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One approach to controlling type 2 diabetes (T2D) is to lower postprandialglucose spikesby slowing down the digestion of carbohydrates and the absorption of glucose in the small intestine. The consumption of walnuts is associated with a reduced risk of chronic diseases such as T2D, suggested to be partly due to the high content of (poly)phenols. This study evaluated, for the first time, the inhibitory effect of a (poly)phenol-rich walnut extract on human carbohydrate digesting enzymes (salivary and pancreatic α-amylases, brush border sucrase-isomaltase) and on glucose transport across fully differentiated human intestinal Caco-2/TC7 monolayers. The walnut extract was rich in multiple (poly)phenols (70 % w/w) as analysed by Folin-Ciocalteau and by LCMS. It exhibited potent inhibition of both human salivary (IC50: 32.2 ± 2.5 µg walnut (poly)phenols (WP)/mL) and pancreatic (IC50: 56.7 ± 1.7 µg WP/mL) α-amylases, with weaker effects on human sucrase (IC50: 990 ± 20 µg WP/mL), maltase (IC50: 1300 ± 80 µg WP/mL), and isomaltase (IC25: 830 ± 60 µg WP/mL) activities. Selected individual walnut (poly)phenols inhibited human salivary α-amylase in the order: 1,3,4,6-tetragalloylglucose > ellagic acid pentoside > 1,2,6-tri-O-galloyl-ß-D-glucopyranose, with no inhibition by ellagic acid, gallic acid and 4-O-methylgallic acid. The (poly)phenol-rich walnut extract also attenuated (up to 59 %) the transfer of 2-deoxy-D-glucose across differentiated Caco-2/TC7 cell monolayers. This is the first report on the effect of (poly)phenol-rich extracts from any commonly-consumed nut kernel on any human starch-digesting enzyme, and suggests a mechanism through which walnut consumption may lower postprandial glucose spikes and contribute to their proposed health benefits.
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Glucose , Juglans , Extratos Vegetais , Polifenóis , Humanos , Polifenóis/farmacologia , Juglans/química , Células CACO-2 , Glucose/metabolismo , Extratos Vegetais/farmacologia , Digestão/efeitos dos fármacos , Nozes/química , Amido/metabolismo , alfa-Amilases/metabolismo , alfa-Amilases/antagonistas & inibidores , Transporte Biológico , Complexo Sacarase-Isomaltase/metabolismoRESUMO
BACKGROUND: Stroke increases subsequent dementia risk yet there are no specific post-stroke therapies to protect cognition. Cardiorespiratory exercise is recommended for secondary prevention of stroke and may be neuroprotective. The Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES) aims to reduce post-stroke secondary neurodegeneration and cognitive decline. During the pandemic, we pivoted to a ZOom Delivered Intervention Against Cognitive decline (ZODIAC) protocol, reducing pandemic-amplified barriers to exercise. METHODS: We present pandemic adaptions for a multicentre phase IIb assessor-blinded randomised controlled trial of ischaemic stroke survivors testing the efficacy and feasibility of an 8-week home-based exercise intervention delivered at 2 months post-stroke. We compare cardiorespiratory exercise (intervention arm) versus balance and stretching (active control arm). Participants are assessed with magnetic resonance imaging (MRI), fitness, blood, microbiome, and neuropsychological tests at three study visits: before and after the exercise intervention and at 12 months. Modifications to the original protocol include pre-exercise safety home visits, commercial delivery of exercise equipment to facilitate assessor blinding, and reconsideration of statistical plan to allow pooling of the studies. We have reduced in-person study visits from 27 to 3. Primary outcome remains between-group (intervention versus control) difference in brain volume change; secondary outcome is between-group difference in global cognitive ability to allow remote administration of a validated cognitive scale. DISCUSSION: Remotely delivered exercise interventions reduce participant burden and may reduce barriers to recruitment. A decrease in the number of in-person study visits can be supported by greater information capture via self-reported questionnaires and phone surveys. TRIAL REGISTRATION: Prospectively ACTRN12616000942459. Registered on July 2016.
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COVID-19 , Disfunção Cognitiva , Terapia por Exercício , Reabilitação do Acidente Vascular Cerebral , Humanos , COVID-19/prevenção & controle , Disfunção Cognitiva/prevenção & controle , Terapia por Exercício/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto , AVC Isquêmico/prevenção & controle , Resultado do Tratamento , Cognição , Aptidão Cardiorrespiratória , Imageamento por Ressonância Magnética , SARS-CoV-2 , Ensaios Clínicos Fase II como AssuntoRESUMO
Elevated blood glucose concentration is a risk factor for developing metabolic dysfunction and insulin resistance, leading to type 2 diabetes and cardiovascular diseases. Nuts have the potential to inhibit α-amylase activity, and so lower postprandial glucose, due to their content of polyphenols and other bioactive compounds. We conducted a systematic literature review to assess the ability of extracts from commonly consumed edible parts of nuts to inhibit α-amylase. Among the 31 included papers, only four utilised human α-amylases. These papers indicated that polyphenol-rich chestnut skin extracts exhibited strong inhibition of both human salivary and pancreatic α-amylases, and that a polyphenol-rich almond skin extract was a potent inhibitor of human salivary α-amylase. The majority of the reviewed studies utilised porcine pancreatic α-amylase, which has â¼86% sequence homology with the corresponding human enzyme but with some key amino acid variations located within the active site. Polyphenol-rich extracts from chestnut, almond, kola nut, pecan and walnut, and peptides isolated from cashew, inhibited porcine pancreatic α-amylase. Some studies used α-amylases sourced from fungi or bacteria, outcomes from which are entirely irrelevant to human health, as they have no sequence homology with the human enzyme. Given the limited research involving human α-amylases, and the differences in inhibition compared to porcine enzymes and especially enzymes from microorganisms, it is recommended that future in vitro experiments place greater emphasis on utilising enzymes sourced from humans to facilitate a reliable prediction of effects in intervention studies.
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Nozes , Extratos Vegetais , alfa-Amilases , Nozes/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Animais , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/metabolismo , Suínos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Polifenóis/farmacologia , Polifenóis/química , Juglans/químicaRESUMO
The high concentration of omega-3 polyunsaturated fats, dietary fibers, vitamins, minerals, and polyphenols found in nuts suggest their regular consumption may be a simple strategy for improving reproductive health. This systematic review and meta-analysis aimed to present up-to-date evidence regarding the association between nut intake and fertility outcomes in males and females. Ovid MEDLINE, Embase, CINAHL, and Scopus were searched from inception to 30 June 2023. Eligible articles were interventional or observational studies in human subjects of reproductive age (18-49 y) that assessed the effects (or association) of dietary nut consumption (for a minimum of 3 mo) on fertility-related outcomes. Random-effects meta-analyses were completed to produce a pooled effect estimate of nut consumption on sperm total motility, vitality, morphology, and concentration in healthy males. Four studies involving 875 participants (646 males, 229 females) were included in this review. Meta-analysis of 2 RCTs involving 223 healthy males indicated consumption of ≥ 60g nuts/d increased sperm motility, vitality, and morphology in comparison to controls but had no effect on sperm concentration. Nonrandomized studies reported no association between dietary nut intake and conventional sperm parameters in males, embryo implantation, clinical pregnancy or live birth in males and females undergoing ART. Our meta-analysis shows that including at least 2 servings of nuts daily as part of a Western-style diet in healthy males improves sperm parameters, which are predictors of male fertility. Due to their nutritional profile, nuts were found to have potential to promote successful reproductive outcomes. This trial was registered at PROSPERO (CRD42020204586).
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Nozes , Motilidade dos Espermatozoides , Gravidez , Feminino , Masculino , Humanos , Sementes , Fertilidade , Dieta OcidentalRESUMO
Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model. Selenium was administered via drinking water (1.5 ppm) to pregnant dams from gestational day (GD) 9 to birth, and MIA was induced at GD17 using polyinosinic:polycytidylic acid (poly-I:C, 20 mg/kg via intraperitoneal injection). Foetal placenta and brain cytokine levels were assessed using a Luminex assay and brain elemental nutrients assessed using inductively coupled plasma- mass spectrometry. Adult offspring were behaviourally assessed using a reinforcement learning paradigm, the three-chamber sociability test and the open field test. MIA elevated placental IL-1ß and IL-17, and Se supplementation successfully prevented this elevation. MIA caused an increase in foetal brain calcium, which was prevented by Se supplement. MIA caused in offspring a female-specific reduction in sociability, which was recovered by Se, and a male-specific reduction in social memory, which was not recovered by Se. Exposure to poly-I:C or selenium, but not both, reduced performance in the reinforcement learning task. Computational modelling indicated that this was predominantly due to increased exploratory behaviour, rather than reduced rate of learning the location of the food reward. This study demonstrates that while Se may be beneficial in ameliorating sociability deficits caused by MIA, it may have negative effects in other behavioural domains. Caution in the use of Se supplementation during pregnancy is therefore warranted.
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Transtorno do Espectro Autista , Efeitos Tardios da Exposição Pré-Natal , Selênio , Camundongos , Animais , Feminino , Gravidez , Masculino , Humanos , Comportamento Animal/fisiologia , Selênio/farmacologia , Placenta , Modelos Animais de Doenças , Poli I-C/farmacologia , Suplementos NutricionaisRESUMO
CONTEXT: Globally, depression affects more than 322 million people. Studies exploring the relationship between diet and depression have revealed the benefits of certain dietary patterns and micronutrients in attenuating the symptoms of this disorder. Among these micronutrients, selenium stands out because of its multifaceted role in the brain. OBJECTIVE: To assess the impact of selenium intake and status on symptoms of depression. DATA SOURCES: A systematic search was performed in databases, including PubMed, Web of Science, EMBASE, PsycINFO, Scopus, and gray literature (on April 6, 2021, updated on January 28, 2022), without restrictions of date, language, or study type. DATA EXTRACTION: Studies of adults (18-60 y of age) with depression or depressive symptoms were included. Data on selenium biomarkers and/or intake were included. The risk of bias was assessed using the Joanna Briggs Institute checklists. DATA ANALYSIS: Of the 10 studies included, 2 were cohorts (n = 13â983 and 3735), 3 were cross-sectional (n = 736, 7725, and 200), 1 was case-control (n = 495), and 4 were randomized controlled trials (n = 30, 11, 38, and 63). Several studies have indicated that low selenium intake or concentration may be associated with symptoms of depression. However, this association was inconsistent across the studies included in this systematic review; due to the high heterogeneity, it was not possible to perform meta-analyses. The main contributing factors to the high heterogeneity include the different methodological designs, methods for diagnosing depression, selenium assessment, and clinical conditions. CONCLUSION: Overall, there is insufficient evidence to support a positive role of selenium status in depression. Studies with more accurate methods and adequate assessment of selenium status are needed to better understand the role of this nutrient in depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021220683.
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As, Pb and Hg are common environmental contaminants in low- and middle-income countries. We investigated the association between child toxicant exposure and growth and development and determined if this association was mitigated by Se concentration. Toxicant concentrations in fingernail samples, anthropometry and Bayley's Scales of Infant Development, 3rd edition domains were assessed in 36-month-old children whose mothers had been part of a randomised controlled trial in rural Vietnam. Multivariable regression analyses were performed to estimate the effect of toxicant exposure on clinical outcomes with adjustments for potential confounders and interaction with fingernail Se concentration. We analysed 658 children who had data for at least one physical or developmental outcome, and at least one toxicant measurement, and each of the covariates. Fingernail As concentration was negatively associated with language (estimate per 10 % increase in As: -0·19, 95 % CI: (-0·32, -0·05)). Pb was negatively associated with cognition (estimate per 10 % increase in Pb: -0·08 (-0·15, -0·02)), language (estimate per 10 % increase in Pb: -0·18 (-0·28, -0·10)) and motor skills (estimate per 10 % increase in Pb: -0·12 (-0·24, 0·00)). Hg was negatively associated with cognition (estimate per 10 % increase in Hg: -0·48, (-0·72, -0·23)) and language (estimate per 10 % increase in Hg -0·51, (-0·88, -0·13)) when Se concentration was set at zero in the model. As Se concentration increased, the negative associations between Hg and both cognition and language scores were attenuated. There was no association between toxicant concentration and growth. As, Pb and Hg concentrations in fingernails of 3-year-old children were associated with lower child development scores. The negative association between Hg and neurological development was reduced in magnitude with increasing Se concentration. Se status should be considered when assessing heavy metal toxicants in children and their impact on neurodevelopmental outcomes.
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Observational studies indicate that selenium may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Transcriptomic exploration of the aetiology and progression of NAFLD may offer insight into the role selenium plays in this disease. This study compared gene expression levels of known selenoprotein pathways between individuals with a healthy liver to those with NAFLD. Publicly available gene expression databases were searched for studies that measured global gene expression in liver samples from patients with steatosis and non-alcoholic steatohepatitis (NASH) and healthy controls (with [HOC] or without [HC] obesity). A subset of five selenoprotein-related pathways (164 genes) were assessed in the four datasets included in this analysis. The gene TXNRD3 was less expressed in both disease groups when compared with HOC. SCLY and SELENOO were less expressed in NASH when compared with HC. SELENOM, DIO1, GPX2, and GPX3 were highly expressed in NASH when compared to HOC. Disease groups had lower expression of iron-associated transporters and higher expression of ferritin-encoding sub-units, consistent with dysregulation of iron metabolism often observed in NAFLD. Our bioinformatics analysis suggests that the NAFLD liver may have lower selenium levels than a disease-free liver, which may be associated with a disrupted iron metabolism. Our findings indicate that gene expression variation may be associated with the progressive risk of NAFLD.
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BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease globally. Nuts and seeds, due to their unique nutrient composition, may provide health benefits for the prevention of NAFLD. To date, no research has investigated the association between nut and seed intake and NAFLD prevalence in a non-Mediterranean Western population. OBJECTIVES: This study aimed to explore the association between nut and seed intake with NAFLD and metabolic biomarkers in a US representative sample. METHODS: This cross-sectional study used data from 25,360 adults involved in the 2005-2018 NHANES, including adults (aged ≥18 y) with negative serology for hepatitis B and C and nonexcessive alcohol consumption. NAFLD was assessed using the fatty liver index (FLI); metabolic biomarkers were also assessed; nut and seed intake was evaluated from two 24-h dietary recalls. ANOVA and Poisson regression were used to establish the relation between nut and seed intake categories and NAFLD prevalence. RESULTS: Nut and seed consumption was associated with a reduced prevalence of NAFLD. In females, in the fully adjusted model, this was significant across all nut and seed consumption categories but was most prominent in the moderate consumption group (7%, 15%, and 14% risk reduction in low, moderate, and adequate consumption categories, respectively, compared with nonconsumers). In males, moderate intake of nuts and seeds demonstrated a significantly lower prevalence of NAFLD (9%) compared with nonconsumers. CONCLUSIONS: Daily consumption for nuts and seeds was associated with a lower prevalence of NAFLD in non-Mediterranean, US adults, although the benefits seem to be greater in females across all categories of nut and seed consumption groups compared with nonconsumers. Both males and females presented with lower prevalence of NAFLD with intakes of 15-30 g/d.
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Hepatopatia Gordurosa não Alcoólica , Nozes , Adulto , Idoso , Estudos Transversais , Dieta , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Inquéritos Nutricionais , PrevalênciaRESUMO
Although literature has been consistently showing an increased risk of type 2 diabetes (T2DM) in populations with high exposure to selenium, there is a lack of information quantifying the association between diabetes-related markers and the nutritional status of selenium. Therefore, we aimed to investigate the association between blood selenium concentration and glucose markers in a representative sample of the US population, which is known to have moderate to high exposure to selenium. This cross-sectional analysis included 4,339 participants ≥18 years from the 2013 to 2018 National Health and Nutrition Examination Survey (NHANES). All participants were assessed for whole blood selenium concentration, fasting plasma insulin and glucose, HbA1c, and HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). In this cohort, all participants presented with adequate selenium status [196.2 (SD: 0.9) µg/L] and 867 (15%) had diabetes mellitus. Selenium was positively associated with insulin, glucose and HOMA-IR in models adjusted for age and sex. When the models were further adjusted for smoking status, physical activity, metabolic syndrome and BMI, the associations with insulin and HOMA-IR remained but the association with glucose was no longer significant. A 10 µg/L increase in selenium was associated with 1.5% (95% CI: 0.4-2.6%) increase in insulin and 1.7% (95% CI: 0.5-2.9%) increase in HOMA-IR in fully adjusted models. There was no evidence of an association between selenium and diabetes prevalence. Our findings corroborate the notion that selenium supplementation should not be encouraged in populations with high dietary intake of selenium.
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BACKGROUND: Nuts are nutrient-rich and reported to provide some cognitive and cardiometabolic health benefits, but limited studies have focused on older adults. This study investigated the cross-sectional relationship between habitual nut intake, dietary pattern and quality, cognition and non-alcoholic fatty liver disease (NAFLD) in older adults. METHODS: Older adults (≥ 60 years) from the NHANES 2011-12 and 2013-14 cohorts, who had complete data on cognitive function (as CERAD total, delayed recall, animal fluency and digit-symbol substitution test) and variables to calculate the Fatty Liver Index (FLI), an indicator of NAFLD, were included (n = 1848). Nut intake and diet quality (Healthy Eating Index 2015) were determined using two 24-hour diet recalls. Participants were categorised into one of four groups based on their habitual nut intake: non-consumers (0 g/d), low intake (0.1-15.0 g/d), moderate intake (15.1-30.0 g/d) or met recommendation (> 30 g/d), with all outcomes compared between these nut intake groups. RESULTS: Cognitive scores of older adults were the lowest in non-consumers and significantly highest in the moderate intake group, with no further increase in those who consumed nuts more than 30 g/d (p < 0.007). FLI was the lowest among older adults with moderate nut intake but the associations disappeared after adjusting for covariates (p = 0.329). Moderate nut intake was also associated with better immediate and delayed memory in older adults with high risk of NAFLD (FLI ≥ 60) (B = 1.84 and 1.11, p < 0.05 respectively). Higher nutrient intake and better diet quality (p < 0.001) were seen with higher nut intake but did not influence energy from saturated fat intake. Factor analysis revealed 'Nuts and oils' as one of the four major dietary patterns associated with better cognition and lower FLI scores. CONCLUSIONS: Moderate nut intake (15.1-30.0 g/d) may be sufficient for better cognitive performance, but not NAFLD risk of older adults in the US.
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Hepatopatia Gordurosa não Alcoólica , Nozes , Idoso , Cognição , Estudos Transversais , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Inquéritos Nutricionais , Estados Unidos/epidemiologiaRESUMO
Diet is considered an important modifiable lifestyle factor capable of attenuating early cognitive changes in healthy older people. The inclusion of nuts in the diet has been investigated as a dietary strategy for maintenance of brain health across the lifespan. This review aimed to present up-to-date evidence regarding the association between nut intake and cognitive performance. Four databases (Ovid MEDLINE, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus, and Embase) were systematically searched from inception to April 2020. Eligible articles were interventional or observational studies in humans aged ≥18 y that measured the effects (or association) of nuts (almond, hazelnut, macadamia, pistachio, walnut, pecan, pine nut, Brazil nut, cashew, peanut) on cognitive outcomes. Out of the 2374 articles identified in the searches, 22 involving 43,793 participants met the criteria and were ultimately included in this review. Memory (immediate and delayed), attention, processing speed, executive function, and visual-spatial ability, as well as risk of mild cognitive impairment, were the outcomes investigated. Lack of consistency across the studies regarding study design, types of nut used, and cognitive outcomes measured resulted in inconsistent evidence that the regular consumption of mixed nuts has a protective effect on cognition in adults of different ages. Nonetheless, we observed that studies targeting populations with a higher risk of cognitive decline tended to find a more favorable outcome. Furthermore, homogeneous findings were observed in the studies that specifically addressed the association between walnut consumption and cognitive performance: out of the 6 studies, including 2 randomized controlled trials, only 1 did not find a positive association.
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Nozes , Prunus dulcis , Adulto , Idoso , Alérgenos , Arachis , Cognição , HumanosRESUMO
BACKGROUND: Direct supplementation or food fortification with iron are two public health initiatives intended to reduce the prevalence of iron deficiency (ID) and iron deficiency anaemia (IDA) in 4-24-month-old infants. In most high-income countries where IDA prevalence is < 15%, the recommended daily intake levels of iron from supplements and/or consumption of fortified food products are at odds with World Health Organisation (WHO) guidelines that recommend shorter-term (3 months/year) supplementation only in populations with IDA prevalence > 40%. Emerging concerns about delayed neurological effects of early-life iron overexposure have raised questions as to whether recommended guidelines in high-income countries are unnecessarily excessive. This systematic review will gather evidence from supplementation/fortification trials, comparing health outcomes in studies where iron-replete children did or did not receive additional dietary iron; and determine if replete children at study outset were not receiving additional iron show changes in haematological indices of ID/IDA over the trial duration. METHODS: We will perform a systematic review of the literature, including all studies of iron supplementation and/or fortification, including study arms with confirmed iron-replete infants at the commencement of the trial. This includes both dietary iron intervention or placebo/average dietary intakes. One reviewer will conduct searches in electronic databases of published and ongoing trials (Medline, Web of Science, Scopus, CENTRAL, EBSCO [e.g. CINAHL Complete, Food Science and Technology Abstracts], Embase, ClinicalTrials.gov, ClinicalTrialsRegister.eu and who.it/trialsearch), digital theses and dissertations (WorldCat, Networked Digital Library of Theses and Dissertations, DART-Europe E-theses Portal, Australasian Digital Theses Program, Theses Canada Portal and ProQuest). For eligible studies, one reviewer will use a data extraction form, and a second reviewing entered data for accuracy. Both reviewers will independently perform quality assessments before qualitative and, if appropriate, quantitative synthesis as a meta-analysis. We will resolve any discrepancies through discussion or consult a third author to resolve discrepancies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement will be used as the basis for reporting. DISCUSSION: Recommended iron supplementation and food fortification practices in high-income countries have been criticised for being both excessive and based on outdated or underpowered studies. This systematic review will build a case for revisiting iron intake guidelines for infants through the design of new trials where health effects of additional iron intake in iron-replete infants are the primary outcome. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018093744.
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Anemia Ferropriva , Alimentos Fortificados , Ferro da Dieta , Pré-Escolar , Humanos , Lactente , Anemia Ferropriva/prevenção & controle , Canadá , Suplementos Nutricionais , Europa (Continente) , Ferro da Dieta/administração & dosagem , Estado Nutricional , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
Selenium is an essential trace element in human health and therefore its concentration in biological samples (biofluids and tissues) is used as an indicator of health and nutritional status. In humans, selenium's biological activity occurs through the 25 identified selenoproteins. As total selenium concentration encompasses both functional selenoproteins, small selenocompounds and other selenium-binding proteins, selenium speciation, rather than total concentration, is critical in order to assess functional selenium. Previously, quantitative analysis of selenoproteins required laborious techniques that were often slow and costly. However, more recent advancements in tandem mass spectrometry have facilitated the qualitative and quantitative identification of these proteins. In light of the current alternatives for understanding selenium biochemistry, we aim to provide a review of the modern applications of electrospray ionisation mass spectrometry (ESI-MS) as an alternative to inductively coupled plasma mass spectrometry (ICP-MS) for qualitative and quantitative selenium speciation.
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Proteínas de Ligação a Selênio/análise , Selênio/análise , Selenoproteínas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Oligoelementos/análise , Cromatografia Líquida de Alta Pressão/métodos , HumanosRESUMO
Dyshomeostasis of copper and zinc is linked to neurodegeneration. This study investigated the relationship between circulating copper and zinc and copper/zinc ratios and cognitive function, symptoms of depression and anxiety, and neurotrophic factors in older Australian adults. In this cross-sectional study (n = 139), plasma copper, serum zinc, and neurotrophic factors (brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor, and insulin-like growth factor-1) were assessed. Cognition was assessed using the Cogstate battery and the Behavior Rating Inventory (BRI) of Executive Function (Adult version). Symptoms of anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. Copper (ß = -0.024; 95% CI = -0.044, -0.004; p = 0.019) and copper/zinc ratio (ß = -1.99; 95% CI = -3.41, -0.57; p = 0.006) were associated with lower depressive symptoms, but not cognition. Plasma copper had a modest positive association with BDNF (ß = -0.004; 95% CI = 0.000, 0.007; p = 0.021). Zinc was not associated with any of the outcomes. In conclusion, greater circulating copper concentrations and higher copper/zinc ratios were associated with lower depressive symptoms (but not cognition), with copper also positively associated with BDNF concentration, in a sample of community-dwelling older adults.
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Ansiedade/sangue , Cognição/fisiologia , Cobre/sangue , Depressão/sangue , Angústia Psicológica , Zinco/sangue , Idoso , Idoso de 80 Anos ou mais , Austrália , Feminino , Humanos , MasculinoRESUMO
Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0.32 mg sodium selenate, 3 times daily), or supranutritional (10 mg, 3 times daily) groups. We measured total selenium, selenoproteins, and inorganic selenium levels, in serum and CSF, and compared against cognitive outcomes. Supranutritional selenium supplementation was well tolerated and yielded a significant (p < 0.001) but variable (95% CI = 13.4-24.8 µg/L) increase in CSF selenium, distributed across selenoproteins and inorganic species. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not deteriorate in Mini-Mental Status Examination (MMSE) as non-responsive group (p = 0.03). Pooled analysis of all samples revealed that CSF selenium could predict change in MMSE performance (Spearman's rho = 0.403; p = 0.023). High-dose sodium selenate supplementation is well tolerated and can modulate CNS selenium concentration, although individual variation in selenium metabolism must be considered to optimize potential benefits in AD. The Vel002 study is listed on the Australian and New Zealand Clinical Trials Registry ( http://www.anzctr.org.au /), ID: ACTRN12611001200976.
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Doença de Alzheimer/tratamento farmacológico , Antioxidantes , Ácido Selênico , Selênio , Oligoelementos , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Ácido Selênico/administração & dosagem , Ácido Selênico/sangue , Ácido Selênico/líquido cefalorraquidiano , Selênio/administração & dosagem , Selênio/sangue , Selênio/líquido cefalorraquidiano , Oligoelementos/administração & dosagem , Oligoelementos/sangue , Oligoelementos/líquido cefalorraquidianoRESUMO
Selenium was suggested to play a role in modulating cognitive performance and dementia risk. Thus, this study aimed to investigate the association between selenium status and cognitive performance, as well as inflammatory and neurotrophic markers in healthy older adults. This cross-sectional study included 154 older adults (≥60 years) from Victoria, Australia. Participants were assessed for cognitive performance (Cogstate battery), dietary selenium intake (two 24-h food recalls), plasma selenium concentration, inflammatory markers (interleukin (IL)-6, -8, -10, tumor necrosis factor-alpha and adiponectin) and neurotrophic factors (brain-derived neurotrophic factor, vascular endothelial growth factor and insulin-like growth factor 1). Dietary selenium intake was adequate for 85% of all participants. The prevalence of selenium deficiency was low; only 8.4% did not have the minimum concentration in plasma required for optimization of iodothyronine 5' deiodinases activity. Multiple linear regression analysis revealed that plasma selenium was not associated with cognitive performance, inflammatory markers nor neurotrophic factors, independent of age, sex, body mass index (BMI), habitual physical activity, APOE status, education, and history of cardiovascular disease. The lack of association might be due to the optimization of selenoproteins synthesis as a result of adequate selenium intake. Future prospective studies are recommended to explore potential associations of selenium status with age-associated cognitive decline.
Assuntos
Cognição , Disfunção Cognitiva , Estado Nutricional , Selênio/sangue , Adiponectina/sangue , Idoso , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/sangue , Disfunção Cognitiva/etiologia , Estudos Transversais , Citocinas/sangue , Feminino , Humanos , Inflamação/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Modelos Lineares , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Selênio/deficiência , Fator A de Crescimento do Endotélio Vascular/sangue , VitóriaRESUMO
PURPOSE: Considering that oxidative stress is implicated in the pathogenesis and progression of different health conditions, we aimed to evaluate whether the redox balance of a healthy Brazilian population is associated with GPX1 polymorphisms, selenium status, lipid profile, and anthropometric and lifestyle parameters. METHODS: 343 healthy adults were assessed for redox balance markers [glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity; malondialdehyde (MDA) and oxygen radical absorption capacity (ORAC)]; genotyped for the polymorphisms GPX1 Pro198Leu (rs1050450), -602A/G (rs3811699) and Arg5Pro (rs8179169); evaluated for selenium biomarkers (plasma, erythrocyte, and urine) and intake; and assessed for lipid profile. Anthropometric (BMI) and lifestyle data (physical activity, current smoking habit and alcohol consumption) were collected. Multivariable regression models were applied to investigate the possible associations. RESULTS: Although there were no differences in GPx activity according to GPX1 Pro198Leu and -602A/G polymorphisms, this redox balance marker was positively associated with erythrocyte selenium and negatively associated with the presence of a minor allele of Pro198Leu. SOD activity was positively associated with the presence of a minor allele for these polymorphisms. ORAC showed the same pattern among Leu and G carriers and was positively associated with Leu allele presence, BMI and alcohol intake. MDA was only associated negatively with the male sex and plasma selenium. CONCLUSIONS: Our findings suggest that the redox balance of a Brazilian healthy population is associated with GPX1 polymorphisms (Pro198Leu and -602A/G), selenium status, BMI, sex, smoking habit and alcohol consumption.
Assuntos
Glutationa Peroxidase/genética , Mutação de Sentido Incorreto , Estresse Oxidativo , Polimorfismo de Nucleotídeo Único , Selênio/sangue , Adulto , Antropometria , Brasil , Estudos Transversais , Feminino , Genótipo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Oxirredução , Fatores Sexuais , Adulto Jovem , Glutationa Peroxidase GPX1RESUMO
Melatonin is an endogenous pleiotropic molecule which orchestrates regulatory functions and protective capacity against age-related ailments. The increase in circulating levels of melatonin through dietary supplements intensifies its health benefits. Investigations in animal models have shown that melatonin protects against Alzheimer's disease (AD)-like pathology, although clinical studies have not been conclusive. We hypothesized that melatonin induces changes in the brain that prevent or attenuate AD by increasing resilience. Therefore, we treated healthy nontransgenic (NoTg) and AD transgenic (3xTg-AD) 6-month-old mice with a daily dose of 10 mg/kg of melatonin until 12 months of age. As expected, melatonin reversed cognitive impairment and dementia-associated behaviors of anxiety and apathy and reduced amyloid and tau burden in 3xTg-AD mice. Remarkably, melatonin induced cognitive enhancement and higher wellness level-related behavior in NoTg mice. At the mechanism level, NF-κB and proinflammatory cytokine expressions were decreased in both NoTg and 3xTg-AD mice. The SIRT1 pathway of longevity and neuroprotection was also activated in both mouse strains after melatonin dosing. Furthermore, we explored new mechanisms and pathways not previously associated with melatonin treatment such as the ubiquitin-proteasome proteolytic system and the recently proposed neuroprotective Gas6/TAM pathway. The upregulation of proteasome activity and the modulation of Gas6 and its receptors by melatonin were similarly displayed by both NoTg and 3xTg-AD mice. Therefore, these results confirm the potential of melatonin treatment against AD pathology, by way of opening new pathways in its mechanisms of action, and demonstrating that melatonin induces cognitive enhancement and brain resilience against neurodegenerative processes.