High Folate Research Articles

Spatial Transcriptomics and Single-Nucleus Multi-Omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development

Spatial Transcriptomics and Single-Nucleus Multi-Omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development

Folic acid supplementation during fattening period affects growth and nutritional metabolism in Japanese Black beef cattle

The folate requirements for beef cattle have not been established. Therefore, we investigated whether rumen-unprotected folic acid supplementation during the fattening period affects carcass traits and nutritional metabolism in Japanese Black beef cattle. Eighteen Beef cattle aged 16 months were divided into three groups: control, low folic acid supplementation (0.43 g DM/day), and high folic acid supplementation (0.86 g DM/day). Treatment was administered for 12 months. Folic acid supplementation dose-dependently increased serum folate levels, suggesting that supplemental folic acid can be absorbed into the body. Folic acid supplementation dose-dependently decreased serum vitamin B12 levels, while plasma total homocysteine and methylmalonic acid levels—markers for deficiency of folate and/or vitamin B12—were unaffected. Thus, the treatment did not clearly affect the nutritional status of these vitamins. Supplementation increased body weight, with no negative effects on other carcass traits. The levels of insulin-like growth factor 1, retinol, albumin, and some amino acids in serum or plasma were affected by supplementation. These results suggest that rumen-unprotected folic acid supplementation during the fattening period could increase the body weight of Japanese Black beef cattle and the mechanism of action may be related to growth-related hormones and/or the metabolism of some nutrients, including folate.

Co-cultivation of selected Lactiplantibacillus plantarum strains with starter cultures under osmotic stress increases folate content and enhances product quality in fermented dairy

This study aimed to identify lactic acid bacteria (LAB) strains with high folate production potential to enhance the folate content in fermented dairy products. From 284 LAB strains sourced from fermented vegetables and dairy, six were selected for their outstanding folate production. Among these, Lactiplantibacillus plantarum TXZ2-26 and L. plantarum FJ2-3 demonstrated strong synergistic interactions with the starter culture, resulting in an increased total LAB cell count after co-cultivation. The effects of five different stress conditions on the growth, folate production, and expression of key folate-synthesis genes (folE, folP, folQ, folB, folK) in the two strains were further examined, revealing that the two strains demonstrated increased folate production under 3% NaCl stress. Finally, both unstressed and NaCl-stressed strains were used in the fermentation of goat and cow milk alongside the starter culture. The results revealed that the addition of L. plantarum TXZ2-26 and FJ2-3 significantly boosted the folate content of the fermented dairy products and improved their physicochemical properties, with the stressed strains exhibiting a more pronounced effect. These findings underscore the potential of L. plantarum TXZ2-26 and FJ2-3 as effective probiotics for producing folate-enriched fermented foods.

Exploring the effects of pemetrexed on drug resistance mechanisms in human lung adenocarcinoma and its association with PGRMC1

According to the 2022 cancer statistics of the World Health Organization, lung cancer ranks among the top ten causes of death, with lung adenocarcinoma being the most prevalent type. Despite significant advancements in lung cancer therapeutics, many clinical limitations remain, primarily due to the development of drug resistance. The present study investigated the effects of pemetrexed on the drug resistance mechanisms in human lung adenocarcinoma and its association with progesterone receptor membrane component 1 (PGRMC1) expression. Given that KRAS-mutant lung adenocarcinoma cell lines (e.g., A549) exhibit a high folate synthesis activity, pemetrexed, which is structurally similar to folate, was selected as the therapeutic drug. The present study used a lung adenocarcinoma cell line (A549) and established a drug-resistant lung adenocarcinoma cell line (A549/PEM). The findings demonstrated that PGRMC1 expression was elevated in the A549/PEM cells. It has been hypothesized that PGRMC1 regulates iron absorption through heme binding, resulting in a preference for iron-related cell death pathways (ferroptosis). Our findings indicate that drug-resistant lung adenocarcinoma cells with high PGRMC1 levels exhibit elevated antioxidant activity on the cell membrane and increased reliance on iron-dependent cell death pathways. This suggests a correlation between PGRMC1 and pemetrexed-induced iron-dependent cell death. Our study contributes to the development of more effective therapeutic strategies to improve the prognosis of patients with lung adenocarcinoma, particularly those facing drug resistance challenges.

Maternal Serum Folate During Pregnancy and Congenital Heart Disease in Offspring

The association of folate supplementation with congenital heart disease (CHD) prevention is controversial. To examine the association of maternal serum folate levels at early to midpregnancy with CHD risk in offspring. This case-control study recruited participants from one of China's largest cardiac referral centers between 2015 and 2018. CHD cases and non-CHD controls were matched according to maternal age at a ratio of 1:4. Data were analyzed from May to August 2023. Maternal serum levels of folate, vitamin B12, and homocysteine were measured around the gestational age of 16 weeks. The primary outcome was CHD, which was confirmed using echocardiography. The association between CHD risk in offspring with maternal folate levels was measured using adjusted odds ratios (aORs) with 95% CIs in conditional logistic regression analyses. Interactions between folate, vitamin B12, and homocysteine and CHD were estimated on a multiplicative scale. A total of 129 CHD cases with ventricular septal defect as the most common phenotype and 516 matched controls were included. The mean (SD) maternal age at pregnancy was 31.6 (5.3) years. There was a U-shaped association between maternal serum folate levels at early to midpregnancy and CHD risk in offspring. Compared with the offspring in the second and third quartiles of maternal folate, those in the lowest (aOR, 3.09; 95% CI, 1.88-5.08) and highest quartiles (OR, 1.81; 95% CI, 1.07-3.06) had increased odds of CHD. The ORs were higher when applying the World Health Organization criteria to determine the normal range for serum folate levels. Interaction analyses suggested that the adverse associations between low and high maternal folate and CHD risk might be further magnified by vitamin B12 deficiency or elevated homocysteine. In this case-control study of CHD, low maternal serum folate levels in early to midpregnancy were associated with an increased CHD risk in offspring, and excessively high folate levels were also associated with an elevated CHD risk. Further investigation is needed to make causal inferences for the observed associations and elucidate the underlying mechanisms.

Expose to high doses of folic acid during pregnancy causes adolescent anxiety- and depression-like behaviors in offspring mice

The effects of high doses of folic acid (FA) during pregnancy on anxiety- and depression-like behaviors in adolescent offspring mice were determined and the potential underlying mechanisms were elucidated. Pregnant C57BL/6 mice were randomly assigned to Control (2 mg/kg in feed), high FA (20 mg/kg in feed), and ultrahigh FA (40 mg/kg in feed) groups. The physiological development of the offspring, their preweaning neurobehavioral milestones, and adolescent behaviors indicative of anxiety and depression were assessed. High doses of FA during pregnancy delayed key developmental milestones such as pinna detachment, fur appearance, and incisor eruption. Furthermore, it triggered anxiety-like behavior in the passive avoidance test and led to depression-like behavior, as reflected by reduced movement distance in the center zone and decreased shuttling frequency in the light-dark box test and open field test. Additionally, brain tissues of the offspring exhibited increased expression of the microglia marker ionized calcium-binding adaptor molecule 1 and the Nod-like receptor protein 3 inflammasome. These findings suggest that high doses of FA during pregnancy may impair physiological development and increase the susceptibility of the offspring to anxiety- and depression-like behaviors, potentially mediated through the induction of low-grade inflammation in the brain.

Excess Folic Acid Exposure Increases Uracil Misincorporation into DNA in a Tissue-Specific Manner in a Mouse Model of Reduced Methionine Synthase Expression

BackgroundFolate and vitamin B12 (B12) are cofactors in folate-mediated 1-carbon metabolism (FOCM), a metabolic network that supports synthesis of nucleotides (including thymidylate [dTMP]) and methionine. FOCM impairments such as a deficiency or imbalance of cofactors can perturb dTMP synthesis, causing uracil misincorporation into DNA. ObjectiveThe purpose of this study was to determine how reduced expression of the B12-dependent enzyme methionine synthase (MTR) and excess dietary folic acid interact to affect folate distribution and markers of genome stability in mouse tissues. MethodsHeterozygous Mtr knockout mice (Mtr+/–) model the FOCM-specific effects of B12 deficiency. Folate accumulation and vitamer distribution, genomic uracil concentrations, and phosphorylated histone H2AX (γH2AX) immunostaining were measured in male Mtr+/+ and Mtr+/− mice weaned to either a folate-sufficient control (C) diet (2 mg/kg folic acid) or a high folic acid (HFA) diet (20 mg/kg folic acid) for 7 wk. ResultsExposure to the HFA diet led to tissue-specific patterns of folate accumulation, with plasma, colon, kidney, and skeletal muscle exhibiting increased folate concentrations compared with control. Liver total folate did not differ. Although unmetabolized folic acid (UMFA) increased 10-fold in mouse plasma with HFA diet, UMFA accounted for <0.2% of total folate in liver and colon tissue. Exposure to HFA diet resulted in a shift in folate distribution in colon tissue with higher 5-methyl-THF and lower formyl-THF than in control mice. Mtr heterozygosity did not impact folate accumulation or distribution in any tissue. Mice on HFA diet exhibited higher uracil in genomic DNA and γH2AX foci in colon. Similar differences were not seen in liver. ConclusionsThis study demonstrates that folic acid, even when consumed at high doses, does not meaningfully accumulate in mouse tissues, although high-dose folic acid shifts folate distribution and increases uracil accumulation in genomic DNA in colon tissue.

Red blood cell folate level is associated with periodontitis in American adults: results from the NHANES 2009–2014

BackgroundRed blood cell (RBC) folate is an indicator of long-term folate nutrition. Whether there is an association between RBC folate and periodontitis is unclear. This study aimed to use the NHANES database to determine whether RBC folate is associated with moderate/severe periodontitis.MethodsA cross-sectional analysis of 10,151 participants in the NHANES database from 2009 to 2014 was performed. Multivariate logistic regression was used to analyze the independent relationship between RBC folate and moderate/severe periodontitis. The generalized additive model (GAM), restricted cubic splines (RCS), smooth curve fitting, and threshold effect analysis were used to explore the dose–response relationship and the potential nonlinear relationship between RBC folate and periodontitis. Finally, subgroup analysis and interaction tests were performed to determine the effect of covariates on the relationship between RBC folate and moderate/severe periodontitis.ResultsAfter adjusting for all confounders, there was a negative association between RBC folate concentration and moderate/severe periodontitis. The lowest fraction Q1 (< 360 ng/mL) of RBC folate concentration was used as the reference group, multivariable-adjusted ORs and 95% CIs of the second (360-463 ng/mL), third (464-569 ng/mL), fourth (570-732 ng/mL), and the highest quintile (> 733 ng/mL) categories were 0.88 (0.77, 1.01), 0.83 (0.72, 0.96), 0.77 (0.67, 0.90), 0.65 (0.56, 0.77) respectively. Additionally, a threshold nonlinear association was found between RBC folate (ng/mL) log2 transformation and moderate/severe periodontitis.ConclusionThis cross-sectional study revealed a negative relationship between RBC folate and moderate/severe periodontitis within a certain threshold range. Dentists and policymakers should pay closer attention to oral hygiene and health care for people with low or high RBC folate levels. Further causal and longitudinal research mechanisms are needed to validate our findings.

Spatial Transcriptomics and Single-Nucleus Multi-omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development.

Folate, an essential vitamin B9, is crucial for diverse biological processes including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Here, we employed mouse model and spatial transcriptomics and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.

Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy.

Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane-dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.

Vitamin B6, B12, and Folate's Influence on Neural Networks in the UK Biobank Cohort.

One-carbon metabolism coenzymes may influence brain aging in cognitively unimpaired adults. Baseline data were used from the UK Biobank cohort. Estimated intake of vitamin B6, B12, and folate was regressed onto neural network functional connectivity in five resting-state neural networks. Linear mixed models tested coenzyme main effects and interactions with Alzheimer's disease (AD) risk factors. Increased B6 and B12 estimated intake were linked with less functional connectivity in most networks, including the posterior portion of the Default Mode Network. Conversely, higher folate was related to more connectivity in similar networks. AD family history modulated these associations: Increased estimated intake was positively associated with stronger connectivity in the Primary Visual Network and Posterior Default Mode Network in participants with an AD family history. In contrast, increased vitamin B12 estimated intake was associated with less connectivity in the Primary Visual Network and the Cerebello-Thalamo-Cortical Network in those without an AD family history. The differential patterns of association between B vitamins and resting-state brain activity may be important in understanding AD-related changes in the brain. Notably, AD family history appears to play a key role in modulating these relationships.

Maternal serum unmetabolized folic acid concentration following multivitamin and mineral supplementation with or without folic acid after 12 weeks gestation: A randomized controlled trial.

Pregnant women are advised to take folic acid (FA) supplements before conception and during the first trimester of pregnancy. Many women continue FA supplementation throughout pregnancy, and concerns have been raised about associations between excessive FA intake and adverse maternal and child health outcomes. Unmetabolized folic acid (UMFA) is found in serum after high FA intakes and is proposed as a biomarker for excessive FA intake. We aimed to determine if removing FA from prenatal micronutrient supplements after 12 weeks of pregnancy reduces serum UMFA concentrations at 36 weeks gestation. In this double-blind, randomized controlled trial conducted in South Australia, 103 women with a singleton pregnancy were randomly assigned at 12-16 weeks gestation to take a micronutrient supplement containing noFA or 800 µg/day FA from enrollment until 36 weeks gestation. Ninety women (0 µg/day FA n = 46; 800 µg/day FA n = 44) completed the study. Mean, UMFA concentration was lower in the women randomized to the 0 µg/day group compared to the 800 µg/day FA group, 0.6 ± 0.7 and 1.4 ± 2.7 nmol/L, respectively. The adjusted mean difference (95% CI) in UMFA between the groups was [-0.85 (-1.62, -0.08) nmol/L, p = 0.03]. Maternal serum and red blood cell folate concentrations were lower in the 0 µg/day FA group than in the 800 µg/day group (median 23.2 vs. 49.3 and1335 vs. 1914 nmol/L, respectively; p < 0.001). Removing FA at 12-16 weeks gestation from prenatal micronutrient supplements reduced the concentration of UMFA at 36 weeks gestation.

High red blood cell folate is associated with an increased risk of diabetes death among a hypertensive cohort

The relationship between folate and diabetes remains inconclusive, possibly because of folate measured differentially between studies. Interference from mandatory folic acid fortification (FAF) has also been blamed. With both folate intake and circulating concentration measured, we assessed the relationship between folate and the risk of diabetes death in a hypertensive cohort established before FAF. We hypothesized that the association between folate and diabetes death is measurement dependent. We analyzed the data of 3133 hypertensive adults aged ≥19 years who participated in the Third National Health and Nutrition Examination Survey (1991–1994) and were followed up through December 31, 2010. Hazard ratios of diabetes death were estimated for participants with high (4th quarter) folate compared with those with moderate (2nd and 3rd quarters) or low (1st quarter) concentrations of folate. Dietary folate intake, total folate intake (including folate from supplements), serum, and red blood cell (RBC) folate were measured. After 42,025 person-years of follow-up, 165 diabetes deaths were recorded, and a dose-response positive association was observed between diabetes death and RBC folate. The adjusted hazard ratios of diabetes death were 1.00 (reference), 1.42 (95% CI. 1.20–1.68), and 2.21 (1.73–2.82), respectively, for hypertensive adults with low, moderate, and high RBC folate. No association was detected between diabetes death and serum folate concentration, folate intake, or either dietary intake or total intake. With minimized interference from FAF, neither dietary nor serum folate was associated with diabetes death, but elevated RBC folate was associated with a high risk of diabetes deaths among hypertensive patients.

High Dietary Folic Acid Supplementation Reduced the Composition of Fatty Acids and Amino Acids in Fortified Eggs.

The study aimed to evaluate the effects of dietary folic acid (FA) on the production performance of laying hens, egg quality, and the nutritional differences between eggs fortified with FA and ordinary eggs. A total of 288 26-week-old Hy-Line Brown laying hens (initial body weights 1.65 ± 0.10 kg) with a similar weight and genetic background were used. A completely randomized design divided the birds into a control group and three treatment groups. Each group consisted of six replicates, with twelve chickens per replicate. Initially, all birds were fed a basal diet for 1 week. Subsequently, they were fed a basal diet supplemented with 0, 5, 10, or 15 mg/kg FA in a premix for a duration of 6 weeks. Supplementation of FA could significantly (p < 0.05) enhance the FA content in egg yolks, particularly when 10 mg/kg was used, as it had the most effective enrichment effect. Compared to the control group, the Glu content in the 10 and 15 mg/kg FA groups showed a significant (p < 0.05) decrease. Additionally, the contents of Asp, Ile, Tyr, Phe, Cys, and Met in the 15 mg/kg FA group were significantly (p < 0.05) lower compared to the other groups. Adding FA did not have significant effects on the levels of vitamin A and vitamin E in egg yolk, but the vitamin D content in the 5 and 10 mg/kg FA groups showed a significant (p < 0.05) increase. Furthermore, the addition of FA did not have a significant effect on the levels of Cu, Fe, Mn, Se, and Zn in egg yolk. The dietary FA did not have a significant effect on the total saturated fatty acids (SFA) and polyunsaturated fatty acid (PUFA) content in egg yolk. However, the total monounsaturated fatty acid (MUFA) content in the 5 and 10 mg/kg groups significantly (p < 0.05) increased. These changes in nutritional content might be attributed to the increased very low-density lipoprotein (VLDL) protein content. The significant decrease in solute carrier family 1 Member 1 (SLC1A1), solute carrier family 1 Member 2 (SLC1A2), and solute carrier family 1 Member 3 (SLC1A3) gene expression compared to the control group appeared to be the reason for the decrease in amino acid content in egg yolk within the dietary FA group. The findings suggest that the appropriate addition of FA can enhance the levels of MUFA and vitamin D in egg yolks, thereby improving their nutritional value. Excessive intake of FA can decrease the effectiveness of enriching FA in egg yolk and impact the enrichment of certain amino acids. The yolk of eggs produced by adding 10 mg/kg of FA to the feed contains the optimal amount of nutrients. This study informs consumers purchasing FA-fortified eggs.

Risk of Excess Maternal Folic Acid Supplementation in Offspring.

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

Mango Consumption Was Associated with Higher Nutrient Intake and Diet Quality in Women of Childbearing Age and Older Adults.

Nutritional equity has been recognized as a priority in nutrition research, as reiterated by the new life-stage approach utilized by the Dietary Guidelines for Americans. Two of the life stages focused on are pregnant and lactating females as well as older adults, due to their unique nutritional needs and unique chronic health conditions. Both groups have low intakes of several nutrients, including those of public health concern, and suboptimal diet quality, underlining the importance to improve their dietary intakes. Incorporating fruit into their diets could help alleviate these gaps. Thus, the objective of the current study is to expand upon our current knowledge of the benefits of fruit within these two subgroups that DGA guidelines focus on and determine nutrient and food group intake as well as diet quality in women of childbearing age (WCA; as a proxy for pregnant and/or lactating females, n = 16,774) and older adult (n = 18,784) mango consumers compared with non-consumers, using NHANES 1988-1994 and 1999-2018. Both WCA and older adult mango consumers had greater than 20% higher intakes of fiber and vitamin C and WCA consumers had upwards of 10% higher folate, magnesium, and potassium intakes compared with non-consumers. Both groups of consumers had lower intake of saturated fat and older adults had lower intakes of protein and vitamin B12. Diet quality was 16 and 13% higher in WCA and older adult consumers compared with non-consumers, respectively. Additionally, mango consumers had lower beef, poultry, fish, and solid fat intakes and WCA consumers had higher whole grain intakes compared with non-consumers. This study suggests incorporating mango into the diet could increase select nutrient intake as well as diet quality in specific life stages of adult Americans.

The German guideline "Obesity in pregnancy": comparison with the international approach.

Obesity is an increasing problem, even in young women of reproductive age. Obesity has a negative impact on conception, the course of pregnancy, and neonatal outcomes. Caring for obese pregnant women has becoming an important aspect of standard prenatal care. The Guideline "Obesity and Pregnancy" of the German Society of Gynecology and Obstetrics aims to create evidence-based recommendations which can be used to improve the care of obese pregnant women. As obesity is a worldwide problem, many societies for obstetrics and gynecology have created national guidelines. We reviewed the following guidelines for obesity and pregnancy: American College of Obstetricians and Gynecologists (ACOG) 2021, Royal College of Obstetrics and Gynecology (RCOG) 2018; AND Society of Obstetricians and Gynecologists of Canada (SOGC) 2019. These guidelines were compared to the German guideline. There are some variations between the guidelines, though no major contradictions exist. Disparities were found regarding the recommendations for substitution of high folic acid and Vitamin D. Furthermore, the recommended time for screening for gestational diabetes and the methods to control fetal growth differ between the guidelines. Regarding place of birth, RCOG allows delivery in midwifery-led units in the absence of other high-risk circumstances, while others request facility of care by neonatologists and medical staff trained in care of obese women. Induction of labor at term due to increased risk of intrauterine demise is mostly limited to women with a body mass index of 40 kg/m2. Only one guideline considers induction of all obese women. For intrapartum management, the majority allows tolerating of longer labor times to delivery if fetal monitoring is sufficient and fetal stress is excluded. Special encouragement of breastfeeding and healthy lifestyle is commonly recommended; only in the Canadian guideline, postpartum depression evaluation is requested due to the overall high prevalence of depression and anxiety in obese women. All guidelines consider pregnancies in obese women as high-risk pregnancies and emphasize the need for preconception counseling. There are special needs in pregnancy care and in the intrapartum and postpartum management to be observed.

Association Between High Blood Folate Levels and Glaucoma in a Representative Korean Population.

This study aimed to investigate the association between folate levels and the prevalence of glaucoma. This nationwide population-based cross-sectional study included 1790 participants aged ≥40 years. We analyzed data regarding the participants obtained in the 2016-2018 Korean National Health and Nutrition Examination Survey. The diagnosis of glaucoma was defined according to the International Society of Geographical and Epidemiological Ophthalmology criteria. Logistic regression analyses were used to investigate the relationship between blood folate levels and glaucoma. There was a significantly lower prevalence of glaucoma in the highest quartile of blood folate levels than in the lowest quartile, after adjusting for confounding factors such as age, sex, systemic hypertension, diabetes, hypercholesterolemia, and smoking (odds ratio [OR] = 0.470; 95% confidence interval [CI], 0.291-0.759; P for trend = 0.017). There was a significantly lower risk of glaucoma in the highest quartile of blood folate levels than in the lowest quartile among women (OR = 0.188; 95% CI, 0.099-0.357; P for trend <0.001) and younger participants (OR =0.443; 95% CI, 0.229-0.856; P for trend = 0.045). Our findings indicate a strong inverse correlation between blood folate levels and glaucoma.

Folic acid for the primary prevention of stroke: a systematic review and meta-analysis.

Results from studies were inconsistent with regard to the effect of folic acid on the primary prevention of stroke. The aim of this study was to analyze the association between folic acid and the primary prevention of stroke using the data from observational studies and randomized controlled trials (RCTs). Eligible publications published until June 2024 were searched in the database of PubMed, Web of Science and Embase. This study included all observational studies and RCTs of folic acid with first stroke as the reporting endpoints. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled in the random-effects model to assess the effect of folic acid on the primary prevention of stroke. Results from 12 observational publications with 16 research, including 312,320 participants, were combined to explore the association between dietary folic acid intake and the primary prevention of stroke. The results showed that high dietary folic acid intake was associated with a 17% reduction in stroke incidence (RR:0.83; 95% CI: 0.73-0.94), and the effect of dietary folic acid was greater in areas without grain fortification (RR:0.80; 95% CI: 0.67-0.95). The pooled results from 12 RCTs, totaling 75,042 participants, indicated that folic acid supplementation was not associated with the stroke primary prevention (RR:0.92; 95% CI: 0.80-1.05), but folic acid supplementation was effective in areas without grain fortification (RR:0.78; 95% CI: 0.68-0.89). Our meta-analysis demonstrated that dietary folic acid is effective in stroke primary prevention, and folic acid supplementation is effective in stroke primary prevention only in areas without grain fortification. https://www.crd.york.ac.uk/PROSPERO/#myprospero, identifier CRD42024516991.

A Case Report of Oral Ulcer in Rheumatoid Arthritis: A Diagnostic and Management Dilemma

Chronic oral ulcer in patients with rheumatoid arthritis is a diagnostic challenge in primary health care. The possible causes include the disease itself, side effect of treatment, malignancy and infections. This is a case of a 63-year-old woman with underlying rheumatoid arthritis presented with chronic solitary oral ulcer. She was on oral methotrexate (MTX) and high dose folic acid for five years with good compliance. Tissue biopsy showed marked inflammatory cells infiltration and nuclear hyperchromatism with no evidence of malignancy nor infection. The ulcer was resolved after completing antifungal treatment for six weeks following failure of improvement after empirical antibiotic, elimination of possible trauma and discontinuation of MTX. The fungal staining was negative. There are possibilities of false negative results, thus broadened diagnosis with repeated and further investigations are recommended in cases who did not respond to conventional treatment.