng/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups. In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.

Folic acid - influence on male fertility, spermatogenesis, sperm DNA fragmentation and subsequent growth of the embryo and fetus

Introduction: Men's infertility is a multifactorial disorder. According to scientific literature, among men with reduced fertility, growing interest in folic acid is observed. This review describes the effect of folic acid on spermatogenesis, sperm concentration, sperm DNA fragmentation and the growth of the embryo and fetus. Material and methods: The work was based on the articles published in PubMed, medical books and websites. Results: Folic acid affects the trajectory of embryo growth in pregnancy conceived spontaneously, there is a negative correlation between the concentration of folic acid in the semen and the indicator of sperm DNA fragmentation and sperm concentration are statistically higher in folic acid supplements. Conclusions: The results suggest that the father's exposure to folic acid before conception may affect the health of his offspring, and therefore care before conception should be changed from an approach focused on a woman to a couple-based approach.

High Serum Folate Concentration, Vitamin B12 Deficiency, and Anthropometric Nutritional Status in Brazilian Children Aged 6–59 Months: Data from the Brazilian National Survey of Child Nutrition

BackgroundVitamin B12 and folate are key nutrients that help children reach their full potential in growth and development; however, little is known about the status of these vitamins in Brazilian children. ObjectivesTo describe the serum concentrations of vitamin B12 and folate, to investigate the association between high folate concentration (HFC) and vitamin B12 deficiency, and to evaluate the association between vitamin B12 and stunting/underweight in Brazilian children aged 6–59 mo. MethodsData from 7417 children aged 6–59 mo collected during the Brazilian National Survey on Child Nutrition were used. Serum concentrations of vitamin B12 of <150 pmol/L and folate of <10 nmol/L were classified as deficient, and folate concentrations of >45.3 nmol/L were classified as HFC. Children with length/height-for-age z-score of less than −2 were considered stunted, and those with weight-for-age z-score of less than −2 were underweight. Logistic regression models were performed. ResultsIn Brazil, 14.2% (95% CI: 12.2, 16.1) of children aged 6–59 mo had vitamin B12 deficiency, 1.1% (95% CI: 0.5, 1.6) had folate deficiency, and 36.9% (95% CI: 33.4, 40.3) had HFC. Vitamin B12 deficiency was higher in children from the northern region of Brazil (28.5%), between 6 and 24 mo (25.3%), whose mothers had lower formal education (0–7 y; 18.7%). Children with HFC had 62% lower odds (OR: 0.38; 95% CI: 0.27, 0.54) of vitamin B12 deficiency than those with normal/deficient folate. Children with vitamin B12 deficiency and normal/deficient folate had higher odds of stunting (OR: 1.58; 95% CI: 1.02, 2.43) than children without vitamin B12 deficiency and normal/deficient folate. ConclusionsVitamin B12 deficiency is a public health problem among Brazilian children aged <2 y with vulnerable socioeconomic status. HFC was inversely associated with vitamin B12 deficiency, and lower odds of stunting were observed in children with HFC and vitamin B12 deficiency than in those with vitamin B12 deficiency and normal/deficient folate.

Does maternal genetic liability to folate deficiency influence the risk of antiseizure medication-associated language impairment and autistic traits in children of women with epilepsy?

BackgroundPrenatal exposure to antiseizure medication (ASM) may lead to low plasma folate concentrations and is associated with impaired neurodevelopment. ObjectivesTo examine whether maternal genetic liability to folate deficiency interacts with ASM-associated risk of language impairment and autistic traits in children of women with epilepsy. MethodsWe included children of women with and without epilepsy and with available genetic data enrolled in the Norwegian Mother, Father, and Child Cohort Study. Information on ASM use, folic acid supplement use and dose, dietary folate intake, child autistic traits, and child language impairment was obtained from parent-reported questionnaires. Using logistic regression, we examined the interaction between prenatal ASM exposure and maternal genetic liability to folate deficiency expressed as polygenic risk score of low folate concentrations or maternal rs1801133 genotype (CC or CT/TT) on risk of language impairment or autistic traits. ResultsWe included 96 children of women with ASM-treated epilepsy, 131 children of women with ASM-untreated epilepsy, and 37,249 children of women without epilepsy. The polygenic risk score of low folate concentrations did not interact with the ASM-associated risk of language impairment or autistic traits in ASM-exposed children of women with epilepsy compared with ASM-unexposed children aged 1.5–8 y. ASM-exposed children had increased risk of adverse neurodevelopment regardless of maternal rs1801133 genotype {adjusted odds ratio [aOR] for language impairment aged 8 y was 2.88 [95% confidence interval (CI): 1.00, 8.26] if CC and aOR 2.88 [95% CI: 1.10, 7.53] if CT/TT genotypes}. In children of women without epilepsy aged 3 y, those with maternal rs1801133 CT/TT compared with CC genotype had increased risk of language impairment (aOR: 1.18; 95% CI: 1.05, 1.34). ConclusionsIn this cohort of pregnant women reporting widespread use of folic acid supplements, maternal genetic liability to folate deficiency did not significantly influence the ASM-associated risk of impaired neurodevelopment.