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Folic acid absorption in women with a history of pregnancy with neural tube defect.

Folic acid absorption was compared in nonpregnant women with a history of pregnancy with a neural tube defect (cases)(n = 10) with that of control women (n = 10) with a normal pregnancy history. [2H4]folic acid was administered in an oral dose (400 micrograms) to fasting case and control subjects after a 30-d saturation protocol involving daily ingestion of two 1-mg folic acid supplements. Serum and red blood cell folate concentrations were not different for case and control subjects before or during the saturation protocol (P > 0.05). The percentage (x +/- SD) of the oral dose of [2H4]folic acid excreted in 24-h urine collections postdose was not different (P > 0.05) for case compared with control subjects (9.05 +/- 2.25% and 11.10 +/- 3.41%, respectively). These data suggest that the absorption of folic acid routinely consumed in supplements and fortified food products is not impaired in women with a history of a pregnancy with a neural tube defect. Further case-controlled studies are needed to compare the absorption of the predominant dietary form of the vitamin.

Administration, Oral↗

[Plasma concentrations of folic acid, vitamin B12 and progesterone of cyclic bitches, bitches during pregnancy and induced abortion and bitches with pyometra].

The aim of this study was to investigate the plasma concentrations of folic acid, vitamin B12 and progesterone at different stages of the sexual cycle and pregnancy, during induced abortion and in bitches with pyometra. Bitches (n = 97) were assigned to groups as follows: a) oestrous cycle (n = 42) b) pregnancy (n = 25) c) induction of abortion (n = 10 and d) pyometra (n = 20). Oestrous cycle stages were determined by vaginal inspection and cytology. Pregnancies were estimated by ultrasound (5.0 Mhz; linear transducer; Schimadzu) at days 15-25, 35-45 and 46-63 of pregnancy. Treatments for the induction of abortion were started between days 25 and 35 after mating (5 microg/kg cabergoline daily, Galastop; 5-10 microg/kg Alfaprostol every other day, Gabbrostim). Diagnosis of pyometra was confirmed by ultrasound and vaginoscopy. Folic acid and vitamin B12 concentrations did not differ among different stages of the oestrous cycle. The mean concentration of folic acid during early pregnancy (days 15-25) exceeded levels of later stages (days 46-63): 9.4 +/- 3.7 microg/ml and 4.7 +/- 1.8 microg/ml, respectively (p < 0.01). A positive correlation between folic acid and vitamin B12 was determined in pregnant dogs ( r = 0.925; p < 0.02). Before the induction of abortion, the concentration of folic acid was 9.6 +/- 5.2 microg/ml; during abortion it decreased to 5.0 +/- 3.2 microg/ml (p < 0.01). A significant correlation (r = 0.925; p < 0.02) between progesterone and folic acid was obtained in bitches with abortion. The mean concentration of folic acid in bitches with pyometra significantly differed from that of bitches at different stages of the oestrous cycle (p < 0.05). The mean concentration of folic acid was significantly lower in metoestrous bitches when compared to bitches with pyometra (p < 0.05). The decrease of serum concentrations of folic acid during pregnancy and induced abortion show that fetal growth and abortion caused higher consumption of folic acid. Concerning bitches did not show any deficiency symptoms, which is why it can be concluded that this decrease is physiological.

Abortion, Veterinary↗

Risk of gestational hypertension in relation to folic acid supplementation during pregnancy.

The authors investigated the association between folic acid supplementation and gestational hypertension. The study population included women with nonmalformed infants in the United States and Canada who were participating in the Slone Epidemiology Center Birth Defects Study between 1993 and 2000. Women were interviewed within 6 months after delivery about sociodemographic and medical factors, the occurrence of hypertension with or without preeclampsia, and multivitamin use in pregnancy. Relative risks, adjusted for weight, parity, twin pregnancy, diabetes, smoking, education, and family income, were estimated using Cox regression models. Of 2,100 women, 204 (9.7%) reported gestational hypertension (onset after the 20th week of gestation). The multivariate-adjusted relative risk of developing gestational hypertension during the month after folic acid supplementation, compared with not using folic acid during that same month, was 0.55 (95% confidence interval: 0.39, 0.79). This finding suggests that folic acid-containing multivitamins may reduce the risk of gestational hypertension.

Adult↗

High prevalence of folic acid and vitamin B12 deficiencies in infants, children, adolescents and pregnant women in Venezuela.

BACKGROUND: There is increased worldwide concern about the consequences of folic acid and vitamin B12 deficiencies on health, which include megaloblastic anemia, neural tube defects and cardiovascular disease. OBJECTIVE: This study intended to determine the prevalence of folic acid and vitamin B12 deficiencies in vulnerable groups in labor and poor socioeconomic strata of the Venezuelan population. METHODS: A total of 5658 serum samples were processed to determine folic acid and vitamin B12 concentrations. The study involved three surveys performed during 2001-2002 and included infants, children, adolescents and pregnant women from labor and poor socioeconomic strata of the population. The method used was a radio immunoassay designed for the simultaneous measurement of serum folic acid and vitamin B12. RESULTS: The prevalence of folic acid deficiency was higher than 30% for all groups studied, reaching 81.79% in adolescents. Vitamin B12 deficiency was 11.4% in samples collected nationwide, but there was also a similar prevalence of high serum levels. The prevalence of folic acid and vitamin B12 deficiencies in pregnant women reached 36.32 and 61.34%, respectively. CONCLUSION: This work shows that there is a high prevalence of folic acid deficiency, especially in women of reproductive age, pregnant adolescents and in the whole population studied in Vargas state. This situation requires immediate intervention as supplementation or food fortification programs.

Adolescent↗

[The concentrations of homocysteine, folic acid and vitamin B12 in alcohol dependent male patients].

UNLABELLED: Metabolism of homocysteine (sulphur-containing amino acid) is accomplished in the remethylation cycle where vitamin B12 and folic acid are essential coenzymes. Markedly elevated homocysteine concentrations have been observed in patients with nutritional deficiencies of vitamin B12 and folate. Hyperhomocysteinemia in alcohol abusers may result from malnutrition and disorder of intestine absorption. AIM: The aim of the study was the estimation of homocysteine, folic acid and vitamin B12 concentrations in alcohol dependent male patients. METHOD: 71 males with a clinical diagnosis of alcohol dependence (ICD-10) have been examined. The investigated parameters have been determined in the blood serum, the homocysteine by means of immunochemical method, vitamin B12 and folic acid by means of immunoenzymatic assay. RESULTS: Serum homocysteine concentration was significantly higher and serum folic acid concentration was lower in alcohol dependent men than in controls. Mean concentrations of folic acid and vitamin B12 were significantly lower in patients with hyperhomocysteinemia than in men with normal homocysteine concentration. The highest correlation was indeed noticed between folate deficiency and the intensity of hyperhomocysteinemia. CONCLUSIONS: The development of hyperhomocysteinemia is associated with alcohol dependence that is also a probable cause of folate and vitamin B12 deficiency.

Adult↗

The role of folic acid and Vitamin B12 in genomic stability of human cells.

Folic acid plays a critical role in the prevention of chromosome breakage and hypomethylation of DNA. This activity is compromised when Vitamin B12 (B12) concentration is low because methionine synthase activity is reduced, lowering the concentration of S-adenosyl methionine (SAM) which in turn may diminish DNA methylation and cause folate to become unavailable for the conversion of dUMP to dTMP. The most plausible explanation for the chromosome-breaking effect of low folate is excessive uracil misincorporation into DNA, a mutagenic lesion that leads to strand breaks in DNA during repair. Both in vitro and in vivo studies with human cells clearly show that folate deficiency causes expression of chromosomal fragile sites, chromosome breaks, excessive uracil in DNA, micronucleus formation and DNA hypomethylation. In vivo studies show that Vitamin B12 deficiency and elevated plasma homocysteine are significantly correlated with increased micronucleus formation. In vitro experiments indicate that genomic instability in human cells is minimised when folic acid concentration in culture medium is >227nmol/l. Intervention studies in humans show: (a) that DNA hypomethylation, chromosome breaks, uracil misincorporation and micronucleus formation are minimised when red cell folate concentration is >700nmol/l folate; and (b) micronucleus formation is minimised when plasma concentration of Vitamin B12 is >300pmol/l and plasma homocysteine is <7.5micromol/l. These concentrations are achievable at intake levels in excess of current RDIs i.e. more than 200-400microgram folic acid per day and more than 2microgram Vitamin B12 per day. A placebo-controlled study with a dose-response suggests that based on the micronucleus index in lymphocytes, an RDI level of 700microgram/day for folic acid and 7microgram/day for Vitamin B12 would be appropriate for genomic stability in young adults. Dietary intakes above the current RDI may be particularly important in those with extreme defects in the absorption and metabolism of these Vitamins, for which ageing is a contributing factor.

Cells, Cultured↗

Sex-related differences in effect of ethanol administration and folic acid supplementation on pancreatic amylase in rats.

The present study was designed to determine whether folic acid supplement is sufficient to reverse the negative effects of ethanol consumption on amylase activity during gestation, lactation, and growth. Moreover, this study investigated the sex-related differences in amylase content in the pancreatic tissue, serum, and urine. The animals were randomized into three groups: Control group (CG) received water and a basic rat diet during pregnancy, lactation, and growth; Ethanol-rats (EG) were fed an ethanol diet during pregnancy, the suckling period, and growth until death; and Ethanol + folic acid group (E + FG) were handled the same way as those of EG, except they received a folic acid supplement from reproduction until the end of experimental period. Our results showed that ethanol consumption decreased the pancreatic amylase level in offspring rats at 2 months postpartum. Folic acid supplementation did not alter pancreatic amylase activities. In offspring males, ethanol administration decreased serum amylase activity at 2 months postpartum. Folic acid supplementation in males resulted in higher serum amylase levels than those corresponding to the ethanol-fed group. In females, no significant differences between groups in serum amylase levels were found. Ethanol consumption decreased urinary amylase excretion (at 30 days and 2 months postpartum), but the folic acid-supplemented group showed a more pronounced decrease in urine amylase activity than in the ethanol-fed group. At 30 days postpartum, no sex difference in urinary amylase was identified. However, in general, males showed higher values for urine amylase than females at 2 months postpartum. A folic acid-supplemented diet exerts an advantageous effect on amylase in serum in offspring males at 2 months postpartum of mothers fed ethanol during gestation and lactation periods, because amylase renal absorption is increased. In offspring females, amylase renal absorption is also increased, but we did not observed an advantageous effect on amylase in serum. It may be that sexual differentiation in females at 2 months postpartum exerts a definitive effect on amylase in serum. We found a sex-related difference in amylase activities; therefore, we suggest that in future all results of the exocrine pancreas function, in male and female animals, be analyzed separately.

Amylases↗

Absorption of folic acid by everted segments of rat jejunum.

1. Everted rings of rat intestine were used to study the initial uptake rate of folic acid at various concentrations and incubation temperatures in vitro.2. Folic acid was accumulated linearly for periods of at least 30 min.3. The initial uptake rate was found to reach a constant value as the concentration of folic acid in the incubation medium was increased above 5 x 10(-6)M.4. Reducing the temperature of incubation from 37 to 27 degrees C gave small Q(10) values at either end of the concentration range.5. Transfer of folic acid into the serosal compartment of everted sacs was shown to undergo a rate reduction in the same concentration range.6. A mechanism for folic acid transport is suggested in which folic acid is converted to the neutral species at the mucosal surface in an acid microclimate.

Animals↗

Effects of once-a-week or daily folic acid supplementation on red blood cell folate concentrations in women.

OBJECTIVE: Our aim was to determine if a once-a-week folic acid supplement increases women's red blood cell folate to concentrations (>905 nmol/l) that are associated with a low risk of bearing a child with a neural tube defect. DESIGN: Randomized control trial. SETTING: General community. SUBJECTS: In total, 114 nonpregnant women (18-40 y) volunteers, with red blood cell folate concentrations between 295 and 905 nmol/l at screening. INTERVENTION: Women were randomized to receive a once-a-week 2800 microg folic acid supplement, a daily 400 microg folic acid supplement or a daily placebo for 12 weeks. RESULTS: The mean (95% CI) red blood cell folate concentrations increased during the 12-week intervention from 608 (553-668) to 900 (828-978) in the weekly folic acid group (P<0.05) and from 615 (560-677) to 1053 (957-1158) nmol/l in the daily group (P<0.05) during the trial. At week 12, 49% of women ingesting the weekly folic acid supplement had red blood cell folate concentrations greater than 905 nmol/l compared to 74% of women ingesting the daily supplement. CONCLUSION: A once-a-week 2800 microg folic acid supplement can increase women's red blood cell folate to concentrations associated with a reduced risk of bearing a child with a neural tube defect, but is less effective than a 400 microg daily supplement. Use of a weekly folic acid supplement over at least 12 weeks before conception by women of child-bearing age may prevent neural tube defects. FUNDING: The Otago Medical Research Foundation (Laurenson Award). Healtheries (New Zealand) provided the supplements.

Adult↗

Folic acid metabolism and its disruption by pharmacologic agents.

Folic acid metabolism in eukaryotic cells consists of a network of enzymatic reactions in which 1-carbon (C1) units at three different oxidation states are 1) interconverted while linked to the 5- and/or 10-positions of tetrahydrofolate, or 2) added to, or taken from, tetrahydrofolate. Particularly important in the latter category are reactions involving C1-tetrahydrofolate adducts in the synthesis of inosinate, thymidylate, serine, and methionine. Tetrahydrofolate, a central component of the network, can be generated from: 1) folate, via the NADPH-dependent dihydrofolate reductase; 2) 5-methyltetrahydrofolate via the methyl B12-dependent methionine synthetase; or 3) 5-formyltetrahydrofolate via a sequence of reactions beginning with the ATP-dependent isomerization to 5,10-methenyltetrahydrofolate or via transfer of the formyl group to glutamate. Because of the close relationship of folic acid metabolism to cell replication, folate-dependent enzymes provide excellent targets for cancer chemotherapy. This potential has not yet been realized, however, except for dihydrofolate reductase and thymidylate synthetase, which are strongly inhibited by the anti-cancer agents methotrexate (MTX) and FUra. The following enzymes are particularly attractive as targets for future exploitation in chemotherapy: 1) the two transformylases involved in purine nucleotide synthesis, 2) serine hydroxymethyltransferase, 3) methionine synthetase, and 4) methylenetetrahydrofolate dehydrogenase. Suggestions are also made for the development of new agents based upon a strategy of enzyme-targeted chemotherapy.

Folic Acid↗

A folate-rich diet is as effective as folic acid from supplements in decreasing plasma homocysteine concentrations.

Background & Aims: At least 500 mug of folic acid are required daily to treat hyperhomocysteinemia. To reach this amount by dietary changes alone may be difficult because food has a low folic acid content and bioavailability. No studies have compared the effects of similar amounts of additional folate derived from a combination of folate-rich and fortified foods or folic acid from supplements on plasma total homocysteine (tHcy) concentrations, which was the aim of this study. Methods: Twenty male patients with hyperhomocysteinemia and coronary artery disease were included in a randomized, crossover intervention trial. Patients were treated daily with a combination of foods containing approximately 500 mug of folate or with one 500 mug capsule of synthetic folic acid over two five-week periods separated by a five-week wash-out period. Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: -15.9 to -1.2) and synthetic folic acid capsules by 8% (95% CI: -13.3 to -2.7). Conclusions: This study shows, for the first time in the literature, that a folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy concentrations and adds further support to the recommendation of those diets to prevent cardiovascular disease.

Journal Article↗

Folic acid and neural tube defects in pregnancy: a review.

Neural tube defects (NTDs) are common fetal malformations. They are multifactorial in origin, with folic acid as the primary known environmental factor. It is recommended that all women consume 0.4 mg of synthetic folic acid daily if there is any possibility of becoming pregnant. Women who have had a previous pregnancy affected by NTD should increase their folic acid intake to 4.0 mg daily periconceptually. The purpose of this article is to review the relationship between folic acid and NTDs. It also discusses how the knowledge and use of folic acid has affected the incidence of NTDs, and ways in which the knowledge and use of folic acid before pregnancy can be increased.

Female↗

Knowledge of periconceptional folic acid for the prevention of neural tube defects. The missing links. Northeastern Ontario Primary Care Research Group.

BACKGROUND: Periconceptional folic acid supplementation is effective in preventing primary and secondary neural tube defects (NTDs) and other congenital defects. However, debate exists regarding the effectiveness of public and physician education on patient knowledge and compliance. OBJECTIVE: To examine the level of knowledge about the usefulness of periconceptional folic acid supplementation in a sample of patients from primary care practices. DESIGN: Cross-sectional survey. A confidential, anonymous questionnaire was completed by patients before physician encounters. A maximum of 20 consecutive female patients from each of 3 age groups (16-24, 25-32, and 33-40 years) were recruited from each primary care practice. SETTINGS: Twenty-two Canadian teaching practices affiliated with the Northeastern Ontario Primary Care Research Group. OUTCOME: Women's knowledge of periconceptional folic acid supplementation for the prevention of NTDs. RESULTS: Of 1125 eligible female patients between the ages of 16 and 40 years visiting their family physician in 1996, 1124 (99.9%) completed the questionnaire. General awareness of NTDs was high (62.7%); however, knowledge that these defects were preventable was lower (22.5%). Only 7.8% of the women made the association between folic acid intake and NTDs. The specific knowledge that NTDs could be prevented with folic acid supplementation before conception was identified by 1.8% of the sample. Pregnant participants were at least twice as likely to be informed about the link. Interpractice variability existed with respect to knowledge of folic acid supplementation. CONCLUSION: Knowledge of periconceptional folic acid supplementation for the prevention of NTDs was low in this sample and is likely to be reflected in missed opportunities to prevent an important class of congenital malformations.

Adolescent↗

More folic acid for everyone, now.

Research during the last 5 years has made it clear that people who do not take folic acid supplements are at increased risk for functional folate deficiency, which has been proven to cause spina bifida and anencephaly and also has been associated with an increased risk for occlusive cardiovascular disease. The overriding folate policy issue is how to increase dramatically the folate consumption of 75% of the population who are now consuming 0.4 mg of folic acid in a supplement. The most expeditious way to increase consumption is through fortification of a food staple. Public health programs are also needed to educate people about the vital importance of increased consumption of folic acid vitamin supplements and of food rich in natural folates. It is urgent that fortification of cereal-grain products be implemented now. The level proposes by FDA would accomplish some prevention, but much more prevention would occur if the fortification were 2.5 times that level. Fortification at the higher level would prevent about 1000 spina bifida and anencephaly birth defects each year and perhaps as many as 50,000 premature deaths each year from coronary disease. Available data have not demonstrated that increasing consumption of folic acid by 0.1 to 0.25 mg of folic acid a day is harmful. If a policy needs to be established on the assumption that people who take vitamin supplements could be harmed, a good policy option ia available; require that all folic acid vitamin supplements also contain 0.4 mg of vitamin B-12.

Adult↗