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[Effect of folic acid on metabolic processes in wounds].

In experiments on rats the effect of folic acid on the redox and energy-producing processes as well as upon the synthesis of collagen and protein fractions of the muscular tissue in the area of the wound was investigated. Low doses of folic acid are shown to intensify in the muscles of intact animals anaerobic, and in the wound muscles--aerobic processes. High doses of folic acid produce an opposite effect on the wound muscles, by intensifying anaerobic processes. Folic acid manifests itself as an activator of anabolic processes by intensifying the gluconeogenesis in the wound tissues, the biosynthesis of collagen in the muscles of intact animals, and to a lesser degree in the muscles of surgically treated animals.

Animals↗

Population-based case control study of folic acid supplementation during pregnancy.

Previous studies have demonstrated that periconceptional folic acid/multivitamin supplementation reduced the occurrence of neural tube defects. A case control analysis has been conducted in the dataset of the Hungarian Case Control Surveillance of Congenital Abnormalities, 1980-1991. In the study period, 54.9% of 30,663 pregnant women who had healthy babies (negative control group) were supplemented with high doses (in general 2 x 3 mg) of folic acid per day. In those 17,300 pregnant women who had offspring with congenital abnormalities, the rate of folic acid supplementation was 50.4%. Exposure histories: preconceptional, I, II, III, and IV-IX postconceptional months were determined by record reviews and questionnaire assessment. The case control pair analysis showed a significant protection after folic acid supplementation during the critical period of cardiovascular defects, neural tube defects, cleft lip with or without cleft palate and posterior cleft palate.

Case-Control Studies↗

Effect of folic acid plus glycine supplement on uterine prostaglandin and endometrial granulocyte-macrophage colony-stimulating factor expression during early pregnancy in pigs.

The objective was to determine the effects of folic acid+glycine supplement on uterine metabolism of prostaglandin and mRNA expression of endometrial granulocyte-macrophage colony-stimulating factor (GM-CSF) in nulliparous (NYL) and multiparous Yorkshire-Landrace (YL) sows, and in multiparous Meishan-Landrace sows (ML). In each of these three groups, sows were randomly assigned to two treatments: 15 ppm folic acid+0.6% glycine or no supplement. The dietary supplement was given from the estrus before mating to slaughter on Day 25 of pregnancy. At slaughter, endometrial tissue was collected to determine endometrial expression levels of GM-CSF mRNA, cyclooxygenase-1 (COX1) and -2 (COX2) and to evaluate in vitro endometrial secretion of prostaglandin E2 (PGE2) secretion. Allantoic fluid samples were also collected to determine the concentration of PGE2, prostaglandin F2alpha (PGF2alpha), estradiol-17beta (E2), progesterone (P4), and transforming-growth factor-beta2 (TGF-beta2). The allantoic contents of PGF2alpha, E2 and P4, and endometrial in vitro secretion of PGE2 were not significantly influenced by the folic acid+glycine supplement. The folic acid+glycine supplement tended (P<0.07) to increase allantoic content of PGE2 and TGF-beta2 in all sows and increased (P<0.05) endometrial expression of COX2, especially in NYL sows. The endometrial expression of COX1 was decreased (P<0.05) by folic acid+glycine supplement, especially in multiparous YL sows. The allantoic contents of PGE2 and PGF2alpha were not significantly affected by sow type. However, NYL sows had higher (P<0.05) endometrial in vitro secretion of PGE2 and allantoic content of P4 than multiparous YL and ML sows. The allantoic content of E2 was also higher (P<0.05) in NYL sows than in multiparous ML sows only. The allantoic content of TGF-beta2 was lower (P<0.05) in multiparous ML than in multiparous YL only sows. Finally, in YL and NYL sows, folic acid+glycine supplement decreased (P<0.05) the endometrial expression of GM-CSF but not in ML sows. In summary, folic acid+glycine supplement altered endometrial expression of GM-CSF and uterine metabolism of prostaglandins during the post-attachment period of porcine embryos but some of these effects were manifest only in Meishan and nulliparous sows.

Allantois↗

Folic Acid improves baroreceptor sensitivity in hypertension.

In hypertension baroreceptor-mediated modulation of heart rate is impaired, resulting in a decreased vagal control. Reactive oxygen species produced locally in the vasculature decrease baroreceptor sensitivity. Folic acid has antioxidant properties. Therefore, the aim of this study was to test whether folic acid improves baroreceptor function in hypertension. Twenty-one male patients with hypertension not taking any drugs for 2 weeks participated in the study and were randomized to folic acid 5 mg or matching placebo. Cardiac and vascular sympathetic baroreceptor functions were tested before and after a single dose of folic acid or placebo with two different methods: the alpha-coefficient method and the phenylephrine (PE) and sodium nitroprusside (SNP) bolus method. In the folic acid group both methods showed significantly improved cardiac and vascular sympathetic baroreceptor sensitivity compared with placebo. This study provides evidence that folic acid improves cardiac and vascular sympathetic baroreceptor sensitivity in hypertensive patients, which suggests an improved vagal control and an enhanced baroreceptor modulation of sympathetic vasomotor tone. Thus, folic acid may represent a novel treatment for prevention of orthostatic dysregulation and/or arrhythmic complications resulting from baroreceptor dysfunction.

Antioxidants↗

Rapid and specific high-pressure liquid chromatographic assay for folic acid in multivitamin-mineral pharmaceutical preparations.

A high-pressure liquid chromatographic assay for folic acid in multivitamin-mineral pharmaceutical formulations was developed. The internal standard solution used for sample extraction contained a chelating agent, pentetic acid, for prevention of metal ion-catalyzed degradation of folic acid in th prepared samples. Samples were chromatographed using a paired-ion mobile phase (water-methanol, approximately 76:24; 0.015 M phosphate buffer, pH 7.0; and 0.3% tetrabutylammonium hydroxide) on a column packed with octadecylsilane bonded to microparticulate silica gel. Sample preparation was rapid, and total chromatographic time was approximately 20 min. The method was accurate, precise, and highly specific. Folic acid and the internal standard, methylparaben, were separated from other tablet components and a number of potential impurities and degradation products of folic acid.

Capsules↗

Folic acid prevents neural tube defects: international comparison of awareness among obstetricians/gynecologists and urologists.

AIM: It has been suggested that periconceptional intake of folic acid prevents risks of having fetuses afflicted with neural tube defects. We aim to internationally investigate knowledge of the role of folic acid and attitudes toward the life-style of young women of child-bearing age among obstetricians/gynecologists and urologists. METHODS: A questionnaire was sent to obstetricians/gynecologists and urologists residing in Japan, South Korea, Taiwan, North America, Europe, Australia and New Zealand by post or e-mail. The investigation was conducted between December 2002 and November 2004. RESULTS: A mean of 91% of obstetricians/gynecologists and 56% of urologists are aware of the role of folic acid, where Asian urologists knew less compared to those of North America, Europe, Australia and New Zealand. A majority of doctors always, or occasionally, recommend folic acid supplements or multivitamins, well-balanced meals, and the cessation of smoking and drinking. An average of 85% of doctors believes information on folic acid should be disseminated to young women. CONCLUSIONS: A majority of obstetricians/gynecologists and urologists know the importance of periconceptional folic acid in reducing the risk of neural tube defects and have been advising young women to improve their lifestyle.

Awareness↗

Association of neural tube defects and folic acid food fortification in Canada.

Many women do not receive folic acid supplements before conception. In response, most of Canada's cereal grain products were being fortified with folic acid by January, 1998, thereby providing an additional 0.1-0.2 mg per day of dietary folate to the Canadian population. We assessed the effect of supplementation on prevalence of open neural tube defects in the province of Ontario. Among 336 963 women who underwent maternal serum screening over 77 months, the prevalence of open neural tube defects declined from 1.13 per 1000 pregnancies before fortification to 0.58 per 1000 pregnancies thereafter (prevalence ratio 0.52, 95% CI 0.40-0.67, p<0.0001). At a population level, folic acid food fortification is associated with a pronounced reduction in open neural tube defects.

Adult↗

Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study.

BACKGROUND: High concentrations of homocysteine and low concentrations of vitamin B-12 and folic acid are frequently observed in subjects with dementia. OBJECTIVE: We assessed whether serum concentrations of homocysteine, vitamin B-12, or folic acid predict cognitive decline in old age. DESIGN: This was a prospective, population-based, longitudinal study of 599 subjects (Leiden 85-Plus Study, Netherlands). The subjects were administered a battery of cognitive tests (including the Mini Mental State Examination, the Stroop test, a letter digit coding test, and a word recall test) at 85 y of age and yearly thereafter until 89 y of age. Serum concentrations of homocysteine, vitamin B-12, and folic acid were measured at 85 and 89 y of age. Cross-sectional associations between serum concentrations and cognition were assessed at 85 and 89 y of age. The association between baseline serum concentrations and subsequent longitudinal cognitive decline was assessed with the use of mixed linear models. RESULTS: In the cross-sectional analyses, serum concentrations of homocysteine and folic acid were significantly associated with cognitive performance, but serum concentrations of vitamin B-12 were not. In the longitudinal analyses, there were no significant associations of serum concentrations of homocysteine, vitamin B-12, or folic acid with rate of cognitive decline. CONCLUSIONS: Elevated serum concentrations of homocysteine and reduced folic acid are associated with cognitive impairment in elderly persons but do not predict an increased rate of cognitive decline. The association of high serum concentrations of homocysteine and low folic acid with cognitive impairment in old age is likely to be a consequence of disease and not a contributory cause.

Aged↗

Estimation of individual intakes of folate in women of childbearing age with and without simulation of folic acid fortification.

OBJECTIVES: The objectives of this study were to examine variability of folate intake in order to estimate the number of days needed to accurately estimate intakes in women of childbearing age and to simulate the effect of folic acid fortification of cereals and grains on individual folate intake. DESIGN: Observational study of food intake over a 60-day period. SAMPLING: A convenience sample of 21 women completed food records on randomly assigned days within a 60-day period. OUTCOMES MEASURED: Folate intake and variance ratios of folate intake. STATISTICAL ANALYSIS: Repeated measures analysis of variance. RESULTS: Six days of food records were needed to describe folate intake of these women of childbearing age (18 to 45 years) with 20% attenuation of a correlation coefficient between dietary folate intake and another biological variable. Seven days of records were needed with simulated folic acid fortification (assuming fortification of 140 micrograms folic acid per 100 g flour) and 5 days were needed with supplements containing 200 to 400 micrograms folic acid in addition to folic acid fortification. Food folate intake was 288 +/- 195 micrograms; only 2 of the participants consumed the recommended 400 micrograms. With fortification, folate intake increased to 550 +/- 279 micrograms without supplements and 609 +/- 327 micrograms with supplements. APPLICATIONS: Individual intakes of folate should be assessed with at least 7 days of dietary records (20% attenuation). In this sample, when folic acid fortification was added to dietary intake, routine supplementation was not necessary to achieve folate intakes of 400 micrograms in the majority of participants. The practice of routine folic acid supplementation should be considered carefully to ensure that individual intakes of folate do not exceed the upper limits of safety.

Adult↗

[Vitamin B12, folic acid and mental function in the elderly].

Elderly people is a vulnerable population group to specific nutrient deficiencies as vitamin B12 and folic acid, which are closely related to mental functions deterioration, especially of cognitive functions. This study was aimed to measure B12 vitamin and folic acid indicators and to establish relationships to mental function. 53 elderly, older than 60 years, living in a geriatric home were assessed. The dietary intake was evaluated by the direct weighed method, serum B12 vitamin and folic acid by radioimmunoanalysis and mental function by Foltein's mini-mental test. Dietary intake for Vit B12 was adequate and deficient for folic acid while serum levels were within normal range. Vitamin B12 levels were at marginal or deficiency values in 26,4% of the elderly and folic acid deficiency was present in 43.4%. 49% of the elderly had mental function alterations and B12 vitamin levels were significantly lower in this group. A positive association between age and mental function (elderly below 80 years had lower risk of mental impairment) and between serum B12 and mental function were found. Elderly were at risk of deficiency for both vitamins and age and mental function were associated to this risk. Further evaluation including other nutrients should be performed.

Age Factors↗

[6S]5-methyltetrahydrofolate or folic acid supplementation and absorption and initial elimination of folate in young and middle-aged adults.

OBJECTIVES: To assess the effects of supplementation with the diastereoisomer of 5-methyltetrahydrofolate ([6S]5-methylTHF), as an alternative supplement for folic acid, on folate absorption and elimination, in two age groups. DESIGN: A randomized, double-blind intervention study. SUBJECTS: A total of 12 young (<30 y) and 12 middle-aged (> or =50 y) healthy volunteers were recruited. METHODS: Volunteers were randomized to receive daily supplementation with 400 mug folic acid or equimolar amounts of [6S]5-methylTHF during 5 weeks. Before and after supplementation, absorption and initial elimination were calculated following oral [(2)H(2)]folic acid test doses using isotope kinetics in plasma. RESULTS: Folic acid absorption was lower in the middle-aged as compared to the young adults, both before (P = 0.03) and after (P = 0.05) supplementation. In the young adults, absorption decreased by 22% after [6S]5-methylTHF and increased by 21% after folic acid (P = 0.02). In the other age group, no such changes were found. The folate rate constant of elimination increased after folic acid supplementation in the young (+50%; P = 0.05) but not in the middle-aged (+18%; P = 0.5) adults. CONCLUSIONS: Young adults show increased folate turnover after folic acid supplementation relative to the effect of [6S]5-methylTHF supplementation. Similar differences are not observed in middle-aged adults, in whom folic acid absorption was found to be lower as compared to the young adults. SPONSORSHIP: Financial support was received from the European Union 5th Framework Programme (Grant QLRT-1999-00576).

Adult↗

The effects of folic acid in the prevention of neural tube development defects caused by phenytoin in early chick embryos.

STUDY DESIGN: The effects of phenytoin and folic acid on the development of neural tube defects in early chick embryos were studies. OBJECTIVE: To investigate the effects of folic acid in the prevention of neural tube development defects. SUMMARY OF BACKGROUND DATA: Several studies have shown that phenytoin selectively inhibits neural tube closure. Folic acid supplementation has been reported to decrease the occurrence of neural tube defects. METHODS: This study shows the effects of folic acid in preventing neural tube development defects caused by phenytoin in chicks based on light microscopy, transmission electron microscopy, and histopathological examination. Forty-five fertile Hubbard Broil eggs, all at Stage 8 (four somite) of development, were divided into three equal groups: Group 1 embryos (n = 15), the control group, were explanted and grown for 18 hours in a nutrient medium (thin albumin). Group 2 embryos (n = 15) were explanted and grown for 18 hours in a nutrient medium containing 500 microg/mL of phenytoin. Group 3 embryos (n = 15) were explanted and grown for 18 hours in a nutrient medium containing 500 microg/mL of phenytoin and 0.4 microg/mL of folic acid. RESULTS: After the incubation period, 86.6% of the control embryos (Group 1) had intact neural tubes; 80% of Group 2 and 46.6% of Group 3 embryos showed neural tube defects. CONCLUSIONS: The results of this study suggest that phenytoin causes neural tube defects, whereas folic acid decreases the incidence of neural tube development defects caused by phenytoin in early chick embryos.

Animals↗

Effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in premalignant gastric lesions.

AIM: To evaluate the effects of folic acid on epithelial apoptosis and expression of Bcl-2 and p53 in the tissues of premalignant gastric lesions. METHODS: Thirty-eight patients, with premalignant gastric lesions including 18 colonic-type intestinal metaplasia (IM) and 20 mild or moderate dysplasia, were randomly divided into a treatment group (n = 19) receiving folic acid 10 mg thrice daily and a control group (n = 19) receiving sucralfate 1,000 mg thrice daily for 3 mo. All patients underwent endoscopies and four biopsies were taken prior to treatment and repeated after concluding therapy. Folate concentrations in gastric mucosa were measured with chemiluminescent enzyme immunoassay. Epithelial apoptosis and the expression of Bcl-2 and p53 protein in gastric mucosa were detected with flow cytometric assay. RESULTS: The mean of folate concentration in gastric mucosa was 9.03+/-3.37 microg/g wet wt in the folic acid treatment group, which was significantly higher than 6.83+/-3.02 microg/g wet wt in the control group. Both the epithelial apoptosis rate and the tumor suppressor p53 expression in gastric mucosa significantly increased after folic acid treatment. In contrast, the expression of Bcl-2 oncogene protein decreased after folic acid therapy. CONCLUSION: These data indicate that folic acid may play an important role in the chemoprevention of gastric carcinogenesis by enhancing gastric epithelial apoptosis in the patients with premalignant lesions.

Adult↗

Insufficient folic acid intake in the Netherlands: what about the future?

BACKGROUND: In 1993 all women of childbearing age in the Netherlands were advised to take a daily 0.5 mg folic acid pill to reduce the risk for neural tube defects. This study describes both recent and past awareness and use of folic acid supplements in relation to socio-economic status in the Northern Netherlands. The consequences of a recent report of the Dutch Health Council report will be discussed as well. METHODS: In the most recent cross-sectional study (November 2000), pregnant women filled out a questionnaire. Out of 473 women, 461 were willing to cooperate. The highest fulfilled level of education was taken as an indicator for socio-economic status. RESULTS: Seventy-seven percent (n = 357) of the respondents had heard about folic acid before being pregnant. Sixty-three percent (n = 289) knew about the protective effect for NTDs and 33% (n = 151) knew the entire advised period. Sixty-one percent (n = 265) of the respondents used folic acid in some part of the advised period and 36% (n = 164) used it in the entire advised period. Higher educated women knew more about folic acid and used it significantly more often in the periconceptional period than lower educated women. CONCLUSIONS: Because compliance to proper use of folic acid was poor, food fortification in the Netherlands must be seriously considered. The Dutch Health Council wants to limit the fortification of food products to those products that are especially aimed for women who wish to become pregnant. The fortification of specific products instead of staple foods is a missed chance to reduce NTDs and possibly other birth defects and cardiovascular defects as well.

Adult↗

The study of neural tube defects after the Human Genome Project and folic acid fortification of foods.

The implementation of folic acid fortification will eliminate a proportion of neural tube defects (NTD). As a result, the etiologic and clinical profiles of the developmental disorder may both change. In the assessment of NTD as it evolves, the bioinformatics structure and content of the Human Genome Project will find vital application. One important development will be an enhanced understanding of the role of folic acid in global regulation of gene expression through epigenetic processes. In addition, bioinformatics will facilitate coordination of research in the basic sciences with clinical investigations to better define remaining etiologic factors.

Animals↗

Assessment of the potential effect of incremental increases in folic acid intake on neural tube defects in Australia and New Zealand.

OBJECTIVE: To estimate the number of neural tube defects that could be prevented in Australia and New Zealand by increasing levels of folic acid intake. METHODS: Available data on prevalence of neural tube defects in Australia and New Zealand, folic acid supplement use and serum folate were used in a published model to estimate the number of neural tube defects that could be prevented in Australia and New Zealand for increments of folic acid intake from 0.1 mg daily to 1 mg daily. RESULTS: An increase of 0.2 mg folic acid per day was estimated to result in the prevention of 49 (95% CI 27-84) neural tube defects per year in Australia and 11 (95% CI 6-18) in New Zealand. A separate estimation for Indigenous Australians found that 0.2 mg of folic acid daily could prevent 7 (95% CI 4-11) neural tube defects in Indigenous infants per year. CONCLUSIONS: These data should be useful in considering primary preventive strategies for neural tube defects, including the possible introduction of mandatory fortification of food with folic acid. The estimates are imprecise because of limitations in the data used in the model. IMPLICATIONS: More representative and precise data on neural tube defects, serum folate levels and use of folic acid supplements from all Australian States and New Zealand are needed to refine the output from the model and to provide a baseline assessment of folate status against which to measure the effects of any future interventions to prevent neural tube defects.

Australia↗