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PubMed2000

Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?

BACKGROUND: Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. METHODS AND RESULTS: In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2) combined serum nitrite/nitrate concentrations, and (3) plasma von Willebrand factor concentration. Baseline characteristics of the 2 groups were similar. At the end of the study, both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [mean (95% CI) 39.0 (29.8 to 51.0) versus 7.7 (6.6 to 8.9) microg/L and 739 (613 to 891) versus 220 (184 to 262) microg/L, respectively; both P<0.001]. Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [15.1 (14.1 to 16.2) versus 20.1 (18.2 to 22.2) micromol/L; P<0.001], there were no significant differences in endothelium-dependent dilation, combined serum nitrite/nitrate concentrations, or plasma von Willebrand factor concentration between the 2 groups. CONCLUSIONS: High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure. This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia.

Aged↗
PubMedDate not supplied

Pregnancy planning: a determinant of folic acid supplements use for the primary prevention of neural tube defects.

OBJECTIVE: Daily consumption of supplements containing 400 micrograms of folic acid in the periconception period may reduce the risk of neural tube defects (NTDs) by as much as 70%. However, despite explicit recommendations, folic acid consumption among women likely to become pregnant remains low. The objectives of this study were: to evaluate women's knowledge and beliefs with regard to folic acid; to estimate the frequency of vitamin supplement consumption; and to identify its determinants during the periconception period. METHODS: In 1999-2000, a questionnaire was completed by 1,240 pregnant women in 10 Quebec hospitals. RESULTS: Seventy percent of the respondents were aware of the preventive role of folic acid but only 25% had taken the recommended dose of supplements during the periconception period. Supplement consumption is associated with the pregnancy planning intensity score (OR: 1.06; 95% CI: 1.02-1.11), knowledge score (OR: 1.11; 95% CI: 1.07-1.16) and belief in the usefulness of supplements (OR: 1.56; 95% CI: 1.02-2.39). CONCLUSION: These results indicate that further efforts are needed to inform the population and promote the optimal use of folic acid supplements.

Dietary Supplements↗
PubMed1985

[Folic acid deficiency anemia caused by therapy in chronic renal insufficiency].

The turbidimetric determination of folic acid concentration in serum and erythrocytes was made by means of a spectrophotometer multiscan in 35 conservatively treated patients with chronic renal failure with a minimum creatine retention of 309 mumol/l and in 63 hemodialysed patients with terminal renal insufficiency. The result showed a statistically significant diminution of serum folic acid concentration in those patients treated in a conservative manner and a significant diminution of plasmatic and erythrocytic folate++ activity in patients under hemodialysis. There was a correlation between the folic acid concentration and the hemoglobin level in both groups of patients, whereas there was no correlation to the number of leukocytes and thrombocytes. A protein deficiency diet or loss of dialysis through the capillary membrane could be found to be the cause for the loss of folic acid. The possibility of folate++ substitutive therapy and its performance was discussed and recommended for selected indications.

Adult↗
PubMed1963

INTESTINAL ABSORPTION OF TRITUM-LABELLED FOLIC ACID IN IDIOPATHIC STEATORRHEA: EFFECT OF A GLUTENFREE DIET.

The intestinal absorption of folic acid in patients with idiopathic steatorrhea was studied by the oral administration of tritium-labelled folic acid in a dosage of 15 mug./kg. Results were expressed as a percentage of the orally administered folic acid radioactivity excreted in the urine over 24 hours. The mean excretion of radioactivity in 38 normal subjects was 48.2 +/- 16.6% (mean +/- SD), whereas eight patients with untreated idiopathic steatorrhea excreted only 16.7 +/- 3.4% (mean +/- SE).The ability of the gluten-free diet to correct this absorptive defect was demonstrated by the finding of normal values in 11 patients in complete clinical remission for periods exceeding six months after institution of the diet. Serial studies in individual patients indicated that a significant improvement was obtainable in as short a period as two weeks following exclusion of gluten from the diet.

Administration, Oral↗
PubMed1982

Effect of phenytoin on folic acid uptake in isolated intestinal epithelial cells.

The anticonvulsant drug phenytoin was found to inhibit the uptake of folic acid into isolated chick intestinal epithelial cells. At a concentration of 100 micrograms/ml the drug inhibited the cellular accumulation of folic acid by 60%. The efflux of folic acid from preloaded cells was not affected by the drug. The inhibition was observed at an acidic pH of 5.8 and at a neutral pH of 7.4. Both the Na+-dependent and the Na+-independent components of folate uptake were inhibited. Phenytoin had no effect on the uptake of the glucose analog 3-O-methylglucose. Thus it was concluded that the effect of phenytoin on folate uptake was not due to changes in Na+ fluxes, concentration gradients or energy metabolism, and suggested instead a direct effect on the folic acid uptake system.

Animals↗
PubMed2000

Optimised extraction of folic acid from multivitamin-mineral preparations for liquid chromatographic analysis.

Degradation of folic acid may occur during extraction of multivitamin-mineral preparations. The degradation may be caused by presence of ions such as Fe3+ and Cu2+, however, the buffer composition may also be critical. This study presents an optimised extraction procedure tested on 24 different products of multivitamin-mineral tablets. The present method yielded mean recoveries of 97% (n = 20) for folic acid and prevented degradation of folic acid in at least 24 h in extracts from multivitamin-mineral tablets.

Chromatography, High Pressure Liquid↗
PubMed1982

Renal tubular transport of folic acid and methotrexate in the monkey.

The renal excretion of folic acid and methotrexate (MTX) was investigated in pentobarbital-anesthetized cynomolgus, rhesus, and AFrican green monkeys by standard clearance and stop-flow techniques. The renal clearance of folic acid was below inulin clearance at all plasma concentrations studied; the (U/P)folic/(U/P)In ratio increased from 0.26 at a concentration of 0.03 mM to a plateau value of 0.9 at concentrations above 0.2 mM, indicating net reabsorption by a saturable system. In stop-flow experiments, base-line (U/P)folic/(U/P)In ratios during free-flow periods were below 1.0, but increased by twofold in stop-flow samples derived from the proximal tubule, indicating net secretion during stopped flow. The stop-flow pattern of MTX excretion was similar, except the base-line flow pattern of MTX excretion was similar, except the base-line (U/P)MTX/(U/P)In ratio exceeded 1.0, indicating net secretion during both free-flow and stopped-flow periods. Secretion of both compounds was inhibited by p-aminohippuric acid and other organic acids but not by L-glutamic acid. It is concluded that folic acid is transported bidirectionally, while evidence was obtained only for secretion of MTX.

Animals↗
PubMed1999

[Folic acid].

One-carbon derivatives of tetrahydrofolate, the coenzyme form of the vitamin folic acid, play a key role in DNA synthesis and cell replication, through their involvement in the biosynthesis of purine nucleotides and the amino acids. Although the most conspicuous symptom of folic acid deficiency is pernicius anemia, it has been observed that the lack of folate intake during the pregnancy induce the incidence of neural tube defects such as apina bifida. Recently, it has been reported that clinical progression of coronary heart disease and cerebral peripheral vascular disease occurred at a high rate in hyperhomocysteinemia with low folate content in plasma. Consequently, the nutritional importance of folate has been increasingly recognized.

Female↗
PubMed2000

Effects of folic acid and amino acids supplementation on zinc intestinal absorption in the progeny of ethanol-treated rats.

This study was designed to examine the effects of supplementation with folic acid and amino acids in dams that consumed ethanol during gestation and lactation to see whether there is an improvement in the intestinal absorption of zinc in pup rats on the 21st day after birth. The rats were randomized into two groups: Ethanol-rats (EG) were administered ethanol during the pregnancy and lactation periods; the ethanol-folic acid group (EFG) received a folic acid and amino acid supplement concomitantly with ethanol administration during pregnancy and lactation. The dams were mated to obtain the first offspring. Two sets of experiments were performed on the offspring at 21 days after birth. In general, in the first set, jejunal zinc absorption in the offspring of EG and EFG groups showed a gradual increase along with increased perfusion time at all assayed concentrations. Jejunal zinc absorption expressed as nmol/intestinal surface was higher in the ethanol-folic acid group than in ethanol animals at all assayed concentrations except at 25 microM concentration. In the second set of experiments, distal ileum zinc absorption in the offspring of ethanolfolic acid dams showed a significant increase at all concentrations tested. These results indicate that supplementation of folic acid and amino acids to dams that consume ethanol during gestation and lactation increase serum and milk zinc levels, although the zinc ingestion is lower. In pups of the supplemented dams, the jejunal and ileal absorption of zinc increased; as a consequence, the serum zinc levels increased. The activity of alcohol dehydrogenase, a metaloenzyme dependent on zinc levels, also increased.

Amino Acids↗
PubMed2001

Comparative use and knowledge of preconceptional folic acid among Spanish- and English-speaking patient populations in Phoenix and Yuma, Arizona.

OBJECTIVE: The goal of the study was to compare levels of use and knowledge regarding the importance of periconceptional folic acid intake among Spanish- and English-speaking patient populations. STUDY DESIGN: A survey was distributed to 315 pregnant patients seeking care at Phoenix Perinatal Associates. English (n = 183) and Spanish (n = 132) language surveys were completed by patients over a 6-month period. Results were analyzed to determine the level of use and understanding in relation to the importance of periconceptional folic acid in the prevention of neural tube defects by primary language and educational level. RESULTS: Fewer than 1 in 12 patients surveyed (7.9%) were aware of a specific association between folic acid intake and the prevention of neural tube defects. Thirty-five percent of Spanish-speaking patients and 56.3% of English-speaking patients (difference, P <.001) were aware of nonspecific benefits of vitamin intake and the prevention of congenital malformations. A mere 1.2% of women with <4 years of high school education were consuming a multivitamin supplement preconceptionally compared with 46% of those with any education beyond high school (P <.0001). Spanish-speaking patients were significantly less likely to be consuming a vitamin supplement preconceptionally when compared with English-speaking patients (3.7% vs 22.4%; P <.0001). Among the 25 patients who demonstrated a specific knowledge of the ability of folic acid intake to prevent neural tube defects, 92% were English speaking compared with 8% who were Spanish speaking (P <.0001). CONCLUSIONS: There is a critical lack of use and understanding regarding the importance of periconceptional folic acid intake to prevent neural tube defects. Our Spanish-speaking population and those with less formal education appear particularly vulnerable to not benefiting from the advantages of periconceptional folic acid. Educational efforts at promoting knowledge and use of folic acid need to incorporate strategies addressing the Spanish-speaking population.

Adolescent↗
PubMed1995

[Prevention of neural tube defects by folic acid administration in early pregnancy. Joint recommendations of the German Society of Nutrition, Gynecology and Obstetrics, Human Genetics, Pediatrics. Society of Neuropediatrics].

OBJECTIVE: Is folic acid supplementation for the prevention of neural tube defects effective? How could periconceptional folic acid supplementation be recommended in Germany and actually put into practice? METHODS: Analysis of the available literature and of the German health care system. RESULTS: According to the available data, it is likely that the rate of neural tube defects can be reduced by periconceptional folic acid. Matters of concern regarding its practical implementation are: difficulties regarding the information of the target group; the presently rare ingestion of vitamin supplements by women of child-bearing age in Germany; the lack of suitable folic acid preparations. CONCLUSIONS: Several German societies have recommended folic acid supplements for women who plan to become pregnant: 4 mg for those at high risk (previous child with neural tube defect) and 0.4 mg/daily for women without a particular risk.

Dose-Response Relationship, Drug↗
PubMed2004

Serum vitamin B12 and folic Acid levels in acute cerebral atherothrombotic infarction.

Hyperhomocysteinemia is an independent risk factor for atherothrombotic cerebral stroke. Vitamin B12 and folic acid are important determinants of homocysteine metabolism. We aimed to evaluate the relationship, if present, between vitamin B12 and folic acid levels and acute cerebral stroke in this study. Blood aliquots drawn within 24 hours after the stroke from hospitalized patients (n=66) with the diagnosis of acute ischemic cerebrovascular episode and also blood samples from 38 healthy controls without any vascular risk factor were analyzed. With a competitive, chemoluminescence assay, serum levels of vitamin B12 and folic acid were measured in blood samples taken within 24 hours after the stroke. The differences and correlations were tested using frequency test, student-t test and multivariate analysis. Mean serum vitamin B12 levels were significantly lower in the patients than in the control subjects, 245.40 (S.D.: 72.9) and 343.2 (S.D.: 113.0) pg/ml respectively (p=0.0001). This difference was independent from other risk factors. Likewise, mean serum folic acid levels were lower in the patients than in the control subjects, 4.62 (S.D.: 1.94) and 5.97 (S.D.: 1.19) ng/ml, respectively (p=0.003). Mean serum levels of vitamin B12 and folate at the convalescence phase were 253.05 (S.D.: 68.78) pg/ml and 4.48 (S.D.: 2.08) ng/ml, respectively; the values obtained at the acute phase were not significantly different from the values obtained at the convalescence phase. We conclude that low vitamin B12 and folic acid concentrations are associated with an increased risk of stroke, and the relationship for vitamin B12 is independent from the other known modifiable stroke risk factors. For understanding the effects of B12 and folate in stroke patients, more detailed follow-up studies with long period are needed.

Acute Disease↗
PubMed1992

Fibre in enteral formulae: effects of sugar-beet versus soy fibre on zinc and folic acid absorption in human subjects.

The present study was conducted to compare the effect of soypolysaccharide (Fibrem) and sugar-beet (Fibrex) on zinc and folic acid absorption when incorporated into enteral formulae. Following an overnight fast, 15 adults were challenged with an oral dose of zinc (60 mg) and folic acid (600 mug) given with enteral formula without fibre, or with 15g of dietary fibre from Fibrem or Fibrex. Serum concentrations of zinc and folic acid were measured at zero-time and at hourly intervals for up to 5h. Results showed that Fibrem caused a significant decrease in the concentrations of zinc and folic acid. However, Fibrex caused a slight increase in serum zinc concentration and a less pronounced decrease in serum folic acid concentration as compared to Fibrem. We conclude that for patients who are at risk of zinc or folic acid deficiency, the fibre source in enteral formulae should be selected carefully.

Journal Article↗
PubMed2004

Assessment of Turkish women's knowledge concerning folic acid and prevention of birth defects.

OBJECTIVES: In Turkey, the incidence of neural tube defects (NTDs) is 30.1 per 10,000 births. For this reason it seems an important problem for women of childbearing age. Adequate periconceptional consumption of folic acid could prevent NTDs. Most women are unaware of this recommendation. The objectives of this study were to evaluate women' knowledge and beliefs with regard to folic acid, and to estimate the consumption frequency of vitamin supplements periconceptionally and during the first trimester of pregnancy. DESIGN: Eight hundred and eighteen married women who had delivered a live-born infant within the previous 12 months completed the questionnaire. Each subject participated in a 20-minute interview, with the questionnaire comprising multiple-choice statements. A random sample of 10 public health centres was drawn from 27 in three districts in Konya where about 50% of the population lives. RESULTS: Only 22% of subjects had heard or read about folic acid. Thirteen per cent of women indicated knowledge of the direct link between folic acid supplementation and NTD prevention. The knowledge was greatest among 26- to 35-year-olds. Women with a university degree were more likely to have heard about folic acid than were less-educated women. CONCLUSION: The results indicate that further government efforts are needed to inform the population and promote the optimal use of folic acid supplements and folate-enriched foods. It is the responsibility of national authorities to increase health education concerning folic acid and the prevention of NTDs in their countries.

Adolescent↗
PubMed1989

Effect of dietary folic acid supplementation on sow performance through two parities.

One hundred fifty-three gilts were maintained in three breeding groups and fed gestation-lactation diets supplemented with either 0 (control), 1.65 or 6.62 mg of supplemental folic acid/kg of diet for two consecutive parities. Serum folate concentrations of sows were linearly (P less than .05) increased by dietary additions of folic acid during both gestation and lactation, but serum glucose and urea concentrations were unaffected by treatment. Serum folate concentrations decreased from breeding to d 60 and 90 of gestation and then increased through lactation for all treatments. Number of pigs born and live pigs at birth, d 14 and d 21 were quadratically (P less than .05) increased by folic acid additions. Average pig weights were similar among treatments (P greater than .10) on both d 0 and 14 of lactation but were less (P less than .01) than the other treatment groups on d 21 for pigs from sows fed the 1.65 mg/kg treatment. Litter weights were quadratically (P less than .01) increased on d 0 and d 14 by folic acid supplementation. Sow weight gain and backfat thickness loss were unaffected by treatment during gestation (P greater than .06); sow weight loss and backfat thickness loss increased quadratically with increasing level of folic acid during lactation (P less than .06 and .05, respectively). More control sows exhibited estrus by d 7 postweaning than sows receiving folic acid supplementation in parity I (P less than .05); however, no differences (P greater than .10) were detected among treatments by d 14, nor were any differences observed by d 7 in parity II. Conception rate was unaffected by folic acid additions. Dietary folic acid supplementation improved sow reproductive performance by increasing the number of pigs born alive.

Administration, Oral↗
PubMed2001

Folic acid. Preconception knowledge and use by infertile women.

OBJECTIVE: To assess knowledge of preconception folic acid intake (PFAI) and its use by infertile women and to compare it to results from a national survey of reproductive-age women. STUDY DESIGN: New patients presenting to a reproductive medicine practice were surveyed regarding their knowledge and use of PFAI. Results were compared to those of a national survey of reproductive age women. RESULTS: Eighty-six women were surveyed. Infertile women were more aware of the benefits of PFAI than the control population (65% vs. 13%) and used it more frequently (52% vs. 29%). Although infertile women knowledgeable about PFAI were more likely to take folic acid (chi 2 = 24.90, P < .001), 30% of women who were aware of the benefits of PFAI did not take it. CONCLUSION: Preconception folic acid knowledge and use were higher among infertility patients presenting to a reproductive medicine practice than in the general population. Nonetheless, in this highly motivated population, only half were taking folic acid, and knowledge alone did not ensure usage. To effectively decrease the incidence of neural tube defects, food fortification may be more effective than education focusing on vitamin supplementation.

Adult↗
PubMed1995

Periconceptional folic acid and neural tube defects: public health issues.

This review examines evidence linking periconceptional folic acid intake to neural tube defects (NTDs) and related public health issues in the United States and developing countries. Sources of information were identified through on-line searches (Medline, UCAT-University of Connecticut) and by contacting researchers in the field. The distribution of NTDs varies across regions. Recurrent NTDs can be prevented with high-dosage folic acid supplementation during periconception, but it is not clear if such a protective effect can be achieved with lower dosages or in low-NTD-risk populations. Overall, it appears that women with a previous NTD pregnancy should receive folic acid supplementation during periconception under medical guidance. Dietary counseling regarding foods rich in folate should be given to all women of childbearing age. However, primary prevention of NTDs through widespread food fortification with folic acid seems unwarranted in both the United States and developing countries due to the low prevalence of NTDs relative to other problems and a potentially unfavorable benefit/risk ratio.

Developing Countries↗
PubMed2004

The binding of folic acid and 5-methyltetrahydrofolate to folate-binding proteins during gastric passage differs in a dynamic in vitro gastrointestinal model.

Despite its low natural folate concentration, milk is responsible for 10-15% of the daily folate intake in countries with a high dairy consumption. Milk products can be considered as a potential matrix for folate fortification, e.g., with synthetic folic acid, to enhance the daily intake of folate. In untreated milk, the natural folate, 5-methyltetrahydrofolate (5-CH3-H4folate), is bound to folate-binding proteins (FBP). In this study, the extent of binding to FBP for folic acid and 5-CH3-H4folate was investigated in a dynamic in vitro model simulating human gastric passage. Protein binding of folic acid and 5-CH3-H4folate was characterized using gel-exclusion chromatography. Before gastric passage, folic acid and 5-CH3-H4folate were bound mainly to FBP (76-79%), whereas 7% was free. Folic acid remained bound to FBP to a similar extent after gastric passage. For 5-CH3-H4folate, the FBP-bound fraction gradually decreased from 79 to 5% and the free fraction increased from 7 to 93%. Although folic acid enters the proximal part of the intestine bound to FBP, 5-CH3-H4folate appears to be present mainly as free folate in the duodenal lumen. The stability of FBP was similar in both folate/FBP mixtures, i.e., 70% of the initial FBP content was retained after gastric passage. This study indicated that FBP are partly stable during gastric passage but have different binding characteristics for folic acid and 5-CH3-H4folate in the duodenal lumen. This could result in different bioavailability from folic acid- and 5-CH3-H4folate-fortified milk products.

Animals↗