RESUMO
PURPOSE: The aim of this study was to investigate circulating folic acid (FA) and predict circulating FA concentrations in the population related to dietary intake, vitamin concentrations, and interaction with the genetic variants involved in folate metabolism. METHODS: Data were from the 'Health Survey of São Paulo' a cross-sectional population-based survey, conducted in São Paulo City, Brazil. The participants (n = 750) provided fasting blood samples and food intake data. Folate, homocysteine, and B6 and B12 vitamins were assayed. DNA was isolated, and the genotypes for polymorphisms involved in folate metabolism were determined. A generalized linear model was performed to predict circulating FA concentration. RESULTS: The circulating FA was detected in 80.0% of the population, with a median concentration of 1.6 nmol/L (IQR 0.5-2.9). The increase of circulating FA concentrations was directly associated with total folate concentration (ß coeff. 1.03; 95% CI 1.02-1.04), age (ß coeff. 1.01; 95% CI 1.01-1.02), current smoker (ß coeff. 1.51; 95% CI 1.16-1.97), self-reported skin color (ß coeff. 1.83; 95% CI 1.51-2.20), as well as interaction between folate concentration and 19-bp deletion polymorphism in DHFR (ß coeff. 1.02; 95% CI 1.01-1.03), and inversely associated with vitamin B6 (ß coeff. 0.99; 95% CI 0.98-0.99). CONCLUSIONS: In the current study, the presence of detectable circulating folic acid is high, and its concentration is elevated compared with other populations. Age, smoking, lower concentration of vitamin B6 and genetic variant are associated with increased levels of circulating FA. Further researches are needed to acknowledge and guarantee the safety of exposure to folic acid, especially in countries which have mandatory fortification.
Assuntos
Dieta/métodos , Ácido Fólico/sangue , Variação Genética , Complexo Vitamínico B/sangue , Adolescente , Adulto , Brasil , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To investigate the association between serum unmetabolized folic acid (UMFA) concentrations and folic acid from fortified foods and nutrients known as dietary methyl-group donors (folate, methionine, choline, betaine and vitamins B2, B6 and B12) in participants exposed to mandatory fortification of wheat and maize flours with folic acid. METHODS: Cross-sectional study carried out with 144 healthy Brazilian participants, both sexes, supplement nonusers. Serum folate, UMFA, vitamin B12 and total plasma homocysteine (tHcy) were biochemically measured. Dietary intake was assessed by 2 non-consecutive 24-hour dietary recalls (24-HRs) and deattenuated energy-adjusted nutrient data were used for statistical analysis. RESULTS: Ninety eight (68.1%) participants were women. Median (interquartile range) age was 35.5 (28.0-52.0) years. Elevated serum folate concentrations (>45 nmol/L) were found in 17 (11.8%), while folate deficiency (<7 nmol/L) in 10 (6.9%) participants. No one had vitamin B12 deficiency (<148 pmol/L). An elevated serum UMFA concentration was defined as > 1 nmol/L (90th percentile). UMFA concentrations were positively correlated with folic acid intake and negatively correlated to choline, methionine and vitamin B6 intakes. Participants in the lowest quartile of UMFA concentrations had lower dietary intake of total folate (DFEs) and folic acid, and higher dietary intake of methionine, choline and vitamin B6 than participants in the highest quartile of UMFA. Folic acid intake (OR [95% CI] = 1.02 [1.01-1.04)] and being a male (OR [95% CI] = 0.40 [0.19-0.87) were associated with increased and reduced odds for UMFA concentrations > 0.55 nmol/L (median values), respectively. CONCLUSION: UMFA concentrations were directly influenced by folic acid intake from fortified foods in a healthy convenience sample of adult Brazilians exposed to mandatory flour fortification with folic acid.
Assuntos
Dieta , Farinha , Ácido Fólico/sangue , Alimentos Fortificados , Complexo Vitamínico B/sangue , Adulto , Brasil/epidemiologia , Colina/administração & dosagem , Feminino , Ácido Fólico/administração & dosagem , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/epidemiologia , Homocisteína/sangue , Humanos , Masculino , Metionina/sangue , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Riboflavina/administração & dosagem , Triticum , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/epidemiologia , Vitamina B 6/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Adulto Jovem , Zea maysRESUMO
Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers.Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells.Results: Serum folate concentrations increased by â¼5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9- and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (>1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both).Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp.
Assuntos
Suplementos Nutricionais/efeitos adversos , Ácido Fólico/efeitos adversos , Mediadores da Inflamação/sangue , Interleucina-8/sangue , Células Matadoras Naturais , Fator de Necrose Tumoral alfa/sangue , Adulto , Brasil , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Humanos , Imunidade/efeitos dos fármacos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Estado Nutricional , Estudos Prospectivos , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Valores de Referência , Tetra-Hidrofolato Desidrogenase/genética , Tetra-Hidrofolato Desidrogenase/metabolismo , Fator de Necrose Tumoral alfa/genética , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/efeitos adversos , Complexo Vitamínico B/sangueRESUMO
Although frank symptomatic biotin deficiency is rare, some evidence suggests that marginal biotin deficiency occurs spontaneously in a substantial proportion of women during normal human pregnancy and might confer an increased risk of birth defects. Herein I review 1) advances in assessing biotin status, including the relation between acylcarnitine excretion and biotin status; 2) recent studies of biotin status in pregnancy; 3) advances in understanding the role of biotin in gene expression and the potential roles of biotinylated proteins that are neither histones nor carboxylases; and 4) novel large-dose biotin supplementation as therapy for multiple sclerosis. The review concludes with a summary of recent studies that have reported potentially dangerous erroneous results in individuals consuming large amounts of biotin for measurements of various plasma hormones for common clinical assays that use streptavidin-biotin technology.
Assuntos
Biotina , Expressão Gênica/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Estado Nutricional , Complicações na Gravidez/prevenção & controle , Complexo Vitamínico B , Animais , Biotina/sangue , Biotina/deficiência , Biotina/farmacologia , Biotina/uso terapêutico , Biotinilação , Carnitina/análogos & derivados , Carnitina/metabolismo , Feminino , Hormônios , Humanos , Esclerose Múltipla/sangue , Gravidez , Complicações na Gravidez/sangue , Estreptavidina , Complexo Vitamínico B/sangue , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêuticoRESUMO
Background: Folate deficiency, vitamin B-12 deficiency, and anemia can have adverse effects on birth outcomes. Also, low vitamin B-12 reduces the formation of metabolically active folate.Objectives: We sought to establish the baseline prevalence of and factors associated with folate deficiency and insufficiency, vitamin B-12 deficiency, and anemia among women of childbearing age (WCBA) in Belize.Methods: In 2011, a national probability-based survey was completed among Belizean nonpregnant WCBA aged 15-49 y. Blood samples for determination of hemoglobin, folate (RBC and serum), and vitamin B-12 (plasma) and sociodemographic and health information were collected from 937 women. RBC and serum folate concentrations were measured by microbiologic assay (MBA). Folate status was defined based on both the WHO-recommended radioproteinbinding assay and the assay adjusted for the MBA.Results: The national prevalence estimates for folate deficiency in WCBA, based on serum and RBC folate concentrations by using the assay-matched cutoffs, were 11.0% (95% CI: 8.6%, 14.0%) and 35.1% (95% CI: 31.3%, 39.2%), respectively. By using the assay-matched compared with the WHO-recommended cutoffs, a substantially higher prevalence of folate deficiency was observed based on serum (6.9% absolute difference) and RBC folate (28.9% absolute difference) concentrations. The prevalence for RBC folate insufficiency was 48.9% (95% CI: 44.8%, 53.1%). Prevalence estimates for vitamin B-12 deficiency and marginal deficiency and anemia were 17.2% (95% CI: 14.2%, 20.6%), 33.2% (95% CI: 29.6%, 37.1%), and 22.7% (95% CI: 19.5%, 26.2%), respectively. The adjusted geometric means of the RBC folate concentration increased significantly (P-trend < 0.001) in WCBA who had normal vitamin B-12 status relative to WCBA who were vitamin B-12 deficient.Conclusions: In Belize, the prevalence of folate and vitamin B-12 deficiencies continues to be a public health concern among WCBA. Furthermore, low folate status co-occurred with low vitamin B-12 status, underlining the importance of providing adequate vitamin B-12 and folic acid intake through approaches such as mandatory food fortification.
Assuntos
Deficiência de Ácido Fólico/epidemiologia , Ácido Fólico/sangue , Estado Nutricional , Deficiência de Vitamina B 12/epidemiologia , Vitamina B 12/sangue , Complexo Vitamínico B/sangue , Adolescente , Adulto , Anemia/sangue , Anemia/epidemiologia , Belize/epidemiologia , Eritrócitos/metabolismo , Feminino , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/complicações , Hemoglobinas/metabolismo , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Prevalência , Fatores de Risco , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/complicações , Adulto JovemRESUMO
BACKGROUND: It is uncertain whether vitamin B-12 supplementation can improve neurophysiologic function in asymptomatic elderly with low vitamin B-12 status or whether folate status affects responses to vitamin B-12 supplementation. OBJECTIVE: We assessed the effects of a single intramuscular injection of 10 mg vitamin B-12 (which also contained 100 mg vitamin B-6 and 100 mg vitamin B-1) on vitamin B-12 status and neurophysiologic function in elderly community-dwelling Chileans with low serum vitamin B-12 concentrations who were consuming bread fortified with folic acid. DESIGN: A pretreatment and posttreatment study was conducted in 51 participants (median ± SD age: 73 ± 3 y; women: 47%) with serum vitamin B-12 concentrations <120 pmol/L at screening. Vitamin B-12 status was defined by combining vitamin B-12, plasma total homocysteine (tHcy), methylmalonic acid (MMA), and holotranscobalamin into one variable [combined indicator of vitamin B-12 status (cB-12)]. The response to treatment was assessed by measuring cB-12 and neurophysiologic variables at baseline and 4 mo after treatment. RESULTS: Treatment increased serum vitamin B-12, holotranscobalamin, and cB-12 (P < 0.001) and reduced plasma tHcy and serum MMA (P < 0.001). Treatment produced consistent improvements in conduction in myelinated peripheral nerves; the sensory latency of both the left and right sural nerves improved on the basis of faster median conduction times of 3.1 and 3.0 ms and 3.3 and 3.4 ms, respectively (P < 0.0001). A total of 10 sensory potentials were newly observed in sural nerves after treatment. Participants with high serum folate at baseline (above the median, ≥33.9 nmol/L) had less improvement in cB-12 (P < 0.001) than did individuals whose serum folate was less than the median concentration (i.e., with a concentration <33.9 nmol/L). CONCLUSION: Asymptomatic Chilean elderly with poor vitamin B-12 status displayed improved conductivity in myelinated peripheral nerves after vitamin B-12 treatment and an interaction with folate status, which was detected only with the use of cB-12. This trial was registered at www.controlled-trials.com as ISRCTN02694183.
Assuntos
Suplementos Nutricionais , Ácido Fólico/sangue , Fibras Nervosas Mielinizadas/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12 , Idoso , Chile , Feminino , Alimentos Fortificados , Homocisteína/sangue , Humanos , Masculino , Ácido Metilmalônico/sangue , Fibras Nervosas Mielinizadas/fisiologia , Estado Nutricional , Nervos Periféricos/fisiologia , Vitamina B 12/sangue , Vitamina B 12/farmacologia , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/sangue , Complexo Vitamínico B/sangue , Complexo Vitamínico B/farmacologia , Complexo Vitamínico B/uso terapêuticoRESUMO
BACKGROUND: The only treatment for celiac disease is the gluten-free diet. Few studies have assessed the nutritional adequacy of this diet, especially of B vitamins related to homocysteine metabolism. The aim of this study was to assess the nutritional status and serum concentrations of B vitamins involved in homocysteine metabolism, and to determine whether the dietary intake of these vitamins are meeting Dietary Reference Intakes in celiac patients. METHODS: A cross-sectional study enrolled a total of 20 celiac patients (36.3 ± 13.7 years old; 65% women), following strict gluten-free diet (GFD) and 39 healthy controls matched by sex and age. The dietary intake was assessed by 3-day food records, and serum concentrations of homocysteine and vitamins B6, B12, and folate were determined after overnight fasting. Comparisons between the two groups were performed by Student's t test or Mann-Whitney U-test, for continuous variables. Pearson's chi-square test or Fisher's exact test was used for categorical variables. An alpha level of 5% were considered significant. RESULTS: Celiac patients had lower serum folate concentrations (7.7 ± 3.5 ng/mL, P < 0.05) than controls. All celiac patients had folate intake below the Estimated Average Requirement (EAR) (130.8 ± 53.6 µg/d). However, only a small proportion of celiac patients had hyperhomocysteinemia. CONCLUSIONS: Celiac patients treated with GFD presented inadequacy of dietary folate intake and low-serum concentrations of folate, suggesting that more attention should be given to the quality of the nutrients offered by the GFD, as it constitutes a lifelong treatment.
Assuntos
Doença Celíaca/sangue , Ácido Fólico/sangue , Homocisteína/sangue , Vitamina B 12/sangue , Vitamina B 6/sangue , Complexo Vitamínico B/sangue , Adulto , Doença Celíaca/dietoterapia , Estudos Transversais , Registros de Dieta , Dieta Livre de Glúten , Feminino , Humanos , Masculino , Necessidades Nutricionais , Estado NutricionalRESUMO
BACKGROUND: Preeclampsia is a pregnancy-related pathological condition triggered by an abnormal placentation which produces endothelial dysfunction (ED). ED, in turn, is associated with an increase in homocysteine (hcy) and asymmetric dimethylarginine (ADMA); these molecules are also increased when some of the B-vitamins are deficient. It is unclear whether increases in hcy and ADMA during preeclampsia are the result of ED, or the consequence of a B-vitamin deficiency. OBJECTIVE: To evaluate hcy, ADMA, folic acid (FA), vitamin B6 and B2 concentrations in patients with preeclampsia. METHODS: In a cross-sectional design 19 patients with severe preeclamp- sia (preeclampsia) and 57 with normal pregnancy (no-preeclampsia), paired by gestational age and body mass index, were studied. Plasma hcy, ADMA, FA and vitamins B6 and B12 were determined. Non-parametric statistics was used for between-groups comparisons and regression analyses to evaluate interactions among molecules. RESULTS: 72% of women were vitamin B deficient, 40% were deficient of B12 and 4% of FA. Preeclamptic patients presented hcy and ADMA concentrations higher than no-preeclamptic ones. Inferential analyses demonstrated that: hcy and ADMA are increased during preeclampsia independently from vitamins blood concentration; that the risk for pre- eclampsia is associated with high hcy but not with vitamins deficiency; and that the ratio L-arginine:ADMA decreases the preeclampsia risk. CONCLUSION: In patients with preeclampsia, increases of hcy and ADMA are associated with ED, but not with deficiency of the vitamins involved in their metabolism.
Assuntos
Arginina/análogos & derivados , Homocisteína/sangue , Pré-Eclâmpsia/fisiopatologia , Complexo Vitamínico B/sangue , Adolescente , Adulto , Antioxidantes/metabolismo , Arginina/sangue , Biomarcadores/metabolismo , Estudos Transversais , Feminino , Humanos , Gravidez , Estudos Prospectivos , Análise de Regressão , Deficiência de Vitaminas do Complexo B/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the usefulness of serial determinations of asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations during pregnancy to predict pre-eclampsia, taking into account maternal obesity and B vitamin status. DESIGN: Longitudinal study. SETTING: Two obstetric referral hospitals. SAMPLE: Two hundred and fifty-two of 411 women invited to participate in the study. METHODS: The women made monthly visits from ≤20 weeks of gestation until delivery for measurements of plasma ADMA, Hcy, and vitamins B6 , B12, and folic acid, and for the recording of clinical information. MAIN OUTCOME MEASURE: Early elevations in plasma ADMA and Hcy related to the development of pre-eclampsia. RESULTS: Of the 252 women who completed the study, 179 had no complications, 49 developed pre-eclampsia, and 24 presented with complications other than pre-eclampsia. ADMA and Hcy increased gradually throughout pregnancy in the pre-eclampsia group, independent of maternal B-vitamin status and obesity, but remained constant in women with no complications. Relative to the preceding month, ADMA and Hcy levels increased 1 month prior to the onset of pre-eclampsia: 124 ± 27 nmol (P < 0.001) and 1177 ± 278 nmol (P = 0.001), respectively, in the pre-eclampsia group. The group of women with no complications did not show any significant changes. Increases of 80 nmol ADMA and 1000 nmol Hcy at 1 month prior to the onset of pre-eclampsia demonstrated the best potential for prediction. CONCLUSIONS: Increased ADMA and Hcy levels precede clinical manifestations of pre-eclampsia. Therefore, serial determinations of their concentrations may be helpful in identifying women at risk. TWEETABLE ABSTRACT: Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk.
Assuntos
Arginina/análogos & derivados , Ácido Fólico/sangue , Homocisteína/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Complexo Vitamínico B/sangue , Deficiência de Vitaminas do Complexo B/sangue , Adulto , Arginina/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pré-Eclâmpsia/epidemiologia , Valor Preditivo dos Testes , Gravidez , Fatores de Risco , Reino Unido/epidemiologia , Deficiência de Vitaminas do Complexo B/epidemiologiaRESUMO
OBJECTIVE: To analyse the relationship between serum folate (SF), vitamin B12 and impaired cognitive function in the Chilean elderly. DESIGN: We analysed the relationships between impaired cognitive function and age, SF (µg/l) and vitamin B12 (pg/ml) with Student's t test, as well as between impaired cognitive function and gender, educational level, residence area, diabetes and hypertension with the χ 2 test. Multiple logistic regressions with interactions were estimated to assess the impact of SF on impaired cognitive function according to these methods. SETTING: Chile. SUBJECTS: Older adults (>65 years, n 1051), drawn from representative households of a national prevalence study, assessed using the Modified Mini Mental Status Examination (MMMSE). Individuals with altered MMMSE scores (≤13 points) were sequentially assessed using the Pfeffer Functional Activities Questionnaire (PFAQ). RESULTS: Multivariate models using the MMMSE demonstrated an increased risk of impaired cognitive function for seniors who had hypertension, diabetes and higher vitamin B12 levels. SF and its square (SF2) were statistically significant, indicating that this predictor of impaired cognitive function displays a U-shaped distribution. The interaction between SF and vitamin B12 was not statistically significant. Models using the MMMSE plus PFAQ suggested that urban residence decreased the risk of impaired cognitive function, whereas male gender, older age, vitamin B12 levels and hypertension increased this risk. The variables SF and SF2 and the SF × vitamin B12 interaction were statistically significant (P<0.05). The risk of impaired cognitive function depended on different combinations of SF and vitamin B12 levels. When SF was low, a one-unit increase in SF (1 µg/l) diminished the risk. When SF was elevated, a further increase in SF raised the risk, especially at low vitamin B12 levels. CONCLUSIONS: The relationship between folate, vitamin B12 and impaired cognitive function warrants further study.
Assuntos
Transtornos Cognitivos/sangue , Cognição/efeitos dos fármacos , Deficiência de Ácido Fólico/sangue , Ácido Fólico/sangue , Deficiência de Vitamina B 12/sangue , Vitamina B 12/sangue , Complexo Vitamínico B/sangue , Atividades Cotidianas , Fatores Etários , Idoso , Chile , Transtornos Cognitivos/complicações , Estudos Transversais , Feminino , Deficiência de Ácido Fólico/complicações , Avaliação Geriátrica , Humanos , Hipertensão/complicações , Masculino , Avaliação Nutricional , Estado Nutricional , Fatores Sexuais , Inquéritos e Questionários , População Urbana , Deficiência de Vitamina B 12/complicaçõesRESUMO
OBJECTIVES: The aim of this study was to investigate neuropsychological performance and biomarkers of oxidative stress in patients with obstructive sleep apnea and the relationships between these factors. METHODS: This was an observational, cross-sectional study of 14 patients (36.0±6.5 years old) with obstructive sleep apnea and 13 controls (37.3±6.9 years old). All of the participants were clinically evaluated and underwent full-night polysomnography as well as neuropsychological tests. Blood samples were used to assay superoxide dismutase, catalase, glutathione and homocysteine, as well as vitamins E, C, B11 and B12. RESULTS: The patients performed poorly relative to the controls on several neuropsychological tests, such as the attention test and tests of long-term memory and working memory/executive function. They also had lower levels of vitamin E (p<0.006), superoxide dismutase (p<0.001) and vitamin B11 (p<0.001), as well as higher concentrations of homocysteine (p<0.02). Serum concentrations of vitamin C, catalase, glutathione and vitamin B12 were unaltered. Vitamin E levels were related to performance in the backward digit span task (F = 15.9; p = 0.002) and this correlation remained after controlling for age and body mass index (F = 6.3, p = 0.01). A relationship between superoxide dismutase concentrations and executive non-perseveration errors in the Wisconsin Card Sorting Test (F = 7.9; p = 0.01) was also observed. CONCLUSIONS: Decreased levels of antioxidants and lower performance on the neuropsychological tasks were observed in patients with obstructive sleep apnea. This study suggests that an imbalance between antioxidants and pro-oxidants may contribute to neuropsychological alterations in this patient population.
Assuntos
Cognição/fisiologia , Estresse Oxidativo , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Antioxidantes/análise , Biomarcadores/sangue , Índice de Massa Corporal , Pressão Positiva Contínua nas Vias Aéreas , Estudos Transversais , Feminino , Homocisteína/sangue , Humanos , Masculino , Memória de Curto Prazo , Pessoa de Meia-Idade , Testes Neuropsicológicos , Polissonografia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/psicologia , Superóxido Dismutase/sangue , Complexo Vitamínico B/sangue , Vitamina E/sangueRESUMO
OBJECTIVES: The aim of this study was to investigate neuropsychological performance and biomarkers of oxidative stress in patients with obstructive sleep apnea and the relationships between these factors. METHODS: This was an observational, cross-sectional study of 14 patients (36.0±6.5 years old) with obstructive sleep apnea and 13 controls (37.3±6.9 years old). All of the participants were clinically evaluated and underwent full-night polysomnography as well as neuropsychological tests. Blood samples were used to assay superoxide dismutase, catalase, glutathione and homocysteine, as well as vitamins E, C, B11 and B12. RESULTS: The patients performed poorly relative to the controls on several neuropsychological tests, such as the attention test and tests of long-term memory and working memory/executive function. They also had lower levels of vitamin E (p<0.006), superoxide dismutase (p<0.001) and vitamin B11 (p<0.001), as well as higher concentrations of homocysteine (p<0.02). Serum concentrations of vitamin C, catalase, glutathione and vitamin B12 were unaltered. Vitamin E levels were related to performance in the backward digit span task (F = 15.9; p = 0.002) and this correlation remained after controlling for age and body mass index (F = 6.3, p = 0.01). A relationship between superoxide dismutase concentrations and executive non-perseveration errors in the Wisconsin Card Sorting Test (F = 7.9; p = 0.01) was also observed. CONCLUSIONS: Decreased levels of antioxidants and lower performance on the neuropsychological tasks were observed in patients with obstructive sleep apnea. This study suggests that an imbalance between antioxidants and pro-oxidants may contribute to neuropsychological alterations in this patient population. .
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cognição/fisiologia , Estresse Oxidativo , Apneia Obstrutiva do Sono/fisiopatologia , Antioxidantes/análise , Índice de Massa Corporal , Biomarcadores/sangue , Pressão Positiva Contínua nas Vias Aéreas , Estudos Transversais , Homocisteína/sangue , Memória de Curto Prazo , Testes Neuropsicológicos , Polissonografia , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/psicologia , Superóxido Dismutase/sangue , Complexo Vitamínico B/sangue , Vitamina E/sangueRESUMO
A high prevalence of low serum vitamin B-12 concentrations has been reported in studies and surveys in Latin America including Mexico, but the functional consequences are unknown. This randomized controlled trial assessed the response to a high-dose vitamin B-12 supplementation of women in rural Querétaro, Mexico. Participants aged 20-59 y were stratified at baseline to deficient, marginal, and adequate status groups (serum vitamin B-12, 75-148, 149-220, and >220 pmol/L, respectively), and each group was randomized to vitamin B-12 treatment (single dose of 1 mg i.m. then 500 µg/d orally for 3 mo, n = 70) or placebo (n = 62). Measures at baseline and 3 mo included: complete blood count, serum vitamin B-12, holotranscobalamin (holoTC), folate, ferritin, C-reactive protein (CRP), bone alkaline phosphatase, and methylmalonic acid (MMA) and plasma total homocysteine (tHcy). At baseline, 11% of the women were vitamin B-12 deficient and 22% had marginal status. HoloTC was low (<35 pmol/L) in 23% and correlated with serum vitamin B-12 (r = 0.7; P < 0.001). Elevated MMA (>271 nmol/L) and tHcy (>12 µmol/L) occurred in 21 and 31%, respectively, and correlated with serum vitamin B-12 (r = -0.28, P < 0.0007 and r = -0.20, P < 0.01, respectively). Supplementation increased serum vitamin B-12 and holoTC and lowered MMA and tHcy, normalizing all values except for elevated tHcy in 21% of the women. Supplementation did not affect hematology or bone-specific alkaline phosphatase. Vitamin B-12 supplementation normalized biochemical indicators of vitamin B-12 status in the treatment group but did not affect the functional outcomes measured.
Assuntos
Remodelação Óssea , Suplementos Nutricionais , Vitamina B 12/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Adulto , Fosfatase Alcalina/sangue , Proteína C-Reativa/metabolismo , Feminino , Ferritinas/sangue , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Modelos Logísticos , Ácido Metilmalônico/sangue , México , Pessoa de Meia-Idade , Estado Nutricional , População Rural , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/fisiopatologia , Complexo Vitamínico B/sangue , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effects on anencephaly risk of the interaction between the maternal profile of folate, vitamin B12 and homocysteine and the 677CâT polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). DESIGN: Case-control study paired (1:1) on maternity clinic, date of birth and state of residence. Cases of anencephaly were identified using the Registry of the Mexican Neural Tube Defect Epidemiological Surveillance System. Case and control mothers were selected from the same maternity departments. All mothers completed a structured questionnaire and blood samples were obtained to determine the MTHFR 677CâT polymorphism and biochemical profile. SETTING: Mexico, Puebla and Guerrero states, Mexico. SUBJECTS: A total of 151 mothers of cases and controls were enrolled from March 2000 to February 2001. We had complete information on biochemical profile and MTHFR C677T polymorphism for ninety-eight mothers of cases and ninety-one mothers of controls. RESULTS: The adjusted models show that the risk of anencephaly in mothers with 677TT genotype was reduced by 18 % (OR = 0·82; 95 % CI 0·72, 0·94) for each 1 ng/ml increment in serum folate. In terms of tertiles, mothers with 677TT genotype with serum folate levels in the upper tertile (>14·1 ng/ml) had a 95 % lower risk to have a child with anencephaly than mothers with serum folate levels in the first and second tertiles (P trend = 0·012). CONCLUSIONS: Our data agree with the hypothesis of a gene-nutrient interaction between MTHFR 677CâT polymorphism and folate status. We observed a protective effect on anencephaly risk only in mothers with 677TT genotype as serum folate levels increased.
Assuntos
Anencefalia/genética , Ácido Fólico/sangue , Homocisteína/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Vitamina B 12/sangue , Adulto , Anencefalia/epidemiologia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Lactente , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , México/epidemiologia , Gravidez , Fatores de Risco , Inquéritos e Questionários , Complexo Vitamínico B/sangueRESUMO
BACKGROUND: High daily intake of folic acid (FA) could determine health risks in some populations. AIM: To review the Chilean FA wheat flour fortification and to identify the existence of populations at risk. MATERIAL AND METHODS: We categorized the FA levels in flour 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 flour fortification (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-fortification. RESULTS: There is great variability in FA flour: 10-20% samples without FA and 10-30% 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-fortification estimated daily DFE from serum folate in women, men and elderly people show: 99% of women, 100% of men and the elderly people have intakes higher than EAR. Additionally 2.3% of women and 6% of men would have intakes near the UL. CONCLUSIONS: The flour FA levels and serum folate levels in some populations show increased FA post-fortification intakes, which could lead to greater risk suggesting a revision of the fortification level.
Assuntos
Farinha/análise , Ácido Fólico/efeitos adversos , Alimentos Fortificados/efeitos adversos , Necessidades Nutricionais , Estado Nutricional/fisiologia , Complexo Vitamínico B/efeitos adversos , Adolescente , Adulto , Idoso , Pão/análise , Criança , Chile , Inquéritos sobre Dietas/métodos , Inquéritos sobre Dietas/estatística & dados numéricos , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Alimentos Fortificados/análise , Humanos , Masculino , Fatores de Risco , Fatores Socioeconômicos , Fatores de Tempo , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangueRESUMO
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
Disorders of propionate metabolism are autosomal recessive diseases clinically characterized by acute metabolic crises in the neonatal period and long-term neurological deficits whose pathophysiology is not completely established. There are increasing evidences demonstrating antioxidant properties for L-carnitine, which is used in the treatment of propionic and methylmalonic acidemias to increase the excretion of organic acids accumulated in tissues and biological fluids of the affected patients. In this work we aimed to evaluate lipid (malondialdehyde content) and protein (carbonyl formation and sulfhydryl oxidation) oxidative damage in plasma from patients with propionic and methylmalonic acidemias at the moment of diagnosis and during treatment with L-carnitine. We also correlated the parameters of oxidative damage with plasma total, free and esterified L-carnitine levels. We found a significant increase of malondialdehyde and carbonyl groups, as well as a reduction of sulfhydryl groups in plasma of these patients at diagnosis compared to controls. Furthermore, patients under treatment presented a marked reduction of the content of protein carbonyl groups, similar to controls, and malondialdehyde content in relation to patients at diagnosis. In addition, plasma total and free L-carnitine concentrations were negatively correlated with malondialdehyde levels. Taken together, the present data indicate that treatment significantly reduces oxidative damage in patients affected by disorders of propionate metabolism and that l-carnitine supplementation may be involved in this protection.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Proteínas Sanguíneas/análise , Carnitina/administração & dosagem , Carnitina/sangue , Lipídeos/sangue , Propionatos/metabolismo , Pré-Escolar , Suplementos Nutricionais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estresse Oxidativo/efeitos dos fármacos , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/sangueRESUMO
BACKGROUND: The methylenetetrahydrofolate reductase (MTHFR), glutamate carboxypeptidase II (GCPII) and reduced folate carrier (RFC1) gene polymorphisms were associated with folate status. We investigated the effects of these polymorphisms on serum folate (SF) and folate-related metabolites in mothers and their neonates. METHODS: Cobalamin (Cbl), SF, total homocysteine (tHcy), methylmalonic acid (MMA), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH) were measured in 275 healthy women and their neonates. MTHFR C677T, GCPII C1561T and RFC1 A80G polymorphisms were determined by PCR-RFLP. RESULTS: Maternal tHcy was affected individually by MTHFR C677T and GCPII C1561T polymorphisms and by combined genotypes MTHFR 677TT/GCPII 1561CC and MTHFR 677TT/RFC1 80AG. The MTHFR and RFC1 polymorphisms were not associated with variations in vitamins or SAM, SAH and MMA in neonates. Neonatal tHcy was predicted directly by maternal tHcy and inversely by maternal SF, neonatal Cbl and neonatal RFC1 80G allele (AG+GG genotypes). Maternal MMA and SAM/SAH were predicted by creatinine and Cbl, respectively. Neonatal MMA was predicted by maternal MMA and GCPII 1561T allele (CT+TT genotypes) and by neonatal Cbl. CONCLUSIONS: Maternal tHcy was affected by MTHFR C677T, RFC1 A80G and GCPII C1561T polymorphisms. Maternal GCPII C1561T variant was associated with neonatal MMA. Neonatal RFC1 A80G polymorphism influenced tHcy in neonates.
Assuntos
Ácido Fólico/metabolismo , Glutamato Carboxipeptidase II/genética , Polimorfismo Genético/genética , Gravidez/metabolismo , Proteína Carregadora de Folato Reduzido/genética , Complexo Vitamínico B/metabolismo , Adulto , Brasil/epidemiologia , DNA/genética , Desenvolvimento Embrionário/efeitos dos fármacos , Etnicidade , Feminino , Ácido Fólico/sangue , Homocisteína/sangue , Humanos , Recém-Nascido , Ácido Metilmalônico/sangue , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa , S-Adenosil-Homocisteína/sangue , S-Adenosilmetionina/sangue , Fatores Socioeconômicos , Vitamina B 12/sangue , Complexo Vitamínico B/sangue , Adulto JovemRESUMO
OBJECTIVE: We assessed the impact of high serum folate concentration on erythrocyte S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) concentrations, SAM/SAH ratio, CpG methylation levels across the promoter region of the extracellular superoxide dismutase (ec-SOD) gene, and ec-SOD activity in healthy men. METHODS: Serum folate levels were measured in 111 subjects who were categorized in quintiles according to their folate status. Subjects located at the lowest, middle, and upper quintiles were selected for assessment of SAM and SAH by high-performance liquid chromatography, C677T genotype of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, ec-SOD methylation of CpG sites in lymphocytes genomic DNA by bisulfate treatment, and ec-SOD activity by a chemical assay. RESULTS: Sixteen subjects were in the lowest serum folate quintile (<23.6 nmol/L), 17 in the middle (>34-<42 nmol/L), and 14 in the highest (>45nmol/L). SAM concentration was higher in the upper than in the middle and lowest quintiles (5.57 +/- 1.58, 2.52 +/- 0.97, 2.29 +/- 1.2 micromol/L; P < 0.0001). SAH concentration was higher in the upper compared with the lowest quintile (0.76 +/- 0.24 versus 0.52 +/- 0.23 micromol/L, P < 0.001). There were no differences in the SAM/SAH ratio, ec-SOD activity, methylation status of CpG sites of the ec-SOD gene, and TMTHFR C677T genotype between groups. CONCLUSION: Serum folate concentrations in the highest quintile among healthy humans are associated with increased erythrocyte SAM and SAH concentrations, but not with SAM/SAH ratio or with methylation levels of CpG sites across the promoter region of the ec-SOD gene. Further research is required to determine if these findings are beneficial or harmful.
Assuntos
Ácido Fólico/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , Estado Nutricional , S-Adenosil-Homocisteína/sangue , S-Adenosilmetionina/sangue , Superóxido Dismutase/metabolismo , Adulto , Idoso , Cromatografia Líquida de Alta Pressão/métodos , Genótipo , Humanos , Masculino , Metilação , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Pessoa de Meia-Idade , Superóxido Dismutase/genética , Complexo Vitamínico B/sangue , Adulto JovemRESUMO
This study examined the socio-demographic, lifestyle, gynecological, and obstetric factors associated with serum or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6 among low-income women in São Paulo, Brazil. Serum concentrations of folic acid and vitamin B12 were measured by fluoroimmunoassay, while plasma vitamin B6 and homocysteine levels were measured by reversed-phase high performance liquid chromatography. Independent variables were initially selected by Pearson correlation or Kruskal-Wallis test (p < 0.20). Based on cut-off values, altered concentrations of homocysteine, folic acid, and vitamins B12 and B6 were found in 20%, 6%, 11%, and 67% of participants, respectively. Age was positively correlated with vitamin B6 and homocysteine plasma concentrations (p < 0.001). Body mass index was positively correlated with vitamin B6 plasma concentration (p < 0.001). Multiple linear regression models accounted for 10.2%, 5.8%, 14.4%, and 9.4% of folic acid, vitamins B12 and B6, and homocysteine plasma or serum concentrations, respectively. In this study, socio-demographic, lifestyle, gynecological, and obstetric variables showed important predictive value for serum or plasma levels of the biochemical indicators assessed.