Adequate Folate Research Articles

Folates, bacteria and ageing: insights from the model organism C. elegans in the study of nutrition and ageing.

The relationship between nutrition and ageing is complex. The metabolism and synthesis of micronutrients within the gut microbiome can influence human health but is challenging to study. Furthermore, studying ageing in humans is time-consuming and difficult to control for environmental factors. Studies in model organisms can guide research efforts in this area. This review describes how the nematode Caenorhabditis elegans can be used to study how bacteria and diet influence ageing and inform follow-on studies in humans. It is known that certain bacteria accelerate ageing in C. elegans. This age-accelerating effect is prevented by inhibiting folate synthesis within the bacteria, and we propose that in the human microbiome, certain bacteria also accelerate ageing in a way that can be modulated by interfering with bacterial folate synthesis. Bacterial-derived folates do not promote ageing themselves; rather, ageing is accelerated by bacteria in some way, either through secondary metabolites or other bacterial activity, which is dependent on bacterial folate synthesis. In humans, it may be possible to inhibit bacterial folate synthesis in the human gut while maintaining healthy folate status in the body via food and supplementation. The supplement form of folic acid has a common breakdown product that can be used by bacteria to increase folate synthesis. Thus, supplementation with folic acid may not be good for health in certain circumstances such as in older people or those with an excess of proteobacteria in their microbiome. For these groups, alternative supplement strategies may be a safer way to ensure adequate folate levels.

Folate fortification for spina bifida: preventing neural tube defects.

Neural tube defects (NTDs), such as spina bifida and anencephaly, are severe congenital anomalies affecting the development of the brain and spine. These conditions are often linked to folic acid deficiency during early pregnancy, a modifiable risk factor. While high-income countries have implemented mandatory folic acid fortification in staple foods, resulting in significant reductions in NTD prevalence, low- and middle-income countries (LMICs) continue to experience disproportionately high rates of these birth defects. Folic acid supplementation and fortification are proven interventions for preventing NTDs, but many LMICs face political, financial, and logistical barriers to implementing these programs. This paper highlights the importance of mandatory folic acid fortification as a cost-effective public health intervention and advocates for its expansion in LMICs. It reviews the successes of fortification programs in high-income countries, explores alternative food vehicles like rice for regions with different dietary staples, and discusses the potential of multi-nutrient fortification strategies. Additionally, this paper emphasizes the need for global collaboration, enhanced monitoring and evaluation, and public health education campaigns to ensure that women of reproductive age, especially in LMICs, receive adequate folic acid. By addressing these challenges, the global health community can significantly reduce the incidence of NTDs, improve maternal and child health, and promote health equity worldwide. The time to act is now, as the benefits of folic acid fortification far outweigh the costs of inaction.

A simple and efficient electrochemical sensor for folic acid determination on Ti(OH)4 modified carbon paste electrode

Folic acid (FA) has a crucial function in pregnant women and anemic patients. Having adequate FA prior to and during the gestation period can protect the brain of the child and spine from significant birth abnormalities. It reduces the risk of stroke, heart disease and some types of cancers, etc. Thus, FA is employed as a reliable biomarker in the early identification of various disorders. In the present study, we synthesized titanium tetra hydroxide [Ti(OH)4] nanoparticles (NPs) by precipitation method with annealing at 100 °C, which is used to modify carbon paste electrode (Ti(OH)4 /MCPE). FA is detected here by voltammetry method using Ti(OH)4/MCPE in the phosphate buffer of pH 6 and compared with bare and TiO2-400, TiO2-600 and TiO2-800 °C NPs MCPE. Based on ac-impedance spectra, the conductivity of Ti(OH)4/MCPE was found to be higher, and consequently this electrode showed excellent sensitivity of 5.5 µA µM−1 cm−2. Lower detection limit (1.3 nM) was observed in the concentration range of 0.4–30 μM by differential pulse voltammetry. The Ti(OH)4/MCPE was also effective for the determination of FA in real samples such as orange, banana, spinach and tablet. The electrochemical sensor investigated here showed excellent stability (92 %) up to 30 days.

Protective effects of diversified diets for dietary folate adequacy and serum homocysteine in breastfeeding mothers amid historic drought.

The United Nations recommends that women consume ≥5 food groups, also known as the minimum dietary diversity score for women (MDD-W), for nutritional health. This is increasingly unattainable for populations in climate hot zones coping with food insecurity by prioritizing calories over dietary breadth. Breastfeeding mothers may be particularly vulnerable to adverse health impacts of low dietary diversity due to elevated nutritional requirements for lactation. We investigated how the protective effects of MDD-W for folate adequacy varies by MDD-W score and mother-infant life history characteristics. We conducted a secondary analysis of cross-sectional data from breastfeeding mothers (n = 228) in northern Kenya, surveyed during the 2006 Horn-of-Africa drought. Logistic regression models for adequate dietary folate (and vitamins B12 and B6) and normal homocysteine (folate-replete status) evaluated the effect of MDD-W alone and in interaction with infant/maternal characteristics. MDD-W (as ordinal or dichotomous variable) was positively associated with adequate folate (and vitamin B12). Having male infant was inversely associated with adequate dietary folate. MDD-W was generally unassociated with homocysteine. However, there was an interaction between MDD-W and sex of the infant. Namely, MDD-W ≥ 3 predicted increased probability of normal homocysteine among mothers with female infants but not male infants. Diets consisting of three or more food groups may protect adequate folate intake for many breastfeeding mothers. More research is needed to establish what level of dietary diversity would protect against hyperhomocysteinemia during breastfeeding and what factors promote or hinder the benefit of diversified diets on maternal folate nutrition.

Epidemiology of neural tube defects in Finland: a nationwide register study 1987-2018.

Our aim was to evaluate the prevalence, mortality, regional and sex distribution of neural tube defects (NTDs) in Finland. Data for this population-based study were collected from 1987 to 2018 from the national health and social welfare registers. There were in total 1634 cases of NTDs, of which 511 were live births, 72 pregnancies ended in stillbirth and 1051 were terminations of pregnancy due to fetal anomaly (TOPFA). The total prevalence of NTDs was 8.6 per 10 000 births and it increased slightly annually (OR 1.008; 95% CI: 1.002, 1.013) during the 32-year study period. The birth prevalence of NTDs decreased (OR 0.979; 95% CI: 0.970, 0.987), but the prevalence of TOPFA increased annually (OR 1.024; 95% CI 1.017, 1.031). The perinatal mortality of NTD children was 260.7 per 1000 births and the infant mortality was 184.0 per 1000 live births, whereas these measures in the general population were 4.6 per 1000 births and 3.3 per 1000 live births, respectively. There was no difference in the NTD prevalence between males and females (P-value 0.77). The total prevalence of NTDs varied from 7.1 to 9.4 per 10 000 births in Finland by region. Although the majority of NTDs are preventable with an adequate folic acid supplementation, the total prevalence increased in Finland during the study period when folic acid supplementation was mainly recommended to high-risk families and to women with folic acid deficiency. NTDs remain an important cause of infant morbidity and mortality in Finland.

Association between early spontaneous abortion and homocysteine metabolism.

The purpose of this study is to explore the effects of homocysteine (HCY) metabolism and related factors on early spontaneous abortion. We conducted a hospital-based case-control study and included a total of 500 cases and 1,000 controls in Shaanxi China. Pregnant women waiting for delivery in the hospital were interviewed to report their characteristics and other relevant information during pregnancy. The unconditional Logisitic regression model was applied to assess the association between early spontaneous abortion and HCY metabolism and related factors. The multiplicative model was applied to assess the effects of interaction of HCY metabolism and related factors on early spontaneous abortion. The logit test method of generalized structural equation model (GSEM) was used to construct the pathway diagram of HCY metabolism and related factors affecting early spontaneous abortion. Folic acid supplementation and adequate folic acid supplementation during periconception were the protective factors of early spontaneous abortion (OR = 0.50, 95% CI: 0.38-0.65; OR = 0.44, 95% CI: 0.35-0.54). The serum folate deficiency, higher plasma HCY in early pregnancy, the women who carried the MTHFR 677TT genotype were the risk factors of early spontaneous abortion (OR = 5.87, 95% CI: 1.53-22.50; OR = 2.94, 95% CI: 1.14-7.57; OR = 2.32, 95% CI: 1.20-4.50). The women's educational level and maternal and child health care utilization affected the occurrence of early spontaneous abortion by influencing the folic acid supplementation during periconception. The folic acid supplementation during periconception affected the occurrence of early spontaneous abortion by influencing the level of serum folate or plasma HCY in early pregnancy. The maternal MTHFR 677 gene polymorphism affected the occurrence of early spontaneous abortion by influencing the level of serum folate in early pregnancy. In terms of the risks for early spontaneous abortion, there was multiplicative interaction between higher plasma HCY in early pregnancy, serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 1.76, 95% CI: 1.17-4.03), and there was multiplicative interaction between higher plasma HCY and serum folate deficiency in early pregnancy (OR = 3.46, 95% CI: 2.49-4.81), and there was multiplicative interaction between serum folate deficiency in early pregnancy and maternal MTHFR 677TT genotype (OR = 3.50, 95% CI: 2.78-5.18). The above interactions are all synergistic. The occurrence risk of early spontaneous abortion was significantly increased if multiple factors existed at the same time. Our study is the first time to construct the pathway of HCY metabolism and related factors affecting early spontaneous abortion, and provides a comprehensively new idea to prevent and reduce the occurrence of spontaneous abortion.

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

Folate, also known as vitamin B9, facilitates the transfer of methyl groups among molecules, which is crucial for amino acid metabolism and nucleotide synthesis. Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.

Assessment of blood one-carbon metabolism indexes during mid-to-late pregnancy in 397 Chinese pregnant women.

One-carbon metabolism (OCM) significantly influences fetal growth and neurodevelopment through transferring methyl group to biomolecules, during which folate, methionine, choline and betaine function as methyl donor nutrients, while vitamin B2, B6, B12 function as enzyme cofactors, and homocysteine (Hcy) and S-adenosyl methionine (SAM) are functional metabolites. This study aimed to assess blood OCM index levels and explore their relationships among Chinese pregnant women. Data were obtained from the baseline of the Mother-Child Nutrition and Health Cohort Study. Pregnant women, voluntarily recruited from September 2020 to June 2022 during antenatal examinations in five Chinese cities at 24-32 gestational weeks, provided fasting venous blood samples. Measurements included RBC and serum folate, serum vitamin B2, B6, B12, choline, betaine, methionine, total Hcy (tHcy), and plasma SAM. Sociodemographic characteristics and pregnancy-related conditions were collected via a self-designed questionnaire. Of 397 participants, 82.6% were in mid-pregnancy (24-27 gestational weeks) and 17.4% were in late-pregnancy (28-32 gestational weeks). Serum folate, vitamin B6, and B12 deficiencies were 2.5, 1.3, and 8.3%, respectively. Elevated tHcy (≥10 μmol/L) was observed in 1.8% of pregnant women. Elderly pregnant women (aged 35 and above) exhibited significantly lower serum methionine levels (p < 0.05), while multiparous women had lower RBC folate levels (p < 0.05), and lower serum methionine and vitamin B12 levels (p < 0.10, not statistically significant). Partial correlation analysis revealed positive associations between RBC folate and cofactor vitamin B12 (r = 0.244, p < 0.05) in the folate cycle, as well as significant correlations between two methyl donor paths [serum folate was significantly related to serum choline (r = 0.172) and betaine (r = 0.193)]. As functional biomarkers of OCM, serum tHcy exhibited negative associations with RBC folate (β = -0.330, p < 0.05) and vitamin B6 (β = -0.317, p < 0.05), and plasma SAM displayed a positive association with serum betaine (β = 0.610, p < 0.05), while negatively associated with serum vitamin B6 (β = -0.181, p < 0.05). The blood OCM exhibited imbalances during mid-to-late pregnancy, characterized by lower levels of folate, vitamin B6, and B12, alongside elevated tHcy levels. Adequate folate and vitamin B6 emerged as significant predictors of lower tHcy levels. Additionally, serum betaine showed a positive correlation with plasma SAM. This suggests the importance of not only ensuring sufficient folate but also optimizing other OCM-related nutrients throughout pregnancy.

Relationship Between Folate and Depression: A Systematic Review

Introduction: The relationship between folate (or folic acid) and depression is increasingly recognized in mental health and nutrition. Folate is essential for DNA synthesis, cell repair, and neurotransmitter production, while depression is a widespread mental disorder marked by sadness and disinterest. Observational studies and narrative reviews indicate a correlation between low folate levels and a higher risk of depression, as folate is crucial for synthesizing neurotransmitters like serotonin and dopamine, which regulate mood. Methodology: The primary objective of this study is to investigate the relationship between folate levels and depressive symptoms. This will be achieved through a systematic review and meta-analysis of randomized clinical trials (RCTs). Conclusion: It is important the role of folic acid (vitamin B9) in mental health, specifically its relationship with depression and how adequate levels of this nutrient may help reduce symptoms or the risk of developing depressive disorders. Must be highlighted that folate is crucial for synthesizing neurotransmitters like serotonin and dopamine, which regulate mood. Maintaining adequate folate levels is crucial for mood health, and targeted supplementation can be beneficial for individuals suffering from depression linked to folate deficiency.

Impact of folic acid supplementation on the epigenetic profile in healthy unfortified individuals – a randomized intervention trial

ABSTRACT Folate is an essential mediator in one-carbon metabolism, which provides methyl groups for DNA synthesis and methylation. The availability of active methyl groups can be influenced by the uptake of folic acid. We conducted a randomized intervention trial to test the influence of folic acid supplementation on DNA methylation in an unfortified population in Germany. A total of 16 healthy male volunteers (age range 23–61 y) were randomized to receive either 400 μg (n = 9) or 800 μg (n = 7) folic acid supplements daily for 8 weeks. Infinium Human Methylation 450K BeadChip Microarrays were used to assay site-specific DNA methylation across the genome. Microarray analyses were conducted on PBL DNA. We estimated several epigenetic clocks and mean DNA methylation across all autosomal probes on the array. AgeAccel was estimated as the residual variation in each metric. In virtually all participants, both serum and red blood cell (RBC) folate increased successively throughout the trial period. Participants with a larger increase in RBC folate had a larger increase in DNAmAge AgeAccel (Spearman Rho: 0.56, p-value = 0.03). No notable changes in the methylome resulting from the folic acid supplementation emerged. In this population with adequate folate levels derived from diet, an increase in RBC folate had a modest impact on the epigenetic clock predicting chronologic age.

Factors Associated with SARS-CoV-2 Infection Evaluated by Antibody Response in a Sample of Workers from the Emilia-Romagna Region, Northern Italy.

Factors associated with SARS-CoV-2 infection risk are still debated. This case-control study aims to investigate the possible relationship between SARS-CoV-2 infection, evaluated through antibody response, and the main sociodemographic, occupational, clinical-anamnestic, and biochemical factors in a population of Modena province (Northern Italy), mainly workers. Both workers who voluntarily joined the screening campaign proposed by companies and self-referred individuals who underwent serological testing were enrolled. Subjects with antibody positivity were recruited as cases (n = 166) and subjects tested negative (n = 239) as controls. A questionnaire on sociodemographic, occupational, and clinical data was administered through telephone interviews. Serum zinc/iron/copper/chromium/nickel, vitamins D/B12, folates, triglycerides, and LDL/HDL/total cholesterol were measured. Cases lived more often in urban areas (61.8% vs. 57%). Cases and controls did not differ significantly by working macrocategories, but the percentage of workers in the ceramic sector was higher among cases. Low adherence to preventive measures in the workplace was more frequent among seropositives. Folate concentration was significantly lower among cases. Therefore, adequate folate levels, living in rural areas, and good adherence to preventive strategies seem protective against infection. Workers in the ceramic sector seem to be at greater risk; specific factors involved are not defined, but preventive interventions are needed.

Vitamin B and One-Carbon Metabolite Profiles Show Divergent Associations with Cardiometabolic Risk Markers but not Cognitive Function in Older New Zealand Adults: A Secondary Analysis of the REACH Study

BackgroundVitamin B inadequacies and elevated homocysteine status have been associated with impaired cognitive and cardiometabolic health with aging. There is, however, a scarcity of research investigating integrated profiles of one-carbon (1C) metabolites in this context, including metabolites of interconnected folate, methionine, choline oxidation, and transsulfuration pathways. ObjectivesThe study aimed to examine associations between vitamins B and 1C metabolites with cardiometabolic health and cognitive function in healthy older adults, including the interactive effects of Apolipoprotein E-ε4 status. MethodsThree hundred and thirteen healthy participants (65-74 y, 65% female) were analyzed. Vitamins B were estimated according to dietary intake (4-d food records) and biochemical status (serum folate and vitamin B12). Fasting plasma 1C metabolites were quantified by liquid chromatography with tandem mass spectrometry. Measures of cardiometabolic health included biochemical (lipid panel, blood glucose) and anthropometric markers. Cognitive function was assessed by the Computerized Mental Performance Assessment System (COMPASS) and Montreal Cognitive Assessment (MoCA). Associations were analyzed using multivariate linear (COMPASS, cardiometabolic health) and Poisson (MoCA) regression modeling. ResultsOver 90% of participants met dietary recommendations for riboflavin and vitamins B6 and B12, but only 78% of males and 67% of females achieved adequate folate intakes. Higher serum folate and plasma betaine and glycine concentrations were associated with favorable cardiometabolic markers, whereas higher plasma choline and homocysteine concentrations were associated with greater cardiometabolic risk based on body mass index and serum lipids concentration values (P< 0.05). Vitamins B and homocysteine were not associated with cognitive performance in this cohort, though higher glycine concentrations were associated with better global cognitive performance (P = 0.017), episodic memory (P = 0.016), and spatial memory (P = 0.027) scores. Apolipoprotein E-ε4 status did not modify the relationship between vitamins B or 1C metabolites with cognitive function in linear regression analyses. ConclusionsVitamin B and 1C metabolite profiles showed divergent associations with cardiometabolic risk markers and limited associations with cognitive performance in this cohort of healthy older adults.

Association of MTHFR polymorphism, folic acid and vitamin B12 with serum homocysteine levels in pregnant women.

Homocysteine is known to be associated with adverse vascular and metabolic effects, as well as pregnancy complications. Its serum levels are influenced by the function of the enzyme methylenetetrahydrofolate reductase (MTHFR) and the dietary intake of folic acid, vitamin B12, and methionine. In this cross-sectional study, we investigated the association of genetic polymorphisms of the MTHFR gene with vitamin status in pregnant women during mandatory folic acid supplementation. The study included 102 pregnant women between 24 and 28 weeks of gestation who were attending regular outpatient examinations at the maternity clinic. Homocysteine, folic acid, vitamin B12 levels, and MTHFR gene polymorphisms (C677T and A1298C) were analyzed. Significant associations were found between vitamin B12 and folic acid levels with homocysteine (P < 0.001), with lower serum levels of these vitamins being associated with higher homocysteine levels. Surprisingly, there was no significant association between MTHFR genetic polymorphisms and serum homocysteine levels, likely attributed to the supplementation of folic acid and vitamin B12 in vitamin supplements for pregnant women, which counteracts the effect of the mutation. Remarkably, a high prevalence of MTHFR gene mutations was found, with the C677T polymorphism present in 56.9% and the A1298C polymorphism in 87.2% of pregnant women. These findings emphasize the importance of adequate folic acid and vitamin B12 intake during pregnancy to regulate homocysteine levels. Although the MTHFR gene mutations were highly prevalent, their influence on homocysteine levels in this population appears to be mitigated by vitamin supplementation. Further research is warranted to explore the impact of these mutations on other aspects of pregnancy outcomes. The trial is registrated at Clinicaltrail.gov (NCT04952324).

Prenatal folic acid supplement/dietary folate and cognitive development in 4-year-old offspring from the Japan Environment and Children’s Study

We evaluated the association between maternal prenatal folic acid supplement use/dietary folate intake and cognitive development in 4-year-old offspring (N = 3445) using data from the Japan Environment and Children’s Study. Cognitive development was evaluated using the Kyoto Scale of Psychological Development 2001. Multiple regression analysis revealed that offspring of mothers who started using folic acid supplements pre-conception had a significantly higher language-social developmental quotient (DQ) (partial regression coefficient 1.981, 95% confidence interval 0.091 to 3.872) than offspring of mothers who did not use such supplements at any time throughout their pregnancy (non-users). Offspring of mothers who started using folic acid supplements within 12 weeks of gestation had a significantly higher cognitive-adaptive (1.489, 0.312 to 2.667) and language-social (1.873, 0.586 to 3.159) DQ than offspring of non-users. Regarding daily dietary folate intake from preconception to early pregnancy, multiple regression analysis revealed that there was no significant association with any DQ area in the 200 to < 400 µg and the ≥ 400 µg groups compared with the < 200 µg group. Maternal prenatal folic acid supplementation starting within 12 weeks of gestation (but not adequate dietary folate intake from preconception to early pregnancy) is positively associated with cognitive development in 4-year-old offspring.

Nutritional deficiency and MTHFR gene polymorphism in obstetrics

: This study was carried out to determine the association of folic acid deficiency, vitamin B12 deficiency, hyperhomocysteinemia and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with obstetrical events linked to folic acid deficiency like neural tube defects (NTD); unexplained abruption placentae (AP), recurrent pregnancy loss (RPL) and preterm labour(PTL).: In the present study 87 pregnant females with past or present history of either neural tube defect (NTD), abruptio placentae, recurrent pregnancy loss (RPL) or preterm labour and 100 pregnant females without any such history were enrolled. Serum levels of folic acid, vitamin B12 and homocysteine in these females were estimated using chemiluminescence and Polyacrylamide gel electrophoresis (PAGE) was used to detect MTHFR gene polymorphism.: No significant association was observed between serum folic acid levels and NTD (p = 0.495), RPL (p = 0.832) or preterm labour (p = 0.724). However, folic acid deficiency had significant association with the occurrence of abruptio placenta (p = 0.001). Serum vit B12 deficiency was found to be a significant risk factor only in patients with RPL. Increased homocysteine revealed significant association with RPL (p= 0.024), abruption placentae (p=0.002) and preterm labour (0.015). No polymorphism in MTHFR gene could be revealed in the above pregnancy complications.: In the present study, deficiency of folic acid was uncommon probably due to its routine supplementation throughout the first trimester. However, preconceptional folic acid supplementation still needs to be emphasized to build up adequate folic acid levels required during embryogenesis. The relationship between vit B12 and RPL needs studies on larger number to establish the association before supplementation is suggested. MTHFR677 gene polymorphism may have remained undetected due to small sample size.

Contrasting Association of Maternal Plasma Biomarkers of Smoking and 1-Carbon Micronutrients with Offspring DNA Methylation: Evidence of Aryl Hydrocarbon Receptor Repressor Gene–Smoking–Folate Interaction

BackgroundMaternal prenatal smoking is known to alter offspring DNA methylation (DNAm). However, there are no effective interventions to mitigate smoking-induced DNAm alteration. ObjectivesThis study investigated whether 1-carbon nutrients (folate, vitamins B6, and B12) can protect against prenatal smoking-induced offspring DNAm alterations in the aryl hydrocarbon receptor repressor (AHRR) (cg05575921), GFI1 (cg09935388), and CYP1A1 (cg05549655) genes. MethodsThis study included mother-newborn dyads from a racially diverse US birth cohort. The cord blood DNAm at the above 3 sites were derived from a previous study using the Illumina Infinium MethylationEPIC BeadChip. Maternal smoking was assessed by self-report and plasma biomarkers (hydroxycotinine and cotinine). Maternal plasma folate, and vitamins B6 and B12 concentrations were obtained shortly after delivery. Linear regressions, Bayesian kernel machine regression, and quantile g-computation were applied to test the study hypothesis by adjusting for covariables and multiple testing. ResultsThe study included 834 mother-newborn dyads (16.7% of newborns exposed to maternal smoking). DNAm at cg05575921 (AHRR) and at cg09935388 (GFI1) was inversely associated with maternal smoking biomarkers in a dose-response fashion (all P < 7.01 × 10−13). In contrast, cg05549655 (CYP1A1) was positively associated with maternal smoking biomarkers (P < 2.4 × 10−6). Folate concentrations only affected DNAm levels at cg05575921 (AHRR, P = 0.014). Regression analyses showed that compared with offspring with low hydroxycotinine exposure (<0.494) and adequate maternal folate concentrations (quartiles 2–4), an offspring with high hydroxycotinine exposure (≥0.494) and low folate concentrations (quartile 1) had a significant reduction in DNAm at cg05575921 (M-value, ß ± SE = −0.801 ± 0.117, P = 1.44 × 10−11), whereas adequate folate concentrations could cut smoking-induced hypomethylation by almost half. Exposure mixture models further supported the protective role of adequate folate concentrations against smoking-induced aryl hydrocarbon receptor repressor (AHRR) hypomethylation. ConclusionsThis study found that adequate maternal folate can attenuate maternal smoking-induced offspring AHRR cg05575921 hypomethylation, which has been previously linked to a range of pediatric and adult diseases.

Fortification of the Food Supply with Folic Acid to Prevent Neural Tube Defects Is Not Yet Warranted

The relationship between adequate folate intake by pregnant women and reduced risk of delivering infants with neural tube defects (NTDs) has raised the public health issue of increasing folate in take among women of reproductive age. The U.S. Food and Drug Administration has proposed fortifying cereal and grain products with folate, although at a level less than half that recommended by its sister agency, the Centers for Disease Control and Prevention. We question the wisdom of fortifying foods with folate at this time, given a variety of uncertainties, which include the following: 1) the fact that neural tube defects seem to be a multifactorial group of disorders that are polygenie as well, so folate will not help in all or perhaps even in most cases; 2) the incidence of NTDs, which varies geographically, has been decreasing in the United States for years; 3) fortifying more food with folate may pose safety concerns for some not at risk for NTDs; 4) no dose-response relationship has been established between folate and NTDs; and 5) fortification in this case would represent a conceptually new intervention strategy for addressing what may be a metabolic abnormality where pharmacological doses of a nutrient may be required. Launching a major nutritional intervention before better understanding the relationship between nutrients and NTDs and without reasonable assurance that it will not shift health risks from one group (developing embryos) to another (primarily adults with pernicious anemia) might prove ineffective and/or harmful.

A Food Industry Perspective on Folic Fortification

The U.S. Public Health Service (PHS) has recommended that all women of childbearing years, capable of becoming pregnant, consume 400 fig folic acid/d to reduce their risk of having a neural tube defect (NTD)-affected pregnancy. The U.S. Food and Drug Administration subsequently proposed a fo late fortification scheme for cereal grains, which also allowed the continued fortification of breakfast cereals at 0.1 mg per serving. To determine the contribution of ready-to-eat breakfast cereals (RTEC) to folate in takes in women of childbearing years, data were ana lyzed from the U.S. Department of Agriculture’s 1989-1991 Continuing Survey of Food Intakes by In dividuals and 1987-1988 Nationwide Food Consumption Survey. Women consuming RTEC have higher intakes of folate than women reporting no RTEC consumption. Recent reports indicate that most women are unaware of the PHS recommendation to consume more folate, and many health professionals are not advising women of the need to consume adequate folate during the childbearing years. The food industry has been an effective communicator of health and nutrition messages and should be encouraged to raise awareness about the role of folate in NTDs. Better analysis also needs to be conducted to identify women at risk of low folate intakes, so that targeted educational efforts can be made and appropriate vehicles identified for delivering folate to these women.

Maternal gestational diabetes in singleton pregnancies conceived by ART may be modified by periconceptional B vitamins.

The risk of maternal gestational diabetes mellitus (GDM) may be influenced by pregnancies conceived through assisted reproductive technology (ART). However, the influence of the dosage of B vitamins (folate, vitamin B6 and vitamin B12) on GDM weren't considered. Thus, we hypothesized that periconceptional B vitamins could modify maternal GDM in singleton pregnancies conceived by ART. This study is a prospective cohort study using data from 3,252 women with singleton pregnancies and received a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. We included an interaction term in the multivariable logistic and linear regression models, respectively, to test our hypothesis. Women who underwent ART were significantly associated with the incidence of GDM compared with spontaneous pregnancy women. The adjusted odds ratio (aOR) was 1.59, and the 95% confidence interval (CI) was 1.08-2.34. ART pregnancies also elevated OGTT (oral glucose tolerance test) 1-h blood glucose levels and OGTT 2-h blood glucose levels (P < 0.05). A positive association between dietary vitamin B6 (aOR = 1.60, 95% CI: 1.13-2.27), dietary vitamin B12 (aOR = 1.88, 95% CI: 1.34-2.64) and dietary folate (aOR = 1.66, 95% CI: 1.19-2.32) with GDM risk comparing the highest to the lowest quartile (all P trend < 0.001). The aORs of GDM for inadequate (< 400 μg/day), adequate (400-800 μg/day), and excessive (> 800 μg/day) supplemental folate intake were 1.00, 0.93, and 1.30, respectively (P trend = 0.033). Since only the supplemental folate illustrates a statistically significant interaction with ART (P for interaction < 0.05), the association between ART and GDM and OGTT blood glucose levels stratifying by supplemental folate were further evaluated. These increased risks of GDM (aOR = 1.62, 95% CI: 1.39-3.39) and the regression coefficients (β) of 1-h blood glucose (β = 0.76, 95% CI: 0.39-1.13) and 2-h blood glucose (β = 0.60, 95% CI: 0.29-0.92) in the multiple linear regression model were significant only in the ART group with excessive supplemental folate (> 800 μg/day). The risk of GDM is significantly elevated, particularly among those women who conceived ART with the intake of excessive supplemental folate (> 800 μg/day).

Dietary intake of folate and the frequency of its deficiency in children with type 1 diabetes mellitus and healthy children

Adequate folate intake is essential for a child’s growth. There is lack of information about the prevalence of this nutrient deficiency in the Ukrainian population, including children. The aim of the study was to evaluate the dietary intake of folate and determine the frequency of folate deficiency in children with Type 1 diabetes mellitus (T1D) and healthy children. Determination of folate in serum was performed by ELISA. Folate level &lt;3 ng/ml was diagnosed as a folate deficiency. Among all observed children the folate deficiency was diagnosed in 23 (32.9%): in 6 (17.1%) patients with T1D and in 17 (48.6%) healthy children (P ≤ 0.01). The mean level of serum folate in patients with T1D was (5.09 ± 2.16) ng/ml and (3.72 ± 1.87) ng/ml in healthy children (P ≤ 0.01). The average daily intake of folate with food was (138.68 ± 70.37) µg, without difference between T1D (12.00 ± 3.51 yr.) and healthy groups (10.83 ± 3.24 yr.), and it was more than two times lower than age requirements (300 µg/day). However, it was self-reported that 15 (48.9%) children of T1D group received vitamin supplementation one time in six months, while in healthy children only 6 (17.1%) children received vitamins (P ≤ 0.01). In conclusion, the frequency of folate deficiency is high in the pediatric population. Nutrition does not provide the necessary intake of folate, which indicates the need for additional folate supplementation. Keywords: children., deficiency, diabetes mellitus, dietary intake, folate