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PubMed2005

Folic acid treatment increases homocysteine remethylation and methionine transmethylation in healthy subjects.

Folic acid treatment decreases plasma total homocysteine concentrations in healthy subjects, but the effects on homocysteine metabolism are unknown. In the present study, we investigated the effect of 3 weeks of oral treatment with 5 mg of folic acid on one-carbon flux rates in 12 healthy subjects, using in vivo stable isotope methods. In addition, we determined the effect of folic acid on blood concentrations of amino acids which may have regulatory roles in homocysteine metabolism, i.e. homocysteine, AdoMet (S-adenosylmethionine), AdoHcy (S-adenosylhomocysteine), serine and glycine. Primed, continuous infusions with [2H3-methyl-1-13C]methionine were used to determine flux rates of methionine transmethylation, homocysteine remethylation and homocysteine trans-sulphuration. Metabolic homocysteine clearance was defined as the ratio of trans-sulphuration and plasma homocysteine level. Folic acid treatment increased the homocysteine remethylation rate by 59% [95% CI (confidence interval), 13-97%; P = 0.02] and methionine transmethylation rate by 20% (95% CI, 3-41%; P=0.03). Plasma total homocysteine concentration (-18%; 95% CI, -28 to -9%; P<0.01) and the serine/glycine ratio (-20%; 95% CI, -63 to -6%; P<0.01) decreased significantly, and the AdoMet/AdoHcy ratio (11%; 95% CI, 1-20%; P = 0.02) increased significantly. Changes in one-carbon flux rates did not correlate significantly with changes in plasma concentration of these amino acids. In conclusion, folic acid treatment lowered plasma homocysteine concentration and increased whole-body remethylation and transmethylation flux in healthy subjects.

Adult↗
PubMed2002

DNA methylation in Folbp1 knockout mice supplemented with folic acid during gestation.

Periconceptional folic acid supplementation has been shown to prevent up to 70% of neural tube and other birth defects in humans; however, the mechanism is still unknown. In this study, we tested whether defective intracellular folate transport, as achieved by inactivation of the murine folate-binding protein 1 (Folbp1), affects global DNA methylation in the liver and brain from gestational day (GD) 15 embryos. Complete Folbp1 inactivation is embryolethal but can be reversed by maternal folinic acid (FA) supplementation, and thus we also tested the effect of FA supplementation on DNA methylation in Folbp1 fetuses. Overall, the extent of global DNA methylation seems to be similar across all genotypes in unsupplemented control Folbp1 mice; however, explicit conclusions regarding Folbp1(-/-) fetuses were not possible because only a single living unsupplemented fetus was viable at GD 15. FA supplementation induced global DNA hypomethylation across all genotypes. FA-induced hypomethylation is most likely due to its ability to inhibit the enzyme glycine hydroxymethyltransferase, thereby inhibiting the homocysteine remethylation cycle necessary to regenerate S-adenosylmethionine, the methyl donor for DNA methyltransferases. Our hypothesis was that due to defective folate transport in Folbp1(-/-) embryos and fetuses, DNA would be hypomethylated, thereby altering the temporal expression of critical genes necessary for normal embryonic development. However, these results suggest that an extended examination of changes in DNA methylation prior to GD 15 is required to unequivocally prove or disprove the hypothesis.

Animals↗
PubMed2001

Carrier-mediated transport of folic acid in BeWo cell monolayers as a model of the human trophoblast.

Using cultured BeWo cells as a model of human trophoblast, we investigated whether carrier-mediated transport of folic acid occurs. BeWo cells, which were derived from human choriocarcinoma, were cultured on a tissue culture plate or in a permeation chamber. When the cells reached confluence, drug uptake or transport experiments were performed. The uptake of [(3)H]folic acid by BeWo cells occurred at a much lower rate at 4 degrees C than at 37 degrees C. The uptake of [(3)H]folic acid was saturable at higher concentrations and inhibited by typical metabolic inhibitors, sodium azide and 2,4-dinitrophenol. The uptake of [(3)H]folic acid was significantly increased with decreasing pH of the incubation buffer and markedly inhibited by 4,4'-diidothiocyanostilbene-2,2'-disulfonic acid (DIDS). Analogs of folic acid, methotrexate and 5-methyltetrahydrofolate, inhibited the uptake of [(3)H]folic acid by BeWo cells. Kinetic analysis using Lineweaver-Burk plots revealed that methotrexate competitively inhibited the uptake of [(3)H]folic acid and folic acid competitively inhibited the uptake of [(3)H]methotrexate. In transport experiments, the permeation of [(3)H]folic acid from the apical-to-basal side was greater than that from the basal-to-apical side, and the transport of [(3)H]folic acid from the apical-to-basal side was inhibited by an excess of folic acid. The findings obtained in the present study confirm the existence of an asymmetric, carrier-mediated transport system for folic acid and its analog, methotrexate, across BeWo cells, a representative of the human trophoblast.

2,4-Dinitrophenol↗
PubMed2003

Folic acid and reduction of plasma homocysteine concentrations in older adults: a dose-response study.

BACKGROUND: Elevated homocysteine concentrations, a likely risk factor for cardiovascular disease, can be lowered effectively with folic acid. The minimum dose of folic acid required for maximal reduction of homocysteine concentrations is not yet known reliably. OBJECTIVE: We aimed to determine the lowest folic acid dose that decreases plasma homocysteine concentrations adequately in healthy older adults. DESIGN: A dose-response trial with a randomized, double-blind, parallel-group, placebo-controlled design was carried out among 316 Dutch men and women aged 50-75 y. Subjects received daily for 12 wk either a placebo or 1 of the 6 following folic acid doses: 50, 100, 200, 400, 600, or 800 micro g. The relative changes in plasma homocysteine concentration in response to increasing doses of folic acid were used to calculate the dose-response curve. An adequate dose of folic acid was defined as the dose that induced >or= 90% of the maximal reduction in homocysteine concentration. RESULTS: The relative decrease in plasma homocysteine concentration was associated exponentially with increasing doses of folic acid. From the dose-response curve, the adequate daily dose of folic acid was estimated to be 392 micro g, which decreased plasma homocysteine concentrations 22%. CONCLUSION: In older adults, daily supplementation with folic acid effectively lowers plasma homocysteine concentrations, and a daily dose of approximately 400 micro g is the minimum dose required for adequate homocysteine reduction.

Aged↗
PubMed1997

Factors affecting the use of folic acid supplements in pregnant women in Glasgow.

BACKGROUND: Use of folic acid supplements preconception, and during the first trimester, is associated with a reduced incidence of first and subsequent neural tube defects. The Department of Health guidelines recommend the use of folic acid supplements by all women planning a pregnancy. AIM: To ascertain the proportion using folic acid supplements and the factors affecting their use. METHOD: Questionnaires were distributed postpartum to the 515 women who delivered normal babies in three maternity units in Glasgow over a four-week period. RESULTS: Forms were completed by 487 (95%) women. Only 57% took supplements at some point during their pregnancy, and only 21% took them before conception. Failure to take supplements was significantly associated with unplanned pregnancy, younger age, and previous pregnancies. Lack of awareness of the potential benefits associated with folic acid use was the commonest reason cited by women for not taking supplements. CONCLUSIONS: Increased health education through health care professionals and mass media campaigns can improve awareness and thereby increase the use of supplements in planned pregnancies. However, 42% of women in our study had unplanned pregnancies. Intake of folic acid supplements in this group can only be increased by improvements in dietary intake within the population as a whole, and by fortification of commonly ingested foods.

Female↗
PubMed2003

Estimated folic acid intakes from simulated fortification of the New Zealand food supply.

AIM: To identify a folic acid food fortification programme that will maximise the percentage of women of child-bearing age receiving at least 400 microg folic acid/day, the amount shown to reduce the risk of neural tube defect-affected pregnancies, while not putting population groups at risk of excessive intakes. METHODS: 1997 New Zealand National Nutrition Survey data and a computer modelling programme were used to estimate folic acid intakes from simulated fortification scenarios. RESULTS: Breads fortified with folic acid at 150 microg/50 g, white flour at 100 microg/35 g and liquid milk at 200 microg/200 ml, were found to be the best fortification scenarios. Thirty one percent, 21% and 18% of women of child-bearing age received > or = 400 microg folic acid/day from the fortification of bread, white flour and milk respectively. CONCLUSIONS: The most effective scenario for folic acid fortification is bread fortified at 150 microg/50 g. However, it is impossible to fortify food at a level that ensures the majority of women of child-bearing age receive more than 400 microg folic acid/day without exposing some people to excessive amounts of folic acid. The current public health message encouraging women to select folic acid fortified foods and take folic acid supplements, needs to continue.

Adolescent↗
PubMed2006

Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials.

CONTEXT: Epidemiologic studies have suggested that folate intake decreases risk of cardiovascular diseases. However, the results of randomized controlled trials on dietary supplementation with folic acid to date have been inconsistent. OBJECTIVE: To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease. DATA SOURCES: Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted. STUDY SELECTION: From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point. DATA EXTRACTION: Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol. DATA SYNTHESIS: Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease. CONCLUSIONS: Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.

Cardiovascular Diseases↗
PubMed2006

Lack of inhibition of the anti-malarial action of sulfadoxine-pyrimethamine by folic acid supplementation when used for intermittent preventive treatment in Gambian primigravidae.

Folic acid is frequently given to pregnant women at the same time as intermittent preventive treatment (IPTp) with sulfadoxine/pyrimethamine (SP), but it is not known if it interferes with the anti-malarial activity of SP. To investigate this concern, 1,035 Gambian primigravidae were randomized to receive either folic acid (500-1,500 microg/day) together with oral iron (522) or oral iron alone (513) for 14 days at the same time as they received IPTp with SP. On presentation, 261 women (25%) had Plasmodium falciparum asexual parasitemia. Prevalences of parasitemia on day 14 after treatment were similar in both groups: 5.7% (26 of 458) in the iron plus folic acid group and 4.9% (22 of 446) in the iron alone group (risk difference = 0.74%, 95% confidence interval [CI] = -2.2% to 3.7%). Parasitologic cure was observed in 116 (91%) of 128 of women who were parasitemic on presentation and who received iron and folic acid and in 122 (92%) of 133 women who received iron alone (difference = 1.1%, 95% CI = -5.6% to 8.0%). Women who received folic acid and iron had a slightly higher mean hemoglobin concentration at day 14 than women who had received iron alone (difference = 0.14 g/dL, 95% CI = 0.01-0.27 g/dL). The results of this study suggest that in an area of low SP resistance, administration of folic acid to pregnant women in a dose of 500-1,500 mug/day will not interfere with the protective effect of SP when used for IPTp.

Adolescent↗
PubMed2004

Methylenetetrahydrofolate reductase C677T polymorphism, folic acid and riboflavin are important determinants of genome stability in cultured human lymphocytes.

We tested the hypothesis that methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, folic acid deficiency and riboflavin deficiency, independently or interactively, are important determinants of genomic stability, cell death, cell proliferation and homocysteine (Hcy) concentration in 9-d human lymphocyte cultures. Lymphocytes of seven wild-type (CC) and seven mutant (TT) homozygotes were cultured under the four possible combinations of deficiency and sufficiency of riboflavin (0 and 500 nmol/L) and folic acid (20 and 100 nmol/L) at a constant L-methionine concentration of 50 micromol/L. Viable cell growth was 25% greater in TT than in CC cells (P<0.05) and 32% greater at 100 nmol/L folic acid than at 20 nmol/L folic acid (P=0.002). The comprehensive cytokinesis-block micronucleus assay was used to measure micronuclei (MNi; a marker for chromosome breakage and loss), nucleoplasmic bridges (NPB; a marker of chromosome rearrangement) and nuclear buds (NBUD, a marker of gene amplification). The MNi levels were 21% higher in TT cells than in CC cells (P<0.05) and 42% lower in the high folic acid medium than in the low folic acid medium (P<0.0001). The NBUD levels were 27% lower in TT cells than in CC cells (P<0.05) and 45% lower in the high folic acid medium than in the low folic acid medium (P<0.0001). High riboflavin concentration (500 nmol/L) increased NBUD levels by 25% (compared with 0 nmol/L riboflavin) in folate-deficient conditions (20 nmol/L folic acid medium; P<0.05), and there was an interaction between folic acid and riboflavin that affected NBUD levels (P=0.042). This preliminary investigation suggests that MTHFR C677T polymorphism and riboflavin affect genome instability; however, the effect is relatively small compared with that of folic acid.

Adult↗
PubMed2003

[Changes in plasma zinc and folic acid concentrations in pregnant adolescents submitted to different supplementation regimens].

Zinc and folic acid nutritional status was evaluated in 74 low-income pregnant adolescents ranging from 13 to 18 years of age who received prenatal care at the Evangelina Rosa Maternity Hospital in Teresina, Piau State, Brazil. In order to evaluate the effects of different supplementation regimens on nutritional status, the adolescents were distributed into five groups. Groups I and II received equal amounts of folic acid (250 micro;g) and different doses of iron (ferrous sulfate), 120 and 80 mg, respectively. Groups III and IV received equal amounts of folic acid (250 micro;g) associated with zinc sulfate and iron at doses of 120 and 80 mg, respectively, while group V received only 120 mg of iron (routine dosage). There was a reduction in the zinc plasma concentration, and this decline was significant only in those groups which did not receive zinc supplementation. In relation to combination iron/folic acid and iron/folic acid/zinc, an excellent response was observed for folic acid, and this effect was larger in the groups that received folic acid combined with zinc, suggesting a possible role for zinc in folic acid metabolism.

Adolescent↗
PubMed2005

Folic acid deficiency modifies the haematopoietic response to recombinant human erythropoietin in maintenance dialysis patients.

BACKGROUND: While folic acid deficiency causes macrocytic anaemia in non-renal patients, the relevance of altered folate metabolism in anaemia of end-stage renal disease and its response to rHu-EPO is less clear. METHODS: Ten haemodialysis patients with macrocytic anaemia due to dietary folic acid deficiency were compared to 10 matched (age, duration of dialysis, degree of anaemia) patients with normocytic normochromic anaemia. Nineteen patients received erythropoietin-alpha intravenously thrice weekly. The study design was a prospective crossover (ABA) comparison of the effects of intravenously administered high doses of folic acid on haemoglobin levels and EPO doses, with 6 months active supplementation (B) and two periods of 6 months duration each without folic acid supplementation (A). RESULTS: The two patient groups did not differ at recruitment. Red blood cell folate levels were normal in patients with normocytic anaemia, but they were subnormal in all patients with macrocytic anaemia. Compared to the first period without folic acid supplementation, patients with macrocytic anaemia had significantly higher haemoglobin levels despite lower EPO doses after 6 months high-dose folic acid, and red cells had become normocytic. The removal of folic acid supplementation resulted in re-occurrence of macrocytosis and in a significantly lower response to rHu-EPO. In contrast, high-dose folic acid supplementation had no effect on response to rHu-EPO in patients with normocytic anaemia. CONCLUSIONS: Folic acid deficiency may occur in elderly haemodialysis patients with poor dietary folate intake without regular oral supplementation and may cause hyporesponsiveness to rHu-EPO. Macrocytosis is a simple and cheap indicator for folate deficiency in end-stage renal disease patients on maintenance dialysis.

Adult↗
PubMed2004

Effect of folate-binding protein on intestinal transport of folic acid and 5-methyltetrahydrofolate across Caco-2 cells.

BACKGROUND: Milk products are a potential matrix for fortification with synthetic folic acid or natural 5-methyltetrahydrofolate (5-CH3-H4folate) to enhance the daily folate intake. In milk, folate occurs bound to folate-binding proteins (FBP). Our previous studies with an in vitro gastrointestinal model showed that 70% of the initial FBP content of the milk product was retained in the duodenal lumen. While folic acid remained bound to FBP after gastric passage, 5-CH3-H4folate was mainly present as free folate in the duodenal lumen. AIM OF THE STUDY: To investigate the effect of FBP on the absorption of folic acid and 5-CH3-H4folate from the intestinal lumen. METHODS: The transport of [3H]-folic acid and [14C]-5-CH3-H4folate across enterocytes was studied in the presence or absence of bovine FBP using monolayers of Caco-2 cells grown on semi-permeable inserts in a two-compartment model. The apparent permeability coefficients (P(app)) of folic acid and 5-CH3-H4folate were determined and compared with the permeability of reference compounds for low (mannitol) and high (caffeine) permeability. RESULTS: The transport from the apical to the basolateral side of the Caco-2 cells was higher (P < 0.05) for folic acid (P(app) = 1.7*10(-6) cm/s) than for 5-CH3-H4folate (P(app) = 1.4*10(-6) cm/s) after 2 h incubation to 1 microM folic acid or 5-CH3-H4folate test solutions (pH 7). The permeability of folic acid and 5-CH3-H4folate across Caco-2 monolayers appeared to be higher (P < 0.05) than that of mannitol (P(app) = 0.5*10(-6) cm/s) but lower (P < 0.05) than that of caffeine (P(app) = 34*10(-6) cm/s). The addition of FBP to the medium led to a lower (P < 0.05) intestinal transport and cellular accumulation of folic acid and 5-CH3-H4folate. CONCLUSIONS: Compared to the reference compounds, folic acid and 5-CH3-H4folate showed a moderate permeability across Caco-2 cells, which indicates that folate absorption from the intestinal lumen is not likely to be complete. The intestinal transport of folic acid and 5-CH3-H4folate was found to be dependent on the extent of binding to FBP at the luminal side of the cells.

Biological Transport↗
PubMed1984

Effects of folic acid malnutrition on rotaviral infection in mice.

A study was undertaken to determine if dietary deficiencies of folic acid would influence rotaviral diarrheal disease in infant mice. Female mice were fed diets containing essentially no folic acid, 25% of a normal quantity of folic acid, or a normally recommended quantity of folic acid, beginning at time of breeding and continuing through periods of gestation and lactation. Two-day-old infants from these dams were exposed to purified murine rotavirus or to sterile virus diluent and the severity of the rotaviral infection monitored. Infants from the low folic acid group had significantly lower folate levels in their livers, indicating a deficiency was achieved, and developed more severe disease manifestations than those infants from the dams receiving the normal folic acid levels in their diet. The infection enhancement was seen as increased incidences of diarrhea and a significantly greater number of mice exhibiting high intestinal rotaviral antigen titers. Serum rotavirus antibody titers were below detectable levels in a significant number of these same infants.

Animals↗
PubMed2004

[Awareness of periconceptional consumption of folic acid among urologists and a group of laymen].

OBJECTIVE: The Ministry of Health, Labour and Welfare announced that periconceptional consumption of folic acid will reduce risks of having babies afflicted with Neural Tube Defects (NTDs) in the year of 2000. We assessed awareness of the role of folic acid among urologists and a patient group, how urologists give advices on lifestyle to young women, and what lifestyle the patient group currently maintains. MATERIALS AND METHODS: A postal questionnaire survey was conducted involving 400 urologists randomly selected and a group of 250 female patients afflicted with NTDS and 250 mothers who had given birth to babies having NTDs during the past 7 years. Eighty-four percent of urologists aged 40 years and over and 76% of the patient group aged in their 20s and 30s. Response rates were 56% in the former and 52% in the later. RESULTS: Twenty-six percent of urologists and 92% of the patient group knew an important role folic acid played in prevention of neural tube defects. While 10% of urologists advised to consume multi-vitamins containing folic acid or folic acid supplements, 25% of myelodysplastics and the mothers took them. Sixty-eight percent of doctors advised to take well-balanced food and 82% of the patent group answered that they do. Over 80% of the doctors and the patient group believed that a folic acid campaign is to be organized to inform young women of childbearing age of possible reduction of the risk. CONCLUSION: It is found that proportion of urologists who are aware of a role of periconceptional consumption of folic acid is significantly lower than that of the group of patients (p < 0.0001). Urologists are expected to recognize specific benefits of folic acid in the prevention of NTDs, to advise young women of childbearing age to take well-balanced meals, and to recommend those who wish to be pregnant to consume 400 micrograms of folic acid supplements from 4 weeks before to 12 weeks after conception.

Adult↗
PubMed2006

The prevalence of folic acid deficiency among adolescent girls living in Edirne, Turkey.

PURPOSE: A high incidence of iron-deficiency is a common observation among adolescent girls, whereas only limited data are available regarding the folic acid status of this group. This study was designed to determine the prevalence of biochemical folic acid deficiency in a group of Turkish adolescent girls. METHODS: We surveyed the serum folic acid, complete blood count, and dietary folic acid intake of Turkish adolescent girls after using three-day self-reported food intakes in urban and rural areas of Edirne, Turkey. RESULTS: A sample population was composed of 704 adolescent girls; their serum folic acid levels were found to be adequate for 37.6% (> or = 6 ng/mL), marginal for 46% (3 to 5.9 ng/mL), and at deficient levels for 16.3% (< 3 ng/mL). Folic acid deficiencies were found in 20.1% (36 of 179) and 14.7 % (61 of 416) of adolescent girls from rural and urban areas, respectively. Self-reported three-day folic acid intakes were correlated with the corresponding blood values for this nutrient. In the logistic regression analysis, three factors emerged as significant independent predictors of folic acid deficiency: low income (odds ratio [OR]: 2.4, 95% confidence interval [CI]: 1.3-4.2, p < .001), low vitamin C (OR: 1.9, 95% CI: 1.1-3.5, p < .05), and folic acid intake (OR: 4.8, 95% CI: 2.8-8.1, p < .001). CONCLUSION: Data from the present study may indicate that serum folic acid is low in a group of Turkish adolescent girls. These low values appear to be associated with low income, and low dietary intakes of folic acid and vitamin C.

Adolescent↗
PubMed2005

Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.

Periconceptual folic acid prevents neural tube defects. The effect of folic acid taken throughout pregnancy is unclear, however. We re-analysed data from a large randomised controlled trial performed between 1966 and 1967 and combined the results with those from trials included in a Cochrane review. A total of 2928 women were randomised: 1977 were allocated to placebo, 466 to folic acid 200 microg/day and 485 to folic acid 5 mg/day. Folic acid supplementation was not associated with any difference in mean birthweight, placental weight or gestational age. When combined with trials in the Cochrane review folic acid at high doses was associated with reduced risk of low birthweight (pooled relative risk 0.73 [95% CI 0.53, 0.99]). We found no conclusive evidence of benefit for folic acid supplementation in pregnant women given from time of booking onwards.

Adult↗
PubMed2002

Folic acid intake from fortification in United States exceeds predictions.

In 1996, the U.S. Food and Drug Administration issued a regulation requiring that all enriched cereal-grain products be fortified with folic acid by January 1998. An average increase in folic acid intake of 100 micro g/d was projected as a result of this fortification. The objective of the present study was to estimate the effect of this fortification on the intake of folic acid and total folate, and on the prevalence of individuals with inadequate folate intake and with high folic acid intake. We used data on food and nutrient intake from 1480 individuals who participated in the 5th and 6th examinations of the Framingham Offspring Cohort Study. Fortification was instituted during the 6th examination so that 931 participants were examined before its implementation (nonexposed) and 549 after implementation (exposed). Published data on total folate in enriched cereal-grain products were used to correct folate content in these foods to reflect fortification. Among nonsupplement users, folic acid intake increased by a mean of 190 [95% confidence interval (CI): 176, 204] micro g/d (P < 0.001) and total folate intake increased by a mean of 323 (95% CI: 296-350) micro g dietary folate equivalents (DFE)/d (P < 0.001) in the exposed participants. Similar increases were seen among supplement users exposed to fortification. The prevalence of exposed individuals with total folate intake below the estimated average requirement (320 micro g DFE/d) decreased from 48.6% (95% CI: 44.2-53.1%) before fortification to 7.0% (95% CI: 3.1-10.9%) after fortification in individuals who did not use folic acid supplements. This prevalence was approximately 1% or less for users of supplements both before and after fortification. Prevalence of individuals with folic acid intake above the upper tolerable intake level (1000 micro g folic acid/d) increased only among supplement users exposed to fortification (from 1.3 to 11.3%, P < 0.001). No changes in folic acid intake were observed over time in the nonexposed participants. By these estimations, folic acid fortification resulted in a mean increase in folic acid intake that was approximately twice as large as previously projected.

Adult↗
PubMed2003

The use of folic acid for the prevention of neural tube defects and other congenital anomalies.

OBJECTIVE: To provide information regarding the use of folic acid for the prevention of neural tube defects (NTDs) and other congenital anomalies, in order that physicians, midwives, nurses, and other health-care workers can assist in the education of women in the preconception phase of their health care. OPTION: Folic acid supplementation is problematic, since 50% of pregnancies are unplanned and the health status of women may not be optimal. OUTCOMES: Folic acid supplementation has been proven to decrease or minimize specific birth defects. EVIDENCE: A systematic review of the literature, including review and peer-reviewed articles, government publications, the previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of March 1993, and statements from the American College of Obstetrics and Gynecology, was used to develop a new clinical practice guideline for the SOGC. VALUES: Peer-review process within the committee structure. BENEFITS, HARMS, AND COSTS: The benefit is reduced lethal and severe morbidity birth defects and the harm is minimal. The personal cost is of vitamin supplementation on a daily basis and eating a healthy diet. RECOMMENDATIONS: 1. Women in the reproductive age group should be advised about the benefits of folic acid supplementation during wellness visits (birth control renewal, Pap testing, yearly examination), especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy nutritional diet, as recommended in Canada's Food Guide to Healthy Eating (good or excellent sources of folic acid: broccoli, spinach, peas, Brussels sprouts, corn, beans, lentils, oranges). (III-A) 3. Women who could become pregnant should be advised to take a multivitamin containing 0.4 mg to 1.0 mg of folic acid daily. (II-1A) 4. Women taking a multivitamin with folic acid supplement should be advised not to take more than 1 daily dose of vitamin supplement, as indicated on the product label. (II-2A) 5. Women in intermediate- to high-risk categories for NTDs (NTD-affected previous pregnancy, family history, insulin-dependent diabetes, epilepsy treatment with valproic acid or carbamazepine) should be advised that high-dose folic acid (4.0 mg-5.0 mg daily) supplementation is recommended. This should be taken as folic acid alone, not in a multivitamin format, due to risk of excessive intake of other vitamins such as vitamin A. (I-A) 6. The choice of a 5 mg folic acid daily dose for women considering a pregnancy should be made under medical supervision after minimizing the risk of undiagnosed vitamin B12 deficiency (hypersegmentation of polymorphonuclear cells, macrocystic indices, large ovalocytes, leukopenia, thrombocytopenia, markedly elevated lactate dehydrogenase level, confirmed red blood cell folate level). (II-2A) 7. Signs or symptoms of vitamin B12 deficiency should be considered before initiating folic acid supplementation of doses greater than 1.0 mg. (III-A) 8. A three-generation pedigree on the families of both the pregnant woman and the biological father should be obtained to identify increased risk for congenital birth defects (i.e., NTD, cardiac, chromosomal, genetic). (III-A) 9. Women who become pregnant should be advised of the availability of noninvasive screening tests and invasive diagnostic tests for congenital birth defects (including NTDs): maternal serum "triple marker screen" at 15 to 20 weeks, ultrasound at 16 to 20 weeks, and amniocentesis after 15 weeks of pregnancy if a positive screening test is present. (I-A) VALIDATION: This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used.

Canada↗