Serum Folate Levels Research Articles

Association between serum folate levels and migraine or severe headaches: A nationwide cross-sectional study.

Migraine and severe headaches are common neurological disorders with significant societal impact. Previous research indicates a potential link between serum folate levels and migraine occurrence, yet there is a lack of sufficient relevant studies and more are required. This study aimed to determine the association between a severe headache or migraine and serum folate levels in large populations. Using data from the National Health and Nutrition Examination Survey, we conducted a cross-sectional study. Using multivariable logistic regression models, we investigated the association between serum folate and severe headache or migraine. In a subsequent subgroup analysis, several confounding factors were also explored to investigate the association between migraine and serum folate. A total of 13,351 individuals participated in the study, with 2742 reporting severe headache or migraine in the previous 3 months. Serum folate was negatively associated with severe headache or migraine (odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.28-0.89, P = .018). The stratified analysis revealed this association persisted among female (OR = 0.38, 95% CI = 0.18-0.82, P < .001), individuals aged 20 to 50 years (OR = 0.53, 95% CI = 0.28-0.99, P < .001), and non-Hispanic White participants (OR = 0.38, 95% CI = 0.17-0.87, P < .001). We found that greater levels of serum folate were significantly related to a decreased likelihood of migraine onset, especially among women, young and middle-aged populations, and non-Hispanic White participants. Further research is required to validate and expand upon our results.

Genetic variants in folate metabolism-related genes, serum folate and hepatocellular carcinoma survival: the Guangdong Liver Cancer Cohort study.

Folate metabolism is involved in the development and progression of various cancers. We investigated the association of single nucleotide polymorphisms (SNP) in folate-metabolising genes and their interactions with serum folate concentrations with overall survival (OS) and liver cancer-specific survival (LCSS) of newly diagnosed hepatocellular carcinoma (HCC) patients. We detected the genotypes of six SNPin three genes related to folate metabolism: methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) and 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR). Cox proportional hazard models were used to calculate multivariable-adjusted hazard ratios (HR) and 95 % CI. This analysis included 970 HCC patients with genotypes of six SNP, and 864 of them had serum folate measurements. During a median follow-up of 722 d, 393 deaths occurred, with 360 attributed to HCC. In the fully-adjusted models, the MTRR rs1801394 polymorphism was significantly associated with OS in additive (per G allele: HR = 0·84, 95 % CI: 0·71, 0·99), co-dominant (AG v. AA: HR = 0·77; 95 % CI: 0·62, 0·96) and dominant (AG + GG v. AA: HR = 0·78; 95 % CI: 0·63, 0·96) models. Carrying increasing numbers of protective alleles was linked to better LCSS (HR10–12 v. 2–6 = 0·70; 95 % CI: 0·49, 1·00) and OS (HR10–12 v. 2–6 = 0·67; 95 % CI: 0·47, 0·95). Furthermore, we observed significant interactions on both multiplicative and additive scales between serum folate levels and MTRR rs1801394 polymorphism. Carrying the variant G allele of the MTRR rs1801394 is associated with better HCC prognosis and may enhance the favourable association between higher serum folate levels and improved survival among HCC patients.

Impact of Serum Folate and Vitamin B12 on Mental Health in Patient Admitted at Razi Psychiatric Hospital

Vitamin B12 (cobalamin) is one of the essential vitamins that affect various systems in the body, including the central nervous system and plays an important role in the metabolism of the nervous system, although its exact role under pathological conditions is not fully understood. The present study aimed to assessing vitamin B12 &amp; serum folate in patient admitted at Razi psychiatric hospital. A cross section study subjects were inpatients with psychiatric disorder, patients from 21 to 60 years old. In this group of 40 psychiatric patients, there is no evidence of clinically relevant changes in serum vitamin B12 and folate level. Vitamin B12 deficiency can occur despite “normal” serum cobalamin levels; therefore, measuring homocysteine and methyl malonic acid can decrease false-negative findings.

Associations of polycyclic aromatic hydrocarbons exposure with mortality and effect modification by folate biomarkers in a prospective population

The associations of folate biomarkers and polycyclic aromatic hydrocarbons (PAHs) in the general population remain unclear. Therefore, this study aimed to examine whether folate biomarkers are associated with PAHs, and whether folate biomarkers can mitigate adverse health outcome caused by PAHs. This prospective cohort study included 11,246 participants from the National Health and Nutrition Examination Survey (NHANES), which documented 1303 deaths over a mean follow-up of 9.1 years. Multivariable linear regression models were used to examine the relationship between urinary individual PAHs and folate biomarkers. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios and 95 % CIs for the associations of PAHs and folate biomarkers with CVDs mortality and all-cause mortality. We found negative associations between folate in red blood cells (RBC) and urinary 1-Hydroxyphenanthrene (percentage change for a 2·7 fold-increase in folate −4.19 %, 95 % CI -5.80 % to −2.56 %CI), 2-Hydroxyfluorene (−6.66 %, −7.84 % to −5.49 %), 3-Hydroxyfluorene (−5.78 %, −6.77 % to −4.78 %)) and 1-Hydroxynapthalene (−2.75 %, −3.48 % to −2.01 %). The associations between serum folate and PAHs were consistent with those observed for RBC folate, and negative associations were also found between serum folate and 2-Hydroxynapthalene (−4.10 %, −5.26 % to −2.94 %). Within the lowest quartile of folate levels in RBC, there are strong associations of 2-Hydroxyfluorene, 3-Hydroxyfluorene, 1-Hydroxynapthalene, and 2-Hydroxynapthalene with elevated risk of CVDs mortality [HRs (95 % CI) >1]. As folate levels in RBC increase to the third and fourth quartiles, these associations no longer exist [HRs (95 % CI) <1, P-interaction<0.05]. The positive associations between urinary PAHs and CVDs mortality are also eliminated as serum folate levels rise (HRs (95 % CI) <1, P-interaction<0.05). Furthermore, we also found higher levels of folate in both RBC and serum can greatly reduce the adverse impact of 1-Hydroxynapthalene on all-cause mortality. Consistent results were also validated in daily dietary folate and the folic acid supplement intake. Our study highlighted a robust negative relationship between urinary PAHs and folate. Additionally, folate was found to effectively mitigate mortality caused by PAHs, although we did not observe a direct reduction in mortality attributable to folate.

The Critical Role of Folate in Prenatal Health and a Proposed Shift from Folic Acid to 5-Methyltetrahydrofolate Supplementation

Folate, or vitamin B9, is a water-soluble vitamin essential in periconceptional nutrition. In its active form, tetrahydrofolate, it plays a vital role in DNA methylation and homocysteine breakdown. Maintenance of normal serum folate levels is crucial during pregnancy; deviation from these levels, either in dearth or excess, can lead to various pregnancy and infant complications. This article analyzes existing literature on folate’s absorption pathway in human physiology and reviews the evidence surrounding prenatal supplementation guidelines for folic acid. Prior research supports these guidelines because, in the absence of folate during pregnancy, research has shown an increased incidence of neurodevelopmental defects, food allergies, ophthalmic deficits, and other adverse effects for both mother and child. This significant body of evidence has driven most developed countries to implement folic acid supplementation initiatives, with the World Health Organization recommending a daily 400-µg folic acid supplementation for periconceptional women. As progress continues on a global scale, further efforts should be made to improve folic acid levels in pregnant populations among demographic subgroups. Research supports the use of 5-methyltetrahydrofolate in place of traditional folic acid prenatal supplements based on the increased bioavailability, resistance to genetic polymorphisms, and avoidance of several potential risks associated with folic acid supplements. More research and product development should be done to drive and support this shift in prenatal supplementation trends.

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.

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

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

Comparing Holotranscobalamin and Total Vitamin B12 in Diagnosing Vitamin B12 Deficiency in Megaloblastic Anemia Patients.

Background Megaloblastic anemia is characterized by abnormally large red blood cells caused by a deficiency in either vitamin B12 or folic acid, both of which are essential for DNA synthesis. Vitamin B12 insufficiency can lead to severe neurological damage, making early identification of vitamin B12 deficiency crucial to prevent irreversible harm. Vitamin B12 deficiency results in decreased levels of holotranscobalamin (Holo-TC) and increased levels of methylmalonic acid (MMA). Methylmalonic acid is considered the gold standard for diagnosing B12 deficiency because it is a specific marker that rises when B12 is insufficient, even when serum B12 levels appear normal. Elevated MMA levels reflect impaired B12 metabolism, making it a critical tool for early detection and intervention. Previous research indicates that Holo-TC, the active form of vitamin B12 available to cells, is a more specific diagnostic tool for early vitamin B12 deficiency than total B12. This study aims to determine the diagnostic validity of total vitamin B12 and Holo-TC using MMA as the gold standard in patients with megaloblastic anemia. Methods A total of 95 megaloblastic anemia patients were selected from Jinnah Hospital and Lahore General Hospital, Lahore, Pakistan, after receiving approval from the ethical review committees. This was a cross-sectional study. Whole blood, serum, and urine samples were collected in ethylenediamine tetraacetic acid (EDTA) vials, gel vials, and urine containers, respectively. The EDTA samples were used for complete blood count measurements using a hematology analyzer (Sysmex-XT 1800i, Sysmex America, Inc., Mundelein, IL), while serum and urine samples were employed for the detection of serum folic acid, cobalamin, Holo-TC, and MMA levels through manual enzyme-linked immunosorbent assay (ELISA) techniques. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of Holo-TC and cobalamin were calculated. Results The majority of patients fell within the age group of 20-70 years, with 57% of them being females and 43% males; Holo-TC exhibited a sensitivity of 98.9% and specificity of 50.00%, with a PPV of 98.90% and NPV of 50%. Vitamin B12 demonstrated a sensitivity of 63% and specificity of 50%, with a PPV of 98.33% and NPV of 2.85%. The diagnostic accuracy of Holo-TC and vitamin B12 was observed to be 97.8% and 63%, respectively. Conclusions Between the two, Holo-TC displays higher diagnostic accuracy than vitamin B12 and can serve as the primary test for patients suspected of having vitamin B12 deficiency.

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.

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

Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice.

Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low-folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual's age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.

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.

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.

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

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

Correlation of Co-Morbidities with Symptom Severity of Children with Autism Spectrum Disorder: A Cross-Sectional Survey.

This study aims to identify potential correlations of the severity of symptoms of children with autism spectrum disorder (ASD) with serum nutritional levels, body composition indicators, diet partiality, and sleep disturbances. The cohort of this cross-sectional study included 120 children with ASD and 110 typically developing (TD) children to assess symptoms of ASD, and to measure serum levels of vitamins and minerals and the body composition values. Diet partiality and sleep disturbances were assessed by administering questionnaires. The serum levels of folic acid, copper, and vitamin B were lower in children with ASD than in TD children, while magnesium and homocysteine were higher (p < 0.05). Children with ASD had greater chest circumference, abdominal skinfold thickness, and body mass index (BMI) than TD children (p < 0.05), and higher prevalences of diet partiality and sleep disturbances (p < 0.001). Lower vitamin A levels and higher vitamin D levels were related to social impairment in children with ASD. Moreover, there were significantly positive correlations of BMI, chest circumference, diet partiality, and sleep disturbances with severity of ASD symptoms (p < 0.05). Collectively, rational nutritional supplementation, dietary management, and behavioral interventions are essential for children with ASD.

Association of serum folate concentrations with the mortality of cancer: a prospective cohort study.

The association between serum folate concentrations and the mortality of cancer remains unclear. We aim to investigate the association of serum folate concentrations with all-cause and cause-specific mortality among American adults with cancer. This cohort study included 4535 patients with cancer from National Health and Nutrition Examination Survey (NHANES) 1999 to 2016 and NHANES III (1988-1994). Death outcomes were ascertained by linkage to National Death Index records through 31 December 2019. Cox proportional hazards model and two-piecewise Cox proportional hazards model were used to calculate hazard ratios and 95% confidence intervals for the associations between folate concentrations and the risk of mortality. During a median follow-up of 37,792 person-years, there were 1998 all-cause deaths and 616 cancer deaths. Non-linear and L-shaped associations were observed between serum folate concentrations and the risk of all-cause and cancer mortality among patients with cancer. Notably, the mortality rates reached a plateau at 23.7ng/mL for all-cause mortality and 23.57ng/mL for cancer mortality. When folate levels fell below these thresholds, the risk of all-cause and cancer mortality decreased by approximately 2.1% (HR 0.979; 95% CI 0.969-0.989) and 3.6% (HR 0.964; 95% CI 0.948-0.981), respectively, with each unit increase in the folate concentration up to the thresholds. Our study reveals that low serum folate concentrations are linked to an elevated risk of cancer mortality among individuals with cancer within a certain range and supplementation of folate in cancer patients to achieve specific serum folate level threshold (23.7ng/mL) might reduce the risk of cancer mortality.

Dietary folic acid intake, 13 genetic variants and other factors with red blood cell folate concentration in pregnancy-preparing population

PurposeThis study aims to evaluate a combined effect of dietary folic acid intake, multiple genetic polymorphisms in folate metabolism, and other environmental factors on red blood cell (RBC) folate concentration in pregnancy-preparing population.Methods519 pregnancy-preparing subjects (260 couples) were investigated. Dietary intake was measured by 3-day dietary recalls. 13 Single Nucleotide polymorphisms (SNPs) reported in association with one-carbon metabolism including the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C were genotyped. RBC folate concentration was measured using chemiluminescence assay. Hierarchical regression was applied for covariate selection. Factors showed significance(p < 0.0125) on RBC folate level was included for prediction model construction and R2 estimation. Validation cohort analysis was performed as post-hoc analysis if applicable.ResultsThe median RBC folate was 212.8 ng/ml. Only 10% took folic acid supplementation within three months. Based on hierarchical selection, folic acid supplementation, genetic polymorphism (especially TT genotype of MTHFR C677T), serum folate level were determinants of the variance of RBC folate concentrations, with adjusted R2 of 0.178–0.242. MTHFR A1298C polymorphism, sex difference with other socio-demographic and lifestyle factors (age, BMI, alcohol drinking, smoking, education, occupation) explained little to change in RBC folate level. Validation in another sub-cohort(n = 8105) had adjusted R2 of 0.273.ConclusionIn pregnancy-preparing subjects, folic acid supplementation, serum folate level and TT allele of MTHFR C677T polymorphism were determinants of the total variance of RBC folate level, which explained 19.8% variance in our subjects and 27.3% in the validation cohort. Food folate intake, sex and other environmental factors explained little to RBC folate level.

Plasma homocysteine and longitudinal change in cognitive function among urban adults

BackgroundCross-sectional and longitudinal studies have inconsistently linked cognitive performance and change over time to an elevated level of homocysteine (Hcy), with few conducted among urban adults. MethodsLongitudinal data [Visit 1 (2004–2009) and Visit 2 (2009–2013)] were analyzed from up to 1430 selected Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) participants. Baseline and follow-up blood Hcy was measured, while 11 cognitive function test scores were assessed at either of these two visits. Overall, sex- and race-stratified associations were evaluated using mixed-effects linear regression models, adjusting for key potential confounders. Interaction effects between Hcy and serum levels of folate and vitamin B-12 were also tested. ResultsWe found that greater LnHcyv1 was significantly associated with poorer baseline attention based on higher Loge (TRAILS A, in seconds) [β (SE): 0.101 (0.031), P = 0.001]. Heterogeneity was also found by sex and by race. Most notably, among men only, LnHcyv1 was associated with faster decline on the BVRT (# of errors), a measure of visuo-spatial memory (β (SE): 0.297(0.115), P = 0.010, reduced model); while among African American adults only, an elevated and increasing LnHcy over time was associated with faster rate of decline on Loge (TRAILS B, in seconds) [β (SE): +0.012 (0.005), p = 0.008], a measure of executive function. Interactions between Hcy, folate and vitamin B-12 blood exposures were also detected. ConclusionsIn summary, sex- and race-specific adverse association between elevated Hcy and cognitive performance over time were detected among middle-aged urban adults, in domains of attention, visuo-spatial memory and executive functioning.