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[The effect of folic acid fortification on the reduction of neural tube defects].

Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.

Brazil↗

Hyperhomocysteinemia, vascular function and atherosclerosis: effects of vitamins.

Homocysteine is a metabolic product of methyl group donation by the amino acid methionine. Moderate elevation of plasma homocysteine (>15 microM) is most commonly caused by B-vitamin deficiencies, especially folic acid, B(6) and B(12). Genetic factors, certain drugs and renal impairment may also contribute. Homocysteine has several potentially deleterious vascular actions. These include increased oxidant stress, impaired endothelial function, stimulation of mitogenesis, and induction of thrombosis. Homocysteine also appears to increase arterial pressure. In humans, experimental induction of hyperhomocysteinemia by methionine loading rapidly causes profound impairment of endothelium-dependent dilatation in both resistance and conduit arteries. This endothelial dysfunction can be reversed by administration of antioxidants. Epidemiological evidence suggests that homocysteine acts as an independent risk factor for atherosclerosis, thrombosis and hypertension. Prospective studies have shown that elevated plasma homocysteine concentrations in the top quintile of the population (>12 microM) increase risk of cardiovascular disease by about 2-fold. There are currently no data available from randomized, controlled trials of the effects of lowering plasma homocysteine on atherothrombotic events. Nonetheless, it would seem appropriate to screen for and treat hyperhomocysteinemia in individuals with progressive or unexplained atherosclerosis. Folic acid and vitamins B(6) and B(12) are the mainstay of therapy. Treatment of moderately elevated plasma homocysteine in patients without atherosclerosis should be deferred until the completion of randomized outcome trials.

Arteriosclerosis↗

Doubling the number of women consuming vitamin supplement pills containing folic acid: an urgently needed birth defect prevention complement to the folic acid fortification of cereal grains.

The major known environmental causes of birth defects are ancient agents that have been in the environment for centuries but have been only recently discovered-rubella, alcohol, and folic acid deficiency. In the United States, we have made great progress in preventing congenital rubella syndrome. We also have a great opportunity to prevent spina bifida and anencephaly (SBA) by increasing the number of women who daily consume vitamin supplements containing folic acid. Even with the recently announced grain fortification regulations, there are 45 million women unprotected from an SBA-affected pregnancy. This article suggests that a substantial educational campaign could, over a 5-year period, double the number of women consuming folic acid supplement pills and make a substantial contribution toward preventing SBA.

Anencephaly↗

Birth defects in Arkansas: is folic acid fortification making a difference?

BACKGROUND: Since 1998, fortification of grain products with folic acid has been mandated in the United States, in an effort to reduce the prevalence of neural tube defects (NTDs). Published reports have shown a reduction in the prevalence of spina bifida since fortification was mandated, but no published studies have reported a reduction in birth defects, other than NTDs, that are postulated to be associated with folic acid deficiency. This study was performed to determine if fortification has reduced the prevalence of NTDs and other birth defects in Arkansas. METHODS: Using data from the Arkansas Reproductive Health Monitoring System, prevalences were computed for thirteen specific birth defects with prior evidence supporting a protective effect of folic acid or multivitamins. Prevalences were calculated using data for live births to Arkansas residents for 1993-2000. Exposure to folic acid fortification was classified by birth year as "pre-fortification" (1993-1995), "transition" (1996-1998) or "post-fortification" (1999-2000). Logistic regression analysis was used to compute crude and adjusted prevalence odds ratios comparing the identified time periods. RESULTS: Prevalences decreased between the pre- and post-fortification periods for spina bifida, orofacial clefts, limb reduction defects, omphalocele, and Down syndrome, but only the decrease in spina bifida was statistically significant (prevalence odds ratio 0.56; 95% confidence interval, 0.37, 0.83). CONCLUSION: In Arkansas, the prevalence of spina bifida has decreased since folic acid fortification of foods was implemented. Similar studies by other birth defects surveillance systems are needed to confirm a preventive effect of fortification for malformations other than spina bifida.

Adult↗

Treatment of vitiligo vulgaris with narrow band UVB (311 nm) for one year and the effect of addition of folic acid and vitamin B12.

Narrow band UVB is succeeding psoralen and UVA irradiation as the main treatment of vitiligo vulgaris in several European countries. Vitamin B12 and folic acid deficiency in some vitiligo patients has prompted researchers to investigate the efficacy of these vitamins in the treatment of vitiligo. In the present controlled study we investigated the value of narrow band UVB phototherapy in the treatment of vitiligo and the possible additive effect of vitamin B12 and folic acid. Twenty-seven patients with long-term stable vitiligo were included and randomized in a "UVB only" (UVB) or "UVB combined with vitamin B12 and folic acid" (UVB+) group. Patients were irradiated thrice weekly for one year, whilst repigmentation was carefully monitored. In 92% (25/27) of the patients up to 100% repigmentation was seen. Repigmentation was notable in lesions on the face, neck and throat, lower arm, chest, back and lower legs, whilst repigmentation on the hands, wrists, feet and ankles proved to be minimal. Maximum repigmentation rates did not differ significantly between the UVB group and the UVB+ group. Our study reconfirms that narrow band UVB phototherapy is an effective treatment for vitiligo and shows that co-treatment with vitamin B12 and folic acid does not improve the outcome of treatment of vitiligo with narrow band UVB phototherapy.

Analysis of Variance↗

Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study.

Changes in the folate and vitamin B12 status in the body influence the extent of uracil misincorporation (UrMis) into DNA, which is one of the biomarkers of genomic stability and, thus, portends a risk of cancer. In our study, the level of UrMis into DNA was evaluated by the comet assay (using the specific DNA repair enzyme, uracil DNA glycosylase) in leukocytes from blood donated by healthy young women with positive folate balance achieved by 4 weeks of folic acid supplementation (400 microg/day). The nutritional status was evaluated on the basis of nine food diaries recorded by the subjects during two winter months. The data were computerized, and the intake of nutrients and micronutrients was estimated using the DIETA 2 program (Food and Nutrition Institute, Warsaw, Poland) linked to recently updated Polish food tables. The plasma folate and vitamin B12 concentration, as well as methylenetetrahydrofolate reductase (MTHFR) polymorphisms, were evaluated to determine their influence on the level of UrMis into DNA. The mean value of B12 intake for all subjects reached 100% of the Polish recommended dietary allowances (RDA), whereas the mean value of folate intake, before folate supplementation, was 50%, suggesting moderate deficiency. Folic acid supplementation brought the folate intake way above the RDA, and plasma folate concentration in each individual was above the deficient range (mean value 14.67 ng/ml). The UrMis did not correlate with the plasma folate concentration, but the level of UrMis was significantly lower in subjects with plasma vitamin B12 concentration above 400 pg/ml (P=.02) only after folic acid supplementation. The concentration of folate in plasma correlated (P<or=.05) with the wild-type MTHFR homozygote 1298 AA but not with the MTHFR 677 genotype. When subjects were grouped according to genotype, the mean concentration of folate in plasma was significantly lower in subjects with the MTHFR 677 (CT+TT) polymorphism, which was accompanied by a lower UrMis, compared to individuals with the CC genotype. The significantly higher concentrations of folate in serum, accompanied by increased UrMis, were seen in subjects with the combined MTHFR 1298 (AC+CC) genotype, as compared to the 1298 AA wild type. Our results suggest that more than 400 pg/ml of vitamin B12 in plasma in subjects with a positive folate balance is critical for genomic stability and indicate that the amount of UrMis into DNA is related to the MTHFR genotype.

Adult↗

Drugs producing vitamin deficiencies.

Many drugs produce vitamin deficiencies. They belong to the most important and common therapeutical classes: analgesics, antianemics, antibacterial and antiblastic agents, antibiotics, antidiabetics, antimalarials, antiphlogistics, antipyretics, diuretics, laxatives and purgatives, tranquilizers and anticonvulsives, radiomimetics, hormones and vitamins themselves. The vitamin deprivation processes may be produced by a variety of mechanisms and may involve all vitamins. Recent experiments indicate that there is a competition for binding sites on proteins between vitamin C and salicylate and between dicoumarol and vitamin K. Usually a drug exerts a "devitaminizing" action with respect to only one vitamin. However there are examples of multiple vitamin deficiencies induced by a single drug, like salicylate which deprives the organism of vitamins C, K and pantothenate. These deficiencies may develop either all at the same time or successively. A direct and concomitant vitamin depriving action occurs when an antibiotic blocks the production of vitamins by the enteric flora. A different mode of action occurs in the drug induced folic acid deficiency, which in turn induces a deficiency of vitamin B12. It has been reported that a vitamin deficiency may result from intake of high pharmacological doses of other vitamins. These data need confirmation in patients treated with high doses of nicotinic acid. The drug induced vitamin deficiencies are studied with the same methodology employed for avitaminoses in general; hence they can be diagnosed using the same criteria.

Analgesics↗

Profile of anemia in chronic renal failure patients: comparison between predialyzed and dialyzed patients at the Division of Nephrology, Department of Internal Medicine, Sanglah Hospital, Denpasar, Bali, Indonesia.

AIM: To explore the profile of anemia in pradialytic and dialytic CRF patients at the Division of Nephrology, Department of Internal Medicine, Sanglah Hospital, Denpasar, from January to June 2000. METHODS: There were 26 chronic dialyzed patients and 26 pradialyzed patients. Technicon H-1 was used to examine peripheral blood count; blood urea nitrogen and serum creatinine were examined using standard technique. MEIA (microparticle enzyme immunoassay) was used for serum folic acid and serum B12 level. RESULTS: Of 52 CRF patients, hemoglobin (Hb) levels ranged from 4.6 g/dl to 15.1 g/dl with a mean of 9.3 +/- 2.7 g/dl. Hematocrit levels ranged from 15.3% to 49.3%, with a mean of 29.8 +/- 7.9%. There was a significant difference in the hemoglobin and hematocrit levels of chronic dialyzed and pradialyzed patients. The prevalence of anemia (according to the WHO's criteria) among CRF patients was 84.5% (45/52), with the prevalence in chronic dialyzed patients being 100% and 73.1% in pradialyzed patients. If a hemoglobin level of less than 10 g/dl is used as a cut off point, the prevalence of anemia in dialyzed patients was 96.2% and 30.8% among pradialyzed patients. The severity of anemia among 26 dialyzed patients was: severe in 2 cases (8%), moderate in 16 cases (64%) and mild in 7 cases (28%), while in pradialytic patients the severity of anemia was: moderate in 4 patients (50%) and mild in 4 (50%). The morphology of 33 anemic patients was normocrhomic normocytic in 26 (78.8%) cases, slightly macrocytic in 7 (21.2%) cases, and no hypochromic anemia was found. Two anemic patients were associated with low serum folic acid (1 patient with macrocytic anemia and the other case with normochromic normocytic anemia). The serum B12 level was found to be normal in all cases. There was no significant correlation between the severity of anemia and serum creatinine levels or duration of hemodialysis. CONCLUSION: Anemia is a hallmark for CRF patients with a high prevalence of anemia and moderate degree of anemia. Most of anemic cases were normochromic normocytic. Loss of renal mass could be the principle mechanism. In a small proportion of patients, folic acid deficiency may be the cause of anemia. In this study, iron deficiency anemia was not likely an important factor since no hypochromic anemia was found.

Adult↗

Effect of nitrous oxide on folate and vitamin B12 metabolism in patients.

Exposure to nitrous oxide (N2O) markedly enhances excretion of formic acid and formiminoglutamic acid (FIGLU) in the urine of rats, suggesting a disruption in the normal pathways of folic acid metabolism secondary to an N2O-induced inactivation of methionine synthase. We tested whether surgical patients (23 having total hip replacements and 26 having resection of acoustic neuromas) exposed to isoflurane alone or combined with N2O responded similarly. We found no increase in urinary formic acid and FIGLU in patients exposed to N2O for hip replacement, but a small, transient increase in the FIGLU-to-creatinine ratio in those undergoing resection of acoustic neuromas (mean duration of anesthesia = 9.3 h). This increase peaked at the end of anesthetic exposure and returned toward control levels by the first day after anesthesia and surgery. Low preoperative levels of red blood cell folate and low-normal levels of serum vitamin B12 did not predict an increase in formic acid or FIGLU in response to N2O. Although an occasional patient may prove highly susceptible to and develop signs of severe vitamin B12 and folic acid deficiency after exposure to N2O, our findings suggest that this is a rare event.

Adult↗

Vitamin B12, folic acid, and the nervous system.

There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.

Animals↗

Folic acid: neurochemistry, metabolism and relationship to depression.

The associations of folic acid and its derivatives with depressive disorder are reviewed. Derivatives of folic acid such as biopterins and the synthesis of S-adenosyl methionine (SAM) are known either to be associated with improvement or to have a direct therapeutic effect in depressive disorder. Studies investigating plasma and red cell folic acid levels in depressed patients have used differing assay methodologies which make comparison difficult, although there is substantial evidence of the association between depressive disorder (particularly severe depression) and low folic acid levels. The few studies available suggest folic acid has either antidepressant properties or can act as an augmenting agent for standard antidepressant treatment. A recently discovered genetic variant (5,10 MTHFR) leading to altered folic acid metabolism may explain why some individuals are vulnerable to the effects of folic acid deficiency, despite adequate intake. The links of 5,10 MTHFR to the presence of depressive disorder in the community are being investigated.

Brain↗

Use of folic acid-fortified milk in the elderly population.

Folic acid deficiency is common in the elderly population, resulting in anaemia, dementia, many neurological sequelae and an indirect role in atheromatous disease. An increase in natural food folate is relatively ineffective at increasing folate status and the use of folate fortification of foodstuffs is recommended. The aim of our study was to assess the benefits of folic acid-fortified milk to the folate status of an elderly institutionalised population. 49 subjects received fortified milk as part of their daily diet for at least 6 months (active group) and 40 subjects received unfortified milk (control group). Our results showed a mean serum folate level in the active group of 5.81 (1.1-17.6) microgram/l compared to the control group mean of 2.16 (0.5-9.4) microgram/l (p < 0.001; normal range for serum folate 2.7-20 microgram/l). Similarly the mean red cell folate level in the active group of 316.5 (130-905) microgram/l was significantly higher than the control group mean of 196.1 (95-490) microgram/l (p < 0.001; normal range for red cell folate 150-1,000 microgram/l). Our results suggest that folic acid-fortified milk is an efficacious and acceptable method of administration of folic acid in the elderly population and we recommend the use of folic acid-fortified milk in the regular daily diet of the elderly population.

Aged↗

Predictive values of erythrocyte indices for tests of iron, folic acid, and vitamin B12 deficiency.

The probabilities of low transferrin saturation, folic acid, or vitamin B12 levels in association with various erythrocyte indices was determined from the prevalences of these abnormalities and the distributions of the indices among 206 hospitalized and 1,000 ambulatory anemic patients. At mean corpuscular hemoglobin (MCH) greater than 30 pg, the probability of low transferrin saturation was 0.04 for hospitalized patients and 0.14 for ambulatory anemic patients. For MCH less than 27 pg, the corresponding probabilities were 0.52 and 0.67. The probabilities of low vitamin B12 or folic acid levels among hospitalized anemic patients were 0.0011 for mean corpuscular volume (MCV) less than 95 cu micron and 0.18 for MCV greater than or equal to 95 cu micron, indicating that measurements of these vitamins are of very limited value in most cases of anemia. These findings indicate that in some patients, the erythrocyte indices are sufficiently predictive for or against deficiency states to facilitate decisions regarding further diagnostic tests, as opposed to the increasing tendency to order such tests regardless of the indices.

Anemia, Hypochromic↗

[Hematologic changes in patients under long-term hemodialysis and hemofiltration treatment with special reference to serum concentrations of folic acid and vitamin B 12].

The incidence of macrocytic anemia has been investigated in 32 patients on maintenance hemodialysis (mean age 46 years, mean duration of dialysis treatment 27.5 months), in 18 patients with combined hemodialysis (HD) and hemofiltration (HF) treatment (mean age 42 years, mean duration of combined HD and HF treatment 6.3 months) and in 32 patients after renal transplantation (mean age 41 years, mean observation period since successful renal transplantation 55.2 months). Also investigated were serum levels of vitamin B12 (radioassay kit 57Co) and folic acid (radioassay kit 125J). Macrocytosis (MCV greater than 96 fl) was observed in 38% of the patients on maintenance hemodialysis, in 44% of the patients with combined HD and HF treatment, and in 47% of the renal transplant recipients. In the chronically dialysed patients, in contrast to the patients with combined HD and HF treatment, the mean serum folic acid level was significantly lower (p less than 0.005) than that of healthy controls. Serum levels of vitamin B12 were within the normal range in all patients. There were no significant differences in serum levels of folic acid and vitamin B12 between the patients with MCV greater than 96 fl and MCV less than or equal to 96 fl. Nor was there a correlation between the serum levels of folic acid or vitamin B12 and mean corpuscular volume. These results suggest that folic acid deficiency is of minor importance in the complex pathogenesis of anemia in hemodialysed patients.

Adult↗

[Assessment of nutritional education and iron supplement impact on prevention of pregnancy anemia].

INTRODUCTION: Iron and folic acid deficiencies are the major causes of health problems among pregnant women and children, with a significant negative impact on economic and social development. OBJECTIVE: From April 2002 to April 2003 at the Gilberto Mejía Mejía Hospital (Rionegro, Antioquia), the prenatal program was assessed for its impact on a cohort of pregnant women concerning knowledge of the following nutritional parameters: iron and folic acid functions, their source foods and bioavailability, supplement intake and tolerance, and globular indexes. METHODS: A sample of 42 pregnant women was subjected to a nutritional education program along with the administration of a supplement consisting of 60 mg elemental iron, 400 microg folic acid, and 70 mg vitamin C. This formulation was prepared specifically for the study by Laboratorio Profesional Farmacéutico, LAPROFF. The effect of the educational program was measured by knowledge changes about how patient behaviours affect nutrient bioavailability via source foods intake, as well as recognition of the tolerance limits of supplements and potential effect of non-adherance. The physiological status of each patient was measured by three hematologic variables--hemoglobin, hematocrit, and ferritin. RESULTS: A positive understanding of how to improve nutritional practices was observed. With the supplements, 94.4% of women did not show anaemia at the end of pregnancy. These results agree with those in other, similar populations and indicate that implementation of prenatal control programs by educational and supplement administration is worthwhile.

Adolescent↗