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PubMed1994

Concentrations of folates in ruminal content of steers: responses to a dietary supplement of folic acid in relation with the nature of the diet.

In an attempt to evaluate the ruminal effects of dietary supplements of folic acid, eight steers (352 +/- 27 kg BW) fitted with a ruminal cannula were randomly assigned to a replicated 4 x 4 Latin square design. The treatments were 70% rolled barley + 30% timothy hay (HC), HC + 2 mg of folic acid per kilogram of BW (HC + FA), 30% rolled barley + 70% timothy hay (HF), and HF + 2 mg of folic acid per kilogram of BW (HF + FA). After 5 wk of adaptation to the dietary treatments, ruminal contents were sampled over three consecutive days, at 1, 2, 4, 8, 12, and 23 h after feed distribution. Concentrations of folates in solid and liquid ruminal fractions were increased by the dietary supplement of folic acid (P = .0001) and by the ingestion of concentrate compared with hay-based diets (P < .05). Preprandial concentrations of serum folates were not affected by the nature of the diet when steers received no folic acid but the increase of serum folates induced by the dietary supplement of folic acid was more important in steers fed concentrates than in those fed hay-based diets (diet x supplement of folic acid interaction P = .002). Microbial protein (P = .004) and microbial mass (P = .002) in ruminal fluid were increased with concentrate-based diets compared with hay-based diets; folic acid did not have any effect on these variables (P > .05). In conclusion, concentrations of folates in ruminal contents were affected by dietary supplements of folic acid and by the nature of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1992

Localized deficiencies of folic acid in aerodigestive tissues.

The notion that requirements for folic acid may be higher in some tissues than others, resulting in localized deficiencies in spite of blood levels in the normal range was first suggested by the observation of megaloblastic changes in the cervical epithelium that responded to folate supplementation. Theoretically, such deficiencies may arise from elevated folate turnover in response to rapid tissue proliferation or repair; inactivation or alteration of its function by external agents such as tobacco, alcohol, or drugs; or altered metabolism or tissue uptake caused by an inborn error. Marginal dietary intake could aggravate these effects on cells at risk. Evidence for the possible existence of localized folate deficiencies in the aerodigestive tract includes lower circulating folate levels in smokers as compared with nonsmokers; yet lower circulating levels in smokers with bronchial metaplasia; lower folate levels in scrapings of the buccal mucosa of smokers than non-smokers; apparent improvement in bronchial atypical metaplasia in smokers supplemented with folic acid; lower erythrocyte folate levels and higher prevalence of cellular features compatible with folate deficiency in geographic areas and individuals in South Africa at high risk for esophageal cancer; and a trend toward a lower prevalence of colonic dysplasia in ulcerative colitis patients who use folic acid supplements. These observations, as well as animal and in vitro studies, also suggest that folate deficiency may be co-carcinogenic. Further research in this area will be aided by the development of animal models of localized folate deficiency and of methodologies capable of measuring folate levels in minute quantities of tissues and exfoliated cells.

Colitis, Ulcerative↗
PubMed2006

Inadequate compliance with periconceptional folic acid supplementation in South Australia.

BACKGROUND: Despite recommendations for women to take folic acid supplements, there has been little reduction in the number of neural tube defect cases occurring each year. AIMS: To assess the level of compliance of pregnant women to recommendations for folic acid supplementation in South Australia, and audit the labelled content in reported supplements used. METHODS: A survey was conducted from May to September 2005 with 304 pregnant women recruited from antenatal clinics at the Lyell McEwin Health Service, the Women's and Children's Hospital and the Modbury Hospital in Adelaide. RESULTS: Full compliance with supplementation recommendations for both timing and dose was achieved by 30% of women. Partial compliance was achieved by 43%, while 27% took no folic acid supplements. CONCLUSIONS: There is currently poor compliance with folic acid supplementation around conception. Additional food fortification may better achieve an adequate daily level of folic acid.

Adult↗
PubMed1996

Blood folic acid and vitamin B12 in relation to neural tube defects.

OBJECTIVE: To determine the relation between blood folic acid and serum vitamin B12 in neural tube defect pregnancies using data from the MRC Vitamin Study and a literature review of all studies. DESIGN: Stored blood samples collected as part of a randomised trial of vitamin supplementation in the prevention of neural tube defects were retrieved from affected pregnancies (cases) and unaffected pregnancies (controls). Four controls were matched with each case by centre, maternal age and duration of storage of the blood sample. The samples had been collected from women at entry to the trial, immediately before the women became pregnant, and at around 12 weeks of pregnancy. Our results were combined with those already published from other studies to obtain an overall assessment of blood folic acid and vitamin B12 in relation to neural tube defects. SETTING: Blood samples were collected as part of the MRC Vitamin Study. The collaborating centres were in the United Kingdom, Hungary, Israel, Australia, Canada and Russia. PARTICIPANTS: Twenty-seven women with neural tube defect pregnancies and 108 matched controls with unaffected pregnancies. RESULTS: Serum and red cell folic acid and serum vitamin B12 levels were lower in the cases than in controls at each of the three occasions when blood samples were collected, but no comparison was significant (P > 0.05). A systematic review of all studies from the literature showed that on average, during the 1st trimester of pregnancy, serum folic acid was 0.6 ng/ml lower in neural tube defect pregnancies (P < 0.01), red cell folic acid was 77 ng/ml lower (P < 0.001) and serum vitamin B12 was 38 ng/l lower (P < 0.001). A logistic regression showed no association between serum B12 and neural tube defects after allowing for serum folic acid. CONCLUSION: our results are consistent with other evidence that folic acid and vitamin B12 levels are lower in women with neural tube defect pregnancies and consistent with evidence from randomised trials which showed that folic acid is protective.

Female↗
PubMedDate not supplied

Chemiluminescence inhibition assay for folic acid using flow injection analysis.

A new flow injection method for the determination of folic acid is described. A fast oxidation reaction occurred when folic acid was mixed with potassium ferricyanide generating ferrocyanide which then inhibited the chemiluminescent reaction of ferricyanide and luminol in alkaline medium. The decrease of chemiluminescence intensity was correlated with the folic acid concentration in the range 0.1-21 microg/mL; the detection limit for the assay was 0.03 microg/mL (3sigma). A complete analysis of folic acid, including sampling and washing, could be performed within 2 min with a relative standard deviation of less than 4.0%. The proposed method has been applied successfully to the determination of folic acid in pharmaceutical preparations.

Ferricyanides↗
PubMed1999

The influence of folic acid supplement on the outcome of pregnancies in the county of Funen in Denmark. Part I.

OBJECTIVE: To determine whether a supplement of folic acid given preconceptionally or early in pregnancy had any influence on, birth weight, incidence of preterm labour, low birth weight and small for gestational age. Furthermore, the aim was to elucidate, whether the outcome differed following the administration of two different dosages of folic acid, namely 2.5 and 1.0 mg. MATERIAL: All women in the childbearing age living on the island of Funen, Denmark (population 500,000) were offered a supplement of folic acid over a period of 3 years and 3 months. 14,021 women, who gave birth to 13,860 single-born and 325 multiborn children, were registered. A total of 8184 women took part in the double-blind randomized trial: 2310 had a supplement of folic acid without being randomized and 2721 women received no folic acid supplement. No information regarding the use of folic acid was available in 806 pregnancies. Abortions (512) were excluded. RESULTS AND CONCLUSIONS: A supplement 1.0 mg folic acid had the same effect as 2.5 mg. The effects of supplementing the diet with folic acid given preconceptionally or in the first half of pregnancy in an affluent Northern country were a slight increase of birth weight and a decrease in the incidence of preterm labour, infants with low birth weight and small for gestational age. The greatest effect was seen in the groups receiving folic acid preconceptionally.

Birth Weight↗
PubMed2006

The effects of folic acid and nitric oxide synthase inhibition on coronary flow and oxidative stress markers in isolated rat heart.

The aim of this study was to assess the effects of folic acid on coronary flow and oxidative stress markers with or without non-specific inhibition of nitric oxide synthase by L-NAME in isolated rat hearts. The hearts of male Wistar albino rats (n = 12, age 8 weeks, body mass 180-200 g) were retrograde perfused according to the Langendorff technique at gradually increased constant perfusion pressure (40-120 cmH2O). Coronary flow and markers of oxidative stress: nitrite outflow, superoxide anion production, and index of lipid peroxidation (by measuring thiobarbituric acid reactive substances) in coronary effluent were calculated. The experiments were performed during control conditions and in presence of folic acid (100 microM) alone or folic acid (100 microM) plus L-NAME (30 microM). Control values of coronary flow varied in range from 4.37 +/- 0.10 ml/min/g wt at 40 cmH2O to 12.05 +/- 0.42 ml/min/g wt at 120 cmH2O. Nitrite outflow varied from 1.68 +/- 0.17 nmol/min/g wt at 40 cmH2O to 3.56 +/- 0.17 nmol/min/g wt at 120 cmH2O and was parallel with coronary perfusion pressure-coronary flow curve. Folic acid significantly increased coronary flow (40-120 cmH2O, 5.63 +/- 0.10 ml/min/g wt and 15.2 +/- 0.42 ml/min/g wt, respectively) and was accompanied by significant increase in nitrite outflow (2.28 +/- 0.29 nmol/min/g wt at 40 cmH2O to 6.66 +/- 0.50 nmol/min/g wt at 120 cmH2O). In addition, folic acid significantly decreased superoxide anion production especially at upper coronary perfusion pressure values (60% at 120 cmH2O) and increased index of lipid peroxidation (37.16% at 120 cmH2O), respectively. Folic acid plus L-NAME did not change control values of coronary flow significantly. However, folic acid plus L-NAME increased nitrite outflow especially at upper coronary perfusion pressure values (43.05% at 120 cmH2O) and did not change significantly superoxide anion production or index of lipid peroxidation versus control values, respectively. The results clearly showed that on isolated rat hearts at gradually increased constant perfusion pressure, folic acid increased coronary flow, increased nitrite outflow, decreased superoxide anion production, and increased index of lipid peroxidation. These effects were reversed or blocked by L-NAME thus demonstrating mediation or at least participation of NO in the mechanism of the folic acid-induced effects.

Animals↗
PubMed1999

Folic acid inhibition of EGFR-mediated proliferation in human colon cancer cell lines.

Although accumulating evidence suggests a chemopreventive role for folic acid in colon cancer, the regulation of this process in unknown. We hypothesize that supplemental folic acid exerts its chemopreventive role by inhibiting mucosal hyperproliferation, an event considered to be central to the initiation of carcinogenesis in the gastrointestinal tract. The present investigation examines the effect of supplemental folic acid on proliferation of Caco-2 and HCT-116 colon cancer cell lines. Furthermore, because certain tyrosine kinases, particularly epidermal growth factor receptor (EGFR), play a role in regulating cell proliferation, we also examined the folic acid-induced changes in tyrosine kinase activity and expression of EGFR. In Caco-2 and HCT-116 cells, maintained in RPMI 1640 medium containing 1 microg/ml folic acid, we observed that the supplemental folic acid inhibited proliferation in a dose-dependent manner. Pretreatment of HCT-116 and Caco-2 cell lines with supplemental folic acid (1.25 microg/ml) completely abrogated transforming growth factor-alpha (TGF-alpha)-induced proliferation in both cell lines. Tyrosine kinase activity and the relative concentration of EGFR were markedly diminished in both cell lines following a 24-h exposure to supplemental folic acid. The folic acid-induced inhibition of EGFR tyrosine kinase activity in colon cancer cell lines was also associated with a concomitant reduction in the relative concentration of the 14-kDa membrane-bound precursor form of TGF-alpha. In conclusion, our data suggest that supplemental folic acid is effective in reducing proliferation in two unrelated colon cancer cell lines and that EGFR tyrosine kinase appears to be involved in regulating this process.

Anticarcinogenic Agents↗
PubMed2003

Folic acid supplementation in dementia: a preliminary report.

Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients. The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients (only 7 completers) with dementia and low-normal folic acid levels. This is the first study evaluating folic acid or placebo in patients with dementia. Subjects had low-normal baseline folic acid levels. The magnitude of change between baseline and second testing was not statistically significant between the 2 groups. However, there was a trend for the folate group to perform worse on two specific cognitive measures, suggesting a possible trend toward worsening of some cognitive abilities after the folic acid. The folic acid in very high doses was well tolerated. Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia.

Aged↗
PubMed2003

Folic acid with or without vitamin B12 for cognition and dementia.

BACKGROUND: Folates are vitamins essential to the development of the central nervous system. Insufficient folate activity at the time of conception and early pregnancy can result in congenital neural tube defects. In adult life folate deficiency has been known for decades to produce a characteristic form of anaemia ("megaloblastic"). More recently degrees of folate inadequacy, not severe enough to produce anaemia, have been found to be associated with high blood levels of the amino acid homocysteine. Such degrees of folate inadequacy can arise because of insufficient folates in the diet or because of inefficient absorption or metabolic utilisation of folates due to genetic variations. Conventional criteria for diagnosing folate deficiency may be inadequate for identifying people capable of benefiting from dietary supplementation. High blood levels of homocysteine have been linked with the risk of arterial disease, dementia and Alzheimer's disease. There is therefore interest in whether dietary supplements of folic acid (an artificial chemical analogue of naturally occurring folates) can improve cognitive function of people at risk of cognitive decline associated with ageing or dementia, whether by affecting homocysteine metabolism or through other mechanisms. There is a risk that if folic acid is given to people who have undiagnosed deficiency of vitamin B12 it may lead to neurological damage. Vitamin B12 deficiency produces both an anaemia identical to that of folate deficiency but also causes irreversible damage to the central and peripheral nervous systems. Folic acid will correct the anaemia of vitamin B12 deficiency and so delay diagnosis but will not prevent progression to neurological damage. For this reason trials of folic acid supplements may involve simultaneous administration of vitamin B12. Apparent benefit from folic acid given in the combination would therefore need to be "corrected" for any effect of vitamin B12 alone. A separate Cochrane review of vitamin B12 and cognitive function is being prepared. OBJECTIVES: To examine the effects of folic acid supplementation, with or without vitamin B12, on elderly healthy and demented people, in preventing cognitive impairment or retarding its progress. SEARCH STRATEGY: Trials were identified from a search of the Cochrane Dementia and Cognitive Improvement Specialized Register Group on 9 April 2003 using the terms: folic acid, folate, vitamin B9, leucovorin, methyltetrahydrofolate, vitamin B12, cobalamin, cyanocobalamin, dementia, cognitive function, cognitive impairment, Alzheimer's disease, vascular dementia, mixed dementia and controlled trials. MEDLINE and EMBASE (both all years) were searched for additional trials on healthy people. SELECTION CRITERIA: All double-blind placebo-controlled randomized trials, in which supplements of folic acid with or without vitamin B12 were compared with placebo for elderly healthy people or people with any type of dementia or cognitive impairment. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria and assessed study quality. One reviewer extracted and analysed the data. In comparing intervention with placebo, weighted mean differences, and standardized mean difference or odds ratios were estimated. MAIN RESULTS: Four randomized controlled trials fulfilled the inclusion criteria for this review. One trial (Bryan 2002) enrolled healthy women, and three (Fioravanti 1997; Sommer 1998; VITAL 2003) recruited people with mild to moderate cognitive impairment or dementia with or without diagnosed folate deficiency. Fioravanti 1997 enrolled people with mild to moderate cognitive impairment or dementia as judged by scores on the Mini-Mental State Examination (MMSE) and Global Deterioration Scale and with serum folate level<3ng/l. One trial (VITAL 2003) studied the effects of a combination of vitamin B12 and folic acid on patients with mild to moderate cognitive impairment due to Alzheimer's disease or mixed dementia. The analysis from the included trials found no benefit from folic acid with or without vitamin B12 in comparison with placebo on any measures of cognition and mood for healthy or cognitively impaired or demented people: Folic acid effect and healthy participants: there was no benefit from of oral 750 mcg folic acid per day for five weeks compared with placebo on measures of cognition and mood of 19 healthy women aged 65 to 92. Folic acid effect and people with mild to moderate cognitive decline or dementia: there were no statistically significant results in favour of folic acid with or without vitamin B12 on any measures of cognitive function. Scores on the Mini-Mental State Examination (MMSE) revealed no statistically significant benefit from 2 mg per day folic acid plus 1mg vitamin B12 for 12 weeks when compared with placebo (WMD 0.39, 95% CI -0.43 to 1.21, P=0.35). Cognitive scores on the Alzheimer's Disease Scale (ADAS-Cog) showed no statistically significant benefit from 2 mg /day folic acid plus 1 mg /day vitamin B12 for 12 weeks compared with placebo (WMD 0.41, 95% -1.25 to 2.07, P=4.63). The Bristol Activities of Daily Living Scale (BADL) revealed no benefit from 2mg per day of folic acid plus 1 mg vitamin B12 for 12 weeks in comparison with placebo (WMD -0.57, 95%CI -1.95 to 0.81, P=0.42). None of the sub tests of the Randt Memory Test (RMT) showed statistically significant benefit from 15 mg of folic acid orally per day for 9 weeks when compared with placebo. One trial (Sommer 1998) reported a significant decline compared with placebo in two cognitive function tasks in demented patients who had received high doses of folic acid (10 mg /day) for unspecified periods. One trial (VITAL 2003) showed that 2 mg folic acid plus 1 mg vitamin B12 daily for 12 weeks significantly lowered serum homocysteine concentrations (P <0.0001). REVIEWER'S CONCLUSIONS: There was no beneficial effect of 750 mcg of folic acid per day on measures of cognition or mood in older healthy women. In patients with mild to moderate cognitive decline and different forms of dementia there was no benefit from folic acid on measures of cognition or mood. Folic acid plus vitamin B12 was effective in reducing the serum homocysteine concentrations. Folic acid was well tolerated and no adverse effects were reported. More studies are needed.

Cognition↗
PubMed1998

Folic acid for the prevention of congenital anomalies.

UNLABELLED: Paediatricians need to be aware of the broad implications that sufficient maternal folic acid intake has on the wellbeing of the embryo and fetus. There is now strong evidence that adequate periconceptional maternal folic acid supplementation during critical periods of organ formation is associated with reduction in both the occurrence and recurrence of neural tube defects, congenital heart defects (particularly conotruncal heart defects), obstructive urinary tract anomalies, limb deficiencies, orofacial clefts and congenital hypertrophic pyloric stenosis. Inadequate maternal folic acid intake is associated with preterm deliveries, intra-uterine growth retardation, placental abruption and infarction, while maternal folic acid supplementation is associated with a reduction in preterm deliveries and intra-uterine growth retardation. Recently adequate folic acid intake in adults has been associated with a reduction in adult cardiovascular disease and some cancers. A common mutation in the 5,10 methylenetetrahydrofolate reductase gene has been identified which produces a thermolabile variant of 5,10 methylenetetrahydrofolate reductase with reduced enzyme activity. The common mutation is a risk factor both for neural tube defects and adult cardiovascular diseases. Folic acid acts to increase the activity of the variant methylenetetrahydrofolate reductase thereby reducing plasma homocysteine levels. However the polymorphism does not explain all of the protective effects of folic acid. CONCLUSION: Primary prevention of birth defects by adequate periconceptional folic acid supplementation is a major public health opportunity and has wide implications in reducing both mortality and morbidity due to birth defects and several adult diseases. It follows that there would also be a curbing of health care costs related to those disorders.

Adult↗
PubMed2005

An exploration of health effects of folic acid in pregnancy beyond reducing neural tube defects.

OBJECTIVES: First, to examine the biological basis of why folic acid may have health effects beyond its proven effect of reducing neural tube defects; and second, to explore current controversial policies of folic acid supplementation and food fortification. METHODS: We searched MEDLINE for English-language papers published from 1991 to 2003, using the key words "folic acid" and "folate." The literature search was restricted to human studies. Of 8986 publications identified, 65 were relevant to the objectives of this paper. RESULTS: Analysis of the literature revealed that a major mechanism of folic acid in improving infant health may be related to its effect in correcting maternal folate-homocysteine-methylenetetrahydrofolate reductase metabolic defects. Conversely, exposure to high levels of folic acid may have such adverse health effects as increased risk of neurologic disorders in the general population. CONCLUSIONS: Randomized trials or well-designed prospective cohort studies are needed to assess the effects of folic acid on various pregnancy outcomes. To enable an examination of the association between folic acid and rare outcomes, such as a specific category of birth defects and fetal and neonatal deaths, it is necessary to recruit a large number of pregnant women to participate in such studies.

Dietary Supplements↗
PubMed2004

[Effects of folic acid cooperated with soybean isoflavone on the neural tube defects pregnant rats].

OBJECTIVE: To study the effect of folic acid cooperating with soybean isoflavone on the oxidative status of neural tube defects (NTDs) pregnant rats induced by cyclophosphamide, to observe the relationship of the two factors, folic acid and the isoflavone and to look for the best co-intervention group. METHODS: The 100 pregnant rats of 2.5-3 months old were randomly divided into the control group, model group, co-intervention groups and solo-intervention groups. The animals were executed on the 20th day of gestation as to examining the levels of antioxidative indices (GSH, GSH-Px, Se, Mn, Fe) in blood. The incidence rates of NTDs were calculated. RESULTS: The interaction of folic acid and isoflavone had significant effect on the indices related with antioxidation (P < 0.05). Folic acid 0.7 mg/kg cooperated with isoflavone 160 mg/kg had the best intervention effects in our study. Compared with the solo-intervention by folic acid 1.4 mg/kg and isoflavone 320 mg/kg, the effect of co-intervention (folic acid 0.7 mg/kg cooperated with isoflavone 160 mg/kg) was significantly better (P < 0.05). CONCLUSION: Folic acid should be the main protective factor of NTDs, and isoflavone might reinforce the protective effects of folic the acid on NTDs by increasing the antioxidative ability, however, the effect is related with the ratio of the two factors.

Animals↗
PubMed1962

Absorption of folic acid from the small intestine of the rat.

The absorption of folic acid from segments of the small intestine of the rat has been measured in situ with tritium-labelled folic acid. The fraction absorbed was independent of concentration below 10(-6) M but was depressed to half at 4x10(-5) M. Direct measurements of fluxes showed that the mucosal --> serosal flux was about 14 times the serosal --> mucosal flux, and therefore that uptake of folic acid is an active process. In the ileum but not in the duodeno-jejunum, absorption was depressed by the presence of electrolyte. There was little difference in absorptive capacity between jejunum and ileum nor was there any significant change in animals suffering from a dietary deficiency of folic acid.

Animals↗
PubMed2000

The use of folic acid supplementation in psoriasis patients receiving methotrexate: a survey in the United Kingdom.

There is little literature on the use of folic acid supplementation in psoriasis patients being treated with methotrexate. Under the auspices of the British Association of Dermatologists we surveyed, using a questionnaire, the use of folic acid supplementation with methotrexate therapy for psoriasis by dermatologists in the UK. Six-hundred and fifteen questionnaires were sent and 153 responses were received (25%). One-hundred and fourteen of the responders (75%) used folic acid supplementation with methotrexate in psoriasis patients. Thirty (26%) of these used folic acid supplementation in all patients taking methotrexate and 84 (74%) used folic acid only under certain circumstances, the most common of which was an elevated erythrocyte mean corpuscular volume. Forty-six per cent of respondents believed that folic acid supplementation reduced nausea and 60% believed that folic acid did not interfere with the efficacy of methotrexate. A wide variety of dosing regimens were used for folic acid supplementation. In the absence of guidelines and controlled trials, there is great variation in the indication for use, dosing regimens used and beliefs regarding methotrexate supplementation for psoriasis. Randomized controlled trials are necessary to address these questions.

Dermatologic Agents↗
PubMed1996

Folic acid in the prevention of birth defects.

Maternal use of folic acid prior to conception reduces the risk for neural tube defects. In addition, other birth defects may be prevented by the periconceptional use of folic acid. Homocysteine-methionine metabolism appears to be altered in women with pregnancies affected by neural tube defects; however, the specific mechanisms of causation are not yet known. Fortification of flour with folic acid has been approved by the Food and Drug Administration, although at a level that still requires folic acid supplementation as recommended by the Public Health Service for all women of childbearing age to prevent neural tube defects.

Congenital Abnormalities↗