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PubMed2007

Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply.

BACKGROUND: Folic acid fortification in the United States became mandatory January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We evaluated the impact of folic acid fortification on orofacial clefts using United States birth certificate data for 45 states and the District of Columbia. METHODS: Prevalence ratios (PRs) were calculated comparing orofacial cleft prevalence among births prefortification (1/1990-12/1996) and postfortification (10/1998-12/2002), based on fortification status at conception. The JoinPoint Regression Program and exponentially weighted moving average charts (EWMA) were used to assess the timing of any statistically significant changes in prevalence. Data were stratified by maternal race/ethnicity, age, smoking, and timing of prenatal care. RESULTS: Orofacial clefts declined following folic acid fortification (PR=0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant decrease in the fourth quarter of 1998. The JoinPoint graph had one change in slope, with a significant quarterly percent change (-0.34) between 1996 and 2002. The decline in orofacial clefts occurred in non-Hispanic Whites but not other racial/ethnic groups, nonsmokers but not women who reported smoking during pregnancy, and women who received prenatal care in the first trimester but not women who began receiving care later in pregnancy. CONCLUSION: Folic acid fortification in the United States was associated with a small decrease in orofacial cleft prevalence, with the timing of the decline consistent with the introduction of fortification. The decline is much smaller than that observed for NTDs, but nonetheless suggests an additional benefit of this public health intervention.

Cleft Lip↗
PubMed1977

Epilepsy and folic acid.

With 15 cases of epilepsy as the subject, studies were made of the therapeutic effects of folic acid on psychiatric symptoms and clinical seizures. Folic acid proved effective for a part of chronic and prolonged psychiatric symptoms shown by epileptic patients and brought on slight improvement in hyperexcitability, aggressiveness, bad humor and slowness of psychomotor activities. Improvement in mood was also observed. However, incidence of clinical fits increased in three cases. Electroencephalograms showed the desynchronizing phenomenon following oral administration of folic acid. Appearance or increase of spikes was noted in six cases. The epileptic group showed significantly low folic acid level in both serum and spinal fluid compared with the non-epileptic group. When folic acid was administered orally to the epileptic group, the serum folic acid level increased easily but the folic acid level in spinal fluid hardly increased.

Adult↗
PubMed1986

Assessment of cytogenetic response to folic acid deprivation in rat lymphocytes.

Rat lymphocyte cultures were initiated in minimal essential medium containing 0, 0.01, 1.0, or 10 mg/l of folic acid to investigate the influence of folic acid on cell kinetics, chromosome aberration, and sister chromatid exchange (SCE) frequencies. No significant difference was observed between cultures with and without folic acid in mitotic index or cell cycle kinetics as judged by the numbers of average lymphocyte divisions. However, a sequential reduction in the number of chromatid gaps occurred as the concentration of folic acid increased. On the other hand, addition of folic acid did not significantly affect the SCE frequency. Although folic acid does not seem to alter SCE formation, its significant influence in the reduction of chromatid gaps suggests that caution should be exercised in selecting a medium regarding folic acid content especially because gaps alone are produced by certain dose levels of some chemical clastogens.

Animals↗
PubMed1971

Effect of folic acid by mouth on cerebrospinal fluid homovanillic acid and 5-hydroxyindoleacetic acid concentration.

Administration of 30 mg folic acid by mouth caused a significant fall in cerebrospinal fluid homovanillic acid concentration in 11 subjects. There was no significant change of 5-hydroxyindoleacetic acid concentration. The fall was less marked in five patients on anticonvulsant medication and failed to reach statistical significance. Neither homovanillic acid nor 5-hydroxyindoleacetic acid concentrations changed significantly when 15 mg folic acid was given in divided dosage for one, two, and four weeks. The effect appeared to be related to the height of serum-folate levels reached and to be independent of cerebrospinal fluid-folate levels, which did not change significantly. Possible mechanisms and their potential therapeutic application are discussed.

Administration, Oral↗
PubMed2001

Chemiluminescence flow sensor for folic acid with immobilized reagents.

A novel chemiluminescence (CL) sensor for folic acid combined flow-injection (FI) technology was presented in this paper. The analytical reagents involved in the CL reaction, including luminol and hexacyanoferrate(III), were both immobilized on an anion-exchange column in FI system. The CL signal produced by the reaction between luminol and hexacyanoferrate(III), which were eluted from the column through sodium phosphate injection, was decreased in the presence of folic acid. The CL emission was correlated with the folic acid concentration in the range from 0.01 to 15 microg ml(-1), and the detection limit was 3.5 ng ml(-1) folic acid (3sigma). At a flow rate of 2.0 ml min(-1), including sampling and washing, could be performed in 2 min with a relative standard deviation of < 2.5%. The flow sensor could be reused more than 300 times and has been applied to the analysis of folic acid in pharmaceutical preparations. and the recovery was from 97.4% to 100.4%.

Ferricyanides↗
PubMed1999

Folic acid deficiency and cancer: mechanisms of DNA instability.

Folic acid deficiency in humans has been linked with megaloblastic anaemia, neural tube defects in the neonate, and heart disease. Folate has also been implicated in the development of cancer, especially cancer of the colorectum. There appear to be two principal mechanisms through which low folate status may increase the risk of malignancy. Folate deficiency, by reducing intracellular S-adenosylmethionine (SAM), can alter cytosine methylation in DNA, leading to inappropriate activation of proto-oncogenes and induction of malignant transformation. Alternatively, folic acid is crucial for normal DNA synthesis and repair. Folate deficiency may cause an imbalance in DNA precursors, uracil misincorporation into DNA, and chromosome breakage. This chapter briefly describes the epidemiological data supporting the involvement of folic acid in the aetiology of cancer. It also assesses the evidence from cellular, animal and human studies that folic acid can modulate DNA by such mechanisms.

Animals↗
PubMed1983

Effect of a synthetic folic acid analogue, 9-methyl-pteroylglutamic acid, on fetal chondrogenesis: ultrastructural observations.

Maternally administered folic acid antagonists (x-methyl-PGA and 9-methyl-PGA) are known to produce various skeletal malformations in the neonate. These defects are thought to be due in part to abnormal metabolism and/or deposition of various extracellular matrix components, i.e., collagen and glycosaminoglycans. Experimental reduction of glycosaminoglycan biosynthesis in vitro has been shown previously to alter the spatial orientation and normal pattern of collagen fibrillogenesis. Furthermore, dietary withdrawal of folic acid concomitant with maternal administration of 9-methyl-PGA has been shown to result in abnormal collagen, uronic acid, and hexosamine metabolism by fetal limbs. In the present study pregnant rats were exposed to a transitory folic acid deficiency from day 11 to 14 of gestation and fetal tibias (mid-diaphyseal region) were examined with the electron microscope on day 18 of gestation. Although we were unable to ascertain any aberrant patterns of fibrillogenesis and orientation with respect to collagen, this particular teratogenic regimen resulted in an altered pattern of chondrocyte development when observed at the ultrastructural level.

Abnormalities, Drug-Induced↗
PubMed1997

[Folic acid use for women desiring offspring: the family physician's response].

OBJECTIVE: To establish to what extent general practitioners (GP's) are familiar with the folic acid campaign of the Netherlands Bureau for Food and Nutrition Education, display a positive attitude regarding use of folic acid tablets by women who would like to become pregnant and factually provide information on folic acid. DESIGN: Cross-sectional, descriptive. SETTING: Regions: Central Brabant, Achterhoek, Randstad and Northern Netherlands. METHOD: In 1996 a printed questionnaire was sent to 300 GP's selected at random. It contained questions about knowledge, attitude and management regarding the use of folic acid by women who would like to become pregnant and with a normal risk to have a child with a neural tube defect. RESULTS: The response was high (81%). Most GP's were familiar with the national campaign on folic acid (87%), but 18% considered themselves insufficiently informed about the education campaign and/or the folic acid recommendations. Half the GP's considered use of folic acid tablets by women who would like to become pregnant as important, while two-thirds were of the opinion that it contributed to medicalization of the pregnancy. Most GP's (82%) thought that pregnant women who had not used folic acid tablets might develop feelings of guilt. Nevertheless, 64% recommended use of folic acid tablets and 63% were willing to write a prescription if the woman asked for it. Seventy-five per cent of the GP's reported that they themselves suggested use of folic acid tablets to women who they assumed would like to become pregnant, although most stated they sometimes forgot (58%). The percentages of GP's who sometimes or always suggested folic acid tablets during a contraception advice after delivery or who advised women who would like to become pregnant to switch to a diet rich in folic acid, were much smaller (29 and 37%, respectively). CONCLUSION: Although a large number of the GP's mentioned potential problems, the majority actively cooperated in promoting use of folic acid by women who would like to become pregnant.

Cross-Sectional Studies↗
PubMed1975

Serum and red cell folate activity and folic acid absorption in patients with hookworm infection.

Red cell and serum folate levels and folic acid absorption were studied in patients with hookworm infection. The mean value of serum folic acid level was found to be significantly lower than that of the normal subjects and 32% of cases had serum folic acid level less than 4 ng/ml. The red cell folate content in all patients studied were within the normal limits. The mean value of the folic acid absorption was also lower than that of the normal. Six out of 13 patients absorbed folic acid less than 38%, the lowest value obtained from the normal subjects. These findings indicated that there was a negative balance of folic acid in some patients with hookworm infection which was probably due to impairment in absorption.

Adolescent↗
PubMed2006

Effect of vitamin C and folic acid on seed vigour response and phenolic-linked antioxidant activity.

Folic acid and vitamin C were used in the concentration range of 0-500muM as exogenous growth enhancers to stimulate pea (Pisum sativum) seedling vigour. The results suggest that a concentration of 50muM folic acid and 500muM vitamin C were optimum in maximally enhancing seed vigour and potentially seedling performance according to both agronomic and biochemical seed vigour parameters. Results indicated that germination percentage, shoot weight, shoot height, and root length were enhanced in folic acid and vitamin C treated plants compared to control plants. The levels of enhanced phenolic content in response to folic acid and vitamin C treatments were highest on days 8 and 10. Evaluation of critical biochemical parameters indicated that the average glucose-6-phosphate dehydrogenase (G6PDH) activity and proline content in response to treatments were higher than control and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Key enzymes, guaiacol peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) were also higher in response to treatments and correlated to enhanced phenolic content and DPPH-based antioxidant activity. Taken together, these studies support the hypothesis that the proline-linked pentose phosphate pathway stimulates phenolic synthesis and related free-radical scavenging antioxidant activity. Further, this proline-linked pentose phosphate pathway stimulation in response to folic acid and vitamin C was also correlated to antioxidant enzyme response indicated by the stimulation of GPX, SOD, and CAT activities. Therefore, this study indicates the enhancement of seed vigour response by folic acid and vitamin C as reflected in both agronomic and biochemical responses, and this occurred through the stimulation of phenolic-linked antioxidant response that is likely positively modulated through the proline-linked pentose phosphate pathway.

Analysis of Variance↗
PubMed1989

Folic acid safety and toxicity: a brief review.

Oral folic acid (pteroylglutamic acid) is generally regarded as not toxic for normal humans but it may cause neurological injury when given to patients with undiagnosed pernicious anemia. The vitamin should be given with caution to drug-treated epileptic patients because seizure control may be affected. Some studies suggest that folic acid supplements interfere with intestinal zinc absorption in humans and animals but others do not confirm such an effect. The weight of current evidence favors the view that daily supplements of 5-15 mg folic acid do not have significant adverse effects on Zn nutriture in healthy nonpregnant subjects. Because antifolate medications are now being used to treat a wide range of malignant and nonmalignant disorders, further investigation is needed concerning folate metabolism and the safety of supplements in patients with these disorders.

Anemia, Pernicious↗
PubMed1966

Folic acid deficiency in leukemia and lymphomas.

Serum folic acid levels and the urinary excretion of Figlu have been studied in patients with leukaemia or lymphomas. The results indicate that folic acid deficiency is a common complication of these diseases. Bone marrow examinations of those with evidence of such a deficiency frequently show megaloblastic erythropoiesis. The Figlu test appears to be a useful screening test for folic acid deficiency in patients with leukaemia or lymphomas.

Adolescent↗
PubMed2005

Folic acid calls to poison centers in Texas, 1998-2003.

Folic acid (folacin, pteroylglutamic acid) is a monoglutamate form of the water-soluble B vitamin that is involved in the synthesis of nucleotides and amino acids and the normal maturation of red blood cells. This study describes the folic acid calls received by Texas poison centers during 1998-2003. There were 650 calls involving folic acid as a single-ingredient product, of which 55.1% were human exposures. Children age <6 years accounted for 80.1% of the human exposures. Patients were managed outside of the health care facilities in 92.1% of the cases. Of those cases with a known medical outcome, 94.8% had no clinical effects. This study found folic acid exposures reported to poison centers were unlikely to have more than minor adverse affects.

Adolescent↗
PubMed2002

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of L-folinic or folic acid.

BACKGROUND: We have previously reported that a daily oral high dose of l-folinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients does not provide significantly greater reduction in fasting total homocysteine (tHcy) levels than an equimolar dose of folic acid. The present study uses the affinity/HPLC method to analyze the distribution of plasma folate forms in patients who received l-folinic acid versus those who received folic acid. This was done to investigate claims that renal insufficiency is associated with impaired folate interconversion, a stance that is supportive of the premise that tHcy lowering in these patients is more efficacious with folinic acid and other reduced folates, than folic acid. METHODS: Forty-eight chronic and stable hemodialysis patients were block-randomized, based on their screening predialysis tHcy levels, sex, and dialysis center, into two groups treated for 12 weeks with oral folic acid at 15 mg/day or an equimolar amount (20 mg/day) of oral l-folinic acid. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1 mg/day of oral vitamin B12. Folate distribution was determined in plasma of 46 participants (Folinic acid group, N = 22; Folic acid group, N = 24) by using the affinity/HPLC method, with electrochemical (coulometric) detection. RESULTS: Both groups had similar baseline geometric means of plasma total folate and similar folate forms distribution. Following treatment, both groups demonstrated similar marked elevation in plasma total folate (geometric mean of the increase: Folinic acid group, +337 ng/mL; Folic acid group, +312 ng/mL; P = 0.796). In the folinic acid-treated group, practically all of the increase in total folate was due to 5-methyltetrahydrofolate. In the folic acid-treated group 5-methyltetrahydrofolate accounted for 35% of the increase in total folate and the remainder was unmethylated folic acid. CONCLUSIONS: Data from the present findings suggest that defects in folate absorption or impairment in folate interconversion are not the cause of the persistent hyperhomocysteinemia in hemodialysis patients.

Folic Acid↗
PubMed2001

A quantitative stable-isotope LC-MS method for the determination of folic acid in fortified foods.

A stable-isotope liquid chromatography-mass spectrometry (LC-MS) assay was developed for the quantitative determination of folic acid in fortified foods. Folic acid was extracted from food samples into a phosphate buffer, purified on a C-18 Sep-Pak cartridge, and analyzed by LC-MS in the negative ion mode using electrospray ionization. The analyte was quantified using (13)C(5)-folic acid as an internal standard. The coefficient of variation for the precision of the method was 5.6% based on the analysis of four sample replicates. The accuracy of the method was assessed using a standard method of addition of folic acid to a shredded whole-wheat cereal. The quantitative determination of folic acid in this matrix was linear over 1 order of magnitude having a concentration range of 2.4 to 24 microg/g of food (or 0.05 to 0.5 microg of analyte injected into the LC-MS). The overall quantitative efficiency of the method was evaluated using a standard reference material (infant formula SRM 1846). The method was applied to the determination of folic acid in several test samples (fortified breakfast cereals), and the values were in accord with the manufacturer's claim. This method advances a LC-MS technique for the determination of folic acid in fortified foods based on stable-isotope dilution methodology. The specificity of the technique and quantitative accuracy of the method in various food substrates suggests that the method may be adapted for routine analysis in other fortified foods.

Avena↗
PubMed1994

[Determination of serum vitamin B12 and folic acid by non boil (new standard) radioassay].

On purpose to study the radioassay of serum vitamin B12 and folic acid using non boil methods in with these two vitamins were released from their endogenous binding proteins with alkaline denaturation and separated the bound vitamins from the free ones with the magnetic iron particles coated these vitamin binders (purified hog intrinsic factor and beta-lactoglobulin from cow milk) were evaluated on precision and accuracy, compared with boil radioassay. 1. The reproducibilities of non boil method were 4.5 +/- 2.5% on vit. B12 and 3.5 +/- 0.2% on folate (n = 10), respectively. 2. The recovery test of the two serum vitamins with the use of cyanocobalamin and pteroylglutamic acid (J.P.) were finely showed the rations of 95.2-99.0% for vit. B12 and 101.0-108.0% for folic acid. And that of folic acid use of 5-methyl-tetrahydro-pteroylglutamic acid was showed the ratios of 101.0-104.0%. The values of folic acid measured by this method were found slightly higher than non boil method using conventional standard. 3. The correlation coefficient between non boil method and boil method were 0.987 and regression equation was showed y = 0.97x + 73.59 for vit. B12 (n = 75) and r = 0.932, y = 1.02x-0.08 (n = 78) for folic acid. 4. Normal range of serum total vit. B12 concentration was 210-920 (484 +/- 160 pg/ml, n = 259) and that of folic acid was 2.5-9.2 (5.2 +/- 1.4 ng/ml, n = 257), as well as boil method. 5. Accordingly it was considered that non boil (new standard) method was excellent for estimation of vitamin B12 and folic acid clinical status.

Female↗
PubMed1977

Anemia in the elderly patients with special reference to folic acid status.

To investigate the role of folic acid deficiency in the pathogenesis of anemia in the elderly, hematological examinationa and assays of serum iron, vitamin B12 and folate were carried out on the 86 elderly patients admitted to a home for the aged. Means of red blood cell counts, hemoglobin levels and hematocrit were 385.3 x 10(4)/mm3, 12g/dl and 36%, respectively. These levels were lower than any other report in Japan. Anemia was detected in 23 out of 86 patients. Judging from mean corposcular volume and mean corposcular hemoglobin, most of them were normocytic and normochromic. Although low serum levels of iron and folate were rather frequently observed, the results on hematological examinations suggest that deficiency of these factors alone is not the cause of the anemia in the elderly patients. Rapid clearance of 5-methyl-tetrahydrofolic acid and increased excretion of formiminoglutamic acid after histidine loading were revealed in some of those who had subnormal serum folate levels. Therefore, supplementation of folic acid is recommended to those who had poor dietary intake.

Aged↗