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.

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.

Fortificación de harina de trigo con ácido fólico y hierro en Uruguay; implicancias en la nutrición / Fortification of wheat flour with folic acid and iron in Uruguay; implications for nutrition

This study assessed folic acid (FA) and iron (Fe) content in flour fortified according to the levels regulated by law, and estimate the degree of adequacy of FA and Fe contained in French bread with the recommended dietary allowances (RDAs) and tolerable upper limits for different groups of Uruguayan population. Ten samples of flour and bread were analyzed. The median value for added FA and of the total Fe in flour was 2.3 and 48 mg/kg respectively. The recommended intake of bread covers the median value between 27% and 90% of the RDAs for Fe and between 69% and 104% of dietary folate equivalents in different groups. To sum up, fortification levels in flour adjusted to, exceeded or did not reach the regulated levels. Bread was a basic means to help cover RDAs in vulnerable people.

La presente investigación evaluó el contenido de ácido fólico (AF) y hierro (Fe) en harinas fortificadas y comparar con los niveles de adición legislados, estimando el grado de adecuación de AF y Fe contenidos en pan francés con las ingestas diarias recomendadas (RDAs) y los límites máximos tolerables para distintos grupos de la población uruguaya. Se analizaron diez muestras de harina y de pan. El valor de la mediana de AF adicionado y del Fe total, en harinas fue 2.3 y 48 mg/kg respectivamente. La ingesta recomendada de pan cubre en el valor de la mediana entre un 27% y 90% de las RDAs de Fe y entre el 69% y 104% de Equivalentes Dietarios de Folatos en diferentes grupos. En conclusión, los niveles de fortificación en harina adecuaron, superaron o no alcanzaron lo legislado. El pan constituyó un vehículo básico para cubrir las RDAs en la población vulnerable.

Valores de referencia de ácido fólico para la población venezolana / Reference values of folic acid for the Venezuelan population

En esta revisión de las recomendaciones de ácido fólico para Venezuela, se presentan las definiciones adoptadas a nivel mundial conocidas como Ingestas Dietéticas de Referencia (DRIs por Dietary Reference Intakes) que incluyen: Ingesta Dietética Recomendada (RDA), Requerimiento Promedio Estimado (EAR), Ingesta Adecuada (AI) y Niveles de Ingesta Máximos Tolerables (UL). En contraste con la situación en algunos países, donde se comienza a considerar un ajuste en las políticas de fortificación de alimentos con ácido fólico para evitar su exceso, en Venezuela varios estudios muestran una elevada prevalencia de deficiencia de este nutriente. Los datos nacionales no son suficientes para establecer los requerimientos, por lo tanto, al igual que en la revisión del año 2000, las recomendaciones actuales se basan en las definidas para la población de Estados Unidos. Las Ingestas Dietéticas Recomendadas (RDA) para Venezuela son: menores de 1 año 65-80 μg/día, niños 150- 300 μg/día, adolescentes y adultos 400 μg/día, embarazadas 600 μg/día y lactancia 500 μg/día. El Requerimiento Promedio Estimado (EAR) es: niños 120-250 μg/día, adolescentes 330 μg/ día y adultos 320 μg/día, embarazadas 520 μg/día y lactancia 450 μg/día. Los Niveles de Ingesta Máximos Tolerables (UL) son: niños 300-600 μg/día, adolescentes 800 μg/día y adultos 1000 μg/día, embarazadas y madres entre 14 y 18 años 800 μg/ día y para embarazadas y lactantes mayores 1000 μg /día. Es importante seguir evaluando la situación de este nutriente, con la finalidad de diseñar políticas adecuadas y eficientes que puedan controlar en ciertos grupos de la población tanto la deficiencia como el exceso.

The review on folic acid requirements for Venezuela comprise the definitions adopted worldwide known as Dietary Reference Intakes (DRIs) that include Recommended Dietary Allowance (RDA), Estimated Average Requirement (EAR), Adequate Intake (AI) and Tolerable Upper Intake Levels (UL). In contrast with the situation in some countries, that required adjustments in fortification policies in order to avoid excessive folic acid consumption, in Venezuela several studies show an elevated prevalence of deficiency. National evidence at this point is insufficient to establish the recommendation, and as in the 2000 review of the Venezuelan RDAs, the actual recommendations are based on the reported for the United States population. The Recommended Dietary Allowances for Venezuela are 65-80 μg/day for infants less than 1 year old, 150-300 μg/day for children and 400 μg/day for adolescents and adults, increasing to 600 μg/day during pregnancy and to 500 μg/day during lactation. The estimated average requirement is 120-250 μg/day for children, 330 μg/day for adolescents, 320 μg/day for adults, 520 μg/day for pregnancy and 450 μg/day during lactation. The tolerable upper intake levels for folic acid are 300-600 μg/day for children, 800 μg/day for adolescents and 1000 μg/day for adults. During pregnancy and lactation the UL is 800 μg/day for pregnant and lactating women between 14 and 18 years of age, and 1000 μg /day for older pregnant and lactating women. The continuous evaluation of folic acid status is important to design adequate and efficient policies to control both, the deficiency and the excess of folic acid consumption.

Fortificación de la harina de trigo con ácido fólico en Chile: Consecuencias no intencionadas / Flour fortifcation with folic acid in Chile: Unintended consequences

Background: High daily intake of folic acid (FA) could determine health risks in some populations. Aim: To review the Chilean FA wheat four fortifcation and to identify the existence of populations at risk. Material and Methods: We categorized the FA levels in four samples (percentil P) (2005-2008) and estimated intake of FA (mg/d) in adults from apparent bread consumption according to different levels (P20, 50 and 95) and children consumption (8-13 years) considering socioeconomic status (SES), bread/g/d intake (P20, 50 and 75) and regulated level of four fortifcation (2.2 mg FA/100 g). Daily Dietary Folate Equivalent (DFE) consumption was estimated from serum folate in adults and elderly people (both sexes). We calculated the percentage of population with FA intakes over the estimated average requirement (EAR) and maximum level (UL) pre and post-fortifcation. Results: There is great variability in FA four: 10-20 percent samples without FA and 10-30 percent with levels > 2.2 mg/100 g. Adult daily consumption (2-4 day/loaves) could determine FA intakes close to UL. Children daily bread consumption (low socioeconomic level) > P75 have intakes close to UL. Post-fortifcation estimated daily DFE from serum folate in women, men and elderly people show: 99 percent of women, 100 percent of men and the elderly people have intakes higher than EAR. Additionally 2.3 percent of women and 6 percent of men would have intakes near the UL. Conclusions: The four FA levels and serum folate levels in some populations show increased FA post-fortifcation intakes, which could lead to greater risk suggesting a revision of the fortifcation level.

Folates and vitamin B12 status in patients with multiple myeloma.

Serum and red cell folate, serum Vitamin B12 and Vitamin B12 binding proteins were multiple myeloma. Half of these patients were anaemic with a predominant macrocytic type. Altogether 17 and 33 percent had low serum and red cell folate levels, respectively. Low serum Vitamin B12 level was found in one third of these patients. Both TCI and TCIII increased while TCII decreased, while was different from the previous report of extremely elevated TCII in some patients with multiple myeloma. There was a direct relationship between serum Vitamin B12 and saturation of TCI. These finding indicated that folic acid and Vitamin B12 deficiency were relatively common in patients with multiple myeloma. The possible mechanisms of these vitamins deficiency were discussed in this paper.

Serum and red cell folates in patients with leukaemia and lymphomas.

It has been suggested that leukaemia and lymphomas may cause folic acid depletion. The supporting evidence were obtained from urinary excretion of folic acid, rate of clearance of injected folic acid from the plasma and serum folic acid assays. However, no data red cell folate levels has been reported, the present study was there fore undertaken. Serum and red cell folate levels were determined in 144 patients with acute lymphocytic leukaemia, acute myeloblastic leukaemia, chronic myelocytic leukaemia, Hodgkin’s disease and non-Hodgkin’s lymphoma. The mean serum and red cell folate values in these patients were significantly lower than those of normal subjects. About 21.5% and 28.5% of these patients had serum folate levels lower than 3 ng/ml and red cell folate levels lower than 100 ng/ml, respectively. The elevated MCV and MCH values were also found in 42% and 30% of the patient’s groups. These findings indicated that some patients with leukaemia and lymphomas had macrocytiosis which was highly due to folic acid deficiency. The deficiency may be caused by various factors such as increased requirement due to an elevated production of leukaemic cells with higher folic acid content than normal leucocytes, poor dietary folic acid intake due to loss of appetite and intestinal malabsorption of lolic acid.