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PubMed2002

Content of folic acid and free homocysteine in blood serum of human papillomavirus-infected women with cervical dysplasia.

The authors estimated the concentrations of folic acid and free homocysteine in the blood serum of women with CIN III (cervical intraepithelial neoplasia-Burghard's classification) infected with DNA HPV (human papillomaviruses) of type 16 and/or 18. The control group consisted of 49 patients with normal cytological smears without HPV infection. Types 16 and/or 18 DNA HPV were found in 50 patients. This women qualified for the studied group. The sequence of DNA HPV type 16 and/or 18 was identified with the PCR method (polymerase chain reaction). The high-performance liquid chromatography (HPLC) method was employed to evaluate the levels of folic acid and free homocysteine in the blood serum of the examined patients. Significantly lower levels of folic acid and higher levels of free homocysteine were observed in the blood serum of HPV-positive patients with CIN III. The correlation was found between serum concentrations of folic acid and free homocysteine in both groups.

Adult↗
PubMed2004

Folic acid and vitamin E supplementation effects on homocysteinemia, endothelial function and plasma antioxidant capacity in young myocardial-infarction patients.

We examined the effects of folate (either alone or co-supplemented with Vitamin E) on endothelial function in hyperhomocysteinimic patients and correlated results with serum antioxidant capacity. A randomized trial was carried out in 30 young patients with recent acute myocardial infarction (AMI) and high plasma homocysteine concentrations. Intervention consisted of high doses of folate, either alone (group A) or in combination with Vitamin E (group B), for three months. Main outcome measures were endothelial function, serum antioxidant capacity, and homocysteinemia. Folic acid treatment reduced plasma homocysteine concentrations in both groups by 41% and, as compared with baseline values, was associated with a significant (P<0.001) improvement of endothelial function (from 0.322 (0.03) to 0.450 (0.02)mm in group A and from 0.338 (0.03) to 0.584 (0.04)mm in group B). However, there was no difference in endothelial function improvement between folic acid and folic acid plus Vitamin E group. Plasma antioxidant capacity significantly (P<0.001) increased in both groups. In conclusion, beneficial effects of folic acid on vasomotion appear to be independent of antioxidant action but, rather, seem to be strongly associated with reduction of homocysteinemia. Confirming previous reports, the effects of Vitamin E are still equivocal.

Adult↗
PubMed1997

Quantitative responses of serum folate to increasing intakes of folic acid in healthy women.

OBJECTIVES: Health authorities are advising people to increase folate intake and more foods are being fortified with folic acid. Estimation of dietary folate is difficult because nutrient data bases lack this nutrient in many countries and bioavailability is variable. To see if serum folate can be used to reflect effective folate intake, we have measured serum folate after healthy women had taken different doses of pure folic acid supplements in the nutritional range. METHODS: A total of 20 volunteer subjects took part in one or more of three experiments, six of them took part in all three. In each experiment subjects took two different doses of folic acid, each for three weeks. Experiment (1) 100 micrograms then 1000 micrograms/d; experiment (2) 500 micrograms then 1500 micrograms/d; experiment (3) 1000 then 2000 micrograms/d. Serum folate was measured after overnight fast with a homogenous enzyme binding assay kit. In experiment (3) red cell folates were also measured. RESULTS: It took three weeks' of the same supplement for serum folate to reach its full higher value. Mean serum folates of small groups of subjects were significantly higher with each higher dose of supplement. The biggest increase was for the first 100 micrograms that is in the range of intake from unfortified foods. The curve of serum folate against folic acid supplement intake shows that serum folate of groups of people, properly standardized, can provide a practical method for assessing adequacy or change of people's folate intake. Red cell folates were less responsive.

Administration, Oral↗
PubMed2006

Effects of routine oral iron supplementation with or without folic acid for women during pregnancy.

BACKGROUND: It has been suggested that routine intake of supplements containing iron or combination of iron and folic acid during pregnancy improves maternal health and pregnancy outcomes. OBJECTIVES: To assess the efficacy, effectiveness and safety of routine antenatal daily or intermittent iron supplementation with or without folic acid during pregnancy on the health of mothers and newborns. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June 2005). Additionally, we contacted relevant organizations for the identification of ongoing and unpublished studies. SELECTION CRITERIA: All randomised or quasi-randomised trials evaluating the effect of routine supplementation with iron or combination of iron and folic acid during pregnancy. DATA COLLECTION AND ANALYSIS: We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion and one author extracted data. We collected information on randomisation method, allocation concealment, blinding and loss to follow up. The primary outcomes included maternal and infant clinical and laboratory outcomes. MAIN RESULTS: Forty trials, involving 12706 women, were included in the review. Overall, the results showed significant heterogeneity across most prespecified outcomes. Heterogeneity could not be explained by standard sensitivity analyses including quality assessment; therefore, all results were analysed assuming random-effects. Very limited information related to clinical maternal and infant outcomes was available in the included trials. The data suggest that daily antenatal iron supplementation increases haemoglobin levels in maternal blood both antenatally and postnatally. It is difficult to quantify this increase due to significant heterogeneity between the studies. Women who receive daily antenatal iron supplementation are less likely to have iron deficiency and iron-deficiency anaemia at term as defined by current cut-off values. Side-effects and haemoconcentration are more common in women who receive daily iron supplementation. No differences were evident between daily and weekly supplementation with regards to gestational anaemia; haemoconcentration during pregnancy appears less frequent with the weekly regimen. The clinical significance of hemoconcentration defined as haemoglobin greater than 130 g/L remains uncertain. AUTHORS' CONCLUSIONS: Further studies are needed to assess the effects of routine antenatal supplementation with iron or a combination of iron and folic acid on clinically important maternal and infant outcomes.

Anemia, Iron-Deficiency↗
PubMed2006

[The frequency of twin pregnancies increased in a Chilean hospital associated with periconceptional flour folic acid supplementation].

BACKGROUND: A significant increase in the frequency of twins has been described in the literature as a secondary effect of perinatal supplementation with folic acid. AIM: To verify if the frequency of twins increased in a Chilean hospital, after the start of flour folic acid supplementation. MATERIAL AND METHODS: The frequency of twins was compared in the University of Chile Clinical Hospital, before and after the start of flour fortification with folic acid. RESULTS: There was a 34% increase in the frequency of twins during the post fortification period (2001-2004) as compared with the previous period (1998-2000). A decrease in the frequency of male twins, when compared with single newborns, was also observed in the post fortification period. There was a higher frequency of stillborns among twins, when compared with single newborns. CONCLUSIONS: The frequency of twin pregnancies increased after flour folic acid supplementation in sample of Chilean population.

Chile↗
PubMed2001

Kinetics of folate turnover in pregnant women (second trimester) and nonpregnant controls during folic acid supplementation: stable-isotopic labeling of plasma folate, urinary folate and folate catabolites shows subtle effects of pregnancy on turnover of folate pools.

To investigate the effects of pregnancy on folate metabolism, we conducted an 84-d study in second-trimester (gestational wk 14-25) pregnant women (n = 6) and nonpregnant controls (n = 6) with stable-isotopic tracer methods. All subjects were fed a diet containing approximately 272 nmol/d (120 microg/d) folate from food, along with supplemental folic acid that contained 15% [3',5'-(2)H(2)] folic acid ([(2)H(2)]folic acid) during d 1--41 and that was unlabeled during d 42--84 to yield a constant total folate intake of 1.02 or 1.93 micromol/d (450 or 850 microg/d). Isotopic enrichment of plasma folate, urinary folate and the urinary folate catabolites para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (ApABG) was determined at intervals throughout the study. The labeling of pABG and ApABG reflected that of tissue folate pools from which the catabolites originate. After the intake of labeled folic acid was terminated on d 41, labeling of urinary folate exhibited a biphasic exponential decline with distinct fast and slow components. In contrast, during d 42--84, the enrichment of urinary pABG and ApABG exhibited primarily monophasic exponential decline, and plasma folate underwent little decline of labeling during this period. Pregnant women and controls did not differ in estimates of body folate pool size and most aspects of the excretion of labeled urinary folate and catabolites, rates of decline of excretion, and areas under the curves for folate and catabolite excretion. Pregnant women, however, tended to have a slower rate of decline of pABG than ApABG and higher enrichment at d 42 of ApABG and pABG. These data support and extend our previous findings indicating that pregnancy (gestational wk 14--26) causes subtle changes in folate metabolism but does not elicit substantial increases in the rate or extent of folate turnover at these moderately high folate intakes.

4-Aminobenzoic Acid↗
PubMed1982

[Role of folic acid and its amino derivatives in the mechanism of action of low doses of formaldehyde on the organs].

The presence of the relationship between the content of formaldehyde and folic acid in solution and tissue has been studied. It has been demonstrated that folic acid and its amino derivatives reduce the content of formaldehyde in solution by over 50%. During the build up of the increased content of folic acids and its analogs, there takes place diminution of the content of exogenous formaldehyde in all the test organs. This was interpreted as evidence of a close interplay with folic acid metabolism as regards the mechanism of action of exogenous formaldehyde introduced with a purpose of organ conservation.

Aminopterin↗
PubMed1993

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Adult↗
PubMed1998

Worsening in seizure frequency and severity in relation to folic acid administration.

We report a case of increase in seizure frequency and severity in a 26-year-old woman receiving folic acid at a dosage of 0.8 mg/day. She had symptomatic partial epilepsy with simple and complex seizures treated with carbamazepine. She was planning pregnancy and we prescribed folic acid for prevention of neural-tube defects. In the next few days she had a generalized tonic-clonic seizure for the first time and a significant increase in seizure frequency. Because of the temporal relation between the seizure worsening and the administration of folic acid, we hypothesize a role of folic acid in provoking seizures, as has been reported in the literature.Copyright Lippincott-Raven Publishers

Journal Article↗
PubMed2003

Effects of ethanol and folic acid consumption during pregnancy and lactation on basal enzymatic secretion in the duodenal juice of offspring rats.

OBJECTIVES: Studies on duodenal juice enzyme activities were carried out on suckling Wistar rats born to dams given ethanol during gestation and suckling. The results were compared with offspring of dams given diets containing no ethanol. Comparisons were also made with offspring of dams given ethanol and folic acid supplementation to observe whether a folate supplement could sufficiently reverse the negative effect of ethanol consumption. METHODS: The dams were fed increased amounts of ethanol (5% to 20%, vol/vol) in tap water for 4 wk. The maximum quantity, 20% ethanol, was given to the dams during pregnancy and lactation. Offspring animals were randomized into three groups: control (CG), ethanol treated (EG), and ethanol plus folic acid (EFG). RESULTS: Body weight at birth and at 21 d after birth and pancreatic weight were lower in offspring after ethanol treatment. Folic acid supplement increased these parameters in the EFG. Under basal conditions, decreases in amylase, lipase, and chymotrypsin activities in the duodenal juice after ethanol treatment were detected. Serum and urine amylase activities also decreased in the EG and EFG. These changes were different in the ethanol-treated progenitors. In these progenitors, ethanol treatment increased serum amylase levels. In the offspring, amylase activities in the EFG decreased with respect to the CG; however, an increase in the EG was observed. In dams the folic acid supplement did not significantly alter the serum amylase activities. Lipase and chymotrypsin activities in the EFG were similar to those in the EG. An increase of serum and urine amylase in the EFG with respect to the EG was found. CONCLUSIONS: Our findings indicated that, under basal conditions, ethanol treatment during gestation and lactation negatively affects the digestive function in offspring. The effects of ethanol were slightly attenuated in rats supplemented with folic acid for amylase activities. Although extrapolation from animal studies can be tenuous, the present findings may explain the use of folic acid in the prevention of damage induced by ethanol to increase the amylase levels to physiologic concentrations.

Amylases↗
PubMed2003

Effect of folic acid supplementation on plasma zinc concentrations of young women.

OBJECTIVE: Women of reproductive age are advised to consume supplements or fortified foods containing at least 400 microg/d folic acid for the prevention of neural tubes defects. Concerns exist about the adverse effects of folic acid on zinc status. METHODS: Seventy-eight women (18 to 49 y) were assigned for 12-wk to receive either a placebo or a 400 microg/d folic acid supplement. RESULTS: At 12-wk mean (95% CI) red cell folate increased by 431 (350-511) nmol/L in the supplemented group relative to placebo (P < 0.001) but there was no change in plasma zinc in either group (P = 0.213). CONCLUSIONS: Folic acid supplementation does not reduce plasma zinc concentrations in women of childbearing age.

Adolescent↗
PubMedDate not supplied

Controlled trials of very high dose folic acid, vitamins B12 and B6, intravenous folinic acid and serine for treatment of hyperhomocysteinemia in ESRD.

BACKGROUND: Hyperhomocysteinemia is seen in most hemodialysis (HD) patients and is an independent risk factor for cardiovascular disease. Homocysteine metabolism via remethylation requires activated folate and vitamin B12 and metabolism via transsulfuration requires serine and vitamin B6. Prior studies have shown highly variable effects of supplemental B vitamin and folate therapy for hyperhomocysteinemia. We undertook a fully controlled trial with abnormally high doses of folic acid alone or with supplemental vitamin B6 and B12 compared with active folate alone or with serine. METHODS: Two prospective studies were undertaken in hemodialysis patients. In the first study (protocol A), hyperhomocysteinemia was treated in 77 patients with 30 or 60 mg folic acid with or without vitamins B6 and B12 for eight weeks and compared with matching placebos. In the second study (protocol B), hyperhomocysteinemia was treated in 37 patients with intravenous folinic acid given alone or with serine and compared with matching placebos. All patients received the standard of care treatment with a multivitamin tablet before and throughout the protocol to test the hypothesis that additional therapy is required over and above the routine therapy for maximum reduction in total homocysteine (tHcy). RESULTS: Normal volunteers; The mean (SD) tHcy of 128 normal subjects was 6.5 (4) micromol/L. Protocol A; Plasma folate increased significantly in the groups given folic acid at both four and eight weeks (P = 0.0001 at both time points). Plasma vitamin B12 was significantly increased at four weeks (P = 0.0018) but not at eight weeks (P = 0.064) in those given Vitamin B12. However, tHcy did not differ between treatment groups at baseline (P = 0.63), four weeks (P = 0.79) or eight weeks (P = 0.74). Protocol B: Plasma folate increased significantly at four weeks in those receiving folinic acid (P = 0.0001) but tHcy was not significantly different between groups (P = 0.92). In neither study was there any significant change in tHcy comparing before and during any treatment intervention. CONCLUSIONS: In our studies high dose oral folic acid, intravenous folinic acid, vitamins B6 and B12 and oral serine were ineffective at lowering tHcy in patients on hemodialysis when given folic acid, folinic acid serine or B vitamins in addition to routine folic acid and B vitamin supplements.

Administration, Oral↗
PubMed2004

Scientific evidence supporting folic acid fortification of flour in Australia and New Zealand.

BACKGROUND: Fortification of flour with folic acid is a safe, sustainable, and cost-effective approach for preventing spina bifida and anencephaly, and it is likely to confer multiple health benefits to the adult population. Scientists and advocates are bringing this intervention to the attention of policymakers in countries around the world, and consequently the demand for sound, science-backed policy rationale is increasing. METHODS: We recently prepared this scientific review for scientists, physicians, and advocates who were promoting mandatory folic acid fortification of flour in Australia and New Zealand. This short document references the most relevant published scientific data and national and international recommendations from other countries and presents an argument for fortification based on demonstrated need, proven effectiveness, safety, and multiple health benefits. CONCLUSIONS: With some modifications, this document could be utilized in other countries considering fortification of flour or other staple products with folic acid.

Anencephaly↗
PubMed2007

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.

BACKGROUND: Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score < 34) in senior participants in the 1999-2002 US National Health and Nutrition Examination Survey. DESIGN: The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148 pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of the reference range for serum vitamin B-12-replete participants with normal creatinine. RESULTS: After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05), but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment.

Aged↗
PubMed2005

[Effect of heptral and folic acid on the hepatic functions during toxic hepatitis].

The aim of study was to evaluate effectiveness of heptral (S-Adonosylmethionine-Adomet) and folic acid during the acute toxic damage of the liver induced by carbon tetrachloride. Experiments have been carried out on pubertal rats. The carbon tetrachloride intoxication was performed by subcutaneous injection of CCL(4) 1 ml/kg dissolved in 1 ml of olive oil. The activity of aspartat-and alaninaminotransferases, alkaline phosphatase, the content of free and total billirubine in the blood, as well as total oxidant and antioxidant activity of the blood, were measured by the spectrophotometric techniques. Oxidative stress, cytolyses of the hepatocytes and cholestasis were observed during CCL(4) intoxication. Heptral, and in less degree, folic acid improved liver function during the acute toxic damage, but complex therapy with heptral and folic acid revealed more expressive hepatoprotective effect. It is suggested that better positive effect of complex therapy with heptral and folic acid compared with monotherapy by each drug is probably associated with resynthesis of methionine from homocystein (toxic metabolite of adenosylmethionine) by folate. This combination allows reducing the side effects of heptral induced by homocysteine.

Animals↗
PubMed2006

Antiatherogenic and radioprotective role of folic acid in whole body gamma-irradiated mice.

Free radical mediated oxidative damage is one of the prime factors for atherogenic changes in humans. We have shown that the folic acid administration reduced the risk of the atherogenic factors induced by gamma-radiation. Folic acid administration prevented the radiation induced increase in the plasma lipoprotein lipase activity and also prevented the radiation-induced increase in the hepatic cholesterol and triglycerides levels. These results indicate the role of folic acid as an antiatherogenic agent. Further, we also report the radioprotective property of folic acid as demonstrated by reduction in the radiation induced membrane damage as measured by lipid peroxidation products and DNA damage, which was measured by alkaline comet assay.

Animals↗
PubMed1999

Sustained reduction of hyperhomocysteinaemia with folic acid supplementation in predialysis patients.

BACKGROUND: Moderate hyperhomocysteinaemia, as occurs in chronic renal failure patients, is an established independent risk factor for atherosclerotic arterial occlusive accidents, the incidence of which is abnormally high in such patients. Folic acid supplementation has been shown to reduce plasma homocysteine level in end-stage renal disease patients treated with haemodialysis or peritoneal dialysis, but its long-term effects in predialysis patients had not been assessed. METHODS: We prospectively treated a total of 78 predialysis patients with folic acid for at least 1 year (range 12-74 months) together with oral pyridoxine and vitamin B12 supplements. Of the patients, 67 received 5 mg folic acid three times per week, whereas the other 11 patients who were treated with recombinant erythropoietin received 5 mg/day. Plasma fasting total homocysteine concentration was determined at baseline, after 3 months and at the end of follow-up. RESULTS: Mean (+/-SD) plasma total homocysteine level decreased from 21.2+/-6.4 micromol/l at baseline to 14.2+/-4.6 at 3 months and remained at 12.8+/-3.7 micromol/l at the end of follow-up (average duration 2.8 years), whereas plasma creatinine rose from 268+/-129 to 399+/-234 micromol/l. Mean plasma folate concentration rose from 19+/-12 to 47+/-13 nmol/l and mean plasma vitamin B12 rose from 237+/-119 to 347+/-191 pmol/l from baseline to end of follow-up. CONCLUSIONS: Moderate folic acid supplementation (2.15 mg/day) allows a substantial (40% as a mean) and sustained (up to 6 years) reduction of plasma total homocysteine level in predialysis uraemic patients without any detectable side effect. Folic acid supplementation may thus contribute to lower the risk of accelerated atherosclerosis in such patients.

Adult↗
PubMed2002

Syntheses of labeled vitamers of folic acid to be used as internal standards in stable isotope dilution assays.

[2H4]Folic acid was synthesized by deuterating p-aminobenzoic acid, which was then coupled to glutamic acid and 6-formylpterin. Using [2H4]folic acid as starting component enabled the preparation of labeled vitamers tetrahydrofolate, 5-formyltetrahydrofolate, 5-methyltetrahydrofolate, and 10-formylfolate which were characterized by electrospray mass spectrometry and collision-induced dissociation. The mass spectrometric studies confirmed that the compounds could be used as internal standards in stable isotope dilution assays.

4-Aminobenzoic Acid↗