Effect Of Folic Acid Supplementation Research Articles

Association between maternal folic acid supplementation in pregnancy and abnormal fetal growth: Evidence from a birth cohort baseline survey.

The prevention of abnormal fetal growth can improve the health status of children during infancy and in the future. However, the effect of folic acid supplementation on fetal weight for gestational age is unclear. To investigate the effect of folic acid supplementation during pregnancy on abnormal fetal growth. This study was an observational study based on a baseline survey of the Jinan birth cohort. Multivariate logistic regression models were constructed to analyze the effects of folic acid supplementation on the risk of abnormal fetal growth and the stratified analyses were used to assess effects of folic acid supplementation in different subgroups. A total of 6501 pairs of mothers and single live births met inclusion and exclusion criteria in the 6640 pairs baseline population of a birth cohort. The proportion for appropriate-for-gestational-age (AGA), Small-for-gestational-age (SGA), and Large-for-gestational-age (LGA) were 73.0%, 5.2%, and 21.7% (1413/6501) among the study population. For the delivery of SGA, cumulative folic acid supplementation for more than 4 months was a protective factor in the mothers who were <35 years of age (OR=0.76, 95% CI: 0.58-0.99) or primiparas (OR=0.73, 95% CI: 0.54-0.98). While, for the delivery of LGA, folic acid supplementation during pregnancy was also a protective factor among the mothers who had 13 years of educational time or more (OR=0.69, 95% CI: 0.51-0.94). Cumulative supplementation of folic acid for more than 4 months may be appropriate to reduce the risk of SGA for mothers aged <35 years and primiparas. Continuing to take folic acid supplements after the first trimester may increase the risk of LGA for multiparas and women with lower education time.

Anatomical, behavioral, and cognitive teratogenicity associated with valproic acid: a systematic review.

Recent guidance from UK health authorities strongly cautions against the use of valproic acid (VPA) in persons under 55 because of reevaluated risk of teratogenicity. To summarize the extant literature documenting VPA-associated anatomical, behavioral, and cognitive teratogenicity. Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, Web of Science, and Google Scholar were searched in accordance with PRISMA guidelines. Collected data covered study design, participant characteristics, anatomical, behavioral, or cognitive effects, and folic acid outcomes. 122 studies were identified meeting inclusion comprised of studies evaluating anatomical (n=67), behavioral (n=28), and cognitive (n=47) teratogenicity. Twenty studies were identified reporting on the risk mitigation effects of folic acid supplementation. Prenatal VPA exposure is associated with anatomical teratogenicity including major congenital malformations (odds ratio [OR] 2.47-9.30; p<0.005). Behavioral teratogenicity including autism (OR 1.70-4.38), impaired motor development (OR 7.0), and ADHD (OR 1.39) are also significantly associated with VPA exposure. VPA was associated with intellectual disability and low IQ (hazard ratio [HR] 2.4-4.48, verbal intelligence: Spearman's ρ=-0.436, respectively). Teratogenic effects were dose-dependent across all domains and were significant when compared with controls and other antiepileptic drugs (eg, carbamazepine, lamotrigine, and levetiracetam). Folic acid supplementation does not significantly reduce the hazard associated with VPA. VPA is significantly associated with anatomical, behavioral, and cognitive teratogenicity. Folic acid supplementation does not abrogate the risk of teratogenicity associated with VPA exposure. Available evidence supports recommendations to reduce VPA exposure in women of reproductive age.

Folic Acid Supplementation for Blood Pressure Reduction in Hypertension: A Meta-Analysis

Background: Hypertension is a major risk factor for cardiovascular disease. While antihypertensive medications are the cornerstone of treatment, adjunctive therapies like folic acid supplementation have gained attention for their potential to lower blood pressure. This meta-analysis aims to comprehensively assess the impact of folic acid supplementation on blood pressure in hypertensive individuals. Methods: A systematic search of electronic databases (PubMed, Embase, Cochrane Library) was conducted from January 2018 to December 2023 to identify randomized controlled trials (RCTs) evaluating the effect of folic acid supplementation on blood pressure in adults with hypertension. Data on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were extracted. A random-effects model was used to pool data, and heterogeneity was assessed using the I² statistic. Results: Twenty-three RCTs involving 2,853 hypertensive participants were included. Folic acid supplementation was associated with a significant reduction in SBP (mean difference [MD] -2.93 mmHg, 95% confidence interval [CI] -4.11 to -1.75, p &lt; 0.00001), DBP (MD -1.87 mmHg, 95% CI -2.63 to -1.11, p &lt; 0.00001), and MAP (MD -2.21 mmHg, 95% CI -3.01 to -1.41, p &lt; 0.00001) compared to placebo or control. Subgroup analyses revealed that the blood pressure-lowering effect of folic acid was more pronounced in individuals with low baseline folate levels, those with higher baseline blood pressure, and in studies with longer durations of supplementation. Conclusion: Folic acid supplementation appears to be a safe and effective adjunctive therapy for reducing blood pressure in hypertensive individuals. These findings support the potential role of folic acid in improving cardiovascular outcomes in this population.

The Effect of Folic Acid Supplementation in the First Trimester of Pregnancy on Perinatal Outcomes: A Retrospective Cohort Study

Background: The purpose of this study is to compare the perinatal outcomes of pregnant women who received folic acid (FA) supplements to those who did not, using a large sample size. Methods: This study was conducted retrospectively at Konya Training and Research Hospital between 2016 and 2020. The study included pregnant women who took FA and those who did not. We obtained sociodemographic data and perinatal outcomes of all pregnant women from the electronic record system. We learned about folic acid usage from the e-prescription tracking system. Results: Out of the total sample size of 2393 patients, n = 861 (35.97%) received FA supplements during pregnancy, while n = 1532 (64.02%) did not. The gestational age at birth in the group receiving FA was higher than in the group not receiving FA (271.59 ± 13.83 days vs. 270.09 ± 15.27 days, p = 0.005). The group that did not take FA had more neonatal intensive care unit (NICU) admissions than the group that did (5.09% vs. 2.90%, p = 0.011). In the group that took FA, there were n = 17 (1.97%) patients with gestational diabetes (GDM), whereas in the group that did not use FA, there were n = 15 (0.98%) patients with GDM (p &lt; 0.001). Conclusions: The group taking FA supplements had a higher gestational age at birth and GDM, while admission to the NICU were lower compared to the group not taking FA supplements.

Folic Acid as a Potential Vitamin in Glycemic Control: A Systematic Review.

This systematic review aims to examine the relationship between serum folate level and folic acid supplements with glycemic control parameters (fasting blood glucose (FBG), insulin level, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and Hemoglobin A1C (HbA1c)) in adult individuals with current studies. In this study, which was designed as a systematic review, the searches were performed on Web of Science, Science Direct, Medline, Wiley, and Cochrane Library databases between April 10, 2023, and May 10, 2023, and the searches were updated between October 16, 2023, and November 14, 2023. Of the 1855 studies obtained from the screening, 17 met the criteria and were included in the systematic review. The PROSPERO system registered the study protocol (ID: CRD42023472434). Although no significant correlation was found between serum folate levels and glycemic control parameters in most of the cross-sectional studies included in this systematic review, most of the randomized controlled trials showed that glycemic control parameters (FBG, insulin, HOMA-IR) decreased significantly in the intervention group receiving folic acid supplementation compared to the control group. However, study durations were short, and HbA1c needed to be evaluated in most studies. This makes it difficult to get information about the long-term effects of folic acid supplementation. More comprehensive studies should be conducted to draw more precise conclusions about the relationship between folic acid levels and folic acid supplementation with glycemic control parameters.

Effect of Folic Acid Supplementation on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

Effect of Folic Acid Supplementation on Glycemic Control in Patients with Type 2 Diabetes Mellitus.

The effect of folic acid supplementation and folate deficiency on embryo implantation

Implantation is a critical stage of pregnancy, which occurs in a short period of interaction between the receptive endometrium and the embryo. Folic acid (FA) is a synthetic derivative of folate and is recommended as a pre-conceptional supplement. However, the impact of different doses of FA supplementation and folate deficiency during the early stages of pregnancy requires further investigation. The aim of this study was to investigate the possible effects of FA supplementation and folate deficiency on expression of Estrogen Receptor Alpha (ER-α), Vascular Endothelial Growth Factor-A (VEGFA), and Integrin alpha V and beta3 (Integrin αVβ3). A total of 32, 6–8-week old Wistar albino rats were divided into four groups of control, folate-deficiency, low-dose, and high-dose FA supplement groups. After five weeks of FA supplementation and folate deficiency model formation, mated rats were sacrificed on the 5th gestational day (GD), and implantation sites were collected. The expression of ER- α, VEGFA, and Integrin αVβ3 in the implantation sites were examined with immunohistochemistry and real-time PCR. The results revealed that the mRNA levels of ESR1, VEGFA, and Integrin αV and β3 were significantly increased in the high-dose FA group and significantly decreased in the folate deficiency group compared to the control group (p < 0.05). Based on these results, it can be concluded that FA supplementation before pregnancy has positive effects on the maintenance of pregnancy, and folate deficiency may lead to implantation disorders.

Letter to the Editor ‘Folic acid and plasma lipids: Interactions and effect of folate supplementation’

Letter to the Editor ‘Folic acid and plasma lipids: Interactions and effect of folate supplementation’

Abstract 2170: Effects of folic acid supplementation on early stages of colitis-associated carcinogenesis

Abstract Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by persistent mucosal inflammation extending throughout the colon. Due to compromised intestinal surface integrity and the prolonged use of medication, individuals with UC often develop a folate deficiency, requiring folic acid (FA) supplementation. Prior findings from this group indicate that FA supplementation, at clinically relevant levels, promotes UC-associated dysplasia. Supplementation with FA resulted in an increased multiplicity of dysplasia and a significant elevation in the expression of several inflammatory genes (e.g. IL-6, Cox-2, Iκκ-β) within the colonic mucosa of mice with UC. Genome-wide expression profiling of normal and dysplastic colonic epithelial cells from mice treated with different doses of FA revealed differentially expressed genes were enriched for members of the ERK and NF-κB pathways. Subsequent in vitro analyses, utilizing isogenic RKO colon adenocarcinoma cells exposed to various doses of FA, demonstrated the downregulation of ERK and p-ERK in wild type (WT) p53+/+ cells, while an increase in expression was observed in p53−/− cells at the protein level. The goal of this study is to investigate the role of the MAPK/ERK pathway in the development of UC-associated neoplasms. An in vitro model that faithfully reproduces the inflamed microenvironment in the context of WT vs. mutant p53, the putative gatekeeper of UC-associated carcinogenesis, is needed to enhance our understanding of early changes in the colon that are induced by FA and drive tumor formation. Colon organoids are being generated by isolating crypts from WT p53+/+ and mutant p53+/515A mice. These organoids are then co-cultured with mouse macrophages (RAW264.7 cells) in inserts to stimulate crosstalk between the macrophages and colonic epithelial cells, as in the inflamed colon. Analyses demonstrate that the macrophages express pivotal inflammatory cytokines characteristic of UC, including IL-1β, IL-10, TNF-α, and IL-6, irrespective of the presence or absence of LPS stimulation. Co-cultured organoids and macrophages will be exposed to different concentrations of FA for various lengths of time, and the impact of treatment on the levels of ERK, p-ERK, and p65 will be assessed. The ability of p-ERK to mediate the transcriptional activation of NF-κB and its downstream effector IL-6 will also be evaluated. Subsequent investigations employing this innovative experimental model will reveal the mechanisms by which FA supplementation promotes the progression of UC-associated dysplasia. Given the potential risks associated with FA supplementation in individuals with UC, there is an urgent need to translate these results to a clinical setting. (Supported by CA262551 and the Timothy and Aurora Hughes Cancer Research Fund). Citation Format: Ariane Rocha Bartolomeu, Wen-Chi Chang, Lisa Vanderveer, Kristen N. Harvey, Mitchell Cheung, Harry S. Cooper, Margie Lee Clapper. Effects of folic acid supplementation on early stages of colitis-associated carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2170.

Maternal exposure to folate antagonists and susceptibility to congenital heart disease in offspring: A systematic review and meta-analysis.

The objective of this meta-analysis was to determine whether maternal exposure to folate antagonists is associated with increased rates of congenital heart disease in offspring. A comprehensive search for articles in the MEDLINE (PubMed) and EMBASE databases published up to 21 August 2023 was performed. The search strategy was not limited by study design but only for articles in the English language. Analysis of 6 cohort studies and 5 cross-sectional studies, published between 1976 and 2020, showed significant increase in rate of congenital heart disease (odds ratio 1.55, 95% confidence interval, 1.28-1.87) when exposed to folate antagonists compared with the control. Further subgroup analysis showed the increased rate for exposure to both dihydrofolate reductase inhibitors and antiepileptic drugs separately. No differences were observed when analyses were stratified by timing of study. Administration of folate antagonists within the 12-week period preceding conception and throughout the second and third months of gestation exhibited a statistically significant elevation in the susceptibility to congenital heart diseases. Notably, the protective effect of folic acid supplementation was reported in cases of congenital heart disease linked to dihydrofolate reductase inhibitors but not that associated with antiepileptic drugs.

Sperm DNA methylation defects in a new mouse model of the 5,10-methylenetetrahydrofolate reductase 677C>T variant and correction with moderate dose folic acid supplementation.

5,10-Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that plays a key role in providing methyl groups for DNA methylation, including during spermatogenesis. A common genetic variant in humans (MTHFR 677C>T) results in reduced enzyme activity and has been linked to various disorders, including male infertility. A new animal model has been created by reproducing the human equivalent of the polymorphism in mice using CRISPR/Cas9. Biochemical parameters in the Mthfr 677TT mice recapitulate alterations found in MTHFR 677TT men. Our aims were to characterize the sperm DNA methylome of the Mthfr 677CC and TT mice on a control diet (2 mg folic acid/kg diet) and assess the effects of folic acid supplementation (10 mg/kg diet) on the sperm DNA methylome. Body and reproductive organ weights, testicular sperm counts, and histology were examined. DNA methylation in sperm was assessed using bisulfite pyrosequencing and whole-genome bisulfite sequencing (WGBS). Reproductive parameters and locus-specific imprinted gene methylation were unaffected by genotype or diet. Using WGBS, sperm from 677TT mice had 360 differentially methylated tiles as compared to 677CC mice, predominantly hypomethylation (60% of tiles). Folic acid supplementation mostly caused hypermethylation in sperm of males of both genotypes and was found to partially correct the DNA methylation alterations in sperm associated with the TT genotype. The new mouse model will be useful in understanding the role of MTHFR deficiency in male fertility and in designing folate supplementation regimens for the clinic.

Mendelian randomization to evaluate the effect of folic acid supplement on the risk of Alzheimer disease.

We conducted a study to evaluate the impact of folic acid supplementation on the risk of Alzheimer disease (AD). A Mendelian randomization (MR) analysis model assessed the causal effects of folic acid supplementation on AD, utilizing data from recent genome-wide association studies. Effect estimates were scrutinized using various methods: inverse-variance weighted (IVW), simple mode, weighted mode, simple median, weighted median, penalized weighted median, and the MR-Egger method. The sensitivity analysis assessed heterogeneity and pleiotropy of individual single nucleotide polymorphisms (SNPs) using the IVW method with Cochran Q statistics and MR Egger intercept, respectively. Additionally, a leave-one-out sensitivity analysis determined potential SNP-driven associations. Both fixed-effect and random-effect IVW models in the MR analysis revealed a reduced risk of AD associated with folic acid supplementation (odds ratio, 0.930; 95% CI, 0.903-0.958, P < .001; odds ratio, 0.930; 95% CI, 0.910-0.950, P < .001) based on 7 SNPs as instrumental variables. The reverse MR analysis indicated no causal association between AD and folic acid supplementation. This study, utilizing genetic data, suggests that folic acid supplementation may potentially reduce the risk of AD and provides novel insights into its etiology and preventive measures.

The effect of folic acid supplementation on damage caused by chronic cerebral hypo-perfusion in the hippocampus: the role of antioxidant agents and homocysteine

The effect of folic acid supplementation on damage caused by chronic cerebral hypo-perfusion in the hippocampus: the role of antioxidant agents and homocysteine

Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial

BackgroundFolic acid (FA) is the oxidized form of folate found in supplements and FA-fortified foods. Most FA is reduced by dihydrofolate reductase to 5-methyltetrahydrofolate (5mTHF); the latter is the form of folate naturally found in foods. Ingestion of FA increases the plasma levels of both 5mTHF and unmetabolized FA (UMFA). Limited information is available on the downstream metabolic effects of FA supplementation, including potential effects associated with UMFA. ObjectiveWe aimed to assess the metabolic effects of FA-supplementation, and the associations of plasma 5mTHF and UMFA with the metabolome in FA-naïve Bangladeshi adults. MethodsSixty participants were selected from the Folic Acid and Creatine Trial; half received 800 μg FA/day for 12 weeks and half placebo. Plasma metabolome profiles were measured by high-resolution mass spectrometry, including 170 identified metabolites and 26,541 metabolic features. Penalized regression methods were used to assess the associations of targeted metabolites with FA-supplementation, plasma 5mTHF, and plasma UMFA. Pathway analyses were conducted using Mummichog. ResultsIn penalized models of identified metabolites, FA-supplementation was associated with higher choline. Changes in 5mTHF concentrations were positively associated with metabolites involved in amino acid metabolism (5-hydroxyindoleacetic acid, acetylmethionine, creatinine, guanidinoacetate, hydroxyproline/n-acetylalanine) and 2 fatty acids (docosahexaenoic acid and linoleic acid). Changes in 5mTHF concentrations were negatively associated with acetylglutamate, acetyllysine, carnitine, propionyl carnitine, cinnamic acid, homogentisate, arachidonic acid, and nicotine. UMFA concentrations were associated with lower levels of arachidonic acid. Together, metabolites selected across all models were related to lipids, aromatic amino acid metabolism, and the urea cycle. Analyses of nontargeted metabolic features identified additional pathways associated with FA supplementation. ConclusionIn addition to the recapitulation of several expected metabolic changes associated with 5mTHF, we observed additional metabolites/pathways associated with FA-supplementation and UMFA. Further studies are needed to confirm these associations and assess their potential implications for human health. Trial registration numberThis trial was registered at https://clinicaltrials.gov as NCT01050556.

Effect of Folic Acid Supplementation on the Liver Function in Chronic Schizophrenia Patients

Oxidative stress caused by free radicals and long-term antipsychotic use in chronic schizophrenic patients may result in liver cell damage and impaired liver function. Folic acid is an exogenous antioxidant that can boost the antioxidant defense mechanism (Glutathione Reductase), lowering free radicals and improving liver function. Determine the correlation between adjuvant folic acid and liver function in chronic schizophrenic patients. This was a placebo-controlled, double-blinded randomized control trial. The study sample included 36 patients in the control group and 36 patients in the treatment group. Subjects were patients who had suffered from schizophrenia for at least 2 years and received antipsychotics. Research subjects in the treatment group received folic acid supplementation. The intervention was conducted for 21 days during hospitalization. The level of AST (U/L) and ALT (U/L) was measured before and after supplementation. Following folic acid supplementation, AST levels were significantly improved (26.950 U/L compared to prior to treatment 33.09 U/L, p= &lt;0.001). ALT levels after treatment were increased but there was no significant difference observed (p= 0.835). Folic acid supplementation improves AST levels significantly.

Reducing the Risk of Birth Defects Associated with Maternal Influenza: Insights from a Hungarian Case—Control Study

Influenza viruses can cause several complications during pregnancy. Therefore, we aimed to investigate the effects of influenza on the development of congenital abnormalities (CAs) by analyzing the database of the Hungarian Case–Control Surveillance of Congenital Abnormalities (HCCSCA). In our multicenter, case–control, population-based study, we processed clinician-reported outcomes and diagnoses collected in the HCCSCA. The case group included newborns with different non-chromosomal birth defects, while the controls were newborns without CAs. Maternal influenza, as a risk factor for CAs, was analyzed by using a logistic regression model and odds ratios with 95% confidence intervals (CIs). Our results showed that maternal influenza in the first trimester was associated with increased odds of developing non-chromosomal CAs (OR: 1.41, CI: 1.28–1.55). There were increased odds of neural tube defects (OR: 2.22, CI: 1.78–2.76), orofacial clefts (OR: 2.28, CI: 1.87–2.78), and congenital heart defects (OR: 1.28, CI: 1.10–1.49) after influenza infection. In all cases, we found a protective effect of folic acid supplementation in the first trimester. In summary, the odds of non-chromosomal birth defects are higher after maternal influenza in the first trimester, and folic acid or pregnancy vitamin supplementation and antipyretic therapy may reduce the effect of maternal influenza during the first trimester.

Folic acid supplementation in a mouse model of diabetes in pregnancy alters insulin sensitivity in female mice and beta cell mass in offspring.

Epidemiological studies have reported discrepant findings on the relationship between folic acid intake during pregnancy and risk for gestational diabetes mellitus (GDM). To begin to understand how folic acid impacts metabolic health during pregnancy, we determined the effects of excess folic acid supplementation (5× recommendation) on maternal and fetal offspring metabolic health. Using a mouse (female C57BL/6J) model of diet-induced diabetes in pregnancy (western diet) and control mice, we show that folic acid supplementation improved insulin sensitivity in the female mice fed the western diet and worsened insulin sensitivity in control mice. We found no unmetabolized folic acid in liver from supplemented mice suggesting the metabolic effects of folic acid supplementation are not due to unmetabolized folic acid. Male fetal (gestational day 18.5) offspring from folic acid supplemented dams (western and control) had greater beta cell mass and density than those from unsupplemented dams; this was not observed in female offspring. Differential sex-specific hepatic gene expression profiles were observed in the fetal offspring from supplemented dams but this differed between western and controls. Our findings suggest that folic acid supplementation affects insulin sensitivity in female mice, but is dependent on their metabolic phenotype and has sex-specific effects on offspring pancreas and liver.

The Effect of Folic Acid Supplementation on Endothelial Function and Arterial Stiffness Markers in Adults: A Systematic Review and Meta-Analysis.

Folic acid might improve endothelial function, but the results are inconclusive. This systematic review evaluated the effect of folic acid supplementation on endothelial parameters and arterial stiffness in adults. The study protocol was registered with the PROSPERO database (CRD42021290195). The PubMed, Web of Sciences, Cochrane and Scopus databases were searched to identify English-language randomised controlled trials of the effect of folate supplementation on arterial stiffness and endothelial function markers in adults. There were significant differences between the effect of folic acid and placebo on flow-mediated dilation (random-effects model, standardized mean differences (SMD): 0.888, 95% confidence interval (CI): 0.447, 1.329, p < 0.001) and monocyte chemotactic protein 1 (random-effects model, SMD: -1.364, 95% CI: -2.164, -0.563, p < 0.001), but there was no significant difference in the central pulse wave velocity (fixed-effects model, SMD: -0.069, 95% CI: -0.264, 0.125, p = 0.485) and peripheral pulse wave velocity (fixed-effects model, SMD: -0.093, 95% CI: -0.263, 0.077, p = 0.284). In conclusion, folic acid might have a favourable effect on endothelial function but may not affect arterial stiffness. Further studies are needed to confirm these results.

Molecular regulatory mechanism of key LncRNAs in subclinical mastitic cows with folic acid supplementation

BackgroundFolic acid is a water-soluble B vitamin (B9), which is closely related to the body’s immune and other metabolic pathways. The folic acid synthesized by rumen microbes has been unable to meet the needs of high-yielding dairy cows. The incidence rate of subclinical mastitis in dairy herds worldwide ranged between 25%~65% with no obvious symptoms, but it significantly causes a decrease in lactation and milk quality. Therefore, this study aims at exploring the effects of folic acid supplementation on the expression profile of lncRNAs, exploring the molecular mechanism by which lncRNAs regulate immunity in subclinical mastitic dairy cows.ResultsThe analysis identified a total of 4384 lncRNA transcripts. Subsequently, differentially expressed lncRNAs in the comparison of two groups (SF vs. SC, HF vs. HC) were identified to be 84 and 55 respectively. Furthermore, the weighted gene co-expression network analysis (WGCNA) and the KEGG enrichment analysis result showed that folic acid supplementation affects inflammation and immune response-related pathways. The two groups have few pathways in common. One important lncRNA MSTRG.11108.1 and its target genes (ICAM1, CCL3, CCL4, etc.) were involved in immune-related pathways. Finally, through integrated analysis of lncRNAs with GWAS data and animal QTL database, we found that differential lncRNA and its target genes could be significantly enriched in SNPs and QTLs related to somatic cell count (SCC) and mastitis, such as MSTRG.11108.1 and its target gene ICAM1, CXCL3, GRO1.ConclusionsFor subclinical mastitic cows, folic acid supplementation can significantly affect the expression of immune-related pathway genes such as ICAM1 by regulating lncRNAs MSTRG.11108.1, thereby affecting related immune phenotypes. Our findings laid a ground foundation for theoretical and practical application for feeding folic acid supplementation in subclinical mastitic cows.

Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.