Serum Folate Concentrations Research Articles

Assessing the association between the methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism on blood folate concentrations: a systematic review and meta‐analysis of trials and observational studies (LB311)

Background: The methylenetetrahydrofolate reductase (MTHFR) 677C→T polymorphism is a risk factor for neural tube birth defects (NTDs). The T allele produces an enzyme with reduced folate processing capacity, which has been shown to produce lower blood folate concentrations in some studies.Objective: To assess the association between MTHFR C677T genotypes (CC, CT, TT) and blood folate concentrations among women aged 12‐49 years.Design: We conducted a systematic review of literature published between 1/1992‐7/2013 to identify controlled trials and observational studies that reported serum, plasma, or red blood cell (RBC) folate concentrations and MTHFR C677T genotype. We applied a Bayesian random‐effects model to predict differences in blood folate concentrations between MTHFR C677T genotypes, stratified by folate assay.Results: Thirty‐eight studies met criteria for inclusion. Serum/plasma folate concentrations showed a consistent genotype trend with the highest concentrations for CC (CC > CT > TT) regardless of assay type. RBC folate concentrations measured by microbiologic assay also demonstrated this trend; however, this trend was reversed (CC < CT < TT) in studies using protein‐binding assays.Conclusions: Meta‐analyses results showed blood folate concentrations differed by assay type and genotype. Previous evidence has shown that RBC folate concentrations measured with a radioimmunoassay requires adjustment for genotype‐dependent folate recovery; our results suggest that other protein‐binding assays could have similar limitations. Compared to CC individuals, TT individuals have lower blood folate concentrations, which may increase a woman’s risk for an NTD‐affected pregnancy.

Nutritional adequacy of goat milk infant formulas for term infants: a double-blind randomised controlled trial

The safety and nutritional adequacy of goat milk infant formulas have been questioned. The primary aim of the present study was to compare the growth and nutritional status of infants fed a goat milk infant formula with those of infants fed a typical whey-based cow milk infant formula. The secondary aim was to examine a range of health- and allergy-related outcomes. A double-blind, randomised controlled trial with 200 formula-fed term infants randomly assigned to receive either goat or cow milk formula from 2 weeks to at least 4 months of age was conducted. A cohort of 101 breast-fed infants was included for comparison. Weight, length and head circumference were measured at 2 weeks and 1, 2, 3, 4, 6 and 12 months of age. Nutritional status was assessed from serum albumin, urea, creatinine, Hb, ferritin, and folate and plasma amino acid concentrations at 4 months. Z-scores for weight, length, head circumference and weight for length were not different between the two formula-fed groups. There were differences in the values of some amino acids and blood biomarkers between the formula-fed groups, but the mean values for biomarkers were within the normal reference range. There were no differences in the occurrence of serious adverse events, general health, and incidence of dermatitis or medically diagnosed food allergy. The incidence of parentally reported blood-stained stools was higher in the goat milk formula-fed group, although this was a secondary outcome and its importance is unclear. Goat milk formula provided growth and nutritional outcomes in infants that did not differ from those provided by a standard whey-based cow milk formula.

A new potential risk factor in patients with erectile dysfunction and premature ejaculation: folate deficiency.

We investigated serum folic acid (FA) levels in patients with erectile dysfunction (ED) and/or premature ejaculation (PE). Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time (IELT) was measured during a 4 weeks baseline period. Levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, total testosterone), homocysteine (Hcys), and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation (CIPE). The abridged International Index of Erectile Function-5 (IIEF-5) questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED (7.61 ± 3.97 ng ml−1), PE (9.37 ± 3.40 ng ml−1), and ED/PE (8.84 ± 4.28 ng ml−1) patients than in healthy men (12.23 ± 5.76 ng ml−1, P < 0.05). No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls (P > 0.05). There were positive correlations between serum FA concentrations and CIPE scores (r = 0.530, P < 0.01), IIEF-5 scores (r = 0.589, P < 0.01), and IELT (r = 0.445, P < 0.01); negative correlations with Hcys concentrations (r = −0.487, P < 0.01) were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.

The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism

Objective. To investigate the joint effects of the single nucleotide polymorphisms (SNPs) of genes in the folic acid pathway on homocysteine (Hcy) metabolism. Methods. Four hundred women with normal pregnancies were enrolled in this study. SNPs were identified by MassARRAY. Serum folic acid and Hcy concentration were measured. Analysis of variance (ANOVA) and support vector machine (SVM) regressions were used to analyze the joint effects of SNPs on the Hcy level. Results. SNPs of MTHFR (rs1801133 and rs3733965) were significantly associated with maternal serum Hcy level. In the different genotypes of MTHFR (rs1801133), SNPs of RFC1 (rs1051266), TCN2 (rs9606756), BHMT (rs3733890), and CBS (rs234713 and rs2851391) were linked with the Hcy level adjusted for folic acid concentration. The integrated SNPs scores were significantly associated with the residual Hcy concentration (RHC) (r = 0.247). The Hcy level was significantly higher in the group with high SNP scores than that in other groups with SNP scores of less than 0.2 (P = 0.000). Moreover, this difference was even more significant in moderate and high levels of folic acid. Conclusion. SNPs of genes in the folic acid pathway possibly affect the Hcy metabolism in the presence of moderate and high levels of folic acid.

Estimation of Serum and Erythrocyte Folate Concentrations in the New Zealand Adult Population within a Background of Voluntary Folic Acid Fortification1–3

National data on the blood folate status of New Zealand adults is lacking. The objective of this study was to describe the blood folate status and examine the predictors of blood folate status in a national sample of adults from New Zealand, a country with voluntary folic acid fortification. The 2008/09 New Zealand Adult Nutrition Survey was a nationwide multistage systematic random cross-sectional survey. Serum and erythrocyte folate concentrations were measured by microbiologic assay. The survey included 4721 participants aged ≥15 y, 3359 of whom provided a nonfasting blood sample. Biochemical folate status was measured in 3277 participants. The median serum and erythrocyte folate concentrations were 23 and 809 nmol/L, respectively. The prevalence of biochemical folate deficiency, defined as plasma folate <6.8 nmol/L or erythrocyte folate <305 nmol/L, was 2%. Having breakfast daily compared with never eating breakfast was associated with 53% higher serum and 25% higher erythrocyte folate concentrations; consumers of fortified yeast extract spread had 17% higher serum and 14% higher erythrocyte folate concentrations than nonconsumers; daily users of folate-containing supplements compared with nonusers had 48% higher serum and 28% higher erythrocyte folate concentrations. The prevalence of biochemical folate deficiency in New Zealand adults is low. Participants who ate breakfast more frequently, consumed folate-fortified yeast, or used a daily folate supplement had higher blood folate concentrations.

Vitamin B12 and Folate Status in Sudanese Psychiatric Patients

Background: The contribution of B12 and folate deficiencies to pathophysiology of psychiatric illnesses is well known worldwide, however it was not evaluated in Sudanese psychiatric patients. Aim: To assess the association between the neuropsychiatric syndromes and the levels of both vitamin B12 and folic acid in Sudanese psychiatric patients. Materials and Methods: The study involved a test group of 100 psychiatric patients and an age/gender matched control group of 100 subjects with no past history of psychiatric illness. Laboratory investigations, including complete blood count (CBC), serum vitamin B12 and folate concentrations were done to all studied subjects. Significance of the difference in the means of the studied variables and the association between psychiatric illnesses and both B12 or folic acid deficiencies were assessed using appropriate statistical tests. Results: Most of hematological indices were significantly less in psychiatric patients, although their means were within normal range. The serum concentrations of vitamin B12 in the psychiatric patients (M±SD = 527.9 ± 305. 8 pg/ml) were significantly lower compared with the control group (M±SD = 590.5± 186.1 pg/ml, P = 0.001). There was significant association between B12 deficiency and psychiatric illnesses (P = 0.014). Six percent of the psychiatric patients were suffering from B12 deficiency while none the control group was suffering from the same deficiency. The serum concentrations of folic acid were comparable in both studied groups (M±SD = 7.2 ± 1.7 ng/ml, 7.2 ± 2.6 ng/ml in the control and test groups respectively, P > 0.05). There was no folic acid deficiency in both test and control groups. Conclusion: There was association between vitamin B12, but not folic acid, deficiency and psychiatric diseases in studied Sudanese subjects. Most of the hematological indices were significantly less in psychiatric patients, although their means were within normal range. The significantly lower levels of vitamin B12 deficiency were not associated with megaloblastic changes.

Homocysteine in dogs with systemic inflammatory response syndrome

To compare serum concentrations of homocysteine in healthy dogs and those fitting the criteria for systemic inflammatory response syndrome and to compare these values to commonly measured B-vitamins. Study dogs were classified into non-infectious systemic inflammatory response syndrome or sepsis groups and blood was drawn on Day 1 of the patient's hospitalisation for measurement of serum homocysteine, folate and cobalamin concentrations. Homocysteine concentration was measured in 51 clinically healthy dogs to serve as the control group. A statistically significant difference was found between the homocysteine concentrations of the healthy group when compared to non-infectious systemic inflammatory response syndrome and sepsis groups. Homocysteine values were not correlated with folate, cobalamin or APPLEfast severity scores. Homocysteine concentrations were significantly lower in sick dogs when compared to the control group, which is dissimilar to the human population. The clinical significance of homocysteine changes in critically ill dogs is currently unknown.

Review of Commonly Used Clinical Pathology Parameters for General Gastrointestinal Disease with Emphasis on Small Animals

A wide variety of markers are available to assess the function and pathology of the gastrointestinal (GI) tract. This review describes some of these markers with special emphasis given to markers used in dogs and cats. Small intestinal disease can be confirmed and localized by the measurement of serum concentrations of folate and cobalamin. Fecal α1-proteinase inhibitor concentration can increase in individuals with excessive GI protein loss. A wide variety of inflammatory markers are available for a variety of species that can be used to assess the inflammatory activity of various types of inflammatory cells in the GI tract, although most of these markers assess neutrophilic inflammation, such as neutrophil elastase, calprotectin, or S100A12. N-methylhistamine can serve as a marker of mast cell infiltration. Markers for lymphocytic or eosinophilic inflammation are currently under investigation. Exocrine pancreatic function can be assessed by measurement of serum concentrations of pancreatic lipase immunoreactivity (PLI) and trypsin-like immunoreactivity (TLI). Serum PLI concentration is increased in individuals with pancreatitis and has been shown to be highly specific for exocrine pancreatic function and sensitive for pancreatitis. Serum TLI concentration is severely decreased in individuals with exocrine pancreatic insufficiency.

Serum Vitamin B12 and Folate Concentrations and the Effect of the Mediterranean Diet on Vulnerable Populations

Low vitamin B12 and folate levels in expectant mothers may lead to low stores in babies. The aim of this study was to determine the frequencies of vitamin B12 and folate deficiencies in pregnant women and neonates, and to assess the effect of maternal vitamin status on babies’ vitamin levels in the Aegean region of Turkey, where the Mediterranean diet (mainly fresh fruits and vegetables) is adopted. We studied 72 pregnant women and their singleton-term babies. Venous blood samples of expectant mothers were collected 1 h before delivery and cord blood of babies were obtained at birth. The mean vitamin B12 in maternal and cord blood serum was 163.1 ± 72.0 pg/mL and 146.2 ± 102.5 pg/mL, and the mean folate, 9.8 ± 4.8 ng/mL and 15.8 ± 3.8 ng/mL, respectively. There were statistically significant correlation between maternal and cord blood serum vitamin B12 (r = 0.61, P = .04) and folate levels (r = 0.65, P < .001). 70.8% of the mothers and 83.9% of the babies were vitamin B12 deficient (<200 pg/mL). Neither group showed folate deficiency. The mean level of vitamin B12 in mothers significantly varied by the type of diet (241.6 (72.1) pg/mL versus 155.9 (68.2) pg/mL; P = .012). Vitamin B12 deficiency in pregnant women and neonates may be a public health problem in our community. The Mediterranean diet in these vulnerable groups may be an aggravating factor for vitamin B12 deficiency. Prenatal screening of all expectant mothers, prenatal supplementation of vitamin B12, and an increase in animal-source food intake may improve expectant mother's vitamin B12 level.

Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: Reasons for Geographic and Racial Differences in Stroke study 2003–2007

The United States implemented mandatory folic acid fortification of enriched cereal grains in 1998. Although several studies have documented the resulting decrease in anemia and folate deficiency, to our knowledge, no one has determined the prevalence of folate-deficiency anemia after fortification. We determined the prevalence of folate deficiency and folate-deficiency anemia within a sample of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The REGARDS cohort is a prospective cohort of 30,239 black and white participants living in the contiguous United States. We measured serum folate concentrations in a random sample of 1546 REGARDS participants aged ≥50 y with baseline hemoglobin and red blood cell mean corpuscular volume measurements. Folate deficiency was defined as a serum folate concentration <6.6 nmol/L (<3.0 ng/mL), and anemia was defined as a hemoglobin concentration <13 g/dL in men and <12 g/dL in nonpregnant women (WHO criteria). Folate-deficiency anemia was defined as the presence of both folate deficiency and anemia. The mean hemoglobin concentration was 13.6 g/dL, and 15.9% of subjects had anemia. The median serum folate concentration was 34.2 nmol/L (15.1 ng/mL), and only 2 of 1546 participants 0.1%) were folate deficient. Both subjects were African American women with markedly elevated C-reactive protein concentrations, macrocytosis, and normal serum cobalamin concentrations; only one subject was anemic. Overall, the prevalence of folate-deficiency anemia was <0.1% (1 of 1546 subjects). Our data suggest that, after mandatory folic acid fortification, the prevalence of folate-deficiency anemia is nearly nonexistent in a community-dwelling population in the United States.

Recovery from Possible Late‐Onset Alzheimer's Dementia? Evidence from a Longitudinal Community‐Based Age‐Cohort Study

Recovery from Possible Late‐Onset <scp>A</scp>lzheimer's <scp>D</scp>ementia? Evidence from a <scp>L</scp>ongitudinal <scp>C</scp>ommunity‐<scp>B</scp>ased <scp>A</scp>ge‐<scp>C</scp>ohort <scp>S</scp>tudy

Absence of Association Between Serum Folate and Preeclampsia in Women Exposed to Food Fortification

To evaluate serum folate concentration early in pregnancy and any association with hypertensive disorders of pregnancy in a population exposed to folic acid supplementation and food fortification. This is a nested case-control study based on a prospective cohort of 7,929 pregnant women recruited in the Quebec City metropolitan area, including 214 participants who developed a hypertensive disorder of pregnancy and 428 normotensive participants in the control group matched for parity, multiple pregnancy, smoking status, gestational, and maternal age at inclusion, and duration of blood sample storage. Serum folate levels were measured at a mean of 14 weeks of gestation. More than 98% of the participants took folic acid or multivitamins before the end of the first trimester. Mean serum folate levels were accordingly high and there were no differences between women who further developed a hypertensive disorder of pregnancy compared with women in the control group (60.1 nmol/L compared with 57.9 nmol/L; P=.51). The proportion of participants with serum folate below the 10th percentile (less than 22.3 nmol/L) of age-matched women in our outpatient population was similar between groups (P=.66) and no participant had levels generally defined as folate deficiency (less than 10 nmol/L). In a general cohort of pregnant women benefiting from a national policy of folic acid food fortification combined with a high adherence to folic acid supplementation, serum folate levels are high and do not differ between women who develop a hypertensive disorder of pregnancy and women who remain normotensive. Further supplementation with higher doses is unlikely to be beneficial in such populations. II.

Early Biochemical and Hematological Response to Intramuscular Cyanocobalamin Therapy in Vitamin B12-Deficient Patients

Background: Data on early biochemical and hematological responses to cobalamin therapy in vitamin B₁₂-deficient patients are scarce. Therefore, we investigated whether cobalamin injections would include prompt biochemical and hematological responses in vitamin B₁₂-deficient patients. Subjects and Methods: Seven female patients (mean age: 69.4 years, range: 61-78) with a mean serum cobalamin level of 104 ± 38 pmol/l mean ± SD and 7 male patients (mean age: 67.0 years, range: 53-78) with a mean serum cobalamin level of 84 ± 40 (±SD) participated in the study. They were administered 1 mg i.m. cyanocobalamin per week for 3 weeks. Blood samples were collected before and 1, 3, 7, 14 and 21 days after cobalamin injection. The concentrations of plasma aminothiols and serum methylmalonic acid (MMA) were measured with high-performance liquid chromatography and gas chromatography/mass spectrometry, respectively, and hematological parameters were determined with a hematological analyzer. Results: Already 1 day after intramuscular Cobalamin injections, the concentrations of serum vitamin B₁₂ and plasma total cysteine were significantly increased while the concentrations of serum folate, plasma total homocysteine and serum MMA were decreased. Mean cell volume was also significantly decreased first after 14 days of therapy. Conclusion: Intramuscular cobalamin administration causes swift and significant changes in plasma aminothiols, whereas the first change in hematological parameters was detected only after 14 days.

Homocysteine, folate, vitamin B-12, and 10-y incidence of age-related macular degeneration

Epidemiologic evidence of a relation between serum total homocysteine (tHcy), vitamin B-12, and folate and age-related macular degeneration (AMD) is inconsistent and unresolved. In this cohort study, we aimed to investigate associations between intakes and serum concentrations of folate and vitamin B-12 or serum tHcy and 10-y AMD incidence. Serum folate, vitamin B-12, and tHcy were determined from blood samples drawn in 1997-1999 from cohort members aged ≥55 y. AMD was assessed in 1760 survivors from retinal photographs taken in 2002-2004 and 2007-2009. Total intakes of folate and vitamin B-12 were assessed by using a food-frequency questionnaire. After adjustment for age, sex, current smoking, white blood cell count, and fish consumption, each 1-SD increase in serum tHcy was associated with increased risk of incident early and any AMD [ORs (95% CIs): 1.33 (1.09, 1.63) and 1.33 (1.11, 1.60), respectively]. Participants with a serum vitamin B-12 deficiency (<185 pmol/L) had higher risk of incident early and late AMD [ORs (95% CIs): 1.58 (1.06, 2.36) and 2.56 (1.38, 4.73), respectively]. Folate deficiency (<11 nmol/L) was associated with 75% and 89% increased risk of incident early and any AMD, respectively, 10 y later. Participants who reported supplementary vitamin B-12 intake had 47% reduced risk of incident any AMD (OR: 0.53; 95% CI: 0.33, 0.85). Elevated serum tHcy and folate and vitamin B-12 deficiencies predicted increased risk of incident AMD, which suggests a potential role for vitamin B-12 and folate in reducing AMD risk.

Serum vitamin B6, folate, and homocysteine concentrations and oxidative DNA damage in Japanese men and women

ObjectiveHigher vitamin B status has been linked to a lower risk for cancer, but the underlying mechanism remains elusive. The aim of the present study was to examine the association of pyridoxal, folate, and homocysteine (Hcy) with urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage. MethodsThe participants were 500 employees (293 men and 207 women), ages 21 to 66 y, of two municipal offices in Japan. Serum pyridoxal and Hcy concentrations were measured using high-performance liquid chromatography (HPLC) method, and serum folate concentrations were measured using chemiluminescent immunoassay. Urinary 8-OHdG concentrations were measured using HPLC method. Multiple regression was used to estimate means of 8-OHdG for each tertile of pyridoxal, folate, and Hcy with adjustment for potential confounders. ResultsIn multivariate analysis, 8-OHdG concentration was inversely associated with pyridoxal concentration in men (P for trend = 0.045) but not in women. The association in men was confined to non-smokers (P for trend = 0.033) or those who consumed no or < 20 g/d of ethanol (P for trend = 0.048). 8-OHdG concentrations were not appreciably associated with folate and Hcy concentrations. ConclusionThe results suggest that vitamin B6, but not folate and homocysteine, plays a role against oxidative DNA damage in Japanese men.

Effect of Dietary Folic Acid Supplementation on Growth Performance and Hepatic Protein Metabolism in Early-Weaned Intrauterine Growth Retardation Piglets

To investigate the effects of dietary supplementation with folic acid on growth performance, hepatic protein metabolism and serum biochemical indices of early-weaned intrauterine growth retardation (IUGR) piglets, 24 male (Duroc×(Landrace×Yorkshire)) weaned (14-d-old) IUGR piglets were randomly divided into 3 treatments with 8 replicates of 1 piglet per replicate. The piglets in each treatment were fed basal diet supplementation with either 0 (control), 5 and 10 mg kg−1folic acid. The trial lasted for 21 d. Dietary folic acid supplementation reduced average daily feed intake (ADFI) (P<0.05). In addition, the average daily gain (ADG) in 10 mg kg−1 folic acid group was significantly decreased (P<0.01) and the ratio of feed:gain (F/G) increased slightly (P>0.05). Serum folic acid concentration increased (P<0.01) with increasing folic acid inclusion, however, serum homocysteine concentration decreased significantly (P>0.01). Enhanced serum urine nitrogen (SUN) and diminished serum total protein (TP) as well as liver TP content were observed in 10 mg kg−1 folic acid group (P<0.05). Furthermore, the relative mRNA expressions of insulin-like growth factor 1 (IGF-1) and mammalian target of rapamycin (m-TOR) in liver were respectively tended to reduce (P=0.06) and significantly downregulated (P<0.05) in 10 mg kg−1 group, in compared with 5 mg kg−1 group. However, when compared with control group, folic acid supplementation had no significant effect on the mRNA abundance of IGF-1 and m-TOR. The results indicated that supplementation with 10 mg kg−1 folic acid impaired growth performance and hepatic protein metabolism of early-weaned IUGR piglets while 5 mg kg−1 folic acid enriched diet exerted limited positive effects.

Obesity affects short-term folate pharmacokinetics in women of childbearing age

Maternal folate status and body mass index (BMI) are independent risk factors for neural tube defects (NTD). Population-based studies have identified an inverse association between serum folate and BMI, after adjusting for intake. The objective of this intervention study was to compare the relationship between BMI and the short-term pharmacokinetic response to an oral dose of folic acid. Healthy obese (BMI 30.0 kg m(-2); n=16) and normal-weight (BMI 18.5-24.9 kg m(-2); n=16) women of childbearing age (18-35 years) were administered a single oral dose of folic acid (400 μg). Blood samples were collected over a 10-h period to evaluate the serum folate response. Fasting baseline serum folate was lower in the obese group (P=0.005); in contrast, red blood cell folate was higher (P=0.05). Area-under-the-curve for the absorption phase (0-3 h) and peak serum folate concentrations were lower in obese versus normal-weight women (P<0.005). Overall serum folate response (0-10 h) was lower in obese versus normal-weight women (repeated-measures ANOVA, P=0.001). Data suggest body distribution of folate is significantly affected by obesity, and, should pregnancy occur, may reduce the amount of folate available to the developing embryo. These findings provide additional support for a BMI-adjusted folic acid intake recommendation for NTD risk reduction.

Detectable levels of unmetabolized folic acid in Canadian pregnant women

Unmetabolized folic acid (UMFA) in the circulation has been purported to mediate some adverse health outcomes associated with high folic acid (FA) intake. FA supplementation and mandatory FA fortification have significantly increased folate intake and blood levels in Canada. Furthermore, women are advised to take FA supplements before and during pregnancy to prevent neural tube defects. There is limited information regarding the prevalence and level of UMFA in pregnant women consuming FA containing supplements in the postfortification era. We determined the relationship between plasma UMFA and dietary folate intake, FA supplement use and folate blood measurements in 344 Canadian pregnant women participating in the prospective PREFORM Study at 11–16 wks gestation. 90% women reported FA supplement use (≥1mg FA/d) during the first trimester. UMFA determined by LC‐MS/MS was detected in 98% of participants, with a median(range) of 1.17(0.07–244.05nmol/L). UMFA represented 2.7% of total serum folate. Plasma UMFA was correlated with supplemental FA (rs=0.19, p=0.001), serum (rs=0.62, p&lt;0.01) and RBC (rs=0.17, p=0.001) folate concentrations. Further studies are warranted to determine functional ramifications of detectable UMFA and their link to health outcomes of the mother and offspring.Grant Funding Source: CIHR (MOP# 106446)

Serum Folate but Not Vitamin B-12 Concentrations Are Positively Associated with Cognitive Test Scores in Children Aged 6–16 Years

Folate and vitamin B-12 are important for nervous system functioning at all ages, with important roles in functions such as neurotransmitter synthesis. Although studies suggest a relation between folate and vitamin B-12 and cognitive function in the elderly population, there is relatively less evidence regarding these vitamins and children's cognitive function. The purpose of the study was to examine the associations of serum folate and vitamin B-12 with cognitive performance in children 6–16 y old in the NHANES III, conducted from 1988 to 1994, prior to the implementation of folic acid fortification. A cross-sectional analysis was conducted using data on 5365 children 6–16 y old from NHANES III. Serum folate and vitamin B-12 concentrations were measured, along with performance, on the Wide Range Achievement Test-Revised and the Wechsler Intelligence Scale for Children-Revised. Associations of B vitamins with cognitive performance were assessed using linear regression models adjusted for various covariates. Higher serum concentrations of folate were associated with higher reading and block design scores after adjusting for various covariates. For example, compared with the lowest quartile of folate, children in the highest quartile scored 3.28 points or 0.19 SD units higher on the reading test (P < 0.05). Vitamin B-12 was not associated with any of the test scores. In the largest study to date, higher folate concentrations were associated with better reading and block design scores. These associations appear to be biologically plausible and merit further study.

Response of serum and red blood cell folate concentrations to folic acid supplementation depends on methylenetetrahydrofolate reductase C677T genotype: Results from a crossover trial

By increasing blood folate concentrations, folic acid supplementation reduces risk for neural tube defect-affected pregnancies, and lowers homocysteine concentrations. We assessed response of red blood cell (RBC) and serum folate to folic acid supplementation, and examined association of response with the genetic polymorphism C677T of the methylenetetrahydrofolate NAD(P)H (MTHFR) gene. Randomized, controlled, crossover trial with two folic acid supplement treatment periods and a 30-week washout period. The primary outcome is blood folate (serum and RBC) concentrations. Volunteers (n = 142) aged 18-69 were randomized to two of three doses (0, 200, and 400 μg) of folic acid for 12 weeks. Serum folate response depended on treatment period with significant responses to 200 μg seen only in the second treatment periods (4.4 ng/mL or 3.4 ng/mL). Additionally, serum folate increased as folic acid dose increased to 400 μg (p < 0.01) and response was greater after the washout period (8.7 ng/mL), than after a 6-week run-in (2.3 ng/mL). The differential change attributable to a daily supplement of 400 μg compared to 200 μg was 96.8 ng/mL; while the change attributable to 400 μg compared to 0 μg was 121.4. Increases in RBC folate concentrations with 400 μg occurred within MTHFR gene mutation (C677T); and in the African American group. Serum folate concentration is responsive to modest increases in folic acid intake. RBC folate increases only with higher additional doses of folic acid supplementation, and this is true for each MTHFR C677T genotype.