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PubMed1992

In vivo folate kinetics during chronic supplementation of human subjects with deuterium-labeled folic acid.

Six healthy men (22-31 y) were supplemented for 4 wk with folic acid labeled with deuterium [3',5'-2H2; 3.6 mumol/d (1.6 mg/d)] to permit evaluation of in vivo kinetics of this vitamin. Total folate in urine, serum and erythrocytes was determined by microbiological assay, and isotopic labeling of urinary and erythrocyte folate was determined by gas chromatography-mass spectrometry. During supplementation, serum folate reached maximal concentration in approximately 18 d, whereas excretion of total and deuterium-labeled folates increased rapidly and reached isotopic steady state in 1-2 wk. Isotopic labeling of erythrocyte folate increased continually over the entire supplementation period. Upon cessation of supplementation, red blood cell folate and urinary folate excretion (total and labeled) decreased linearly. The decline in total serum folate could be described with a biexponential model that yielded a slow-phase half-life of 18.7 +/- 2.3 d. This model also indicated a turnover of 4.5% of the total body folate pool per day. Pool sizes of total body folate before and after supplementation (at steady state) were calculated to be 10 mumol (4.4 mg) and 98.9 mumol (43.7 mg), respectively. These kinetic data and stable isotope methodology may be used to address a wide range of experimental questions related to folate metabolism.

Adult↗
PubMed1991

Effect of feeding regimen on behavior of growing-finishing pigs supplemented or not supplemented with folic acid.

The effect of restricted feeding on the frequency of abnormal behaviors and gastric ulcers was investigated in 72 market pigs. Half of the pigs were fed restricted (R) amounts of feed twice a day (0800 and 1600) and received 90 to 95% of the intake recorded for the other half, which were allowed ad libitum (A) access to feed with addition of feed once a day at 0800. In each feeding group, 24 pigs were supplemented with folic acid. The animals were housed in pairs and the behavior of each animal was recorded during 24 h at 18 and 20 wk of age. The results showed that the A group ate more frequently during light hours than the R group at 18 wk, but not at 20 wk. However, the frequency of eating behavior was higher in the R group than in the A group at 20 wk during the 2 h after feed distribution. Feeding regimen had an effect on the frequency of redirected behaviors during the 2 h preceding feed distribution. The percentage of time spent nibbling on the penmate was higher in R than in A pigs at 18 wk, whereas that of rooting on the penmate was higher at 20 wk. Moreover, the proportion of pigs performing redirected behaviors was higher in the R than in the A group at both ages. The overall frequency of gastric ulcers was similar in pigs given the two feeding treatments, but severe ulcers were more frequent in the R than in the A group. Some interactions were also found between feeding regimen and folic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed2004

Effect of folic Acid supplementation on the folate status of buccal mucosa and lymphocytes.

Folate deficiency may be associated with an increased risk of cancer at certain sites. There is a need to measure folate status and putative biomarkers of cancer risk in the same target tissue, or in surrogate tissues. A study was carried out to develop a method for the rapid measurement of folate in human buccal mucosa and lymphocytes and to evaluate the responsiveness of this measurement in both tissues to folic acid supplementation in healthy subjects, relative to conventional markers of folate status. Three hundred and twenty-three adults, ages between 20 and 60 years, were screened for RBC folate concentrations. Sixty-five subjects with red cell folate between 200 and 650 nmol/L participated in a randomized, double blind, placebo-controlled, folic acid (1.2 mg) intervention trial, lasting 12 weeks. As anticipated, a significant baseline correlation (r = 0.36, P < 0.01) was observed between red cell folate and plasma 5-methyltetrahydrofolate (5-MeTHF). Lymphocyte total folate was significantly associated with plasma 5-MeTHF (r = 0.28, P < 0.05) and plasma total homocysteine concentration (r = -0.34, P < 0.05). Buccal mucosa total folate showed no correlation with either red cell folate or 5-MeTHF, but was significantly associated with lymphocyte total folate (r = 0.35, P < 0.01). Supplementation elicited a significant increase in lymphocyte total folate (P < 0.01), and this was strongly associated with the increase in RBC total folate (P < 0.01) and plasma 5-MeTHF (P < 0.01). Buccal mucosa total folate was not influenced by folate supplementation. Methods have been developed for the rapid measurement of lymphocyte and buccal mucosal total folate. Lymphocyte folate is sensitive to folate intake and is reflected by plasma 5-MeTHF.

Adolescent↗
PubMed1977

Acute folate deficiency associated with intravenous nutrition with aminoacid-sorbitol-ethanol: prophylaxis with intravenous folic acid.

Preoperative folate levels were initially normal in 30 patients with gastrointestinal tract disease but fell within 48 h by 60-95% in 20 patients who received intravenous nutrition for 6-12 d with aminoacid-sorbitol-ethanol (ASE). This depression persisted in patients not given folate supplements. Folate levels in 10 control patients not given ASE showed only minimal decline. Haematological changes were reduced to a minimum in 10 patients given 0.5 mg i.v. folic acid daily whilst eight unsupplemented patients showed evidence of megaloblastic haemopoiesis. Three of these eight patients developed thrombocytopenia and/or leukopenia which was fatal in one patient.

Aged↗
PubMed1988

Effect of therapy with vitamin B12 and folic acid on elderly patients with low concentrations of serum vitamin B12 or erythrocyte folate but normal blood counts.

To help understand the haematological significance of the low concentrations of serum vitamin B12 and erythrocyte folate occurring in elderly patients, 17 acute admissions to a geriatric unit with a low concentration of serum vitamin B12 or erythrocyte folate but a normal blood count were treated with vitamin B12 and folic acid for 3 months. Bone marrow deoxyuridine suppression was abnormal in 3 of these 17 patients, 2 of whom also had megaloblastic change in the marrow. With treatment, the MCV fell in 13 of the 17, and the average MCV fell from 90.5 to 87.9 fl (p = 0.007), but the mean Hb did not change. Ten untreated similar patients showed no change in their MCV over the same period, but the mean Hb fell from 14.0 to 13.1 g/dl (p = 0.04). Thus the low concentrations of serum vitamin B12 or erythrocyte folate found in approximately a quarter of acutely admitted elderly patients may indicate true tissue deficiency of these vitamins, even when the blood count is normal.

Blood Cell Count↗
PubMed1984

Cytogenetic investigations in mentally retarded and normal males from 14 families with the fragile site at Xq28. Results of folic acid treatment on fra(X) expression.

Lymphocyte cultures from 27 mentally retarded males aged 1 year to 77 years, and from 11 normal brothers from a total of 14 families with the fragile X segregating have been examined cytogenetically employing three different culture methods including methods for induction of fra(X) by FUdR (flourodeoxyuridine) or MTX (methotrexate). All mentally retarded males showed unequivocal fra(X) expression. No statistically significant correlation between fra(X) expression and age could be demonstrated. No enhancement with FUdR was observed. Fibroblast cultures from 10 retarded males expressed fra(X) in a dose-response relationship to increasing concentrations of FUdR. None of the normal males showed fra(X). In vivo folic acid treatment of seven mentally retarded males resulted in marked reduction in fra(X) expression in lymphocyte cultures grown in medium 199. However, reinduction was achieved by FUdR or MTX, except in one case who temporarily received very high doses of folic acid.

Adolescent↗
PubMed1972

Folic acid and the methylation of homocysteine by Bacillus subtilis.

1. Cell-free extracts of Bacillus subtilis synthesize methionine from serine and homocysteine without added folate. The endogenous folate may be replaced by tetrahydropteroyltriglutamate or an extract of heated Escherichia coli for the overall C(1) transfer, but tetrahydropteroylmonoglutamate is relatively inactive. 2. Extracts of B. subtilis contain serine transhydroxymethylase and 5,10-methylenetetrahydrofolate reductase, which are non-specific with respect to the glutamate content of the folate substrates. Methyl transfer to homocysteine requires a polyglutamate folate as methyl donor. These properties are not affected by growth of the organism with added vitamin B(12). 3. The synthesis of methionine from 5-methyltetrahydropteroyltriglutamate and homocysteine has the characteristics of the cobalamin-independent reaction of E. coli. No evidence for a cobalamin-dependent transmethylation was obtained. 4. S-Adenosylmethionine was not a significant precursor of the methyl group of methionine with cell-free extracts, neither was S-adenosylmethionine generated by methylation of S-adenosylhomocysteine by 5-methyltetrahydrofolate. 5. A procedure for the isolation and analysis of folic acid derivatives from natural sources is described. 6. The folates isolated from lysozyme extracts of B. subtilis are sensitive to folic acid conjugase. One has been identified as 5-formyltetrahydropteroyltriglutamate; the other is possibly a diglutamate folate. 7. A sequence is proposed for methionine biosynthesis in B. subtilis in which methyl groups are generated from serine and transferred to homocysteine by means of a cobalamin-independent pathway mediated by conjugated folate coenzymes.

Alcohol Oxidoreductases↗
PubMed2004

Use of folic acid casei medium reveals trimethoprim susceptibility of Lactobacillus species.

AIM: Lactobacilli have been reported to have intrinsic resistance to trimethoprim. The susceptibility of lactobacilli to trimethoprim on different media was investigated in order to search for a phenotypic test method that could indicate the presence of acquired resistance genes. METHODS AND RESULTS: Strains of Lactobacillus acidophilus, Lact. paracasei, Lact. rhamnosus and Lact. plantarum were susceptibility tested with E-tests on folic acid casei medium (FACM), MRS and defined medium 1. The effects of addition or removal of nucleosides and thymidine phosphorylase were investigated. E-tests on FACM yielded reproducible minimal inhibitory concentrations (MICs) for trimethoprim but addition of nucleosides was necessary for growth of Lact. acidophilus. MICs for the tested strains were 0.125-0.19, 0.25-3 and 0.064-0.19 microg ml(-1) for Lact. paracasei, Lact. rhamnosus and Lact. plantarum, respectively. With the addition of deoxyuridine and deoxyadenosine to FACM the MICs of Lact. acidophilus were 0.064-1 microg ml(-1). CONCLUSIONS, SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacilli do not have intrinsic resistance to trimethoprim. The results show that trimethoprim susceptibility testing of the tested Lactobacillus species is possible and indicate that transferable resistance genes are absent in all the tested strains.

Anti-Infective Agents↗
PubMed2004

The effect of oral folic acid on glutathione, glycaemia and lipids in Type 2 diabetes.

Plasma homocysteine is an established risk factor for vascular disease and precursor of the anti-oxidant glutathione. This study was designed to investigate the relationship of changes in homocysteine (Hcy) induced by oral folate to glutathione and measures of glycaemia and lipid metabolism in Type 2 diabetes (T2DM). Twenty-seven patients (26 male, 1 female, aged 48-68 years) with T2DM and microalbuminuria were treated with folic acid 10 mg daily for 3 months. During the study, diastolic blood pressure (p=0.04), HbA1c (p=0.04), serum triglycerides (p=0.04) and serum total/HDL-cholesterol ratio (p=0.004) all increased and serum HDL-cholesterol fell (p=0.006). The increased red cell folate correlated with a reduction in microalbuminuria (p=0.001). Overall, plasma glutathione increased (p=0.016) despite reduction in its precursor Hcy (p<0.001). Change in glutathione correlated inversely with change in HbA1c (p<0.02), total cholesterol (p=0.003) and triglycerides (p<0.02) and positively with HDL-cholesterol (p=0.033). Increase in glutathione correlated with levels of vitamin B6 (p<0.05). Metformin treatment protected against the rise in blood pressure (BP) (p=0.02), independently of changes in plasma glutathione. In summary, oral folic acid supplementation in T2DM reduced plasma Hcy and increased glutathione levels. HbA1c, triglycerides and HDL-cholesterol deteriorated during the trial: their levels correlated inversely with changes in glutathione. The increase in glutathione may depend on an adequate supply of B6, as changes in glutathione correlated with vitamin B6 levels. Reduced Hcy and increased glutathione may both mediate improvement in vascular function and outcome. Some aspects of the response to folate may be different in patients on metformin.

Adult↗