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Folic acid enrichment of bread does not appear to affect zinc absorption in young women.

BACKGROUND: In several countries cereals are now enriched with folic acid to reduce the risk of neural tube defects. Human studies suggest that folic acid interferes with zinc absorption. This raises concerns about the zinc status of high-risk groups such as infants, pregnant women, and older persons. OBJECTIVE: We sought to determine the effect of added folic acid on zinc absorption from white bread with high and low zinc contents. DESIGN: Zinc absorption was measured in 15 healthy women (22-33 y), each of whom consumed 4 single meals spaced 2 wk apart in a randomized crossover design. The servings of bread (100 g) differed in zinc and folic acid contents as follows: A, 1.2 mg Zn and 17 microg folic acid; B, 1.2 mg Zn and 144 microg folic acid; C, 3.0 mg Zn and 17 microg folic acid; and D, 2.9 mg Zn and 144 microg folic acid. Meals were extrinsically labeled with 65Zn and absorption was estimated from whole-body retention measurements. Folate status was assessed by measuring plasma and erythrocyte folate and plasma homocysteine concentrations. RESULTS: Mean (+/-SD) zinc absorption did not differ significantly in relation to the folate content of the breads at either the low zinc content (38.8 +/- 13.5% and 40.6 +/- 16.5% for A and B, respectively; P = 0.74) or the high zinc content (26.7 +/- 9.3% and 22.7 +/- 6.6% for C and D, respectively; P = 0.16). There was no significant correlation between folate status and zinc absorption (r < 0.3, P > 0.1). CONCLUSION: Fortification of white bread with a commonly used amount of folic acid did not appear to influence zinc absorption at either a high or a low zinc content.

Adult↗

Folic acid supplements during early pregnancy and likelihood of multiple births: a population-based cohort study.

BACKGROUND: Folic acid supplements are recommended for women of childbearing age to prevent neural tube defects in their offspring. Results of some studies, however, suggest an increase in multiple births associated with use of vitamin supplements that contain folic acid during pregnancy. Our aim was to assess this association. METHODS: We used data from a population-based cohort study from which we assessed the occurrence of multiple births in women (n=242015) who had participated in a campaign to prevent neural tube defects with folic acid supplements (400 microg per day) in China. Folic acid use was ascertained before pregnancy outcome was known. We studied the relation between multiple births and any use of folic acid pills before or during early pregnancy; additionally, we investigated mechanisms by which folic acid could potentially affect the occurrence of multiple births by examining pill-taking at three time periods: before ovulation, around the time of fertilisation, and after conception. FINDINGS: 1496 (0.62%) multiple births occurred in a cohort of 242015 women who had registered with the study between October, 1993, and September, 1995, and who had a pregnancy not affected by a birth defect; the rate of multiple births in women who did and did not take folic acid before or during early pregnancy was 0.59% and 0.65%, respectively (rate ratio 0.91; 95% CI 0.82-1.00). INTERPRETATION: Our findings suggest that consumption of folic acid supplements during pregnancy is not associated with an increased occurrence of multiple births.

Adult↗

[Vitamin B12 and folic acid in chronic kidney failure and after kidney transplantation].

Vitamin B12 in plasma, folic acid in plasma and erythrocytes were examined in 11 patients in the polyuric stage of chronic renal failure without dialyzation treatment, in 38 patients included in a long-term dialyzation programme before and after 3 months' oral administration of folic acid--(2 X 5 mg week)--and in 23 patients after transplantation of the kidneys. In none of the examined groups vitamin B12) and folic acid deficiency in plasma was detected. A reduced folic acid level in erythrocytes, but still in the reference range, was found in patients in the long-term dialyzation programme without supplementation. Supplementation with folic acid increased its concentration in plasma 4.5 times and in red cells 5.5 times. Haemodialysis did not influence the concentration of the examined indicators in plasma and red cells. According to the recorded results it is not necessary to supplement patients in long-term dialyzation programme and after renal transplantation with vitamin B12 and folic acid, if their dietary protein intake is not restricted.

Female↗

Reversible malabsorption of folic acid in the elderly with nutritional folate deficiency.

In normal subjects, the folic acid absorption (TRIFA test) was independent of age and sex. Among 53 geriatric patients with nutritional folate deficiency, impaired absorption of folic acid was present in 19 (36%). After treatment with folic acid for 4 weeks, the absorption returned to normal. It is concluded that folate deficiency per se can produce a malabsorption syndrome resulting in further depletion of folate. Protein deficiency and weight loss alone do not impair the absorption of folic acid.

Adult↗

Ambulant photodynamic therapy of superficial malignomas with 5-ALA in combination with folic acid and use of noncoherent light.

This study reports our first results of ambulant photodynamic treatment with 5-aminolevulinic acid (5-ALA) in combination with folic acid and subsequent illumination with a noncoherent light source. The compound was topically applied to avoid total body skin sensitivity which occurs in the case of systemic administration. If no therapeutic response could be proved, we added folic acid to 5-ALA for a further treatment attempt. Illumination was performed by broad band red thermic light to also excitate reaction products with absorption bands located near to that of the sensitizer. As a result, we observed a response in all cases, however, in some cases only after the addition of folic acid.

Administration, Topical↗

Folic acid has a disinhibitory action in the rat hippocampal slice preparation.

The effects of folic acid on synaptic transmission in the hippocampal slice have been studied. Application of folic acid (0.1-1 mM) increased the size of population spikes recorded extracellularly in the CAl pyramidal cell layer and caused the appearance of multiple population spikes. Intracellular recording revealed that folic acid had no consistent effect on the membrane potential, but greatly reduced the rapid chloride-mediated phase of the inhibitory postsynaptic potential (IPSP) evoked by ortho- and antidromic stimulation. The slower, potassium-mediated phase of the IPSP was usually enhanced. Furthermore, folic acid abolished spontaneous IPSPs recorded with potassium chloride-filled microelectrodes. All of these effects were quickly reversible when the drug was washed from the chamber. Finally bath-applied folic acid reduced the hyperpolarization produced by iontophoretically applied GABA. Based on these results, we conclude that folic acid produces its excitatory effects on hippocampal pyramidal cells by a disinhibitory action which involves a postsynaptic blockade of GABA responses.

Animals↗

Folic acid awareness and use among women with a history of a neural tube defect pregnancy--Texas, 2000-2001.

The use of folic acid is a critical component in preventing birth defects. Health-care providers should take advantage of all health-care visits to counsel not only women at high risk (i.e., those with a history of having an infant with a neural tube defect [NTD]) but all women regarding the importance of folic acid use. A study conducted in Texas confirmed that white and Hispanic mothers were equally likely to recall receiving postpartum advice to use folic acid; however, Hispanic women were much less likely to use folic acid, compared with white women. This report covers data from May 2000 through November 2001. A study was conducted in Texas to determine whether women at high risk recall and follow recommendations to use folic acid. The study included 195 women at high risk and 223 control mothers who gave birth to infants without birth defects. These women participated in a telephone interview for a population-based case-control study of NTDs. Approximately 56.4% (110 of 195) of mothers who had infants affected by an NTD recalled receiving postpartum advice to use folic acid, compared with 25.6% (57 of 223) of control mothers (p < 0.01). Among nonpregnant case mothers, 54 (32.7%) of 165 reported regular use of supplements containing folic acid, and 53 (25.2%) of 210 nonpregnant control mothers reported this behavior (p = 0.11). Among case mothers, use of folic acid was significantly higher for whites (64.7%) versus Hispanics (16.5%) (p < 0.001); for women with some college education (57.1%) versus no college education (20.2%; p < 0.001); for women who were trying to get pregnant (66.7%) versus those using birth control (38.3%) or reporting using no contraceptive method (18.8%) (p = 0.001); and for women who reported receiving advice to use folic acid (40.9%) versus those who did not (22.2%; p = 0.01). Findings from this study support the need to implement NTD recurrence prevention activities in Texas. Data also identify a need for educational strategies in Texas that target Hispanic women at high risk, especially those who primarily speak Spanish. Further efforts should be made to determine why Hispanic women have low rates of folic acid use (e.g., the cost of vitamins and language and cultural barriers). On the basis of a review of research and current practice, recommendations developed by the Public Health Service include 1) women at risk for a recurrent NTD-affected pregnancy should take 0.4 mg of folic acidper day; and 2) if a woman at high risk is planning a pregnancy, she should consult her physician regarding taking the higher dose of 4.0 mg per day.

Adult↗

Chromatographic assays for folic acid.

TLC and high-pressure liquid chromatographic (HPLC) assays for folic acid were developed. In the TLC procedure, the folic acid band was extracted from the silica gel after development and determined spectrophotometrically by an oxidation and Bratton-Marshall sequence. A column packed with octadecylsilane chemically bonded to microparticulate silica gel was used for the HPLC assay. Potentiometric determination of water in folic acid samples was necessary to obtain accurate purity values. In a comparison of four assay methods, a direct colorimetric method gave precise, but unspecific, results, while the USP XIX colorimetric method lacked both precision and specificity. The two chromatographic methods were both precise and specific and gave the same assay results. Both methods separated p-aminobenzoic acid, N-(p-amino-benzoyl)-L-glutamic acid, 2-amino-1,4-dihydro-4-oxo-6-pteridinecarboxylic acid, 2-amino-4(1H)-pteridinone, and several unidentified impurities from folic acid.

Chromatography, High Pressure Liquid↗

Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid.

The natural diastereoisomer [6S]-5-methyltetrahydrofolate ([6S]-5-MTHF) may be a safer fortificant than folic acid for neural tube defect (NTD) prevention because it is unlikely to mask vitamin B-12 deficiency. An inverse relationship between NTD risk and blood folate concentrations has been reported. In this randomized, placebo-controlled, double-blind trial, we compared the effects of [6S]-5-MTHF and folic acid supplementation for 24 wk on plasma folate and red cell folate (RCF) in women of childbearing age (18-49 y). Women (n = 104) were randomly assigned to receive a supplement containing [6S]-5-MTHF (113 micro g/d), folic acid (100 micro g/d) or placebo. The mean estimated linear increase in plasma folate concentration was 0.3 [95% confidence interval (CI): 0.1, 0.5], and 0.4 (0.2, 0.6) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. The mean estimated linear increase in RCF was 7.4 (95% CI: 4.5, 10.3), and 8.3 (4.4, 12.3) nmol/(L. wk) in the [6S]-5-MTHF and folic acid groups, respectively. There were no differences in the slopes between the [6S]-5-MTHF group and the folic acid group in either plasma folate (P = 0.48) or RCF (P = 0.70). At 24 wk, estimated mean increases in plasma folate concentrations were 6.9 (95% CI: 1.7, 12.2) and 9.2 (3.3, 15.1) nmol/L, and in RCF, 251 (143, 360) and 275 (148, 402) nmol/L, in the [6S]-5-MTHF and folic acid groups, respectively, relative to the placebo group. These data suggest that low dose [6S]-5-MTHF and folic acid supplementation increase blood folate indices to a similar extent. A steady state in the blood indices had not been reached by 24 wk.

Adolescent↗

[Awareness and periconceptional use of folic acid among non-western and western women in the Netherlands following the 1995 publicity campaign].

OBJECTIVE: To investigate the influence of ethnicity on the awareness and use of folic acid by pregnant women. DESIGN: Secondary data analysis. METHOD: Using the data on 1555 women, collected during a cross-sectional study conducted among pregnant women with good knowledge of the Dutch language in 1996, the authors determined what was known about the recommendation to use folic acid around the time of conception and what the actual use was. Women were defined as either 'western' or 'non-western' on the basis of the place of birth of the woman and her parents. RESULTS: Of the 1555 pregnant women, 74 (5%) were non-western or of non-western descent. Non-western women more often had a lower educational level than western women (51% versus 34%; p = 0.002) and more often had an unintended pregnancy (24% versus 8%; p < 0.0001). 41% of the non-western women had heard of the recommendation to use folic acid before pregnancy, compared to 79% of the western women (p < 0.0001). However, the use of folic acid was not significantly different between non-western and western women (56% versus 69%) if they had been aware of the recommendation to use folic acid before pregnancy. Awareness of the recommendation to use folic acid was higher in older women (OR: 1.46; 95% CI: 1.13-1.89), women of western descent (0.27; 0.16-0.47), women with a higher level of education (0.35; 0.27-0.45) and in case of planned pregnancy (0.45; 0.31-0.67). The use of folic acid, restricted to women who were aware of the recommendation to use folic acid before their pregnancy, was higher in older women (1.37; 1.05-1.80) and lower in those with more previous pregnancies (0.57; 0.43-0.75) and in case of an unplanned pregnancy (0.55; 0.34-0.88). CONCLUSION: Although non-western women had less knowledge of the recommendation to use folic acid than western women, the use of folic acid was not significantly different from that by western women if they had been aware of the recommendation to use folic acid before pregnancy. Continued education on folic acid targeting non-western and western women is important.

Adolescent↗

Promotion of folate for the prevention of neural tube defects: knowledge and use of periconceptional folic acid supplements in Western Australia, 1992 to 1995.

To assess changes in knowledge and use of folic acid supplements in relation to a statewide health promotion project for the prevention of neural tube defects, we surveyed general practitioners, pharmacists, women of child-bearing age and pregnant women in Western Australia. We also collected data on wholesale sales of folic acid supplements. By the end of the project, 56.5 per cent of general practitioner respondents knew that the recommended dose of folic acid was 0.5 mg and 70 per cent offered folic acid supplements to women planning pregnancy, 82.5 per cent of responding pharmacists knew the recommended dose, and 87.5 per cent reported an increase in sales of 0.5 mg folic acid. Wholesale sales of 0.5 mg folic acid increased markedly in Western Australia compared with other states. From shopping centre surveys of women of child-bearing age we estimated that their knowledge of the association between folate and spina bifida increased from 8.2 per cent before the project to 67.5 per cent 2.5 years later, and doctors were a major source of information for women. In a 1995 survey of a sample of pregnant women, 43.1 per cent with planned pregnancies had taken folic acid supplements periconceptionally, compared with 19.1 per cent in a similar survey in 1993.

Adult↗

Knowledge among young people about folic acid and its importance during pregnancy: a survey in the Federal State of Saxony-Anhalt (Germany).

Periconceptional folic acid supplementation is recommended to prevent congenital malformations, mainly neural tube defects, but only 7% of pregnant women in Saxony-Anhalt (Germany) take folic acid at least 4 weeks before conception and in the first 3 months of pregnancy. From March to June 2004, we sent standardized questionnaires about folic acid and its importance during pregnancy to 33 schools in the Federal State of Saxony-Anhalt. A total of 4332 young people aged 1521 years completed the questionnaire, of which 2632 were girls (61%) and 1685 were boys (39%). The majority of them (61%) had heard about folic acid, but only 5% knew that it is a vitamin and 0.7% were aware of the physiological functions of folic acid. Only 22% of the young people answered that folic acid should be taken before and during pregnancy, whereas almost all respondents knew other precautions during pregnancy, e.g. "no smoking" and "no alcohol". Our survey shows that the level of awareness of the importance of folic acid at schools is very low. We suggest that the problem of folic acid should be included in the curricula of biology classes at schools to spread the knowledge of this subject among young people.

Adolescent↗

Treatment with different doses of folic acid in haemodialysis patients: effects on folate distribution and aminothiol concentrations.

BACKGROUND: Hyperhomocysteinaemia is highly prevalent among haemodialysis patients and may contribute to their increased cardiovascular risk. Treatment with pharmacological doses of folic acid lowers the plasma homocysteine concentration in these patients. The purpose of the present study was to expand the knowledge about such treatment by testing the effects of stepwise increases in the dose of folic acid on the concentrations of plasma and red blood cell folate as well as the total plasma concentrations of homocysteine (tHcy), cysteine (tCys), and glutathione (tGSH) in patients on chronic hemodialysis. METHODS: Fourteen stable haemodialysis patients completed the study which consisted of four consecutive periods, each of 6 weeks duration: (i) no treatment with folic acid (control period); (ii) 5 mg of folic acid three times per week (15 mg/week); (iii) 5 mg of folic acid daily (35 mg/week); (iv) 10 mg of folic acid daily (70 mg/week). RESULTS: Neither plasma or red cell folate nor plasma aminothiol concentrations changed significantly during the control period. The mean red cell folate concentration doubled during the administration of folic acid at the dose of 15 mg/week but at higher doses the further rise was only marginal. The mean folate concentration in plasma increased steeply especially at the higher doses of folic acid. During treatment with 15 mg/week of folic acid, tHcy fell by a mean of 36%, tGSH increased by a mean of 34%, but tCys was unaffected. Increases in the dose of folic acid did not augment these responses. CONCLUSIONS: The maximal effect on tHcy seemed to be obtained already at the lowest given dose of folic acid (15 mg/week). At that dose, the red blood cells approached folate saturation, which may reflect the situation in other cells that participate in homocysteine metabolism and explain why further increases in the dose of folic acid are not effective from a tHcy-lowering point of view.

Biomarkers↗

Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

BACKGROUND AND METHODS: Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. RESULTS: Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). CONCLUSIONS: Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Adult↗

The influence of folic acid on the frequency of epileptic attacks.

A double blind trial of folic acid against placebo was carried out on out-patients with epilepsy treated with Phenytoin. There was a minimum period on treatment of one year. While the group receiving folic acid in the treatment period showed a significant improvement in seizure frequency, the placebo group also showed some improvement. It is concluded that the improvement while on folic acid was not due to the folic acid treatment alone. The subjective well-being of patients was not influenced by folic acid therapy.

Adult↗

Effect of folic acid on human oral epithelium in vitro.

The cytomorphological effects of folic acid were studied using in vitro established human oral epithelium. It was demonstrated that a concentration twice that used clinically (200 micrograms/ml) did not induce marked cytotoxic reaction in the cultured cells. The most pronounced changes were observed in cultures exposed to 200 micrograms/ml folic acid both in primary culture and subculture. The cultures displayed areas of degenerating cells showing oedema and increased translucency of the cytoplasm, flattened cells with distinct tonofilaments and atypical mitotic figures. Identical changes were found in cultures exposed to 50 and 100 micrograms/ml folic acid but to a lesser extent than in 200 micrograms/ml. These changes indicated that folic acid increased the number of cells undergoing terminal differentiation. From this study we suggested that folic acid when applied topically may play a role in local stimulation of epithelial cell differentiation leading to enhanced healing of oral ulcers.

Cells, Cultured↗