Folate Concentrations Research Articles

Unmetabolized folic acid and organ fibrosis: Are they nefarious partners?

Recent publications raise the possibility that folic acid (FA), specifically unmetabolized folic acid (UMFA), might promote the progression of organ fibrosis via signaling through folate receptors, leading to excessive extracellular matrix production by myofibroblasts and other cell types. Clinical research over the past two decades adds credence to this largely unexplored contention. FA is a synthetic form of folate, first made in 1945, that has been added to the food supply in the US since 1998 to decrease neural tube defects; subsequently, other countries have followed suit. Notably, synthetic FA, compared to natural dietary folates, is metabolized differently, and potentially activates cellular signaling pathways, leading to fibrosis progression. Although FA food supplementation programs have resulted in a roughly 2-fold increase in serum folate concentrations and a decrease in the prevalence of neural tube defects, other concerns have surfaced. As such, due to the incomplete metabolism of ingested FA, before it can enter cellular processes, most individuals exhibit concentrations of unmetabolized folic acid (UMFA) in the circulation. We hypothesize that it is UMFA, but not natural occurring food folates, which in part promotes the progression of organ fibrosis in many systems. We feel the issue is relevant since organ fibrosis is involved in nearly half of all mortality in industrialized nations. Finally, this proposed nexus of UMFA and organ fibrosis might have preventive and therapeutic implications, and more research is needed on the topic.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016

BackgroundAlthough adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. ObjectivesWe aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. MethodsWe conducted cross-sectional analyses of 2100 individuals aged 6–18 y enrolled in the National Health and Nutrition Examination Survey, 2011–2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. ResultsIn multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [β: −1.566; 95% confidence interval: −2.935, −0.196], 1.423 (−1.423; −2.689, −0.157), 1.309 (−1.309; −2.573, −0.044), 1.530 (−1.530; −2.918, −0.142), and 1.381 (−1.381; −2.641, −0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (−0.888; −1.677, −0.099) ng/mL decrease in the serum folate. ConclusionsHigher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Role of Peritoneal Equilibration Test in Assessing Folate Transport During Peritoneal Dialysis

BACKGROUNDLow plasma folate levels have been reported in patients undergoing hemodialysis and peritoneal dialysis (PD) in clinical studies. However, folate transport has never been mentioned as a factor contributing to low plasma folate levels in patients undergoing PD. The peritoneal equilibrium test (PET) assesses the plasma creatinine level and glucose transport abilities. This study aimed to evaluate the association between plasma folate levels and folate transport during PD based on PET grades. METHODSThis study recruited 50 patients who underwent PD for ≥ 3 months and were categorized according to PET grades. Data regarding plasma folate levels and dialysate folate were collected. The primary outcomes were the relationship between the PET grade and plasma folate level and between the PET grade and dialysate-to-plasma folate concentration ratio (D/P folate). Furthermore, the difference in the plasma folate level and D/P folate between men and women was assessed. RESULTSThe plasma folate level and the D/P folate significantly differed among the four PET groups (both p < 0.001). PET grade was significantly negatively correlated with plasma folate levels (r=-0.56, p < 0.001) and positively correlated with D/P folate (r=0.686, p < 0.001). In subgroup analysis, neither the plasma folate level nor the D/P folate significantly differed between men and women. CONCLUSIONSOur study provides clinical evidence that the PET grade is associated with the plasma folate level and D/P folate, regardless of sex. Larger cohort studies are warranted to assess the importance of folate supplementation during PD based on PET grades.

Folic Acid–Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India

India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Change in median serum folate levels between baseline and study end point as the primary outcome of the study. A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. ClinicalTrials.gov Identifier: NCT06174883.

Update on the impact of voluntary folic acid fortification of corn masa flour on red blood cell folate concentrations-National Health and Nutrition Examination Survey, 2011-March 2020.

Folic acid is a micronutrient that is effective at preventing neural tube defects (NTDs). In 2016, the FDA authorized the voluntary fortification of corn masa flour (CMF) with folic acid to reduce disparities in NTDs among infants of women who do not regularly consume other fortified cereal grains, in particular Hispanic women of reproductive age (WRA). We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020 assessing the impact of voluntary fortification of CMF on the folate status of Hispanic WRA. We analyzed folic acid usual intake and red blood cell (RBC) folate concentrations among non-pregnant, non-lactating Hispanic WRA, comparing pre-fortification (2011-2016) to post-fortification (2017-March 2020) data. RBC folate concentrations were used to create model-based estimation of NTD rates. The proportion of Hispanic WRA with folic acid usual intakes <400 μg/d did not change (2011-2016: 86.1% [95% Confidence Interval, CI: 83.7-88.5]; 2017-March 2020: 87.8% [95% CI: 84.8-90.7]; p = .38) nor did the proportion of Hispanic WRA with RBC folate below optimal concentrations (<748 nmol/L, 2011-2016: 16.0% [95% CI: 13.7-18.2]; 2017-March 2020: 18.1% [95% CI: 12.1-24.0]; p = 0.49). Model-based estimates of NTD rates suggest further improvements in the folate status of Hispanic WRA might prevent an additional 157 (95% Uncertainty Interval: 0, 288) NTDs/year. Voluntary fortification of CMF with folic acid has yet to have a significant impact on the folate status of WRA. Continued monitoring and further research into factors such as fortified product availability, community knowledge, and awareness of folic acid benefits would inform and improve future public health interventions.

Pre-pregnancy training of women with early pregnancy loss and adenomyosis, taking into account folate cycle gene polymorphisms

Polymorphisms in folate cycle genes (methylene tetrahydrofolate reductase – MTHFR, methionine synthase reductase – MTRR and methionine synthase – MTR) and associated hyperhomocysteinemia and folate deficiency play an important role among multiple genetic causes early pregnancy loss.The results of studies examining the influence of polymorphic variants of the folate cycle genes in women with pregnancy losses are quite contradictory. It has been proven that prescribing folic acid preparations or in combination with other vitamins and trace elements at the stage of preparation for pregnancy and during pregnancy significantly reduces the risk of miscarriage and pregnancy loss, is an important prevention of defects in the development of the nervous system of the fetus and disorders of the autistic spectrum in newborns and children. Adenomyosis remains a complex and urgent problem in obstetrics and gynecology, as today there is convincing evidence of the negative impact of adenomyosis both on fertility and on the course and outcomes of pregnancy.The objective: to study the prevalence of folate cycle gene polymorphisms and to assess the effectiveness of vitamin-mineral complex use in the pre-gravid preparation taking into account the genetic peculiarities of folate metabolism in women with early pregnancy loss (EPL) and adenomyosis.Materials and methods. Data from the examination at the stage of pre-gravid preparation of 40 women with early pregnancy loss – EPL (5–13 weeks of gestation) and adenomyosis, which were included in the main group, and 34 women with adenomyosis without a history of EPL (control group) were analyzed.Resuts. In 73,5% of women of the control group, the C/C genotype of the MTHFR 677 C&gt;T gene prevailed, in women with EPL and adenomyosis, a significant increase in the frequency (50%) of the heterozygous polymorphism for this C/T allele of the MTHFR 677 gene and a decrease in the frequency of detection of neutral A/A allele and increased frequency (80%) of MTHFR 1298 gene allele polymorphism (A/C and C/C). In women with EPL and adenomyosis, a significant increase in homocysteine (12,8±2,3мμmol/l) and a deficiency of folic acid (5,0±0,9 ng/ml) in blood serum compared to reference values were found.Conclusions. The use of vitamin-mineral complex, which includes betaine (200 mg), cystine (200 mg), zinc (10 mg), niacin (16 mg), folic acid (in the form of 5-MTHF-glucosamin – 400 mcg), vitamin B12 (in the form of methylcobalamin – 2.5 mcg), vitamin B6 (1.4 mg) and riboflavin (1.4 mg), 1 tablet 1-2 times a day for 3 months for the pre-gravid preparation leaded to significant decrease of homocysteine concentration, normalization of folic acid concentration. This formed favorable conditions for pregnancy course and for risk reduction of possible obstetrical complications.

Development and validation of a cognitive dysfunction risk prediction model for the abdominal obesity population.

This study was aimed to develop a nomogram that can accurately predict the likelihood of cognitive dysfunction in individuals with abdominal obesity by utilizing various predictor factors. A total of 1490 cases of abdominal obesity were randomly selected from the National Health and Nutrition Examination Survey (NHANES) database for the years 2011-2014. The diagnostic criteria for abdominal obesity were as follows: waist size ≥ 102 cm for men and waist size ≥ 88 cm for women, and cognitive function was assessed by Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Word Learning subtest, Delayed Word Recall Test, Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The cases were divided into two sets: a training set consisting of 1043 cases (70%) and a validation set consisting of 447 cases (30%). To create the model nomogram, multifactor logistic regression models were constructed based on the selected predictors identified through LASSO regression analysis. The model's performance was assessed using several metrics, including the consistency index (C-index), the area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA) to assess the clinical benefit of the model. The multivariate logistic regression analysis revealed that age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were significant predictors of cognitive dysfunction in individuals with abdominal obesity (p < 0.05). These predictors were incorporated into the nomogram. The C-indices for the training and validation sets were 0.814 (95% CI: 0.875-0.842) and 0.805 (95% CI: 0.758-0.851), respectively. The corresponding AUC values were 0.814 (95% CI: 0.875-0.842) and 0.795 (95% CI: 0.753-0.847). The calibration curves demonstrated a satisfactory level of agreement between the nomogram model and the observed data. The DCA indicated that early intervention for at-risk populations would provide a net benefit, as indicated by the line graph. Age, sex, education level, 24-hour total fat intake, red blood cell folate concentration, depression, and moderate work activity were identified as predictive factors for cognitive dysfunction in individuals with abdominal obesity. In conclusion, the nomogram model developed in this study can effectively predict the clinical risk of cognitive dysfunction in individuals with abdominal obesity.

Supplementation with antioxidant micronutrients in pregnant women with obesity: a randomized controlled trial.

Obesity increases maternal morbidity and adversely affects child health. Maternal inflammation may play a role in adverse outcomes. The objective of this study was to determine whether providing a higher dose of antioxidant micronutrients to pregnant women with obesity would raise concentrations of key antioxidant vitamins and impact inflammation and oxidative stress during pregnancy. This was a double-blind, randomized controlled trial. We recruited pregnant women with a body mass index (BMI) ≥ 30 kg/m2 at their initial prenatal visit ( < 13 weeks gestation) and collected blood and urine samples at baseline, 24-28 weeks, and 32-36 weeks to measure micronutrient concentrations (vitamin C, E, B6 and folate), markers of inflammation (C-reactive protein, interleukin-6, 8, and 1β) and oxidative stress (8-epi-PGF2α and malondialdehyde). We collected maternal and infant health data from enrollment to delivery as secondary outcomes. We enrolled 128 participants (64 in each arm), and 98 (49 in each arm) completed follow-up through delivery. Both groups received a standard prenatal vitamin containing the recommended daily allowance of micronutrients in pregnancy. In addition, the intervention group received a supplement with 90 mg vitamin C, 30 αTU vitamin E, 18 mg vitamin B6, and 800 μg folic acid, and the control group received a placebo. The intervention group had higher vit B6 (log transformed (ln), β 24-28 weeks: 0.76 nmol/L (95% CI: 0.40, 1.12); β 32-36 weeks: 0.52 nmol/L (95% CI: 0.17, 0.88)) than the control group. Vitamins C, E, erythrocyte RBC folate concentrations did not differ by randomization group. The intervention did not impact biomarkers of inflammation or oxidative stress. There were no differences in maternal or neonatal clinical outcomes by randomization group. Higher concentrations of antioxidant vitamins during pregnancy increased specific micronutrients and did not impact maternal inflammation and oxidative stress, which may be related to dosing or type of supplementation provided. Clinical Trial Identification Number: NCT02802566; URL of the Registration Site: www. gov .

Mango (Mangifera indica L) var Banganapalli: Impact of in-situ intervention on folic acid concentration and its changes in physicochemical property

Fruits are a source of vitamins. Mango is one of the abundantly nutritional fruits. Vitamin B9, or folic acid, is one of the important vital amines due to its role in preventing neural deficiency. Several beneficial micro-organisms are used for the synthesis of folic acid. In this study, Lactobacillus acidophilus, Leuconostoc mesenteroides, Streptococcus thermophilus, and Saccharomyces cerevisiae were used. Saccharomyces cerevisiae synthesized folic acid as compared to other organisms. There were five different concentrations of mango pulp that were analyzed for folic acid synthesis (5%, 10%, 15%, 20%, and 30%). The initial concentration of pulp was 133.37 mg kg−1, but after fermentation with four micro-organisms it got reduced. As compared to the other three organisms, Saccharomyces cerevisiae synthesizes 17.15 mg kg−1, 30.14 mg kg−1, 28.62 mg kg−1, 21.70 mg kg−1, and 21.78 mg kg−1, respectively, at different pulp concentrations of 5%, 10%, 15, 20%, and 30%. Vitamin C increased to 320 mg as compared to the control, and there was no significant difference between the four micro-organisms. Antioxidants also showed positive results at different concentrations of pulp. There was an increase in titratable acidity and a decrease in pH recorded for the 24 h fermentation period. In this variety, the color of mango pulp slightly changes to yellow shades due to the breakdown of pigments, so this effects the *b value in between the pulp concentrations. Data supports the enrichment of folic acid, which will further support the utilization of beneficial micro-organisms in food beverages.

Association of serum folic acid levels in response to fasting blood glucose in early pregnancy with the risk of gestational diabetes mellitus: A retrospective cohort study

ObjectiveWith increasingly prevalent folic acid consumption in early pregnancy, concerns about its potentially negative effect on maternal metabolism have been raised. Recent findings regarding folic acid levels in the first trimester and the risk of gestational diabetes mellitus have been inconclusive. The aim of this study was to investigate the association of folic acid status in early pregnancy with gestational diabetes mellitus as well as examine whether glucose levels can be modulated by folic acid status during the same first trimester. MethodsThis was a retrospective cohort study based on 27 128 Chinese pregnant women who registered during their first prenatal visit from January 2015 to December 2019. Serum folic acid and fasting blood glucose concentrations were measured during the 9th to 13th gestational weeks. Binary logistic regression was applied to estimate the odds ratios of gestational diabetes mellitus by using the serum folic acid levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes mellitus, we established subgroups, in which analyses were stratified by age (<25, 25–29, 30–34, and ≥35 y), parity (nulliparous and parous), prepregnancy body mass index (< 18.5, 18.5–23.9, and ≥ 24 kg/m2), and family history of diabetes (yes and no). ResultsThe positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher in those in the middle (Q3) and higher (Q4) quartiles compared with those in Q1 and Q2. A higher risk for gestational diabetes mellitus was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63; 95% CI, 4.56–6.95, and Q4: odds ratio = 5.57; 95% CI, 4.68–6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 and Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots had a positive correlation of serum folic acid level with fasting blood glucose concentration as well as risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level. ConclusionsOur findings underscore the importance of maintaining an appropriate folic acid concentration for preserving a lower risk of gestational diabetes mellitus, especially in women with relatively higher blood glucose in early pregnancy. Additionally, folic acid concentration > 32.5 nmol/L may be considered a risk factor for gestational diabetes mellitus. This research suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive folic acid intake.

Folate receptor alpha autoantibodies in the serum of patients with relapsing–remitting multiple sclerosis (RRMS)

Multiple sclerosis (MS) is a potentially progressive, autoimmune neurologic disorder of the central nervous system (CNS), resulting from an autoimmune attack on central nervous system white matter. Folate deficiencies are linked to DNA instability and breakdown of phospholipid membranes and thus might affect myelin integrity. Folic acid exerts its effects through its receptors (FRs). Folate receptor alpha autoantibodies (FRAA) can block folate transport to the brain. Due to important role of folate in the pathogenesis of MS, in this project we aimed to study FRAA serum levels in patients with relapsing remitting multiple sclerosis (RRMS). Fifty-four patients with RRMS and 58 healthy individuals were enrolled in this study. Serum samples were collected from all participants and folate receptor alpha autoantibody (FRAA) serum concentration was measured by Enzyme-linked immunosorbent assay (ELISA). The results showed that FRAA serum levels in patients with RRMS is 67.20±19.79ng/ml as compared to controls which was 37.32±13.26ng/ml. Significant increase in folate receptor autoantibody serum concentration was seen in patients with RRMS when compared to control group (P=0.007). The results showed that a high concentration of folate receptor autoantibody is associated with RRMS. We have also found that 85.18% (46/54) of patients with RRMS were positive for serum FRAA, whereas the prevalence in controls was only 46.55% (27/58). It is concluded that serum FRAA are more prevalent in RRMS patients than controls. The findings also suggest that FRAA might be involved in the pathophysiology of RRMS.

Folate in the United States Population and its Association with Congestive Heart Failure.

To investigate the relationship between red blood cell (RBC) folate and congestive heart failure (CHF). We extracted the concentrations of RBC folate and collated CHF information from the National Health and Nutrition Examination Survey (NHANES) survey (12820 individuals). Weighted univariate logistic regression, weighted multivariate logistic regression, and restrictive cubic spline (RCS) were used to assess the relationship between RBC folate concentrations and CHF. The unadjusted model showed that the highest tertile group of RBC folate concentration was significantly associated with a higher risk of CHF compared to the lowest tertile group of RBC folate levels (odds ratio [OR] = 3.09; 95% confidence interval [CI], 2.14-4.46). Similar trends were seen in the multivariate-adjusted analysis (OR = 1.98; 95% CI: 1.27-3.09). The OR was 1.0 when the predicted RBC folate exceeded 2757 nmol/L in the RCS model, indicating that the risk of CHF was low and relatively stable up to a predicted RBC folate level of 2757 nmol/L, but began to increase rapidly thereafter (p = 0.001). The risk of CHF may be increased either by high RBC folate concentrations (highest tertile of RBC folate or 2637 nmol/L) or by folate deficiency. Considering the two sides of the association between RBC folate and CHF, there is a need for large-scale clinical research to better investigate if the association between RBC folate and CHF is a cause-effect relationship, what are the underlying pathophysiological basis, as well as to identify optimal dietary folate equivalent (DFE) and RBC folate concentration intervals.

Coronary Artery Disease Is Related to Methylation Disorders Caused by the c.1286A&gt;C MTHFR Polymorphism and to Low Serum 5-MTHF and Folic Acid Concentrations—Preliminary Results

Background: Single nucleotide polymorphisms in gene encoding is the key enzyme in the folates pathway, methyltetrahydrofolate reductase (MTHFR), which causes methylation disorders associated with coronary artery disease (CAD). We evaluated associations between methylation disorders caused by MTHFR gene polymorphisms and the blood folate concentrations (folic acid, 5-MTHF) in CAD patients. Methods: Study group: 34 patients with CAD confirmed by invasive coronary angiography (ICA). Controls: 14 patients without CAD symptoms or significant coronary artery stenosis, based on ICA or multislice computed tomography (MSCT) with coronary artery calcification (CAC) scoring. Real-time PCR genotyping was assessed using TaqMan™ probes. Folic acid and 5-MTHF concentrations in blood serum were determined using Liquid Chromatography-Mass Spectrometry (LC-MS). Results: The c.[1286A&gt;C];[1286A&gt;C] MTHFR polymorphism occurred significantly more often in (CAD+) patients compared to the (CAD−) cohort and to the selected general European “CEU_GENO_PANEL” population sample. The concentration of 5-MTHF and folic acid in subgroups of CAD+ patients with methylation disorders categorized by genotypes and CAD presence (CAD+) was always lower in CAD+ subgroups compared to non-CAD individuals (CAD−). Conclusions: Further studies on a larger scale are needed to implicate the homozygous c.1286A&gt;C MTHFR variant as CAD genetic marker and the 5-MTHF as CAD biomarker. Identification of high CAD risk using genetic and phenotypic tests can contribute to personalized therapy using an active (methylated) form of folic acid (5-MTHF) in CAD patients with MTHFR polymorphisms.

One-carbon metabolite supplementation increases vitamin B12, folate, and methionine cycle metabolites in beef heifers and fetuses in an energy dependent manner at day 63 of gestation.

One-carbon metabolites (OCM) are metabolites and cofactors which include folate, vitamin B12, methionine, and choline that support methylation reactions. The objectives of this study were to investigate the effects of moderate changes in maternal body weight gain in combination with OCM supplementation during the first 63 d of gestation in beef cattle on (1) B12 and folate concentrations in maternal serum (2) folate cycle intermediates in maternal and fetal liver, allantoic fluid (ALF), and amniotic fluid (AMF) and (3) metabolites involved in one-carbon metabolism and related metabolic pathways in maternal and fetal liver. Heifers were either intake restricted (RES) and fed to lose 0.23 kg/d, or fed to gain 0.60 kg/d (CON). Supplemented (+ OCM) heifers were given B12 and folate injections weekly and fed rumen-protected methionine and choline daily, while non-supplemented (-OCM) heifers were given weekly saline injections. These two treatments were combined in a 2 × 2 factorial arrangement resulting in 4 treatments: CON-OCM, CON + OCM, RES-OCM, and RES + OCM. Samples of maternal serum, maternal and fetal liver, ALF, and AMF were collected at slaughter on day 63 of gestation. Restricted maternal nutrition most notably increased (./ ≤ 0.05) the concentration of vitamin B12 in maternal serum, 5,10-methylenetetrahydrofolate and 5,10-methenyltetrahydrofolate in maternal liver, and cystathionine in the fetal liver; conversely, maternal restriction decreased (P = 0.05) 5,10-methylenetetrahydrofolate concentration in fetal liver. Supplementing OCM increased (P ≤ 0.05) the concentrations of maternal serum B12, folate, and folate intermediates, ALF and AMF 5-methyltetrahydrofolate concentration, and altered (P ≤ 0.02) other maternal liver intermediates including S-adenosylmethionine, dimethylglycine, cystathionine Glutathione reduced, glutathione oxidized, taurine, serine, sarcosine, and pyridoxine. These data demonstrate that OCM supplementation was effective at increasing maternal OCM status. Furthermore, these data are similar to previously published literature where restricted maternal nutrition also affected maternal OCM status. Altering OCM status in both the dam and fetus could impact fetal developmental outcomes and production efficiencies. Lastly, these data demonstrate that fetal metabolite abundance is highly regulated, although the changes required to maintain homeostasis may program altered metabolism postnatally.

Breastfeeding and biomarkers of folate and cobalamin status in Norwegian infants: a cross-sectional study

Abstract Folate and vitamin B12 (cobalamin) are essential for growth and development. This cross-sectional study aims to describe folate and vitamin B12 status according to infant age and breastfeeding practices in Norwegian infants. Infants aged 0–12 months (n = 125) were recruited through public health clinics. We registered breastfeeding status and measured serum concentrations of folate, cobalamin, total homocysteine (tHcy), and methylmalonic acid (MMA). The associations between infant age, breastfeeding, and biomarker concentrations were estimated in regression models. The mean (SD) age was 24 (16) weeks, and 42% were exclusively breastfed, 38% were partially breastfed, and 21% were weaned. Overall, median (IQR) folate, cobalamin, tHcy, and MMA concentrations were 47 (35–66) nmol/L, 250 (178–368) pmol/L, 6.99 (5.69–9.27) µmol/L, and 0.35 (0.24–0.83) µmol/L, respectively. None of the infants were folate deficient, 15% were vitamin B12 deficient (&lt; 148 pmol/L), and 23% had low vitamin B12 status (148–221 pmol/L). Elevated tHcy (&gt; 6.5 μmol/L) and MMA (&gt; 0.26 μmol/L) were found in 62% and 69% of the infants, respectively. Compared to weaned, exclusively or partially breastfed infants were younger and had 46% higher tHcy concentrations (P &lt; 0.001), in addition to 47% and 39% lower cobalamin concentrations (P &lt; 0.001), respectively. However, the observed biomarker concentrations appeared to be independent of infant age. In conclusion, low vitamin B12 status was prevalent and appeared to be more common in the younger exclusively breastfed compared to older weaned infants. The implications of low vitamin B12 status in infancy are unknown and require further investigation.

The Performance of Nanofiltration Membrane in Concentrating Folic Acid from Fermented Mungbean (Phaseolus radiatus L.) by Rhizopus oligosporus Strain-C1 and Rhizopus sp. for Recovery Efficiency of Natural Folic Acid

This research was conducted to evaluate the performance of the nanofiltration (NF) membrane in concentrating permeate obtained from the ultrafiltration (UF) membrane of fermented mung bean. The procedure was performed to determine both the best flux and efficiency of recovering folic acid from the multi-filtration process. Feed A and Feed B were used as ultrafiltered permeate of fermented mung bean (Phaseolus radiatus L.) obtained using Rhizopus oligosporus strain-C1 and Rhizopus sp., respectively. These feeds were subjected to the NF membrane installed in crossflow filtration (CFF) module system at room temperature, flow rate ~7.5 L/min. and transmembrane pressure (TMP) of 10 bar for 0, 15, 30, 45, 60, 75 and 90 minutes. The results showed that based on the optimum flux, the best performance of the NF membrane for Feed A and B was achieved at 15 and 15 min, with permeate flux of 32.22 and 20.44 L/m2.h., respectively. Retentate A and B contained folic acid concentrations of 308.51 and 297.53 μg/mL, as well as total solids of 1.39% and 2.20%. Meanwhile, permeate A and B yielded folic acid concentrations of 106.88 and 63.77 μg/mL, with total solids of 0.22 and 0.32%. Under the NF process conditions, retentate A and B showed observed rejection (Robs) rates of folic acid at 65.35 and 78.56%, as well as total solids of 84.34 and 85.36%, respectively. There was also a 9.75 and 3.10% increase in folic acid with a 4.18% and 17.31% rise in total solids compared to the initial condition at 0 minutes. Molecular weight analysis of folic acid in permeate A and B after 15 min. and 15 min. of processing were dominated by monomer with a MW of 442.17 Da. Meanwhile, mass spectra of feed B for a processing time of 15 min. were dominated by monomers with MW of 442.19 and 442.47 Da, both with a relative intensity of 100%.

The Impact of Folic Acid-Fortified Iodized Salt on Serum Folate Concentration in Women of Reproductive Age- A Longitudinal Interventional Study Based in South India

The Impact of Folic Acid-Fortified Iodized Salt on Serum Folate Concentration in Women of Reproductive Age- A Longitudinal Interventional Study Based in South India

Association between Serum Folate and Vaginal High-Risk Human Papillomavirus Infections in United States Women

BackgroundSerum concentration of folate was inversely associated with cervical intraepithelial neoplasia and cervical cancer in some studies. The association between folate and human papillomavirus (HPV) infection, a necessary cause of cervical cancer, has not been well elucidated. ObjectivesWe evaluated whether serum folate concentrations were associated with high-risk HPV (hrHPV) infection. MethodsThe study population was 11,801 females, aged 18–59 y, enrolled in the National Health and Nutrition Examination Survey (NHANES), from 2003 to 2016, in the United States. In this cross-sectional study, prevalence ratios (PRs) of vaginal hrHPV were calculated using logistic regression models, by quintiles of serum folate. ResultsFemales in the lowest quintile had <21.3 nmol/L of folate. Approximately 23% of the females (2733/11,801) were hrHPV positive. In age-adjusted models, folate was significantly associated with hrHPV infection. The PRs and 95% confidence intervals (CIs) were (PR: 1.52; 95% CI: 1.37, 1.70) for the first, (PR: 1.29; 95% CI: 1.15, 1.44) for the second, (PR: 1.19; 95% CI: 1.06, 1.34) for the third, and (PR: 1.09; 95% CI: 0.96, 1.23) for the fourth quintiles, compared with the females in the highest quintile, with a significant P value for trend, <0.0001. The association remained statistically significant after the models were further adjusted for lifestyle and sexual risk factors for hrHPV infection; the females in the lowest quintile were more likely to have hrHPV infection than those in the highest quintile (PR: 1.40; 95% CI: 1.11, 1.53). ConclusionsResults from this sample of females in the United States suggest that serum folate concentration is inversely associated with hrHPV infection.

Optimizing the Synthesis of Folic Acid Conjugated Silver Nanoparticles by Box-Behnken Design to Target Breast Cancer Cells

In this study, the synthesis of folic acid conjugated silver nanoparticles (FA&amp;AgNPs) was optimized. FA&amp;AgNPs were synthesized by reduction of silver nitrate with folic acid, which is widely used to target folate receptors in cancer cells. Five independent variables (stirring speed, AgNO3 concentration, folic acid concentration, AgNO3 volume/folic acid volume, and temperature) that were effective on silver nanoparticle synthesis were determined. Based on the independent variables, an experimental plan consisting of 46 experiments was created using the Box-Behnken design (BBD). Nanoparticle formation, physical color change, UV-Vis absorption spectroscopy, Dynamic Light Scattering (DLS) analysis, and Fourier Transform Infrared (FTIR) analysis were evaluated. The mean particle size and zeta potential of FA&amp;AgNPs produced under optimized conditions were measured as 207±4.3 nm and -51.6 mV±2.5, respectively. Cytotoxicity tests were performed to evaluate the anticancer activity of FA&amp;AgNPs in breast cancer cell lines. The IC50 values for MDA-MB-231 breast cancer cells at 24 hours and 48 hours were 20.0 µg/mL and 16.9 µg/mL, respectively, and 26.3 µg/mL and 31.5 µg/mL for MCF-7 cells. The findings indicated that FA&amp;AgNPs have the potential to be an effective anticancer agent in breast cancer cells.

Study of the association of polymorphisms of the folate cycle enzyme gene with the degree of cognitive and affective disorders in patients in the post-covid period

Recently, molecular genetic studies have become widespread, and demonstrated the importance of DNA and histone methylation processes in the epigenetic regulation of gene expression. The aim of this study was to detect the association of polymorphisms of the folate cycle enzyme gene methylenetetrahydrofolate reductase (MTHGFR) with the degree of cognitive and affective disorders and the serum level of homocysteine and folic acid in 41 post-covid patients. Hematological and laboratory indices, serum concentration of C-reactive protein, D-dimer, homocysteine and folic acid were determined. MTHGFR polymorphisms for C677T and A1298C mutations were determined by polymerase chain reaction in real time. According to the MTHGFR C677T genotype variant, the examined patients were divided into 3 groups: 1) 21 persons (male/female 10/11) with homozygous CC genotype; 2) 17 ones (male/female 12/5) with heterozygous CT genotype; 3) 3 persons with a recessive homozygous TT genotype (all men). Six months after the end of the acute phase of the coronavirus disease, patients were surveyed using questionnaires to assess the psycho-emotional state: cognitive function, anxiety and depression. No significant difference was found in the average scores of cognitive function, anxiety and depression in patients of group 1 and 2. Individuals of the group 1 C677C, who had an additional recessive homozygous C1298C mutation (group 1a, n=6), were characterized by an elevated level of homocysteine, which showed a high negative correlation with serum folate (r= -0.95). A small group of individuals with the recessive homozygous T677T genotype (group 3, all men) was distinguished by an older age, the presence of cardiovascular diseases, type 2 diabetes (2 cases out of 3), more severe manifestations of COVID-19, which forces us to pay attention to potentially increased risk of complications in such patients and requires further investigation. Correlation relationships between assessments of cognitive function, anxiety, depression and serum levels of homocysteine and folate in patients with different genotypes of MTHGFR C677T were recorded. Therefore, the use of a molecular genetic approach made it possible to pay attention to the possible predisposition to hyperhomocysteinemia in individuals who have a folic acid deficiency, and different combination of alleles of the MTHGFR gene C677T and A1298C.