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PubMedDate not supplied

Folic acid and total parenteral nutrition.

The stability of folic acid in a variety of solutions used for parenteral nutrition has been determined over a 2-wk period. Provided that the acidity of the solution remains above pH 5.0 the folate, in the concentrations usually used for parenteral nutrition, will remain stable in solution, and all of the folate added to the solution will be delivered to the patient. The applicability of this in vitro work to a group of patients requiring parenteral nutrition was assessed, in order to determine a suitable dose. A dose of 0.2 mg of folic acid daily was inadequate to meet the requirements of these patients. In contrast a dose of 1.2 mg daily for 7 days was sufficient to cause an increase in the serum folate concentration.

Dose-Response Relationship, Drug↗
PubMed1984

Effect of folic acid on the pharmacokinetics of acutely administered phenytoin in pregnant and nonpregnant rats.

The concentrations of both total and free phenytoin in the plasma of epileptic women tend to decrease during pregnancy, suggestive of a pregnancy-associated increase in the metabolic clearance of the drug. On the other hand, the metabolic clearance of free (unbound) phenytoin decreases during pregnancy in rats. One possible reason for this species difference is the routine dietary supplementation of folic acid in human pregnancy and the apparent ability of folic acid to lower phenytoin plasma concentrations even in nonpregnant humans. The purpose of this investigation was to determine the effect of treatment with folic acid on the pharmacokinetics of phenytoin in pregnant and female nonpregnant rats. In one experiment, the treated animals received folic acid in the drinking water, approximately 100-150 micrograms/kg/d, for 19 d. There was no apparent difference between the treated and untreated rats in the pharmacokinetics of a 10-mg/kg iv dose of phenytoin (which was administered to the pregnant rats on the 20th day of gestation), regardless of pregnancy status, In another experiment, pregnant and female nonpregnant rats received either folic acid, 400 micrograms/kg/d, or an equal volume of the solvent only, by gastric intubation for 19 d. The next day (which was the 20th day of gestation for the pregnant rats), the animals received an intravenous injection of phenytoin, 30 mg/kg. Again, pretreatment with folic acid had no apparent effect on the pharmacokinetics of phenytoin in both pregnant and nonpregnant rats. However, the results of this investigation confirm previous observations of dose-dependent phenytoin pharmacokinetics in rats and of decreased clearance of free phenytoin in late pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Is it possible to prevent cleft palate by prenatal administration of folic acid? An experimental study.

OBJECTIVE: In this study, folic acid was tested for its antiteratogenic effects on experimentally induced cleft palate in animals. DESIGN: Eleven pregnant Lew 1 A dams (75 fetuses) received 200 mg/kg procarbazine via gastric tubing on postconception (p.c.) day 14 to induce a cleft palate (CP); seven of the pregnant dams (45 fetuses) were additionally given 4 mg/kg folic acid subcutaneously from the 14th to the 17th day p.c. As a control group, three more pregnant dams (24 fetuses) were not treated with the drugs mentioned above. All fetuses were delivered by Caesarian section on day 20 p.c. OUTCOMES MEASURED: All fetuses were weighed and examined macroscopically with a stereomicroscope. Each fetal head was cut into 35 frontal sections and scrutinized histologically. RESULTS: None of the control fetuses (n = 24) exhibited a cleft. Without folate administration, 90% of the fetuses (27 of 30) that received procarbazine exhibited a CP. After additional prenatal folate administration, this rate remained virtually unchanged (91%; 41 of 45). However, the proportion of complete (total) CP (4%) was significantly (p <.0001) lower than in the group without folate (53%). Cleft-associated microgenia and microglossia were also significantly less frequent when folate was administered prenatally: microgenia was reduced by 22% (p =.029) and microglossia by 24% (p =.032). CONCLUSIONS: On the basis of these results, folate has a partial ameliorating effect on the teratogenicity of procarbazine given to pregnant rats. Additional studies are necessary on the effect of folate in different species, also taking cleft lip and CP into consideration.

Animals↗
PubMedDate not supplied

Folic acid treatment in males and females with fragile-(X)-syndrome.

Ten males with the fragile X (fra(X] syndrome were treated with folic acid (10 mg/day) for 4 months in a double-blind design study. To eight heterozygotes with mental impairment and fra(X), folic acid was given for 4 months (10 mg/day) in an effort to study possible beneficial effects of folic acid. Psychological and cytogenetic testing were carried out during the trial. There was no improvement in concentration, fine motor co-ordination, or comprehension in the adult male and female patients of the study. One patient showed improvement under a control medications. In the females, improvement was seen only in the youngest patient, a 5-year-old girl. Folate treatment does not seem to be effective in fra(X) adults, but may have some effect in children of both sexes with the disorder. Cytogenetic studies using peripheral lymphocytes showed that the fra(X) frequency decreased significantly (t = 0.00856; 1% level) only in cells cultured in a folic acid-free medium but not in cells cultured in a medium with added antifolate (methotrexate). This shows a "contamination effect" of folate-free culture medium after oral folic acid treatment of these patients. The decrease of fra(X) involves primarily the early-replicating X when culturing with folic acid-free medium. A synergistic suppression effect of "external folate" and BrdU is the most likely explanation of this phenomenon.

Adolescent↗
PubMed2000

[Preventing neural tube defects with periconceptional folic acid supplementation: a population-based intervention program in the China].

OBJECTIVES: To evaluate the effectiveness of periconceptional use of 400 microgram folic acid only on the prevention of neural tube defects (NTDs). METHOD: As part of a public health campaign in areas of high (North) and low (South) NTDs prevalence in the China during 1993 and 1995, 130 142 pill takers and 117 689 non-pill takers were recruited. Women were asked to begin taking a pill containing only 400 microgram of folic acid daily from the time of their premarital examination until the end of the first trimester of pregnancy. The outcomes of these pregnancies were ascertained through 1996. RESULTS: We identified 102 NTDs among offspring of pill takers and 173 NTDs among offspring of non-pill takers. The NTDs rate in offspring of non-pill takers was 4.8 per thousand (16/3 318) and 1.0 per thousand (28/28 625) in the south; while the rate in pill takers was 1.0 per thousand (13/13 012) in the north and 0.6 per thousand in the south. 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 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). 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% confidence interval, 3 to 64 percent). CONCLUSION: Periconceptional intake of supplements containing only 400 microgram folic acid can reduce the risk for NTDs in areas of high and low NTDs prevalence.

Adult↗
PubMed2004

Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values.

OBJECTIVE: Folic acid fortification of breads and grains was implemented in the United States in 1998 in an attempt to reduce the incidence of neural tube defects. Outcome data from birth registries have shown a 20% drop-less than originally predicted. In this study, we ascertain if the impact of folic acid fortification is better seen at the time of midtrimester prenatal diagnosis by looking at incidence of high maternal serum alpha-fetoprotein (MSAFP) values. METHODS: Data regarding MSAFP levels in 61,119 patients undergoing maternal serum screening at a large commercial laboratory were categorized by multiples of the median (MoM). The data were compared between 2 groups: before mandatory supplementation in the United States in 1997 and after mandatory supplementation in 2000. High MSAFP values were further categorized as high (2.75-4.00 MoM) or very high (more than 4.00 MoM). Data were analyzed by chi(2) analysis. RESULTS: Comparative data showed a 32% decrease of patients with MoM greater than 2.75 + (2.5% -1.7%). Further categorizations revealed similar decreases. CONCLUSION: The introduction of folic acid fortification has produced a profound decrease in the number of high MSAFP values, reflective of a decreased incidence of neural tube defects. Our results help to validate the decision to fortify food with folic acid, which represents a highly successful public health policy for primary prevention of birth defects. LEVEL OF EVIDENCE: II-2

Cohort Studies↗
PubMed1977

New colorimetric method for folic acid assay in dosage forms.

A new colorimetric method has been developed for estimating folic acid. The British Pharmacopoeial method has been modified to reduce folic acid to 2,4,5-triamino-6-hydroxy-pyrimidine (TAHP), which is treated with ninhydrin to yield a stable purple complex. Participation of 5-amino and 6-hydroxy groups of TAHP in the color reaction with ninhydrin is suggested on the basis of experimental evidence. The color obtained has an absorbance maximum at 555 nm and obeys Beer's law in the concentration range of 4.5 to 45 microng folic acid/ml. The method has been successfully used for assaying folic acid, its tablets, and injections.

Colorimetry↗
PubMed2004

Hyperhomocysteinaemia & folic acid supplementation in patients with high risk of coronary artery disease.

BACKGROUND & OBJECTIVES: Many traditional independent risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia, smoking, male sex, old age, etc., contribute to the development of coronary artery disease (CAD). Hyperhomocysteinaemia is an independent risk factor of CAD but the role of plasma homocysteine (Hcy) in high risk patients (> or = 3 risk factors) is not known. We investigated the role of plasma Hcy, folic acid, vitamin B12 in patients with high risk (> or = 3 risk factors) of CAD and effects of supplementation of folic acid in the patients with hyperhomocysteinaemia. METHODS: The plasma Hcy levels in 152 patients with > or = 3 risk factors of CAD and 136 patients with 1-2 risk factors and 48 individuals with no risk factors were measured using high performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and vitamin B12 levels were also measured in these patients with immunoassays. The patients with hyperhomocysteinaemia were treated with 5 mg of folic acid for 8 wk, and plasma levels of Hcy were measured after treatment. RESULTS: The plasma Hcy level was significantly higher in the patients with > or = 3 risk factors of CAD than in those with 1-2 risk factors and controls. The plasma levels of folic acid and vitamin B12 were significantly lower in the patients with > or = 3 risk factors of CAD compared to those with 1-2 risk factors and controls. The Hcy levels in the patients with > or = 3 risk factors of CAD significantly reduced by 33.5 per cent after 8 wk folic acid administration. INTERPRETATION & CONCLUSION: Plasma Hcy level was elevated significantly in patients with > or = 3 risk factors of CAD. Hyperhomocysteinaemia appears to play an important role in the pathogenesis of CAD. Folic acid supplementation may be useful in reducing plasma Hcy level in high risk patients with hyperhomocysteinaemia.

Adult↗
PubMed1975

Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis.

From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil.

Agar↗
PubMed1980

Folic acid: crystal structure and implications for enzyme binding.

The crystal and molecular structure of folic acid dihydrate has been determined by x-ray diffraction. Folic acid is in an extended conformation with the pteridine ring in the keto form. The C(4) oxygen and N(10) atoms are on the same side of the molecule, hydrogen-bonded to the same water. This conformation has the pteridine rotated approximately 180 degrees away from the orientation of the pteridine ring of methotrexate bound to dihydrofolate reductase. The folic acid pteridine and phenyl rings interact in a stacking manner which is suggestive of the type of associations these groups could form in a complex of folate, dihydrofolate reductase, and reduced nicotinamide adenine dinucleotide phosphate.

Binding Sites↗
PubMed2006

Effect of folic acid and betaine supplementation on flow-mediated dilation: a randomized, controlled study in healthy volunteers.

OBJECTIVES: We investigated whether lowering of fasting homocysteine concentrations, either with folic acid or with betaine supplementation, differentially affects vascular function, a surrogate marker for risk of cardiovascular disease, in healthy volunteers. As yet, it remains uncertain whether a high concentration of homocysteine itself or whether a low folate status--its main determinant--is involved in the pathogenesis of cardiovascular disease. To shed light on this issue, we performed this study. DESIGN: This was a randomized, placebo-controlled, double-blind, crossover study. SETTING: The study was performed at Wageningen University in Wageningen, the Netherlands. PARTICIPANTS: Participants were 39 apparently healthy men and women, aged 50-70 y. INTERVENTIONS: Participants ingested 0.8 mg/d of folic acid, 6 g/d of betaine, and placebo for 6 wk each, with 6-wk washout in between. OUTCOME MEASURES: At the end of each supplementation period, plasma homocysteine concentrations and flow-mediated dilation (FMD) of the brachial artery were measured in duplicate. RESULTS: Folic acid supplementation lowered fasting homocysteine by 20% (-2.0 micromol/l, 95% confidence interval [CI]: -2.3; -1.6), and betaine supplementation lowered fasting plasma homocysteine by 12% (-1.2 micromol/l; -1.6; -0.8) relative to placebo. Mean (+/- SD) FMD after placebo supplementation was 2.8 (+/- 1.8) FMD%. Supplementation with betaine or folic acid did not affect FMD relative to placebo; differences relative to placebo were -0.4 FMD% (95%CI, -1.2; 0.4) and -0.1 FMD% (-0.9; 0.7), respectively. CONCLUSIONS: Folic acid and betaine supplementation both did not improve vascular function in healthy volunteers, despite evident homocysteine lowering. This is in agreement with other studies in healthy participants, the majority of which also fail to find improved vascular function upon folic acid treatment. However, homocysteine or folate might of course affect cardiovascular disease risk through other mechanisms.

Journal Article↗
PubMed1984

Folic acid utilization from high fiber diets in rats.

This study was designed to examine the effect of several sources of dietary fiber on the utilization of folic acid added to the diets of rats. Weanling rats were given a low folacin basal diet for 21 days, divided into various groups and then fed folic acid (pteroylglutamic acid) and/or fiber-supplemented diets for 7 or 8 days. The slope of the liver folacin response was measured as an indicator for utilization of added folic acid. Fecal folacin excretion was measured as an indicator of unabsorbed dietary folacin plus folacin synthesis by intestinal bacteria. There was no detectable effect of cellulose, xylan, pectin or wheat bran on the utilization of added folic acid. Liver and fecal folacin content indicated that some fiber sources contributed additional available folacin to the animals from intestinal synthesis or naturally occurring folacin. Cellulose acted as a simple dietary dilutant and had no significant effect on the utilization of added folic acid or total fecal folacin excretion. Xylan stimulated intestinal folacin synthesis, and this was reflected in higher fecal and liver folacin content. Wheat bran and beans (two varieties of each) contained measurable folacin or stimulated synthesis of bacterial folacin, which appeared to be available to the rat.

Animals↗
PubMed1980

Radioisotope binding capacity of serum in folic acid, vitamin B12 and ferritin in haematologic and rheumatologic patients.

In addition to the usual parameters for haematologic an rheumatologic diseases folic acid, vitamin B12, and ferritin were investigated by radioisotope studies. In some groups folic acid was lower compared to controls, and it is possible that the disease causes the deficiency of folic acid absorption and distribution. Vitamin B12 was only slightly decreased, thus, the values may be assumed to be close to normals. Transferrin ankylosing spondylitis is similar to that of controls, however, transferrin increases in rheumatoid arthritis and in mixed groups containing patients various diseases. Finally, the deficiency of folic acid absorption can be assumed to be caused by the symptoms of the disease, whereas in the case of inflammatory diseases and in mixed group transferrin increased.

Adult↗
PubMed1997

Knowledge and use of folic acid by women of childbearing age--United States, 1997.

Each year in the United States, approximately 4000 pregnancies are affected by spina bifida and anencephaly. Babies born with spina bifida usually survive, often with serious disability, but anencephaly is invariably fatal. The B vitamin folic acid can reduce the occurrence of spina bifida and anencephaly by at least 50% when consumed daily before conception and during early pregnancy. In 1992, the Public Health Service (PHS) recommended that all women of childbearing age who are capable of becoming pregnant consume 400 microg of folic acid daily. Folic acid can be obtained from multivitamins or certain other supplements and from some fortified breakfast cereals. It is found naturally in orange juice, green leafy vegetables, and beans; however, it is difficult to obtain the recommended 400 microg daily through diet alone. This report summarizes findings from a survey conducted during January and February 1997 that indicate modest increases since 1995 in knowledge about and consumption of folic acid among U.S. women aged 18-45 years and highlights the need for additional public health efforts to take full advantage of this prevention opportunity.

Adult↗
PubMed1995

Folic acid supplementation improves erythropoietin response.

Therapy with recombinant human erythropoietin (rhEPO) has become most valuable for the treatment of renal anemia in patients with various chronic renal diseases. For the first time this study presents data showing that rhEPO affects the metabolism of folic acid. There were 13 patients enrolled; they suffered from different chronic renal diseases and showed an impaired responsiveness to rhEPO therapy. Before starting rhEPO therapy the mean corpuscular volume of erythrocytes (MCV) was measured; MCV was 90.4 fl. During rhEPO therapy the MCV increased significantly by 14.8 fl (p < 0.05). The developing macrocytic anemia was overcome when folic acid was administered additionally for a mean period of 3.14 +/- 3 months. Hematocrit (Hct) also responded accordingly. Whereas Hct did not increase adequately during the exclusive treatment with rhEPO, an increase in Hct from 23 +/- 3.3 to 30 +/- 4.2% (p < 0.01) was observed after the addition of folic acid. These results are rather remarkable as folic acid serum levels were clearly within the normal range during the whole study period. So it can be concluded that rhEPO therapy results in an increased demand for folic acid. Even if serum concentrations are within the normal range, the administration of folic acid will enhance the effectiveness of rhEPO therapy so that the rhEPO dosage can be reduced.

Aged↗
PubMed1993

The effects of periconceptional folic acid and vitamin supplementation on maternal folate levels and on neurulating hamster embryos in vivo.

We studied the effects of periconceptional oral supplementation of folic acid and vitamins on the maternal red blood cell (RBC) folate level of golden hamsters (Mesocricetus auratus, Waterhouse). The effects of folate deficiency and supplementation on the process of neurulation and the incidence of resorptions were evaluated. Groups of at least eleven mature virgin female hamsters were placed on one of six specific regimens which started two weeks prior to mating and continued until sacrifice on day nine of pregnancy. Just prior to sacrifice, blood samples were drawn by cardiac puncture to measure maternal folic acid levels in red blood cells. The staging of the embryos was based on O'Rahill's modification of Streeter's developmental horizons in human embryos. Considerable variation was observed in the stage of embryonic development of 9-day-old hamster embryos, both between littermates and between litters of the same gestational age. A high overall incidence of open neural tubes was observed, which did not reflect neural tube closure failures. A folate-free diet caused retardation of the embryonic development, although maternal folate levels were unaffected (p < 0.01). The RBC folate levels in the animals which received oral supplementation with folic acid was significantly higher than that in the unsupplemented controls (p < 0.001). Folic acid supplementation alone increased the RBC folate level significantly more than combined supplementation with multivitamins (p < 0.001). The data indicate that oral supplementation with folic acid and/or multivitamins produce adequate maternal RBC folate levels. An inadequate maternal folate intake can affect the growth of neurulating embryos even if the maternal RBC folate levels are still sufficient.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed2005

Use of dietary supplements containing folic acid among women of childbearing age--United States, 2005.

Neural tube defects (NTDs) are serious birth defects of the spine (spina bifida) and brain (anencephaly), affecting approximately 3,000 pregnancies each year in the United States. Daily periconceptional consumption of 400 mug of folic acid, as recommended by the Public Health Service (PHS) since 1992, reduces the occurrence of NTDs by 50%-70%. The Food and Drug Administration ordered mandatory fortification with folic acid of U.S. cereal grain products, beginning in 1998. However, despite a 26% reduction in NTDs, not all women of childbearing age receive adequate levels of folic acid from their diets. Therefore, increasing the number of women who take dietary supplements containing 400 mug of folic acid daily remains an important component of NTD prevention. This report summarizes results from the 2005 March of Dimes Gallup survey, which determined a decrease in the proportion of childbearing-aged women who reported taking folic acid in dietary supplements daily, from 40% in 2004 to 33% in 2005, returning to a level consistent with that reported during 1995-2003. These results emphasize the need for innovative programs to increase folic acid consumption to further reduce NTDs.

Adult↗
PubMed1997

The factors associated with effective folic acid prophylaxis in the peri-conceptional period in women attending an ante-natal clinic.

The aim of this study was to examine whether folic acid supplements had been taken and dietary folate intake increased in 662 pregnant women attending the antenatal clinic at St Mary's Hospital, Portsmouth. An assessment was also made of the factors that influenced correct compliance with the recommendations of the Expert Advisory Group on folic acid. Thirty-seven percent (245/662) women had taken folic acid supplements and 26.4% (175/ 662) increased their dietary folate before or during early pregnancy. The majority of women who commenced folic acid supplements after conception did so after the neural tube had closed (220/247). Women were more likely to have adhered to the Expert Advisory Group's recommendations if the pregnancy was planned, the woman was primiparous, there was no past or family history of neural tube defect and the patient had the correct existing knowledge of folic acid prophylaxis. The relevance of these findings to the current Health Education Authority's folic awareness campaign is discussed.

Journal Article↗