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PubMed1978

Inactivation of the chemoattractant folic acid by cellular slime molds and identification of the reaction product.

Enzymes inactivating the chemoattractants folic acid and pterin were detected in extracellular, intracellular, and particulate fractions obtained from Dictyostelium discoideum strains NC4 and AX-2 and Polysphondylium violaceum. The products of the inactivation reaction were analyzed by thin-layer chromatography and UV spectroscopy. Results obtained indicate that folic acid and pterin were deaminated to 2-deamino folic acid and lumazine, respectively.

Aminohydrolases↗
PubMed1984

Chemiluminescence from an erythrocyte folic acid oxidase from normal individuals and from cancer patients.

Folic acid oxidase from erythrocytes oxidatively cleaves folic acid at the C-9-N-10 bond to yield pterin-6-aldehyde and p-aminobenzoyl glutamic acid, with the concomitant generation of singlet oxygen. The emission from singlet oxygen is proportional to the enzyme activity. DABCO was used as a singlet oxygen emission enhancer to increase the sensitivity of the measurement. In general, pregnant women show high enzymatic activity, but the emission is strongly quenched by DABCO. This is contrary to normal and cancer cases in which an increase in the emission was observed. This effect is larger in cancer cases. These results are presented as a potential method for detecting physiological and pathological human conditions.

Erythrocytes↗
PubMed2006

[6S]-5-Methyltetrahydrofolate is at least as effective as folic acid in preventing a decline in blood folate concentrations during lactation.

BACKGROUND: Studies in nonpregnant, nonlactating women suggest that folate supplementation in the form of 5-methyltetrahydrofolate ([6S]-5-methylTHF) is at least as effective as folic acid in increasing blood folate indexes. No data, however, are available on the effect of supplemental [6S]-5-methylTHF on blood folate concentrations during lactation. OBJECTIVE: We assessed the relative effectiveness of [6S]-5-methylTHF, a placebo, and folic acid in maintaining blood folate indexes during lactation in a sample of healthy Canadian women consuming folic acid-fortified foods. DESIGN: This study was designed as a 16-wk, randomized, placebo-controlled intervention. Pregnant women (n = 72) advised to consume a folic acid-containing prenatal supplement (1000 microg/d) during pregnancy were enrolled at 36 wk gestation. After delivery, the women were randomly assigned to receive [6S]-5-methylTHF (416 microg/d, 906 nmol/d) or a placebo or were assigned to a folic acid (400 microg/d, 906 nmol/d) reference group. RESULTS: At 16 wk of lactation, the mean red blood cell (RBC) folate concentration in women in the [6S]-5-methylTHF group (2178; 95% CI: 1854, 2559 nmol/L) was greater than that in the folic acid (1967; 1628, 2377 nmol/L; P < 0.05) and placebo (1390; 1198, 1613 nmol/L; P < 0.002) groups after adjustment for baseline concentrations (36 wk gestation). The distribution of folate forms in RBCs did not differ significantly between the [6S]-5-methylTHF and placebo groups. However, the folic acid group had greater amounts of 5-formylTHF (P < 0.03). CONCLUSION: [6S]-5-MethylTHF appeared to be as effective as, and perhaps more effective than, folic acid in preserving RBC folate concentrations during lactation.

Adult↗
PubMed1995

[Megaloblastic changes in cervical epithelium associated with oral contraceptives and changes after treatment with folic acid].

OBJECTIVE: To study the influence of oral contraceptives on cervical epithelium, serum and red blood cell folate levels of users and to observe the changes after treatment with folic acid. METHODS: Morphology of cervical epithelium, serum folate and red blood cell folate levels were studied in 101 women who had used oral contraceptives for over 6 months and 33 intrauterine devices users served as controls, 29 women using oral contraceptives with cervical megaloblastic changes were treated with folic acid (5mg daily) for 3-4 weeks and followed up for observation on morphological changes of cervical epithelium. RESULTS: The mean nuclear diameter of cervical epithelial cells was larger in the oral contraceptive group than that in the control group (P < 0.001). Megaloblastic changes in cervical epithelium occurred in 29 women in the oral contraceptive group (28.7%). There was significant difference in the occurrence of cervical megaloblastic changes between the two groups (P < 0.01). The level of red blood cell folate was lower in the oral contraceptive group than that in the control group (P < 0.05). There was no difference in serum folate, hemoglobin and neutrophil nuclear index between the two groups (P > 0.05). The mean nuclear diameter of cervical epithelial cells decreased significantly (P < 0.001) and multinuclear and vacuolar changes disappeared after folic acid therapy in 26 women with megaloblastic changes. CONCLUSIONS: Oral contraceptives reduced folate storage in the body and resulted in megaloblastic changes in cervical epithelium. This condition was improved with folic acid therapy.

Adult↗
PubMed1995

Folic acid as a cancer-preventing agent.

Higher intakes of folic acid-rich foods such as vegetables, legumes, and whole grains are associated with lower incidence of carcinomas in international comparisons and case-control studies. Deficiency of folic acid in experimental studies causes DNA damage that resembles the DNA damage seen in cancer cells. The requirement for folic acid in DNA synthesis and DNA methylation provides a plausible mechanism for a mutagenic effect of a low-folate diet. It is suggested that cancer can be initiated by DNA damage that results from folic acid deficiency. The relatively low level of folic acid in North American diets might be the underlying reason for high rates of many cancers in North America.

Animals↗
PubMed2004

Absorption of D(+)-xylose, cobalamin, and folic acid after autologic-allotopic ileum mucosa transplantation in beagles.

BACKGROUND/PURPOSE: Ileum mucosa transplantation in a demucosed colon coat was developed as a new method for small bowel elongation. In an animal model, the authors investigated the absorptive capacity of the transplanted mucosa for D(+)-xylose, cobalamin (vitamin B12), and folic acid. METHODS: Ileum mucosa was transplanted in a vascularized demucosed segment of transverse colon in 18 beagle dogs. The colon coat-ileum mucosa complex then was integrated in the ileal continuity. Absorptive capacity for D(+)-xylose, cobalamin, and folic acid was measured before and 4 weeks after transplantation. The results were compared and analyzed with the Students' t test for matched pairs. All determined blood values with P values less than.05 were considered to show a significant reduction in the absorptive capacity of the transplanted ileum mucosa. RESULTS: Fifteen minutes after application there was no significant difference in the absorption of D(+)-Xylose and cobalamin between normal and transplanted ileum mucosa (P >.1). Absorption of folic acid in the transplanted segment was lower but not significant (P <.1). After 30 minutes D(+)-xylose and cobalamin again showed no difference between the absorptive capacity of normal and transplanted ileum mucosa (P >.1), whereas folic acid continued with the tendency toward an impaired absorption (P <.1). However, after 60 minutes, the difference of the absorptive capacity of the transplanted ileum mucosa was significant (P <.05) for folic acid. D(+)-xylose showed a tendency for an impaired uptake (P <.1), whereas absorption of cobalamin did not differ significantly after transplantation (P >.1). CONCLUSIONS: Experimental autologic-allotopic ileum mucosa transplantation is a feasible new method for small bowel elongation in an animal model. Examination of the absorptive capacity of the transplanted ileum mucosa showed a normal uptake for cobalamin, while there was an impaired absorption of D(+)-xylose and folic acid.

Animals↗
PubMed2002

Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age.

BACKGROUND: Ongoing clinical trials are investigating whether lowering plasma homocysteine reduces the risk of vascular disease. If so, food fortification with folic acid will be the likely result, and sub-optimal amounts are likely to be preferred, for safety reasons. Dose-finding studies are needed before the outcomes of these trials, to establish the benefits and risks of folic acid consumption over the widest intake range likely to be encountered. AIM: To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women. DESIGN: Double-blind, randomized placebo-controlled trial. METHODS: Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 microg/day of folic acid. Red-cell folate and plasma homocysteine were measured at baseline and after 10 weeks supplementation. RESULTS: Median red cell folate levels increased significantly in the 200 microg(p=0.0001) and 400 microg(p=0.0001) groups; but not in the placebo (0 microg) (p=0.25) or the 100 microg (p=0.5) groups. Only the 200 microg and the 400 microg groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 micromol/l (already optimally low) were removed from the analysis, there were significant plasma homocysteine decreases in all three treatment groups, but not the placebo group. DISCUSSION: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.

Adult↗
PubMed2003

Effects of folic acid supplementation on inflammatory and thrombogenic markers in chronic smokers. A randomised controlled trial.

INTRODUCTION: Cigarette smoking may induce pro-inflammatory and pro-thrombotic changes. It is not known whether these abnormalities are caused at least partly by increased homocysteine levels. We investigated whether lowering homocysteine by folic acid supplementation might reduce the plasma concentration of inflammatory and thrombogenic markers in chronic smokers. MATERIAL AND METHODS: Twenty-four healthy cigarette smokers (age 37.8+/-2.5 years, mean+/-SEM) were randomly assigned to 4 weeks of folic acid 5 mg/day or placebo. The following parameters were measured before and after treatment: (1) markers of inflammation (C-reactive protein, CRP, and white cell count, WCC); (2) blood coagulation screen (Activated Partial Thromboplastin time Ratio, APTR, and International Normalized Ratio, INR); (3) pro-thrombotic markers (fibrinogen, factor VIII coagulant activity, VIII:C, von Willebrand factor, vWF, and D-dimer). RESULTS: Folic acid induced a significant reduction in homocysteine (10.8+/-0.6 vs. 8.2+/-0.5 micromol/l, p<0.001), plasma fibrinogen (3.15+/-0.14 vs. 2.87+/-0.14 g/l, p<0.05), and D-dimer (102+/-44 vs. 80+/-26 microg/l, p<0.05) concentrations. By contrast, no significant changes were observed in CRP (2.2+/-0.7 vs. 1.7+/-0.7 mg/l), WCC (7.2+/-0.5 vs. 6.8+/-0.5 10(9) cells/l), APTR (0.91+/-0.02 vs. 0.93+/-0.02), INR (0.92+/-0.01 vs. 0.91+/-0.01), vWF (103+/-8 vs. 102+/-9 U/dl), and VIII:C (120+/-8 vs. 107+/-8 U/dl) levels. Changes in folic acid plasma concentrations were significantly and negatively correlated with changes in fibrinogen (r=-0.48, p=0.01) but not with changes in D-dimer (r=-0.15, p=0.5) levels. Changes in plasma homocysteine concentrations did not correlate with changes in either fibrinogen or D-dimer. No significant changes in homocysteine, inflammatory and thrombogenic markers were observed in the placebo group. CONCLUSIONS: Short-term folic acid supplementation had no significant effects on inflammatory markers but induced a significant reduction in plasma fibrinogen and D-dimer concentrations in healthy chronic smokers. Thus, folic acid might have an anti-thrombotic effect in this high-risk group independent of the homocysteine lowering effect.

Adult↗
PubMed1996

Folic acid supplementation--when and how.

The periconceptional intake of 400 micrograms of folic acid can prevent 50-70% of neural tube defects. It is difficult to achieve this intake with diet alone, even with the recently approved levels for grain-food fortification. Therefore, a daily multivitamin with folic acid is recommended for all women of childbearing potential. Obstetrician-gynecologists should exercise every opportunity to educate their patients to this end. Although raised as a concern, the potential of masking the megaloblastic anemia of pernicious anemia is unlikely with these levels of supplementation, and considering the rarity of the disease in women of reproductive age.

Female↗
PubMed2005

Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials.

BACKGROUND: Dietary supplementation with B vitamins that lower blood homocysteine concentrations is expected to reduce cardiovascular disease risk, but there has been uncertainty about the optimum regimen to use for this purpose. OBJECTIVE: The objectives were to ascertain the lowest dose of folic acid associated with the maximum reduction in homocysteine concentrations and to determine the additional relevance of vitamins B-12 and B-6. DESIGN: A meta-analysis of 25 randomized controlled trials involving individual data on 2596 subjects assessed the effect on plasma homocysteine concentrations of different doses of folic acid and of the addition of vitamins B-12 and B-6. RESULTS: The proportional reductions in plasma homocysteine concentrations produced by folic acid were greater at higher homocysteine (P < 0.001) and lower folate (P < 0.001) pretreatment concentrations; they were also greater in women than in men (P < 0.001). After standardization for sex and to pretreatment plasma concentrations of 12 micromol homocysteine/L and 12 nmol folate/L, daily doses of 0.2, 0.4, 0.8, 2.0, and 5.0 mg folic acid were associated with reductions in homocysteine of 13% (95% CI: 10%, 16%), 20% (17%, 22%), 23% (21%, 26%), 23% (20%, 26%), and 25% (22%, 28%), respectively. Vitamin B-12 (x: 0.4 mg/d) produced 7% (95% CI: 4%, 9%) further reduction in homocysteine concentrations, but vitamin B-6 had no significant effect. CONCLUSIONS: Daily doses of > or =0.8 mg folic acid are typically required to achieve the maximal reduction in plasma homocysteine concentrations produced by folic acid supplementation. Doses of 0.2 and 0.4 mg are associated with 60% and 90%, respectively, of this maximal effect.

Adolescent↗
PubMed1978

[Effect of chronic alcohol administration and of folic acid deficiency on iron absorption].

The influence of chronic alcohol ingestion and artificially induced folic acid deficiency on iron absorption has been measured in rabbits by whole body counter. Results show that chronic alcohol ingestion does not modify iron absorption. Folic acid deficiency increases iron absorption by two probable mechanisms: first by increased plasma iron turnover (PIT), which parallels ineffective erythropoiesis, and second by a probable direct effect on the intestinal mucous membranes. This second mechanism appears to be independent of PIT: concomitant deficiency of folic acid and alcohol ingestion produces an increase in iron absorption without modification of PIT. Experience with drugs inhibiting protein synthesis suggests that this increase may be mediated by decreased protein synthesis.

Alcoholism↗
PubMed2003

Effect of folic acid on fenofibrate-induced elevation of homocysteine and cysteine.

BACKGROUND: An elevated total plasma homocysteine (tHcy) level is considered to be an independent risk factor for atherosclerosis. It has been reported that lipid-lowering therapy with fibric acid derivatives (fibrates) increases tHcy and total plasma cysteine (tCys) levels. The aim of this study was to determine whether therapy with folic acid, a potent tHcy-lowering agent, could modify the fenofibrate-induced elevation of plasma aminothiols. METHODS: Patients with combined hyperlipidemia (n = 37) were randomized to receive 9 weeks of treatment with micronized fenofibrate 200 mg/day (F group) or fenofibrate 200 mg/day plus folic acid 10 mg/every other day (F+F group). tCys and tHcy levels were determined before and after the therapy with high performance liquid chromatography. RESULTS: The tHcy level increased significantly in the F group by 51.3% and in the F+F group by 14.6% (between-group difference P =.001). Total plasma cysteine (tCys) increased similarly after both treatments (P =.72). The serum creatinine level increased in the F group by 20.7% and in F+F group only by 9.8% (P =.04). The increase of tHcy level in F group correlated with an increase of tCys and creatinine levels (r = 0.74 and 0.64, respectively). The effects on the lipid profile did not differ by treatment group. CONCLUSIONS: Folic acid effectively reduces the fenofibrate-induced elevation of tHcy and creatinine, but it does not affect the elevation of the tCys. Folic acid has neutral effect on the lipid-lowering action of fenofibrate. Clinical efficacy of fenofibrate might be improved by folic acid coadministration.

Cholesterol↗
PubMed1997

High performance liquid chromatographic determination of folic acid and its photodegradation products in the presence of riboflavin.

A high performance liquid chromatographic procedure was developed to determine folic acid and its photodegradation products, p-aminobenzoic acid, pterine-6-carboxylic acid, p-aminobenzoyl-L-glutamic acid, and pteroic acid in the presence of riboflavin. The method involves reversed phase, paired-ion chromatography on mu-BondaPak C18 column using a UV detector (254 nm), and isocratic solvent system (at ambient temperature) comprising 0.017 M monobasic potassium phosphate, tetrabutyl ammonium hydroxide solution (20%, aqueous) and methanol (870:15:250, v/v). The range of quantitation for the individual compounds was found to be: p-aminobenzoic acid, 0.01 - 1.25 x 10(-5) M; pterine-6-carboxylic acid, 0.01-2.0 x 10(-5) M; p-aminobenzoyl-L-glutamic acid, 0.02-2.0 x 10(-5) M; pteroic acid, 0.02-2.5 x 10(-5) M; folic acid, 1.0-5.0 x 10(-5) M; riboflavin, 1.0-5.0 x 10(-5) M. Linear regression analysis of the data demonstrates adequate performance of the method in terms of accuracy and precision (R. S. D. 3%). The method is specific, rapid and convenient and has been applied to photodegradation studies of folic acid in the presence and absence of riboflavin.

4-Aminobenzoic Acid↗
PubMed2005

[Differences in folic-acid policy and the prevalence of neural-tube defects in Europe; recommendations for food fortification in a EUROCAT report].

The European Registration Of Congenital Anomalies and Twins (EUROCAT), a network of 40 European registries of congenital anomalies, has published a special report on the prevention of neural-tube defects by, periconceptional folic-acid supplementation in Europe. This report reviews the progress made in 17 European countries since i99I in terms of developing and implementing public health policies to raise periconceptional folate status. Data on the prevalence of neural-tube defects in 1980-2000 were also analysed. - At the beginning of 2002, 10 of the 17 countries had an official government recommendation that women planning a pregnancy should take folic-acid supplementation daily. Only 7 countries implemented official health-education initiatives. - Despite the various measures taken to date, the majority of women in all countries surveyed are not taking periconceptional folic-acid supplements. Even in the Netherlands, where the percentage of planned pregnancies is estimated at 85%, only 36% of women take folic-acid supplements during the advised period. - Overall, the number of neural-tube defects has not decreased in Europe. A slight decrease was seen in those countries with an official policy regarding periconceptional folic-acid supplementation. - It is clear from the report that more effective prevention of neuraltube defects could be achieved with folic-acid fortification of staple foods; this approach has led to a reduction in the prevalence of neuraltube defects in the US and Canada. This approach can also prevent the majority of neural-tube defects in unplanned pregnancies and reduce the socioeconomic differences in prevalence.

Adult↗
PubMed2004

Effect of folic acid fortification of foods on folate intake in female smokers with cervical dysplasia.

OBJECTIVE: We investigated the effect of folic acid fortification of enriched cereal grains on folate intake in women of predominantly childbearing age at high risk for cervical cancer. METHODS: Subjects in this cross-sectional study were 77 women randomized between November 1999 and December 2000 in the Women's Intervention to Stay Healthy (WISH), a clinical trial evaluating the effect of a tobacco control intervention on the progression of cervical dysplasia. All subjects were cigarette smokers, had a previously abnormal Papanicolaou test, and were positive for high-risk human papillomavirus at entry. Dietary intake was assessed with food-frequency questionnaires completed at the baseline visit for WISH. The effect of folic acid fortification on folate intake was assessed by using pre- and postfortification folate databases to estimate folate intake. RESULTS: Mean folate intake assessed with the postfortification database was 63% higher than intake assessed with the prefortification database: 417 versus 256 microg/d of dietary folate equivalents (P < 0.0001). The proportion of subjects below the estimated average requirement for folate was smaller after fortification than before fortification: 40.3% versus 75.3% (P < 0.0001). Several foods, including white bread, cheese dishes, spaghetti, and rice, became major sources of folate as a result of fortification. CONCLUSIONS: Folic acid fortification resulted in an increased intake of folate in these subjects. However, even with fortification, folate intake in a large proportion of these women remained below recommended levels. These results should be considered before decisions regarding future levels of folic acid fortification are made.

Adolescent↗
PubMedDate not supplied

The influence of folic acid on the picrotoxin-sensitive site of the GABAa-receptor complex.

The site of action responsible for the convulsive effect of folic acid was investigated in vitro. Folic acid (ECmax 5 x 10(-4) M) enhances the binding of the cage convulsant [3H]t-butylbicycloorthobenzoate ([3H]TBOB) to rat brain membranes, namely to 130% of control in the absence of GABA and to over 300% of control in the presence of physiological concentrations of GABA. Analysis of the binding parameters reveals that folic acid increases the apparent number of [3H]TBOB binding sites.

Animals↗
PubMed2003

Folic acid mediated attenuation of loss of heterozygosity of DCC tumor suppressor gene in the colonic mucosa of patients with colorectal adenomas.

Loss of heterozygosity (LOH) and/or inactivation of tumor suppressor genes are implicated in the initiation and progression of many malignancies, including colorectal cancer. Although accumulating evidence suggests a chemopreventive role for folate in colorectal cancer, regulatory mechanisms are poorly understood. The primary objective of the current investigation was to determine whether folic acid would prevent LOH of the three tumor suppressor genes, deleted in colorectal cancer (DCC), adenomatous polyposis coli (APC) and p53 in macroscopically normal appearing rectal mucosa of patients with adenomatous polyps. In addition, the effect of folic acid on rectal mucosal proliferation was determined. Twenty patients were randomized in a double-blind study to receive either folic acid 5mg once daily or identical placebo tablets for 1 year. Genomic DNA and total protein were extracted from the rectal mucosa at baseline and after 1 year of treatment and analyzed for LOH and protein levels of APC, DCC and p53 genes. In addition, paraffin-embedded mucosal specimens were analyzed for proliferating cell nuclear antigen (PCNA) immunoreactivity, as a measure of cellular proliferative activity. Folate supplementation prevented LOH of DCC gene in five out of five (100%) patients who demonstrated baseline heterozygosity, whereas two out of four (50%) placebo-treated patients with baseline heterozygosity demonstrated allelic loss. Mucosal protein levels of DCC were also reduced in 7 of 10 (70%) placebo-treated patients compared to only 2 of 10 (20%) of patients treated with folate. Levels increased, however, in eight and three patients in the folic acid and placebo groups, respectively (P<0.02). Folic acid caused no change in allelic status of either APC or p53 gene. Folate supplementation caused a small, but not statistically significant, 16% reduction in mucosal proliferation, whereas placebo treatment resulted in a 88% (P<0.05) increase in this parameter, when compared with the corresponding baseline values. Our results indicate that folic acid prevents an increase in proliferation and arrests LOH of DCC gene and also stabilizes its protein in normal appearing rectal mucosa of patients with colorectal adenomas. Taken together, our data suggest that one of the ways folate may exert its chemopreventive effect is by stabilizing certain tumor suppressor gene(s) and preventing further increases in proliferation.

Adenoma↗
PubMed1997

[Changes in serum levels of folic acid after total gastrectomy].

The Authors, in consideration that Folic Acid is assimilated in the upper alimentary tract, effected a comparative study between its seric levels in normal patients and in patients submitted to gastrectomy for gastric cancer, at different times from the operation. In the patients of the first group, Folic Acid levels were not correlated with sex, but to age, decreasing with the increasing of it. In gastrectomized patients, serum levels, also if acceptable, were always lower than in control cases, and gradually decreasing with the increasing of the age. The Authors conclude that, obviously, intestinal assimilation and endogenous reserves are able to counterbalance for enough long time the insufficient alimentary absorption.

Aged↗