Impact of Maternal Folic Acid Supplementation on Descendants' Kidney in Adulthood / Impacto da suplementação materna com ácido fólico no rim dos descendentes na vida adulta

Abstract Supplementation with folic acid (FA) during gestation has been recommended by medical society all over the world, but some studies have shown that intake of high folic acid diet may unleash damages to the descendants. Objectives: Describing the effects of maternal supplementation with FA during gestation on offspring's kidney at late life stages. Data Source: It is a systematic review by which were consulted the following databases: Medline, through Pubmed, Lilacs, and SciELO. The research was performed using the keywords "Folic acid", "Gestation" and "Kidney". Study Selection: Eight studies were regarded for this systematic review. Data Collection: Only studies that evaluated folic acid consumption during gestation and its effects exclusively on descendants' kidney at several phases of life were regarded. Results: Gestational FA intake did not change the renal volume, glomerular filtration rate and the expression of some essential genes in the kidney of puppies whose dams were supplemented with FA. Maternal consumption of double FA plus selenium diet was effective in preserving antioxidant enzymes activity in the kidney of descendants from mothers exposed to alcohol. FA supplementation decreased some gross anomalies in the puppies caused by teratogenic drug despite of had not been effective in preventing some renal architectural damages. Conclusion: FA supplementation did not cause renal toxicity; it exerted an antioxidant protective effect and mitigated some renal disorders caused by severe aggressions.

Resumo A suplementação com ácido fólico (AF) durante a gestação tem sido recomendada pela sociedade médica em todo o mundo, mas alguns estudos têm mostrado que a ingestão de altas quantidades de ácido fólico na dieta pode desencadear danos aos descendentes. Objetivos: Descrever os efeitos da suplementação materna com AF durante a gestação no rim da prole em fases tardias da vida. Fonte de Dados: Trata-se de uma revisão sistemática realizada através da consulta das seguintes bases de dados: Medline, através da Plataforma Pubmed, Lilacs e Scielo. A pesquisa foi realizada utilizando-se as palavras-chave "Ácido Fólico", "Gestação" e "Rim". Seleção dos Estudos: Oito estudos foram considerados para esta revisão sistemática. Coleta de Dados: Foram incluídos estudos que abordaram o consumo de ácido fólico durante a gestação e seus efeitos exclusivamente no rim dos descendentes em diferentes fases da vida. Resultados: O consumo gestacional de AF não alterou o volume renal, a taxa de filtração glomerular e a expressão de alguns genes essenciais no rim dos filhotes de mães suplementadas com AF. A associação de AF e selênio na dieta materna foi eficaz na preservação da atividade de enzimas antioxidantes no rim da prole de mães expostas ao álcool. O consumo de AF diminuiu algumas anomalias importantes nos filhotes causadas por drogas teratogênicas, apesar de não ter sido eficiente na prevenção de alguns danos a arquitetura renal. Conclusão: A suplementação com AF não causou toxicicdade renal, exerceu efeito protetor antioxidante e mitigou algumas desordens renais causadas por agressões severas.

Association of periconceptional folate supplements and FOLR1 and FOLR2 gene polymorphisms with risk of congenital heart disease in offspring: A hospital-based case-control study / 中南大学学报(医学版)

OBJECTIVES@#Maternal periconceptional folic acid supplement is by far the most effective primary prevention strategy to reduce the incidence of congenital heart disease (CHD) in offspring. It was revealed that the underlying mechanisms are complex, including a combination of genetic and environmental factors. The purpose of this study is to investigate the association between periconceptional folic acid supplement, the genetic polymorphisms of maternal folic acid receptor 1 gene (FOLR1) and folic acid receptor 2 gene (FOLR2) and the impact of their interaction on the risk of CHD in offspring, and to provide epidemiological evidence for individualized folic acid dosing in hygienic counseling.@*METHODS@#A case-control study on 569 mothers of CHD infants and 652 mothers of health controls was performed. The interesting points were periconceptional folate supplements, single nucleotide polymorphisms (SNPs) of maternal FOLR1 gene and FOLR2 gene.@*RESULTS@#Mothers who took folate in the periconceptional period were observed a decreased risk of CHD [adjusted odds ratio (aOR)=0.58, 95% CI 0.35 to 0.95]. Our study also found that polymorphisms of maternal FOLR1 gene at rs2071010 (G/A vs G/G: aOR=0.67, 95% CI 0.47 to 0.96) and FOLR2 gene at rs514933 (T/C vs T/T: aOR=0.60, 95% CI 0.43 to 0.84; C/C vs T/T: aOR=0.55, 95% CI 0.33 to 0.90; the dominant model: T/C+ C/C vs T/T: aOR=0.59, 95% CI 0.43 to 0.81; and the addictive model: C/C vs T/C vs T/T: aOR=0.70, 95% CI 0.56 to 0.88) were significantly associated with lower risk of CHD [all P<0.05, false discovery rate P value (FDR_P)<0.1]. Besides, significant interaction between periconceptional folate supplements and rs2071010 G→A (aOR=0.59, 95% CI 0.41-0.86) and rs514933 T→C (aOR=0.52, 95% CI 0.37 to 0.74) on CHD risk were observed (all P<0.05, FDR_P<0.1).@*CONCLUSIONS@#Periconceptional folate supplements, polymorphisms of FOLR1 gene and FOLR2 gene and their interactions are significantly associated with risk of CHD. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings.

Carcinoma de células escamosas de la lengua / Squamous cell carcinoma of the tongue

Las neoplasias de la lengua son los tumores más comunes de la cavidad bucal y la mayoría pertenecen a carcinomas de células escamosas. Presentamos dos casos de carcinomas de la lengua, correspondientes a un carcinoma escamoso moderadamente diferenciado y un carcinoma verrugoso, en mujeres de mediana edad con factores de riesgo oncogénicos. Estos tumores pueden tener diversos grados de diferenciación, los cuales determinan su pronóstico y tratamiento.

Tongue neoplasms are the most common in the oral cavity, and the majority correspond to squamous cell carcinomas. We present two cases of tongue carcinomas, corresponding to moderately differentiated squamous cell carcinoma and verrucous carcinoma, in middle-aged women with oncogenic risk factors.These tumors can have various degrees of differentiation, which determine their prognosis and treatment.

Morfea superficial / Superficial morphea

La morfea superficial es una variante rara de morfea que se distingue de la clásica tanto en la clínica como en la histopatología. Se caracteriza por máculas hipopigmentadas o hiperpigmentadas, con mínima o ninguna induración, sin síntomas asociados, contractura ni atrofia. En la histopatología, se observa un compromiso limitado a las fibras colágenas en la dermis reticular superficial. Se comunica el caso de una paciente con diagnóstico de morfea superficial tratada con fototerapia ultravioleta B y metotrexato.

Superficial morphea is a rare variant of morphea that is distinguished from the classic variant both clinically and histopathologically. It is characterized by hypo or hyperpigmented patches with minimal to no induration, without associated symptoms, without contracture or atrophy. At the histopathological level, a limited involvement of collagen fibers is observed at the level of the uperficial reticular dermis. The case of a patient with superficial morphea treated with ultraviolet B phototherapy and methotrexate is presented.

Hierro y ácido fólico: natural, enriquecido, fortificado y suplementos. Análisis de las fuentes alimentarias en la Ciudad de Buenos Aires / Iron and folic acid: natural, enriched, fortified, and supplements. Analysis of food sources in the Autonomous City of Buenos Aires

Introducción. La fortificación y suplementación son estrategias para la prevención de carencias de micronutrientes. El objetivo fue describir la procedencia de la ingesta del hierro y ácido fólico a lo largo del ciclo vital de la población de la Ciudad Autónoma de Buenos Aires. Población y métodos. Análisis de la información de la Primera Encuesta Alimentaria y Nutricional de la Ciudad Autónoma de Buenos Aires 2011, que tomó una muestra probabilística por conglomerados. El consumo se recabó con recordatorio de 24 horas. Se calculó el aporte de hierro y ácido fólico, y se categorizó en contenido natural, harina de trigo enriquecida, leche del Plan Materno Infantil, alimentos fortificados y suplementos. Resultados. De los 5369 individuos evaluados, prácticamente, la totalidad obtenía hierro y ácido fólico de contenido natural (el 58 % y el 29 % del consumo, respectivamente). Más del 90 % consumía harina de trigo enriquecida, que aportaba el 28 % del hierro y el 54 % del ácido fólico. Los alimentos fortificados mostraron consumo y aporte muy variable. La leche del Plan Materno Infantil mostró muy baja participación, inclusive en grupos específicos. El aporte de suplementos fue bajo, excepto en < 2 años (el 30 % consumía suplementos de hierro, que aportaban el 38 % de este).Conclusión. Además del aporte natural de los alimentos, la harina de trigo enriquecida representó una importante contribución en el consumo de ácido fólico y hierro de esta población; los alimentos fortificados y los suplementos tuvieron una participación diferente según el grupo etario.

Introduction. Fortification and supplementation are two strategies for micronutrient deficiency prevention. The objective of this study was to describe the source of iron and folic acid intake throughout the life cycle in the population of the Autonomous City of Buenos Aires.Population and methods. Analysis of the information collected in the First Survey on Nutritional Food Intake of the Autonomous City of Buenos Aires (2011), which had a probability cluster sampling design. Consumption was assessed by means of a 24-hour recall. Iron and folic acid intake was estimated and categorized into natural content, enriched wheat flour, milk from the Maternal and Child Plan, fortified foods, and supplements.Results. Out of the 5369 studied individuals, practically all got iron and folic acid from natural contents (58 % and 29 % of intake, respectively). More than 90 % consumed enriched wheat flour, which provided 28 % of iron and 54 % of folic acid. Fortified food consumption and intake varied greatly. Milk intake from the Maternal and Child Plan was small, even in specific groups. Intake from supplements was low, except in children < 2 years old (30 % consumed iron supplements, which accounted for 38 % of iron).Conclusion. In addition to natural intake from foods, enriched wheat flour accounted for a major source of folic acid and iron in this population; intake from fortified foods and supplements varied by age group.

Papel protector del ácido fólico en un biomodelo de intoxicación alcohólica prenatal en ratas Wistar / Protective role of folic acid in a biomodel of prenatal alcohol intoxication in Wistar rats

Introducción: el etanol es un agente teratógeno cuyo consumo excesivo representa un importante problema de salud a nivel mundial. Objetivo: demostrar el papel protector del ácido fólico sobre el Sistema Nervioso Central y las dimensiones craneofaciales, en un biomodelo de intoxicación alcohólica prenatal en ratas Wistar. Métodos: estudio experimental con crías de tres grupos de ratas gestantes: sin intoxicación alcohólica; con 5 ml de etanol al 40 por ciento durante la gestación y con 5 ml de etanol al 40 por ciento más 200 µg/día de ácido fólico. Se evaluó en las crías la presencia de meningocele, encefalocele y microcefalia, y se midieron las dimensiones craneofaciales. Se utilizó la comparación de proporciones para muestras independientes, la prueba de Kruskal-Wallis y se estimó una asociación de riesgo estadísticamente significativa para un intervalo de confianza del Odds-Ratio que no contenga la unidad. Resultados: la suplementación con ácido fólico en ratas gestantes con intoxicación alcohólica, evitó en las crías la aparición de encefalocele, redujo la microcefalia, la disminución del diámetro biparietal y de la distancia entre los globos oculares, sin embargo, no logró evitar totalmente los daños en el Sistema Nervioso Central, ni impedir la disminución del diámetro anteroposterior ni de la distancia poro nasal-oreja. Conclusión: el biomodelo demostró el efecto tóxico del etanol y la protección del ácido fólico sobre el Sistema Nervioso Central y algunas dimensiones craneofaciales de las crías. Una dosis superior de ácido fólico a la utilizada en el experimento, pudiera ser recomendada para lograr una mayor protección de la descendencia(AU)

Introduction: ethanol is a teratogenic agent and its excessive consumption represents a major worldwide health problem. Objective: to demonstrate the protective role of folic acid on the Central Nervous System and craniofacial dimensions in a biomodel of prenatal alcohol intoxication in Wistar rats. Methods: an experimental study with offspring of three groups of pregnant rats: without alcohol intoxication; with 5 ml of 40 percent ethanol during gestation and with 5 ml of 40 percent ethanol plus 200 µg/day of folic acid. The presence of meningocele, encephalocele and microcephaly was evaluated in the offspring and the craniofacial dimensions were measured. The comparison of proportions for independent samples, the Kruskal-Wallis test and a statistically significant risk association was estimated for an Odds-Ratio confidence interval not containing the unit. Results: supplementation with folic acid in pregnant rats with alcohol intoxication prevented the onset of encephalocele of the offspring, reduce the microcephaly, diminution of the biparietal diameter and the distance between the eyeballs, however the damage of the Central Nervous System could not completely avoided, and not prevent the reduction of the anteroposterior diameter or the nasal-ear pore distance. Conclusion: the biomodel demonstrated the toxic effect of ethanol and the protection of folic acid on the Central Nervous System and some craniofacial dimensions of the offspring. A higher dose of folic acid, than the one used in the research, could be recommended to achieve a better protection of the offspring(AU)

Ácido fólico y embarazo, ¿beneficio o riesgo? / Folic acid and pregnancy, benefit or risk?

RESUMEN El consumo de ácido fólico se ha relacionado con la disminución en la incidencia de malformaciones congénitas y deficiencias obstétricas, pero existen criterios de que no siempre su uso tiene los efectos favorables esperados para la madre y su descendencia. Con el objetivo de estructurar los presupuestos teóricos que sustentan el beneficio y el riesgo del consumo de ácido fólico para el embarazo, se realizó una búsqueda sobre el tema consultándose 37 referencias bibliográficas actualizadas. El ácido fólico ostenta dos grandes funciones en el organismo: la síntesis y reparación de los ácidos nucleicos, así como la síntesis del aminoácido metionina a partir de la homocisteina, esta última, al acumularse en el organismo se asocia a defectos congénitos y enfermedades crónicas del adulto. A partir de estos aspectos se corrobora que su consumo antes y durante el embarazo es beneficioso pues previene defectos del tubo neural, algunas cardiopatías congénitas, hendiduras bucofaciales, síndrome de Down, desórdenes del espectro autista, infecciones obstétricas, preeclampsia, hemorragia uterina, desprendimiento abrupto de la placenta, retardo del crecimiento intrauterino y prematuridad. El consumo excesivo de más de 5 mg/día se ha asociado a anemia por deficiencia de vitamina B12, déficit de zinc, crecimiento intrauterino retardado y prematuridad; en modelos animales acelera la transformación maligna de tumores existentes. Se concluye que el ácido fólico contribuye a preservar una embriogénesis y placentación normal y no se han demostrado efectos adversos por su uso, pero debe ser consumido en la dosis adecuada y por prescripción médica.

ABSTRACT Acid folic intake has been related to the decrease in the incidence of congenital malformations and obstetric deficiencies but there are criteria about folic acid not always achieving the expected favorable results for mothers and their descendants. A search on the theme was carried out with the objective of structuring the theoretical assumptions upholding the benefit and risk of folic acid intake for pregnancy. 37 updated bibliographic references were consulted. The folic acid has two main functions in the organism: nucleic acids´ synthesis and repair, and also the synthesis of the methionine amino acid from homocystein; when the last one accumulates in the organism, it is associated to congenital defects and adults´ chronic diseases. Beginning from these aspects, it is stated that the intake before and after pregnancy is beneficial because it prevents defects of the neural tube, some congenital deficiencies, oral facial clefts, Down syndrome, autism spectrum disorders, obstetric infections, preeclampsia, uterine hemorrhage, sudden placental abruption, intrauterine grow retardation and prematurity. The excessive intake of more than 5 mg/d has been associate to anemia due vitamin B12 deficiency, zinc deficiency, intrauterine retarded grow and prematurity; in animal models it speeds up the malignant transformation of existent tumors. The authors arrived to the conclusion that folic acid contributes to preserving a normal embryogenesis and placentation, and that no adverse effects have been demonstrated, nevertheless it should be taken in adequate doses and for medical prescription.

Percepções de gestantes acerca do cuidado pré-natal na atenção primária à saúde / Percepciones de gestantes acerca del cuidado prenatal en la atención primaria a la salud / Perceptions of pregnant women about prenatal care in primary health care

Resumo OBJETIVO Compreender as percepções das gestantes acerca do cuidado recebido durante o pré-natal, no âmbito da atenção primária à saúde. MÉTODO Estudo qualitativo, baseado na Grounded Theory. A coleta de dados foi realizada de agosto a dezembro de 2016, através de entrevista semiestruturada com 12 gestantes que realizaram acompanhamento pré-natal na atenção primária do município de Florianópolis/SC/Brasil. A coleta e análise dos dados foram realizadas concomitantemente. Na análise de dados utilizou-se a codificação aberta e axial. RESULTADOS Foram elaboradas três categorias, sendo elas: O cuidado antes e durante a gestação. Participação em grupos de gestantes e, Cuidado de qualidade durante a gestação. CONCLUSÃO As percepções das gestantes acerca do cuidado recebido durante o pré-natal estão relacionadas à atenção dispensada, ao acolhimento humanizado, consideração da subjetividade da gestante e amparo nos momentos difíceis que tornam este período satisfatório.

Resumen OBJETIVO Comprender las percepciones de las gestantes acerca del cuidado recibido durante el prenatal, en el ámbito de la atención primaria a la salud. MÉTODO Estudio cualitativo, basado en la Grounded Theory. La recolección de datos fue realizada de agosto a diciembre de 2016, a través de entrevista semiestructurada con 12 gestantes en la atención primaria a la salud del municipio de Florianópolis/SC/Brasil. La recolección y análisis de los datos se realizaron concomitantemente. En el análisis de datos se utilizó la codificación abierta y axial. RESULTADOS Fueron elaboradas tres categorías, siendo ellas: El cuidado antes y durante la gestación, Participación en grupos de gestantes y, Cuidado de calidad durante la gestación. CONCLUSIÓN Las percepciones de las gestantes acerca del cuidado recibido durante el prenatal están relacionadas la atención dispensada, acogida humanizada, consideración de la subjetividad de la gestante y amparo en los momentos difíciles que hacen este período satisfactorio.

Abstract OBJECTIVE To understand the perceptions of pregnant women about the care received during prenatal care, in the field of primary health care. METHOD Qualitative study, based on Grounded Theory. Data collection was performed from August to December 2016, through a semi-structured interview with 12 pregnant women who received prenatal care in the city of Florianópolis/SC/Brazil. Data collection and analysis were performed concomitantly. Data analysis was performed using open and axial coding. RESULTS Three categories were elaborated: Care before and during gestation, Participation in groups of pregnant women, and Quality care during pregnancy. CONCLUSION The perceptions of the pregnant women about the care received during the prenatal care is related to the care given, humanized reception, consideration of the pregnant woman's subjectivity and support in the difficult moments that make this period satisfactory.

Ácido fólico em excesso: efeitos sobre o metabolismo das vitaminas B2 e B6, o catabolismo do triptofano e a resposta imune / Folic acid excess: effects on vitamin B2 and B6 metabolism, tryptophan catabolism and immune response

Introdução: A suplementação com ácido fólico (AF) é recomendada em algumas condições para evitar a deficiência de folato, como para mulheres no período periconcepcional e durante a gestação. Atualmente, existe uma preocupação quanto ao consumo excessivo de AF pela população pelo uso de suplementos com altas doses dessa vitamina. As vitaminas B6 e B2 agem como cofatores no metabolismo de um carbono, e o uso de altas doses de AF pode influenciar o metabolismo de ambas vitaminas e, consequentemente, interferir em metabolismos importantes das quais elas participam, como a via das quinureninas, e no sistema imune. Objetivo: Avaliar os efeitos da intervenção diária com uma alta dose de AF (5 mg) por 90 dias sobre marcadores do estado das vitaminas do complexo B, e as consequências sobre os metabólitos da via das quinureninas e o sistema imune em adultos saudáveis. Material e Métodos: 64 indivíduos saudáveis foram submetidos à intervenção diária com 5 mg de AF por 90 dias. Coletas de sangue foram realizadas antes (baseline) e após 45 e 90 dias de intervenção. As concentrações séricas de folato e vitamina B12 foram avaliadas por métodos microbiológicos. As concentrações séricas das vitaminas B6 (piridoxal 5'-fosfato (PLP), piridoxal (PL) e ácido 4-piridóxico (PA)), B2 (riboflavina e flavina mononucleotídeo (FMN)), B1 (tiamina e tiamina monofosfato (TMP)) e B3 (ácido nicotínico, nicotinamida e N1-metilnicotinamida), bem como de triptofano, quinurenina e metabólitos, foram avaliadas por LC-MS/MS. A proteína C-reativa ultrassensível (PCRus) foi determinada por imunoturbidimetria, e as concentrações séricas de interleucina (IL)-6, IL-8, IL-10, interferon gama (IFN-γ) e fator de necrose tumoral alfa (TNF-α) foram avaliadas por ensaio multiplex. A expressão de RNAm de DHFR (dihidrofolato redutase), MTHFR (metilenotetrahidrofolato redutase), IL8, TNFA e IFNG em leucócitos mononucleares (PBMC) foram avaliadas por PCR em tempo real. O número de células T regulatórias (Treg) (CD3+, CD4+, CD25high, FoxP3+, CD127-) foi avaliado após incubação dos PBMC com PMA e ionomicina ou veículo por 18h, por imunofenotipagem. Resultados: Houve um grande aumento das concentrações de folato sérico após 45 e 90 dias de intervenção com AF. Não houve diferença nas concentrações de vitamina B12 antes e após a intervenção. As concentrações séricas de PLP foram semelhantes antes e após a intervenção, entretanto, um aumento de PL sérico foi observado após 45 e 90 dias, e de PA após 45 dias, quando comparado ao baseline. Riboflavina e FMN foram maiores após 45 e 90 dias em relação ao baseline. A tiamina sérica foi menor após 45 dias, e as concentrações de TMP foram maiores após 90 dias quando comparados aos períodos anteriores. Não houve diferença nas concentrações de vitamina B3 antes e após a intervenção. Dentre os metabólitos da via das quinureninas, apenas o ácido antranílico apresentou aumento após 45 e 90 dias, enquanto o ácido picolínico diminuiu após 90 dias. PCRus, IL-6, IL-8, IL-10, IFN-γ e TNF-α séricos foram semelhantes no baseline e após a intervenção. Um aumento da expressão de RNAm de DHFR e TNFA foi observado após, respectivamente, 90 dias e 45 e 90 dias de intervenção. Após 90 dias de intervenção com AF, foi observada diminuição do número de células Treg após estímulo com PMA e ionomicina. Conclusão: O uso diário de 5 mg de AF foi associado a alterações nas concentrações séricas de marcadores do estado de vitaminas do complexo B e da via das quinureninas, bem como a diminuição do número de células Treg

Introduction: Folic acid (FA) supplementation is recommended in some conditions to avoid folate deficiency, as women during periconceptional period and pregnancy. Currently, there is a concern about the excessive consumption of FA by population by using supplements with high doses of this vitamin. Vitamins B6 and B2 are cofactors of enzymes of one carbon metabolism and, consequently, may disturb key metabolism in which they participate, as kynurenine pathway, and the immune system. Aim: To assess the effects of a daily intervention with high dose of FA (5 mg) for 90 days on biomarkers of complex B vitamins status and its outcomes in kynurenine pathway metabolites and immune system in healthy adults. Material and Methods: 64 healthy individuals were submitted to a daily intervention with 5 mg of FA for 90 days. Blood samples were collected before (baseline) and after 45 and 90 days of intervention. Serum folate and vitamin B12 were assessed by microbiological assays. Serum vitamin B6 (pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (PA)), vitamin B2 (riboflavin and flavin mononucleotide (FMN)), vitamin B1 (thiamin and thiamin monophosphate)) and vitamin B3 (nicotinic acid, nicotinamide and N1-methylnicotinamide), as well as tryptophan, kynurenine and metabolites, were assessed by LC-MS/MS. C-reactive protein (hs-CPR) was assessed by immunoturbidimetry, and serum interleukin (IL)-6, IL-8, IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were assessed by multiplex assay. Mononuclear leukocytes mRNA expression of DHFR (dihydrofolate reductase), MTHFR (methylenetetrahydrofolate reductase), IL8, TNFA and IFNG were assessed by real time PCR. Regulatory T Cell (Treg) number (CD3+, CD4+, CD25high, FoxP3+, CD127-) was determined after mononuclear leukocytes incubation with PMA and ionomycin or vehicle for 18h, by immunophenotyping. Results: A great increase on serum folate was observed after 45 and 90 days of FA intervention. No differences in serum vitamin B12 were observed before and after intervention. Serum PLP was similar before and after intervention, however, an increase in serum PL was observed after 45 and 90 days, and in PA after 45 days, when compared to baseline. Riboflavin and FMN were increased after 45 and 90 days than in baseline. Serum thiamine was decreased after 45 days than in baseline. Serum TMP was increased after 90 days when compared with previous timepoints. No differences in vitamin B3 were observed after and before FA intervention. Among kynurenine pathway metabolites, anthranilic acid was increased after 45 and 90 days, while picolinic acid was decreased after 90 days. hs-CPR, serum IL-6, IL-8, IL-10, IFN-γ and TNF-α were similar at baseline and after intervention. An increase on mRNA expression of DHFR and TNFA was observed after, respectively, 90 days and 45 and 90 days of intervention. After 90 days of FA intervention, it was observed a decrease on Treg cell number after PMA and ionomycin stimulation. Conclusion: Daily use of 5 mg of FA was associated with changes in serum markers of B-complex vitamins status and kynurenine pathway, as well as decreased number of Treg cells

¿Es efectiva la potenciación con folato para el trastorno depresivo mayor? / Is augmentation with folate effective for major depressive disorder?

INTRODUCCIÓN: En una proporción importante de los pacientes con depresión, el tratamiento antidepresivo no lleva a una respuesta satisfactoria. Actualmente se postula que la coadministración de nutrientes estandarizados farmacológicamente (nutracéuticos), como el folato en este caso, podrían potenciar los efectos de los antidepresivos. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que en conjunto incluyen nueve estudios primarios, de los cuales, ocho son ensayos aleatorizados. Concluimos que la potenciación con folato en el tratamiento del trastorno depresivo mayor probablemente resulta en poca o nula diferencia en los síntomas depresivos. Pudiese ser interesante evaluar el efecto de formas de presentación específicas del folato o en población con déficit objetivado.

INTRODUCTION: Antidepressant treatment does not lead to a satisfactory response in a significant proportion of patients with depression. It has been postulated that co-administration of pharmacologically standardized nutrients (nutraceuticals), such as folate, would potentiate the effect of antidepressants. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified four systematic reviews including nine studies overall, of which eight were randomized trials. We concluded augmentation with folate for the treatment of major depressive disorder probably results in little or no difference in depressive symptoms. It would be interesting to evaluate the effects of specific presentation forms of folate or in population with objective folate deficit.

Folatos y embarazo, conceptos actuales: ¿Es necesaria una suplementación con Acido Fólico? / Folate and pregnancy, current concepts: It is required folic acid supplementation?

El aporte de folatos durante el embarazo es esencial para un desarrollo fetal y placentario adecuados y para la salud del individuo a largo plazo. Su deficiencia puede inducir alteraciones y patologías fetales como bajo peso al nacer, recién nacidos de pre término y defectos del tubo neural (DTN). Por ello, varios países han decidido implementar políticas públicas de fortificación de alimentos con ácido fólico (AF). Chile inició la fortificación de la harina de trigo con AF en el año 2000, logrando reducir en un 43% la prevalencia de DTN. Sin embargo, además de la elevada ingesta de pan de nuestra población (principal alimento fortificado con AF), muchas mujeres embarazadas consumen suplementos de AF, lo que podría estar superando las concentraciones máximas de AF recomendadas. Adicionalmente, si la dieta materna es reducida en vitamina B12 (vit B12), se alteraría la razón óptima folatos/vit B12 lo que modificaría la metilación de genes específicos y otras vías metabólicas pudiendo afectar el desarrollo fetal y la salud de los recién nacidos a largo plazo. Creemos que, transcurridos 17 años del inicio de la fortificación de la harina de trigo con AF, es necesario evaluar los posibles efectos secundarios de un alto consumo de AF, no solo durante el embarazo, sino también en la población general. Presentamos antecedentes acerca del mecanismo de acción de folatos y vit B12 a nivel celular, y conceptos actuales sobre las posibles consecuencias de un aporte materno elevado de AF sobre la descendencia.

Folate intake during pregnancy is essential for an adequate fetal and placental development and for the long time health of the individual. Its deficiency may induce fetal pathologies, including neural tube disease (NTD). Therefore, several countries implemented public policies to fortify foods with folic acid (FA). Chile started the fortification of wheat flour with FA in the year 2000, decreasing a 43% the prevalence of NTD. However, despite the high consumption of bread (the main fortified food with FA) by our population, a high number of pregnant women consume FA supplements, thus, over passing the maximal recommended FA intake. Additionally, if the diet is reduced in vitamin B12, the optimal ratio folates/vit B12 may be altered, thus inducing changes in the methylation of specific genes and other metabolic pathways, affecting fetal development and the long-term health of the neonates. We think that, after 16 years of the initiation of the fortification of wheat flour with FA, it is necessary to evaluate the possible side effects of a high intake of FA in the pregnant population and their offspring. This article shows antecedents about mechanisms of folates and vit B12 at cellular level, and their possible consequences of an elevated FA maternal intake on the offspring.

The mortality rate after hospital discharge in patients with myelomeningocele decreased after implementation of mandatory flour fortification with folic acid / Redução da taxa de mortalidade após a alta hospitalar em pacientes com mielomeningocele depois da implementação da fortificação obrigatória das farinhas com ácido fólico

ABSTRACT Objective: To evaluate the mandatory folic acid fortification of flour on mortality rates after the hospital discharge of children born with myelomeningocele, the most affected age group and the most frequent cause of death. Methods: A retrospective study of 383 children born with myelomeningocele from January 1990 to December 2013 in a high-fetal-risk reference hospital. Results: A total of 39 patients died (10.1%),of which 23 (6%) died after discharge. Most children who died were younger than 12 months of age. The most frequent cause of death was infection of the central nervous system, followed by urinary tract sepsis and infections of the respiratory system. Symptomatic Chiari II malformation was the most frequent comorbidity factor. Conclusion: Although there was no significant difference in infant mortality before and after folic acid fortification, there was a significant reduction in deaths after hospital discharge in babies born after implementation of mandatory folic acid fortification

RESUMO Objetivo: Avaliar a fortificação obrigatória de farinhas com ácido fólico nas taxas de mortalidade após a alta hospitalar de crianças nascidas com mielomeningocele, a faixa etária mais atingida e a causa mais freqüente de morte. Métodos: Estudo retrospectivo de 383 crianças nascidas com mielomeningocele de janeiro de 1990 a dezembro de 2013, em um hospital de referência de alto risco fetal. Resultados: Um total de 39 pacientes morreram (10,1%), dos quais 23 (6%) morreram após a alta. A maioria das crianças que morreram não alcançaram 12 meses de idade. A causa mais frequente de morte foi infecção do sistema nervoso central, seguido por sépsis, infecções do trato urinário e do sistema respiratório. A malformação de Chiari Tipo II foi a comorbidade mais freqüente. Conclusão: Apesar de não haver diferença significativa na frequência de mortalidade de recém-nascidos, antes e depois da fortificação obrigatória com ácido fólico, houve uma redução significativa no número de mortes após a alta hospitalar em bebês nascidos após a implementação da fortificação obrigatória das farinhas com ácido fólico.

Fisuras labio-palatinas y fortificación de la harina con ácido fólico en Chile: an exploratory study / Cleft lip/palate and flour fortification with folic acid in Chile

Background: The effect of food fortification with folic acid on the incidence of lip-palate fissures (FLP) is under discussion. Aim: To calculate the rate of hospital discharges due to cleft lip and palate (CLP) and explore whether they decreased after the start of folic acid fortification in Chile. Material and Methods: The hospital discharge databases published by the Chilean Ministry of Health were analyzed. The trends of discharge rates due to CLP of children of less than one year of life (ICD-10 Q350-379 code) and live births (lb) were calculated from 1986 to 2012. Variables such as incidence of rubella, poverty rate, obesity in pregnant women, and percentage of women who smoked or drank alcohol in the last month were included. The relative risk (RR) of CLP pre-fortification (1986-1999) and post-fortification (2000-2010) was calculated. Mixed and Prais-Winsten models were used to adjust other variables. Results: The hospital discharge rate due to CLP decreased from 1.88 x 1,000 lb during 1986-1996 to 1.68 x 1,000 lb (RR = 1.09 (95% CI 1.05-1.14, p < 0.001). Prais-Winsten and Mixed models, determined that folic acid fortification is the variable explaining this decrease. During 2004-2011, hospital discharge rates for cleft lip decreased but there was an increase in the figures for cleft lip and palate. Conclusions: The 9% decrease in hospital discharge rates for CLP is concomitant with wheat folic acid fortification.

Folic acid and diseases - supplement it or not? / Ácido fólico e doenças - suplementá-lo ou não?

SUMMARY Introduction: folic acid is a water soluble vitamin, which is synthetically-produced and found in fortified foods and supplements. Folate is found naturally in plants, such as the dark green leafy vegetables. Folate is not synthesizedde novo by humans, therefore the daily requirements are met from the dietary intake of folic acid supplements or food rich in this vitamin. Folate deficiency could lead to numerous common health problems. Hyperhomocysteinemia and the possibility of malignancy developments are the long term consequences of this deficit albeit contradictory findings on these claims. Methods: the articles included in this review focused on recent updated evidence-based reports and meta-analyses on the associations of the serum folate/folic acid and the various diseases found globally. Results: the benefit of folic acid supplementation in the pre-conception period for the prevention of neural tube defects (NTDs) was well established and it was suggested that counseling sessions should be given to women with previous pregnancies affected by NTDs. However, supplementation of folic acid and its medicinal effects in the treatment of other diseases were contradictory and unclear. Conclusion: more detailed investigations into the health benefits of folic acid are needed before it could be recommended for supplementation, treatment or prevention of some of the diseases discussed in this review.

RESUMO Introdução: ácido fólico é uma vitamina solúvel em água produzida sinteticamente e encontrada em alimentos e suplementos enriquecidos. O folato é encontrado naturalmente em plantas, como vegetais folhosos verde-escuros. O folato não é sintetizado de novo por seres humanos; portanto, as necessidades diárias são satisfeitas a partir da ingestão de suplementos de ácido fólico ou alimentos ricos nessa vitamina. A deficiência de folato pode levar a inúmeros problemas de saúde comuns. Hiper-homocisteinemia e a possibilidade de desenvolver malignidades são as consequências a longo prazo desse déficit, ainda que os resultados sejam contraditórios sobre essas afirmações. Métodos: os artigos incluídos nesta revisão tratam de relatórios recentes atualizados com base em provas e metanálises sobre a associação entre o folato/ácido fólico e várias doenças encontradas globalmente. Resultados: o benefício da suplementação de ácido fólico no período de pré-concepção para a prevenção de defeitos do tubo neural (DTN) foi bem estabelecido e foi sugerido que sessões de aconselhamento devem ser providas às mulheres com gravidezes anteriores afetadas por DTN. No entanto, os benefícios da suplementação de ácido fólico e os efeitos medicinais no tratamento de outras doenças são contraditórios e pouco claros. Conclusão: investigações mais detalhadas sobre os benefícios do ácido fólico são necessárias antes que a suplementação seja recomendada para tratamento ou prevenção de algumas das doenças discutidas nesta revisão.

Effect of folic acid in a modified experimental model of anorectal malformations adriamycin-induced in rats

PURPOSE: To determine the effect of a single dose of adriamycin (ADR) to induce anorectal malformations (ARMs) and determine the effect of folic acid (FA) in this model. METHODS: Ten female Wistar rats were divided randomly in two groups. Group A - ADR; Group B - FA+ADR. Dams from group B received daily, since two weeks before the pregnancy to the end of pregnancy, FA (50mg/kg) by gavage. Dams from both groups received ADR (6mk/kg) by intraperitoneal injection on gestational day (GD) 8. Their fetuses were harvested by cesarean section on GD21 and were examined looking for ARMs. The thickness of anal stratified squamous epithelium (ASSE) and intestinal epithelium (IE) were analyzed. p≤0.05*. RESULTS: 81 fetuses were harvested. The number of fetuses; number of ARMs; mean (∆%) (± SD) were determined to be, respectively: ADR - 41[29;65%(±37%)] versus FA+ADR - 40[04;16%(±36%)] (p=0.05). AMRs were significantly lower in FA+ADR group than in ADR group (p=0.05). The thickness (µm) of ASSE (± SD) and IE (± SD) were measured, respectively: ADR - [25.98(±0.74) and 19.48(±1.68)] versus FA+ADR - [24.74(±0.91) and 24.80(±0.81)] (p<0.005). The thickness of IE was significantly enlarged when FA was given (p<0.005). CONCLUSIONS: Single dose of adriamycin on D8 was able to induce anorectal malformations. Folic acid reduces the number and enlarged the IE of ARMs ADR-induced.

Polimorfismo do gene timidilato sintase e nível plasmático total de homocisteína em um grupo de pacientes turcos com artrite reumatoide: relação com a atividade da doença e toxicidade ao metotrexato / Thymidylate synthase genetic polymorphism and plasma total homocysteine level in a group of Turkish patients with rheumatoid arthritis: relationship with disease activity and methotrexate toxicity

Resumo Introdução: Relata-se que o polimorfismo do gene timidilato sintase (TS) e a homocisteína têm relação com o metabolismo do metotrexato (MTX), com achados conflitantes. O objetivo deste estudo foi determinar os níveis de homocisteína e a frequência de polimorfismos de repetição tripla (TS3R) e dupla (TS2R) do gene TS em um grupo de pacientes turcos com AR e avaliar sua associação com a toxicidade ao MTX e a atividade da doença. Métodos: Foram incluídos no estudo 64 pacientes com AR e 31 indivíduos no grupo controle, com média de 48,7 ± 12,5 e 46,2 ± 13,4 anos. Foram obtidas as características demográficas e foi registrado o número de pacientes que relataram efeitos adversos ao MTX no grupo AR. Foram analisados os níveis de homocisteína e os polimorfismos TS2R/TS3R. Foi determinada a distribuição de genótipos de acordo com a toxicidade ao MTX e a atividade da doença. Resultados: Os dados demográficos foram semelhantes entre os pacientes e controles. Todos faziam suplementação de ácido fólico a uma dose média de 5 mg/semana. Dos 64 pacientes, 36 apresentaram efeitos adversos ao tratamento com MTX. Encontrou-se uma frequência de polimorfismos TS2R e TS3R semelhante nos grupos AR e controle. Encontrou-se que os polimorfismos TS2R e TS3R eram semelhantes em pacientes com e sem eventos adversos relacionados com o MTX. O nível médio de homocisteína também foi similar em pacientes com e sem polimorfismo do gene TS, mas era mais elevado (12,45 μmol/L vs. 10,7 μmol/L) em pacientes com do que sem efeitos adversos relacionados com o MTX. O nível médio de homocisteína se correlacionou com o VHS no grupo AR. Conclusões: Os níveis de homocisteína podem afetar a atividade da doença e a toxicidade ao MTX, mas os polimorfismos 2 R e 3 R no gene TS não se correlacionaram com a toxicidade ao MTX em pacientes com AR que recebem suplementação de ácido fólico. São necessários mais estudos para esclarecer os polimorfismos em outras enzimas que podem ser responsáveis pela toxicidade ao MTX em pacientes com AR.

Abstract Background: The polymorphism of thymidylate synthase (TS) gene and homocysteine are reported to have a relationship to methotrexate (MTX) metabolism, with conflicting results. The aim of this study was to determine homocysteine levels and the frequency of TS gene triple repeat (TS3R) and double repeat (TS2R) polymorphisms in a group of Turkish RA patients and evaluate its association with MTX toxicity and disease activity. Methods: Sixty-four patients with RA and 31 control subjects with a mean age of 48.7 ± 12.5 and 46.2 ± 13.4 years were enrolled for the study. Demographic characteristics were obtained and a number of patients with MTX-related adverse affects were recorded in the patient group. The homocysteine levels and TS2R/TS3R polymorphisms of the TS gene were analyzed and the distribution of genotypes according to MTX toxicity and disease activity was determined. Results: The demographic properties were similar between the patient and control subjects. Folic acid supplementation with a mean dose of 5 mg folic acid/week was present in all patients. Thirty-six of the 64 patients showed adverse effects to MTX treatment. The respective frequency of TS2R and TS3R polymorphisms was found to be similar in the patient and control groups. TS2R and TS3R gene polymorphisms were found to be similar in patients with and without MTX-related adverse events. The mean homocysteine level was also similar in patients with and without TS gene polymorphism, but was found to be higher (12.45 μmol/L vs 10.7 μmol/L) in patients with MTX-related side effects than in patients without side effects. The mean level of homocysteine was correlated with levels of ESR in the patient group. Conclusions: In conclusion, homocysteine levels might affect the disease activity and toxicity of MTX but 2R and 3R polymorphisms in the TS gene were not related with MTX-related toxicity in RA patients receiving folate supplementation. Further studies are needed to illuminate the polymorphisms in other enzymes that might be responsible for the MTX toxicity in patients suffering from RA.

Efeitos do ácido fólico não metabolizado na metilação global do DNA, na expressão de RNAm dos genes de DHFR, MTHFR, interferon-γ, TNF-α e interleucina-8, e na citotoxicidade das células NK / Effects of unmetabolized folic acid on global DNA methylation, on mRNA expression of DHFR, MTHFR, interferon-α, TNF-α and interleukin-8 genes, and on NK cells cytotoxicity

Com o início da fortificação de farinhas com ácido fólico (AF) no Brasil, a partir 2004, a população passou a estar exposta de modo compulsório a maiores quantidades desta vitamina. Sabe-se que o AF na sua forma sintética pode não ser completamente convertido para formas metabolicamente ativas, levando ao aparecimento de uma fração não metabolizada no organismo. Este fato é mais preocupante nos indivíduos que além da fortificação, fazem uso terapêutico dessa vitamina, como em pacientes com anemias hemolíticas (esferocitose hereditária (EH), ß-talassemia heterozigótica (ß-TH), entre outras). O objetivo desse estudo foi avaliar se as concentrações séricas de AF não metabolizado (UMFA) afetam a metilação global do DNA; a expressão de RNAm de genes da DHFR, MTHFR, interferon-γ, TNF-α e interleucina (IL)-8; e a citotoxicidade de células NK. Foram incluídos 27 pacientes com EH, 50 indivíduos com ß-talassemia heterozigótica (ß-TH) e 136 indivíduos saudáveis. Outros 30 indivíduos saudáveis foram incluídos num estudo de intervenção com 5mg/dia de AF durante 90 dias. Foram realizadas as análises de: ácido fólico sérico, eritrocitário e UMFA, vitamina B12, homocisteína total; expressões de RNAm dos genes de MTHFR, DHFR, IFN-γ, TNF-α e IL-8; citotoxicidade das células NK; metilação global do DNA e citocinas séricas IL6, IL-8, IL10, IFN-γ e TNF-α. Resultados: Os pacientes EH apresentaram maiores concentrações de AF (sérico, eritrocitário e UMFA) que seus controles, sendo que 55,5% (método microbiológico) e 74,1% (método LC-MS/MS) apresentaram concentrações suprafisiológicas da vitamina, e 74,1% apresentaram concentrações aumentadas de UMFA. No grupo ß-TH foi observado maiores concentrações de folato eritrocitário comparado ao controle e 22% dos indivíduos tinham concentrações suprafisiológicas de AF. No estudo de intervenção, após 45 e 90 dias de uso de AF as concentrações suprafisiológicas estavam presentes em 93,3% dos indivíduos e 100% deles apresentavam concentrações aumentadas de UMFA. Não foram observadas diferenças nas taxas de metilação global do DNA entre os grupos EH e ß-TH quando comparados aos seus controles e não foi verificada correlação entre metilação global e concentrações de UMFA. Tanto EH quanto ß-TH apresentaram maior expressão de RNAm de IL-8, quando comparados aos seus controles. No grupo de intervenção houve maior expressão de IL-8 após 45 dias de uso de AF quando comparado ao período pré-intervenção. Foi mostrada uma correlação inversa entre as concentrações de folato eritrocitário com o número de células NK no grupo EH e com a capacidade citotóxica das células NK no grupo total (EH + controle). No grupo intervenção foi observado menor número e menor capacidade citotóxica das células NK após 90 dias de uso de AF. Conclusões: O uso de AF 5mg/dia foi associado com aumento expressivo das concentrações de folato sérico, eritrocitário, UMFA, na expressão de RNAm de genes da citocina inflamatória IL-8 e redução do número e da citotoxicidade das células NK. Dessa forma, altas doses de AF podem resultar em alterações de componentes do sistema imune podendo prejudicar os mecanismos de vigilância celular das células NK. Os nossos achados sugerem que é importante o acompanhamento terapêutico dos pacientes que fazem uso de AF, especialmente aqueles indivíduos que fazem uso crônico desta vitamina por longo tempo, como os pacientes com anemias hemolíticas, mulheres que desejam engravidar e gestantes

With the beginning of the fortification of flour with folic acid (FA) in Brazil, since 2004, the population has been exposed compulsorily to larger amounts of this vitamin. It is known that FA in its synthetic form can not be completely converted to metabolically active forms, leading to the appearance of an unmetabolized fraction in the body. This fact is more worrying in subjects beyond fortification, make therapeutic use of this vitamin, such as patients with hemolytic anemia (hereditary spherocytosis (HS), ß-thalassemia heterozygotic (ß-TH), among others). The aim of this study was to evaluate if serum concentrations of unmetabolized FA (UMFA) affect the global DNA methylation; mRNA expression of DHFR, MTHFR, interferon-γ, TNF-α and interleukin (IL)-8 genes; and on cytotoxicity of NK cells. It was included 27 patients EH, 50 subjects ß-TH and 136 healthy subjects. Another 30 healthy subjects were included in an intervention study with 5 mg/FA daily during 90 days. Analyzes performed were: serum and erythrocyte folate, and UMFA, vitamin B12, tHcy; mRNA expression of MTHFR, DHFR, IFN-γ, TNF-α and IL-8 genes; cytotoxicity of NK cells; global DNA methylation and serum cytokines IL6, IL-8, IL10, IFN-γ and TNF-α. Results: EH patients presented higher FA concentrations (serum, erythrocytes and UMFA) than controls ones, and 55.5% (microbiologic method) and 74.1% (LC-MS/MS method) showed supraphysiologic concentrations of vitamin, and 74.1% presented increased concentrations of UMFA. In ß-TH group, it was observed higher erythrocyte folate concentrations compared with the control and 22% of subjects had supraphysiological concentrations of FA. In the intervention study, after 45 and 90 days of FA use, supraphysiological concentrations were present in 93.3% of subjects and 100% of them showed increased concentrations of UMFA. It was not observed differences in global methylation of DNA between EH and ß-TH groups when compared to their controls and it was not observed significant correlation between global DNA methylation and UMFA levels. Both EH and ß-TH showed higher mRNA expression of IL-8 gene, when compared to controls. In the intervention group, there was higher mRNA expression of IL-8 gene after 45 days of FA use when compared to pre-intervention period. It was demonstrated an inverse correlation between erythrocyte folate levels and the number of NK cells in EH group; and cytotoxic capacity of NK cells on total group (EH + control). In intervention group, it was observed fewer number and lower cytotoxic capacity of NK cells after 90 days of AF use. Conclusions: The use of AF 5mg daily was associated with a significant increase in serum and erythrocytes folate levels, accompanied by increase in UMFA levels, an increase in mRNA expression of IL-8 gene, and reduction of the number and the cytotoxicity capacity of NK cells. Thus, high doses of AF can result in modifications of the immune system components, which may damage the cell surveillance mechanisms of NK cells. Our findings suggest that is important the therapeutic follow up of patients that are using AF, especially those subjects with chronic use of this vitamin, such as patients with hemolytic anemia, women who wish to become pregnant and pregnant women

Folic acid intake by pregnant women from Vale do Jequitinhonha, Brazil, and the contribution of fortified foods / Consumo de ácido fólico por gestantes do Vale do Jequitinhonha, Brasil, e a contribuição dos alimentos fortificados

The folate deficiency can result in irreversible health damage, such as the neural tube defects. The aim of this article is to determine the folate intake of pregnant women in Vale do Jequitinhonha, Minas Gerais state, Brazil, one of the poorest regions in the world. A descriptive, cross-sectional study was done in 2013 with 492 pregnant women attending the basic health units run by the public health service (Sistema Único de Saúde, SUS) in 15 municipalities. A standard questionnaire was used to gather the data, which included socioeconomic indicators and a food frequency questionnaire. The data were analyzed and compared statistically based on prevalence ratios and 95% confidence intervals. The prevalence of inadequate folate intake was associated with some socioeconomic factors: it was higher amongst the low income and less educated women, in younger women and those who had fewer meals per day. The prevalence of inadequate folate intake in the diet was 94.7% when the contribution of food fortification was not considered, 49.2% taking into account fortified foods, and 17.1% considering food folate, fortified foods, and supplementation with folic acid. We conclude that fortifying foods with folic acid at the current levels reduces the inadequacy of folate intake in the diet, but not enough to assure safe levels and to meet the nutritional requirements of pregnant women in Brazil.

A deficiência de folato pode acarretar prejuízos irreversíveis como os defeitos do tubo neural. O objetivo deste artigo é determinar o padrão de consumo de folato por gestantes no Vale do Jequitinhonha, Minas Gerais, Brasil, uma das regiões mais pobres do mundo. A pesquisa descritiva do tipo transversal foi realizada com 492 gestantes atendidas em Unidades Básicas de Saúde do SUS em 15 municípios do Vale do Jequitinhonha no ano de 2013. Para a coleta de dados foi utilizado um questionário padronizado, que inclui um questionário socioeconômico e inquérito de frequência alimentar. Os dados foram analisados e comparados estatisticamente através de razão de prevalências e intervalo de confiança de 95%. A prevalência de consumo insuficiente de folato mostrou-se associada com alguns fatores socioeconômicos: foi maior em gestantes com baixa renda, de baixa escolaridade e em gestantes mais jovens e que realizavam menos refeições por dia. Observou-se que a prevalência de consumo insuficiente de folato na dieta foi de 94,7% desconsiderando a inclusão de alimentos fortificados, 49,2% considerando a dieta com alimentos fortificados e 17,1% considerando a dieta, a fortificação e a suplementação medicamentosa com ácido fólico. Conclui-se que a fortificação de alimentos com ácido fólico nos níveis atuais reduz a inadequação do consumo na dieta, mas não é suficiente para suprir as necessidade e garantir os níveis seguros da oferta deste nutriente entre gestantes brasileiras.

Bajo consumo de folatos en venezuela: urge una política de prevención y fortificación de alimentos / Folate intake deficit in venezuela address a policy for prevention and food fortification

El acido fólico (AF) es indispensable durante los primeros 28 días de la gestación, cuando por lo general la madre aún no sabe que está embarazada y seguirá siendo indispensable durante todo el ciclo vital. Hace más de dos décadas se reportó el rol del ácido fólico (AF) en la prevención de los defectos del tubo neural. El AF también se ha involucrado en la prevención del deterioro de la función cognitiva del adulto mayor. Esta revisión analiza los resultados de cinco estudios en Venezuela realizados entre los años 2003 hasta el 2010. Posterior a esta fecha no se encontró ninguna publicación similar. Los estudios son transversales, no probabilísticos, realizados en adolescentes (n=114), mujeres en edad fértil (n=243), embarazadas (n=863; n=104) y en el adulto mayor (n=53). Los estados donde se realizaron son el Distrito Capital, Carabobo y Lara. Los métodos para cuantificar el consumo de AF fueron: recordatorio de 24 horas, cuestionario de frecuencia de consumo, registro de 7 días y pesada de alimentos. La deficiencia en el consumo osciló entre 19% y 93%. Los estudios no son de ámbito nacional, los cuales reportan un problema de salud pública. Se recomienda realizar estudios nacionales que muestren la prevalencia de déficit, aunado al desarrollo de una política integral para prevenir y tratar la deficiencia de AF, que contemple las estrategias de fortificación de un alimento de consumo masivo, la fortificación complementaria, la suplementación y la diversificación de la dieta a través de la educación alimentaria(AU)

Folic acid (FA) is essential during the first 28 days of pregnancy, when most mothers still do not know that they are pregnant and will remain essential throughout the life cycle. More than two decades ago the role of FA acid in the prevention of neural tube defects was first reported. AF is also involved in preventing the deterioration of cognitive function in the elderly. The aim of this manuscript is to review and analyze the results of five surveys conducted from 2003 to 2010. After this date no similar publications were found. Studies were cross-sectional, with non probabilistic samples, collected in adolescents (n = 114), women of childbearing age (n = 243), pregnant women (n = 863, n = 104) and elders (n = 53). The geographical regions studied were the Capital, Carabobo and Lara States. Methods for measuring the intake of FA were: 24-hour recall, food frequency questionnaire, register of seven days and weigh of food. Deficit of intake varied among groups, it ranged from 19% to 93%. These studies came from non national representative samples, although showed a public health problem regarding this micronutrient. We recommend developing a national representative research that show the prevalence of the situation, moreover, the development of a comprehensive food policy to prevent and treat FA deficiency, which contemplates strategies of food fortification, home fortification, supplementation and diet diversification using nutrition education(AU)