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PubMed1999

Determinants of folic acid knowledge and use among antenatal women.

BACKGROUND: Although recommendations on folic acid use were issued by health authorities in a number of countries in the early 1990s, uptake of peri-conceptional folic acid is still disappointingly low. Regardless of food fortification policies, folic acid promotion will probably be required in most countries to optimize folate levels among women of child-bearing age. The aim of this study was to examine folic acid knowledge and use, and their determinants among antenatal women in the east of Ireland in 1997. METHODS: Three hundred antenatal women attending their initial booking appointment in three Dublin maternity hospitals were surveyed. An interviewer-administered questionnaire was used with questions on folic acid knowledge and use, and demographic and obstetric questions. A univariate analysis of data was undertaken followed by a multivariate analysis using logistic regression to determine factors predicting knowledge and use of folic acid. RESULTS: Seventy-six per cent of respondents had heard of folic acid, 16 per cent had taken it before pregnancy and 51 per cent during pregnancy. Women who had planned their pregnancy, were married and were relatively affluent were significantly more likely to have heard of folic acid, to know that it could prevent neural tube defects and to have taken it peri-conceptionally. Less affluent women tended to use their general practitioner (GP) more as a source of information and advice than those who were better off. In multivariate analysis, marriage and planned pregnancy were important predictors of folic acid knowledge whereas planned pregnancy advice given before pregnancy and relative affluence were predictive of peri-conceptional use. CONCLUSIONS: Many women know of folic acid but do not take it peri-conceptionally. Women may associate folic acid with pregnancy and less with pre-pregnancy. Greater emphasis on peri-conceptional use should improve folic acid uptake. Focusing on less affluent women for folic acid promotion by GPs and other primary care professionals is also important.

Adult↗
PubMed1999

Accumulation of plasma reduced folates after folic acid administration.

The pharmacokinetics of folic acid, and resultant metabolites thereof, have been determined after administration orally and intravenously at 25 mg/m2 and 125 mg/m2. Saturation behavior was observed for uptake of folic acid into plasma and with regard to metabolism to methylenetetrahydrofolate and tetrahydrofolate as well as methyltetrahydrofolate. Repetitive oral administration every 6 hours resulted in consistently elevated levels of each metabolite pool with the same general saturation behavior as observed with single dose administration. This repetitive oral administration is concluded to be a suitable means to provide uniform elevation of metabolites that could offer protection from undesirable toxic effects of drugs such as MTA.

Administration, Oral↗
PubMed1984

Nonrandom distribution of methotrexate-induced aberrations on human chromosomes. Detection of further folic acid sensitive fragile sites.

Eleven folic acid sensitive fragile sites (3p14, 7p13, 7q31.1, 7q32, 9q32, 11p13, 14q23, 15q22, 16q23, Xp22.2, Xq22) were detected in one individual, eight of them previously unknown. These sites seem to bear each its specific sensitivity to folic acid deficiency. Six of the sites were observed simultaneously on both homologous chromosomes in at least one cell. Each of these 11 sites was also found in at least one among 12 individuals further examined. Some of these individuals showed six of these 11 sites. The fragile site 3p14 was detected in all individuals examined. The homologous sites 3p14 of one individual differed from each other in their frequency of lesions induced by methotrexate as well as fluorodeoxyuridine. This observation suggests that folic acid sensitivity is a property inherent in the chromatin of an individual chromosome at the site involved in fragility. This property seems to be responsible for the nonrandom fragility at that site and also for the individual sensitivity of each chromosomal site.

Cells, Cultured↗
PubMed1997

Impact of schedule on leucovorin potentiation of fluorouracil antitumor activity in dietary folic acid deplete mice.

A dietary folic acid depleted mouse model was established and used to evaluate the relationship between elevation of reduced folates after leucovorin (LV) administration and potentiation of fluorouracil (FU) response of an implanted tumor. C3H mouse mammary adenocarcinomas from mice maintained on a folic acid deplete diet had modestly decreased methylenetetrahydrofolate and tetrahydrofolate levels, and were somewhat less responsive to FU alone compared with replete animals. LV administration resulted in a substantial increase in tumor folate by 1 hr that returned to near basal levels by 12 hr. Reduced folates were elevated to a lesser extent in animals on a standard diet. Tumor growth was suppressed approximately 80% when FU was administered to depleted animals 1 hr after LV administration, compared with approximately 50% suppression in control mice. LV administered 12 hr before FU resulted in tumor growth stimulation that was consistent with the pronounced growth stimulation when LV was administered without FU. These results show that dietary folic acid depletion can lead to a more responsive FU/LV model and that administration of LV at an improper time before FU not only can fail to potentiate but also can result in tumor growth stimulation.

Adenocarcinoma↗
PubMed2000

[The importance of folic acid in current medicine].

Lately, folic acid deficiency is gaining a predominant role in the pathogenesis of congenital malformations and cardiovascular diseases in adults. The planning of individual and population preventive strategies for these diseases must consider this deficiency. This paper reviews the anatomical, biochemical and molecular bases of neural tube defects and cardiovascular diseases in adults. In these two frequent diseases, folic acid supplementation has shown a clear cut protective effect.

Adult↗
PubMed1982

Altered jejunal surface pH in coeliac disease: its effect on propranolol and folic acid absorption.

1. Propranolol and folic acid absorption were studied separately in healthy subjects, non-coeliac patients and patients with treated and untreated coeliac disease. 2. The surface pH of jejunal biopsy samples was measured with a pH electrode. 3. When compared with values found in healthy subjects, plasma propranolol levels were elevated in coeliac disease and, in contrast, serum folic acid levels were depressed after oral administration of the drug. Jejunal surface pH was more alkaline in the coeliac groups than in the healthy and non-coeliac subjects. 4. Pharmacokinetic analysis of the plasma drug levels allowed evaluation of the rate constants associated with absorption and elimination. The absorption rate constant was decreased for folic acid in the coeliac group, but increased for propranolol. These changes correlated with variation in surface pH. 5. Although the changes in drug disposition in treated and untreated coeliac disease are the result of several factors, it is suggested that jejunal surface pH may affect the rate of absorption and therefore the plasma concentration-time profile of drugs which undergo dissociation.

Adolescent↗
PubMed1987

[Plasma kinetics and elimination of folic acid].

The plasma kinetics and elimination of folic acid were studied in 11 healthy subjects after saturation with a multivitamin preparation. A radioassay was utilized for the determination of folic acid. After the i.m. injection of 1.1 mg folic acid sodium, a maximum plasma level of 63.7 +/- 14.3 nmol/l was reached after 0.69 +/- 0.26 h. The elimination half-life time amounted to 1.53 +/- 0.46 h. Based on the injected amount of folic acid, the cumulative increase in elimination within 24 h amounted to 9.4% +/- 3.1%. Within the first 6 h 81.4% +/- 6.1% of the administered folic acid appeared in the urine and in the following 4 h 17.3% +/- 5.4%.

Adult↗
PubMed1981

The effects of ascorbic acid, vitamin B6, vitamin B12, and folic acid supplementation on the breast milk and maternal nutritional status of low socioeconomic lactating women.

In this double-blind study, the effects of ascorbic acid, vitamin B6, vitamin B12, and folate supplementation on the maternal nutritional status and vitamin content of breast milk in 16 low socioeconomic lactating women were studied. Nine subjects were administered a commercial multivitamin-multimineral supplement and seven were given placebos. Milk samples were collected four times per day at 4-h intervals from 5 to 7 and 43 to 45 days postpartum. Fasting blood samples were taken from all mothers at the end of each milk collection period. Dietary records of all foods consumed were kept from 4 to 7 and 42 to 45 days postpartum. There were no significant differences in milk or plasma levels of ascorbic acid between the unsupplemented and supplemented groups. Both the EGPT index and milk concentration of vitamin B6 were significantly different (p less than 0.01) between the unsupplemented and supplemented groups. The milk concentrations of vitamin B12 increased significantly (p less than 0.05) in the supplemented group, as did the milk concentrations of folate (p less than 0.01). Because of consistently low levels of dietary vitamin B6 and folic acid in this group of low socioeconomic lactating women, either dietary changes or supplements could be necessary to maintain recommended levels of these vitamins in the womens' breast milk.

Ascorbic Acid↗
PubMed1995

Folic acid requirements of broilers.

1. Dietary folic acid requirements of broilers were studied in three experiments using wheat- and maize-based practical diets. Requirements were assessed on the basis of performance and metabolic criteria. 2. Growth and food conversion efficiencies were optimised with supplements of 1.5 mg folic acid/kg added to basal mash starter diets. The dietary folic acid requirement of broilers was estimated to be in the range of 1.7 to 2.0 mg/kg. 3. Red blood cell phosphoribosylpyrophosphate concentrations and dihydrofolate reductase activities did not show consistent changes over the range of dietary folate concentrations studied but plasma folate concentrations responded markedly to dietary folate supplementation. 4. Adding choline to diets in amounts greater than the normal requirement did not spare the requirement for folic acid. 5. It is suggested that minimum folic acid supplements for pelleted practical diets should be in the order of 2.5 to 3 mg/kg.

Animals↗
PubMed2005

Elderly psychiatric patients at risk of folic acid deficiency: a case controlled study.

In the elderly, folic acid deficiency may result in psychiatric symptoms or the increases in severity of other organic and non-organic mental diseases. We aimed to characterize elderly, community-dwelling, newly admitted patients to a large urban psychiatric hospital who are suffering from untreated folic acid deficiency in comparison with elderly inpatients who do not suffer from this deficiency. During a 2-year period, all subjects aged 65 years or older admitted to the large psychiatric center were tested for levels of serum folic acid levels. Subjects suffering from folic acid deficiency were compared (unpaired t-test) with matched patients with normal serum levels. Of the 293 newly admitted elderly patients 45 (15.7%) suffered from folic acid deficiency. Mean age for the folic acid deficient group was 77.3+/-8.1 years, 38% were diagnosed as suffering from dementia, 22% were depressed and 51% were living alone. In the comparison group mean age was 77.3+/-6.3 years, 33% were diagnosed as suffering from dementia, 24% were suffering from depression and 57% were living alone. We conclude that we could not find any "characteristic" of elderly subjects at risk of folic acid deficiency.

Aged↗
PubMed2003

Supplementation with micronutrients in addition to iron and folic acid does not further improve the hematologic status of pregnant women in rural Nepal.

Iron deficiency is one of the main causes of anemia during pregnancy, although other micronutrient deficiencies may play a role. We examined the effects of daily antenatal and postnatal supplementation with four combinations of micronutrients on maternal hematologic indicators in a double-masked randomized controlled community trial. Communities, called sectors, were randomly assigned to supplementation with folic acid (400 microg), folic acid plus iron (60 mg), folic acid plus iron and zinc (30 mg) and folic acid plus iron, zinc and 11 other micronutrients, each at the approximate recommended daily allowance for pregnancy all given with vitamin A as retinol acetate (1000 microg retinol equivalent), or vitamin A alone as the control group. Hemoglobin (Hb) and indicators of iron status were assessed at baseline and at 32 wk of gestation. At 6-wk postpartum, Hb assessment was repeated using a finger stick. Severely anemic women (Hb < 70 g/L) were treated according to WHO recommendations. Folic acid alone had no effect on maternal anemia or iron status. Hb concentrations were 14 g/L, [95% confidence limits (CL), 8.3-19.2], 10.0 g/L (CL, 5.2-14.8) and 9.4 g/L (CL, 4.7-14.1) higher in the groups receiving folic acid plus iron, folic acid plus iron and zinc and folic acid plus iron, zinc and multiple micronutrients, respectively, relative to the control. Anemia in the third trimester was reduced by 54% with folic acid plus iron, by 48% with folic acid plus iron and zinc and by 36% with folic acid plus iron, zinc and multiple micronutrients supplementation, relative to the control (P < 0.05). Thus, the combinations of folic acid plus iron and zinc and folic acid plus iron, zinc and multiple micronutrients provided no additional benefit in improving maternal hematologic status during pregnancy compared with folic acid plus iron. The level of compliance and baseline Hb concentrations modified the effect of iron.

Dietary Supplements↗
PubMed1971

Folates in plasma and bile of man after feeding folic acid--3H and 5-formyltetrahydrofolate (folinic acid).

During the 1st hr after feeding folic acid-(3)H ((3)H-PteGlu) to fasting human volunteers, plasma S. faecalis and (3)H activity were elevated to an equivalent degree, whereas after this, the (3)H activity exceeded S. faecalis activity, which suggests gradual conversion of folic acid-(3)H to methyltetrahydrofolate-(3)H (5-CH(3)H(4) PteGlu). The increase of L. casei activity exceeded the increase of S. faecalis and (3)H activity, which is consistent with flushing of endogenous methyltetrahydrofolate from the tissues by the administered folic acid-(3)H. Feeding of 5-formyltetrahydrofolate (+/-5CHOH(4)PteGlu) produced a large increase of plasma L. casei activity and only a slight increase of S. faecalis and P. cerevisiae activity, which is consistent with very rapid conversion of folinic acid to methyltetrahydrofolate. Bile folate concentration determined microbiologically was 2.3-9.8 times plasma folate. 40-80% of the bile folate was S. faecalis-active and 20-35% P. cerevisiae-active. Chromatography of bile folates on TEAE-cellulose showed several folates including four tentatively identified as 10-formyltetrahydrofolate (10-CHO-H(4)PteGlu), 10-formylfolate (10-CHO-PteGlu), and/or 10-formyldihydrofolate (10-CHOH(2)PteGlu), methyltetrahydrofolate, and possibly a triglutamate folate. After folate ingestion bile folate concentration increased rapidly. The distribution of bile folates measured by microbiological assay was similar after either folic or folinic acid feeding. Most of the (3)H label of folic acid-(3)H appeared in the biological folates of bile rather than in the folic acid fraction, which shows that the administered folic acid was rapidly transformed to other folates. Folate polyglutamate deconjugating enzyme activity was found to be much less than in serum. Polyglutamates of the type found in yeast were not found in bile. It is suggested that biliary folate may reflect the hepatic intracellular oligoglutamate folate pool rather than the folate as it appears in the hepatic portal blood.

Bile↗
PubMed1981

Influence of routine administration of folic acid and iron during pregnancy.

Haematological and folic acid status were assessed in 200 women in the 6th month of pregnancy. Folic acid deficiencies with no or little haematological impairment were found in one third of the cases, and their occurrence increased when the socioeconomic level was low. During the last trimester of pregnancy, the women were given either iron alone or iron and folic acid supplementation. In the mothers, the rise of folate values in serum and red blood cells, in the folic acid-supplemented group, had no obvious haematological consequences, showing that iron therapy alone can, in developed countries, prevent the anaemia in pregnancy. In the infants, there was no difference in the haematological indices, whatever the mothers' treatment had been. However, a significant difference appeared for the gestational age and, therefore, the height and weight. Folic acid supplementation during pregnancy increased its duration by virtually 1 week.

Adult↗
PubMed1988

Adsorptive stripping voltammetric assay of folic acid in human serum.

Folic acid was voltammetrically measured after preconcentration by adsorption at the static mercury drop electrode. Phase selective AC voltammetry provided the most sensitive stripping signal. After previous analyte extraction, using liquid-solid extraction with a C-18 reversed phase cartridge, the method was suitable for folic acid measurement in human serum. The detection limit was 5.9 x 10(-9) M with an overall precision of 9.9% (R.S.D.; n = 7) at the concentration level of 1.0 x 10(-7) M with a mean recovery of 57%.

Journal Article↗
PubMed1995

Enhanced antitumor activity for the thymidylate synthase inhibitor 1843U89 through decreased host toxicity with oral folic acid.

The purpose of this investigation was to determine whether antitumor selectivity of the third generation thymidylate synthase inhibitor 1843U89 could be enhanced by a combination of the drug with folic acid. The effects of folic acid on toxicity of 1843U89 to the dog and mouse and on antitumor efficacy of 1843U89 in the mouse were studied. These data were compared to the effect of folic acid on the in vitro cell culture antitumor activity of 1843U89. The sensitivity of eight cancer cell lines (three ovarian, one colon, one ileocecal, one epidermoid, one osteosarcoma, and one breast line) to 1843U89 was tested in vitro in the presence and absence of folic acid. Folic acid concentrations greater than 100 microM were required to decrease 1843U89 activity in seven of the cell lines. Only the activity in HCT-8, the ileocecal line, was reserved at folic acid concentrations below 100 microM. Oral folic acid given 30 min prior to an i.v. dose of 1843U89 increased the maximally tolerated dose and the lethal dose of 1843U89, both in dogs and in thymidine-depleted mice. In mice, oral folic acid produced little or no effect upon the antitumor efficacy of 1843U89 in two of three tumor cell lines in vivo. HCT-8, the line that was sensitive to folate reversal in vitro, was also sensitive in vivo. The results show that an oral dose of folic acid 30 min prior to i.v. 1843U89 can block mouse and dog intestinal toxicity without decreasing efficacy of 1843U89 in two of three human tumor lines in the nude mouse. Thus, the data reported here indicate that the antitumor selectivity of 1843U89 may be enhanced through a combination of 1843U89 with oral folic acid.

Animals↗
PubMedDate not supplied

Folic acid intake of young women.

OBJECTIVE: To investigate the folic acid intake of young women ages 18-24. DESIGN: Nonexperimental, descriptive survey. SETTING: Small private college in western North Carolina. PARTICIPANTS: A convenience sample of 42 female college students ages 18-24. MAIN OUTCOME MEASURES: Survey of demographics, folic acid intake, knowledge of folic acid, and pregnancy contemplation. RESULTS: All participants were found to have an inadequate diet and an inadequate intake of folic acid. Only 33.3% reported taking daily multivitamins. These findings may be attributed to the participants' lack of knowledge about folic acid and the birth defects it helps to prevent. CONCLUSION: Inadequate folic acid intake is common in young women ages 18-24. These young women frequently have poor nutritional habits and are usually noncontemplators of pregnancy.

Adolescent↗
PubMed1979

Cyclic GMP and cyclic AMP changes in response to folic acid pulses during cell development of Dictyostelium discoideum.

Folic acid pulses induced developmental processes in agip 71, a morphogenetic mutant of Dictyostelium discoideum, strain Ax-2. Cells that had received folic acid pulses were able to form EDTA-stable cell aggregates and to complete full differentiation to fruiting bodies. In these cells no autonomous periodic activities were observed by light scattering. Folic acid pulses elicited increases in the concentrations of cyclic GMP and cyclic AMP. In undifferentiated cells, folic acid caused a rapid increase in the level of cyclic GMP without a significant change in the level of cyclic AMP. In an advanced developmental state folic acid caused an increase in cyclic AMP in addition to two successsive peaks of cyclic GMP. Experiments performed with the parent strain, Ax-2, also showed that during the development towards aggregation competence, cells acquired the ability to produce a cyclic AMP peak in response to folic acid.

Cell Adhesion↗