The Folate Concentration and/or Folic Acid Metabolites in Plasma as Factor for COVID-19 Infection

Background: The lowest risk of having a child with a neural tube defect (NTD) was related to red blood cell (RBC) folate concentrations of >906 nmol/L. For NTD prevention, it is recommended that women use periconceptional supplementation of 400 µg/day folic acid. Using this dose previous studies indicate that RBC folate >906 nmol/L was not reached within four weeks of supplementation. Objective: The effectiveness of a multivitamin/multimineral supplement containing 800 µg folic acid (verum) was evaluated using RBC folate concentration exceeding 906 nmol/L as primary endpoint. In addition, the time frame of achieving the threshold level was established as well as the effect of supplementation of other B vitamins on folate metabolism. Subjects and Methods: 46 healthy females received 800 µg/day of folic acid or placebo for 16 weeks. Blood samples were collected in four-week intervals. Plasma and RBC folate were measured with the microbiological method. Results: Mean (±SED) RBC folate increased over time to 1430±53 nmol/L, but did not reach a steady state after 16 weeks of intervention. Mean time to reach the target level was 4.2 ± 3.5 weeks in the verum group. Intake of verum also led to an increase over time of plasma folate. Conclusions: Preventive RBC folate concentration of more than 906 nmol/L can be reached within four weeks of supplementation with daily intake of 800 µg folic acid. With respect to NTD prevention, we suggest the re-evaluation of the current recommendation of folic acid supplementation.

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84 Folate-methionine cycle and folate transport in developing buffalo embryos

Reproduction Fertility and Development ◽

10.1071/rdv32n2ab84 ◽

2020 ◽

Vol 32 (2) ◽

pp. 168

Author(s):

S. Ansari ◽

S. Jamwal ◽

S. Saini ◽

R. Singh ◽

D. Malakar

Keyword(s):

Folic Acid ◽

Carbon Metabolism ◽

Ovarian Tissue ◽

Cumulus Cells ◽

Folate Transport ◽

Nucleotide Synthesis ◽

Folate Concentration ◽

Vitamin B9 ◽

Methionine Cycle ◽

Folate Transporters

Periconceptional folic acid is known to have a major role in the prevention of neural tube defects, leading to global recommendations for folic acid supplementation before and in early pregnancy. Maternal folate throughout pregnancy may have other roles in offspring health, including neurodevelopment and cognitive performance in childhood. Folate and folic acid (vitamin B9) act as a co-enzyme essential for single carbon metabolism, a network of pathways involved in several biological processes including nucleotide synthesis, DNA repair, and methylation reactions. In general, rapidly growing and multiplying cells require an adequate supply of folate. A primary deficiency of natural folate resulting in an increase of the total homocysteine concentration may be detrimental to the quality of the oocyte, subsequent fertilisation, embryogenesis, implantation, and fetal development. However, to date, folate-methionine metabolism and folate transport have not been studied in developing buffalo embryos. The present study details transcript expression for genes encoding key enzymes in the linked folate-methionine cycles in the ovary tissue, cumulus cells, immature oocytes, IVM oocytes, and pre-implantation embryos and also estimates the folate concentration in follicular fluid (FF) of buffalo. The FF was pooled and collected by aspiration of different sizes of surface follicles (2-8mm diameter). The total number of analysed samples was three, with different dilutions and estimation of folate in FF of buffalo done by chemiluminescence assay. Total RNA was extracted from oocytes, cumulus cells, ovarian tissue, and embryos produced from IVF. RT-PCR was performed to analyse the expression of folate-methionine cycle enzymes and folate transporters. Transcripts for all the enzymes of the folate-methionine cycle (i.e. SHMT, MTR, MTRR, MAT1A, MAT2B, GNMT, AHCY, CBS, and DHFR) and folate transporters (FOLR1, FOLR2) and reduced folate carrier (SLC19A1) were expressed in ovarian tissue, cumulus cells, oocytes, and pre-implantation embryos. Immunocytochemical analysis revealed FOLR2 and SLC19A1 protein expression on the plasma membrane and/or cytoplasm of the oocytes and embryos, and FOLR1 in the nucleus of pre-implantation embryos. The folate concentration in FF was 24ngmL−1. This is the first report to examine the concentration of folate in FF and revealed the identification of transcripts in different samples of buffalo species. The presence of these enzymes could have a profound effect on single-carbon metabolism within the ovary and pre-implantation embryo, therefore indicating that folate from FF is being disseminated through folate receptors within oocytes and embryos to participate in the folate pathway. This study advocates the necessity for examination of the result of folate supplementation throughout invitro embryo production for improving the quality and quantity of transferable blastocysts and subsequently live calf births in buffalo.

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Red blood cell folate concentrations in term newborns: recent findings in the Slovak Republic

Biologia ◽

10.2478/s11756-014-0482-5 ◽

2014 ◽

Vol 69 (12) ◽

Author(s):

Tatiana Reváková ◽

Alena Vasilenková ◽

Darina Behúlová ◽

Margita Galliková ◽

Ingrid Brucknerová

Keyword(s):

Folic Acid ◽

Blood Cell ◽

Red Blood Cell ◽

Slovak Republic ◽

The Body ◽

Folate Concentration ◽

Term Newborns ◽

Multivitamin Supplements ◽

Concentration Levels

AbstractFolate plays one of the most important functions for nucleotide biosynthesis and cellular methylation reactions in cells. Folate-mediated one-carbon metabolism is essential for metabolic processes in the human body. During periods of rapid cell growth, such as perinatal period, increased amounts of folate are required. The determination of red blood cell (RBC) folate concentration levels is the most accurate indicator of long-term folate level status in the body. This prospective study determined RBC folate concentration levels on the first day of life from umbilical cord blood samples in the whole group of full-term newborns (n = 150), who were hospitalized at the Department of Neonatology at the University Hospital in Bratislava. Immunochemical analysis for the determination of folate levels in erythrocytes was performed (Roche Diagnostics, Germany). Mothers were asked to select different types of food and use folic acid or other multivitamin supplements containing also folic acid. Our results of RBC folate ranged from 625 to 1748 ng/mL (5th–95th percentile). The median was 935 ng/mL and deficiency was not observed in any sample. RBC folate concentration levels in newborns due to mother’s intake of multivitamin supplements were significantly increased (p = 0.02). No differences were observed in the levels of RBC folate concentration when mothers used only folic acid. The RBC folate concentration tended to change based on many factors on both the mother’s and the newborn’s sides. Our results showed different results of RBC folate when focused on neonatal period and maternal intake of vitamins during pregnancy.

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Folate nutrition in the kid

British Journal Of Nutrition ◽

10.1079/bjn19720127 ◽

1972 ◽

Vol 27 (3) ◽

pp. 571-583 ◽

Cited By ~ 26

Author(s):

J. E. Ford ◽

G. S. Knaggs ◽

D. N. Salter ◽

K. J. Scott

Keyword(s):

Folic Acid ◽

Protein Complex ◽

Blood Circulation ◽

Rapid Decline ◽

Milk Secretion ◽

Folate Binding Protein ◽

Folate Concentration ◽

Trapping Mechanism ◽

Stage Of Lactation ◽

A Minor

1. A study was made on the folate content of goat's milk in relation to stage of lactation, and on the interrelationship between blood and milk folate concentrations in the dam and in the kid.2. In seven goats the folate concentration in the colostrum at parturition ranged from 136 to 300 ng/ml, and averaged 205 ng/ml. The concentration fell sharply during the early days of lactation and by day 14 it averaged only 9.5 ng/ml. This pattern of rapid decline in milk folate concentration with advancing lactation was little affected by daily provision of folic acid parenterally in relatively large amounts.3. The colostrum and milk contained a minor whey protein that combined strongly with folate, and presumably acts as a trapping mechanism to accumulate the vitamin from the plasma into the milk. The milk folate concentration determined by the rate of milk secretion in relation to the availability of free folate in the blood plasma.4. At parturition the plasma folate concentration in the kids was very low – about 1 ng/ml – but by day 2 it had increased to about 28 ng/ml. This folate was protein-bound and accompanied by an excess of free binder protein. It appeared that the folate-protein complex from the colostrums was transmitted intact into the kids' blood circulation.5. The possible importance of the folate-binding protein in regulation of folate metabolism is discussed.

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Hematopoietic Effects of Folic Acid Metabolites in the Megaloblastic Anemias

American Journal of Clinical Nutrition ◽

10.1093/ajcn/7.4.385 ◽

1959 ◽

Vol 7 (4) ◽

pp. 385-389 ◽

Cited By ~ 1

Author(s):

R. WAYNE RUNDLES

Keyword(s):

Folic Acid ◽

Acid Metabolites

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Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz027 ◽

2019 ◽

Vol 109 (5) ◽

pp. 1452-1461 ◽

Cited By ~ 10

Author(s):

Meng-Yu Chen ◽

Charles E Rose ◽

Yan Ping Qi ◽

Jennifer L Williams ◽

Lorraine F Yeung ◽

...

Keyword(s):

Folic Acid ◽

Intervention Group ◽

Population Based ◽

Folic Acid Supplementation ◽

Reproductive Age ◽

Vitamin B ◽

Acid Supplementation ◽

Folate Concentration ◽

Plasma Folate ◽

Vitamin B 12

ABSTRACT Background For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. Objective The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. Methods We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. Results Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3–4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). Conclusions The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

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Impact of Voluntary Folic Acid Fortification of Corn Masa Flour on RBC Folate Concentrations in the U.S. (NHANES 2011–2018)

Nutrients ◽

10.3390/nu13041325 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1325

Author(s):

Arick Wang ◽

Charles E. Rose ◽

Yan Ping Qi ◽

Jennifer L. Williams ◽

Christine M. Pfeiffer ◽

...

Keyword(s):

Folic Acid ◽

Neural Tube ◽

Neural Tube Defects ◽

Hispanic Women ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Folic Acid Fortification ◽

Folate Concentration ◽

Corn Masa ◽

The U.S

Surveillance data have highlighted continued disparities in neural tube defects (NTDs) by race-ethnicity in the United States. Starting in 2016, the Food and Drug Administration (FDA) authorized voluntary folic acid fortification of corn masa flour to reduce the risk of neural tube defects (NTDs) among infants of Hispanic women of reproductive age. To assess the impact of voluntary corn masa fortification, cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 2011–2018 for Hispanic women of reproductive age with available red blood cell (RBC) folate concentrations were analyzed, with additional analyses conducted among Hispanic women whose sole source of folic acid intake was fortified foods (enriched cereal grain products (ECGP) only), excluding ready-to-eat cereals and supplements. RBC folate concentration (adjusted geometric mean) among Hispanic women of reproductive age did not differ between 2011–2016 and 2017–2018, though RBC folate concentration increased significantly among lesser acculturated Hispanic women consuming ECGP only. Concentrations of RBC folate for those born outside the U.S and residing in the U.S <15 years increased from 894 nmol/L (95% CI: 844–946) in 2011–2016 to 1018 nmol/L (95% CI: 982–1162; p < 0.001) in 2017–2018. Primarily Spanish-speaking Hispanic women of reproductive age who only consumed ECGP saw an increase from 941 nmol/L (95% CI: 895–990) in 2011–2016 to 1034 nmol/L (95% CI: 966–1107; p = 0.03) in 2017–2018. By subpopulation, we observed no significant changes in the proportion at risk of NTDs (<748 nmol/L) and no changes in the model-based estimated NTD rates following voluntary corn masa fortification. This analysis suggests that there is a remaining risk among Hispanics for folate sensitive NTDs, though continued monitoring of folate status in future NHANES data cycles will help inform the long-term efficacy of voluntary fortification of corn masa flour.

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Comparison of (6S)-5-methyltetrahydrofolic acidv.folic acid as the reference folate in longer-term human dietary intervention studies assessing the relative bioavailability of natural food folates: comparative changes in folate status following a 16-week placebo-controlled study in healthy adults

British Journal Of Nutrition ◽

10.1017/s0007114509992339 ◽

2009 ◽

Vol 103 (5) ◽

pp. 724-729 ◽

Cited By ~ 16

Author(s):

Anthony J. A. Wright ◽

Maria J. King ◽

Caroline A. Wolfe ◽

Hilary J. Powers ◽

Paul M. Finglas

Keyword(s):

Folic Acid ◽

Intervention Studies ◽

Relative Bioavailability ◽

Food Group ◽

Relative Increase ◽

Natural Food ◽

Folate Concentration ◽

Folate Status ◽

Erythrocyte Folate ◽

Food Folate

Folic acid (pteroylmonoglutamic acid) has historically been used as the reference folate in human intervention studies assessing the relative bioavailability of dietary folate. Recent studies using labelled folates indicated different plasma response kinetics to folic acid than to natural (food) folates, thus obviously precluding its use in single-dose experiments. Since differences in tissue distribution and site of biotransformation were hypothesised, the question is whether folic acid remains suitable as a reference folate for longer-term intervention studies, where the relative bioavailability of natural (food) folate is assessed based on changes in folate status. Healthy adults aged 18–65 years (n163) completed a 16-week placebo-controlled intervention study in which the relative bioavailability of increased folate intake (453 nmol/d) from folate-rich foods was assessed by comparing changes in plasma and erythrocyte folate concentration with changes induced by an equal reference dose of supplemental (6S)-5-methyltetrahydrofolic acid or folic acid. The relative increase in plasma folate concentration in the food group was 31 % when compared with that induced by folic acid, but 39 % when compared with (6S)-5-methyltetrahydrofolic acid. The relative increase in erythrocyte folate concentration in the food group when compared with that induced by folic acid was 43 %, and 40 % when compared with (6S)-5-methyltetrahydrofolic acid. When recent published observations were additionally taken into account it was concluded that, in principle, folic acid should not be used as the reference folate when attempting to estimate relative natural (food) folate bioavailability in longer-term human intervention studies. Using (6S)-5-methyltetrahydrofolic acid as the reference folate would avoid future results' validity being questioned.

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