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p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in ~50% of all human cancers. In its canonical role, p16 inhibits the G1-S phase cell cycle progression through suppression of cyclin dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. Whether other nucleotide metabolic genes and pathways are affected by p16/CDKN2A loss and if these can be specifically targeted in p16/CDKN2A-low tumors has not been previously explored. Using CRISPR KO libraries in multiple isogenic human and mouse melanoma cell lines, we determined that many nucleotide metabolism genes are negatively enriched in p16/CDKN2A knockdown cells compared to controls. Indeed, many of the genes that are required for survival in the context of low p16/CDKN2A expression based on our CRISPR screens are upregulated in p16 knockdown melanoma cells and those with endogenously low CDKN2A expression. We determined that cells with low p16/Cdkn2a expression are sensitive to multiple inhibitors of de novo purine synthesis, including anti-folates. Tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2A-low tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.
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PURPOSE: To investigate certain aspects of hydrocephalus in patients with myelomeningocele. METHODS: We retrospectively analyzed data of 1050 patients with myelomeningocele who underwent surgical treatment between June 1991 and June 2021. These patients were divided into three groups: group 1 consisted of patients who underwent surgery after the first 6 h of life, group 2 consisted of patients who underwent surgery within the first 6 h, and group 3 consisted of patients who underwent surgery during the fetal period and before 26 6/7 weeks of gestation. RESULTS: There were 125, 590, and 335 patients in groups 1, 2, and 3, respectively. In groups 1 and 2, 593 (83%) patients developed hydrocephalus after birth and required ventriculoperitoneal shunt placement in the maternity ward, mainly within the first 4 days of life. In contrast, in group 3, 24 (7.2%) patients required surgery to treat hydrocephalus after birth. Hydrocephalus was the primary cause of mortality in groups 1 and 2, with mortality rates of 35% and 10%, respectively. In group 3, the mortality rate was 0.8% and was not related to hydrocephalus. CONCLUSION: The onset of hydrocephalus is directly related to myelomeningocele closure in neurosurgery.
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Hidrocefalia , Meningomielocele , Feminino , Humanos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Meningomielocele/complicações , Meningomielocele/cirurgia , Procedimentos Neurocirúrgicos , Gravidez , Estudos Retrospectivos , Derivação VentriculoperitonealRESUMO
The whole genome of Weissella cibaria strain UTNGt21O isolated from wild fruits of Solanum quitoense (naranjilla) shrub was sequenced and annotated. The similarity proportions based on the genus level, as a result of the best hits for the entire contig, were 54.84% with Weissella, 6.45% with Leuconostoc, 3.23% with Lactococcus, and 35.48% no match. The closest genome was W. cibaria SP7 (GCF_004521965.1) with 86.21% average nucleotide identity (ANI) and 3.2% alignment coverage. The genome contains 1,867 protein-coding genes, among which 1,620 were assigned with the EggNOG database. On the basis of the results, 438 proteins were classified with unknown function from which 247 new hypothetical proteins have no match in the nucleotide Basic Local Alignment Search Tool (BLASTN) database. It also contains 78 tRNAs, six copies of 5S rRNA, one copy of 16S rRNA, one copy of 23S rRNA, and one copy of tmRNA. The W. cibaria UTNGt21O strain harbors several genes responsible for carbohydrate metabolism, cellular process, general stress responses, cofactors, and vitamins, conferring probiotic features. A pangenome analysis indicated the presence of various strain-specific genes encoded for proteins responsible for the defense mechanisms as well as gene encoded for enzymes with biotechnological value, such as penicillin acylase and folates; thus, W. cibaria exhibited high genetic diversity. The genome characterization indicated the presence of a putative CRISPR-Cas array and five prophage regions and the absence of acquired antibiotic resistance genes, virulence, and pathogenic factors; thus, UTNGt21O might be considered a safe strain. Besides, the interaction between the peptide extracts from UTNGt21O and Staphylococcus aureus results in cell death caused by the target cell integrity loss and the release of aromatic molecules from the cytoplasm. The results indicated that W. cibaria UTNGt21O can be considered a beneficial strain to be further exploited for developing novel antimicrobials and probiotic products with improved technological characteristics.
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Lactic acid bacteria (LAB), widely used as starter cultures for the fermentation of a large variety of food, can improve the safety, shelf life, nutritional value and overall quality of the fermented products. In this regard, the selection of strains delivering health-promoting compounds is now the main objective of many researchers. Although most LAB are auxotrophic for several vitamins, it is known that certain strains have the capability to synthesize B-group vitamins. This is an important property since humans cannot synthesize most vitamins, and these could be obtained by consuming LAB fermented foods. This review discusses the use of LAB as an alternative to fortification by the chemical synthesis to increase riboflavin and folate concentrations in food. Moreover, it provides an overview of the recent applications of vitamin-producing LAB with anti-inflammatory/antioxidant activities against gastrointestinal tract inflammation. This review shows the potential uses of riboflavin and folates producing LAB for the biofortification of food, as therapeutics against intestinal pathologies and to complement anti-inflammatory/anti-neoplastic treatments.
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Ácido Fólico/biossíntese , Alimentos Fortificados , Doenças Inflamatórias Intestinais/terapia , Lactobacillales/metabolismo , Mucosite/terapia , Riboflavina/biossíntese , Animais , Antioxidantes/análise , Fermentação , Alimentos Fermentados , Ácido Fólico/análise , Humanos , Lactobacillales/isolamento & purificação , Riboflavina/análise , Vitaminas/análise , Vitaminas/biossínteseRESUMO
INTRODUCTION: Folates are essential nutrients for fetal development and pregnancy outcomes; they are transported to the fetus during gestation through specific folate transporters located in the placenta. In preterm newborns, we previously showed a lower placental mRNA expression of FOLR1 along with higher folate and lower vitamin B12 cord blood levels. Thereby we aimed to explore FOLR1 methylation in placentas of preterm newborns and hypothesized an increased FOLR1 methylation associated with cord blood folates and vitamin B12 concentrations. METHODS: FOLR1 methylation and mRNA were determined by methylation sensitive - high resolution melting (MS-HRM) and by real-time PCR respectively, in two placental sides of placental tissues: maternal (basal, BP) and fetal plates (chorionic, CP) of moderate preterm infants (32-36 gestational age) and term birth (37-41 gestational weeks). Folates and vitamin B12 were determined by electrochemiluminescence in umbilical cord blood samples from term and preterm newborns. RESULTS: We found that in preterm newborns, FOLR1 mRNA was lower in both plates of placenta compared with term newborns (p < 0,05) and was negatively associated with methylation of FOLR1 in CP. Preterm newborns presented higher folate and lower vitB12 concentrations in cord blood which correlated with increased placental FOLR1 methylation. DISCUSSION: In preterm newborns, placental FOLR1 expression is regulated by epigenetic mechanisms and presumably by maternal concentrations of folate and vitamin B12.
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Epigênese Genética/genética , Receptor 1 de Folato/genética , Recém-Nascido Prematuro , Placenta/metabolismo , Adulto , Metilação de DNA , Feminino , Sangue Fetal/química , Ácido Fólico/sangue , Regulação da Expressão Gênica no Desenvolvimento , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro/sangue , Masculino , Placenta/química , Gravidez , RNA Mensageiro/análise , Vitamina B 12/sangueRESUMO
Methotrexate is used to treat autoimmune and oncologic diseases in children with Down syndrome. However, increased methotrexate-related toxicity is reported in this population. We evaluated differences in the concentrations and distribution of erythrocyte folates in children with Down syndrome as a potential basis for this enhanced toxicity.
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Síndrome de Down/sangue , Ácido Fólico/sangue , Homeostase , Pré-Escolar , Eritrócitos/metabolismo , Ácido Fólico/administração & dosagem , Humanos , Metotrexato/farmacologia , Metotrexato/toxicidade , Projetos Piloto , Estudos de Amostragem , Complexo Vitamínico B/administração & dosagemRESUMO
Micronutrients (folates and vitamin B12) and long chain polyunsaturated fatty acids (LC-PUFAs) are linked through the one carbon cycle. We studied the effects of pre and postnatal high FA/low B12 diets (HFLB12) on hepatic fatty acid metabolism. Pregnant C57BL/6 mice were divided in two groups: control (2 mg folic acid: FA/25 µg vitamin B12/Kg food) and HFLB12 diets (8 mg FA/5 µg vitamin B12/Kg food). Offspring continued on the same diets until 60 days old. We determined hepatic fatty acid profile in dams and offspring and the expression of PPARα, Cpt-1, Acox-1 and Fas and the enzymatic activity of desaturases, all involved in lipid metabolism. In liver of dams, the HFHB12 diet decreased total fatty acids and desaturase activities; in offspring, effects were opposite, being more noticeable in females. Prenatal and postnatal unbalanced folic acid/B12 diets play a crucial role in regulating genes and enzymes involved in lipid metabolism in liver of dams and their offspring in adulthood.
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Ácidos Graxos/metabolismo , Ácido Fólico/administração & dosagem , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/química , Vitamina B 12/administração & dosagem , Acil-CoA Oxidase/metabolismo , Animais , Animais Recém-Nascidos , Ácidos Graxos Dessaturases/metabolismo , Feminino , Ácido Fólico/farmacocinética , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/metabolismo , Cuidado Pós-Natal , Gravidez , Vitamina B 12/farmacocinética , Receptor fasRESUMO
OBJECTIVE: To assess the association between polymorphic variants from SHMT1 and MTHFS genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Chilean population. SUBJECTS AND METHODS: In a sample of 139 Chilean NSCL/P cases and 278 controls, we obtained the genotypes for nine variants of SHMT1 and MTHFS and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models. RESULTS: After correction for multiple comparisons, only the variant rs1979277 (G > A; p.Leu474Phe) from SHMT1 showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42-0.86; p = .0054, q = 0.0488) and dominant models (OR 0.48; 95% CI 0.29-0.75; p = .0009; q = 0.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity. CONCLUSIONS: Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and has a higher frequency in controls than in NSCL/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.
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Fenda Labial/genética , Fissura Palatina/genética , Glicina Hidroximetiltransferase/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Chile , Feminino , Genótipo , Humanos , MasculinoRESUMO
Lactic acid bacteria (LAB) are indigenous microorganisms that have been involved in food fermentations throughout history to preserve food and also to give special characteristics to them. The traditional fermented foods that are still being elaborated in indigenous populations around the world are a potential source of LAB with important biotechnological properties and/or beneficial to health. In a previous work, LAB biodiversity associated with chicha, a traditional maize-based fermented beverage from Northwestern Argentina, was studied, both by culture dependent and independent methods. From that study, 392 isolates were recovered, mostly members of Lactobacillus and Leuconostoc. Biotechnological characterization of representative isolates led to the selection of five strains belonging to the species Lactobacillus plantarum for their ability to produce vitamin B2 (riboflavin) and vitamin B9 (folates), their antimicrobial properties and antibiotics susceptibility. In this work, we present the Whole Genome Sequences (WGS) of these five strains that have been deposited in the Spanish Type Culture Collection: M5MA1 (= CECT 8962), M9MM1 (= CECT 8963), M9MM4 (= CECT 8964), M9MG6 (= CECT 8965), and M9Y2 (= CECT 8966), and a detailed description of their characterization, through a genomic approach, analyzing the genes responsible for these biotechnological properties, making a comparative study of the five genomes and reporting the aspects related to food safety, in accordance with the recommendations of the European Food Safety Authority (EFSA FEEDAP Panel, 2018) aiming at their use in the design of functional foods. The analysis unveiled, for the five strains, the complete set of genes for folate and riboflavin biosynthesis, the absence of pathogenic factors, the presence of CRISPR and cas genes, phage sequences, insertion elements and an aminoglycosides resistance gene, aadA, whose resistance could not be proved phenotypically in any strain. Genomic comparisons showed that strain CECT 8962 was significantly different in terms of genetic content and allowed the identification of carbohydrates metabolism and membrane transport related genes as the main components of the unique and accessory genome.
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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.
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Humanos , Feminino , Gravidez/efeitos dos fármacos , Ácido Fólico/administração & dosagem , Ácido Fólico/efeitos adversos , Ácido Fólico/genética , Placentação/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Ácido Fólico/uso terapêutico , Ácido Fólico/farmacologiaRESUMO
It is known that certain lactic acid bacterial (LAB) strains can produce folates, a B-group vitamin that cannot be synthesized by humans and must be exogenously obtained. The aim of this study was to select folate-producing LAB and evaluate their probiotic characteristics in order to obtain a tuber-based food with elevated folate content. Several LAB strains were isolated from a traditional Andean fermented potato product tocosh and cultured in folate-free culture medium. Five folate-producing strains (29-138â¯ng/mL) were selected to ferment three Andean tubers (potato S. tuberosum spp. andigena, oca Oxalis tuberosa and papalisa Ullucus tuberosus). Sterile purees were inoculated and samples were collected at 0, 6 and 24â¯h of fermentation and after 28â¯days of cold storage. Cell growth, pH and total folate were determined. All selected strains were able to grow and produce folates in the substrates and two Lactobacillus sakei strains, CRL 2209 and CRL 2210, produced the highest folate concentrations (730-1484â¯ng/g after 24â¯h fermentation). These strains were selected to ferment potato substrates supplemented with amaranth (Amaranthus caudathus) and chia (Salvia hispanica) flour to increase the nutritional value. This addition increased folate synthesis in 89-95%. Furthermore, the ability to survive under simulated gastrointestinal conditions was evaluated and cell counts of the 5 strains remained above the recommended for a probiotic candidate (8.0 logâ¯CFU/mL). In conclusion, the selected LAB could be considered potentially probiotic strains and could be used to produce novel tuber based products with elevated folate concentrations. These products could also be used as novel food matrixes for the delivery of probiotic microorganisms.
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Ácido Fólico/análise , Lactobacillales/metabolismo , Probióticos/metabolismo , Solanum tuberosum/metabolismo , Solanum tuberosum/microbiologia , Fermentação , Ácido Fólico/metabolismo , Tecnologia de Alimentos , Modelos Biológicos , TubérculosRESUMO
Folic acid, or pteroyllglutamic acid (PteGlu) is a conjugated pterin derivative that is used in dietary supplementation as a source of folates, a group of compounds essential for a variety of physiological functions in humans. Photochemistry of PteGlu is important because folates are not synthesized by mammals, undergo photodegradation and their deficiency is related to many diseases. We have demonstrated that usual commercial PteGlu is unpurified with the unconjugated oxidized pterins 6formylpterin (Fop) and 6carboxypterin (Cap). These compounds are in such low amounts that a normal chromatographic control would not detect any pterinic contamination. However, the fluorescence of PteGlu solutions is due to the emission of Fop and Cap and the contribution of the PteGlu emission, much lower, is negligible. This is because the fluorescence quantum yield (ΦF) of PteGlu is extremely weak compared to the ΦF of Fop and Cap. Likewise, the PteGlu photodegradation upon UV-A radiation is an oxidation photosensitized by oxidized unconjugated pterins present in the solution, and not a process initiated by the direct absorption of photons by PteGlu. In brief, the fluorescence and photochemical properties of PteGlu solutions, prepared using commercially available solids, are due to their unconjugated pterins impurities and not to PteGlu itself. This fact calls into question many reported studies on fluorescence and photooxidation of this compound.
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Ácido Fólico/química , Pterinas/química , Cromatografia Líquida de Alta Pressão , Ácido Fólico/análise , Espectrometria de Massas , Oxirredução , Fotólise/efeitos da radiação , Pterinas/análise , Espectrometria de Fluorescência , Raios UltravioletaRESUMO
BACKGROUND: Changes in DNA methylation, one of the most studied epigenetic mechanisms, are considered an initial marker for early cancer detection. We evaluated how availability of dietary factors (folates and vitamin B12) involved in one-carbon metabolism may contribute to DNA methylation changes of cancer-related genes in human subjects. METHODS: We studied, by pyrosequencing, the methylation of tumor suppressor gene p16, DNA repair genes MLH1 and MGMT, and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals (n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years. RESULTS: We found that serum folate and to a lesser extent, vitamin B12 concentrations, were significantly correlated with DNA methylation of p16, MLH1, and MGMT, but not with LINE-1. High serum folate concentrations (>45.3 nmol/L) were present in 31.1% of the participants. Although the methylated fraction of CpG sites in p16, MLH1, and MGMT was low (1.17-3.8%), high folate concentrations were significantly associated with methylation at the 3rd tertile of specific CpG sites in all genes with OR between 1.97 and 4.17. CONCLUSIONS: This study shows that a public policy, like food fortification with FA that increases circulating serum folate levels, could affect methylation levels of specific genes linked to cancer risk. Our present results deserve additional studies to clarify the real impact of high FA levels for risk of cancer in a whole population chronically exposed to a fortified food such as wheat flour. TRIAL REGISTRATION: ISRCTN 48153354 and ISRCTN 02694183.
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Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Ácido Fólico/sangue , Proteína 1 Homóloga a MutL/genética , Proteínas Supressoras de Tumor/genética , Idoso , Idoso de 80 Anos ou mais , Chile , Estudos Transversais , Metilação de DNA/efeitos dos fármacos , Epigênese Genética , Feminino , Ácido Fólico/efeitos adversos , Ácido Fólico/farmacologia , Humanos , Elementos Nucleotídeos Longos e Dispersos , Masculino , Análise de Sequência de DNA , Vitamina B 12/sangueRESUMO
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.
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Humanos , Feminino , Gravidez , Recém-Nascido , Alimentos Fortificados , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Cuidado Pré-Natal/métodos , Vitamina B 12/administração & dosagem , Triticum/química , Pão , DietaRESUMO
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.
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Humanos , Pão , Alimentos Fortificados , Micronutrientes , Farinha , Ácido Fólico , Ferro , Estado Nutricional , Recomendações NutricionaisRESUMO
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.
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Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Gravidez , Adulto Jovem , Ácido Fólico/administração & dosagem , Recomendações Nutricionais , Fatores Etários , Peso Corporal , Ingestão de Energia , Valores de Referência , Fatores Sexuais , VenezuelaRESUMO
Hereditary folate malabsorption (OMIM 229050) is a rare autosomal recessive disorder caused by loss-of-function mutations in the proton-coupled folate transporter gene (pcft/SLC46A1) resulting in impaired folate transport across the intestine and into the central nervous system. We report a novel, homozygous, deletion mutation in a child of Nicaraguan descent in exon 2 (c.558-588 del, ss778190447) at amino acid position I188 resulting in a frameshift with a premature stop.
Assuntos
Ácido Fólico/metabolismo , Síndromes de Malabsorção/genética , Transportador de Folato Acoplado a Próton/genética , Deleção de Sequência , Humanos , Lactente , Masculino , NicaráguaRESUMO
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.
Assuntos
Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Farinha/análise , Ácido Fólico/efeitos adversos , Alimentos Fortificados/efeitos adversos , Necessidades Nutricionais , Estado Nutricional/fisiologia , Complexo Vitamínico B/efeitos adversos , Pão/análise , Chile , Inquéritos sobre Dietas/métodos , Inquéritos sobre Dietas/estatística & dados numéricos , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Alimentos Fortificados/análise , Fatores de Risco , Fatores Socioeconômicos , Fatores de Tempo , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangueRESUMO
Folates are the generic term used to designate the class of compounds having a chemical structure and nutritional activity similar to that of folic acid (pteroyl-L-glutamic acid), while folic acid is a synthetic fully oxidized folic acid (FA) form added into foodstuffs and pharmaceutical preparations. Folate deficiency is a well-known risk factor for causing neural tube disorders, cardiovascular diseases, Alzheimer disease, some types of cancer, among others diseases. In Brazil, since June 2004 the Agency for Public Health Surveillance (ANVISA) has established the mandatory enrichment of wheat and corn flours with FA and iron. The present review describes some general approaches on folic acid and folates, including physical-chemical characteristics, bioavailability, biochemistry functions, sources, food fortification, and analytical methodology for performing their quantification in food.
Folato é o termo genérico utilizado para os compostos que apresentam atividade vitamínica similar a do ácido pteroilglutâmico e é usado para descrever as formas da vitamina que ocorrem naturalmente nos alimentos, enquanto que o termo ácido fólico representa a forma sintética encontrada em suplemento medicamentoso e em alimento enriquecido. O folato está diretamente relacionado com a prevenção de defeitos do tubo neural, além da prevenção de outras doenças como problemas cardiovasculares, doença de Alzheimer, alguns tipos de cânceres, entre outras. No Brasil, o Ministério da Saúde determinou que a partir de junho de 2004, todas as farinhas de trigo e de milho fabricadas no país ou importadas devem ser enriquecidas com ferro e ácido fólico. A presente revisão faz uma abordagem geral sobre o ácido fólico e folatos, em que é feita a discussão sobre as características físico-químicas, biodisponibilidade, funções bioquímicas, fontes, uso na fortificação de alimentos e metodologia analítica para sua quantificação em alimentos.