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Folic acid.

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Anemia↗
PubMed2002

Hyperhomocysteinaemia, folate and vitamin B12 in unsupplemented haemodialysis patients: effect of oral therapy with folic acid and vitamin B12.

BACKGROUND: Hyperhomocysteinaemia, a risk factor for atherosclerosis, is common in dialysis patients and particularly in those homozygous for a common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T transition). B-complex vitamin supplements have been shown to lower plasma total homocysteine (tHcy) concentrations, but the respective effectiveness of folate and oral vitamin B12 is not yet known. Our objectives were: (i) to determine the status of folate and vitamin B12 in a cohort of unsupplemented dialysis patients (ii) to assess the homocysteine-lowering effect of a folate supplement and then of a folate supplement with added vitamin B12. The responses were analysed for the C677T genotypes of MTHFR. METHODS: Plasma tHcy, folate and vitamin B12 were measured in 51 haemodialysis patients genotyped for the C677T MTHFR mutation (homozygotes, TT; heterozygotes, CT; without mutation, CC). All patients were then given daily supplements of 15 mg of folic acid for 2 months. They were given daily supplements of 1 mg of vitamin B12 in addition to the folate supplements for a further 2 months. Plasma tHcy, folate and vitamin B12 were monitored after each intervention. RESULTS: At baseline folate and vitamin B12 deficiencies were found in 10% and 6% of the patients. Initial plasma tHcy concentrations were high in all patients (mean 38.1+/-15 micromol/l). CC patients tended to have a lower tHcy concentration than pooled CT and TT patients. After 2 months of folate therapy, tHcy concentration decreased significantly to 20.2+/-7 micromol/l (P<0.001) and no significant differences were observed between the different genotype subgroups (19.4+/-6 for CC, 21.3+/-8 for CT, 18.5+/-4 for TT). A significant positive relationship was found between the reduction of tHcy and its initial value (rho=0.615, P<0.0001). The impact of the added vitamin B12 was negligible since tHcy concentrations did not change for the patients as a whole (19.8+/-7 micromol/l, NS) or in any subgroup (19.1+/-5 for CC, 20.3+/-9 for CT and 20+/-7 micromol/l for TT). CONCLUSIONS: (i) Folate and vitamin B12 deficiencies were observed in 10% and 6% respectively of our unsupplemented dialysis patients. (ii) After folate therapy, tHcy levels decreased significantly in all patients and were identical between the three C677T MTHFR genotype subgroups. (iii) Vitamin B12 supplements are useful in folate treated patients to prevent cobalamin deficiency and its neurological consequences but they did not lower tHcy plasma levels for the patients as a group or for any of the MTHFR subgroups.

Administration, Oral↗
PubMedDate not supplied

[Biosynthesis of folic acid in Eimeria tenella (Coccidia)].

The inhibitory analysis has shown that E. tenella does not include ready folic acid into metabolic process but synthesizes its metabolite, 7:8-dihydrofolic acid (DHFA), from its precursor, para-aminobenzoic acid (PABA), which enters the host's organism. PABA can be fully substituted in the process of metabolism by sulphadimesin (SD) at the molar ratio PABA: SD=1: 16.7. As a concurrent antagonist of PABA SD is 6 times stronger in the parasite-host system of Coccidia than in bacteria in cultural medium. The increase in PABA content in relation to SD more than 1: 16.7 intensifies the viability of Coccidia that is expressed in higher lethality of chicks, which reaches its maximum at PABA : SD=1 : 1.25. A further increase in the content of PABA does not affect the host's lethality. The decrease in PABA in relation to SD lower than 1 : 16.7 reduces the viability of Coccidia. Nucleic bases G, A transforming in the organism into corresponding nucleotids and aminoacids, 1-metionin and glycine, which are the products of biosynthesis with a participation of DHFA, do not stimulate the viability of E. tenella that apparently is associated with the non-capability of the host to assimilate timidin.

4-Aminobenzoic Acid↗
PubMed1995

Direct microtitre plate enzyme immunoassay of folic acid without heat denaturation of serum.

A new and simple method for enzyme immunoassay of folic acid (FA) has been developed, which does not require extraction or heat denaturation of serum. FA-free serum for standards was prepared by a new immunosorbent technique as conventional methods were unsuccessful. The detection limit of the assay is 0.05 ng/ml. Intra- and interassay variabilities ranged between 5-13.3%. Analytical recoveries obtained after spiking with different amounts of FA ranged between 93-110%. We eliminated the interference of endogenous folate binding protein--a major problem in direct FA assay by incubating serum samples (or standards) with FA-HRP conjugate in antibody coated plates at 50 degrees C. Comparison of our data with results obtained by microbiological assay and also by heating samples in alkaline buffer showed good correlation.

Carrier Proteins↗
PubMed1982

Blood vitamin status (B1, B2, B6, folic acid and B12) in patients with alcoholic liver disease.

Blood vitamin status (B1, B2, B6, folic acid and B12) was assessed in 41 patients (M = 39; F = 2) with alcoholic liver disease. Biochemical evidence of thiamine deficiency was observed in all groups of patients. Deficiency of riboflavin was detected in patients with histologically normal liver but not in other groups. All the groups were found to be deficient in pyridoxal-5-phosphate--the active form of vitamin B6 (pyridoxine). Serum folate was decreased in all groups except in those with alcoholic hepatitis: red cell folate was, of course within normal limits in all the groups. Vitamin B12 levels were within normal limits in all groups except the cirrhotic one where it was raised. Clinico-biochemical implications of the findings are discussed. Biochemical changes in blood vitamin status may precede clinical manifestations of a disease process and may have prognostic value.

Adult↗
PubMed2006

Tea polyphenol epigallocatechin-3-gallate inhibits ergosterol synthesis by disturbing folic acid metabolism in Candida albicans.

OBJECTIVES: Elucidation of the mechanism of action of epigallocatechin-3-gallate (EGCG) against Candida albicans and demonstration of the connection between its antifolate activity and other metabolic pathways involved in C. albicans survival are the major objectives of this study. METHODS: C. albicans ATCC 10231 and 12 clinical isolates were used. MICs of EGCG against C. albicans were determined according to NCCLS. C. albicans dihydrofolate reductase (DHFR) was purified using methotrexate-affinity chromatography and its inhibition by EGCG studied by spectroscopic techniques. Synergy experiments were performed by chequerboard tests by combining eight doubling concentrations of EGCG with another eight dilutions of azole compounds or terbinafine. Reversion experiments with leucovorin or S-adenosylmethionine were carried out, and the content of ergosterol was determined by a spectrophotometric method. RESULTS: EGCG is an efficient inhibitor of C. albicans DHFR (K(i) = 0.7 microM). As with other antifolates, the effects of EGCG on C. albicans can be highly attenuated by growing the cells in the presence of leucovorin. EGCG showed synergy with inhibitors of the ergosterol biosynthesis pathway in C. albicans such as azole antifungals and terbinafine. We demonstrate that by disturbing the folate metabolism, EGCG can inhibit ergosterol production. The molecular connection between the pathways is discussed. CONCLUSIONS: EGCG acts as an antifolate compound on C. albicans, disturbing its folic acid metabolism. This effect could explain the molecular mechanism for the synergy between EGCG and azole antifungals, and could represent a starting point for therapies involving antifolates and azoles used as an alternative for the treatment of C. albicans infections.

Antifungal Agents↗
PubMed2006

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

BACKGROUND: Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. PATIENTS-METHODS: In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. RESULTS: Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. CONCLUSIONS: In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

Administration, Oral↗
PubMed2000

Relationship between plasma homocysteine and vitamin status in the Framingham study population. Impact of folic acid fortification.

Recent studies have demonstrated associations between occlusive vascular disease and hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations with emphasis on relationships to vitamins that serve as coenzymes in homocysteine metabolism and to prevalence of carotid artery stenosis. Results showed that homocysteine exhibited strong inverse association with plasma folate and weaker associations with plasma vitamin B12 and pyridoxal-5'-phosphate. We saw similar inverse associations between homocysteine and intakes of folate and vitamin B6, but not vitamin B12. Prevalence of high homocysteine (> 14 mumol/L) was 29.3% in this cohort, and was greatest among subjects with low folate status. Inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine. Prevalence of stenosis > or = 25% was 43% in men and 34% in women, with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (> or = 14.4 mumol/L) compared with those in the lowest quartile (< or = 9.1 mumol/L), after adjustment for sex, age, HDL cholesterol, systolic blood pressure, and cigarette smoking (Ptrend < 0.001). Plasma concentrations of folate and pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex, and other risk factors. Studies using samples from the Framingham Study Offspring Cohort have shown that the US-mandated folic acid fortification of flour and cereal grain products resulted in an increase in the mean folate concentrations from 4.8 to 10.0 ng/mL (P < 0.001) and prevalence of low folate (< 3 ng/mL) decreased from 22.0 to 1.7% (P < 0.001) between the baseline and follow-up visits. Mean homocysteine concentration decreased from 10.1 to 9.4 microM (P < 0.001), and prevalence of high homocysteine (> 13 mumol/L) decreased from 18.7 to 9.8% (P < 0.001) between study visits. There were no statistically significant changes in the control group for folate or homocysteine between examinations. These data indicate a high prevalence of hyperhomocysteinemia in the Framingham Study population, the majority of which can be attributed to vitamin status and that this hyperhomocysteinemia is clinically relevant because of its association with increased risk of occlusive extracranial carotid stenosis. Insufficient levels of folate, and to a lesser extent vitamin B6, appear to predict part of this elevated risk through their role in homocysteine metabolism. These studies also indicate that the recently-implemented fortification of grain and cereal products with folic acid resulted in a substantial decline in plasma homocysteine. The impact of fortification on the US population is likely to be similar; however it awaits the next survey for further confirmation.

Aged↗