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PubMed1997

Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure.

The aim of this 2-year study was to test the hypothesis that folic acid, vitamin B12 and sun exposure could be helpful in treating vitiligo. One hundred patients with vitiligo were treated with oral folic acid and vitamin B12 after being informed that sun exposure might enhance repigmentation. They were requested to keep a record of sun exposure in summer and UVB irradiation in winter. The minimal treatment time suggested was 3-6 months but should be longer if improvement was achieved. Clear repigmentation occurred in 52 patients, including 37 who exposed their skin to summer sun and 6 who used UVB lamps in winter. Repigmentation was most evident on sun-exposed areas, where 38% of the patients had previously noted repigmentation during summer months. Total repigmentation was seen in 6 patients. The spread of vitiligo stopped in 64% of the patients after treatment. Folic acid and vitamin B12 supplementation combined with sun exposure can induce repigmentation better than either the vitamins or sun exposure alone. Treatment should continue as long as the white areas continue to repigment. Further studies are needed to determine ideal minimal dosages of vitamins and UV exposure, as well as treatment time.

Administration, Oral↗
PubMed2004

Florida health care providers' knowledge of folic acid for the prevention of neural tube defects.

OBJECTIVES: The purpose of this study was to determine the impact of an educational program on the knowledge and practice behavior of health care providers regarding folic acid use for the prevention of neural tube defects. METHODS: A survey was mailed to selected Florida health care providers to determine baseline knowledge and practice behavior. After a statewide educational program, another mail survey was sent to the same groups of providers to determine the effect of the campaign. RESULTS: Comparison between the two surveys showed a significant increase in knowledge and in the percentage of health care providers who recommended the periconceptional use of folic acid for the prevention of neural tube defects. Providers graduating in 1992 or later were more likely than those graduating before 1992 to have the appropriate knowledge about folic acid use but were less likely to recommend it to their patients. CONCLUSIONS: Significant gains were made in increasing knowledge and changing practice behavior among selected Florida health care providers. Regardless of the magnitude of these gains, our data show that some health care providers who have regular contact with women of childbearing age still do not know the recommended doses of folic acid or do not recommend its use. This points toward the need for continued education as well as efforts to modify provider behavior.

Adult↗
PubMed1978

Folic acid binding protein in chronic granulocytic leukaemia: the effect of methotrexate.

Folic acid binding protein (FABP) has been measured in the supernatant of leukocytes of 12 patients affected with chronic granulocytic leukaemia (CGL). The folate binding capacity ranged from 1.37 to 697.52 pg/mg protein, showing a considerable heterogeneity. When the supernatant was preincubated with methotrexate (MTX), the inhibition of folic acid binding was complete in some cases whereas in others it was negligible: these findings have been confirmed by studying the 3H-MTX binding capacity by the same supernatants. In this case the range of bound 3H-HTX varied from 0.00 to 927 pg/mg protein. The presence of a binder in the cytoplasm of leukocytes might represent a new step in the regulation of endogenous folate metabolism. The MTX, widely used as an antifolate drug, may also be bound by FABP of CGL leukocytes, although in different amounts from case to case: this finding suggests a new point of interference of MTX in the folate metabolism. It has also been demonstrated that FABP, which is present in serum, may reduce the uptake of folate by leukocytes opening a new field of investigation on the megaloblastic transformation.

Adolescent↗
PubMed1999

Folic acid campaign and evaluation--southwestern Virginia, 1997-1999.

A needs assessment conducted in rural southwestern Virginia in 1996 indicated higher rates of birth defects in that region than in the entire state. In response to these findings, in January 1997 the regional perinatal council conducted a community folic acid information campaign designed to raise awareness about the 1992 Public Health Service recommendation that all women who are capable of becoming pregnant consume 400 microg (0.4 mg) of the B vitamin folic acid every day to decrease their risk for having a pregnancy affected with spina bifida or other neural tube defects (NTDs). This report describes the information campaign and the findings from precampaign and postcampaign surveys, which showed a significant increase in reported awareness and knowledge of the benefits of folic acid and reported knowledge about the sources of folic acid.

Adolescent↗
PubMed1978

Effects of the teratogenic folic acid antagonist, 9-methyl pteroylglutamic acid on uronic acid levels in fetal rat limbs.

Experimental pregnant rats were placed on a transitory folic acid-deficient regimen, i.e. dietary restriction of folic acid plus the teratogen and folic acid antagonist, 9-methyl pteroylglutamic acid; a regimen resulting in multiple congenital skeletal malformations. Controls received a folic acid-supplemented regimen. Accumulation of a primary component of the extracellular matrix, glycosaminoglycans (GAG), was quantitatively evaluated by measuring uronic acid concentrations in fetal limbs. On days 16 and 18 of gestation, fetal limbs were removed, pooled from each litter, and prepared for uronic acid, protein, and DNA quantitation. The treatment results in (1) a decreased rate of protein and DNA accumulation prior to day 16 of gestation, the rate not being affected from day 16 to day 18 of gestation; (2) a trend toward an increased rate of uronic acid accumulation prior to day 16 of gestation, and (3) a decreased rate of uronic acid accumulation from day 16 to day 18 of gestation. Furthermore, our observations confirm our earlier suggestion that there is a decreased rate of accumulation of some nonprotein component(s) in fetal limbs obtained from folic acid-deficient mothers from day 16 to day 18 of gestation.

Animals↗
PubMed1995

Reduced recurrence of orofacial clefts after periconceptional supplementation with high-dose folic acid and multivitamins.

To assess effects of periconceptional multivitamin and folic-acid supplementation on recurrence of cleft lip with or without cleft palate (CL +/- P), we prospectively evaluated 221 pregnancies in women at risk of a child with CL +/- P. The 10-step protocol included multivitamin supplementation with SPOFAVIT (A, B1, B2, B6, C, D3, E, nicotinamide, calcium pantothenicum) and folic acid (10 mg/day), beginning > or = 2 months before planned conception and continuing for > or = 3 months thereafter. A comparison group comprised 1,901 women at risk of a child with CL +/- P who received no supplementation and gave birth within the same period as the study group. In the supplemented group, 3 of 214 informative pregnancies ended with infants with CL +/- P, a 65.4% decrease (observed versus expected value -5.67; P = 0.031, Fisher's exact test); the expected value of 8.7 was calculated based on the incidence of cleft among first-degree relatives among the comparison group. Subset analysis by proband's sex, severity of CL +/- P, and both variables showed highest supplementation efficacy in probands with unilateral cleft (82.6% decrease, P = 0.024, Fisher's exact test). No efficacy was observed for female probands with bilateral CL +/- P. Generally, efficacy was greater for subgroups with unilateral than with bilateral cleft and for male than female probands.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Folic acid food fortification is associated with a decline in neuroblastoma.

BACKGROUND: Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known. METHODS: We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification. RESULTS: An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89). CONCLUSIONS: Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.

Canada↗
PubMed2003

Food fortification with folic acid and twinning among California infants.

This study sought to determine whether a change in twinning prevalence was associated with mandatory folic acid fortification. As of January 1998, it became mandatory in the United States that grain products be fortified with folic acid. The effectiveness of this fortification for neural tube defects has been explored, but other possible implications of fortification has not. We computed the prevalence of twinning among more than 2.5 million California births occurring from 1990 to 1999. The prevalence of twin births in California increased over the last decade with increases observed among most maternal race/ethnic, age, and parity groupings. Unadjusted prevalence measures did not reveal substantial increases in twinning prevalence among these groupings after the fortification period relative to the period immediately preceding it. Analyses that simultaneously adjusted for age, parity, race/ethnicity, sexes of twin pair (as a measure of zygosity), year of birth, and fortification period also did not reveal an association between fortification and twinning. Our results do not suggest a change in twinning prevalence associated with folic acid fortification of the US food supply among women delivering in California.

California↗
PubMed2002

The enrichment of eggs with folic acid through supplementation of the laying hen diet.

In light of evidence supporting a need for humans to increase their dietary folate intakes, experiments were conducted to evaluate the extent to which egg folate levels could be increased. In Study 1, Hyline W36 hens (n = 6/diet) received a barley-based diet, containing 0 or 10 mg/kg of crystalline folic acid, to establish the potential for folate incorporation into table eggs. In Study 2, 70 hens were divided into seven treatment groups (n = 10 hens/diet) and received diets supplemented with 0, 1, 2, 4, 8, 16, or 32 mg folic acid/kg diet. In Study 3, 64 hens received the barley-based diet with or without 4 mg folic acid/kg diet. Eggs were collected and stored for 0, 7, 14, 21, or 28 d, prior to folate determinations. The folate content of eggs was determined by HPLC for 5-methyltetrahydrofolate (the sole form of folate in egg yolk). Results from Study 1 showed that a 10 mg/kg inclusion of folic acid increased folate incorporation into egg yolk (41.0 +/- 0.7 microg /egg) over that of an unsupplemented diet (17.5 +/- 0.7 microg /egg; P = 0.0001). In Study 2, the response of egg folate to dietary folic acid supplementation was saturable, with 90% of maximal egg folate levels established at approximately 4 mg folic acid/ kg diet. Results from Study 3 showed that folate levels are stable, in control and fortified eggs, during 28 d of storage at 4 C. In terms of its nutritional value, one large egg collected from a folic acid-supplemented hen provided approximately 12.5% of the recommended dietary allowance (RDA) for adult humans (RDA = 400 mg/d).

Animal Feed↗
PubMed2001

Targeted drug delivery to chemoresistant cells: folic acid derivatization of FdUMP[10] enhances cytotoxicity toward 5-FU-resistant human colorectal tumor cells.

Current chemotherapy protocols that include fluoropyrimidines, such as 5-fluorouracil (5-FU), are limited by the development of chemoresistance during the course of treatment. Our laboratory has developed a novel class of fluoropyrimidines, FdUMP[N], that are oligodeoxynucleotides (ODNs) composed of some number, N, of 5-fluoro-2'-deoxyuridine-5'-O-monphosphate (FdUMP) nucleotides. Novel synthetic procedures are described that permit conjugation of folic acid to the 5'-OH of FdUMP[10] via a phosphodiester linkage using automated synthesis. The synthetic methods developed are generally applicable for ODN conjugation with folic acid. The folic acid conjugate FA-FdUMP[10] showed improved cytotoxicity toward human colorectal tumor cells (H630), and 5-FU-resistant colorectal tumor cells (H630-10). Enhanced cytotoxicity was observed for FA-FdUMP[10] relative to nonconjugated FdUMP[10] for cells grown under folate-restricted conditions, consistent with cellular uptake being, in part, receptor-mediated. Folate receptor alpha (FRalpha) mRNA was shown by RT-PCR to be overexpressed 26.3-fold in 5-FU-resistant H630-10 cells relative to H630 cells. Thus, FA-FdUMP[N] may prove useful for the treatment of 5-FU-resistant malignancies.

Antineoplastic Agents↗
PubMed2004

The effects of folic acid supplements on coagulation status in pregnancy.

Thromboembolic disease remains the leading cause of maternal death in the UK. Recent literature has proposed that folate status is a strong predictor for venous thrombosis. Using thrombelastography (TEG((R))), we tested the hypothesis that folic acid supplementation is associated with a reduction in whole blood coagulability. Blood samples and questionnaire data were obtained at a mean gestation of 13.6 weeks (SD: 3.8, range: 6-38 weeks) from unselected consecutive women attending for their antenatal booking scan. Of 588 patients, 439 (74.7%) took folic acid. All TEG((R)) parameters were less hypercoagulable in women that had taken folic acid compared with those that had not: mean maximum amplitude (MA) 60.3 versus 62.1; mean difference 1.8; 95% confidence interval 0.8, 2.8; P = 0.0001; mean coagulation index (CI) 0.54 versus 0.85; mean difference 0.31; 95% confidence interval 0.11, 0.5; P = 0.002. There was no difference in the incidence of the homozygous MTHFR mutation in patients taking folic acid (5.53%) compared with those that were not (4.08%). This study suggests that benefit may be derived from longer-term treatment, although large multicentre studies are required to determine whether the relative hypocoagulability is associated with a reduction in risk of venous thrombosis.

Adult↗
PubMed1990

Vitamin B12 and folic acid absorption and hematological status in children with postenteritis enteropathy.

In a group of nine children with postenteritis enteropathy (i.e., persisting small-intestinal mucosal damage and failure-to-thrive after an acute episode of gastroenteritis), absorption capacities for vitamin B12 and folic acid were studied and compared with hematological status in peripheral blood. The fractional absorptions of vitamin B12 (FAB12) and folic acid (FAFol) were determined by means of a double-isotope technique employing a single-stool-sample test. The children were examined when growth retardation was maximal, and examinations were repeated during the late recovery period. In spite of considerable small-intestinal mucosal damage, only the absorption of vitamin B12 was markedly affected, while that of folic acid was almost intact. When growth retardation was maximal, FAB12 was below the normal age-correlated range in half of the children. FAB12 was also severely reduced in all longitudinally observed children when compared with the results obtained during the late recovery period (p less than 0.005). FAFol was below the normal range in one fourth of the children, but the reduction was modest and insignificant when compared with the results of repeated examinations during the late recovery period. A moderate iron deficiency was detected in half the children. High levels of plasma vitamin B12, folic acid, and erythrocyte folate were detected at both early and later examinations, indicating that these parameters were not affected by the reduced absorption capacities. However, if malabsorption and chronic diarrhea are combined with low dietary intake of vitamin B12, as is the case for many children in the Third World, depletion of vitamin B12 stores may result.

Absorption↗
PubMed2005

Protective effects of prenatal administration of folic acid on retinoic acid-induced cellular damages of Meckel's cartilage in rats.

Craniofacial malformations are among the most common congenital deformities. Meckel's cartilage plays a major role in the development of the mandible and is highly susceptible to maternal teratogenic drug use. We therefore investigated possible protective effects of prenatal administration of folic acid on a retinoic-acid induced maxillofacial defect model. Sprague-Dawley pregnant female rats (n=36) were used in this study. Retinoic acid was administered orally at the dose of 40, 60, or 80 mg/kg respectively on gestational day 8. Folic acid of 4.0 mg/kg was injected intraperitoneally on 7th, 8th and 9th days of pregnancy. Animals were sacrificed on the day 17th. Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused severe ultrastructural damages in Meckel's cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg. In addition, there was a marked decrease in the number of degenerated chondrocytes and an improvement in the structure of granular endoplasmic reticulum along with intact nuclei. We conclude that folic acid has protective effects on retinoic acid-induced intracellular damages in Meckel's cartilage.

Animals↗
PubMedDate not supplied

Phenytoin-folic acid interaction: a lesson to be learned.

A case of a patient who developed symptomatic phenytoin-induced folic acid deficiency is reported. Folate supplementation of 5 mg/d was followed by a decrease of serum phenytoin concentration to a subtherapeutic level with a breakthrough seizure. Estimation of phenytoin's Km-Vmax Michaelis-Menten pharmacokinetic parameters in this patient demonstrated that folate supplements indeed caused a significant decrease in the Km value. This decrease correlates with a greater affinity of the metabolizing hepatic enzymes for the drug, and hence, with the resultant increase in phenytoin's metabolism and decrease of its serum concentration and anticonvulsive effect. In an era of increasing knowledge of folate's pivotal role in various diseases, we call attention to this drug-vitamin interaction, and to the previously suggested recommendation that folate supplementation should be initiated whenever phenytoin therapy commences. Because folic acid dosages as low as 1 mg/d may perturbate phenytoin's metabolism, smaller deficiency preventive doses may be the advisable allowance for phenytointreated patients with normal pretreatment folate levels. This suggestion must be confirmed by a prospective study in a large cohort of patients.

Drug Interactions↗
PubMed2006

Do racial and ethnic differences in serum folate values exist after food fortification with folic acid?

OBJECTIVE: The United States food supply has been fortified with folic acid since 1998. Information about folate levels early in pregnancy before the fortification is limited. This study examined the associations between serum folate at first prenatal visit and maternal race/ethnicity, age, vitamin use, and body mass index. STUDY DESIGN: This cross-sectional study assessed serum folate levels among 9421 women who entered prenatal care in 1999 and 2000 in southern California. Information on race/ethnicity, vitamin use, weight, height, and age was obtained from surveys and birth certificates. RESULTS: After adjustment for vitamin use, the strongest predictor of serum folate level, being in the lowest folate quartile (< or = 16 ng/mL) was related independently to being of black, Hispanic, or Asian/Pacific Islander race/ethnicity, being younger age, and being overweight or obese. CONCLUSION: After food fortification with folic acid, differences in serum folate values in pregnant women by maternal race/ethnicity, age, and body mass index persisted.

Adult↗
PubMed1971

Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths.

Folic acid absorption was studied in anesthetized dogs by determining the amount and chemical nature of folate in venous blood emerging from isolated intestinal segments containing free folic acid and/or pteroylpolyglutamates of a known chain length. Chromatographically pure test materials placed in the lumen were prepared by unambiguous solid phase synthetic methods. This synthetic procedure not only yields compounds of known structure, it also provides a means by which glutamic acid residues at any given position in the gamma glutamyl chain can be made radioactive. For example, teropterin (pteroyltriglutamate) was synthesized in such a way that (14)C was present only in the middle glutamic acid unit. Suitable placement of label permitted assessment of the extent of peptide cleavage. The action of plasma conjugase was inhibited by copper chloride. Plasma samples were analyzed by Lactobacillus casei and Streptococcus faecalis assay, by column chromatography, and by quantitative measurement of pteridine-bound radioactivity. It was observed that biologically active folate appeared in the mesenteric vein with either pteroylmono-, di-, tri-, penta-, or heptaglutamate in the lumen. Generally speaking the absorption rate appeared to be inversely related to the length of the gamma glutamyl side chain. Roughly twice as much folic acid appeared in the circulation from (3)H-labeled pteroylmonoglutamate as from (14)C-labeled pteroylpentaglutamate when equimolar amounts of each were placed simultaneously in a single intestinal segment. Pteroylmonoglutamate appeared to be the predominant form entering the blood from each of the precursors tested. However, evidence was obtained that pteroyldiglutamate may enter the mesenteric vein soon after placing pteroyldi-, or triglutamate in the lumen, but not with the higher polyglutamates. Comparison of radioactivity and biological activity patterns suggests little conversion, if any, to reduced or methylated forms during the first 30 min of passage through the intestinal mucosa. We conclude that both pteroylmonoglutamates and pteroyldiglutamates may across the intestinal mucosa of the dog, and that reduction and methylation are not essential to the absorption process.

Animals↗
PubMed2006

Effects of nutrition on zinc, folic acid, and vitamin B12 levels during pregnancy.

In this article, we report the results of a case control study carried out on 290 Turkish pregnant women at 5-24 wk of gestation to determine their zinc, folic acid, and vitamin B12 levels in relation to their nutritional and socioeconomic status. The women were divided into two groups (n=145 each), depending on the stage of gestation. Group I consisted of women in the first trimester of gestation; those in the second trimester were allocated into group II. Twenty-five age-matched, healthy nonpregnant women were selected as controls. The nutritional status of the subjects was determined by means of a survey. Based on this, the women were subdivided into three subgroups: malnourished (PN), moderately nourished (MN), and well nourished (WN). Also from the survey, the socioeconomic status was classified as good (G) or bad (B). A statistically significant decrease on zinc and folic acid was observed in group I women, as their socioeconomic status worsened. In group II, zinc decreased only in the PN and MN subgroups, p<0.001. The folic acid and vitamin B12 levels did not change significantly during the second trimester of gestation in all subgroups. Regarding zinc, nutrition, or dietary habits are more relevant than socioeconomic status, but poor nutrition affects folic acid levels only during the first trimester of gestation.

Adolescent↗
PubMed1998

Folic acid in the treatment of acute watery diarrhoea in children: a double-blind, randomized, controlled trial.

One-hundred and six male children aged 6-23 months with a history of acute watery diarrhoea of less than 72 h duration were randomized to receive either folic acid in a dose of 5 mg at 8-h intervals or placebo for 5 d. There were 54 children in the folic acid group and 52 in the placebo group. The admission characteristics were comparable between the two groups. No significant differences were observed in the intake of oral rehydration solution or stool output between the groups. The mean+/-SD of total stool output (g kg(-1)) was 532+/-476 vs 479+/-354 and the duration (h) of diarrhoea was 108+/-68 vs 103+/-53 in the folic acid vs placebo group, respectively. The findings, therefore, should have a positive influence on preventing the inappropriate use of folic acid in acute diarrhoea.

Acute Disease↗