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Puerto Rican primary physicians' knowledge about folic acid supplementation for the prevention of neural tube defects.

BACKGROUND: We conducted a study of a group of primary physicians in Puerto Rico to evaluate their knowledge about folic acid supplementation to prevent neural tube defects. METHOD: The study design was transverse-correlational. A total of 66 primary physicians in two hospitals (public and private) participated in the study. The sample was nonrandom and opportunistic, and only those physicians present in the hospitals at the moment of distribution of the questionnaires participated. A self-administered and anonymous questionnaire was used. Descriptive statistics and cross-tabular analysis were used to describe the results of this study. Inferential statistics were also used, including Chi square and t-tests to establish the associations/differences between physician knowledge and the independent variables. RESULTS: Of the participants, 87.9% demonstrated an inadequate knowledge about folic acid supplementation for the prevention of neural tube defects as part of preconception care and only 12.1% demonstrated adequate knowledge. Older physicians had greater knowledge about folic acid. Also, women demonstrated greater knowledge about folic acid than did men. Most of the physicians who always recommend supplementation to their patients demonstrated a greater knowledge about folic acid, and all participants with adequate knowledge came from the public hospital. CONCLUSIONS: Despite a concerted effort by the Health Department of Puerto Rico to provide education in the importance of folic acid supplementation to reduce the incidence of neural tube defects, primary physicians in two Puerto Rican hospitals generally have not availed themselves of this training and showed a lack of knowledge on this important clinical issue.

Adult↗

Folic acid deficiency in sickle cell anaemia.

Megaloblastic anaemia responding to folic acid has been reported in a number fo patients with sickle cell anaemia. The incidence of reduced serum and erythrocyte folate levels in such patients remains unclear, however. Serum and erythrocyte folate contents were measured microbiologically in patients with sickle cell anaemia as well as in two control groups with sickle cell trait or normal haemoglobin pattern. Low serum and erythrocyte folate values were significantly more common in 61 sickle-cell patients than in each of the two socio-economically-matched control groups including 61 subjects with Hb AS and 69 blacks with Hb AA. There was no correlation between serum folate and haematocrit or reticulocyte count. The erythrocyte folate, measured before and after removal of reticulocytes, remains a reliable indicator of deficiency of folic acid in sickle-cell patients despite variable degrees of reticulocytes. Folate therapy resulted in higher haematocrits in three of four sickle-cell patients with low serum and low erythrocyte folate values, but in only one of 12 patients with low serum folate and normal erythrocyte folate. These findings are consistent with other observations that folate requirement may be increased in chronic haemolytic disorders and suggest that erythrocyte folate values should be obtained in sickle-cell patients suspected of having folate deficiency.

Adolescent↗

Treatment of iron-deficiency anemia complicated by scurvy and folic acid deficiency.

We present a case of a child with iron-deficiency anemia, folic acid deficiency, and scurvy. His anemia proved refractory to treatment with iron until he received both folic acid and vitamin C supplementation. This case illustrates the importance of the evaluation of ascorbic acid and folate status in treating iron-deficiency anemia initially refractory to iron supplementation, because multiple nutrient deficiencies may coexist.

Anemia, Hypochromic↗

Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial.

OBJECTIVE: To determine the effect of two different weekly doses of folic acid on the toxicity and efficacy of low-dose methotrexate therapy for rheumatoid arthritis. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 79 persons between 19 and 78 years of age who fulfilled the American Rheumatism Association's criteria for rheumatoid arthritis. INTERVENTION: Participants were randomly assigned to visually identical placebo or to 5 mg or 27.5 mg of folic acid each week. MEASUREMENTS: Duration, intensity, and clinical severity of toxic events; efficacy (indices of joint tenderness and swelling and grip strength); plasma and erythrocyte folate levels; and other laboratory variables. RESULTS: Folic acid supplementation at either dose did not affect the efficacy of methotrexate therapy as judged by joint indices and patient and physician assessments of disease. Patients given folic acid supplements had lower toxicity scores than did participants given placebo (P < or = 0.001). Low blood folate levels and increased mean corpuscular volumes were associated with substantial methotrexate toxicity, whereas daily dietary intakes of more than 900 nmol (400 micrograms) of folic acid were associated with little methotrexate toxicity. CONCLUSIONS: Folic acid, an inexpensive vitamin, is safe in a broad range of doses and protects patients with rheumatoid arthritis who are taking methotrexate from toxicity while preserving the efficacy of methotrexate.

Adult↗

Dose-dependent effect of folic acid on the prevention of orofacial clefts.

OBJECTIVE: In 1982, Tolarova(4) found a reduction in the recurrence rate of isolated cleft lip (CL) with or without cleft palate (CP; CL +/- CP) after periconceptional supplementation with a multivitamin including a very high dose (10 mg) of folic acid. The Hungarian randomized, double-blind, controlled trial of periconceptional supplementation with a multivitamin including a physiologic dose (.8 mg) of folic acid did not show any preventive effect on the first occurrence of isolated CL +/- CP and CP. However, the general evaluation of congenital abnormalities in the Hungarian Case-Control Surveillance of Congenital Abnormalities indicated, among others, a reduction of isolated CL +/- CP and CP after the use of high doses of folic acid in the critical period for the development of these congenital abnormalities in the 12-year dataset between 1980 and 1991. We hypothesized that the prevention of orofacial clefts by folic acid has a dose-dependent effect, and this hypothesis was tested in 2 recent Hungarian datasets. DESIGN: In a prospective cohort study, the occurrence of isolated CL +/- CP and CP was studied in the newborn infants born to mothers with or without periconceptional folic acid-containing (.8 mg) multivitamin supplementation. Supplemented women with confirmed pregnancy were recruited from the participants of the periconceptional service. Unsupplemented women were invited to take part in the study after the first visit between the 8th and 12th week of gestation in the antenatal care. Supplemented and unsupplemented women were matched based on age, socioeconomic status, and residence. In contrast, the occurrence of high-dose (in general daily 6 mg) folic acid supplementation was evaluated in the case-control pairs of CL +/- CP and CP, particularly during the critical period of these 2 types of orofacial clefts in the 17 years dataset of the Case-Control Surveillance of Congenital Abnormalities, between 1980 and 1996. Cases were selected from the population-based Hungarian Congenital Abnormality Registry, whereas population controls without congenital abnormality were ascertained from the national birth registry. Two population controls were matched to every case according to sex, week of birth, and district of parental residence. The drug uses, including pregnancy supplements as folic acid, were evaluated based on retrospective self-reported maternal questionnaire and prospective medically documented data of antenatal care logbook. RESULTS: In the prospective cohort study, of 3019 informative offspring (termination of pregnancies in the second and third trimesters because of fetal defect, stillborn fetuses, and liveborn infants) in the supplemented group, 3 had CL +/- CP and 1 was affected with CP, whereas of 3432 informative offspring in the unsupplemented group, 2 had CL +/- CP and 1 had CP. The lack of preventive effect was in agreement with the result of the previous Hungarian randomized double-blind controlled trial; thus, these 2 datasets were combined. The preventive effect of a folic acid containing multivitamin used in the periconceptional period for the first occurrence of isolated CL +/- CP and CP was estimated by the Mantel-Haenszel test. Of 5488 supplemented women, 6 had CL +/- CP, and of 5821 unsupplemented women, 4 had CL +/- CP. Of 5489 supplemented women, 1 had CP, and of 5823 unsupplemented pregnant women, 3 had CP. The Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, included 38 151 population controls (1.8% of the Hungarian births) and 22 865 cases with congenital abnormalities. Within the latter group, 1368 had isolated CL +/- CP, and 596 had CP. A significantly more frequent use of high-dose folic acid (in general daily 6 mg) supplementation was found in controls than in cases of 1246 case-control pairs of CL +/- CP group and of 537 case-control pairs of CP group, respectively. (ABSTRACT TRUNCATED)

Adult↗

[Age-associated changes in the metabolism of vitamin B(12) and folic acid: prevalence, aetiopathogenesis and pathophysiological consequences].

The increasing number of older people is characteristic for most industrialised nations and implicates the known psychosocial and economic consequences. Therefore, an optimal nutrient supply that promotes continuing mental and physical well-being is particularly important. In this respect, vitamin B(12) and folic acid play a major role, since deficiency of both vitamins is associated with the pathogenesis of different diseases such as declining neurocognitive function and atherosclerotic lesions. Vitamin B(12) and folic acid act as coenzymes and show a close molecular interaction on the basis of the homocysteine metabolism. In addition to the serum concentrations of the vitamins, the metabolites homocysteine and methylmalonic acid are sensitive markers of cobalamin and folate status. Depending on the used marker, 3-60% of the elderly are classified as vitamin B(12) deficient and about 29% as folate deficient. Predominantly, this high prevalence of poor cobalamin status is caused by the increasing prevalence of atrophic gastritis type B, which occurs with a frequency of approximately 20-50% in elderly subjects. Atrophic gastritis results in declining gastric acid and pepsinogen secretion, and hence decreasing intestinal digestion and absorption of both B vitamins. This is the reason why an insufficient vitamin B(12) status in the elderly is rarely due to low dietary intake. In contrast, folic acid intake among elderly subjects is generally well below the recommended dietary reference values. Even moderately increased homocysteine levels or poor folate and vitamin B(12) status are associated with vascular disease and neurocognitive disorders. Results of a meta-analysis of prospective studies revealed that a 25% lower homocysteine level (about 3 micromol/L) was associated with an 11% lower ischemic heart disease risk and 19% lower stroke risk. It is still discussed, whether hyperhomocysteinemia is causally related to vascular disease or whether it is a consequence of atherosclerosis. Estimated risk reduction is based on cohort studies, not on clinical trials. Homocysteine initiates different proatherogenetic mechanisms such as the formation of reactive oxygen species and an enhanced fibrin synthesis. Supplementation of folic acid (0.5-5 mg/d) reduces the homocysteine concentration by 25%. Additional vitamin B(12) (0.5 mg/d) induces further reduction by 7%. In secondary prevention, supplementation already led to clinical improvements (reduction of restenosis rate and plaques). Depression, dementia, and mental impairment are often associated with folate and vitamin B(12) deficiency. The biochemical reason of this finding may be the importance of folic acid and vitamin B(12) for the transmethylation of neuroactive substances (myelin, neurotransmitters) which is impaired in vitamin deficiency ("hypomethylation hypothesis"). In recent years, there is increasing evidence for a role of folic acid in cancer prevention. As a molecular mechanism of a preventive effect of folic acid the hypomethylation of certain DNA sections in folate deficiency has been suggested. Since folate and vitamin B(12) intake and status are mostly insufficient in elderly subjects, a supplementation can generally be recommended.

Aged↗

Oral folic acid improves endothelial dysfunction in cigarette smokers.

INTRODUCTION: Endothelial dysfunction is an early manifestation of the atheromatous process and is evident without overt clinical signs or symptoms of the disease. Cigarette smoking has been shown to be associated with endothelial dysfunction in otherwise healthy adults. Although cessation of smoking is the ideal objective, it is not always attainable, and therefore any strategy to prevent early endothelial dysfunction is desirable. Folic acid is currently under review as a rational therapeutic agent in hyperhomocysteinemia. However, folic acid may modify endothelial function independent of its effect on homocysteine. We therefore investigated the effect of folic acid on endothelial function in young otherwise healthy cigarette smokers. METHODS: Volunteer cigarette smokers (n = 10) and control lifelong nonsmokers were enrolled in the study. Baseline folate, vitamin B12, homocysteine, and cholesterol levels were analyzed. Flow-mediated dilatation, an endothelial-dependent phenomenon, was assessed using ultrasonography. This scan was performed at baseline and following 4 weeks of folic acid supplementation (5 mg/day). RESULTS: There were no significant differences in the baseline hematological investigations between the groups. Homocysteine levels were within normal limits in both groups and did not change following folic acid supplementation. Cigarette smokers demonstrated significant endothelial dysfunction compared to controls (P < 0.005). This difference was significantly attenuated by folic acid supplementation (P < 0.005). CONCLUSION: Folic acid significantly improves endothelial function in otherwise healthy cigarette smokers. This provides a potential therapeutic tool in attenuating the atheromatous process in this group.

Administration, Oral↗

Minimum effective dose of folic acid for food fortification to prevent neural-tube defects.

BACKGROUND: Although a daily supplement of 400 micrograms folic acid has been shown to prevent neural-tube defects (NTD), most women do not take the recommended supplement. Thus, food fortification is to be introduced in the USA and is being considered in the UK. Because of safety concerns, the USA has chosen a level of fortification that will increase the average woman's intake by only 100 micrograms. Such an increase, although safe, may be ineffective; but a trial to assess its efficacy would be unethical. Because women with red-cell folate concentrations above 400 micrograms/L have a very low risk of NTD, we undertook a randomised trial of several folic acid doses to find out how much is needed to reach this protective concentration. METHODS: We screened 323 women. 172 with red-cell folate between 150 micrograms/L and 400 micrograms/L were invited to take part in the trial. 121 women were randomly assigned placebo or 100 micrograms, 200 micrograms, or 400 micrograms daily of additional folic acid. Compliance was monitored by having the women sign a dated sheet when taking the tablet. 95 women completed the 6-month study. FINDINGS: There were significant increases in red-cell folate in all folic acid groups. The placebo group showed no significant change. The median incremental changes and median post-treatment concentrations were 67 micrograms/L (95% CI 43-120) and 375 micrograms/L (354-444) in the 100 micrograms/day group, 130 micrograms/L (108-184) and 475 micrograms/L (432-503) in the 200 micrograms/day group, and 200 micrograms/L (125-312) and 571 micrograms/L (481-654) in the 400 micrograms/day group. INTERPRETATION: A fortification programme that delivered 400 micrograms folic acid daily to women would protect against NTD, but at the expense of unnecessarily high exposure for many people. Delivery of 200 micrograms daily is also effective against NTD and safer for the general population. Based on projections from the positive folate balance in the group that received 100 micrograms daily, this dose taken continually, as it will be in fortified food, will also produce an important decrease in NTD.

Adult↗

Folic acid and reproductive performances of sows.

Two-hundred nine sows were used in a 2 X 2 split-plot unbalanced design to measure the effect of folic acid against control, and flushing against a normal level of feeding, between weaning and mating on the following variables: serum folates at weaning and at 60 d of gestation, blood hemoglobin (Hb) and hematocrit (Ht) after 15 wk of gestation and reproductive performance at farrowing. Folic acid was administered im according to a schedule that maintained serum folates at approximately the same level between weaning and 60 d of gestation. The treatments had no effect on Hb or Ht after 15 wk of gestation. Average live litter size was 12.0 piglets/litter for sows receiving the folic acid and flushing treatments as compared with 10.5 for sows without any treatment; the main effect of folic acid was significant (P less than or equal to .04). Intralitter variation in birth weight and total litter weight tended to be increased by folic acid administration. Results showed that the administration of folic acid during gestation could appreciably improve the reproductive performance of sows.

Animals↗

[Vitamins C, B12 and folic acid in latent iron deficiency].

The aim of the work was to study the level of vitamins C, B12 and folic acid in latent iron deficiency of different etiology (hipo- and anacid gastritis and menorrhagia). 81 patients with latent iron deficiency were investigated. Vitamin C levels were measured by refractometry, folic acid and vitamin B12 by radioimmune assay. The obtained results showed significant decrease of ascorbic acid and less apparent decrease of folic acid in the blood plasma. The content of vitamin B12 was unchanged. Decrease of vitamin C level is related to the changes of initial stages of iron metabolism and its further absorption. Less apparent changes of folic acid and vitamin B12 indicates, that such important stages of erithropoesis as DNA replication and cell proliferation are intact. Our results indicate to the development of metabolic disorders prior to revelation of iron deficiency anaemia, which need timely correction.

Adolescent↗

Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats.

BACKGROUND: Oxidative stress and enhanced apoptosis may be involved in the induction of embryonic dysmorphogenesis in diabetic pregnancy. Administration of folic acid or vitamin E diminishes embryonic dysmorphogenesis. We aimed to evaluate the effect of combined treatment with folic acid and vitamin E on the disturbed development in embryos of diabetic rats. METHODS: Pregnant nondiabetic and diabetic rats were treated with daily injections of 15 mg/kg folic acid or with 5% vitamin E in the diet. A third group received combined treatment. Day 10 and day 11 embryos were evaluated for development and apoptotic profile. RESULTS: We found increased malformations, resorptions, and profound growth retardation in embryos of diabetic rats compared to control embryos. Vitamin E or folic acid alone, or the 2 compounds combined, normalized embryonic demise. Maternal diabetes caused decreased nuclear factor-kappaB (NF-kappaB) activity and B-cell lymphoma 2 (Bcl-2) protein level, and increased Bcl-2-associated x proteins (Bax) in embryos. Supplementation of vitamin E alone normalized the Bax protein level in a diabetic environment. Administration of folic acid to diabetic rats increased NF-kappaB activity and Bcl-2 protein level. Combined treatment normalized Bcl-2 and Bax protein level in a diabetic environment. CONCLUSIONS: Combined supplementation of folic acid and vitamin E to pregnant diabetic rats diminished diabetes-induced malformations and resorptions, concomitant with normalization of apoptotic protein levels. No treatment completely abolished the embryonic demise; therefore, other mechanisms than oxidative stress and apoptosis are likely to be involved in diabetic embryopathy.

Animals↗

[Homocysteine-induced neural tube defects in chick embryos and protection of folic acid].

To reveal whether homocysteine(HCY) will be able to induce neural tube defects (NTDs) and possible teratogenic mechanisms, and identify the interventional effects of folic acid and vitamin B12 on HCY-induced NTDs, 1274 chick embryos treated with L. D-HCY (0-16 mumol/embryo) were detected by the methods of teratogenic trial, scanning electron microscopy(SEM), Nile blue sulfate vital staining, TdT-mediated dUTP nick end labeling(TUNEL) methylgreen-pyronine special staining for showing nucleic acid, and interventional assay of folic acid and VB12 in different developmental stage. Results showed that HCY could induce teratogenesis in chick neurulation and organogenetic period, in dose-response relationship (P < 0.0001). The main forms of NTDs were exencephaly, cranioschisis and spina bifida. It has been first found that HCY could target excessive apoptosis of cells of embryonic nervous system, which consists with the sites of embryos developing NTDs. HCY could inhibit chick yolk sac vessel formation and blood circulation, and damage amniotic membrane. Under SEM it was observed that HCY resulted in abnormal ultrastructures, for example cavernous damages, atrophied microvilli and so on. After the injection of 5 micrograms/embryo folic acid, the teratogenicity of HCY (8 mumol/embryo) was significantly antagonized, the occurrence rate of NTDs was down from 43.5% to 0(P < 0.05). However, vitamin B12 (1 microgram/embryo) did not obviously attenuate the teratogenicity of HCY in day 6 chick embryos. These data prove that HCY per se causes dymorphogenesis of the neural tube. Apoptosis may play an important role in the etiopathology of NTDs. Folic acid can effectively prevent from the homocysteine-induced NTDS. Causes of homocysteine-induced NTDs may result from interaction or combination of different mechanisms.

Animals↗

Trends and predictors of folic acid awareness and periconceptional use in pregnant women.

OBJECTIVE: The purpose of this study was to describe recent trends in folic acid awareness and use in the periconceptional period among pregnant women in relation to maternal sociodemographic and other relevant factors. STUDY DESIGN: From 1988 to 2002, 16,555 women from the Slone Epidemiology Center Birth Defects Study were interviewed about medication use before and during pregnancy (which included multivitamins and folic acid), about whether they were aware of any vitamins that might decrease the risk of birth defects, and about sociodemographic and medical factors. RESULTS: Awareness of folic acid benefits increased from 0 in 1988 to 50% in 1996 and thereafter. The use of folic acid in the periconceptional period increased from 15% in 1988 to 40% in the last few years. Maternal education was a strong independent predictor of both awareness and use as were ethnicity, whether the pregnancy was wanted, family income, and whether a health care provider was consulted before planning. CONCLUSION: Promoting the use of folic acid supplements, particularly among these disadvantaged groups, is essential to further decrease the prevalence of neural tube defects.

Adult↗

Folic acid and vitamin B12 in vitiligo: a nutritional approach.

When compared with the normal population, patients with vitiligo often showed diminished blood levels of folic acid. In a group of fifteen patients with vitiligo, folic acid levels were below normal in the serum of eleven patients, in the whole blood of five patients, and in the erythrocytes of six patients. Vitamin B12 serum levels were below normal in five of the fifteen patients. Ascorbic acid plasma levels were also lowered in four of the patients. In eight patients prolonged oral administration of folic acid with simultaneous parenteral treatment with vitamin B12 and oral ascorbic acid was followed by definite repigmentation without side effects.

Adolescent↗

Folic acid supplementation.

Neural tube defects represent one of a limited number of congenital conditions for which primary prevention strategies are available. Despite strong clinical evidence to support the preventive effect of supplementary folic acid given prior to conception and continued throughout the first 12 weeks of pregnancy, there is limited recent epidemiological data to support the effectiveness of national folic acid supplementation programs. Whether folic acid fortification of staple foods will provide a more effective means of achieving further reductions in the prevalence rates for this condition remains open to question. Recent advances associating folic acid supplementation, hyperhomocysteinaemia and neural tube defects provide a new insight into the possible pathological mechanism of this and possibly other related congenital conditions.

Dietary Supplements↗

Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease.

BACKGROUND: Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. PATIENTS AND METHODS: Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. RESULTS: Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. CONCLUSIONS: It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.

Adult↗

Folic acid intestinal absorption in newborn rats at 21 day postpartum: effects of maternal ethanol consumption.

This study was designed to examine the effects of prenatal and postnatal exposure of ethanol in the in vivo absorption of free folic acid in the small intestine in pups rats at the 21st day after birth. The rats were accustomed to increasing amounts of ethanol (5 to 20%, vol/vol) in tap water for 1 month. During pregnancy and suckling period, ethanol-fed dams were assigned again to ethanol 20% in drinking water. Two sets of experiments were performed. In the first set, jejunal free folic acid absorption in control group and litters nursed by dams receiving ethanol showed a gradual increase along with the increase of perfusion time at all the assayed concentrations. In general, in litters of ethanol-fed dams, jejunal free folic acid absorption expressed as nmol/intestinal surface, nmol/g tissue wet weight and nmol/g tissue dry weight were higher than in control animals. In the second set of experiments, in distal ileum loops, free folic acid absorption did not occur in control pups, but appeared in litters exposed to ethanol. Milk folic acid levels are significantly decreased in ethanol-treated dams. However, only a slight decrease in the serum folic acid levels occurs in litters of ethanol-fed dams. In conclusion, the results obtained in the present work suggested a different pattern of free folic acid absorption in distal ileum for the two groups. The exposure of rats to ethanol during the pregnancy and suckling period, can affect postnatal development of intestinal functions and could play a role in the genesis of malnutrition observed in the infant.

Animals↗