Higher Folate Concentrations Research Articles

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

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

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

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

Pregnancy, folic acid, and antiseizure medication

Abstract Background Although some antiseizure medications (ASMs) are teratogenic, most people with epilepsy need treatment in pregnancy. The risk of ASM fetotoxicity may be mitigated with folic acid. High-dose folic acid supplementation has traditionally been recommended before and during gestation despite little evidence of efficacy and safety for this patient group. Several studies have investigated the potential benefits and risks of folic acid supplements. Objective To provide an updated overview of the risks, benefits, and rationale for use of folic acid supplementation in relation to pregnant people of childbearing age using ASM. Materials and methods This is a narrative review based on an unstructured literature search of PubMed. We also scrutinized neurological and obstetrical guidelines. Results Antiseizure medication can decrease folate concentrations. In children exposed to ASM prenatally, those born to persons using folic acid supplements periconceptionally had lower risk of adverse neurodevelopment and preterm birth. It remains unclear whether the risk for congenital malformations can be equally alleviated. In studies of the general population, high plasma folate concentrations and/or high-dose folic acid supplements were associated with adverse neurodevelopmental outcomes. This has not been seen in children of mothers with epilepsy. However, an increased cancer risk has been found in children of mothers with epilepsy using high-dose folic acid supplements in pregnancy. Conclusion The optimal folic acid dose is not clear for persons of childbearing potential with epilepsy using ASM. Both low and excess folate status during pregnancy have been associated with adverse neurodevelopment. We propose an individual folic acid supplement dose that should be titrated based on maternal plasma folate concentrations during pregnancy.

Association of Early Pregnancy Perfluoroalkyl and Polyfluoroalkyl Substance Exposure With Birth Outcomes

Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes. To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort. In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022. Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy. Birth weight and gestational age, abstracted from delivery records; birth weight z score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks. The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight z score only among mothers whose dietary folate intake (birth weight: β, -89.13 g; 95% CI, -166.84 to -11.42 g; birth weight z score: -0.13; 95% CI, -0.26 to -0.003) or plasma folate concentration (birth weight: -87.03 g; 95% CI, -180.11 to 6.05 g; birth weight z score: -0.14; 95% CI, -0.30 to 0.02) were below the 25th percentile (dietary: 660 μg/d, plasma: 14 ng/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups. In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.

High Serum Folate Concentration, Vitamin B12 Deficiency, and Anthropometric Nutritional Status in Brazilian Children Aged 6–59 Months: Data from the Brazilian National Survey of Child Nutrition

BackgroundVitamin B12 and folate are key nutrients that help children reach their full potential in growth and development; however, little is known about the status of these vitamins in Brazilian children. ObjectivesTo describe the serum concentrations of vitamin B12 and folate, to investigate the association between high folate concentration (HFC) and vitamin B12 deficiency, and to evaluate the association between vitamin B12 and stunting/underweight in Brazilian children aged 6–59 mo. MethodsData from 7417 children aged 6–59 mo collected during the Brazilian National Survey on Child Nutrition were used. Serum concentrations of vitamin B12 of <150 pmol/L and folate of <10 nmol/L were classified as deficient, and folate concentrations of >45.3 nmol/L were classified as HFC. Children with length/height-for-age z-score of less than −2 were considered stunted, and those with weight-for-age z-score of less than −2 were underweight. Logistic regression models were performed. ResultsIn Brazil, 14.2% (95% CI: 12.2, 16.1) of children aged 6–59 mo had vitamin B12 deficiency, 1.1% (95% CI: 0.5, 1.6) had folate deficiency, and 36.9% (95% CI: 33.4, 40.3) had HFC. Vitamin B12 deficiency was higher in children from the northern region of Brazil (28.5%), between 6 and 24 mo (25.3%), whose mothers had lower formal education (0–7 y; 18.7%). Children with HFC had 62% lower odds (OR: 0.38; 95% CI: 0.27, 0.54) of vitamin B12 deficiency than those with normal/deficient folate. Children with vitamin B12 deficiency and normal/deficient folate had higher odds of stunting (OR: 1.58; 95% CI: 1.02, 2.43) than children without vitamin B12 deficiency and normal/deficient folate. ConclusionsVitamin B12 deficiency is a public health problem among Brazilian children aged <2 y with vulnerable socioeconomic status. HFC was inversely associated with vitamin B12 deficiency, and lower odds of stunting were observed in children with HFC and vitamin B12 deficiency than in those with vitamin B12 deficiency and normal/deficient folate.

Contrasting Association of Maternal Plasma Biomarkers of Smoking and 1-Carbon Micronutrients with Offspring DNA Methylation: Evidence of Aryl Hydrocarbon Receptor Repressor Gene–Smoking–Folate Interaction

BackgroundMaternal prenatal smoking is known to alter offspring DNA methylation (DNAm). However, there are no effective interventions to mitigate smoking-induced DNAm alteration. ObjectivesThis study investigated whether 1-carbon nutrients (folate, vitamins B6, and B12) can protect against prenatal smoking-induced offspring DNAm alterations in the aryl hydrocarbon receptor repressor (AHRR) (cg05575921), GFI1 (cg09935388), and CYP1A1 (cg05549655) genes. MethodsThis study included mother-newborn dyads from a racially diverse US birth cohort. The cord blood DNAm at the above 3 sites were derived from a previous study using the Illumina Infinium MethylationEPIC BeadChip. Maternal smoking was assessed by self-report and plasma biomarkers (hydroxycotinine and cotinine). Maternal plasma folate, and vitamins B6 and B12 concentrations were obtained shortly after delivery. Linear regressions, Bayesian kernel machine regression, and quantile g-computation were applied to test the study hypothesis by adjusting for covariables and multiple testing. ResultsThe study included 834 mother-newborn dyads (16.7% of newborns exposed to maternal smoking). DNAm at cg05575921 (AHRR) and at cg09935388 (GFI1) was inversely associated with maternal smoking biomarkers in a dose-response fashion (all P < 7.01 × 10−13). In contrast, cg05549655 (CYP1A1) was positively associated with maternal smoking biomarkers (P < 2.4 × 10−6). Folate concentrations only affected DNAm levels at cg05575921 (AHRR, P = 0.014). Regression analyses showed that compared with offspring with low hydroxycotinine exposure (<0.494) and adequate maternal folate concentrations (quartiles 2–4), an offspring with high hydroxycotinine exposure (≥0.494) and low folate concentrations (quartile 1) had a significant reduction in DNAm at cg05575921 (M-value, ß ± SE = −0.801 ± 0.117, P = 1.44 × 10−11), whereas adequate folate concentrations could cut smoking-induced hypomethylation by almost half. Exposure mixture models further supported the protective role of adequate folate concentrations against smoking-induced aryl hydrocarbon receptor repressor (AHRR) hypomethylation. ConclusionsThis study found that adequate maternal folate can attenuate maternal smoking-induced offspring AHRR cg05575921 hypomethylation, which has been previously linked to a range of pediatric and adult diseases.

Folate, Choline, and Vitamin B12 Supplementation for Pre-Conceptional and Pregnant Women

Folate, Choline, and Vitamin B12 Supplementation for Pre-Conceptional and Pregnant Women Abstract. Inadequate maternal folate status is associated with higher risk of neural tube defects. The threshold for a good supply of folate (e.g., folate concentration in erythrocytes) is > 906nmol/L for all women who may become pregnant. This quite high folate concentration should already be reached before the onset of pregnancy, which can hardly be achieved with food. Supplementation with folate or folic acid is therefore strongly recommended for all women planning pregnancy (four to eight weeks before the start of pregnancy until the end of the first trimester). Folate supplementation can significantly reduce the risk of neural tube defects at the population level (approximately 50%), but it cannot prevent all cases. Recent studies show that low maternal choline and vitamin B12 intake during pregnancy is also associated with higher risk of neural tube defects. The role of choline in fetal brain development is biologically plausible based on its function as a source of methyl groups, acetylcholine, and cell membrane phospholipids and is not completely interchangeable with folate. Data on the association between maternal choline intake during preconception and the first trimester and fetal brain development suggest a causal relationship. The intake recommendation for choline is 480mg/day for pregnant women and 550mg/day for lactating women. Choline intake (mainly from animal-based diets) averages about 300mg/day and is thus insufficient for optimal supply during pregnancy. To date, no specific recommendations exist for choline supplementation before and during pregnancy. In Europe, prevention approaches at the population level are generally poorly followed. Therefore, individual counseling of young women planning pregnancy is more relevant than ever.

Reduced circulating folate among older adults caused by continuous work: nested cross-sectional study conducted in a country with folic acid fortification program

Population aging is 1 of the biggest challenges facing public health today, and cognitive dysfunction is an important concern. Cognitive impairment may be associated with high folate concentrations and low vitamin B12 concentrations; the latter is a common problem among elderly people. Therefore, we hypothesized there was a high circulating folate concentration among older people living in a country with a mandatory folic acid fortification program. We conducted a cross-sectional study to investigate nutritional status of folate and vitamin B12 among aged people. Three dietary recalls, serum folate (sfolate), erythrocyte (red blood cell) folate (RBC folate), and serum vitamin B12 and homocysteine were collected. Linear regression models were used to investigate factors associated with circulating vitamins. We interviewed 169 participants. Half reported inadequate consumption of folate. However, RBC folate deficiency was observed in 27%, 13% in the serum, and a 10% excess of sfolate. One-quarter reported inadequate consumption of B12, but only 5% had deficiency. Factors negatively associated with circulating folate were continuous work and smoking, and positively associated with polyunsaturated fatty acid. Factor negatively associated with the circulating B12 were use of a dental prosthesis and intake of saturated fatty acid. Permanent investigation of excess of sfolate and B12 deficiency, especially among older adults living in countries exposed to a mandatory folic acid fortification program, is important because of the possible relation to the cognitive function.

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

Deprescribing: What About Vitamins, Minerals, and Other Nutritional Supplements?

Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy.

Food fortification and folic acid supplementation during pregnancy have been implemented as strategies to prevent fetal malformations during pregnancy. However, with the emergence of conditions where folate metabolism and transport are disrupted, such as folate receptor alpha autoantibody (FRαAb)-induced folate deficiency, it is critical to find a folate form that is effective and safe for pharmacologic dosing for prolonged periods. Therefore, in this study, we explored the absorption and tissue distribution of folic acid (PGA), 5-methyl-tetrahydrofolate (MTHF), l-folinic acid (levofolinate), and d,l-folinic acid (Leucovorin) in adult rats. During absorption, all forms are converted to MTHF while some unconverted folate form is transported into the blood, especially PGA. The study confirms the rapid distribution of absorbed folate to the placenta and fetus. FRαAb administered, also accumulates rapidly in the placenta and blocks folate transport to the fetus and high folate concentrations are needed to circumvent or overcome the blocking of FRα. In the presence of FRαAb, both Leucovorin and levofolinate are absorbed and distributed to tissues better than the other forms. However, only 50% of the leucovorin is metabolically active whereas levofolinate is fully active and generates higher tetrahydrofolate (THF). Because levofolinate can readily incorporate into the folate cycle without needing methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) in the first pass and is relatively stable, it should be the folate form of choice during pregnancy, other disorders where large daily doses of folate are needed, and food fortification.

Associations of Maternal rs1801131 Genotype in MTHFR and Serum Folate and Vitamin B12 with Gestational Diabetes Mellitus in Chinese Pregnant Women.

Circumstantial evidence links one-carbon metabolism (OCM) related nutrients, such as folate and vitamin B12, with gestational diabetes mellitus (GDM). However, few studies have evaluated the combined effects of these nutrients with OCM related gene polymorphisms on GDM. This study investigated whether OCM related genetic variants modified the associations of folate and B12 with GDM. Logistic regression was used to estimate odds ratios (ORs) for OCM related nutrients and single nucleotide polymorphisms (SNPs) in genes encoding main OCM related enzymes (MTHFR, MTR, and MTRR) on GDM. Higher folate concentrations were associated with increased GDM risk (OR: 1.59; 95% CI: 1.22, 2.13). However, higher B12 concentrations were associated with reduced GDM risk (OR: 0.76; 95% CI: 0.65, 0.92). Pregnancies with MTHFR rs1801131 G alleles had a significantly lower risk of GDM than pregnancies with T alleles (OR: 0.65; 95% CI: 0.47, 0.91) under the dominant model. The genotype-stratified analysis revealed the association between folate and GDM (OR: 1.66, 95% CI: 1.20, 2.30) or B12 and GDM (OR: 0.80, 95% CI: 0.65, 0.98) was more evident in pregnancies with TT genotype. Higher folate and lower B12 are associated with GDM. Pregnancies with MTHFR rs1801131 TT genotype are more susceptible to OCM nutrient-related GDM.

Reduced Kidney Function Is Associated with Increasing Red Blood Cell Folate Concentration and Changes in Folate Form Distributions (NHANES 2011-2018).

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108–390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.

Plasma selenium and the risk of first stroke in adults with hypertension: a secondary analysis of the China Stroke Primary Prevention Trial

Previous studies have indicated that selenium (Se) may play an important role in cardio-cerebrovascular disease. However, the relation between circulating selenium and risk of first stroke remains inconclusive. We conducted a secondary analysis of the China Stroke Primary Prevention Trial (CSPPT), using a nested case-control design, and aimed to investigate the correlation between Se concentration and first stroke risk in adults with hypertension and examine the potential effect modifiers. In the CSPPT, a total of 20,702 adults with hypertension were randomly assigned to a double-blind daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. A total of 618 first stroke cases and 618 controls matched for age, sex, treatment group, and study site were included in this study. During a median follow-up duration of 4.5 y (IQR: 4.2-4.6 y), there was a significant inverse association between plasma Se and the risk of first stroke (per SD increment; adjusted OR: 0.81; 95% CI: 0.68, 0.96) and ischemic stroke (per SD increment; adjusted OR: 0.76; 95% CI: 0.62, 0.93). Furthermore, a stronger inverse association between plasma Se and first stroke was observed in participants with higher folate concentrations at baseline [≥7.7 ng/mL (median), adjusted OR: 0.67; 95% CI: 0.54, 0.85, compared with <7.7 ng/mL, adjusted OR: 0.98; 95% CI: 0.80, 1.21; P-interaction = 0.008] and those with higher time-averaged systolic blood pressure (SBP) over the treatment period (≥140 mm Hg, adjusted OR: 0.71; 95% CI: 0.58, 0.86, compared with <140 mm Hg, adjusted OR: 0.96; 95% CI: 0.77, 1.20; P-interaction = 0.023). There was a significant inverse association between plasma Se and risk of first stroke in Chinese adults with hypertension, especially among those with higher baseline folate concentrations and those with higher time-averaged SBP over the treatment period. This trial was registered at clinicaltrials.gov as NCT00794885.

The Concept of Folic Acid in Health and Disease.

Folates have a pterine core structure and high metabolic activity due to their ability to accept electrons and react with O-, S-, N-, C-bounds. Folates play a role as cofactors in essential one-carbon pathways donating methyl-groups to choline phospholipids, creatine, epinephrine, DNA. Compounds similar to folates are ubiquitous and have been found in different animals, plants, and microorganisms. Folates enter the body from the diet and are also synthesized by intestinal bacteria with consequent adsorption from the colon. Three types of folate and antifolate cellular transporters have been found, differing in tissue localization, substrate affinity, type of transferring, and optimal pH for function. Laboratory criteria of folate deficiency are accepted by WHO. Severe folate deficiencies, manifesting in early life, are seen in hereditary folate malabsorption and cerebral folate deficiency. Acquired folate deficiency is quite common and is associated with poor diet and malabsorption, alcohol consumption, obesity, and kidney failure. Given the observational data that folates have a protective effect against neural tube defects, ischemic events, and cancer, food folic acid fortification was introduced in many countries. However, high physiological folate concentrations and folate overload may increase the risk of impaired brain development in embryogenesis and possess a growth advantage for precancerous altered cells.

Dietary Supplement Intake, Folate and Vitamin B12 Status, and Cognitive Impairment Among Older Adults, National Health and Nutrition Examination Survey, 2011–2014

ObjectivesCognitive decline is a major public health issue among older adults. Dietary supplement use is common among older adults, and a concern has been raised about high folic acid intake among those with vitamin B12 (vB12) deficiency and exacerbation of cognitive decline. We evaluated supplement intake and folate and vB12 concentrations among older adults with measured cognitive function. MethodsWe used NHANES 2011–2014 data on adults aged 60 + years (n = 3266) and estimated folic acid and vB12 intake from dietary supplements. We defined vB12 insufficiency as serum vB12 concentration ≤ 258 pmol/L and high folate concentrations as either serum folate ≥ 59 nmol/L or RBC folate ≥ 1609 nmol/L. Cognitive impairment was defined as a test score < 34 (< 25th percentile of the distribution) using the Digit Symbol Substitution Test. We adjusted for age, gender, ethnicity, marital status, education, poverty income ratio (PIR), and creatinine/albumin ratio in our analysis. We performed statistical analyses using weighted procedures in SAS-SUDAAN. ResultsOlder adults with cognitive impairment compared to those without were more likely to have less than a high school education; elevated serum methylmalonic acid; lower PIR; or to be non-Hispanic Black or Hispanic. Adults with cognitive decline were also less likely to use folic acid (29.2%) and vB12 (34.3%) supplements compared to those without cognitive decline (43.1% and 46.7%, respectively). Among vB12 insufficient adults, 18.0% were taking a vB12 supplement. After adjustment, compared to persons with normal folate and normal vB12 concentrations, persons with high folate and normal vB12 concentrations had a lower odds of having cognitive (adjusted OR [aOR]: 0.63; 95% confidence interval [CI]: 0.47, 0.85), and persons with high folate and insufficient vB12 concentrations had no significant difference in cognitive decline (aOR: 0.88; 95% CI: 0.36, 2.14). Among those who had cognitive decline with high folate and insufficient vB12 concentrations, 34.3% used a vB12 supplement. ConclusionsOur findings suggest that contrary to previous reports having concurrent high folate and insufficient vB12 concentrations was not associated with cognitive impairment. Adults who reported taking vB12 supplements orally and continue to have low vB12 concentrations may have vB12 malabsorption issues. Funding SourcesNA- CDC.

Serum Folate and All-Cause Mortality is of Non-Linear Relationship Among Population with Chronic Kidney Disease: A Retrospective Cohort Study.

AimA transition toward high serum folate concentrations has been noticed following the mandatory folate fortification. To explore this further, we studied the relationship between folate and health outcomes in population with chronic kidney disease (CKD).MethodsWe retrospectively explored the relationships between serum folate and risk of all-cause death in this population. We analyzed data of 2142 subjects with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999–2006. Vital status was followed through December 31, 2006.ResultsCox regression was used to estimate hazard ratios (HRs) of mortality for individuals with serum folate in rest quintiles compared with individuals with the fourth quintile. After an average follow-up of 57.4 months with 157 deaths recorded, a reversed J-shaped association was revealed after conducting multivariable adjustment. The mortality rate in population with lower and higher folate levels were 8.29% and 12.67%, respectively, and the corresponding adjusted HRs were 2.41 (95% confidence interval, CI=1.32–4.40) and 2.10 (1.20–3.70). Kaplan–Meier curve showed survival benefits for the fourth quintile of serum folate as compared to the first and fifth quintile.ConclusionSerum folate concentrations may influence all-cause mortality in a non-linear pattern in the CKD population. It is reasonable to recommend periodic surveillance in the CKD population to maintain the serum folate concentration in an appropriate level.

Nutrient Intake and Status of German Children and Adolescents Consuming Vegetarian, Vegan or Omnivore Diets: Results of the VeChi Youth Study.

There is a lack of data on associations between modern vegetarian and vegan diets and health among children and adolescents. The aim of the Vechi Youth Study was to cross-sectionally examine anthropometry, dietary intakes and nutritional status in a sample of 149 vegetarian, 115 vegan and 137 omnivore children and adolescents (6–18 years old, mean age: 12.7 ± 3.9 years). Group differences of dietary intake (calculated from three-day dietary records), nutrient biomarker and blood lipid concentrations were assessed using an analysis of covariance, adjusted for sex, age and other covariates. The total energy intake did not differ significantly between groups, but intake of carbohydrates was higher among vegetarians and vegans than among omnivores (p = 0.0002, respectively). The median protein intake exceeded 0.9 g/kg body weight/day in all diet groups and was lowest among vegetarians (p < 0.02). There was no significant difference of haemoglobin, vitamin B2, 25-OH vitamin D3, HDL-C and triglycerides blood concentrations between diet groups. Vegan participants had higher folate concentrations than vegetarian participants (p = 0.0053). Ferritin concentration was significantly higher in omnivores than in vegetarians (p = 0.0134) and vegans (p = 0.0404). Vegetarians had lower concentrations of holotranscobalamin (p = 0.0042) and higher concentrations of methylmalonic acid (p = 0.0253) than omnivores. Vegans had the lowest non-HDL-C and LDL-C concentrations in comparison to vegetarians (p = 0.0053 and p = 0.0041) and omnivores (p = 0.0010 and p = 0.0010). A high prevalence (>30%) of 25-OH vitamin D3 and vitamin B2 concentrations below reference values were found irrespective of the diet group. In conclusion, the Vechi Youth Study did not indicate specific nutritional risks among vegetarian and vegan children and adolescents compared to omnivores.

High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults

BackgroundFolate and vitamin B-12 are essential nutrients for normal cell growth and replication, but the association of serum folate and vitamin B-12 concentrations with mortality risk remains uncertain. ObjectivesThis study was performed to investigate the associations of serum folate and vitamin B-12 concentrations with mortality risk and test whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism modifies these associations. MethodsA total of 3050 Japanese community residents aged ≥40 y were prospectively followed-up for mortality between 2002 and 2012. Cox proportional hazards models and restricted cubic splines were used to estimate HRs and 95% CIs of mortality. ResultsDuring a median follow-up period of 10.2 y, 336 participants died. Higher serum folate concentrations were associated with lower risks of all-cause mortality [multivariable-adjusted HR: 0.73; 95% CI: 0.56, 0.96 for the second tertile (8.8–12.2 nmol/L; median 10.4 nmol/L) and HR: 0.61; 95% CI: 0.46, 0.80 for the third tertile (≥12.5 nmol/L; median 15.6 nmol/L) serum folate concentrations compared with the first tertile (≤8.6 nmol/L; median 7.0 nmol/L)]. This association remained significant in all sensitivity analyses. Spline analyses showed a steady decline in all-cause mortality risk with increasing serum folate concentrations up to 20–25 nmol/L. This association persisted regardless of the MTHFR C677T genotypes. For serum vitamin B-12, the multivariable-adjusted HR of 1.32 (95% CI: 0.97, 1.79) of all-cause mortality was marginally significantly greater in the first tertile compared with the second tertile. This association was attenuated and nonsignificant after the exclusion of participants with a history of cardiovascular disease or cancer, or participants aged ≥85 y at baseline, or deaths in the first 3 y of follow-up. ConclusionsSerum folate concentrations were inversely associated with the risk of all-cause mortality in Japanese adults. Serum vitamin B-12 concentrations were not consistently associated with all-cause mortality risk after accounting for reverse-causation bias.

Plasma Folate Levels in Acutely Ill and Steady State Pediatric Sickle Cell Disease Patients in Ghana.

BackgroundIndividuals with sickle cell disease (SCD) are susceptible to infective conditions that predispose them to hemolysis and anemia. Folic acid is recommended as a preventative measure against anemia in SCD patients; however, there is scarce literature on the implications of this practice.Patients and MethodsPlasma concentrations of folate were measured in acutely ill pediatric SCD patients presenting with malaria or bacteremia and compared with those of SCD patients in steady state, or acutely ill non-SCD patients with confirmed malaria.ResultsThe proportion of individuals with high (>45.3 nmol/L) folate concentrations was 29.5% (13/44), 18.2% (8/44), 33.3% (6/18), and 0% in the SCD-malaria, SCD steady state, SCD bacteremia, and the non-SCD malaria groups, respectively. The proportion of SCD patients with high folate levels did not vary significantly at steady state and during confirmed malaria (p = 0.216), and during acute bacteremia (p = 0.20). The median (interquartile range) plasma folate levels were 34.50 (24.40–52.00 nmol/L), 33.40 (15.83–60.85 nmol/L), 30.85 (24.68–39.65 nmol/L), and 13.30 (10.03–17.18 nmol/L), respectively, in the SCD malaria, SCD bacteremia, SCD steady state, and the non-SCD malaria sub-groups. The median folate levels of SCD steady state, SCD malaria, and SCD bacteremia sub-groups differed significantly (p < 0.0001) when compared with non-SCD patients, but the levels in the SCD bacteremia and malaria groups were not significantly different from the SCD steady state group.ConclusionElevated levels of plasma folate were found in a high proportion of pediatric SCD patients. The implications of such elevated folate levels in pediatric SCD patients are unknown but may suggest a need for review of current recommendations for prophylactic doses of folic acid in SCD patients.

High Serum Folate Concentration Is Associated with Better Lung Function in Male Chronic Obstructive Pulmonary Disease Patients Who Are Current Smokers: Analysis of Nationwide Population-Based Survey.

Folate, folic acid, has a role in mitigating inflammatory reactions in the human body. This study aimed to evaluate the association of serum folate levels with lung function in chronic obstructive pulmonary disease (COPD) patients. Of the 8149 participants of the 2016 Korean National Health and Nutrition Examination Survey (KNHANES), 311 subjects (192 males and 119 females) having COPD defined by the lower fifth percentile of the reference population were selected. Pearson’s correlation coefficient was used to investigate the relationship between serum folate level and lung function measurements. The association between the serum folate level and lung function in patients with COPD was evaluated using multivariable linear regression analysis after adjustment for age, sex, height, high sensitivity C-reactive protein, total calorie intake, residence, smoking status and smoking pack–years, education, and household income. The serum folate level showed a positive correlation with the predicted percentage of forced expiratory volume in one second (FEV1%). In males, a trend for a positive correlation with serum folate level was observed in predicted FEV1%, FEV1 value, predicted percentage of forced vital capacity (FVC%), FVC value, and peak expiratory flow (PEF). No significant correlation between the serum folate level and lung function in females was observed. In the multivariable linear regression model, the serum folate level was associated with an increase in predicted FEV1%, FEV1 value, predicted FVC%, FVC value, and PEF; however, the significance was only observed in males, especially among current smokers. High serum folate level was positively associated with lung function measurements in male COPD patients who were current smokers. Further longitudinal studies are needed to elucidate the underlying mechanisms.