Folate Levels Research Articles

Comparative Analysis of Vitamin D, Folic Acid, and Antioxidant Minerals in Various Stages of Lung Cancer.

Lung cancer continues to be one of the most common causes of death due to lung malignancies globally. Emerging research suggests that vitamins and trace minerals, particularly antioxidants, may play a role in cancer progression and treatment outcomes. This study conducts a comparative analysis of vitamin D, folic acid, and trace minerals (copper, zinc, and magnesium) in various stages of lung cancer patients. A cross-sectional study was conducted with 160 lung cancer patients, categorized into four stages (Stage 1 to Stage 4). Standardized biochemical assays, such as chemiluminescent immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and atomic absorption spectroscopy (AAS), were used to measure the levels of vitamin D, folic acid, copper (Cu), zinc (Zn), and magnesium (Mg) in the blood. The nutrient levels were compared across stages to investigate any significant variations. Vitamin D levels decreased significantly as lung cancer progressed, with Stage 1 showing the highest mean level (33 ng/mL) and Stage 4 the lowest (8 ng/mL). Folic acid levels fluctuated, showing a general decrease in theadvanced stages, with some variations in theintermediate stages. Copper levels showed individual variability without a consistent trend across stages. Zinc levels were higher in early-stage patients and decreased as cancer progressed. Magnesium levels remained relatively stable across all stages. This comparative analysis highlights the potential significance of monitoring vitamin D, folic acid, and trace minerals in lung cancer patients across different stages. The results suggest that these nutrients may play a role in the progression of lung cancer and could serve as biomarkers for disease staging.

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

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

Serum folate levels, but not vitamin B12, are associated with slower progression in carotid intima-media thickness in a population exposed to mandatory folic acid fortification

Serum folate levels, but not vitamin B12, are associated with slower progression in carotid intima-media thickness in a population exposed to mandatory folic acid fortification

A Risk Correlative Model for Sleep Disorders in Chinese Older Adults Based on Blood Micronutrient Levels: A Matched Case-Control Study.

The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults.

Folic acids promote in vitro maturation of bovine oocytes by inhibition of ferroptosis via upregulated glutathione and downregulated Fe2+ accumulation

Bovine embryos by in vitro fertilization have become the primary source of commercial embryo transfers globally. However, the developmental capacity of in vitro maturation (IVM) oocytes is considerably lower than that of in vivo maturation (IVO) oocytes, owing to the production of reactive oxygen species (ROS) via mitochondrial metabolism, which was higher in IVM oocytes than in IVO oocytes. To avoid the negative effects of ROS on embryo quality, folic acid (FA) was supplemented directly into the IVM medium to antagonize ROS production, however, the mechanisms remain unknown. In the present study, five levels of FA (0, 25, 50, 100, and 200 µM) were supplemented into the bovine oocyte culture medium. The maturation, cleavage, and blastocyst formation rates increased by 8.95 %, 6.94 %, and 4.36 %, respectively, in the 50 µM group compared to the 0 µM group. Moreover, 7904 differential genes were identified between 0 µM and 50 µM groups by transcriptome sequencing, and they were mainly enriched in 8 pathways. The glutathione, ROS, and Fe2+ levels in oocytes were found to be associated with ferroptosis. Our results revealed that 50 µM FA promoted the IVM of bovine oocytes and affected the expression of genes involved in the ferroptosis pathway. The downregulation of TFR1 and STEAP3 led to a decrease in intracellular Fe2+ accumulation, and the upregulation of GCL increased oocyte GSH levels, thereby reducing the production of ROS in the ferroptosis pathway. Our study provides a new insight into the molecular mechanisms by which FA promotes bovine oocyte development in vitro.

Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene polymorphisms and five related serum molecular levels in 2587 patients: Associated differentially with adverse pregnancy.

The aim of the study is to investigate the relationship between Methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR) polymorphisms, 5 serum related molecular levels and the risk of adverse pregnancies in different genders. Patients aged from 22 to 38 with a history of adverse pregnancy treated in our genetic eugenics clinic of Henan Provincial People's Hospital are selected. The controls aged from 20 to 34 undergoing eugenics examinations in our genetic eugenics clinic that had no history of adverse pregnancy and at least one healthy child are selected. Sanger sequencing and Chemiluminescence Microparticle Immuno Assay (CMIA) are used for detecting the mutations of MTHFR and MTRR and the 5 serum molecular serum levels. In the female group, MTHFR 677C > T is associated with Recurrent spontaneous abortion (RSA) (P = 0.0017), Chromosomal abnormality (CA) (P = 0.0053), Cleft lip and palate (CLP) (P = 0.0326) and Brain dysplasia (BD) (P = 0.0072); MTHFR 1298A > C is associated with Infertility (P = 0.0026) and BD (P = 0.0382); MTRR 66A > G is associated with CLP (P = 0.0131). In the male group, MTHFR 677C > T is associated with RSA (P = 0.0003), Infertility (P = 0.0013), CA (P = 0.0027) and BD (P = 0.0293). In the female group, the genotype of MTHFR 677C > T is associated with RSA (P = 0.0017), CA (P = 0.0014) and BD (P = 0.0021); MTHFR 1298A > C is associated with Infertility (P = 0.0081) and MTRR 66A > G is associated with Infertility (P = 0.0309). In the male group, the genotype of MTHFR 677C > T is associated with RSA (P = 0.0008), Infertility (P = 0.0096) and CA (P = 0.0165) and MTRR 66A > G is associated with Infertility (P = 0.0158) and congenital heart disease (CHD) (P = 0.0218). In the male group, there is statistically significant difference of the serum Homocysteine (Hcy) levels (P < 0.0001) between adverse pregnancy group and controls.In the female group,there is statistically significant difference of the serum vitamin D levels (P = 0.0015) between adverse pregnancy group and controls. Polymorphic variants in MTHFR and MTRR, serum Folic acid (FA), Hcy and B12 levels in the male group and vitamin D levels in the female group are associated differentially with adverse pregnancy.

Monitoring the Response of Cyclin-Dependent Kinase 4/6 Inhibitors with Mean Corpuscular Volume.

Currently, the combination of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy is a first-line treatment for hormone-receptor-positive and HER2-negative metastatic breast cancer. This study aimed to assess the impact of changes in Mean Corpuscular Volume (MCV) on predicting responses to treatment and survival in patients with hormone-receptor-positive, HER2-negative metastatic breast cancer receiving CDK4/6 inhibitors and endocrine therapy. Retrospectively, data on hemoglobin levels, MCV, B12, folate levels, and survival times were collected from 275 patients. Patients were categorized into two groups based on the degree of MCV change (delta MCV ≤ 10 vs. >10). Kaplan-Meier survival analysis was performed, with significance set at p < 0.05. The average age of the patients was 56.1 ± 12.1 years. In total, 72.7% received CDK4/6 inhibitors as first-line treatment, while 27.3% received them as second-line treatment. Before CDK4/6 inhibitor use, the median MCV level was 87.7 fL (IQR: 83-91), which increased to 98 fL (IQR: 92-103) after treatment (p < 0.001). ECOG performance score, CDK4/6 inhibitor treatment line, type of endocrine therapy, and MCV change were identified as independent predictors of progression-free survival in the Cox regression model. The median progression-free survival for the entire group was 28 months. Patients with MCV delta > 10 had a median progression-free survival of 33 months, compared to 23 months for those with MCV delta ≤ 10 (p = 0.029). There was no significant difference in median overall survival times between the two groups (p = 0.158). This study highlights that patients with MCV delta > 10 had longer median progression-free survival compared to those with MCV delta ≤ 10.

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

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

Bariatric Surgery and Metabolic Status.

Background and Objectives: Obesity is associated with numerous co-morbidities, including dyslipidemia, insulin resistance and diabetes mellitus. Bariatric surgery is the mainstay of treatment for obesity as the only method with confirmed long-term effects in weight reduction and the remission of comorbidities. Postoperative recommendations leading to changes in dietary habits and changes in digestion and absorption in the gastrointestinal tract after bariatric surgery may additionally influence the levels of laboratory parameters that reflect the metabolic and nutritional status. The purpose of the study was to analyze the possible influence of changes in dietary habits after bariatric surgery on those laboratory results that reflect the metabolic and nutritional status. Materials and Methods: This was a retrospective study of 88 patients with a history of bariatric surgery. Data were gathered from before the surgery and at 6 months after the surgery and included diet structure and selected laboratory parameters reflecting the metabolic and nutritional status, i.e., levels of fasting glucose, glycated hemoglobin, cholesterol, low- and high-density lipoproteins, triglycerides, alanine and aspartate aminotransferases, proteins, ferrum, ferritin, vitamin B12, folic acid, vitamin D and calcium, the red blood cell count and the hematocrit. Results: Postoperative festive glucose levels were reduced by 14% and were more significant in patients after Roux-en-Y gastric bypass. There was an increase of 22% in concentrations of high-density lipoproteins. Triglyceride concentrations were reduced by 32%. Aminotransferase levels decreased by 43% for alanine aminotransferase and by 14% for aspartate aminotransferase. Among the changes in dietary habits, post-bariatric patients had a reduced consumption of red meat and an increased consumption of fish, milk and dairy products and wholegrain products. Vitamin D and ferrum levels were higher after the surgery, whereas vitamin B12 and folic acid levels remained unchanged. Conclusions: Improved dietary habits of patients after bariatric surgery may lead to changes in laboratory parameters that reflect the ameliorated metabolic and nutritional status of patients after bariatric surgery.

Folate, Homocysteine, and Adverse Outcomes After Ischemic Stroke.

As a risk factor of cardiovascular diseases, homocysteine can be effectively lowered by folate. However, the associations of folate and homocysteine levels with the prognosis of ischemic stroke remained unclear. A total of 3530 patients with ischemic stroke were included. Serum folate and homocysteine levels were measured at admission. The primary outcome was composite of death and major disability (modified Rankin Scale score≥3) at 3 months after stroke onset. Univariate and multivariate logistic regression models were used. The mediation effect of homocysteine was examined. During follow-up, 1056 participants developed the primary outcome. In the univariate model, participants in the highest quartile of folate had a 29% (95% CI, 0.58-0.87) decreased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with the highest quartile of folate was 0.58 (95% CI, 0.46-0.73) for primary outcome. In contrast, participants in the highest quartile of homocysteine had a 52% (95% CI, 1.24-1.98) increased risk of primary outcome compared with those in the lowest quartile. After multivariate adjustment, the odds ratio associated with highest quartile of homocysteine was 1.57 (95% CI, 1.24-1.98) for primary outcome. In addition, 25.5% of the observed associations between folate and primary outcome was mediated through homocysteine (P=0.012). High folate levels were associated with low risks of death and major disability among Chinese patients with ischemic stroke, and homocysteine partially mediated the observed potential beneficial role of folate.

Serum Homocysteine Levels and Their Relationship With Serum Vitamin B12, Folate, and Ferritin Levels in Transfusion-Dependent Thalassemic Children.

The purpose of this study was to assess serum homocysteine levels and their relationship with serum vitamin B12, folate, and ferritin levels in transfusion-dependent thalassemic children. This study was proposed due to a paucity of literature regarding the status of homocysteine levels in thalassemic children and their relationship with the levels of vitamins and iron overload (serum ferritin values). A descriptive observational study was conducted on transfusion-dependent thalassemic children aged 1-18 years, who were registered at the Thalassemia Day Care Centre (TDCC), Umaid Hospital, Dr. SN Medical College, Jodhpur, over a period of six months. A total of 100 children were enrolled in the study, with a mean age of 8.89±4.50 years. The mean pre-transfusion hemoglobin level in the last six months was 8.23±1.02 gm/dL. The mean serum levels of homocysteine, vitamin B12, folic acid, and ferritin were 10.93±3.72 µmol/L, 164.03±80.54 pg/mL, 7.69±5.77 ng/mL, and 2175.78±1341.39 ng/mL, respectively. A statistically significant negative correlation was detected between serum vitamin B12 concentration and serum homocysteine concentration (r=-0.285, p=0.004). Statistically non-significant positive correlations were detected between serum folic acid and serum homocysteine levels (r=0.033, p=0.748) and between serum ferritin and serum homocysteine levels (r=0.179, p=0.075). A statistically significant negative correlation between serum homocysteine and vitamin B12 levels was noted, whereas statistically non-significant positive correlations were observed between serum homocysteine andserum folic acid levels and between serum homocysteine andserum ferritin levels.

Interrelationships among MTHFR gene polymorphisms, MTRR gene polymorphisms, and HBV gene BCP 1762/1764 mutations with disease progression in Chronic hepatitis B virus infection patients

Objective Chronic hepatitis B virus (HBV) infection is a major disease that seriously affects the health of patients. In this paper, the relationship among MTHFR gene polymorphism, MTRR gene polymorphism and 1762/1764 mutation in the BCP region of HBV gene with disease progression in chronic HBV patients was studied. Methods A total of 144 chronic HBV infection patients from January 2021 to June 2022 in the Third People’s Hospital of Zigong City, were included as the study subjects. These patients were divided into hepatitis B primary liver cancer patients group (PLC) in 51 cases, Non-primary liver cancer patients group (Non-PLC) in 93 cases, Non-PLC is also divided into chronic hepatitis B virus carriers (CHC) in 49 cases, hepatitis B Live cirrhosis(LC) in 44 cases. MTHFR (C677T), MTRR (A66G) and MTHFR (A1298C) genes polymorphisms were detected by PCR-dissolution curve. The level of HBV-DNA was quantified by real-time PCR, and the 1762/1764 mutation site in the BCP region of the HBV gene were detected by ARMS-PCR. Data were statistically analyzed using the SPSS statistical software. Results The proportion of HBV mutations in BCP region 1762/1764 in PLC group was 82.4%, which was higher than that in LC group (63.6%) and CHC group (51.0%), and the differences were statistically significant (p < 0.05). There were no significant differences in the distribution of MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms among CHC, LC and PLC (p > 0.05). The polymorphism distribution of MTHFR C677T, MTRR A66G and MTHFR A1298C genes in patients with chronic hepatitis B virus infection at different stages (CHC, LC and PLC) showed no gender or age differences between and within groups (p > 0.05). Among the patients with MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype, the proportion of HBV mutation in BCP region 1762/1764 in PLC group was higher than that in CHC group and LC group, and the differences were statistically significant (p < 0.05). Folate levels in the PLC group were lower than those in the non-PLC group (CHC and LC patients), and the difference was statistically significant compared with the CHC group (p < 0.05). In different MTHFR C677T and MTRR A66G genotypes, the serum GGT activity were statistically significant between mutant PLC and mutant Non-PLC (p < 0.05). Conclusion MTHFR C677T, MTRR A66G and MTHFR A1298C gene polymorphisms distribution have no gender and age differences in chronic hepatitis B virus infection patients. The mutation of HBV gene BCP region 1762/1764 may be associated with the occurrence and development of liver cancer in patients with chronic HBV infection. Single difference of MTHFR C677T, MTHFR A1298C and MTRR A66G gene polymorphisms may have little effect on the disease progression in patients with chronic HBV infection. MTHFR 677CT + TT, MTRR 66AG + GG and MTHFR 1298AA genotype combined with HBV gene BCP region 1762/1764 mutation may be closely related to the occurrence and development of hepatitis B liver cancer.

Dual folate/biotin-decorated liposomes mediated delivery of methylnaphthazarin for anti-cancer activity

Chemotherapy is an effective strategy for mitigating the global challenge of cancer treatment, which often encounters drug resistance and negative side effects. Methylnaphthazarin (MNZ), a natural compound with promising anti-cancer properties, has been underexplored due to its poor aqueous solubility and low selectivity. This study introduces a novel approach to overcome these limitations by developing MNZ-encapsulating liposomes decorated with folate and biotin (F/B-LP-MNZ). This dual-targeting strategy aims to enhance the anti-cancer efficacy and specificity of MNZ delivery. Our innovative F/B-LP-MNZ formulation demonstrated excellent physicochemical properties, stability, and controlled drug release profiles. In vitro studies revealed that MNZ-loaded liposomes attenuate the toxicity associated with free MNZ while F/B-LP-MNZ significantly increased cytotoxicity against HeLa cells, which express high levels of folate and biotin receptors, compared to non-targeted liposomes. Enhanced cellular uptake and improved dynamic flow attachment further confirmed the superior specificity of F/B-LP in targeting cancer cells. Additionally, our results revealed that F/B-LP-MNZ effectively inhibits HeLa cell migration and adhesion through EMT suppression and apoptotic induction, indicating its potential to prevent cancer metastasis. These findings highlight the potential of dual folate and biotin receptors-targeting liposomes as an effective delivery system for MNZ, offering a promising new avenue for targeted cancer therapy.

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 impact of folic acid/VB12 deficiency on essential hypertension in children and adolescents: from a nested case-control and a cohort study.

To explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated BP in children and adolescents. Both a nested case control and a cohort study were designed to explore the relationship between serum folic acid (FA) or Vitamin B12 (VB12) and elevated blood pressure (BP). All the included participants were from primary school. A total of 326 subjects (116:210) in nested case control were from an established cohort. And 270 participants without hypertension at baseline and followed in 2019 in cohort. FA and VB12 levels were lower in the elevated BP group than in the control group, and homocysteine level was higher than that in the control group. In the elevated BP group, overweight/obese children had lower FA than overweight/obese children in the normal BP group. FA was positively correlated with high-density lipoprotein (HDL) and Apo lipoprotein A (APOA), but negatively correlated with triglyceride (TG). FA was significantly correlated with elevated BP in children and adolescents (β = -0.353, P = 0.032), after adjusting VB12, and homocysteine (HCY), and the interaction effect of FA*HCY was significant. Both systolic and diastolic BP levels were statistically lower in the FA high exposure group than in the FA low exposure group in the cohort study. This study found that FA and vitamin B12 deficiency in childhood was correlated with elevated BP levels, which may affect BP by regulating lipid levels, and confirmed the importance of maintaining high levels of FA and vitamin B12 in childhood either by diet or supplementation.

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.

Exploring the correlation between homocysteine, red blood cell folate and MTHFRC677T genotypes with female infertility.

Aim: To investigate the association between serum homocysteine (HCY) levels, red blood cell folate (RCF) levels, methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and infertility.Materials & methods: Serum HCY and RCF levels and C677T polymorphism of MTHFR gene were analyzed in 149 infertile patients and 223 women of normal reproductive age with healthy childbirth history.Results: The HCY level of MTHFR C677T TT genotype infertility patients was higher than that of women of normal reproductive age, while the RCF level was not significantly different between the two groups.Conclusion: Serum HCY levels increased in infertility patients, and the MTHFR C677T TT genotype in childbearing-aged women are associated with a higher risk of infertility. The results showed that HCY level and MTHFR C677T genotype were closely related to infertility.

The effects of the MTHFR 677C>T (rs1801133) genetic variant on susceptibility and disability worsening in multiple sclerosis patients are mediated by homocysteine

BackgroundInteractions between genetic and environmental variables contribute to the autoimmune inflammatory process in multiple sclerosis (MS). Elevated homocysteine levels, and vitamin D, vitamin B12, and folate deficiencies are some of the environmental factors associated with the pathogenesis of MS. Considering that the relationship between MTHFR 677C>T (rs1801133) genetic variant, homocysteine, and folate in patients with MS remains unclear and that their role were not extensively explored in the clinical course of the disease, we investigated whether this variant and plasma homocysteine and folate levels are associated with MS susceptibility, disability, disability progression, and inflammatory biomarkers. MethodsThe case-control study included 163 patients with MS categorized using the Expanded Disability Status Scale (EDSS) as mild (EDSS<3) and moderate/high (EDSS≥3) disability, and 226 healthy controls (HC). Disability progression was evaluated using Multiple Sclerosis Severity Score (MSSS) and the MTHFR 677C>T variant was genotyped using real time polymerase chain reaction. The plasma levels of some inflammatory biomarkers were determined. Two new composed scores were proposed: the first, namely as inflammatory activity index (IAI), was entered as a latent vector extracted from the macrophage M1 + T helper (Th)1 + Th17 + Th2 + T regulatory (Treg) cytokines, + tumor necrosis factor (TNF)-α+ soluble TNF receptor (sTNFR)-1 + sTNFR2. The second score, namely MS-severity index was entered as a latent vector extracted from the EDSS + MSSS scores + MS diagnosis. ResultsPatients with MS showed higher homocysteine and folate than controls (p < 0.001); homocysteine, and the M1, Th1, Th17, and Th2 Treg cytokine values were different between the three study groups and increased from HC to MS patients with mild disability and to MS patients with moderate/high disability (p < 0.0001). The levels of TNF-α and their soluble receptors sTNFR1 and sTNFR2 were higher in MS patients with EDSS≥3 than in the two other groups (EDSS<3 and HC) (p < 0.001). There was no association between the MTHFR 677 C > T genotypes and MS susceptibility, disability and disability progression (p > 0.05). Moreover, 21.8 % of the disability variance was explained by age, IAI and C-reactive protein (CRP) (all positively associated); 10.9 % of the disability progression variance was predicted by IAI and CRP (both positively) and 25-hydroxyvitamin D (negatively), whereas 54.4 % of the severity index (MS-EDSS-MSSS) was explained by the regression on age, IAI, homocysteine, folate, and CRP (all positively), and adiponectin, body mass index, and 25-hydroxyvitamin D (all negatively), female sex, and the MTHFR 677 TT genotype. In patients and controls, 16.6 % of the variance in the homocysteine was explained by the MTHFR 677 TT genotype and age (both positively), folate (negatively) and male sex. ConclusionThe MTHFR 677C>T variant has an indirect effect on the increase in disability in patients with MS, which also depends on factors such as age, sex, ad folate status.

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

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

Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis.

Objective: Ischemic stroke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, DNA synthesis, plasticity, and cellular proliferation. Folates and choline are two active components of 1C metabolism. We have previously demonstrated that maternal dietary deficiencies during pregnancy and lactation in folic acid or choline result in worse stroke outcomes in offspring. However, there is insufficient data to understand the neuronal mechanisms involved.Methods: Using C57Bl/6J female mice maintained on control, folic acid (0.3 mg/kg) or choline (choline bitrate 300 mg/kg) deficient diets we collected embryonic primary neurons from offspring and exposed them to hypoxic conditions for 6 hours. To determine whether increased levels of either folic acid or choline can rescue reduced neuronal viability, we supplemented cell media with folic acid and choline prior to and after exposure to hypoxia.Results: Our results suggest that maternal dietary deficiencies in either folic acid or choline during pregnancy negatively impacts offspring neuronal viability after hypoxia. Furthermore, increasing levels of folic acid (250 mg/ml) or choline chloride (250 mg/ml) prior to and after hypoxia have a beneficial impact on neuronal viability.Conclusion: The findings contribute to our understanding of the intricate interplay between maternal dietary factors, 1C metabolism, and the outcome of offspring to hypoxic events, emphasizing the potential for nutritional interventions in mitigating adverse outcomes.