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Bioavailability of folic acid from fortified pasteurised and UHT-treated milk in humans.

OBJECTIVE: The aim of this study was to investigate whether milk fortified with folic acid enhances the folate status of humans and whether the presence of folate-binding proteins (FBP) in pasteurised milk affects the bioavailability of folic acid from fortified milk. In untreated and pasteurised milk, folate occurs bound to FBP, while FBP is (partly) denatured in ultra-high-temperature (UHT)-treated milk. The effect of FBP on folate bioavailability is still unclear. DESIGN, SUBJECTS AND SETTING: Healthy, free-living subjects (n=69) aged 18-49 y participated in a 4-week double-blind, placebo-controlled dietary intervention study. INTERVENTION: In addition to a fully controlled diet, the subjects consumed each day 500 ml of pasteurised or UHT milk, either fortified or not with 200 mug folic acid. RESULTS: Consumption of fortified milk increased folate concentrations in serum and in red blood cells (RBC) by 6.6-7.0 nmol/l (P<0.001) and 32-36 nmol/l (P<0.01), respectively. Similarly, plasma homocysteine concentrations were lowered 0.88-0.89 micromol/l (P=0.001) in subjects who consumed fortified milk. The bioavailability of folic acid from pasteurised milk relative to that of folic acid from UHT milk was 74-94% (NS), depending on the parameter used. CONCLUSIONS: Milk fortified to supply an additional 200 microg of folic acid/s substantially increased folate status, and decreased plasma total homocysteine concentrations in young, healthy subjects. Milk is therefore a suitable matrix for fortification to enhance the folate status in humans. No significant effect of endogenous FBP was found on the bioavailability of folic acid from milk.

Adolescent↗

[Periconceptional intake of a folic acid supplement: evaluation of a promotional program].

This study evaluates the efficacy of a regional program promoting periconceptional folic acid intake. Data were collected through a self-administrated questionnaire among 721 (405 for phase I; 316 for phase II) primiparous women. For phase I, 26.1% (CI [Confidence Interval] 95%: 21.9%-30.4%) of respondents took an adequate periconceptional folic acid supplement, whereas this proportion was 31.6% (CI 95%: 26.5%-36.7%) for phase II (p>0.05). For phase I, 62.0% (CI 95%: 57.3%-66.7%) of women recognized the role of folic acid. For phase II, this proportion significantly rose to 70.9% (CI 95%: 65.9%-75.9%). Regional activities promoting periconceptional folic acid intake, if maintained, should be modified to significantly increase the proportion of women taking an adequate amount of folic acid.

Adult↗

An estimation of the requirement for folic acid in gestating sows: the metabolic utilization of folates as a criterion of measurement.

Sows at their second parity were randomly distributed in five groups of seven animals each to determine the dietary concentration of folic acid that optimizes the metabolic utilization of the vitamin during gestation. The groups differed by dietary supplement of folic acid: 0, 5, 10, 15, or 20 ppm. Sows were fed 2.5 kg of diet each day. The response of serum folates and folate binding capacity to treatments and the excretion of urinary folates after an i.v. injection of folic acid were measured. The total daily excretion of urinary folates was corrected according to the response to one i.v. injection of saline on the day preceding the i.v. injection of folic acid. The decrease of total serum folates throughout gestation was less pronounced in the groups fed 15 and 20 ppm of dietary folic acid (supplement x period interaction, P<.06) than it was in the other three treatments. The proportion of i.v. folic acid not recovered in sow urine (injected - excreted) decreased as the amount of dietary folic acid increased to reach a minimum, which differed according to the period (supplement x period interaction, P<.02); it was 15 ppm during wk 1 of gestation and 10 ppm for the other periods studied. The unrecovered folates increased over a dietary concentration of 15 ppm. These minimum values correspond to the most appropriate feed concentration that covered the whole body utilization (tissue and cell metabolism, catabolism, and storage) of folates by the sows and could be interpreted as a reliable index of the requirement.

Animals↗

[Folic acid and prevention of anomalies of foetal neural tube closing in women treated for epilepsy].

Anomalies of neural tube closing are serious malformations which are encountered most often in babies of epileptic women treated with anti-epileptic drugs during pregnancy. Dietary supplementation of folic acid has been suggested as a preventive measure in these cases, based on the long suspected association between folic acid deficiency and congenital malformations. Folic acid deficiency usually results from insufficient dietary intake, or increased requirements during pregnancy. Moreover, certain anti-epileptic drugs can reduce the availability of folic acid. In secondary prevention, the protective effect of folic acid has been clearly demonstrated, whilst epidemiological data suggest that such treatment is also useful in primary prevention. With respect to women with epilepsy, there is a clear consensus as to the interest of dietary supplementation with folic acid before conception and during the first three months of pregnancy (the period of organogenesis), particularly given the fact that side-effects are extremely rare. Apart from recurrence prevention, where a dose of 4mg/day is recommended, no standard dosing guidelines exist. We would suggest that this same dose be used for epileptic patients in pregnancy, particularly if they are treated with barbamazepine or valproic acid.

Adult↗

Folic acid does not inactivate xanthine oxidase.

In response to a recent report (Lewis, A.S., Murphy, L., Mcalla, C., Fleary, M., and Purcell, S. (1984) J. Biol. Chem. 259, 12-15) that folic acid was a potent inactivator of xanthine oxidase, the details of this apparent inactivation were studied. In confirmation, we also found that commercially available folic acid produced a time-dependent progressive inhibition (apparent inactivation) of xanthine oxidase. A plot of the pseudo-first order rate constant of the decay of enzyme activity versus the concentration of folic acid resulted in a straight line. This indicated that the progressive inhibition was caused by a slow second order combination of an inhibitor with the enzyme. The second order rate constant for this association (slope of replot) was 5.7 X 10(3) M-1 S-1. The slowness of this constant together with the observation that complete inactivation did not occur suggested that the progressive inhibition might be due to the slow binding of a high affinity contaminant. This was corroborated by the finding that the association constant was decreased to 1.6 X 10(2) M-1 S-1 after partially purifying the folic acid. The compound most likely to be producing this inhibition is pterin aldehyde (2-NH2-4-OH-pteridine-6-aldehyde), a photolytic breakdown product of folic acid. Pterin aldehyde was found to be a progressive inhibitor of xanthine oxidase with an association constant of 2.2 X 10(5) M-1 S-1. When the apparent association constants of commercial and purified folic acid were adjusted to reflect the pterin aldehyde content (3.6% and 0.2%, respectively), they became similar to the association constant of pterin aldehyde. Thus, it seems that the apparent inactivation of xanthine oxidase by folic acid was caused by the slow binding of contaminating pterin aldehyde.

Animals↗

[Folic acid in the prevention of neural tube defects].

INTRODUCTION: The term neural tube defects (NTD) stands for anencephaly, iniencephaly, cephalocoele and spina-bifida. The cause of these anomalies is failure of brain spinal cord to properly develop, together with their protective shield of skull and spine, around the 4th gestational week. The prevalence of NTD in continental Europe is 11.2 10,000 live births. THE LEVEL OF FOLATES IN SERUM AND NTD: The level of folates in serum can influence the risk of a child affected with NTD. Studies on women with previous pregnancies with NTD showed that supplementary intake of folic acid, with or without other vitamins, preconceptual period throughout the first trimester has a preventive effect on its recurrence. Inadequate intake of folic acid is also connected with preterm delivery, intrauterine growth retardation and placental abruption and infarction. FOLATES IN NUTRITION: It is not folic acid, but folates, from the vitamin B group, that can naturally be found in food. There are several groups of folates that differ in the quantity by which they can be absorbed from food. Folates are temperature and storage sensitive and cooking can cause a significant fall of their concentration in food. FOLIC ACID SUPPLEMENTATION: The mean daily intake of folates by food is 0.218 mg whereas a reference nutritive intake for a woman of reproductive age is 0.2 mg per day. The currently recommended daily dose for prevention of first NTD occurrence is 0.4 mg, so it is clear that a certain amount of folic acid has to be supplemented preconceptionally and during the first trimester. It can be done in two ways, by telling all women to take it before conceiving, or to fortify food with sufficiently high doses of folic acid in order to achieve adequate serum levels. Neither of the ways is ideal, for not all women would take the supplement, and by aggressively fortifying the food, we create a potential hazard to those that do not need it and may have some problems with the excess of it. The best solution would be a widespread campaign about the need for folic acid and the risks of NTD. CONCLUSION: Recommendations of The Expert Advisory Group on Folic Acid in prevention of neural tube defects has several aspects (1) reducing the risk of the first NTD occurrence by preconceptional vitamin supplementation of folic acid in the dose of 0.4 mg day, which would go on until the end of the 12th week (2) reducing the risk of NTD recurrence in offspring of men and women with spina-bifida or with obstetric history affected with NTD by preconceptional vitamin supplementation of folic acid in the dose of 4 mg daily during the first 12 weeks and (3) organizing educational programmes for medical staff as well as the whole population in order to popularize vitamin supplementation.

Female↗

Photodegradation of folic acid during extracorporeal photopheresis.

BACKGROUND: Photodegradation of folic acid (FA) by ultraviolet (UV) radiation is a well-documented photochemical reaction, and decreased serum levels of FA have been found in patients receiving photochemotherapy (psoralen plus UVA). During extracorporeal photopheresis (ECP) leucocytes and plasma are subjected to 8-methoxypsoralen (8-MOP) plus UVA. OBJECTIVES: To investigate whether ECP leads to the photodegradation of FA in the extracorporeal system. METHODS: In 30 patients undergoing ECP on two consecutive days the FA levels were measured in the extracorporeal collected plasma prior to and after UVA exposure. Healthy donor plasma was exposed to 8-MOP and increasing doses of UVA in vitro. In five patients serum folate levels were determined before and after ECP. RESULTS: We found a mean reduction of 44% and 46% on the first and second day of treatment, respectively. This effect could be reproduced in vitro: the irradiation of healthy donor plasma with UVA led to a dose-dependent reduction of FA of up to 54.75% at 16 J cm(-2). This was independent of the presence of 8-MOP and the base concentration of 5-methyltetrahydrofolate; minimal changes were observed for vitamin B(12) and homocysteine, not undergoing photodegradation. Serum folate levels did not change significantly before and after ECP. CONCLUSIONS: We conclude that extracorporeal exposure of plasma to UVA during ECP leads to photodegradation of FA. Further investigations are required to determine the biological effects of folate photoproducts and whether clinically relevant loss of FA might be a consequence of ECP.

Case-Control Studies↗

Knowledge and use of folic acid supplementation: a study of Colorado women whose pregnancies were affected by a fetal neural tube defect.

OBJECTIVES: To determine whether women who have ha da pregnancy in which the fetus is affected by a neural tube defect (NTD) know of current folic acid recommendations; whether the recommendations are followed before or during the pregnancy associated with an NTD and subsequent pregnancies; and to insure that women who have had an NTD-affected pregnancy have access to proper information about NTDs and folic acid recommendations. METHODS: Women living in Colorado who had a pregnancy in 1996 or 1997 in which the fetus had an NTD were interviewed in 1998 about their knowledge and use of folic acid supplementation. RESULTS: Twenty-one of 42 eligible women were interviewed. All women first learned of the folic acid recommendations either during or after their affected pregnancy. Only 23.8% of the women took vitamins containing folic acid during the 1 to 3 months before becoming pregnant. None who had a subsequent pregnancy followed the recommendation to consume 4.0 mg/d of folic acid, beginning at least 1 month before conception. Women who had subsequent pregnancies became pregnant on average of 9 months after their affected pregnancy ended. CONCLUSIONS: Most women who have an NTD-affected pregnancy are unaware of the national folic acid recommendations and do not follow these recommendations for subsequent pregnancies. However, such women are receptive to information about folic acid supplementation. Health care providers and public health officials should consider their role in assuring that education is provided in an effective and timely manner to women with NTD-affected pregnancies.

Adolescent↗

Folic acid prevents nitroglycerin-induced nitric oxide synthase dysfunction and nitrate tolerance: a human in vivo study.

BACKGROUND: In healthy humans, continuous treatment with nitroglycerin (GTN) causes nitric oxide synthase dysfunction, probably through the reduced bioavailability of tetrahydrobiopterin. Recent studies proposed that folic acid is involved in the regeneration of tetrahydrobiopterin in different disease states. Therefore, we investigated whether folic acid administration would prevent this phenomenon. We also sought to determine if folic acid supplementation could prevent the development of tolerance to GTN. METHODS AND RESULTS: On the first visit, 18 healthy male volunteers (aged 19 to 32 years) were randomized to receive either oral folic acid (10 mg once a day) or placebo for 1 week in a double-blind designed study. All subjects also received continuous transdermal GTN (0.6 mg/h). On the second visit, forearm blood flow was measured with venous occlusion strain gauge plethysmography in response to incremental infusions of acetylcholine (7.5, 15, and 30 microgram/min), N-monomethyl-L-arginine (1, 2, and 4 micromol/min), and GTN (11 and 22 nmol/min). Folic acid prevented GTN-induced endothelial dysfunction, as assessed by responses to intraarterial acetylcholine and N-monomethyl-L-arginine (P<0.01). Moreover, in the subjects treated with folic acid plus transdermal GTN, responses to intraarterial GTN were significantly greater than those observed after transdermal GTN plus placebo (P<0.05). CONCLUSION: Our data demonstrate that supplemental folic acid prevents both nitric oxide synthase dysfunction induced by continuous GTN and nitrate tolerance in the arterial circulation of healthy volunteers. We hypothesize that the reduced bioavailability of tetrahydrobiopterin is involved in the pathogenesis of both phenomena. Our results confirm the view that oxidative stress contributes to nitrate tolerance.

Acetylcholine↗

[Prophylaxis of neural tube defects with folic acid in pregnant women from a health district].

OBJECTIVES: To evaluate the knowledge about the prophylaxis of neural tube defects (NTD) with supplements of folic acid and the correct therapeutic compliance. DESIGN: Observational, descriptive study. PARTICIPANTS: 346 pregnant women attending to deliver at the department of obstetrics and gynaecology, university hospital. MATERIAL AND METHODS: The following outcomes were gathered through a questionnaire: demographic variables, previous personal or family history of a pregnancy affected by a NTD, planning of pregnancy, knowledge about the value of the use of folic acid, health professional who prescribed it, and the beginning and duration of the prophylaxis. RESULTS: 95% of the participants used supplements of folic acid during their pregnancy. A 34% was able to describe folic acid as an efficacious method to diminish the incidence of NTD. The percentage of women who used correctly the prophylaxis was significantly greater when it was prescribed by a family physician (P=.003). CONCLUSIONS: A great proportion of women from our health district take folic acid during pregnancy, but just a small percent accomplishes the treatment correctly. The lack of awareness among women about the need for periconceptional folic acid supplements and how it should be taken following the recommendations to prevent NTD are the main reasons for not accomplishing a correct prophylaxis. Family physicians could play an important role as health educators.

Cross-Sectional Studies↗

Relationship of tobacco smoking with serum vitamin B12, folic acid and haematological indices in healthy adults.

OBJECTIVES: To investigate the effects of tobacco smoking on serum vitamin B12, folic acid and haematological parameters in healthy Thai smokers and non-smokers. DESIGN: Cross-sectional study of smokers and non-smokers in a military unit in Bangkok, Thailand. SETTING: A military unit in Thailand. SUBJECTS: One hundred and twenty-three male smokers from a military unit in Bangkok, who participated voluntarily in the study, were investigated. Sixty-six male non-smokers from the same unit were selected as controls. Fasting blood samples were collected for investigation of vitamin B12, folic acid and haematological variables. RESULTS: The serum folic acid concentration of smokers was lower than that of non-smokers, but was not statistically significantly different. Haemoglobin was lower in smokers than in non-smokers; 16.3% of smokers were anaemic compared with only 3.0% of non-smokers. Anaemia was not related to folate deficiency. The white blood cell count was found to be higher in smokers than in non-smokers. CONCLUSION: The results of this study suggest that there were low serum folic acid concentrations in smokers compared with non-smokers, which might contribute to the development of vascular and cardiovascular diseases. The higher white blood cell count might be indicative alterations in the immune functions of smokers.

Adult↗

Spina bifida and anencephaly before and after folic acid mandate--United States, 1995-1996 and 1999-2000.

Neural tube defects (NTDs) are serious birth defects of the spine (e.g., spina bifida) and the brain (e.g., anencephaly) that occur during early pregnancy, often before a woman knows she is pregnant; 50%-70% of these defects can be prevented if a woman consumes sufficient folic acid daily before conception and throughout the first trimester of her pregnancy. In 1992, to reduce the number of cases of spina bifida and other NTDs, the U.S. Public Health Service (USPHS) recommended that all women capable of becoming pregnant consume 400 microg of folic acid daily. Three approaches to increase folic acid consumption were cited: 1) improve dietary habits, 2) fortify foods with folic acid, and 3) use dietary supplements containing folic acid. Mandatory fortification of cereal grain products went into effect in January 1998; during October 1998-December 1999, the reported prevalence of spina bifida declined 31%, and the prevalence of anencephaly declined 16%. Other studies have indicated similar trends. To update the estimated numbers of NTD-affected pregnancies and births, CDC recently analyzed data from 23 population-based surveillance systems that include prenatal ascertainment of these birth defects. This report summarizes the results of that analysis, which indicate that the estimated number of NTD-affected pregnancies in the United States declined from 4,000 in 1995-1996 to 3,000 in 1999-2000. This decline in NTD-affected pregnancies highlights the partial success of the U.S. folic acid fortification program as a public health strategy. To reduce further the number of NTD-affected pregnancies, all women capable of becoming pregnant should follow the USPHS recommendation and consume 400 microg of folic acid every day.

Anencephaly↗

Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

Adolescent↗

Synthesis of zinc-crosslinked thiolated alginic acid beads and their in vitro evaluation as potential enteric delivery system with folic acid as model drug.

The aim of this study is to explore the potential of synthetic modifications of alginic acid as a method to enhance the stability of its complexes with divalent cations under physiological conditions. A fraction of algin's carboxylic acid moieties was substituted with thiol groups to different substitution degrees through conjugating alginate to cysteine to produce alginate-cysteine (AC) conjugates. Infrared spectrophotometry and iodometry were used to characterize the resulting polymeric conjugates in terms of structure and degree of substitution. Moreover, zinc ions were used to crosslink the resulting AC polymers. Folic acid loaded beads were prepared from Zinc-crosslinked AC polymers (AC-Zn) of different cysteine substitution degrees. The generated beads were then investigated in vitro for their capacity to modify folic acid release. AC-Zn polymeric beads resisted drug release under acidic conditions (pH 1.0). However, upon transfer to a phosphate buffer solution (pH 7.0) they released most of their contents almost immediately. This change in drug release behavior is most probably due to the sequestering of zinc cations by phosphate ions within the buffer solution to form insoluble chelates and, to a lesser extent, the ionization of the carboxylic acid and thiol moieties. Removal of zinc ions from the polymeric matrix seems to promote polymeric disintegration and subsequent drug release. A similar behavior is expected in vivo due to the presence of natural zinc sequestering agents in the intestinal fluids. AC-Zn polymers provided a novel approach for enteric drug delivery as drug release from these matrices complied with the USP specifications for enteric dosage forms.

Alginates↗

Periconceptional folic acid exposure and risk of occurrent neural tube defects.

OBJECTIVES: A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs. DESIGN: Case-control study. SETTING: Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario. PARTICIPANTS: Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations. MAIN OUTCOME MEASURES: The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls. RESULTS: The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid-NTD hypothesis and were excluded from further analysis. For daily use of a multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake (P for trend = .02). CONCLUSION: These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk.

Case-Control Studies↗

The responsiveness of plasma homocysteine to small increases in dietary folic acid: a primary care study.

OBJECTIVES: To assess the long term effects of small increases in dietary folic acid on the concentration of plasma homocysteine, an independent risk factor for occlusive vascular disease, in a general population. DESIGN: A randomized double-blind placebo-controlled intervention study. SUBJECTS: One hundred and nineteen healthy volunteers, whose intake of fortified or supplemental folic acid was low, were recruited by letter from the patient register of a large inner-city group general practice. METHODS: Volunteers were randomized to receive unfortified cereals, or cereals fortified with 200 microg of folic acid per portion, with or without other vitamins. Blood samples were taken presupplement and at 4, 8 and 24 weeks on treatment and analysed for plasma homocysteine, cysteine and vitamin B12 and serum and red cell folate. Ninety-four subjects completed the study providing blood samples on all four occasions. RESULTS: There were no significant changes in any measured parameter in those eating unfortified cereals. Overall, folic acid fortification of cereals led to significant increases (P < 0.001) in serum folate (66%), and red cell folate (24%), and a decrease in plasma homocysteine (10%; P < 0.001). There were no changes in vitamin B12 or cysteine. The homocysteine decrease persisted until the end of the study and was primarily seen in those who initially had the highest plasma homocysteine or the lowest serum folate. CONCLUSIONS: If homocysteine is found to be a causative risk factor in occlusive vascular disease, food fortification with physiological levels of folic acid should have a significant impact on the prevalence of the disease in the general population.

Adult↗

High-dose folic acid acutely improves coronary vasodilator function in patients with coronary artery disease.

OBJECTIVES: We investigated the acute effect of orally administered high-dose folic acid on coronary dilator function in humans. BACKGROUND: Folic acid and its active metabolite, 5-methyltetrahydrofolate, increase endothelium-dependent vasodilation in human peripheral circulation. However, the acute effect on coronary circulation is not known. METHODS: Fourteen patients with ischemic heart disease, age 62 +/- 12 years (mean +/- SD), were enrolled in a double-blind, placebo-controlled crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) were determined by positron emission tomography, and myocardial flow reserve was calculated. Each patient was studied after ingestion of placebo and after ingestion of 30 mg folic acid. Myocardial zones were prospectively defined physiologically as "normal" versus "abnormal" on the basis of MBF response to adenosine 140 microg/kg/min (normal = MBF >1.65 ml/min/g). Abnormal and normal zones were analyzed separately in a patient-based analysis. RESULTS: Folate was associated with a reduction in mean arterial pressure (100 +/- 12 mm Hg vs. 96 +/- 11 mm Hg, placebo vs. folate, p < 0.03). Despite the fall in mean arterial pressure, folic acid significantly increased the MBF dose response to adenosine (p < 0.001 using analysis of variance) in abnormal zones, whereas MBF in normal zones did not change. In abnormal segments, folic acid increased peak MBF by 49% (1.45 +/- 0.59 ml/min/g vs. 2.16 +/- 1.01 ml/min/g, p < 0.02). Furthermore, folate increased dilator reserve by 83% in abnormal segments (0.77 +/- 0.59 vs. ml/min/g 1.41 +/- 1.08 ml/min/g, placebo vs. folate, p < 0.05), whereas dilator reserve in normal segments remained unchanged (2.00 +/- 0.61 ml/min/g vs. 2.12 +/- 0.69 ml/min/g, placebo vs. folate, p = NS). CONCLUSIONS: The data demonstrate that high-dose oral folate acutely lowers blood pressure and enhances coronary dilation in patients with coronary artery disease.

Adenosine↗

[Iron, folic acid and vitamin B12 deficiencies related to anemia in adolescents from a region with a high incidence of congenital malformations in Venezuela].

Since in recent years for certain age groups, the main cause of anemia is not iron deficiency, we intended to study the effect of iron, folic acid and vitamin B12 deficiencies on anemia prevalence in adolescents from Venezuela. One hundred adolescents aged between 12 and 19 years participated in the study. Each subject was interviewed about antecedents and habits and a physical examination and a 24-hour food recall questionnaire were performed. From a blood sample, hemoglobin and hematocrit concentrations were determined and serum was separated for quantification of ferritin, folic acid and vitamin B12 concentrations. Prevalence of anemia was 78% and for iron, folic acid and vitamin B12 deficiencies were 34.66, 90.9 and 18.18%, respectively. From anemic cases, 35.89% presented iron deficiency, while 91.02% presented folic acid deficiency. Only 19.23% of adolescents with anemia presented also vitamin B12 deficiency, but all the cases with vitamin B12 deficiency, were anemic. Simultaneous iron and folic acid deficiencies affected 30.76% of anemic cases. The high prevalence of deficiencies found in this work could be explained by insufficient intake and inadequate food habits. The prevalence of anemia was associated to folic acid deficiency rather than to iron deficiency, due to the high prevalence of folic acid deficiency. The high prevalence of nutritional deficiencies found in this work, especially regarding folic acid deficiency, require immediate interventions.

Adolescent↗