Serum Folate Concentrations Research Articles

Folate status in the US population 20 y after the introduction of folic acid fortification

Enriched cereal-grain products have been fortified in the United States for >20 y to improve folate status in women of reproductive age and reduce the risk of folic acid-responsive neural tube birth defects (NTDs). Our objectives were to assess postfortification changes in folate status in the overall US population and in women aged 12-49 y and to characterize recent folate status by demographic group and use of folic acid-containing supplements. We examined cross-sectional serum and RBC folate data from the NHANES 1999-2016. Serum folate geometric means increased from 2007-2010 to 2011-2016 in persons aged ≥1 y (38.7 compared with 40.6 nmol/L) and in women (35.3 compared with 37.0 nmol/L), whereas RBC folate showed no significant change. Younger age groups, men, and Hispanic persons showed increased serum and RBC folate concentrations, whereas non-Hispanic black persons and supplement nonusers showed increased serum folate concentrations. The folate insufficiency prevalence (RBC folate <748 nmol/L; NTD risk) in women decreased from 2007-2010 (23.2%) to 2011-2016 (18.6%) overall and in some subgroups (e.g., women aged 20-39 y, Hispanic and non-Hispanic black women, and supplement nonusers). After covariate adjustment, RBC folate was significantly lower in all age groups (by ∼10-20%) compared with persons aged ≥60 y and in Hispanic (by 8.2%), non-Hispanic Asian (by 12.1%), and non-Hispanic black (by 20.5%) compared with non-Hispanic white women (2011-2016). The 90th percentile for serum (∼70 nmol/L) and RBC (∼1800 nmol/L) folate in supplement nonusers aged ≥60 y was similar to the geometric mean in users (2011-2014). Blood folate concentrations in the US population overall and in women have not decreased recently, and folate insufficiency rates are ∼20%. Continued monitoring of all age groups is advisable given the high folate status particularly in older supplement users.

Effects of micronutrients supplementation on plasma homocysteine level and global cognitive function among older adults in long-term care facilities: a randomized controlled study

Objective To investigate the effects of micronutrient supplementation for the elderly on plasma homocysteine level and cognitive function in institutional older adults. Methods A total of 98 older adults with the score≤11 by mini nutritional assessment short-form aged 65-100 years were enrolled and assigned to either intervention group or control group (n=49 each), with either a package of micronutrient pack or placebo daily, for three months. Fasting blood samples were collected both at baseline and the end of study to detect serum vitamin B12, folate and plasma homocysteine (Hcy) concentrations. Global cognitive function was assessed using the mini-mental state examination (MMSE). The paired t test was used to compare the continuous variables between the two groups after intervention. The relationship between changes in MMSE score and changes in plasma Hcy concentrations was examined by least-squares linear regression. Results Eighty-two patients completed the study, and 17 patients withdrew from the study due to diarrhea and hospital discharge with the drop rate of 17.3%. Compared to the control group, concentrations of serum vitamin B12 (128.8±34.8 vs 13.3±16.0 pmol/L, P=0.003) and folate (21.1±1.6 vs 0.6±0.5 nmol/L, P<0.01) significantly increased in the intervention group over 3-month supplementation, while plasma Hcy levels were remarkably reduced (-5.3±0.7 vs 1.7±0.3 μmol/L, P<0.01). The incidences of deficiency of folate, deficiency of serum vitamin B12and high Hcy all decreased in intervention group. Although individual item scores in MMSE were not changed markedly, change of total MMSE score in intervention group were higher than that in the control group (1.2±3.0 vs -0.2±2.5, P<0.05). Conclusions The supplementation of the micronutrient pack in long-term care facilities can reduce the incidence of hyperhomocysteinemia, and improve the total MMSE score. Key words: Micronutrient; Older adults; Homocysteine; Cognitive function

Simultaneous supplementation with iron and folic acid can affect Slc11a2 and Slc46a1 transcription and metabolite concentrations in rats.

The present study aimed at analysing how dietary folic acid (FA) and Fe deficiency, followed by supplementation with these nutrients, affects the expression of folate and Fe transporters in the duodenum, as well as FA and Fe status. After a deficiency period, Wistar rats were randomised to a group fed with a diet deficient in FA and supplemented with Fe (DFE), a diet deficient in Fe and supplemented with FA, a diet supplemented with Fe and FA (FEFOL), a diet deficient in Fe and FA (D) or a control diet (C). Tissue collection was performed after 2, 10 or 21 d of these diets. Group D had higher Slc11a2 mRNA levels than the DFE group at every time point and there were differences in mRNA levels of Slc46a1 between the DFE and the FEFOL groups at the third time point, but we observed no differences in protein levels between the groups. The DFE and D groups not only had lower serum folate concentrations at every time point but also had the highest homocysteine concentrations. Total Fe binding capacity concentrations were the lowest in the DFE group at the first time point and in the DFE and the FEFOL groups at the final time point. Simultaneous supplementation with FA and Fe resulted in significantly higher Hb concentrations than did supplementation with these nutrients alone. Our findings indicate that dietary FA and Fe deficiency, and subsequent supplementation with these nutrients, affects transcription but not the protein levels of FA and Fe transporters in the duodenum.

Serum and Dietary Folate and Vitamin B12 Levels Account for Differences in Cellular Aging: Evidence Based on Telomere Findings in 5581 U.S. Adults.

Folate and vitamin B12 are essential for a variety of metabolic processes. Both micronutrients have been shown to reduce oxidative stress significantly. The present cross-sectional investigation evaluated the association between serum and dietary folate and vitamin B12 levels and leukocyte telomere length, an index of cellular aging influenced by oxidative stress. The study included 5581 adults from the National Health and Nutrition Examination Survey (NHANES). Because participants were randomly selected, results are generalizable to all civilian, noninstitutionalized U.S. adults. A blood draw provided DNA and serum folate and B12 information. The quantitative polymerase chain reaction method was used to measure telomere length. The Bio-Rad Quantaphase II folate and vitamin B12 radioassay kit was used to quantify levels of folate and vitamin B12. Dietary folate and vitamin B12 were assessed using a multipass 24 h recall. In some models, age, race, smoking pack-years, alcohol use, body mass index, total physical activity, hours fasted before the blood draw, and diabetes status were employed as covariates to minimize their influence. Findings showed that for each additional year of chronological age, telomeres were 15.6 base pairs shorter, on average (F = 378.8, p < 0.0001). Men had shorter telomeres than women after adjusting for all the covariates (F = 6.8, p = 0.0146). Serum (F = 10.5, p = 0.0030) and dietary (F = 5.0, p = 0.0325) folate concentrations were each linearly related to telomere length in women, but not in men, after controlling for age and race. Serum vitamin B12 and telomere length had a nonsignificant, inverse relationship in women, with age and race controlled (F = 2.8, p = 0.1056), but no relation in men. Dietary vitamin B12 was linearly related to telomere length in women, after adjusting for age and race (F = 4.3, p = 0.0468), but not in men. Overall, evidence indicates that folate and vitamin B12 levels, especially folate, account for meaningful differences in cell aging in women, but not in men.

Obesity is associated with folate metabolism.

Objective: The aim of the present study is to perform a systemic review of the previous studies executed on the association between obesity and folate. Method: In the present research, the selected keywords were scanned on the PubMed, Web of Science, Cochrane and Lilac databases between May and June, 2017 through Gazi University's network. In total, 4236 clinical, randomized controlled, cross-sectional and prospective studies were determined and 17 of these that specifically fit the aims of the present research were reviewed. This study involved an electronic literature search of databases on folic acid and obesity published in the English language between 2000 and 2016. Results: Of the 17 studies, 5 were based on folic acid supplementation and 12 were related with participants' folate status. As a general consequence of both intake and serum/status measurements of folic acid supplementation: It was found that obesity-associated metabolic changes might affect individual folate use and obese individuals had lower serum folate levels, although there was no change in folate intake. Conclusion: Overweight and obese individuals have lower serum folate concentrations when compared with individuals with normal weight. It is explained by increased use of folic acid, urinary excretion, dilution of blood volume, different levels in different tissues and changes in the endocrine functions of folate. Individuals with higher Body Mass Indexes have less supplement use, unhealthier diets and donot consume sufficient vegetables and fruits, all of which can affect decrease in folate levels. Furthermore, adiposity may affect folate absorption by intestinal epithelium.

Association of Leukocyte Telomere Length with Mild Cognitive Impairment and Alzheimer’s Disease: Role of Folate and Homocysteine

Background: Leukocyte telomere length (LTL) is associated with the aging process and age-related degenerative diseases. The relation of peripheral blood LTL to mild cognitive impairment (MCI) and Alzheimer’s disease (AD) and the role of folate and homocysteine (Hcy) in this relation remain unclear. Objectives: We aimed to investigate the association between LTL and the risks of MCI/AD, and to explore whether folate and Hcy may play a role in this association. Methods: This case-control study included 129 MCI subjects, 131 AD patients and 134 healthy controls. LTL was assessed using real-time polymerase chain reaction assay. Serum folate levels were tested by chemiluminescence enzyme immunoassay, and serum Hcy levels were measured using the enzymatic cycling method. Data were analyzed using multivariate logistic regression and multivariable linear regression with adjustment for potential confounders. Results: The mean LTL was 1.56 ± 0.25 in controls, 1.44 ± 0.23 in MCI, and 1.28 ± 0.28 in AD patients (p< 0.01). In multivariate logistic regression, subjects in the longest LTL tertile had lower OR for MCI (OR 0.246; 95% CI 0.101–0.597) and AD (OR 0.123; 95% CI 0.044–0.345) in comparison to subjects in the shortest tertile. Shorter LTL was dose-dependently related to the ORs of MCI and AD. Further, serum folate concentration was positively associated with LTL (p < 0.01), while serum Hcy level was negatively associated with LTL (p < 0.05). In stratified analyses, LTL-MCI/AD association varied by serum folate and Hcy level. Conclusions: Shorter LTL is associated with the risks of MCI/AD. Folate and Hcy might play an important role in this association.

&lt;p&gt;Comparison of serum B12, folate and homocysteine concentrations in children with autism spectrum disorder or attention deficit hyperactivity disorder and healthy controls&lt;/p&gt;

ObjectiveWe aimed to investigate the serum concentrations of vitamin B12, folate and homocysteine in children diagnosed with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and healthy controls.Materials and methodsSerum vitamin B12, folate and homocysteine concentrations were measured in 118 children (48 children diagnosed with ADHD, 35 children diagnosed with ASD and 35 healthy controls). Symptom severity in the ADHD and ASD groups was evaluated by the Childhood Autism Rating Scale and Turgay-DSM-IV-Based Screening and Assessment Scale for Disruptive Behavior Disorders. Multivariate analysis of covariance was used to evaluate the effects of diagnosis and gender on biochemical parameters.ResultsThe ADHD and ASD groups and the healthy controls differed significantly regarding vitamin B12 and homocysteine concentrations, but not folate levels. Patients with ASD had the lowest vitamin B12 and the highest homocysteine levels. Vitamin B12 levels correlated negatively with hyperactivity and/orimpulsivity and oppositionality symptoms in children with ADHD. There were no relationships between psychometric evaluations and laboratory measurements in children with ASD. Gender did not affect vitamin concentrations.ConclusionPrevious studies found that vitamin B12 was reduced while homocysteine was elevated among patients with ADHD and ASDs. Our results also support those reported previously. Oppositionality and hyperactivity and/orimpulsivity may be related to vitamin B12 and homocysteine levels in children with ADHD. Further studies are required to define the role of these parameters and effects on the etiology and clinical manifestations of ASD and ADHD.

EVALUATION OF SERUM IRON AND FOLATE LEVELS IN PATIENTS WITH ORAL LEUKOPLAKIA

Objectives &#x0D; &#x0D; To assess the levels of serum folate and iron in patients with and without any visible Oral leukoplakia.&#x0D; To correlate serum folate and iron levels and clinical staging of Oral leukoplakia.&#x0D; To correlate serum folate and iron levels and degree of dysplasia&#x0D; &#x0D; Materials &amp; Methods: The study comprised of 102 patients (34 Oral leukoplakia patients with habit(s), 34 patients with habit(s) and no oral leukoplakia and 34 controls). The conditions were further clinically and histo-pathologically graded. Serum folate concentration was determined by chemi-luminescent immunoassay method from the serum (blood) sample without hemolysis and serum iron concentration was determined by photometric method.&#x0D; Results: The mean folate level ± SD (ng/dl) was found to be 5.17 ± 2.71 ng/dl, 5.29 ± 2.10 ng/dl and 5.37 ± 4.77 ng/dl in Oral leukoplakia patients, patients with habits without Oral leukoplakia and controls respectively. The mean iron level ± SD (μg/dl) was found to be 91.21 ± 28.73 μg/dl, 105.74 ± 33.20 μg/dl and 96.82 ± 38.92 μg/dl in Oral leukoplakia patients, patients with habits without Oral leukoplakia and controls respectively.&#x0D; Conclusion: In patients with habit and without leukoplakia and controls, there was a significant increase in the serum iron level than the oral leukoplakia patients. However, nosignificant differences seen in serum folate level in these three groups. Further studieswith larger sample size should be done to conclude serum folate and iron levels as adiagnostic marker in Oral leukoplakia.&#x0D; Keywords: Diagnosis, Serum folate, serum iron, potentially malignant disorders, potentially malignant disorders, Oral squamous cell carcinoma, malignant transformation, Immuno-assay.

Fortification of wheat and maize flour with folic acid for population health outcomes.

Fortification of wheat and maize flour with folic acid for population health outcomes.

Time course of serum cobalamin, folate, and total iron binding capacity concentrations in pregnant bitches and association with hematological variables and survival.

BackgroundHypocobalaminemia, hypofolatemia and iron deficiency are associated with pregnancy‐related anemia (PRA) and neonatal survival (NS) in women. Similar associations have not been investigated in pregnant bitches.ObjectivesTo investigate time course and associations of serum cobalamin, folate and iron status indicators with hematological variables and NS in pregnant bitches.AnimalsForty‐eight pregnant bitches.MethodsA prospective cohort study. Pregnancy was confirmed by abdominal ultrasonography twice during mid‐ and late pregnancy, concurrently with blood sampling. Associations among pregnancy stage, NS and laboratory variables were assessed by generalized estimating equations.ResultsCompared with midpregnancy, serum cobalamin (adjusted mean [95% confidence interval, CI]) decreased at late pregnancy (430 pg/mL [394‐466] versus 330 pg/mL [303‐357], respectively; P < .001), whereas serum folate did not. Every increment of 1 in parity number or litter size corresponded to 28.6 pg/mL (95% CI, 5.6‐51.6; P = .02) and 20.3 pg/mL (95% CI, 10.9‐29.7; P < .001) decrease in serum cobalamin concentration. Compared with midpregnancy, serum iron (P < .001) and transferrin saturation (P = .01) increased at late pregnancy. The decrease in red blood cell count (P < .001) at late pregnancy was significantly, albeit weakly, correlated with decreasing serum folate concentration (r = 0.33; P = .02). None of the measures was associated with NS.Conclusions and Clinical SignificancePregnancy‐related anemia was common at late pregnancy. Unlike in women, in pregnant bitches, serum iron and transferrin saturation were increased at late pregnancy. Future studies are warranted to investigate the clinical ramifications of hypocobalaminemia in pregnant bitches and the utility of prophylactic folate administration in mitigating PRA.

Serum folate concentrations at diagnosis are associated with hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort study.

Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP &gt; 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.

Anemia and Iron, Vitamin B12, and Folate Deficiencies in Women of Reproductive Age in Ecuador: Results from the Ecuadorian National Health and Nutrition Survey (P10-027-19)

ObjectivesTo examine the burden of anemia and deficiencies of iron, vitamin B12, and folate in women of reproductive age (WRA) in Ecuador. MethodsData from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) were analyzed to examine the burden of anemia and micronutrient deficiencies among 7658 women of reproductive age (12–49 y; n = 7383 non-pregnant, n = 275 pregnant). Venous blood samples were collected, and hemoglobin (Hb) was assessed viathe sodium lauryl sulfate method. Samples were centrifuged, processed, and stored < -50°C until analysis. Serum ferritin (SF), vitamin B12, serum folate, and red blood cell (RBC) folate were measured viachemiluminescence. Hemoglobin was adjusted for altitude; and anemia was defined as Hb <11.0 g/dL in pregnant women and <12.0 g/dL in non-pregnant women. Iron deficiency and insufficiency were defined as SF <15.0 μg/L and <20.0 μg/L, respectively. Vitamin B12 deficiency and insufficiency were defined as <148.0 pmol/L and <221.0 pmol/L; and folate deficiency was defined as serum folate <7.0 nmol/L and RBC folate <342.0 nmol/L. Survey logistic and linear regression were used to examine associations of micronutrients with hemoglobin concentrations and anemia. ResultsIn analyses among non-pregnant women, 11.3% were anemic, 14.4% were iron deficient, and 21.1% had iron insufficiency. A total of 4.3% of women had vitamin B12 deficiency, 23.9% had vitamin B12 insufficiency; and <1% of women were folate deficient. The prevalence of micronutrient deficiencies was higher in pregnant women, compared to non-pregnant women: 31.1% of pregnant women were iron deficient, 43.0% were iron insufficient, 21.3% were vitamin B12 deficient, and 55.4% were vitamin B12 insufficient. In non-pregnant WRA, higher SF (P < 0.0001), vitamin B12 (P < 0.01), and serum folate (P < 0.0001) concentrations were associated with higher Hb concentrations; and higher SF (OR: 0.96, 95% CI: 0.95, 0.97; P < 0.0001) and serum folate (OR: 0.98, 95% CI: 0.97, 0.98; P < 0.0001) concentrations were associated with lower odds of anemia. In pregnant women, SF (P < 0.01) and serum folate (P = 0.002) concentrations were associated with higher hemoglobin concentrations. ConclusionsFindings suggest that the burden of anemia, iron deficiency, and vitamin B12 insufficiency is high among women of reproductive age in Ecuador. Funding SourcesNot applicable.

Folate and Vitamin B12 Status in Women of Reproductive Age in Rural Areas in Haryana, Northern India (P10-117-19)

ObjectivesTo conduct a household and biomarker survey to assess the baseline prevalence of folate deficiency and insufficiency and vitamin B12 deficiency in women of reproductive age prior to the start of a wheat flour fortification program in the Ambala District in Haryana, India. MethodsA multistage cluster probability household and biomarker survey was conducted. Participants were women of reproductive age (18–49 y) who were not pregnant and resided in rural areas of two subdistricts in Ambala District in Haryana. Venous blood samples were collected among 866 women. Plasma, serum, and red blood cells (RBC) were separated by centrifugation, processed, and stored at <-80°C until analysis. RBC and serum folate concentrations were measured using microbiologic assay and serum vitamin B12 was measured via chemiluminescence. Serum folate deficiency was defined as serum folate <7 nmol/L and RBC folate deficiency and insufficiency were defined as RBC folate <305 nmol/L and <748 nmol/L, respectively. Vitamin B12 deficiency was defined as vitamin B12 <200 pg/mL and vitamin B12 marginal deficiency was defined as vitamin B12 ≥200 and <300 pg/mL. ResultsThe geometric mean concentrations for serum folate, RBC folate, and serum vitamin B12 were 12.3 (95% confidence interval [CI]: 11.8, 12.9) nmol/L, 544 (95% CI: 516, 573) nmol/L, and 190 (95% CI: 176, 206) pg/mL, respectively. The prevalence of folate deficiency was 11.3% (95% CI: 9.2, 13.9) for serum folate and 9.7% (95% CI: 7.8, 12.0) for RBC folate, and the prevalence of RBC folate insufficiency was 78.6% (95% CI: 74.8, 82.5). A total of 58.3% (95% CI: 54.2, 62.5) of women were vitamin B12 deficient (<200 pg/mL) and an additional 22.9% (95% CI: 19.7, 26.1) were marginally deficient for vitamin B12. ConclusionsThe magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline for a planned wheat flour fortification program aimed at reducing these micronutrient deficiencies. Funding SourcesCenters for Disease Control and Prevention.

Data mining: Seasonal and temperature fluctuations in thyroid-stimulating hormone

Subacute combined degeneration of the spinal cord (SACD) is a rare neurologic disorder manifesting progressive symptoms of paresthesia and spastic paralysis. Herein we present an autopsy case of SACD caused by folic acid and copper deficiency. A 16-year-old male presented with gradually worsening unsteady gait, and bladder and rectal dysfunction. He had a medical history of T-cell acute lymphoblastic leukemia (T-ALL), diagnosed 1.5 years previously. The patient had undergone chemotherapy, including methotrexate, as well as allogeneic bone mallow transplantation. Laboratory tests revealed normal vitamin B12 and methylmalonic acid concentration, but reduced serum copper, ceruloplasmin and folic acid concentrations. Magnetic resonance imaging revealed symmetrical T2 signal hyperintensities in the posterior and lateral spinal cord. The patient was treated with oral copper, oral folate, and intravenous vitamin B12. A month after this treatment, the patient’s symptoms were unchanged, and 2 months later he died of acute adrenal insufficiency. The pathological findings of the spinal cord were compatible with SACD. Because SACD is usually reversible with early treatment, it should be suspected in high-risk patients undergoing chemotherapy or those who are malnourished with characteristic symptoms of SACD, even in young patients.

Daily supplementation with 5 mg of folic acid in Brazilian patients with hereditary spherocytosis

Patients with hereditary spherocytosis (HS) have increased rates of erythropoiesis and higher folate requirements. In a case-control study of patients with HS, we evaluated the associations between the use of...

Low Maternal Dietary Folate Alters Retrotranspose by Methylation Regulation in Intrauterine Growth Retardation (IUGR) Fetuses in a Mouse Model.

BackgroundMaternal folate deficiency-mediated metabolic disruption is considered to be associated with the risk of intrauterine growth retardation (IUGR), but the exact mechanism remains unclear. The retrotransposon long interspersed nucleotide element-1 (LINE-1), which can induce birth defects via RNA intermediates, plays crucial roles during embryonic development. We investigated potential relationships between maternal folate and DNA methylation, and possible roles of LINE-1 in IUGR.Material/MethodsThe IUGR model was established by feeding female mice 1 of 3 diets – control diet (CD), folate-deficient diet for 2 weeks (FD2w), and folate-deficient diet for 4 weeks (FD4w) – prior to mating. Maternal serum folate, 5-methyltetrahydrofolate (5-MeTHF), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) concentrations and global DNA methylation were assessed by LC/MS/MS method. LINE-1 methylation levels in fetuses were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. LINE-1 expression levels were validated by real-time PCR.ResultsMaternal folate deficiency caused plasma folate and 5-MeTHF levels to decrease and SAH level to increase in the FD4w group. Compared with the CD group, methylation levels of genomic DNA and LINE-1 decreased significantly in placenta and fetal tissues from the FD4w group. Expression of LINE-1 open reading frame 1 (ORF1) protein was elevated in fetal liver tissues. Furthermore, a strong correlation was found between methylation and disrupted one-carbon metabolism, implying that dietary folate plays important roles during embryogenesis.ConclusionsMaternal dietary folate deficiency impaired one-carbon metabolism, leading to global DNA and LINE-1 hypomethylation, and then increased retrotransposition in fetuses, which can lead to IUGR.

Excess Folic Acid Supplementation Before and During Pregnancy and Lactation Activates Fos Gene Expression and Alters Behaviors in Male Mouse Offspring.

Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects and other birth defects. After 20 years mandate food fortification with FA, serum concentration of folate and unmetabolized FA increased significantly in the North American population. But whether excess FA intake impairs neurodevelopment and behavior is still controversial. Here, we treated mice with approximately 2.5-fold (moderate dose of FA, MFA) or 10-fold (high dose of FA, HFA) the dietary requirement of FA 1 week before mating and throughout pregnancy and lactation, and examined behaviors in adult male offspring using open field test, three-chamber sociability and social novelty test, elevated plus maze, rotarod and Morris water maze. We found that early life MFA supplementation increased long-term body weight gain in adults, elevated anxiety-like behavior, and impaired social preference, motor learning and spatial learning ability without modifying motor ability and spatial memory. In contrast, HFA supplementation only induced mild behavioral abnormality. RNA sequencing revealed that FA supplementation altered the expression of brain genes at weaning, among which Fos and related genes were significantly up-regulated in MFA mice compared with control and HFA mice. Quantitative real time-PCR (qRT-PCR) and western blots confirmed the increase of these genes. Our results suggested that FA supplementation during early life stage affected gene expression in weaning mice, and exhibited long-term impairments in adult behaviors in a dose-sensitive manner.

Association Between Maternal Serum Folate Concentrations in the First Trimester and the Risk of Birth Defects: The Hokkaido Study of Environment and Children's Health.

BackgroundLow red blood cell folate concentrations during early pregnancy might cause neural tube defects. However, the association between folate concentrations and birth defects of other neural crest cell-derived organs remains unknown. We investigated the associations between birth defects and first-trimester serum folate concentrations in a birth-cohort study in Japan.MethodsIn total, 14,896 women who were prior to 13 weeks of gestation were enrolled from 2003 through 2012. Birth defect information was obtained from medical records and questionnaires. The association between folate levels in the first trimester and birth defects categorized as ICD-10 cord defects and neural crest cell-derived organ defects was examined. The crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per log-transformed folate concentration were calculated using logistic regression.ResultsBlood samples were obtained at a mean of 10.8 weeks of gestation. Median serum folate level was 16.5 (interquartile range, 13.4–21.5) nmol/L, and the deficiency level (less than 6.8 nmol/L) was 0.7%. There were 358 infants with birth defects. The adjusted odds ratio for any birth defect, ventricular septal defects, and cleft lip was 0.99 (95% CI, 0.74–1.32), 0.63 (95% CI, 0.30–1.33), and 4.10 (95% CI, 0.96–17.58), respectively. There were no significant associations between first-trimester maternal serum folate and the risk of birth defects.ConclusionsWe were unable to demonstrate a relationship between maternal serum folate in the first trimester and birth defects. Potential confounding factors may have influenced our results.

Serum Cobalamin and Folate Concentrations in Common Marmosets (Callithrix jacchus) with Chronic Lymphocytic Enteritis.

Serum cobalamin and folate concentrations can serve as surrogate markers of gastrointestinal disease in dogs and cats, where they can have diagnostic, therapeutic, and prognostic implications. Chronic disease of the gastrointestinal tract, particularly chronic lymphocytic enteritis (CLE), occurs frequently in captive common marmosets. The aims of this study were to validate a commercially available assay for measuring serum cobalamin and folate concentrations in common marmosets, to establish reference intervals for these analytes in healthy marmosets, and to measure serum concentrations in common marmosets with CLE. The commercial assay was linear, accurate, precise, and reproducible for the measurement of serum cobalamin and folate concentrations in common marmosets. In healthy marmosets, the serum cobalamin concentration ranged from 322 to 2642 pg/mL (n = 35) and serum folate concentration from 54.8 to 786.4 ng/mL (n = 37). Low serum folate concentrations were moderately sensitive (greater than 70%) for CLE, and low serum cobalamin concentrations were moderately (greater than 70%) specific for CLE. Both serum cobalamin and folate concentrations were relatively unchanged in marmosets during 120 to 220 d. Serum cobalamin and folate concentrations were stable for approximately 7 y when samples were stored at -80 °C. Additional studies are warranted to further study the clinical implications of low serum cobalamin and folate concentrations in common marmosets.

Serum folate and vitamin B12 status in young Brazilian children.

To assess the nutritional status of folate and vitamin B12 with anaemia in young children. A cross-sectional study was conducted at the primary health-care centres of four Brazilian cities. Folate and vitamin B12 were assessed by fluoroimmunoassay. Multilevel Poisson regression models were used to explore the association of folate and vitamin B12 status in relation to anaemia in young children. Brazil.ParticipantsChildren (n 460) aged 11 to 15 months. The median (interquartile range) of serum folate was 39·7 (28·8-55·3) nmol/l and only four children presented with folate deficiency (&lt;10 nmol/l). Surprisingly, 30·9 % of children presented with serum folate concentrations above the upper limit of detectable values by the commercial kit used for analysis. The frequency of vitamin B12 deficiency (&lt;148 pmol/l) was 15 % and it was inversely associated with the highest tertile of serum folate concentrations (P&lt;0·001). Having high serum folate concentration (≥50·1 nmol/l) and vitamin B12≥148 pmol/l was associated with lower frequency of anaemia in these children (prevalence ratio=0·53; 95% CI 0·30, 0·92). High frequency of elevated serum concentration of folate was found among young Brazilian children and 15 % of them had vitamin B12 deficiency. The combination of high serum folate and normal vitamin B12 status was associated with a lower frequency of anaemia in these children. Improvements in the current strategies to promote healthy food-based complementary feeding along with prevention and control of micronutrient deficiencies are recommended to improve children's health.