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PubMed1989

Folic acid absorption determined by a single stool sample test--a double-isotope technique. The folic acid absorption capacity in children.

The fractional folic acid absorption (FAFol) was determined in 66 patients with various gastrointestinal diseases by a double-isotope technique, employing a single stool sample test (SSST) as well as a complete stool collection. The age of the patients ranged from 2.5 months to 16.8 years (mean 6.3 years). The test dose was administered orally and consisted of 50 micrograms of [3H]folic acid (monoglutamate) (approximately 20 muCi), carmine powder, and 2 mg 51CrCl3 (approximately 1.25 muCi) as the unabsorbable tracer. The whole-body radiation given to a 1-year-old child averaged 4.8 mrad only. The stool and napkin contents were collected and homogenized by the addition of 300 ml chromium sulfuric acid. A 300-ml sample of the homogenized stool and napkin contents, as well as 300 ml chromium sulfuric acid (75% vol/vol) containing the standards, were counted for the content of 51Cr in a broad-based well counter. The quantity of [3H]folic acid was determined by liquid scintillation, after duplicate distillation. Estimated by SSST, the FAFol, which employs the stool with the highest content of 51Cr corresponding to the most carmine-colored stool, correlated closely with the FAFol based on complete stool collection (r = 0.96, n = 39, p less than 0.0001). The reproducibility of FAFol determined by SSST was assessed from repeated tests in 18 patients. For a mean of 81%, the SD was 4.6%, which corresponded to a coefficient of variation of 5.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

Folic acid sensitive birth defects in association with intrauterine exposure to folic acid antagonists.

Since the protective effect of folic acid (FA) on birth defects is well known, it is reasonable to assume intrauterine exposure to FA antagonists increases the risk on these defects. We have therefore performed case-control analyses to investigate the risk of intrauterine exposure to FA antagonists, using data on births from the EUROCAT Northern Netherlands registry from 1997 to 2002. Of the 815 cases, 11 were exposed to a FA antagonist compared to 16 of the 1402 controls. For FA sensitive defects as a group, the study showed no effect after exposure to a FA antagonist (odds ratio (OR)=1.18, 95% CI: 0.55-2.57). We found no effect after exposure to a dihydrofolate reductase inhibitor (DHFRI) (OR 0.44, 95% CI: 0.12-1.54), but we did find a statistically significant effect after exposure to an antiepileptic drug (OR=3.45, 95% CI: 1.04-11.48). This study supports the findings of various other studies on the teratogenicity of antiepileptics. An association between DHFRIs and FA sensitive defects was not found.

Abortion, Induced↗
PubMed2006

The effects of valproic acid, vitamin E and folic acid on ribs of rat fetuses in the prenatal period.

The present study was undertaken to determine histopathologic differences in the ribs of Wistar-albino rat fetuses prenatally exposed to valproic acid (VPA), folic acid (FA) and vitamin E (Vit E), and to compare their differential developmental susceptibility and morphological association with skeletal anomalies. VPA (300 mg/ kg), FA (300mg/kg) and Vit E (250mg/kg) were administered to rats on each of gestation days (GD) 7-9. Fetuses were collected on GD 21 and their ribs were examined for malformations. The fetuses were divided into four groups: blind-trial group, VPA group (vpa), VPA and Vit E group (vpa+vit e), valproic and FA group (vpa+fa). In each group; drug procedure, surgical procedure and histological methods were performed. Later, weights and lengths of fetuses in each group were compared and analyzed by one-way Anova test. As a result, maLformations in fetuses were determined and photographed by Nikon SMZ-2 steromicroscopy, using 2 x objective. Administration of single doses of VPA (300 mg/kg) resulted in weight and length loss between blind-trial and vpa group. However, length and weight differences between the other groups were not significant. The objective of the present study is to analyze morphological and histopathologic changes which may occur in a high-risk experimental model after the administration of VPA. In addition, protective roles of the administration of FA and Vit E are assessed.

Animals↗
PubMed1983

Evaluation of ascorbic acid in protecting labile folic acid derivatives.

The use of ascorbic acid as a reducing agent to protect labile, reduced derivatives of folic acid has been evaluated by high-performance liquid chromatographic separations and Lactobacillus casei microbiological assay of eluate fractions. Upon heating for 10 min at 100 degrees C, solutions of tetrahydropteroylglutamic acid (H4PteGlu) in 2% sodium ascorbate gave rise to 5,10-methylene-H4PteGlu and 5-methyl-H4PteGlu. H2PteGlu acid gave rise to 5-methyl-H4PteGlu and PteGlu. 10-Formyl-H4PteGlu gave rise to 5-formyl-H4PteGlu and 10-formyl-PteGlu. 5-Formyl-H4-PteGlu gave rise to a small amount of 10-formyl-PteGlu. 5-Methyl-H4PteGlu and PteGlu appeared stable to these conditions. These interconversions were not seen when solutions of these folate derivatives were kept at 0 degrees C in 1% ascorbate. These observations indicate that elevated temperatures are necessary for the interconversions of folates in ascorbate solutions. Assays of ascorbic acid solutions indicated the presence of formaldehyde (approximately equal to 6 mM). This was confirmed by the identification of 3,5-diacetyl-1,4-dihydrolutidine by UV, visible, and fluorescence spectroscopy and by thin-layer chromatography of chloroform extracts of the reaction mixture of ascorbic acid solutions, acetylacetone, and ammonium acetate. These results indicate that solutions of sodium ascorbate used at elevated temperatures are not suitable for extracting tissue for the subsequent assay of the individual folic acid derivatives.

Ascorbic Acid↗
PubMed1977

Influence of folic acid on birthweight and growth of the erythroblastotic infant. III. Effect of folic acid supplementation.

Seventeen infants with severe (14) or moderately severe (3) erythroblastosis were given daily oral supplements of 2-5 or 5 mg folic acid from day 16 (average) to 3-2 months (average). Their rate of weight gain, expressed as weight centiles, was followed for 1 year and was compared with that of a very similar group of 34 erythroblastotic infants without folic acid supplements. By the end of the 4th month, just after stopping additional folate intake, the median centiles for weight had risen from the 40th to the 80th centile, while in the untreated control group they rose during this period from the 35th to the 50th centile. During the second half of the year both groups declined in weight centiles, the 'treated' group ending up at the 50th centile for weight, while the control group fell to the 25th.

Birth Weight↗
PubMed1977

Acidic dissociation constants of folic acid, dihydrofolic acid, and methotrexate.

The acidic dissociation constants in the range HO--1.5 to pH 7 of folic acid, dihydrofolic acid, methopterin (N(10)methylfolic acid), and methotrexate have been measured by potentiometric and spectrophotometric titrations. Assignment of these dissociations was made by comparison to model compounds, by proton magnetic resonance measurements, and by examination of associated ultraviolet absorbance changes. For folic acid, the dissociation constants are as follows: N(1), pK' 2.35; N(10), pK' 0.20; N(5), pK' greater than -1.5. For dihydrofolic acid: N(5), pK' 3.84; N(1), pK' 1.38; N(10), pK' 0.28. For methotrexate: N(1), pK' 5.71; gamma-carboxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5), boxyl, pK' 4.70; alpha-carboxyl, pK' 3.36; N(10), pK' 0.50; N(5) pK' greater than -1.5. For methopterin: acidic ionization of amide, pK' 7.68; gamma-carboxyl, pK' 4.62; N(1), pK' 2.40; N(10), pK; 0.36; N(5), pK' greater than -1.5. The pK' values were determined directly for the four compounds at 25 degrees near 0.1 ionic strength, or in 0.1 to 4 M HCl for pK ln 0.1 M NaCl.

Chemical Phenomena↗
PubMed1973

The reproducibility and use of the tritiated folic acid urinary excretion test as a measure of folate absorption in clinical practice: effect of methotrexate on absorption of folic acid.

Investigations into the standardization and reproducibility of the urinary excretion method for determining the absorption of tritiated folic acid were carried out. By proper timing of tissue-loading doses of folic acid a clear difference between the percentage excretion ranges of normal and coeliac subjects was obtained. In addition conditions were found whereby the procedure could be repeated on an individual up to four times with reproducible results. Methotrexate in pharmacological amounts was found to have no inhibitory effect on the human intestinal absorption of a small oral dose (300 mug) of folic acid as determined by this method. This indicates that reduction of folic acid is not necessary for its absorption in man.

Administration, Oral↗
PubMed2002

Folic Acid and Epilepsy.

Folic acid has been a topic of discussion within the epilepsy community for several decades. Folic acid was initially suspected to be epileptogenic (1), but that concern has been resolved, as research has demonstrated that folic acid in less than supraphysiologic concentrations does not promote seizures. Epileptologists are now concerned that folic acid may be too low in persons with epilepsy taking some antiepileptic drugs (AEDs). Low serum and red blood cell levels of folic acid in women of childbearing potential increase the risk of fetal birth defects. For men and women, low levels of folic acid are associated with elevated homocysteine and an increased risk for cardiovascular disease. A convincing argument now develops that routine folic acid supplementation is important for women and men receiving AEDs.

Journal Article↗
PubMed1981

Mass spectrometry of permethylated folic acid analogs.

Folic acid and several analogs have been characterized as their permethylated derivatives. These derivatives are readily evaporated from the solid probe and provide spectra with abundant molecular ions and characteristic fragment ions. This method has been used to confirm the identities of the two methotrexate metabolites, 7-hydroxymethotrexate and 4-amino-4-deoxy-N(10)-methylpteroic acid, which have been isolated from human urine. The permethylation products of the folate cofactors, dihydrofolic acid, tetrahydrofolic acid and leucovorin, are also characterized.

Chromatography, High Pressure Liquid↗