RESUMO
Exposure to arsenic (As) is a major public health concern globally. Inorganic As (InAs) undergoes hepatic methylation to form monomethyl (MMAs)- and dimethyl (DMAs)-arsenical species, facilitating urinary As elimination. MMAsIII is considerably more toxic than either InAsIII or DMAsV, and a higher proportion of MMAs in urine has been associated with risk for a wide range of adverse health outcomes. Efficiency of As methylation differs substantially between species, between individuals, and across populations. One-carbon metabolism (OCM) is a biochemical pathway that provides methyl groups for the methylation of As, and is influenced by folate and other micronutrients, such as vitamin B12, choline, betaine and creatine. A growing body of evidence has demonstrated that OCM-related micronutrients play a critical role in As methylation. This review will summarize observational epidemiological studies, interventions, and relevant experimental evidence examining the role that OCM-related micronutrients have on As methylation, toxicity of As, and risk for associated adverse health-related outcomes. There is fairly robust evidence supporting the impact of folate on As methylation, and some evidence from case-control studies indicating that folate nutritional status influences risk for As-induced skin lesions and bladder cancer. However, the potential for folate to be protective for other As-related health outcomes, and the potential beneficial effects of other OCM-related micronutrients on As methylation and risk for health outcomes are less well studied and warrant additional research.
Assuntos
Arsênio/metabolismo , Carbono/metabolismo , Exposição Ambiental/efeitos adversos , Estado Nutricional/fisiologia , Animais , Arsênio/toxicidade , Água Potável/efeitos adversos , Água Potável/metabolismo , Feminino , Ácido Fólico/administração & dosagem , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/epidemiologia , Deficiência de Ácido Fólico/metabolismo , Alimentos/toxicidade , Humanos , Metilação , Estado Nutricional/efeitos dos fármacos , Estudos Observacionais como Assunto/métodos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismoRESUMO
BACKGROUND: Folate plays an essential role in the prevention of neural tube defects, yet little is known about the folate status of women of reproductive age or to what degree the general population is aware of the importance of folate in early-life development. We aimed to determine folate status in women of reproductive age and pregnant women in Switzerland, and to assess folate awareness in the Swiss population. METHODS: In a convenience sample of 171 women of reproductive age and 177 pregnant women throughout Switzerland, we measured red blood cell (RBC) folate concentration. In a second convenience sample (n = 784, men and women) we assessed folate knowledge with an online survey. RESULTS: RBC folate concentration (median interquartile range) was 442 (366, 564) nmol/L in women of reproductive age and 873 (677, 1177) nmol/L in pregnant women. Folate deficiency (RBC folate <340 nmol/L) was found in 19.9% of women of reproductive age and 2.8% of pregnant women, while 91.8% of women of reproductive age and 52.0% of pregnant women showed folate concentrations indicating an elevated risk of neural tube defects (RBC folate <906 nmol/L). The online survey showed that a high proportion (≥88%) of participants were aware of folate's role in neural tube defect (NTD) prevention and fetal development, yet knowledge about dietary sources and national recommendations of folate supplementation when planning pregnancy were limited. CONCLUSION: The high prevalence of folate inadequacy in Swiss women suggests an elevated risk of neural tube defects and calls for urgent measures to increase folate intakes.
Assuntos
Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/sangue , Ácido Fólico/uso terapêutico , Saúde Pública , Adulto , Suplementos Nutricionais , Feminino , Deficiência de Ácido Fólico/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Defeitos do Tubo Neural/prevenção & controle , Terapia Nutricional , Gravidez , Prevalência , Inquéritos e Questionários , Suíça , Adulto JovemRESUMO
Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.
Assuntos
Cognição , Disfunção Cognitiva/sangue , Disfunção Cognitiva/psicologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/psicologia , Ácido Fólico/administração & dosagem , Ácido Fólico/farmacologia , Homocisteína/sangue , Idoso , Idoso de 80 Anos ou mais , Atrofia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/dietoterapia , Hipocampo/patologia , Humanos , Masculino , Testes de Estado Mental e Demência , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to determine how folate and iron deficiency, and the subsequent supplementation of rats' diet with these nutrients, affects Slc19a1and Tfr2 gene expression and the metabolism of folate and iron. After 28 days of iron-folate deficiency 150 female rats were randomized into five experimental groups receiving a diet deficient in folic acid (FA), an iron-supplemented diet (DFE), an iron-deficient diet supplemented with FA (DFOL), a diet supplemented with iron and FA (FEFOL), and a diet deficient in iron and FA (D); there was also a control group (C). Samples were collected on days 2, 10, and 21 of the experiment. After two days of supplementation, Tfr2 mRNA level were 78 % lower in the DFE group than in the C group (pâ¯<â¯0.05); after 10 days, TfR2 levels in the FEFOL group were 82 % lower than in the C and the DFE group (pâ¯<â¯0.01). However, we did not find any differences at the protein level at any time-point. Hepcidin concentrations were higher in the DFE and the DFEFOL groups than in the D group after 21 days of supplementation (pâ¯<â¯0.01). Transcript and protein abundance of Slc19a1 gene did not differ between the groups at any time-point. Iron metabolism was affected by iron and folate deficiency and subsequent supplementation with these micronutrients, but TFR2 protein was not involved in the regulatory mechanism. Hepcidin expression can be are upregulated after 21 days of supplementation with 150â¯mg of iron/ kg of diet.
Assuntos
Deficiência de Ácido Fólico/metabolismo , Deficiências de Ferro , Fígado/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Antígenos de Histocompatibilidade Menor/metabolismo , Receptores da Transferrina/metabolismo , Proteína Carregadora de Folato Reduzido/metabolismo , Animais , Transporte Biológico , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Ácido Fólico/metabolismo , Ácido Fólico/farmacologia , Deficiência de Ácido Fólico/dietoterapia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepcidinas/metabolismo , Ferro/metabolismo , Ferro/farmacologia , Fígado/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Antígenos de Histocompatibilidade Menor/genética , Ratos Wistar , Receptores da Transferrina/genética , Proteína Carregadora de Folato Reduzido/genéticaRESUMO
Folate is an essential B vitamin and its deficiency is common in many parts of the world. Natural folate produced by microorganisms may be an alternative to chemically synthesized folic acid (FA) as a dietary supplement. Previously, two lactic acid bacteria (LAB) strains, a high folate-producing Lactococcus lactis subsp. lactis KLDS4.0325 and a weak folate-producing Lactococcus lactis subsp. lactis KLDS4.0613, were identified. The aim of this study was to evaluate the effect of milk fermented with L. lactis KLDS4.0325 (folate-enriched fermented milk, FEFM) in alleviating folate deficiency status using murine folate deficiency models. In addition, the link between gut microbiota diversity and folate levels in mice was investigated. Results showed that FEFM increased FA and 5-methyltetrahydrofolate (5-MTHF) concentrations in the whole blood and liver, and decreased plasma homocysteine (Hcy) levels. 16S rDNA sequence analysis also revealed that the supplementation of FEFM (containing 0.6 µg mL-1 folate) and 0.6 µg d-1 FA (FEFM + LFA) significantly improved the poor status of the gut microbiota composition caused by folate deficiency, and the effect was better than that with 1.2 µg d-1 FA (HFA) supplementation. Our findings show that FEFM can be used as a folate-fortified food to alleviate folate deficiency effectively. In addition, it may be considered as a partial or total replacement for synthetic FA.
Assuntos
Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/sangue , Lactococcus lactis , Leite/química , Animais , Modelos Animais de Doenças , Feminino , Fermentação , Deficiência de Ácido Fólico/sangue , Alimento Funcional , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Folic acid (FA) is often consumed as a food supplement and can be found in fortified staple foods in various western countries. Even though FA supplementation during pregnancy is known to prevent severe congenital anomalies in the developing child (e.g., neural tube defects), much less is known about its influence on cognition and neurological functioning. In this review, we address the advances in this field and situate how folate intake during pregnancy, postnatal life, adulthood and in the elderly affects cognition. In addition, an association between folate status and ageing, dementia and other neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis is discussed. While its role in the incidence and severity of these diseases is becoming apparent, the underlying action of folates and related metabolites remains elusive. Finally, the potential of FA as a nutraceutical has been proposed, although the efficacy will highly depend on the interplay with other micronutrients, the disease stage and the duration of supplementation. Hence, the lack of consistent data urges for more animal studies and (pre)clinical trials in humans to ascertain a potential beneficial role for folates in the treatment or amelioration of cognitive decline and ageing-related disorders.
Assuntos
Envelhecimento/metabolismo , Cognição , Ácido Fólico/metabolismo , Doenças Neurodegenerativas/metabolismo , Envelhecimento/efeitos dos fármacos , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/complicações , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/tratamento farmacológico , Deficiência de Ácido Fólico/metabolismo , Humanos , Doenças Neurodegenerativas/complicações , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
BACKGROUND: Within Cambodia, micronutrient deficiencies continue to be prevalent in vulnerable groups, such as women and children. Fortification of staple foods such as rice could be a promising strategy for Cambodia to improve micronutrient status. OBJECTIVE: Our objective was to investigate the impact of multiple-micronutrient fortified rice (MMFR), distributed through a World Food Program school-meals program (WFP-SMP) on serum zinc concentrations and folate status in a double-blind, cluster-randomized, placebo-controlled trial. METHODS: Sixteen schools were randomly assigned to receive one of three different types of extruded-fortified rice (UltraRice Original (URO), UltraRice New (URN), or NutriRice) or unfortified rice (placebo) six days a week for six months. A total of 1950 schoolchildren (6-16 years old) participated in the study. Serum zinc (all groups) and folate (only in NutriRice and placebo group) concentrations were assessed from morning non-fasting antecubital blood samples and were measured at three time points (baseline and after three and six months). RESULTS: After six months of intervention, serum zinc concentrations were significantly increased in all fortified rice group compared to placebo and baseline (0.98, 0.85 and 1.40 µmol/L for URO, URN and NutriRice, respectively) (interaction effect: p < 0.001 for all). Children in the intervention groups had a risk of zinc deficiencies of around one third (0.35, 039, and 0.28 for URO, URN, and NutriRice, respectively) compared to the placebo (p < 0.001 for all). The children receiving NutriRice had higher serum folate concentrations at endline compared to children receiving normal rice (+ 2.25 ng/mL, p = 0.007). CONCLUSIONS: This study showed that the high prevalence of zinc and folate deficiency in Cambodia can be improved through the provision of MMFR. As rice is the staple diet for Cambodia, MMFR should be considered to be included in the school meal program and possibilities should be explored to introduce MMFR to the general population.
Assuntos
Fenômenos Fisiológicos da Nutrição do Adolescente , Fenômenos Fisiológicos da Nutrição Infantil , Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/sangue , Alimentos Fortificados/análise , Estado Nutricional , Valor Nutritivo , Oryza/química , Zinco/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Camboja , Criança , Método Duplo-Cego , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/diagnóstico , Deficiência de Ácido Fólico/fisiopatologia , Humanos , Masculino , Recomendações Nutricionais , Fatores de Tempo , Zinco/deficiênciaRESUMO
OBJECTIVE: To investigate the prevalence of folic acid deficiency in Queensland-wide data of routine laboratory measurements, especially in high-risk sub-populations. DESIGN: Secondary health data analysis. SETTING: Analysis of routine folic acid tests conducted by Pathology Queensland (AUSLAB). PARTICIPANTS: Female and male persons aged 0-117 years with routine folic acid testing between 1 January 2004 and 31 December 2015. If repeat tests on the same person were conducted, only the initial test was analysed (n 291 908). RESULTS: Overall the prevalence of folic acid deficiency declined from 7·5 % before (2004-2008) to 1·1 % after mandatory folic acid fortification (2010-2015; P < 0·001) reflecting a relative reduction of 85 %. Levels of erythrocyte folate increased significantly from a median (interquartile range) of 820 (580-1180) nmol/l in 2008 before fortification to 1020 (780-1350) nmol/l in 2010 (P < 0·001) after fortification. The prevalence of folic acid deficiency in the Indigenous population (14 792 samples) declined by 93 % (17·4 v. 1·3 %; P < 0·001); and by 84 % in non-Indigenous residents (7·0 v. 1·1 %; P < 0·001). In a logistic regression model the observed decrease of folic acid deficiency between 2008 and 2010 was found independent of gender, age and ethnicity (ORcrude = 0·20; 95 % CI 0·18, 0·23; P < 0·001; ORadjusted = 0·21; 95 % CI 0·18, 0·23; P < 0·001). CONCLUSIONS: While voluntary folic acid fortification, introduced in 1995, failed especially in high-risk subgroups, the 2009 mandatory folic acid fortification programme coincided with a substantial decrease of folic acid deficiency in the entire population.
Assuntos
Deficiência de Ácido Fólico , Ácido Fólico , Alimentos Fortificados , Política Nutricional/legislação & jurisprudência , Adulto , Idoso , Estudos de Coortes , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/epidemiologia , Humanos , Masculino , Programas Obrigatórios , Pessoa de Meia-Idade , Havaiano Nativo ou Outro Ilhéu do Pacífico/estatística & dados numéricos , Queensland/epidemiologiaAssuntos
Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Deficiência de Vitamina B 12/prevenção & controle , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/prevenção & controle , Humanos , Fatores de Risco , Vitamina B 12/administração & dosagem , Deficiência de Vitamina B 12/dietoterapia , Complexo Vitamínico B/administração & dosagemRESUMO
In this paper we review the evidence basis for prevention of folic acid-sensitive neural tube defects (NTDs) through public health interventions in women of reproductive age (WRA), the proven vehicles for delivery of folic acid, and what is needed to effectively scale these, and provide a snapshot of potential innovations that require future research. Our primary focus is on the global situation affecting large-scale food fortification (LSFF) with folic acid, in particular the fortification of wheat flour and maize meal. Our overarching conclusion is that folic acid fortification is an evidence-based intervention that reduces the prevalence of NTDs, and that LSFF with folic acid is underutilized. Thus, food fortification with folic acid should be a component of most national public health strategies, in particular where folate status is insufficient and a fortifiable food vehicle, processed by a centralized industry, is consumed regularly by WRA. The evidence shows that there is still much work needed (1) to build the enabling environment and expand programs where there is currently no legislation, (2) to improve the low quality of delivery of existing programs, and (3) to measure and sustain programs by generating new coverage data and demonstrating evidence of impact in low- and middle-income countries.
Assuntos
Ácido Fólico/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Suplementos Nutricionais , Medicina Baseada em Evidências , Feminino , Deficiência de Ácido Fólico/dietoterapia , Alimentos Fortificados , Humanos , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Gravidez , Saúde PúblicaRESUMO
Although folic acid (FA) supplementation is known to influence numerous physiological functions, especially during pregnancy, little is known about its direct effects on the mothers' health. However, this vitamin is essential for the health of the mother and for the normal growth and development of the fetus. Thus, the aim of this study was (1) to evaluate the cognitive effects and biochemical markers produced by the AIN-93 diet (control), the AIN-93 diet supplemented with different doses of FA (5, 10, and 50 mg/kg), and a FA-deficient diet during pregnancy and lactation in female mother rats (dams) and (2) to evaluate the effect of maternal diets on inflammatory parameters in the adult offspring which were subjected to an animal model of schizophrenia (SZ) induced by ketamine (Ket). Our study demonstrated through the Y-maze test that rats subjected to the FA-deficient diet showed significant deficits in spatial memory, while animals supplemented with FA (5 and 10 mg/kg) showed no deficit in spatial memory. Our results also suggest that the rats subjected to the FA-deficient diet had increased levels of carbonylated proteins in the frontal cortex and hippocampus and also increased plasma levels of homocysteine (Hcy). Folate was able to prevent cognitive impairments in the rats supplemented with FA (5 and 10 mg/kg), data which may be attributed to the antioxidant effect of the vitamin. Moreover, FA prevented protein damage and elevations in Hcy levels in the rats subjected to different doses of this vitamin (5, 10, and 50 mg/kg). We verified a significant increase of the anti-inflammatory cytokine (interleukin-4 (IL-4)) and a reduction in the plasma levels of proinflammatory cytokines (interleukin-6 (IL-6)) and TNF-α) in the dams that were subjected to the diets supplemented with FA (5, 10, and 50 mg/kg), showing the possible anti-inflammatory effects of FA during pregnancy and lactation. In general, we also found that in the adult offspring that were subjected to an animal model of SZ, FA had a protective effect in relation to the levels of IL-4, IL-6, and TNF-α, which indicates that the action of FA persisted in the adult offspring, since FA showed a lasting effect on the inflammatory response, which was similar in both the dams and their offspring. In conclusion, the importance of supplementation with FA during pregnancy and lactation should be emphasized, not only for the benefit of the offspring but also for the health of the mother. All this is due to the considerable protective effect of this vitamin against oxidative damage, cognitive impairment, hyperhomocysteinemia, immune function, and also its ability in preventing common processes in post-pregnancy stages, as well as in reducing the risks of neurodevelopmental disorders and enhancing fetal immune development.
Assuntos
Suplementos Nutricionais , Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/administração & dosagem , Efeitos Tardios da Exposição Pré-Natal/dietoterapia , Esquizofrenia/dietoterapia , Complexo Vitamínico B/administração & dosagem , Animais , Modelos Animais de Doenças , Feminino , Deficiência de Ácido Fólico/induzido quimicamente , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Ketamina/toxicidade , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Ratos Wistar , Esquizofrenia/induzido quimicamente , Esquizofrenia/metabolismoRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) patients may be at risk of vitamin B12 and folate insufficiencies, as these micronutrients are absorbed in the small intestine, which is affected by IBD. However, a consensus has not been reached on the association between IBD and serum folate and vitamin B12 concentrations. METHODS: In this study, a comprehensive search of multiple databases was performed to identify studies focused on the association between IBD and serum folate and vitamin B12 concentrations. Studies that compared serum folate and vitamin B12 concentrations between IBD and control patients were selected for inclusion in the meta-analysis. RESULTS: The main outcome was the mean difference in serum folate and vitamin B12 concentrations between IBD and control patients. Our findings indicated that the average serum folate concentration in IBD patients was significantly lower than that in control patients, whereas the mean serum vitamin B12 concentration did not differ between IBD patients and controls. In addition, the average serum folate concentration in patients with ulcerative colitis (UC) but not Crohn's disease (CD) was significantly lower than that in controls. This meta-analysis identified a significant relationship between low serum folate concentration and IBD. CONCLUSIONS: Our findings suggest IBD may be linked with folate deficiency, although the results do not indicate causation. Thus, providing supplements of folate and vitamin B12 to IBD patients may improve their nutritional status and prevent other diseases.
Assuntos
Deficiência de Ácido Fólico/etiologia , Ácido Fólico/sangue , Doenças Inflamatórias Intestinais/fisiopatologia , Estado Nutricional , Deficiência de Vitamina B 12/etiologia , Vitamina B 12/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/fisiopatologia , Doença de Crohn/sangue , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Doença de Crohn/fisiopatologia , Suplementos Nutricionais , Ácido Fólico/metabolismo , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/prevenção & controle , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/metabolismo , Absorção Intestinal , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Vitamina B 12/metabolismo , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/dietoterapia , Deficiência de Vitamina B 12/prevenção & controleRESUMO
BACKGROUND: Periconception maternal nutrition and folate in particular are important factors influencing the incidence of neural tube defects (NTDs). Many but not all NTDs are prevented by folic acid supplementation and there is a pressing need for additional strategies to prevent these birth defects. Other micronutrients such as iron are potential candidates, yet a clear role for iron deficiency in contributing to NTDs is lacking. Our previous studies with the flatiron (ffe) mouse model of Ferroportin1 (Fpn1) deficiency suggest that iron is required for neural tube closure and forebrain development raising the possibility that iron supplementation could prevent NTDs. METHODS: We determined the effect of periconception iron and/or folic acid supplementation on the penetrance of NTDs in the Fpn1ffe mouse model. Concurrently, measurements of folate and iron were made to ensure supplementation had the intended effects. RESULTS: High levels of iron supplementation significantly reduced the incidence of NTDs in Fpn1ffe mutants. Fpn1 deficiency resulted in reduced folate levels in both pregnant dams and embryos. Yet folic acid supplementation did not prevent NTDs in the Fpn1ffe model. Similarly, forebrain truncations were rescued with iron. Surprisingly, the high levels of iron supplementation used in this study caused folate deficiency in wild-type dams and embryos. CONCLUSION: Our results demonstrate that iron supplementation can prevent NTDs and forebrain truncations in the Fpn1ffe model. Surprisingly, high levels of iron supplementation and iron overload can cause folate deficiency. If iron is essential for neural tube closure, it is possible that iron deficiency might contribute to NTDs. Birth Defects Research 109:81-91, 2017. © 2016 The Authors Birth Defects Research Published by Wiley Periodicals, Inc.
Assuntos
Proteínas de Transporte de Cátions/genética , Suplementos Nutricionais , Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/administração & dosagem , Ferro/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Animais , Proteínas de Transporte de Cátions/deficiência , Cruzamentos Genéticos , Modelos Animais de Doenças , Embrião de Mamíferos , Feminino , Deficiência de Ácido Fólico/genética , Deficiência de Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/patologia , Deleção de Genes , Humanos , Fenômenos Fisiológicos da Nutrição Materna , Camundongos , Camundongos Transgênicos , Tubo Neural/anormalidades , Tubo Neural/efeitos dos fármacos , Tubo Neural/metabolismo , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismo , Defeitos do Tubo Neural/patologia , Penetrância , Gravidez , Prosencéfalo/anormalidades , Prosencéfalo/efeitos dos fármacos , Prosencéfalo/metabolismoAssuntos
Síndrome de Fadiga Crônica/enfermagem , Comportamento Alimentar , Adulto , Anemia Ferropriva/dietoterapia , Anemia Ferropriva/enfermagem , Criança , Terapia Combinada , Exercício Físico , Síndrome de Fadiga Crônica/dietoterapia , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/enfermagem , Humanos , Deficiência de Vitamina B 12/dietoterapia , Deficiência de Vitamina B 12/enfermagemRESUMO
Autism spectrum disorders (ASD) consist in a range of neurodevelopmental conditions that share common features with autism, such as impairments in communication and social interaction, repetitive behaviors, stereotypies, and a limited repertoire of interests and activities. Some studies have reported that folic acid supplementation could be associated with a higher incidence of autism, and therefore, we aimed to conduct a systematic review of studies involving relationships between this molecule and ASD. The MEDLINE database was searched for studies written in English which evaluated the relationship between autism and folate. The initial search yielded 60 potentially relevant articles, of which 11 met the inclusion criteria. The agreement between reviewers was κ = 0.808. The articles included in the present study addressed topics related to the prescription of vitamins, the association between folic acid intake/supplementation during pregnancy and the incidence of autism, food intake, and/or nutrient supplementation in children/adolescents with autism, the evaluation of serum nutrient levels, and nutritional interventions targeting ASD. Regarding our main issue, namely the effect of folic acid supplementation, especially in pregnancy, the few and contradictory studies present inconsistent conclusions. Epidemiological associations are not reproduced in most of the other types of studies. Although some studies have reported lower folate levels in patients with ASD, the effects of folate-enhancing interventions on the clinical symptoms have yet to be confirmed.
Assuntos
Transtorno do Espectro Autista/etiologia , Suplementos Nutricionais/efeitos adversos , Medicina Baseada em Evidências , Desenvolvimento Fetal , Ácido Fólico/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna , Adolescente , Fenômenos Fisiológicos da Nutrição do Adolescente , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/prevenção & controle , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Dieta/efeitos adversos , Feminino , Ácido Fólico/sangue , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/fisiopatologia , Deficiência de Ácido Fólico/prevenção & controle , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/etiologia , Hiper-Homocisteinemia/fisiopatologia , Hiper-Homocisteinemia/prevenção & controle , Incidência , Masculino , Gravidez , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
Fundamento: El déficit de ácido fólico durante el embarazo puede derivar en defectos del tubo neural en el feto, bajo peso al nacer y desórdenes del neurodesarrollo como trastornos de la conducta y de la cognición en el niño pero también puede conllevar anemia megaloblástica en la madre así como desprendimiento de la placenta, abortos, partos prematuros, preeclampsia e incluso eclampsia en algunas ocasiones. Objetivo: El objetivo de este trabajo es revisar los principales hallazgos científicos con relación a la importancia fisiológica del ácido fólico durante el embarazo así como los efectos negativos resultantes de un inadecuado nivel de folato periconcepcional, tanto por déficit como por exceso, y la evidencia existente sobre la relación entre suplementación con folato y los diferentes parámetros de salud, tanto de la madre como del recién nacido. Métodos: Se ha realizado una búsqueda amplia en la que se incluyen artículos originales, revisiones y guías de recomendaciones. Resultados/Conclusión: Tanto el déficit como el exceso de ácido fólico durante el embarazo pueden desencadenar efectos adversos para la madre y para el hijo. Por ello, la suplementación de ácido fólico debería ser individualizada para cada mujer teniendo en cuenta sus características fenotípicas, genotípicas y metabólicas (AU)
Background: The folic acid deficit during pregnancy may lead to a neural tube defects in the fetus, low birth weight and neurodevelopmental disorders as behavior disturbance or cognitive disabilities. Also may carry to the megaloblastic anemia in the mother as well as placental abruption, abortion, premature labor, pre-eclampsia and sometimes eclampsia. Objective: The objective of this work is to review the main scientific finds in relation with the physiological importance of folic acid during pregnancy and negative effects resulting of the inadequate level of folate periconceptional, both deficit and excess. Also review the evidence about the relationship between the folate supplementation and the different health parameters in the mother and the newborn. Methods: The search has been wide and this review includes original articles, review articles and recommendation guides. Results/Conclusion: Both deficit and excess folic acid during pregnancy can trigger adverse effects to the mother and the child. Therefore, supplementation with folic acid should be individualized for each woman considering its phenotypic, genotypic and metabolic characteristics (AU)
Assuntos
Humanos , Feminino , Gravidez , Ácido Fólico/administração & dosagem , Saúde Materno-Infantil , Ácidos Pteroilpoliglutâmicos/administração & dosagem , Hiper-Homocisteinemia/dietoterapia , Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/biossíntese , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/complicações , Complicações na Gravidez/dietoterapiaRESUMO
Folate is an essential B vitamin required for the de novo synthesis of purines, thymidylate and methionine. Folate deficiency can lead to mutations and genome instability, and has been shown to exacerbate the genotoxic potential of environmental toxins. We hypothesized that a folic acid (FA) deficient diet would induce genotoxicity in mice as measured by the Pig-a mutant phenotype (CD24-) and micronuclei (MN) in reticulocytes (RET) and red blood cells/normochromatic erythrocytes (RBC/NCE). Male Balb/c mice were fed a FA deficient (0 mg/kg), control (2 mg/kg) or supplemented (6 mg/kg) diet from weaning for 18 wk. Mice fed the deficient diet had 70% lower liver folate (p < 0.001), 1.8 fold higher MN-RET (p < 0.001), and 1.5 fold higher MN-NCE (p < 0.001) than mice fed the control diet. RET(CD24-) and RBC(CD24-) frequencies were not different between mice fed the deficient and control diets. Compared to mice fed the FA supplemented diet, mice fed the deficient diet had 73% lower liver folate (p < 0.001), a 2.0 fold increase in MN-RET (p < 0.001), a 1.6 fold increase in MN-NCE (p < 0.001) and 3.8 fold increase in RBC(CD24-) frequency (p = 0.011). RET(CD24-) frequency did not differ between mice fed the deficient and supplemented diets. Our data suggest that FA adequacy protects against mutagenesis at the Pig-a locus and MN induction in the red blood cells of mice.
Assuntos
Suplementos Nutricionais , Eritrócitos/efeitos dos fármacos , Deficiência de Ácido Fólico/dietoterapia , Ácido Fólico/administração & dosagem , Animais , Dano ao DNA/efeitos dos fármacos , Eritrócitos/metabolismo , Eritrócitos/patologia , Ácido Fólico/metabolismo , Deficiência de Ácido Fólico/genética , Deficiência de Ácido Fólico/metabolismo , Metionina/metabolismo , Camundongos , Reticulócitos/efeitos dos fármacos , Reticulócitos/metabolismo , Reticulócitos/patologiaRESUMO
La cerveza es una bebida natural con bajo contenido en calorías, bajo grado de alcohol, sin grasas ni azúcares y con una cantidad importante de hidratos de carbono, vitaminas y proteínas. Sus cualidades beneficiosas para la salud se basan en la presencia en la cerveza de compuestos antioxidantes (polifenoles), que reducen la presencia de radicales libres en el organismo, y de fitoestrógenos, elementos biosimilares a los estrógenos naturales. En las mujeres gestantes, la cerveza, obviamente sin alcohol, presenta elementos en su composición que la diferencian de otras bebidas fermentadas como es el ácido fólico, vitamina necesaria para prevenir los defectos del tubo neural en el nacimiento o para regular la homocisteína. Con respecto a la lactancia, la suplementación con cerveza sin alcohol, merced a sus polifenoles, aumenta la actividad antioxidante en la leche materna y, por tanto, reduce el estrés oxidativo del neonato tras el nacimiento. En la menopausia, son de especial relevancia sus propiedades antioxidantes, de aporte de vitaminas y nutrientes, por su contenido en fibra y la repercusión de la ingesta de fibra en la salud, así como por su contenido en fitoestrógenos, altamente beneficiosos en la prevención de patologías derivadas del descenso de estrógenos propio de esta etapa de la vida. La osteoporosis, igualmente, es eficazmente combatida por la cerveza. La ingesta de cerveza favorece una mayor masa ósea en las mujeres, independientemente de su estado gonadal (AU)
Beer is a natural beverage low calorie, low degree of alcohol, no fats or sugars and a significant amount of carbohydrates, vitamins, and proteins. Beneficial health qualities are based on the presence in the beer of antioxidant compounds (polyphenols), which reduce the presence of free radicals in the organism, and phytoestrogens, elements biosimilars to natural estrogens. In pregnant women, beer, obviously alcohol-free, presents elements in its composition that differ it from other fermented beverages as it is the folic acid, vitamin necessary to prevent defects of the neural tube in the fetus or regulate homocysteine. With regard to breastfeeding, beer alcohol-free supplementation increases the antioxidant activity in breast milk and therefore reduces the oxidative stress of the newborn after birth In menopause, the presence of antioxidants, vitamins, nutrients, and dietetic fiber, as well as phytoestrogens, is highly beneficial in the prevention of pathologies arising from the decline in estrogens. Osteoporosis also is effectively combated by the beer. The intake of beer, favors a greater bone mass in women, irrespective of their gonadal status (AU)
Assuntos
Adolescente , Adulto , Feminino , Humanos , Cerveja , Antioxidantes/uso terapêutico , Polifenóis/uso terapêutico , Ácido Fólico/uso terapêutico , Deficiência de Ácido Fólico/dietoterapia , Doenças Neurodegenerativas/dietoterapia , Doenças Neurodegenerativas/prevenção & controle , 51397 , Polifenóis/metabolismo , Suplementos Nutricionais , Osteoporose/dietoterapia , Osteoporose/prevenção & controle , LactaçãoRESUMO
OBJECTIVE: The clinical significance and characteristics of neuropathy caused by folate deficiency remain to be established. METHODS: We examined the clinicopathologic features of 18 consecutive patients with neuropathy caused by folate deficiency who presented with low serum folate levels but normal blood thiamine and serum cobalamin levels in the absence of chronic alcoholism. RESULTS: Symptoms were relatively uniform, characterized by slowly progressive polyneuropathy with predominant involvement of the lower extremities, with a tendency to manifest as sensory rather than motor neuropathy and predominant deep rather than superficial sensory loss. The electrophysiologic features were consistent with axonal neuropathy. The histopathologic features of sural nerve biopsy specimens indicated large fiber-predominant axonal loss without segmental demyelination. Although macrocytosis was found in 7 patients, only 3 patients exhibited hemoglobin levels less than 10 g/dL. During the same study period, we found 12 patients who had low blood thiamine levels but normal serum folate and cobalamin levels without chronic alcoholism. Compared with patients who had thiamine-deficiency neuropathy, patients with a folate deficiency showed significantly slower progression (p < 0.01), a tendency to manifest sensory neuropathy (p < 0.05), predominant deep sensory loss (p < 0.01), and preservation of biceps tendon reflexes (p < 0.05). CONCLUSIONS: Folate-deficiency neuropathy was characterized by a slowly progressive and sensory-dominant pattern, which was different from thiamine-deficiency neuropathy (i.e., beriberi neuropathy). This study demonstrates the importance of folate deficiency in the differential diagnosis of neuropathy, particularly in countries where folic acid fortification has not yet been practiced.
Assuntos
Progressão da Doença , Deficiência de Ácido Fólico/complicações , Ácido Fólico/farmacologia , Polineuropatias/fisiopatologia , Complexo Vitamínico B/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alcoolismo/complicações , Beriberi/fisiopatologia , Feminino , Ácido Fólico/administração & dosagem , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/dietoterapia , Deficiência de Ácido Fólico/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Polineuropatias/induzido quimicamente , Polineuropatias/patologia , Nervo Sural/patologia , Resultado do Tratamento , Deficiência de Vitamina B 12/fisiopatologia , Complexo Vitamínico B/administração & dosagemRESUMO
BACKGROUND: Kearns-Sayre syndrome (KSS) is a mitochondrial DNA deletion syndrome that presents with profound cerebral folate deficiency and other features. Preliminary data support the notion that folinic acid therapy might be useful in the treatment of KSS patients. Our aim was to assess the clinical and neuroimaging outcomes of KSS patients receiving folinic acid therapy. PATIENTS: We recruited eight patients with diagnoses of KSS. Four cases were treated at 12 de Octubre Hospital, and the other two cases were treated at Sant Joan de Déu Hospital. Two patients refused to participate in the treatment protocol. METHODS: Clinical, biochemical and neuroimaging data (magnetic resonance imaging or computed tomography scan) were collected in baseline conditions and at different time points after the initiation of therapy. Cerebrospinal fluid 5-methyltetrahydrofolate levels were analysed with HPLC and fluorescence detection. Large-scale mitochondrial DNA deletions were analysed by Southern blot. TREATMENT PROTOCOL: The follow-up periods ranged from one to eight years. Cases 1-4 received oral folinic acid at a dose of 1 mg/kg/day, and cases 6 and 8 received 3 mg/kg/day. RESULTS: No adverse effects of folinic acid treatment were observed. Cerebral 5-methyltetrahydrofolate deficiencies were observed in all cases in the baseline conditions. Moreover, all three patients who accepted lumbar puncture after folinic acid therapy exhibited complete recoveries of their decreased basal cerebrospinal fluid 5-methyltetrahydrofolate levels to normal values. Two cases neurologically improved after folinic therapy. Disease worsened in the other patients. Post-treatment neuroimaging was performed for the 6 cases that received folinic acid therapy. One patient exhibited improvements in white matter abnormalities. The remaining patients displayed progressions in subcortical cerebral white matter, the cerebellum and cerebral atrophy. CONCLUSIONS: Four patients exhibited clinical and radiological progression of the disease following folinic acid treatment. Only one patient who was treated in an early stage of the disease exhibited both neurological and radiological improvements following elevated doses of folinic acid, and an additional patient experienced neurological improvement. Early treatment with high-dose folinic acid therapy seems to be advisable for the treatment of KSS. TRIAL REGISTRATION: Eudrac T2007-00-6748-23.