Red Cell Folate Concentrations Research Articles

Serum Folate, Red Blood Cell Folate, and Zinc Serum Levels Are Related with Gestational Weight Gain and Offspring's Birth-Weight of Adolescent Mothers.

Gestational weight gain below or above the Institute of Medicine recommendations has been associated with adverse perinatal and neonatal outcomes. Very few studies have evaluated the association between serum and red blood cell folate concentrations and gestational weight gain in adolescents. Additionally, zinc deficiency during pregnancy has been associated with impaired immunity, prolonged labor, preterm and post-term birth, intrauterine growth restriction, low birth weight, and pregnancy-induced hypertension. The purpose of our study is to evaluate the association between serum concentrations of zinc, serum folate, and red blood cell folate, with the increase in gestational weight and the weight and length of the newborn in a group of adolescent mothers from Mexico City. In our study, 406 adolescent-neonate dyads participated. The adolescents' median age was 15.8 years old. The predominant socioeconomic level was middle-low (57.8%), single (57%), 89.9% were engaged in home activities, and 41.3% completed secondary education. Excessive gestational weight gain was observed in 36.7% of cases, while insufficient gestational weight gain was noted in 38.4%. Small for gestational age infants were observed in 20.9% of the sample. Low serum folate (OR 2.1, 95% CI 1.3-3.3), decreased red blood cell folate (OR 1.6, 95% CI 1.0-2.6), and reduced serum zinc concentrations (OR 3.3, 95% CI 2.1-5.2) were associated with insufficient gestational weight gain. Decreased serum zinc levels (OR 1.2, 95% CI 1.2-3.4) were linked to an increased probability of delivering a baby who is small for their gestational age. Low serum folate, red blood cell folate, and serum zinc concentrations were associated with gestational weight gain and having a small gestational age baby. Both excessive and insufficient gestational weight gain, as well as having a small gestational age baby, are frequent among adolescent mothers.

Impact of the increasing concentrations of selected perfluoroalkyl acids on the observed concentrations of red blood cell folate among US adults aged ≥20 years.

For the first time (N = 6291), a study was undertaken to estimate associations between the concentratio ns of red blood cell folate (RBCF) and concentration of six perfluoroalkyl acids (PFAAs), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) for US adults aged ≥20 years by fitting regression models for the data from National Health and Nutrition Examination Survey for 2007-2014. In almost consistent fashion, increasing concentrations of PFAAs were associated with decreasing concentrations of RBCF. For the total population, for a 10% increase in the concentrations of PFOA, PFOS, PFDA, PFHxS, PFNA, and PFUnDA, percent decreases in RBCF concentrations were found to be 0.33%, 0.66%, 0.83%, 0.16%, 0.89%, and 0.43%, respectively. RBCF concentrations of PFAAs were found to be 1104, 1042, 100, and 936 nmol/L across the four quartiles of PFOS; 112, 1068, 1009, and 948 nmol/L across the four quartiles of PFDA; 1125, 1054, 1005, and 967 nmol/L across the four quartiles of PFNA; and 1099, 1094, 989, and 952 nmol/L across the four quartiles of PFUnDA. Perfluorinated carboxylic acids with carbon chain length > 8 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 8. Perfluorinated chemicals with a sulfonic group with carbon chain length > 6 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 6. The degree to which concentrations of RBCF decrease varied by age, gender, and race/ethnicity. Non-Hispanic blacks as compared to non-Hispanic whites and Hispanics had the lowest decreases in RBCF concentrations. Mechanisms responsible for negative associations between RBCF and PFAA concentrations are not known and will need to be researched further.

Wellness foods based on the health benefits of fruit: Gold kiwifruit for immune support and reducing symptoms of colds and influenza

Fruits are excellent health foods and ingredients for functional foods. Plant & Food Research is developing new fresh and processed foods to promote gut health and immunity and protect from oxidative stress. The research involves testing using cell-based assays and animal models and validating health benefits in human trials. Using ZESPRI® GOLD Kiwifruit as an example, extracts stimulated human innate and adaptive immunity in vitro and a puree, but not a juice, enhanced a weak gut-associated immune response in mice. To validate an associated health benefit, a human trial determined the effects of gold kiwifruit consumption on symptoms of colds and influenza in older adults (≥ 65 years). Gold kiwifruit consumption significantly reduced head congestion and sore throat symptoms as well as plasma lipid peroxidation and significantly increased plasma vitamin C, α-tocopherol and lutein/zeaxanthin concentrations, and red cell folate concentrations. In a subsequent trial, regular consumption of gold kiwifruit by pre-school children (2-5 years) resulted in an overall reduction in the incidence of cold and influenza-like illnesses as well as a reduction in their symptoms. The results suggest that gold kiwifruit can modulate the immune system in a positive way and that consumption can improve health by reducing symptoms and incidences of colds and influenza, in groups whose immune status may result in a greater risk of contracting these types of infections.

Is low iron status a risk factor for neural tube defects?

Folic acid supplements can protect against neural tube defects (NTDs). Low folate and low vitamin B12 status may be maternal risk factors for having an NTD affected pregnancy. However, not all NTDs are preventable by having an adequate folate/ B12 status and other potentially modifiable factors may be involved. Folate and vitamin B12 status have important links to iron metabolism. Animal studies support an association between poor iron status and NTDs, but human data are scarce. We examined the relevance of low iron status in a nested NTD case-control study of women within a pregnant population-based cohort. Pregnant women were recruited between 1986 and 1990, when vitamin or iron supplementation in early pregnancy was rare. Blood samples, taken at an average of 14 weeks gestation, were used to measure ferritin and hemoglobin in 64 women during an NTD affected pregnancy and 207 women with unaffected pregnancies. No significant differences in maternal ferritin or hemoglobin concentrations were observed between NTD affected and nonaffected pregnancies (case median ferritin 16.9 µg/L and hemoglobin 12.4 g/dl versus 15.4 µg/L and 12.3g/dl in controls). As reported previously, red cell folate and vitamin B12 concentrations were significantly lower in cases. Furthermore, there was no significant association of iron status with type of NTD lesion (anencephaly or spina bifida). We conclude that low maternal iron status during early pregnancy is not an independent risk factor for NTDs. Adding iron to folic acid for periconceptional use may improve iron status but is not likely to prevent NTDs.

Reticulocyte Folate Concentration: A Tool To Monitor Immediate Folate Availability

The utilization of folic acid during erythropoiesis is widely known and accepted in medical literature and deficiency is known to cause a characteristic megaloblastic anemia resulting from the inhibition or ineffective synthesis of DNA. Although the resultant megaloblastic anemia may take considerable time before evidence or symptoms present, there are more acute changes visualized on peripheral smear that are representative of a functional folate deficiency. In addition to erythrocyte macrocytosis, hypersegmentation of neutrophils can also be seen. Often times, despite these visualized changes measurement of serum folate and/or total red cell folate yields a result within the accepted “normal” range of the assay. It has been demonstrated that these visualized characteristics represent a functional folate deficiency and can be overcome with folic acid supplementation regardless of the measured folic acid levels indicating a yet to be understood mechanism of folate utilization. Here, we sought to measure the folic acid levels in the earliest erythrocyte progenitors in peripheral circulation, the reticulocytes. Methods Reticulocytes were isolated using anti-CD71 (the transferrin receptor) coated magnetic beads. After separation, a sample slide was made utilizing methylene blue for visual confirmation of reticulocyte isolation. The reticulocytes were then lysed with citric acid and a Nanodrop-1000 spectrophotometer was used to determine absorbance at 413 nanometers. This absorbance was used to determine the sample hemoglobin concentration from a simple calibration curve. The sample folic acid level was then determined using the lysing method utilizing mouse monoclonal anti-folate binding protein, paramagnetic particles coated in anti-mouse IgG, human serum albumin and milk folate binding protein. Results were calculated as nanogram of folate per gram of hemoglobin. Results Twenty-five samples from normal individuals, not taking folate supplements, were analyzed. The range of results was 2.51 to 17.38 with a mean level of 9.61. Conclusion This protocol effectively and efficiently allows for isolation of reticulocytes in numbers high enough for measurement of folate in nanogram per gram of hemoglobin. By this method we show the normal reticulocyte folate level to be approximately 3-15 ng/g of Hgb. This figure is consistent with the normal red cell folate concentration. Further analysis is planned for comparing these results in patients with a suspected functional folate deficiency but “normal” red cell folate levels. Efficient isolation of reticulocytes and measurement of folate levels will allow us to probe the underlying cause of acute folate deficiency seen in very sick patients. Disclosures: No relevant conflicts of interest to declare.

Bioavailability of folic acid and L‐5‐methyltetrahydrofolic acid in fortified bread: a randomized placebo‐controlled trial

Folic acid fortification has been introduced in several countries to reduce the incidence of neural tube defects. However, it could mask the hematologic signs of vitamin B12 deficiency. L‐5‐methyltetrahydrofolic acid (MTHF), which is unlikely to mask vitamin B12 deficiency, may be a safer fortificant, but is not stable in most food matrices. Microencapsulation of MTHF with antioxidant sodium ascorbate is an effective means of preventing loss during baking and storage. The aim of the study was to investigate the bioavailability of microencapsulated MTHF in bread in a 16‐wk, double‐blind, randomized placebo trial. Healthy volunteers 18–45 y (n=45) were randomly assigned to bread containing MTHF (452 μg), folic acid (400 μg) or placebo. Fasting blood was analyzed for red cell and plasma folate concentrations at baseline, 8, and 16 wks. At 16 wk, after adjustment for baseline concentrations, mean (95% CI) red cell folate was 572 (341, 804) and 428 (200, 656) nmol/L higher in the MTHF (P<0.001) and folic acid (P=0.002) groups, respectively, than in the placebo group. Mean plasma folate was 28 (15, 41) and 26 (13, 39) nmol/L higher in the MTHF (P<0.001) and folic acid (P=0.01) groups, respectively, than in the placebo group. In conclusion, bread fortified with MTHF was at least as effective as folic acid in raising red cell and plasma folate concentrations in this population. (Supported by the Advanced Food Materials Network)

Systemic folate status, rectal mucosal folate concentration and dietary intake in patients at differential risk of bowel cancer (The FAB2 Study)

Folate has been strongly implicated in the aetiology of colorectal cancer. However, the relationship between dietary folate intake, rectal mucosal folate status and colorectal cancer risk is uncertain. The study aimed to estimate nutrient intakes and measure systemic folate status and rectal mucosal folate concentration in people at differential risk of developing colorectal cancer. Two hundred and twenty-eight individuals were recruited from gastroenterology clinics and subdivided into three patient groups: untreated colorectal cancer (n = 43), adenomatous polyps (n = 90) or normal bowel (n = 95). Biopsies from macroscopically normal rectal mucosa and blood were collected and used for the measurement of rectal mucosal 5-methyltetrahydrofolate (5-MeTHF) and systemic markers of folate status, respectively. Nutrient intake was estimated using a validated food frequency questionnaire. Dietary intake variables, plasma 5-MeTHF and red cell folate and plasma homocysteine concentrations were similar in all three subject groups and 95% CI fell within normal range for each variable. Rectal mucosal 5-MeTHF concentration was higher in the normal mucosa of adenomatous polyp patients than in normal subjects (P = 0.055). Rectal mucosal 5-MeTHF was associated significantly with plasma folate (P < 0.001, r = 0.294), red cell folate (P = 0.014, r = 0.305), plasma homocysteine (P = 0.017, r = -0.163) and dietary folate intake (P = 0.036, r = 0.152). This study demonstrates adequate folate status of patients attending gastroenterology clinics for the investigation of bowel symptoms, with no significant difference in dietary intakes or systemic folate status indices according to diagnosis. Rectal mucosal 5-MeTHF concentrations were elevated in adenomatous polyp patients, but failed to reach significance. Further studies are required to determine the biological significance of this observation.

Micronutrient, Antioxidant, and Oxidative Stress Status in Children With Severe Cerebral Palsy

Markers indicative of micronutrient and antioxidant status in children with cerebral palsy (CP) were explored due to these children's well-documented issues with food intake and the limited biochemical literature. Children aged 4 to 12 years with marked CP (n = 24) and controls (n = 24) were recruited. The CP group represented orally (O) or enterally fed (E) children. Concentrations of red cell folate (RCF), magnesium, superoxide dismutase (SOD), glutathione reductase, and peroxidase were measured, as well as serum methylmalonic acid and vitamin C. Plasma hemoglobin, C-reactive protein, α-tocopherol, cholesterol, zinc, protein carbonyls, and total antioxidant capacity were also quantified. Data are reported as mean (SD) and z scores where values differ with age. Many similarities existed, but zinc z scores were reduced in O (-1.10 [0.83]) vs controls (-0.54 [0.54]) (P < .05), as well as for glutathione reductase in O (10.15 [1.69]) vs E (12.22 [2.41]) and controls (11.51 [1.67]) (P < .05). RCF was greatly increased in E (1422 [70]) vs O (843 [80]) and controls (820 [43]) (P < .001). SOD was decreased in E (24.3 [1.4]) vs controls (27.0 [2.8]) (P < .05). Considering their vast impact on physiology, micronutrients should be routinely monitored in orally fed children with swallowing disorders and dietary limitations. Excessive intakes, particularly long term in enterally fed children, should also be monitored in view of their potential for competitive inhibition, particularly at high levels.

Methylation capacity in children with severe cerebral palsy

Methylation cycle and folate-mediated one-carbon metabolism maintenance is important for many physiological processes including neurotransmitter regulation, nerve myelination and DNA synthesis. These processes play an indispensible role in growth and development, as well as in cognitive function and neuromuscular stability, which are key issues in children with severe cerebral palsy (CP). Blood samples were collected from children with severe CP (n = 24) and age-matched typically developing healthy controls (n = 24), as an exploratory study. The CP group was divided into orally (O) or enterally fed via percutaneous endoscopic gastrostomy (E). Concentrations of red cell folate (RCF), methylmalonic acid (MMA), mean cell volume (MCV), homocysteine (Hcy), cystathionine, choline, betaine and urate were assayed. Homocysteine was increased in both O mean (±SD) = 6·28 (±1·81 μM) and E = 6·03 (±1·28), vs. controls = 5·07 (±0·98) P = 0·02. Higher MMA was found in controls = 157 (±54) and O = 141 (±101), vs. E = 88(±21) P = 0·05. RCF was higher in E = 1422 (±70 nM) vs. O = 843 (±80) and controls = 820 (±43) P < 0·001. MCV z-scores were elevated in E = 3·1 (±1·8) and O = 1·1 (±1·1) compared with controls = -0·2 (±1·1) P < 0·001. Urate was significantly reduced in O = -0·64 (±1·38) and E = -0·87 (±0·71), vs. controls = 0·18 (±0·62) P = 0·006. Raised MCV in the presence of elevated red cell folate, adequate B12 status and low plasma urate suggest potential methyltetrahydrofolate trapping and impaired purine synthesis. Well-documented malnutrition issues in O may explain differences between CP groups. These data support the hypothesis of possible dysregulation in methylation capacity and/or folate one-carbon metabolism, although more research is needed to elucidate a precise mechanism.

Marked Gender Difference in Plasma Total Homocysteine Concentrations in Indian Adults with low Vitamin B12

Plasma total homocysteine (tHcy) is higher in men than women. To explore the gender differences in tHcy in relation to determinants of one-carbon metabolism in Indian people with low B₁₂ and adequate folate. The study took place in rural and urban areas of Pune, India. Participants were 441 men from the cross-sectional Coronary Risk of Insulin Sensitivity in Indian Subjects study (CRISIS) and premenopausal wives of 146 men (median ages 38 and 34 years, respectively). Gender difference in fasting tHcy in relation to plasma albumin and creatinine concentrations, lifestyle factors, diet and lean mass, plasma B₁₂ and red cell folate (RCF) was assessed. Prevalence of high tHcy (> 15 µmol/L, median 14.4 µM) was 40 %, low B12 (< 150 pmol/L, 114 pmol/L) 66 %, and low RCF (< 283 nmol/L, 525 nmol/L) 8 %. Men had higher (1.8x) plasma tHcy concentrations (16.2 µmol/L) than women (9.5 µmol/L). Only 50 % of the gender difference was explained by age, lean mass, B₁₂, and RCF. The difference remained after controlling for other explanatory variables. Women with a tHcy of 9.3 µM had the same B₁₂ concentration (129 pmol/L) as men with a tHcy of 15 µM; and for a tHcy of 10.0 µmol/L women had the same RCF concentration (533 nmol/L) as men with a tHcy of 15 µmol/L. Adult Indian women have markedly lower tHcy concentrations compared to men. This suggests a lower threshold for supplementation to improve reproductive and cardiovascular outcomes.

B-vitamin status and cognitive function in older people

Background: Dementia is a growing public health concern; there are currently 750 000 people living with the disease in the UK. By 2025 this number is expected to rise to over a million with costs estimated at over £20 billion per annum (Alzheimer's society, 2010). Diet is considered to play an important role in the development of cognitive impairment with recent research now identifying a role for B vitamins (Kado et al., 2005). The aim of this observational study was to investigate the association between B-vitamin status (in particular, vitamin B12 and folate) and cognitive function in older people. Methods: This study was conducted as part of a larger ongoing observational study of older Irish adults; Trinity Ulster Department of Agriculture (TUDA) study. Patients who were not born in the Republic of Ireland or Northern Ireland and those with severe dementia were excluded. A non-fasting blood sample (50 mL) was collected; routine clinical markers of health were measured as well as B vitamin status [serum folate, red cell folate (RCF), serum B12 and holotranscobalamin (holoTC)]. Cognitive function was measured using various cognitive performance tests including Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Depression and anxiety were measured using the Centre of Epidemiological Studies Depression (CES-D) scale and Hospital Anxiety and Depression (HAD) scale respectively to adjust for these possible confounders of cognitive performance. Data were analysed statistically using independent t tests, chi-squared tests and Pearsons correlations. Ethical approval was granted for the recruitment of patients over the age of 60 years from outpatient clinics and GP practices within two health trusts in Northern Ireland. Results: The cohort (n = 100) was split for analysis purposes into those aged 60–69 years (n = 70) and those aged ≥70 years (n = 30). There were no significant differences between the groups in terms of cognitive scores or B vitamin status (some of the results are shown in Table 1). No significant associations were found between B vitamin status and cognitive scores in the group as a whole or in the younger age group. However, in those aged 70 years or older, folate status (RCF concentrations) was found to be significantly associated with MMSE scores (r = 0.370, P = 0.048) while the association between RCF and RBANS was approaching significance (r = 0.358, P = 0.057) in those aged 70 or older. No associations were found between vitamin B12 and cognitive scores in either of the age sub-groups. Table 1. Differences between those aged 60–69 years and those aged ≥70 years in terms of cognitive scores & B vitamin status Aged 60–69 years Aged ≥70 years P value Mean (SD) Mean (SD) RBANS 86.4 (12.8) 82.5 (14.1) 0.169 MMSE 27.5 (2.7) 27.5 (3.2) 0.822 RCF (nM) 1092.2 (96.9) 1099.0 (96.0) 0.737 Discussion: The results are in line with the current literature (Tettamanti et al., 2006). Some observational data have also found associations between vitamin B12 and cognitive impairment; however, this was not the case with the present study. These findings may suggest a possible role for folate (but not B12) in certain types of dementia, such as Alzheimer's disease, as status was not associated with FAB which is used mainly in the diagnosis of frontotemporal dementia. Conclusion: Future research is warranted to confirm these associations in larger cohort trials involving two time points which will pave the way for randomised controlled trials to examine cause-and-effect relationships between B-vitamin status and cognitive performance.

Cobalamin supplementation improves motor development and gastrointestinal reflux in moderately deficient infants

Folate plays a critical role in the prevention of uracil incorporation into DNA and hypomethylation of DNA. This activity is compromised when vitamin B12 concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation, DNA hypomethylation and mitochondrial DNA deletions. In vivo studies show that folate and/or vitamin B12 deficiency and elevated plasma homocysteine (a metabolic indicator of folate deficiency) are significantly correlated with increased micronucleus formation and reduced telomere length respectively. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is greater than 100 nmol/L. Intervention studies in humans show (a) that DNA hypomethylation, chromosome breaks, uracil incorporation and micronucleus formation are minimised when red cell folate concentration is greater than 700 nmol/L and (b) micronucleus formation is minimised when plasma concentration of vitamin B12 is greater than 300 pmol/L and plasma homocysteine is less than 7.5 μmol/L. These concentrations are achievable at intake levels at or above current recommended dietary intakes of folate (i.e. >400 μg/day) and vitamin B12 (i.e. >2 μg/day) depending on an individual's capacity to absorb and metabolise these vitamins which may vary due to genetic and epigenetic differences.

ORIGINAL ARTICLE: Lack of association between elevated mean red cell volume and haematological toxicity in patients receiving long‐term methotrexate for rheumatoid arthritis

It has been suggested that elevated mean red cell volume (MCV) may be a predictor of haematological toxicity in rheumatoid arthritis (RA) patients receiving methotrexate (MTX). We wished to identify whether there was an association between MCV, red cell folate and haematological toxicity in patients on MTX monotherapy for the long-term management of RA. Evidence of haematological toxicity was sought by note review of patients recruited in a cross-sectional study of MTX monotherapy in RA. Retrospective data included MCVs from before MTX initiation and after 3 and 6 months of treatment. Data were collected prospectively every 6 months for up to 2 years after enrolment. Any record of cytopenia or the development of haematological malignancy was recorded from commencement of MTX until the present day. Red cell folate concentrations were tested on enrolment to the study. A total of 165 patients was included, 74.5% female, median disease duration 7 years (range 3 months-57 years). The median duration of MTX treatment was 74.9 months (range 10-241 months) giving 1030.2 patient-years of MTX exposure. Twenty-four patients (14.5%) had a MCV > 98 fL on study entry. Evidence of haematological abnormality was found in six patients (3.6%); chronic lymphocytic leukaemia (1), persistent lymphocytosis (1), persistent monocytosis (1) and neutropenia (3). There was no association between red cell folate or MCV and haematological toxicity. Neutropenia and pancytopenia are rare side-effects of MTX therapy in this cohort. Elevated MCV or low mean red cell folate does not appear to be associated with haematological malignancy or toxicity in this cohort of patients on long-term MTX therapy.

Homocysteine, red cell, and plasma folate concentrations and birth weight in Italian women: results from a prospective study

Objective. A prospective cohort study conducted in Italy on homocysteine and red cell folate levels in pregnancy and pregnancy outcome.Methods. A cohort of pregnant women was identified in 21 Italian obstetric centers. Women were eligible at 8th–10th week of gestation. All women were followed up to delivery in order to collect information on pregnancy outcome and birth weight (BW).Results. Two hundred forty-four women were included in the analysis. In women not reporting current use of folate at study entry, the median homocysteine levels (μmol/l) were 7.9, 8.1, and 8.5 at the 8th–10th, 16th, and 22nd week of gestation, respectively; the median red cells folate levels (nmol/dl) were 3.9, 6.1, and 7.0. The mean BW tended to be lower in the 2nd and 3rd tertile of homocysteine levels in comparison with the 1st tertile (p < 0.05 at the 8th–10th and 22nd week). The mean week of gestation at birth was higher in subjects in the 2nd and 3rd tertile of red cell folate at the 8th–10th and 16th week of gestation.Conclusion. This study estimated homocysteine and plasma folate levels in Italian pregnant women and suggested that homocysteine level was associated with BW.

Relationship between maternal growth, infant birthweight and nutrient partitioning in teenage pregnancies

Teenagers are susceptible to delivering small-for-gestational-age (SGA) infants. Previous studies suggest that maternal growth may contribute, as a result of preferential nutrient partitioning to the mother. We investigated the impact of maternal growth on birthweight in pregnant teenagers in the UK, and examined endocrine mediators of nutrient partitioning. A prospective observational multicentre study, About Teenage Eating, conducted between 2004 and 2007. Four hospitals in socially-deprived areas of Manchester and London. A total of 500 pregnant adolescents (14-18 years of age) with a singleton pregnancy were recruited at 10-21 weeks of gestation, with follow-up studies on 368 subjects. A cohort of 80 pregnant adults (25-40 years of age) provided a control group for determining growth. Skeletal growth, weight gain and skinfold thickness were measured from first to third trimester, together with maternal levels of micronutrients and metabolic hormones: insulin-like growth factor (IGF) system and leptin. Dietary analyses were performed. SGA birth. Maternal growth was not associated with SGA birth: growing mothers delivered more large-for-gestational-age infants (OR 2.51; P < 0.05). Growers had greater weight gain (P < 0.001), fat accrual (P < 0.001) and red cell folate concentrations (P < 0.01) than non-growers. Maternal IGF-I (P < 0.01) and leptin (P < 0.001) were positively associated with maternal and fetal growth, whereas IGF-I (P < 0.001) was negatively associated. Teenagers that were underweight at booking or with low weight gain were at greater risk of SGA birth. Maternal growth was not detrimental to fetal growth in this UK population of teenagers. Greater weight gain and higher concentrations of IGF-I in growing teenagers may provide anabolic drive for maternal and fetal growth.

The Reduced Folate Carrier (SLC19A1) c.80G&gt;A Polymorphism is Associated with Red Cell Folate Concentrations Among Women

Low folate status may be a consequence of suboptimal intake, transport or cellular utilization of folate and, together with elevated homocysteine, is a recognized risk factor or marker for several human pathologies. As folate transport across cell membranes is mediated in part by the reduced folate carrier (RFC1), variants within SLC19A1, the gene that encodes RFC1, may influence disease risk via an effect on folate and/or homocysteine levels. The present study was undertaken to assess the association between the SLC19A1 c.80G>A polymorphism and folate/homocysteine concentrations in healthy young adults from Northern Ireland. The SLC19A1 c.80G>A polymorphism was not strongly associated with either serum folate or homocysteine concentrations in either men or women. However, in women, but not in men, this polymorphism explained 5% of the variation in red blood cell (RBC) folate levels (P= 0.02). Relative to women with the SLC19A1 c.80GG genotype, women with the GA and AA genotypes had higher RBC folate concentrations. Consequently, compared to women with the SLC19A1 c.80GA and AA genotypes, women who are homozygous for the 80G allele may be at increased risk of having a child affected with a neural tube defect and of developing pathologies that have been associated with folate insufficiency, such as cardiovascular disease.

Social and ethnic differences in folic acid use preconception and during early pregnancy in the UK: effect on maternal folate status

The role of folate supplementation in preventing neural tube defects is well known; however, preconception supplement use continues to be low, especially amongst the socially disadvantaged. The present study explored periconception folic acid supplement use in a socially deprived, ethnically diverse population. Pregnant women (n = 402) in the first trimester of pregnancy were recruited in East London. Using a researcher led questionnaire, details were obtained regarding social class, ethnicity and folic acid use. Red cell folate levels were determined for 367 participants during the first trimester. Although 76% of participants reported using folic acid supplements during the first trimester, only 12% started preconception and a further 17% started before neural tube closure. Mothers from higher social groups or with higher levels of education were more likely to use folic acid and started taking it earlier. Ethnic differences were also seen in preconception usage (Africans, 5%; West Indians, 8%; Asians, 12%; Caucasians, 19%; P = 0.038). Participants who took folic acid supplements had significantly higher mean (SD) red cell folate concentrations than those who took none [936 (*\1.6) and 579 (*\1.6) nmol L(-1), respectively; P < 0.001]. Folic acid supplement use preconception and prior to neural tube closure continues to be low, exhibiting both social and ethnic disparities.

Involvement of ApoE E4 and H63D in Sporadic Alzheimer's Disease in a Folate-Supplemented Ontario Population

Dysregulation of iron homeostasis is implicated in Alzheimer's disease (AD). In this pilot study, common variants of the apolipoprotein E (APOE) and HFE genes resulting in the iron overload disorder of hereditary hemochromatosis (C282Y, H63D and S65C) were evaluated as factors in sporadic AD in an Ontario sample in which folic acid fortification has been mandatory since 1998. Laboratory studies also were done to search for genetic effects on blood markers of iron status, red cell folates and serum B12. Participants included 58 healthy volunteers (25 males, 33 females) and 54 patients with probable AD (20 males, 34 females). Statistical analyses were interpreted at the 95% confidence level. Contingency table and odds ratio analyses supported the hypothesis that in females of the given age range, E4 significantly predisposed to AD in the presence but not absence of H63D. In males, E4 significantly predisposed to AD in the absence of H63D, and H63D in the absence of E4 appeared protective against AD. Among E4+ AD patients, H63D was associated with significant lowering of red cell folate concentration, possibly as the result of excessive oxidative stress. However, folate levels in the lowest population quartile did not affect the risk of AD. A model is presented to explain the experimental findings.

Reassessing folic acid consumption patterns in the United States (1999–2004): potential effect on neural tube defects and overexposure to folate

Background: In the United States, folic acid fortification of cereal- grain foods has significantly increased folate status. However, blood folate concentrations have decreased from their postfortification high as a result, in part, of decreasing food fortification concentrations and the popularity of low-carbohydrate weight-loss diets. Objectives: The objectives of the study were to quantify changes in folate intake after folic acid fortification and to estimate the effect on neural tube defect (NTD) occurrence. Design: Expanding on an earlier model, we used data from 11 intervention studies to determine the relation between chronic folate intervention and changes in steady state serum folate concentrations. With serum folate data from the National Health and Nutrition Examination Survey (NHANES), we used reverse prediction to calculate postfortification changes in daily folate equivalents (DFEs). With the use of NHANES red blood cell folate data and a published equation that related NTD risk to maternal red cell folate concentrations, we calculated NTD risk. Results: Folate intake decreased by ≈130 μg DFE/d from its postfortification high, primarily as a result of changes seen in women with the highest folate status. This decrease in folate intake was predicted to increase the incidence of NTD by 4–7%, relative to a predicted 43% postfortification decrease. In addition, the number of women consuming >1 mg bioavailable folate/d decreased. Conclusions: Folate consumption by women of childbearing age in the United States has decreased. However, the decrease in those women with the lowest folate status was disproportionately small. Consequently, the effect on NTD risk should be less than would be seen if a uniform decrease in folate concentrations had occurred. These results reinforce the need to maintain monitoring of the way fortification is implemented.

Reassessing folic acid consumption patterns in the United States (1999–2004): potential effect on neural tube defects and overexposure to folate

In the United States, folic acid fortification of cereal- grain foods has significantly increased folate status. However, blood folate concentrations have decreased from their postfortification high as a result, in part, of decreasing food fortification concentrations and the popularity of low-carbohydrate weight-loss diets. The objectives of the study were to quantify changes in folate intake after folic acid fortification and to estimate the effect on neural tube defect (NTD) occurrence. Expanding on an earlier model, we used data from 11 intervention studies to determine the relation between chronic folate intervention and changes in steady state serum folate concentrations. With serum folate data from the National Health and Nutrition Examination Survey (NHANES), we used reverse prediction to calculate postfortification changes in daily folate equivalents (DFEs). With the use of NHANES red blood cell folate data and a published equation that related NTD risk to maternal red cell folate concentrations, we calculated NTD risk. Folate intake decreased by approximately 130 microg DFE/d from its postfortification high, primarily as a result of changes seen in women with the highest folate status. This decrease in folate intake was predicted to increase the incidence of NTD by 4-7%, relative to a predicted 43% postfortification decrease. In addition, the number of women consuming >1 mg bioavailable folate/d decreased. Folate consumption by women of childbearing age in the United States has decreased. However, the decrease in those women with the lowest folate status was disproportionately small. Consequently, the effect on NTD risk should be less than would be seen if a uniform decrease in folate concentrations had occurred. These results reinforce the need to maintain monitoring of the way fortification is implemented.