Folate Concentrations Research Articles

Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study

BackgroundEnvironmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. MethodsIn 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004-2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6-15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n=179), paternal preconception (n=122), and maternal pregnancy (n=177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. ResultsThe mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (βmaternal_precon = -1.6, 95% CI -2.7; -0.4; βpaternal_precon = -2.9, 95% CI -4.6; -1.2) for each loge increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. ConclusionsUrinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

Evaluation of laboratory findings indicating pancreatitis in healthy lean, obese, and diabetic cats.

Obesity is a risk factor for diabetes mellitus, which commonly coexists with pancreatitis in cats. However, obesity has not previously been associated with pancreatitis in cats. To evaluate factors affecting serum concentrations of pancreatic lipase immunoreactivity (fPLI), trypsin-like immunoreactivity (fTLI), cobalamin and folate in clinically healthy lean, overweight and obese, or diabetic cats. Seventy-nine client-owned cats (27 healthy lean [LN, BCS 4-5/9], 30 healthy overweight and obese [OW, BCS 7-9/9], and 22 diabetic [DM]) were included. Cross-sectional study. The cats underwent physical examination, and blood tests. Linear regression models compared differences in fPLI, fTLI, cobalamin, and folate concentrations. Fisher's exact test assessed the proportions of cats with fPLI and fTLI indicative of pancreatitis, and hypocobalaminemia. A random forest algorithm identified explanatory variables for cats having fPLI levels indicative of pancreatitis. No LN cats, while 6/30 (20%) of OW and 10/22 (45%) of DM cats had fPLI concentrations indicative of pancreatitis. Body condition score (P = .02) and body weight (P = .002) were positively associated with fPLI levels in LN and OW cats. Higher fPLI, and lower cobalamin concentrations were associated with higher age across groups. Body condition score and body weight were associated with higher fPLI levels in nondiabetic cats. A larger proportion of OW and DM cats had fPLI concentrations indicative of pancreatitis compared to LN cats. Whether this indicates subclinical pancreatitis remains to be determined. Hypocobalaminemia was less frequent in OW compared to DM cats.

The unique presentation of the relationship between red blood cell folate and appendicular skeletal muscle mass: a cross-sectional study

The overconsumption of folic acid has been associated with deleterious health effects; however, the extant body of research on this matter remains controversial. The principal objective of our investigation was to scrutinize the correlation between red blood cell (RBC) folate levels and appendicular skeletal muscle mass (ASM) among adult individuals. A total of 4117 adults aged over 20 years were included. The weighted prevalence of low muscle mass status (LMMS) was 14.50%. The correlation between RBC folate and ASM showed an inverted U-shaped curve. When the RBC folate concentration is below 500 nmol/L, ASM increases with increasing RBC folate concentration. However, when the RBC folate level exceeds 500 nmol/L, ASM decreases with increased RBC folate level. After correcting multiple confounding factors, a positive correlation was found between RBC folate and LMMS (p < 0.001). Compared with the RBC folate first quartile, the multivariable-adjusted ORs and 95% CIs of the second quartile, third quartile, and highest quartile were 1.08(0.81–1.44), 1.06(0.79–1.43), and 1.96(1.47–2.61), respectively. Our research suggested that excessive levels of RBC folate may be associated with an increased risk of LMMS in adults. Thus, being more cautious when considering folic acid supplementation is recommended.

Maternal Nutritional Factors Enhance Birthweight Prediction: A Super Learner Ensemble Approach

Birthweight (BW) is a widely used indicator of neonatal health, with low birthweight (LBW) being linked to higher risks of morbidity and mortality. Timely and precise prediction of LBW is crucial for ensuring newborn health and well-being. Despite recent machine learning advancements in BW classification based on physiological traits in the mother and ultrasound outcomes, maternal status in essential micronutrients for fetal development is yet to be fully exploited for BW prediction. This study aims to evaluate the impact of maternal nutritional factors, specifically mid-pregnancy plasma concentrations of vitamin B12, folate, and anemia on BW prediction. This study analyzed data from 729 pregnant women in Tarragona, Spain, for early BW prediction and analyzed each factor’s impact and contribution using a partial dependency plot and feature importance. Using a super learner ensemble method with tenfold cross-validation, the model achieved a prediction accuracy of 96.19% and an AUC-ROC of 0.96, outperforming single-model approaches. Vitamin B12 and folate status were identified as significant predictors, underscoring their importance in reducing LBW risk. The findings highlight the critical role of maternal nutritional factors in BW prediction and suggest that monitoring vitamin B12 and folate levels during pregnancy could enhance prenatal care and mitigate neonatal complications associated with LBW.

Validated Spectrofluorometric Assay for Folic Acid Determination in Pure and Pharmaceutical Forms via Basic Fuchsin Fluorescence Quenching.

A simple, specific, sensitive, rapid, and cost-effective spectrofluorometric method for quantifying folic acid has been developed using basic fuchsin as a fluorescence quenching agent. This method relies on the quenching effect of folic acid on the inherent fluorescence of basic fuchsin, facilitated by their interaction in Britton-Robinson buffer solution at pH 9, leading to the formation of an ion-associated complex. The decrease in fluorescence intensity of basic fuchsin was measured at 730 nm, with excitation at 365 nm. The method demonstrated a linear relationship (R2 = 0.9977) between the quenching fluorescence intensity (ΔF) and folic acid concentration over the range of 4-20 μg/mL, with a detection limit of 0.17 μg/mL. The method showed no significant interference from common excipients found in pharmaceutical tablets. The results obtained were in good agreement with those from high-performance liquid chromatography, with no significant differences in precision or accuracy. This spectrofluorimetric method was successfully applied to determine the folic acid content in various commercial pharmaceutical tablets.

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy.

The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body's ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Healthy pregnant women were randomized and provided supplements from their first prenatal visit (<12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400µg or 800µg Mix of (6S)-5-Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age.

A mixture of (6S)-5-methyltetrahydrofolate-calcium salt ((6S)-5-MTHF-Ca) and folic acid (FA) from multimicronutrient supplements may show a dose-dependent effect on serum folate concentrations. The study compares fasting concentrations of serum folate spices after 8 weeks of either 400 or 800µgday-1 of 1:1 folate mixture in 172 nonpregnant women. Serum (6S)-5-MTHF concentrations raise from a mean (SD) of 19.1 (13.4) to 73.9 (19.6) nmolL-1 in the 800µg group and from 17.5 (9.4) to 54.5 (21.1) nmolL-1 in the 400µg group (p < 0.001 within-group changes). The raise in serum (6S)-5-MTHF is stronger in the 800µg compared to the 400µg group (p < 0.001 between-group). The prevalence of FA concentrations ≥0.20nmolL-1 increases between baseline and week 8 in both groups, but is not different between the groups (p = 0.116). The mean percentage of (6S)-5-MTHF of total serum folate increases in both intervention groups, but is not different between the groups at 8 weeks (95.5 (4.1)% versus 94.4 (5.7)%, p = 0.309). Supplementation of multimicronutrients with 800µg folate mix for 8 weeks causes higher serum (6S)-5-MTHF concentrations, but not a higher prevalence of detectable FA compares to 400µg folate.

Folic acid, cobalamin, and biotin concentrations in milk samples of sheep, goats, and cows

Milk is an important food obtained from mammals, containing almost all of the nutrients needed for metabolism. The vitamin composition of milk, the first food of mammals, is valuable data for the food industry and public health. This study aimed to determine the levels of folic acid (vitamin B9), cobalamin (vitamin B12), and biotin (vitamin B7) in different milk samples (cow, sheep, goat) using the ELISA method. For this purpose, milk samples from Holstein Cows (n:50), Awassi Sheep (n:50), and Kilis Goats (n:50) available for retail in the Şanlıurfa province of Turkey were collected and analyzed. In this study, the average folic acid content of sheep, goat, and cow milk was found to be 3.45 µg/100 mL, 7.23 µg/100 ml, and 6.64 µg/100 mL, respectively. The average cobalamin content of sheep, goat, and cow milk was 0.70 µg/100 ml, 7.43 µg/100 ml, and 0.58 µg/100 mL, respectively, while the average biotin content of sheep, goat, and cow milk was 2.21 µg/100 mL, 2.21 µg/100 mL, and 2.09 µg/100 mL, respectively. It was noted that the average biotin levels in sheep, goat, and cow milk did not differ significantly. However, significant differences were observed in the quantities of folic acid and cobalamin (P&lt;0.05). Different levels of folic acid were found in milk samples from these three species. Cobalamin levels in goat milk samples were significantly higher, while biotin levels were similar in each milk sample of the species. This study underscores the importance of understanding and considering the diverse vitamin compositions of milk from different mammalian species to ensure comprehensive nutritional intake.

Synergizing Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus with folic acid for enhanced drought resistance in wheat by metabolites and antioxidants

Drought stress imposes a serious challenge to cultivate wheat, restricting its growth. Drought reduces the capability of plant to uptake essential nutrients. This causes stunted growth, development and yield. Traditional ways to increase wheat growth under drought stress have shortcomings. Using plant-growth-promoting rhizobacteria (PGPR) has proved feasible and eco-friendly way to enhance wheat growth even under the drought stress. Combining PGPR in consortiums further boosts up their effects. In this study, we have checked the efficacy of drought-tolerant Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus in combination. These strains were allowed to grow on PEG 6000 with concentrations (-0.15, -0.49, -0.73 and − 1.2) Mega Pascal (MPa) alone and in combination. Furthermore, Fourier transmission infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were used. Their biochemical traits such as solubilization of K, P and Zn and the synthesis of siderophore, indole acetic acid (IAA), protease, amylase, hydrogen cyanide (HCN) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase were done. In addition to this, we investigated the optimum folic acid concentration i.e 150 ppm for wheat against drought stress. We conducted a pot experiment to check the growth-enhancing and drought-mitigating effects of consortium and folic acid alone and in combination. As a result, we found a significantly increased wheat biomass, relative water content (RWC), chlorophyll content, antioxidants including glutathione reductase and total soluble sugars and protein content under all treatments. However, the combined treatment of bacterial consortium and folic acid showed maximum potential to boost wheat growth and survival even under drought. We also investigated the minerals uptake by wheat after the treatments and found maximum nutrient uptake under the co-effect of folic acid and bacterial consortium We believe this is the first study that has investigated the optimal dose of folic acid for wheat. Our research is also novel in that we seek to investigate the effects of folic acid along with a bacterial consortium comprising Bacillus halotolerans, Pseudomonas sihuiensis and Bacillus atrophaeus on wheat grown under the drought stress.

A Comparative Analysis of Folate and Mineral Contents in Freshly Squeezed and Commercial 100% Orange Juices Available in Europe.

Orange juices are widely known for their organoleptic characteristics and potential health benefits derived from their nutritional and functional composition. The aim of this work was to provide comprehensive, up-to-date information on the content of folates and some minerals (Ca, K, Mg, Fe, Mn, and Zn) present in different fresh and commercial orange juices available in the European market, including juices from concentrate (FC) and not from concentrate (NFC). A total of twenty-five juice samples were selected, comprising the most purchased types of commercial juices from France, the United Kingdom (UK), Germany, and Spain, and four fresh squeezed juices (FSJ) made from Spanish oranges. In FSJ, nutrient stability during storage time (0-48 h) was also assessed. Folate concentration was highly variable between commercial samples, with higher contents in FSJ and NFC samples, followed by FC juices. Regarding mineral content, FSJ showed significant differences with FC (except for Mg) and NFC juice samples (except for Ca and Mg), while FC and NFC had similar mineral profiles, except for Ca. Storage time had no significant impact on FSJ folates and minerals. Among commercial juices, the NFC category generally showed the highest content of folates, K, Mg, and Fe, whereas FC juices showed the highest contents of Ca, Mn, and Zn. Some commercial juices met the legal use conditions for a "Source of folate" claim, whereas both commercial and fresh juices met the conditions for a "Source of potassium" claim, according to European and UK regulations.

Improvement of serum folate status in the US women of reproductive age with fortified iodised salt with folic acid (FISFA study).

Mandatory folic acid fortification of enriched grains has reduced neural tube defect prevalence in several countries. We examined salt as an additional vehicle for folic acid fortification. The primary objective was to examine the change in serum folate concentration after 1 month of consumption of fortified iodised salt with folic acid (FISFA) among women of reproductive age. The secondary objectives were to examine (1) the feasibility of implementing FISFA intervention and (2) the acceptability of FISFA. We conducted a pre–post intervention study (January–April 2023). Participants received a FISFA saltshaker with the study salt (1 g of sodium chloride salt fortified with 100 mcg of folic acid) to use instead of regular table salt for 1 month. Serum folate was measured using the Elecsys Folate-III immunoassay method at baseline and 1-month endpoint. Change in serum folate was assessed using a two-tailed Wilcoxon signed rank test for paired samples. Metropolitan city, Southern USA. Non-pregnant, 18–40-year-old women who lived alone/with a partner. Thirty-two eligible women consented to participate, including eleven non-Hispanic-White, eleven non-Hispanic-Black and ten Hispanic. Post-intervention, there was a significant increase in median serum folate concentration of 1·40 nmol/l (IQR 0·74–2·05; P < 0·001) from 24·08 nmol/l to 25·96 nmol/l in an analytical sample of n 29. An increase was seen in 28/29 (93 %) participants. Feasibility: 100 % study consent and compliance. FISFA acceptability: 25 d average use; 1·28 g average daily intake; 96·7 % and 90 % reported taste and colour of FISFA as highly acceptable, respectively. FISFA is an effective approach to increasing serum folate concentrations among women of reproductive age. Findings should be replicated in a larger study.

Study of the relationships of polymorphisms of the folate cycle genes with the levels of homocysteine and folic acid as risk factors of cardiovascular disorders in the post-covid period

Enzymes of the folate cycle participate in the process of remethylation of homocysteine (HC) to methionine, where folates are coenzymes for methyl transfer. The aim of the work was to identify the interrelationships of gene polymorphisms of associations between folate cycle enzyme gene polymorphisms and cardiometabolic risk factors such as increased serum homocysteine levels and folic acid deficiency in patients in the post-covid period. In 51 patients who suffered from COVID-19, a general clinical and laboratory examination, and assessment of serum homocysteine and folic acid concentrations by immunoenzymatic method was carried out. Polymorphisms of the genes: methylenetetrahydrofolate reductase (677C&gt;T and 1298A&gt;C), methionine synthase-reductase (66A&gt;G) and methionine synthase (2756A&gt;G) were determined by real time polymerase chain reaction. For each of the named polymorphisms, the examined patients were divided into 3 groups according to the nucleotide alleles in the corresponding position: 1) homozygous dominant, 2) heterozygous and 3) homozygous recessive. For the methylenetetrahydro­folatereductase gene at position 677, serum levels of homocysteine and folate did not differ between the groups 1 and 2 with genotypes 677 C/C (n=26) and 677C/T (n=21), (p&gt;0.05); in group 3, the recessive genotype 677 T/T was found in only 4 people (8%), that did not allow comparison of indices. The distribution of patients into 3 groups according to the genotype of the same gene at position 1298 revealed that the recessive 1298 C/C mutation in group 3 (n=9) associated with an increased homocysteine level (19.56±1.89 μmol/l), versus 10.68±0.76 (p=0.012) and 11.63±1.25 μmol/l (p=0.013) in groups 1 and 2, with no difference in folate levels between groups. Group 3 differed by a higher degree of obesity, a higher frequency of hypertension disease and chronic heart failure (in 85% of patients in group 3, against 41 and 50% in groups 1 and 2), a higher number of platelets, a longer duration of hospitalization due to COVID-19, a higher level of D-dimer. The study of groups of patients, divided depending on the genotype of methioninesynthase reductase at position 66, showed that carriers of the recessive homozygous 66 G/G mutation (group 3, n=15) had increased serum homocysteine level (16.56±1.64 μmol/l) in comparison with individuals of group 1 (n=17) 66 A/A (10.28±1.17 μmol/l; p=0.004) and group 2 (n=19) 66 A/G (11.32±1.17 μmol/l, p=0.013). In group 3, a longer duration of hospitalization due to COVID-19 was noted (17.15±1.65 vs. 11.88±0.97 days, p=0.008), higher frequency of hypertension (67% vs. 35%) and heart failure (67% against 29%) compared to group 1. The use of a molecular genetic approach made it possible to establish that the presence of recessive mutations of the folate cycle genes is associated with a potential predisposition to hyperhomocysteinemia, thrombophilia, severe forms of cardiometabolic complications and coronavirus disease.

Genome-Wide Association Study Identifies Genetic Polymorphisms for Folate-Related Biomarkers in Chinese Preconception Women

BackgroundSingle-nucleotide polymorphism (SNP) allele frequencies, dietary habits, and folate status and their associations vary across ethnic populations. Little is known about the SNPs accounting for variations of folate-related biomarkers for Chinese preparing-for-pregnant females. ObjectivesWe aimed to identify SNPs contributing to RBC and serum folate, vitamin B-12, and homocysteine concentrations in Chinese female preconception population. MethodsA genome-wide association study was conducted on 1000 randomly selected preconception Chinese women from the Shanghai Preconception Cohort. SNPs were genotyped using Illumina chips, and associations with biomarkers were assessed using simple linear regression models under the assumption of an additive genetic model. Genome-wide significance was considered at P < 10−7. ResultsThe MTHFR rs1801133 was the major genetic coding variant contributing to RBC folate, serum folate, and homocysteine concentrations (P = 2.28 × 10−16; P = 8.85 × 10−8, and P = 2.46 × 10−13, repsectively). It is associated with increased RBC folate (β: 0.154 per additional risk allele after log transform), decreased serum folate (β: −0.951 per additional risk allele), and increased serum homocysteine concentrations (β: 1.153 per additional risk allele). The predominant SNP associated with serum folate was rs147162222 in NTRK2 (P = 2.55 × 10−8), although that associated with homocysteine was rs77025184 located between PDE7B and LINC00271 (P = 4.91 × 10−17). For vitamin B-12, FUT2 rs1047781 was the dominant genetic variant (P = 1.59 × 10−10). The numbers of signals with a P value of <10−7 for RBC folate, serum folate, vitamin B-12, and homocysteine were 12, 18, 8, and 614, respectively. ConclusionsThis study represents the first genome-wide association study focusing on folate-related biomarkers in a Chinese preparing-for-pregnant female population. The contributions of dominent SNPs to each biomarker are partly different from other populations. The rs1801133 (C677T) in MTHFR is the predominant genetic variant contributing to RBC folate and rs1047781 (A385T) in FUT2 as the primary one explaining vitamin B-12. Notably, the intronic rs147162222 and noncoding rs77025184 are the predominant SNPs for serum folate and homocysteine, respectively.

Betaine and B12 Intake, Glutathione Concentration, and MTHFR, PEMT, and MTHFD1 Genotypes Are Associated with Diabetes-Related Parameters in Polish Adults

BackgroundThere is a growing body of evidence on associations between one-carbon metabolism (OCM) and diabetes-related parameters. For this reason, we aimed to examine the associations of plasma choline, betaine, trimethylamine N-oxide (TMAO), glutathione (GSH), serum folate, vitamin B12, dihydrofolate reductase (rs70991108) genotype, methylenetetrahydrofolate reductase (MTHFR) (rs180113) genotype, methylenetetrahydrofolate dehydrogenase (MTHFD1) (rs2236225) genotype, and phosphatidylethanolamine N-methyltransferase (rs7946 and rs12325817) genotype with fasting glucose level, insulin level, and diabetes-related indices. MethodsThe study group consisted of 421 Polish adults aged 20–40 y. Food intake was assessed using a 3-d food diary. Plasma concentrations of choline, betaine, and TMAO were determined by ultra-high-performance liquid chromatography-electrospray ionization mass spectrometry. The total plasma GSH level was measured by high-performance liquid chromatography. Insulin, folate, and vitamin B12 concentrations were estimated by enzyme-linked immunosorbent assay method. Genotyping was performed with TaqMan probes. ResultsGSH level was negatively associated with insulin (β = −0.11, P < 0.05) and gamma-glutamyl transferase (GGTP) (β = −0.12, P < 0.05), and positively associated with fasting glucose (β = 0.11, P < 0.05). Betaine intake was negatively associated with serum insulin concentration (β = −0.13, P < 0.05) and HOMA-IR (β = −0.12, P < 0.05). Choline intake was negatively associated with insulin (β = −0.17, P < 0.01). Serum folate level was negatively associated with GGTP (β = −0.11; P < 0.05). The methylenetetrahydrofolate reductase (MTHFR) CC genotype was associated with higher serum insulin levels (β = 0.15; P < 0.01) and higher HOMA-IR (β = 0.15, P < 0.01), whereas the MTHFD1 AA genotype was negatively associated with Quantitative Insulin Sensitivity Check Index (β = −0.11, P < 0.05). ConclusionsOur findings suggest that higher GSHL and higher intake of betaine, B12, and choline, as well as the TT genotype of MTHFR and the AA genotype of MTHFD1, are associated with lower diabetes-related parameters among adults.

Combined Exposure to Folate and Lead during Pregnancy and Autistic-Like Behaviors among Canadian Children from the MIREC Pregnancy and Birth Cohort.

Folic acid (FA) supplementation may attenuate the associations between gestational exposure to certain chemicals and autism or autistic-like behaviors, but to our knowledge, this has not been assessed for lead. We examined whether the relationship between gestational blood-lead levels (BLLs) and autistic-like behaviors was modified by gestational plasma total folate concentrations, FA supplementation, and maternal methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. We used data from the Maternal-Infant Research on Environmental Chemicals study (2008-2011), a Canadian pregnancy and birth cohort study. Childhood autistic-like behaviors were documented in 601 children 3-4 y of age with the Social Responsiveness Scale-2 (SRS-2), where higher scores denote more autistic-like behaviors. We measured BLLs and plasma total folate concentrations during the first and third trimesters of pregnancy. We also estimated gestational FA supplementation via surveys and genotyped the maternal MTHFR 677C>T single nucleotide polymorphism (SNP). We estimated the confounder-adjusted associations between -transformed BLLs and SRS-2 scores by two indicators of folate exposure and maternal MTHFR 677C>T genotype using linear regression. Third-trimester BLLs were associated with increased SRS-2 scores [; 95% confidence interval (CI): 1.1, 5.5] among participants with low ( percentile), third-trimester, plasma total folate concentrations, but BLL-SRS-2 associations were null (; 95% CI: , 0.5) among those in the middle category ( and percentiles) (p-interaction ). FA supplementation also attenuated these associations. Both folate indicators modified first-trimester BLL-SRS-2 associations, but to a lesser extent. Third-trimester BLL-SRS-2 associations were slightly stronger among participants who were homozygous for the T (minor) allele of the MTHFR 677C>T SNP (; 95% CI: , 3.1) than those without the T allele (; 95% CI: , 0.7), but the difference was not statistically significant (). Folate may modify the associations between gestational lead exposure and childhood autistic-like behaviors, suggesting that it mitigates the neurotoxic effects of prenatal lead exposure. https://doi.org/10.1289/EHP14479.

Expression patterns of folate metabolism-related enzymes in the bovine oviduct: estrous cycle-dependent modulation and responsiveness to folic acid

Folate metabolism is required for important biochemical processes that regulate cell functioning, but its role in female reproductive physiology in cattle during peri- and post-conceptional periods has not been thoroughly explored. Previous studies have shown the presence of folate in bovine oviductal fluid, as well as finely regulated gene expression of folate receptors and transporters in bovine oviduct epithelial cells (BOECs). Additionally, extracellular folic acid (FA) affects the transcriptional levels of genes important for the functioning of BOECs. However, it remains unknown whether the anatomical and cyclic features inherent to the oviduct affect regulation of folate metabolism. The present study aimed to characterize the gene expression pattern of folate cycle enzymes in BOECs from different anatomical regions during the estrous cycle and to determine the transcriptional response of these genes to increasing concentrations of exogenous FA. A first PCR screening showed the presence of transcripts encoding dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase (MTR) in bovine reproductive tissues (ovary, oviduct and uterus), with expression levels in oviductal tissues comparable to, or even higher than, those detected in ovarian and uterine tissues. Moreover, expression analysis through RT-qPCR in BOECs from the ampulla and isthmus during different stages of the estrous cycle demonstrated that folate metabolism-related enzymes exhibited cycle-dependent variations. In both anatomical regions, DHFR was upregulated during the preovulatory stage, while MTHFR and MTR exhibited increased expression levels during the postovulatory stage. Under in vitro culture conditions, ampullary and isthmic cells were cultured in the presence of 10, 50, and 100 μM FA for 24 h. Under these conditions, isthmus epithelial cells exhibited a unique transcriptional response to exogenous FA, showing a pronounced increase in MTR expression levels. Our results suggest that the expression of folate metabolism-related genes in BOECs is differentially regulated during the estrous cycle and may respond to exogenous levels of folate. This offers a new perspective on the transcriptional regulation of genes associated with the folate cycle in oviductal cells and provides groundwork for future studies on their functional and epigenetic implications within the oviductal microenvironment.

Major evidence of nutritional and metabolic management in the context of bariatric surgery: a systematic review

Introduction: Approximately $315 billion is spent annually on the medical cost of obesity in adult patients in the United States alone. According to the American Society for Metabolic and Bariatric Surgery (ASMBS), the rate of bariatric surgery (BS) increased from 158,000 in 2011 to 196,000 in 2015. This increase in invasive techniques does not eliminate unhealthy habits, therefore, lifestyle modifications, such as healthy eating and correct physical activity programs, can improve surgical results. Objective: To establish the main nutritional and metabolic management strategies in the context of bariatric surgery, to modulate and reduce the problems caused by nutrient deficit. Methods: The systematic review rules of the PRISMA Platform were followed. The search was conducted from May to June 2024 in the Web of Science, Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 135 articles were found. 42 articles were fully evaluated and 18 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 22 studies with a high risk of bias and 24 that did not meet GRADE and AMSTAR-2. Most studies presented homogeneity in their results, with X2=79.7%&gt;50%. It was concluded that the recommendations were gathered to assist in individualized clinical practice in the nutritional management of patients with obesity. In general, patients with obesity have significantly lower concentrations of serum iron, folic acid, vitamins A, B6, B12, C, 25-hydroxyvitamin D, and lipid-standardized vitamin E. Before bariatric surgery, nutritional status should be analyzed and preoperative weight loss can be attempted. Very low-calorie diets and very low-calorie ketogenic diets are prescribed in the last months before surgery. It was noted that the recommendations were gathered to assist in individualized clinical practice in the nutritional management of patients with obesity, including nutritional management. Iron status may be affected by adipose tissue inflammation and increased expression of the systemic iron regulatory protein hepcidin. The postoperative recommendation for vitamin B12 (cobalamin) should be 350-500 micrograms/1000 micrograms monthly, and for folate (folic acid) in the postoperative period should be 1000 micrograms per day.

The use of propionic and lactic acid bacteria to produce cobalamin and folate in injera, an Ethiopian cereal-based fermented food

Like in many developing countries, the traditional Ethiopian diet relies mainly on starchy staple foods and often lacks sufficient animal-sourced foods which are crucial for cobalamin intake. Furthermore, the concentration of folate in traditionally prepared injera, an Ethiopian cereal-based fermented staple food, is highly variable and injera contains biologically inactive corrinoids. This study aimed to improve the cobalamin and folate content of injera by using cobalamin-producing Propionibacterium freudenreichii and folate-producing Lactiplantibacillus plantarum strains, both individually and combined. Since injera is fermented using backslopping, we also assessed the ability of these strains to produce cobalamin and folate consistently across successive fermentation batches. Changes in the microbial ecosystem were monitored using real-time PCR. The theoretical contribution of the injera prepared using the selected strains to the cobalamin and folate intake of children and women of reproductive age was also calculated. Results showed that using the selected bacterial strains individually increased cobalamin (up to 19.2 μg/100 g of dry matter) and folate (up to 180.2 μg/100 g of dry matter) levels in the injera dough over several backslopping fermentation batches. Regular consumption of the injera with enhanced vitamin content produced using each strain alone would be capable of fulfilling the entire recommended nutrient intake for cobalamin and up to 29 % of the recommended intake for folate for children and women of reproductive age. However, when the strains were used together, the production of both vitamins was reduced. The presence of certain common endogenous bacterial species and genera exhibited significant variability, highlighting the complex response of the native microbiota to the different inoculation strategies employed. Future experiments should consider selecting a microbial consortium comprising non-competing microorganisms to ensure the simultaneous production of cobalamin and folate in fermented foods.

Serum folate levels and risk of metabolic dysfunction-associated steatotic liver disease: results from a cross-sectional study and Mendelian randomization analysis.

Evidence from observational studies on the association between folate and metabolic dysfunction-associated steatotic liver disease (MASLD) is conflicting. This study aimed to investigate the association between serum folate concentration and MASLD and further assess the causal relationship using Mendelian randomization (MR) analysis. To investigate the causal relationship between serum folate and MASLD, we conducted a cross-sectional study that selected 1,117 participants from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The association between serum folate level and the risk of MASLD was evaluated under a multivariate logistic regression model. In addition, we conducted a two-sample MR study using genetic data from a large genome-wide association study (GWAS) to compare serum folate level (37,465 individuals) and MASLD (primary analysis: 8,434 cases/770,180 controls; Secondary analysis:1,483 cases/17,781 controls) were performed to infer causal relationships between them. Inverse variance weighted (IVW) was used as the primary method of MR Analysis. The results from the NHANES database showed that Tertile 3 group (Tertile 3: ≥ 48.6 nmol/L) had a significantly lower risk (OR = 0.58, 95% CI: 0.38-0.88, p = 0.010) of MASLD than Tertile 1 group (Tertile 1: < 22.3 nmol/L) after complete adjustments. However, in the IVW of MR analysis, there was no causal relationship between serum folate level and MASLD risk in the primary analysis (OR = 0.75, 95% CI: 0.55-1.02, p = 0.065) and secondary analysis (OR = 0.83, 95% CI: 0.39-1.74, p = 0.618). In observational analyses, we observed an inverse association between higher serum folate concentrations and a reduced risk of MASLD. Our MR study generated similar results, but the association failed to reach the significance threshold of p < 0.05, suggesting that our MR study does not support a causal relationship between serum folate levels and MASLD risk. Additional research involving a larger number of cases would contribute to enhancing the confirmation of our preliminary findings.

Association of MTHFR C677T, MTHFRA1298C, and MTRRA66G Gene Polymorphisms with Hyperhomocysteinemia and Its Modulation by the Combined Effect of Vitamin B12 and Folate in Chinese Population with Hypertension

BackgroundIn China, the MTHFR 677T allele, unlike in most Western populations, is a rare genetic variant linked to various disorders. The contributing nutritional and genetic factors to this genetic risk remain unclear. ObjectiveThis study aimed to elucidate the interactions between genetic variations in total homocysteine (tHcy) pathway genes, serum tHcy concentrations, and nutritional factors in a Chinese population with hypertension. MethodsThis study analyzed 1304 Chinese adults with hypertension aged ≥18 y enrolled in the China Precision Nutrition and Health KAP Real World Study (CPNAS). Serum concentrations of vitamin B12 and folate were measured using the magnetic microparticle chemiluminescence method, and tHcy concentrations were measured using Hcy Assay kits. Identification of the MTHFR C677T, MTHFR A1298C, and MTRR A66G polymorphisms was performed via time-of-flight nucleic spectrometry. ResultsOur findings revealed significant sex differences in tHcy concentrations, with males exhibiting higher tHcy concentrations than females (13.95 μmol/L vs. 11.15 μmol/L, P < 0.001). Individuals deficient in both vitamin B12 and folate had an increased risk of hyperhomocysteinemia (H-Hcy) (57.4%). In contrast, the prevalence of H-Hcy was lower among those deficient in either vitamin B12 (31.1%) or folate (23.2%) alone. Significant associations were identified between the MTHFR C677T and A1298C polymorphisms and elevated serum tHcy concentrations, particularly in individuals homozygous for the T allele. Conversely, the MTRR A66G genotype did not show a significant correlation with tHcy concentrations. Optimal vitamin B12 concentrations significantly modulated the genotypic effect on tHcy concentrations, with individuals having adequate vitamin B12 and folate exhibiting low tHcy concentrations, even among high-risk genotypes (TT). ConclusionsAdequate concentrations of folate and vitamin B12 significantly reduce serum tHcy concentrations and mitigate the genotypic impact on tHcy concentrations, highlighting the potential for targeted nutritional interventions to manage cardiovascular risks associated with H-Hcy.This trial was registered at clinicaltrials.gov as ChiCTR2100051983.