Efeito dos aminoácidos de cadeia ramificada na modulação da resposta inflamatória induzida por LPS em células intestinais Caco-2 / Effect of branched-chain amino acids on the inflammatory response modulation induced by LPS in Caco-2 intestinal cells

Introdução: A inflamação é um fator presente na fisiopatologia de doenças, e, o intestino, órgão susceptível a disfunções e à disbiose, que está em constante exposição a microrganismos, pode estar associado a este processo. Por outro lado, aminoácidos de cadeia ramificada (ACR) podem apresentar efeitos anti-inflamatórios em linhagem celular intestinal. Objetivo: Investigar os efeitos da suplementação de ACR, in vitro, na modulação da resposta inflamatória e do estresse oxidativo induzida por LPS em modelo de células intestinais Caco-2. Métodos: As culturas de células foram distribuídas em seis grupos, sendo: dois grupos controle - controle com meio Dulbecco's Modified Eagle's Medium sem ACR (CTL0) e com ACR (CTL) - e quatro grupos suplementados - grupo leucina (LEU), grupo isoleucina (ISO), grupo valina (VAL) e associação de ACR (LIV). Foi adotado um protocolo de pré-tratamento, com os ACR e o LPS. A viabilidade celular foi avaliada pelo ensaio de redução do MTT (brometo de [3-(4,5-dimetiltiazol-2yl 2,5-difenil tetrazolium]). A análise de proteínas (mTOR, AKT, AMPK, NF-kB, TAK-1 e JNK) foi feita por Western Blotting. A dosagem de citocina IL-8 no sobrenadante de cultura celular foi realizada por meio do kit Multiplex para imunoensaio. Foram avaliados componentes do sistema antioxidante relacionado à glutationa (GSH, GSSG e GPx) por meio de kit comercial. Os resultados foram expressos como média ± erro padrão. Resultados: No teste de viabilidade celular por MTT, verificou-se que os grupos tratados com ACR e LPS não apresentaram comprometimento da viabilidade celular em relação ao grupo CTL sem LPS. Os grupos CTL0, CTL, VAL e LIV, quando estimulados com LPS, apresentaram maior capacidade de síntese, in vitro, de IL-8, bem como maior fosforilação das proteínas JNK e NF-kB em relação aos seus respectivos grupos sem LPS. A suplementação. Todavia, as células estimuladas com LPS e suplementadas com leucina e isoleucina apresentaram capacidade de síntese, in vitro, de IL-8 e fosforilação das proteínas JNK e NF-kB que não diferiram significativamente das células suplementadas com esses aminoácidos e não estimuladas com LPS. A ausência de ACR (grupo CTL0) e a suplementação desses aminoácidos, in vitro, em células intestinais Caco-2, tratadas com ou sem LPS, não induziram alteração da atividade da enzima GPx e da razão intracelular GSH/GSSG. Conclusões: Os aminoácidos leucina e isoleucina apresentaram potencial efeito anti-inflamatório nas células Caco-2 por meio da modulação da fosforilação das proteínas JNK e NF-kB, cujo fato está associado à modulação da síntese, in vitro, de IL-8, a qual está envolvida na resposta inflamatória no intestino.

Introduction: Inflammation is a factor present in the pathophysiology of diseases, and the intestine, an organ susceptible to dysfunction and dysbiosis, which is constantly exposed to microorganisms, may be associated with this process. On the other hand, branched-chain amino acids (BCAAs) may have anti-inflammatory effects on intestinal cell lines. Objective: To investigate the effects of ACR supplementation, in vitro, on the modulation of inflammatory response and oxidative stress induced by LPS in a model of intestinal Caco-2 cells. Methods: The cell cultures were divided into six groups, as follows: two control groups - control with Dulbecco's Modified Eagle's Medium without ACR (CTL0) and with ACR (CTL) - and four supplemented groups - leucine group (LEU), isoleucine group (ISO), valine group (VAL) and ACR association (LIV). A pre-treatment protocol was adopted, with ACR and LPS. Cell viability was assessed by MTT reduction assay ([3-(4,5-dimethylthiazol-2yl 2,5-diphenyl tetrazolium] bromide)) Protein analysis (mTOR, AKT, AMPK, NF-kB, TAK -1 and JNK) was performed by Western Blotting. The dosage of cytokine IL-8 in the cell culture supernatant was performed using the Multiplex kit for immunoassay. Components of the antioxidant system related to glutathione (GSH, GSSG, and GPx) were evaluated by commercial kit. The results were expressed as mean ± standard error. Results: In the cell viability test by MTT, it was verified that the groups treated with ACR and LPS did not show impairment of cell viability compared to the CTL group without LPS. The CTL0, CTL, VAL, and LIV groups, when stimulated with LPS, showed a greater capacity for in vitro synthesis of IL-8, as well as greater phosphorylation of JNK and NF-kB proteins in relation to their respective groups without LPS. However, cells stimulated with LPS and supplemented with leucine and isoleucine showed in vitro synthesis capacity of IL-8 and phosphorylation of JNK and NF-kB proteins that did not differ significantly from cells supplemented with these amino acids and not stimulated with LPS. The absence of ACR (CTL0 group) and the supplementation of these amino acids, in vitro, in intestinal Caco-2 cells, treated with or without LPS, did not induce changes in the activity of the GPx enzyme and the intracellular GSH/GSSG ratio. Conclusions: The amino acids leucine and isoleucine had a potential anti-inflammatory effect on Caco-2 cells by modulating the phosphorylation of JNK and NF-kB proteins, which fact is associated with the modulation of the in vitro synthesis of IL-8, which is involved in the inflammatory response in the gut.

Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Associations of blood biomarkers and structural changes in atherosclerosis in the Longitudinal study of adult heath (Elsa-Brasil): emphasis on pre-and postmenopausal women / Associações de biomarcadores sanguíneos e mudanças estruturais na aterosclerose no Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil): ênfase em mulheres na pré e pós-menopausa

Background: Cardiovascular disease is the leading cause of morbidity and mortality in women worldwide. Cardiovascular risk prediction is incomplete and new markers may help in the early identification of atherosclerosis. Brazilian epidemiological data in women are scarce. Objectives: To review the impact of menopause and diabetes on lipids, lipoprotein subfractions and cardiovascular risk; evaluate cardiometabolic risk in women from the ELSA-Brasil, as well as associations of blood biomarkers [lipoprotein subfractions, insulin resistance index (HOMA-IR) and branched-chain amino acids (BCAA)] and structural changes of atherosclerosis [presence of calcium in the coronary arteries (CAC)] according to age and menopausal status. Methods: Cross-sectional baseline analyzes of 2,258 female participants from the São Paulo site of the ELSA-Brasil, stratified by age and menopausal status, with specific sample and eligibility criteria for each paper. Descriptive statistics, between-group comparisons and multiple regression were performed according to the nature and distribution of the variables for each paper. Results: Paper 1: Literature revision enabled conclusions regarding the association of menopause and diabetes with a worse lipid profile, including hypertriglyceridemia, lower levels of HDL-c and HDL2-c, higher levels of HDL3-c and small dense LDL-c. Postmenopausal diabetic women consist of the highest cardiovascular risk level. Paper 2: Comparing pre- and postmenopausal women categorized according to time since menopause [menopausal duration <2 years, 2-5.9 years, 6-9.9 years or ≥ 10 years (n=1916)], postmenopausal women had a worse lipid and lipoprotein subfraction profile and duration of menopause <2 years was independently associated with remnant lipoprotein cholesterol (TRL-c) [7.21 mg/dL (95% CI 3.5910.84)] and smaller denser VLDL3-c [2.43 mg/dL (95%CI 1.023.83)], but no associations of menopausal categories with HDL-c or LDL-c subfractions were found, when taking premenopausal women as reference. Paper 3: Comparing premenopausal ≤ or >45 years and postmenopausal women (n=2047), postmenopausal ones had the worst cardiometabolic risk profile. CAC>0 was found to be associated with TRL-c and dense LDL-c, but not with BCAA levels nor HOMA-IR. Postmenopausal women were about twice as likely to have CAC>0 than younger premenopausal ones [OR 2.37 (95%CI 1.17-4.81)]. Discussion: Our findings suggest that natural menopause is associated with changes in lipoprotein fractions and subfractions (especially in the first 2 years post-menopause) and with calcium deposition in the coronary arteries independently of age and other risk factors, but not with BCAA nor HOMA-IR. Deep investigation on lipid profile and other biomarkers in women approaching to menopause is needed in order to identify cardiovascular risk, prevent cardiovascular outcomes and provide better health conditions.

Introdução: A doença cardiovascular se constitui na principal causa de morbimortalidade em mulheres globalmente. A predição de evento cardiovascular é incompleta e novos marcadores de risco cardiometabólico podem auxiliar na identificação precoce da aterosclerose. Dados epidemiológicos brasileiros no sexo feminino são mais escassos. Objetivos: Revisar o impacto da menopausa e diabetes nas lipoproteínas, subfrações e risco cardiovascular; avaliar o perfil de risco cardiometabólico de mulheres do ELSA-Brasil, bem como associações de marcadores sanguíneos [subfrações de lipoproteínas circulantes, índice de resistência à insulina (HOMA-IR) e aminoácidos de cadeia ramificada (BCAA)] e estruturais [cálcio nas artérias coronárias (CAC)] de aterosclerose segundo sua idade e estado menopausal. Métodos: Análise transversal de dados basais de 2258 mulheres acompanhadas no centro de São Paulo do ELSA-Brasil, estratificadas por idade e estado menopausal, respeitando características amostrais estabelecidas para cada artigo. Estatística descritiva, testes de comparação entre grupos e análises de regressão múltipla foram realizadas conforme natureza e distribuição das variáveis para cada artigo. Resultados: Artigo 1: A revisão da literatura permitiu concluir sobre a associação de menopausa e diabetes com pior perfil lipídico, consistindo de hipertrigliceridemia, baixos níveis de HDL-c e HDL2-c e elevados de HDL3-c e LDL-c pequena e densa. Mulheres menopausadas com diabetes apresentam o maior risco cardiovascular. Artigo 2: Comparando-se mulheres pré-menopausadas com as menopausadas, categorizadas segundo tempo de menopausa [duração <2 anos; 2-5,9 anos; 6-9,9 anos e ≥ 10 anos (n=1916)], aquelas na pós-menopausa apresentaram perfil de lipoproteínas e suas subfrações mais aterogênico e a duração da menopausa <2 anos associou-se independentemente com remanescentes de lipoproteínas ricas em triglicérides (TRL-c) [7,21 mg/dL (IC95% 3,5910,84)] e com a partícula pequena e densa de VLDL3-c [2,43 mg/dL (IC95% 1,023,83)], mas não foram encontradas associações de categorias de menopausa com as subfrações de HDL-c ou LDL-c, considerando-se as pré-menopausadas como referência. Artigo 3: Comparando mulheres pré-menopausadas com idade ≤ ou >45 anos e as menopausadas (n=2047), pior perfil de risco cardiometabólico foi encontrado em mulheres na pós- menopausa. Observou-se associação entre CAC>0 com TRL-c e LDL-c densa, mas não com HOMA-IR e BCAA. Mulheres menopausadas tiveram cerca de 2 vezes mais chance de apresentar CAC>0 quando comparadas com mulheres mais jovens na pré-menopausa [OR 2,37 (IC95% 1,17-4,81)]. Discussão: Nossos achados sugerem que a menopausa natural está associada a alterações no perfil lipídico tradicional e subfrações (especialmente nos primeiros 2 anos pós-menopausa) e ao depósito de cálcio nas artérias coronárias independentemente da idade e de outros fatores de risco, mas não com BCAA e HOMA-IR. Investigação aprofundada do perfil lipídico e outros marcadores de risco cardiovascular em mulheres que se aproximam da menopausa pode melhorar a identificação de risco, prevenção de desfechos cardiovasculares e proporcionar melhores condições de saúde.

Aminoácidos de cadena ramificada: implicaciones en la salud / Branched chain amino acids and health implications

El consumo de proteína y especialmente aminoácidos esenciales juega un papel fundamental en la dieta, ya que suple las necesidades de nitrógeno del organismo y favorece el mantenimiento de estructuras corporales. En los últimos años, la nutrición y la tecnología de los alimentos están experimentando una profunda transformación debido al desarrollo del concepto de alimentos funcionales y nutracéuticos. Tanto las proteínas funcionales como los péptidos bioactivos están cobrando gran importancia ya que, además de su papel nutricional por ser fuente de aminoácidos, son capaces de ejercer diferentes efectos biológicos específicos sobre el sistema inmune, el sistema cardiovascular o el tracto gastrointestinal. Los aminoácidos de cadena ramificada (BCAAs denominación por las siglas en inglés) como lo son la Leucina, Isoleucina y Valina son considerados útiles para el tratamiento y predicción de algunas enfermedades, el presente artículo de revisión, se recopila información acerca de los aminoácidos de cadena ramificada y su uso positivo en el tratamiento de diferentes patologías como enfermedades neurológicas, hepáticas, cardiometabólicas, cáncer, además de su uso en deportistas. Se tuvieron en cuenta los siguientes criterios de inclusión: 1. La búsqueda se realizó en reconocidas bases de datos, 2. Se incluyeron artículos desde el 2006 a la fecha, 3. Se realizó la búsqueda con palabras como aminoácidos de cadena ramificada y efecto en diferentes patologías, con la inclusión de artículos donde se menciona el consumo humano de los mismos, se excluyeron artículos donde los aminoácidos no intervengan de manera positiva en su consumo y tratamiento de enfermedades(AU)

The consumption of protein and especially essential amino acids play a fundamental role in the diet, in order to meet the body's nitrogen needs and the maintenance of body structures. In recent years nutrition and food technology are undergoing a profound transformation due to the development of the concept of functional foods and nutraceuticals. Both functional proteins and bioactive peptides are becoming very important since, in addition to their nutritional role as a source of amino acids, they are capable of exerting different specific biological effects on the immune system, the cardiovascular system or the gastrointestinal tract. Branched-chain amino acids (BCAAs), such as Leucine, Isoleucine and Valine, are considered useful for the treatment and prediction of some diseases. This review article collects information about branched-chain amino acids. and it's positive use in the treatment of different pathologies such as neurological, liver, cardiometabolic diseases, cancer, in addition to it's use in athletes. The following inclusion criteria were taken into account: 1. The search was carried out in recognized databases, 2. Articles were included from 2006 to date, 3. The search was carried out with words such as branched-chain amino acids and effect in different pathologies, with the inclusion of articles where their human consumption is mentioned, articles were excluded where amino acids do not intervene positively in their consumption and treatment of diseases(AU)

Free carnitine and branched chain amino acids are not good biomarkers in Huntington's disease / Carnitina livre e aminoácidos de cadeia ramificada não são bons biomarcadores na doença de Huntington

ABSTRACT Background: Huntington's disease (HD), caused by an expanded CAG repeat at HTT, has no treatment, and biomarkers are needed for future clinical trials. Objective: The objective of this study was to verify if free carnitine and branched chain amino acids levels behave as potential biomarkers in HD. Methods: Symptomatic and asymptomatic HD carriers and controls were recruited. Age, sex, body mass index (BMI), age of onset, disease duration, UHDRS scores, and expanded CAG tract were obtained; valine, leucine, isoleucine, and free carnitine were measured. Baseline and longitudinal analysis were performed. Results: Seventy-four symptomatic carriers, 20 asymptomatic carriers, and 22 non-carriers were included. At baseline, valine levels were reduced in symptomatic and asymptomatic HD carriers when compared to non-carriers. No difference in free carnitine or isoleucine+leucine levels were observed between groups. BMI of symptomatic individuals was lower than those of non-carriers. Valine levels correlated with BMI. Follow-up evaluation was performed in 43 symptomatic individuals. UHDRS total motor score increased 4.8 points/year on average. No significant reductions in BMI or valine were observed, whereas free carnitine and isoleucine+leucine levels increased. Conclusions: Although valine levels were lower in HD carriers and were related to BMI losses observed in pre-symptomatic individuals, none of these metabolites seem to be biomarkers for HD.

RESUMO Introdução: A doença de Huntington (DH), causada por uma repetição CAG expandida no HTT, não possui tratamento e biomarcadores são necessários para futuros ensaios clínicos. Objetivo: Nosso objetivo foi verificar se os níveis de carnitina livre e aminoácidos de cadeia ramificada se comportam como potenciais biomarcadores na DH. Métodos: Portadores sintomáticos e assintomáticos e controles foram recrutados. Idade, sexo, índice de massa corporal (IMC), idade de início, duração da doença, escores UHDRS e trato CAG expandido foram obtidos; valina, leucina, isoleucina e carnitina livre foram medidas. Foram realizadas análises basal e longitudinal. Resultados: Setenta e quatro portadores sintomáticos, 20 portadores assintomáticos e 22 não portadores foram incluídos. No início do estudo, os níveis de valina estavam reduzidos em portadores de DH sintomáticos e assintomáticos quando comparados aos não portadores. Não foram observadas diferenças nos níveis de carnitina livre ou isoleucina + leucina entre os grupos. O IMC dos indivíduos sintomáticos foi menor que o dos não portadores. Níveis de valina correlacionaram-se com o IMC. Avaliação de acompanhamento foi realizada em 43 indivíduos sintomáticos. A pontuação do escore motor total da UHDRS aumentou 4,8 pontos/ano em média. Não foram observadas reduções significativas no IMC ou na valina, enquanto os níveis de carnitina livre e isoleucina+leucina aumentaram. Conclusões: Embora os níveis de valina tenham sido menores nos portadores de DH e estivessem relacionados às perdas de IMC observadas em indivíduos pré-sintomáticos, nenhum desses metabólitos parece ser biomarcador para a DH.

Branched-Chain amino acids intake is negatively related to body adiposity in individuals at cardiometabolic risk / Consumo de aminoácidos de cadeia ramificada está negativamente relacionado com adiposidade corporal em indivíduos com risco cardiometabólico

ABSTRACT Objective To assess the relationship between branched-chain amino acids intake in the current diet and the metabolic and body adiposity markers in a population at cardiovascular risk. Methods This is a cross-sectional study with 282 adults and elderly people from the Cardiovascular Health Care Program of the Universidade Federal de Viçosa. Sociodemographic, anthropometric and body composition data, as well as metabolic biomarkers were collected using standardized protocols. Dietary intake of branched amino acids was assessed using a 24-hour recall. Results Individuals with a higher branched-chain amino acids intake (≥2.6g/day, median value) had lower body fat (29.6 vs 32.2%; p=0.019), and higher serum ferritin (113.2 vs. 60.1mg/dL; p=0.006) and uric acid concentrations (4.4 vs. 4.0; p=0.023). In addition, a lower prevalence of overweight and excessive abdominal fat (p<0.05) was found in the individuals with higher branched-chain amino acids intake. They also had a higher daily intake of fiber, copper, zinc, magnesium, and iron, as well as a lower intake of total lipids. Conclusion In the present study, the intake of branched amino acids is negatively related to total and central adiposity, but more studies are needed to fully elucidate this possible relationship. (Brazilian Registry of Clinical Trials, code RBR-5n4y2g).

RESUMO Objetivo Avaliar a relação entre o consumo de aminoácidos de cadeia ramificada na dieta atual e os marcadores de adiposidade metabólica e corporal em uma população com perfil de elevado risco cardiovascular. Métodos Trata-se de um estudo transversal com 282 adultos e idosos do Programa de Atenção Cardiovascular da Universidade Federal de Viçosa. Dados sociodemográficos, antropométricos e de composição corporal, além de biomarcadores metabólicos, foram coletados utilizando protocolos padronizados. O consumo alimentar de aminoácidos ramificados foi avaliado através de um recordatório de 24 horas. Resultados Indivíduos com maior consumo de aminoácidos de cadeia ramificada (≥2,6g/dia, valor da mediana) apresentaram menores valores de gordura corporal (29,6 vs 32,2%; p=0,019) e maiores valores de séricos de ferritina (113,2 vs. 60,1mg/dL; p=0,006) e ácido úrico (4,4 vs. 4,0; p=0,023). Além disso, foi encontrada uma menor prevalência de sobrepeso e excesso de gordura abdominal (p<0,05) nos indivíduos com maior consumo de aminoácidos de cadeia ramificada. Eles também apresentaram um maior consumo diário de fibra, cobre, zinco, magnésio e ferro, além de um menor consumo de lipídios totais. Conclusão No presente estudo, o consumo de aminoácidos ramificados está negativamente relacionado à adiposidade total e central, porém mais estudos são necessários para elucidar completamente essa possível relação. (Registro Brasileiro de Ensaios Clínicos, código RBR-5n4y2g)

Reimplante dentário após o uso do BCAA como meio de conservação: estudo histométrico em ratos / Dental replantation after the use of BCAA as a preservative: histometric study in rats

A melhor forma de tratamento para os casos de avulsão dentária por trauma é o reimplante imediato, no entanto, existem diversas condições que impedem sua realização. Nesses casos, os meios de conservação tem papel fundamental para a manutenção da integridade do ligamento periodontal do dente avulsionado, dando tempo para que um tratamento adequado seja alcançado. Compostos proteicos como o leite, o soro do leite apresentaram resultados favoráveis para esse fim. Acessibilidade e facilidade de manuseio também contribuem favoravelmente. Existem compostos de aminoácidos que poderiam servir para esse fim, assim o propósito desse estudo foi o de analisar se o BCAA (aminoácidos de cadeia ramificada) possui o mesmo potencial como meio de conservação por também ser um composto proteico. Para isso foram utilizados 50 ratos divididos em 5 grupos de 10 animais. Após a extração do incisivo superior direito, os dentes do grupo (IM) foram reimplantados em seus respectivos alvéolos após 5 minutos; No grupo (L) - os dentes foram imersos em 40 ml de leite bovino pasteurizado (UHT); No grupo (SL) - os dentes foram imersos em 40 ml de soro de leite fresco; No grupo (BC) - os dentes foram imersos em 40 ml de uma solução à base de aminoácidos de cadeia ramificada (7 gramas de pó em 200ml de água); No grupo (SE) - os dentes foram mantidos em meio seco sobre bancada. Os dentes serão mantidos em seus respectivos meios por 60 minutos em temperatura ambiente para serem então reimplantados em seus respectivos alvéolos Os animais receberam, em dose única, antibiótico e analgésico. A eutanásia foi realizada 60 dias após e os espécimes obtidos foram processados para obtenção de lâminas que foram coradas pela Hematoxilina e eosina. Na análise histológica foram analisadas as características da inserção epitelial, do ligamento periodontal, cemento e dentina. Nessas estruturas foi quantificada a ocorrência de reabsorção inflamatória, reabsorção por substituição, total de reabsorção, áreas reparadas por ligamento periodontal, anquilose. Os dados foram submetidos à análise estatística a um nível de significância de 5%. Os resultados demonstraram que a ocorrência de reabsorção radicular foi maior no grupo SE em relação aos demais grupos. Da mesma forma a reabsorção inflamatória foi superior neste grupo em relação aos demais. Maior extensão de infiltrado inflamatório crônico foi encontrado no grupo SE em relação grupo IM. Maior extensão de ligamento periodontal reinserido foi encontrado no grupo IM em relação ao grupo SE. O grupo SE apresentou menor extensão de ligamento periodontal que os demais grupos (p<0,05). Pode-se concluir que o BCAA, assim como o leite e o soro de leite, apresentou resultado histológico semelhante ao reimplante imediato, constituindo uma opção como meio de conservação de dentes avulsionados(AU)

The best form of treatment for cases of dental avulsion due to trauma is immediate replantation, however, there are several conditions that prevent its implementation. In such cases, the preservative means play a fundamental role in maintaining the integrity of the periodontal ligament of the avulsed tooth, allowing time for proper treatment to be achieved. Protein compounds such as milk and whey showed favorable results for this purpose. Accessibility and ease of handling also contribute favorably. There are amino acid compounds that could serve this purpose, so the purpose of this study was to examine whether BCAA (branched chain amino acids) has the same potential as a preservative as it is also a protein compound. For this, 50 rats divided into 5 groups of 10 animals were used. After extraction of the right upper incisor, the teeth of group (IM) were reimplanted in their respective alveoli after 5 minutes; In group (M) - the teeth were immersed in 40 ml of pasteurized bovine milk (UHT); In group (W) - teeth were immersed in 40 ml of fresh whey; In group (BC) - the teeth were immersed in 40 ml of a branched chain amino acid solution (7 grams of powder in 200ml of water); In group (D) - the teeth were kept in a dry medium on a bench. The teeth will be kept in their respective means for 60 minutes at room temperature and then reimplanted in their respective alveoli. The animals received antibiotic and analgesic in a single dose. Euthanasia was performed 60 days later and the specimens obtained were processed to obtain slides that were stained with Hematoxylin and eosin. Histological analysis analyzed the characteristics of epithelial insertion, periodontal ligament, cementum and dentin. In these structures, the occurrence of inflammatory resorption, replacement resorption, total resorption, areas repaired by periodontal ligament, ankylosis were quantified. Data were subjected to statistical analysis at a significance level of 5%. The results showed that the occurrence of root resorption was higher in the D group than in the other groups. Similarly, inflammatory resorption was higher in this group compared to the others. A greater extent of chronic inflammatory infiltrate was found in the SE group than in the IM group. Greater extension of reinserted periodontal ligament was found in the IM group compared to the D group. The D group had less periodontal ligament extension than the other groups (p <0.05). It can be concluded that BCAA, as well as milk and whey, presented histological results similar to immediate replantation, constituting an option as a means of preserving avulsed teeth(AU)

Recent Progress on Branched-Chain Amino Acids in Obesity, Diabetes, and Beyond

Branched-chain amino acids (BCAAs) are essential amino acids that are not synthesized in our body; thus, they need to be obtained from food. They have shown to provide many physiological and metabolic benefits such as stimulation of pancreatic insulin secretion, milk production, adipogenesis, and enhanced immune function, among others, mainly mediated by mammalian target of rapamycin (mTOR) signaling pathway. After identified as a reliable marker of obesity and type 2 diabetes in recent years, an increasing number of studies have surfaced implicating BCAAs in the pathophysiology of other diseases such as cancers, cardiovascular diseases, and even neurodegenerative disorders like Alzheimer's disease. Here we discuss the most recent progress and review studies highlighting both correlational and potentially causative role of BCAAs in the development of these disorders. Although we are just beginning to understand the intricate relationships between BCAAs and some of the most prevalent chronic diseases, current findings raise a possibility that they are linked by a similar putative mechanism.

Isolated branched-chain amino acid intake and muscle protein synthesis in humans: a biochemical review / Consumo isolado de aminoácidos de cadeia ramificada e síntese de proteína muscular em humanos: uma revisão bioquímica

ABSTRACT Alongside a proper diet, ergogenic aids with potential direct and/or indirect physical performance enhancing effects are sought after for improved adaptation to physical training. Nutritional ergogenics include diet composition changes and/or dietary supplementation. Branched-chain amino acids valine, leucine and isoleucine are widely popular among products with ergogenic claims. Their major marketing appeal derives from allegations that branched-chain amino acids intake combined with resistance physical exercise stimulates muscle protein synthesis. Evidence supporting the efficacy of branched-chain amino acids alone for muscle hypertrophy in humans is somewhat equivocal. This brief review describes physiological and biochemical mechanisms underpinning the effects of complete protein source and branched-chain amino acid intake on skeletal muscle growth in the postabsorptive and post-exercise state. Evidence in favor of or against potential anabolic effects of isolated branched-chain amino acid intake on muscle protein synthesis in humans is also examined.

RESUMO No treinamento físico, buscam-se, além de uma dieta adequada, recursos ergogênicos que possam maximizar direta e/ou indiretamente o desempenho físico. Entre as categorias de recursos ergogênicos, o nutricional compreende a modulação da composição dietética e/ou uso de suplementação. A comercialização dos suplementos de aminoácidos de cadeia ramificada valina, leucina e isoleucina possui muita popularidade entre aqueles com alegação ergogênica. O principal marketing está na afirmação de que o consumo isolado de aminoácidos de cadeia ramificada associado ao exercício físico resistido estimula a síntese de proteína muscular. As evidências da eficácia da ingestão isolada de aminoácidos de cadeia ramificada para a hipertrofia muscular em humanos parecem equivocadas. Nesta breve revisão, apresentamos a compreensão fisiológica e bioquímica de como a ingestão de uma fonte completa de proteína e de aminoácidos de cadeia ramificada afeta o crescimento do músculo esquelético no estado pós-absortivo e pós-exercício. Mostramos também as evidências que suportam ou não a afirmação dos potenciais efeitos anabólicos na síntese de proteína muscular dos aminoácidos de cadeia ramificada quando consumidos isoladamente em humanos.

Efeitos dos aminoácidos de cadeia ramificada na resposta inflamatória induzida por lipopolissacarídeo em macrófagos de linhagem celular RAW 264. 7 / Effects of branched-chain amino acids in the inflammatory response induced by lipopolysaccharide in a macrophage cell line RAW 264. 7

Os aminoácidos de cadeia ramificada (ACR) são considerados indispensáveis, pois não podem ser sintetizados endogenamente, sendo facilmente obtidos pela dieta. Entretanto, em determinadas condições clínicas, tanto a ingestão quando a absorção desses aminoácidos pode estar comprometida, levando ao estado hipercatabólico e prejudicando a função imune. O papel imunomodulador dos ACR tem sido relacionado com a melhora no balanço nitrogenado e o aumento da síntese e proliferação de células imunes, bem como, da síntese de mediadores inflamatórios. Entretanto, o mecanismo pelo qual os ACR exercem essas funções supracitadas ainda não é claro na literatura científica. Desta forma, esse trabalho teve como objetivo avaliar os efeitos da suplementação com ACR sobre os parâmetros inflamatórios e moleculares em macrófagos RAW 264.7 estimulados com lipopolissacarídeo (LPS). As culturas celulares foram distribuídas em cinco grupos: CTL - sem suplementação com ACR; LEU - suplementado com leucina (2 mmol/L); ISO - suplementado com isoleucina (2mmol/L); VAL - suplementado com valina (2 mmol/L) e LIV - suplementado com leucina (2 mmol/L), isoleucina (2 mmol/L) e valina (2 mmol/L). O estado inflamatório foi induzido pela adição de LPS (1 µg/mL) ao meio de cultura, seguindo quatro protocolos de tratamento: PT - pré-tratamento; TA - tratamento agudo; TC - tratamento crônico e TT - tratamento tardio. O ensaio de viabilidade celular foi realizado pelo teste MTT e a dosagem de óxido nítrico (NO) pela reação de Griess. As citocinas pró e anti-inflamatórias, e a prostaglandina E2 (PGE2) foram analisadas pelo método de ELISA. Para a avaliação dos parâmetros moleculares foi utilizado o método de western blotting. Houve aumento da viabilidade celular em todos os grupos suplementados em relação ao grupo controle no TA, no TC e no TT. Acerca da síntese de NO, a suplementação com ACR foi capaz de aumentar esse parâmetro em três dos quatro tratamentos propostos (PT, TA e TC). Em relação à síntese de citocinas pró e anti-inflamatórias, o PT e o TC foram mais eficazes em aumentar esse parâmetro em comparação aos outros tratamentos. Não houve diferença entre os grupos em relação à capacidade de síntese de PGE2 e à fosforilação de proteínas intracelulares. A partir dos resultados obtidos é possível concluir que os ACR contribuem significativamente para a viabilidade celular, bem como para a síntese de mediadores pró e anti-inflamatórios, sendo que o protocolo de suplementação se apresenta como fator determinante para obtenção desses resultados. Apesar da literatura científica atribuir grande parte dos efeitos imunomodulatórios à leucina, os resultados obtidos nesse estudo atribuem relevante potencial imunomodulador à isoleucina, abrindo espaço para um importante tema de estudo

Branched chain amino acids (BCAA) are considered indispensable, since they cannot be endogenously synthesized, being easily obtained by diet. However, in certain clinical conditions, both the intake and absorption of these amino acids may be compromised, leading to the hypercatabolic state and impairing the immune function. The immunomodulatory role of BCAA has been associated with the nitrogen balance improvement and the increase of production and proliferation of immune cells, as well as the synthesis of inflammatory mediators. However, the mechanisms by which BCAA modulate the immune system have not yet been completely elucidated. In this sense, this study aimed to evaluate the effects of BCAA supplementation on intracellular mechanisms and inflammatory parameters in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Cell cultures were distributed into five groups: CTL - without ACR supplementation; LEU - supplemented with leucine (2 mmol/L); ISO - supplemented with isoleucine (2mmol / L); VAL - supplemented with valine (2 mmol/L) and LIV - supplemented with leucine (2 mmol/L), isoleucine (2 mmol/L) and valine (2 mmol/L). The inflammatory state was induced by the addition of LPS (1 µg/ml) to the culture medium, following four treatment protocols: PT - pre-treatment; TA - acute treatment; TC - chronic treatment and TT - late treatment. The cell viability assay was performed by the MTT test and the nitric oxide (NO) dosage by the Griess reaction. Pro- and anti-inflammatory cytokines, and prostaglandin E2 (PGE2) were analyzed by ELISA. For the evaluation of the molecular parameters, the western blotting method was used. There was an increase in cell viability in all supplemented groups in relation to the control group in the TA, TC and TT treatments. Regarding NO synthesis, BCAA supplementation was able to increase NO production in three of the four proposed treatments (PT, TA and TC). In relation to the production of pro- and anti-inflammatory cytokines, PT and CT were more effective in increasing this parameter, compared to the other treatments. There was no difference between groups in relation to PGE2 production and intracellular protein phosphorylation. From the obtained results it is possible to conclude that the BCAA significantly contributed to the cell viability, as well as, for the production of pro and anti-inflammatory mediators, and the supplementation protocol presents as determinant factor to obtain these results. Although the scientific literature attributed a large part of the immunomodulatory effects to leucine, the results obtained in this study attribute relevant immunomodulatory potential to isoleucine, opening space for an important study topic

A comparison of metabolomic changes in type-1 diabetic C57BL/6N mice originating from different sources / 한국실험동물학회지

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.

Aminoácidos de cadeia ramificada: consumo dietético e associação com fatores de risco cardiometabólicos em residentes de São Paulo / Branched chain amino acid dietary intake and its association with cardiometabolic risk in residents of São Paulo

Introdução: Os aminoácidos de cadeia ramificada (ACR) compreendem três aminoácidos essenciais tais como, leucina (Leu), isoleucina (Ile) e valina (Val). Estes aminoácidos desempenham um papel importante no corpo humano, como a produção de energia, síntese de proteínas e de muitos neurotransmissores. São escassos os estudos que investigam o consumo de ACR e sua associação com as doenças cardiometabólicas. No entanto, estudos metabolômicos sugerem que os ACR encontrados no plasma podem ser preditores de doenças cardiometabólicas. Objetivos: Avaliar a ingestão de aminoácidos de cadeia ramificada (ACR), leucina (Leu), isoleucina (Ile) e valina (Val) e sua associação com fatores demográficos, socioeconômicos e estilo de vida, e com fatores de risco cardiometabólicos. Metodologia: Os dados foram provenientes do Inquérito de Saúde de São Paulo, estudo transversal de base populacional com amostra representativa de residentes do município de São Paulo, de ambos os sexos e com idade igual ou superior a 12 anos. O consumo alimentar foi avaliado por meio de dois recordatórios de 24 horas, não consecutivos. Utilizou-se um questionário estruturado para obter informações socioeconômicas, demográficas e de estilo de vida. Também foram coletadas amostras de sangue, pressão arterial, o peso, a estatura e circunferência da cintura dos indivíduos. Os analitos avaliados foram glicemia plasmática de jejum, triacilgliceróis (TG), lipoproteína de alta densidade (HDL), lipoproteína de baixa densidade (LDL), colesterol total (CT), proteína C reativa ultrassensível (PCRu), homocisteína e leptina séricas (LEP). As análises estatísticas foram realizadas utilizando o software Stata®, versão 13 com nível de significância de 0,05. Resultados: A ingestão total de ACR foi de 217,14 mg / kg×d (Leu: 97,16 mg / kg×d, Ile: 56,44 mg / kg×d, Val: 63,54 mg / kg×d). Em adolescentes a ingestão de ACR foi negativamente associada ao sexo feminino e a raça autodeclarada não branca. Nos adultos a ingestão de ACR foi negativamente associada ao sexo feminino e fumantes. A renda familiar per capita foi positivamente associada nos adolescentes e adultos. E não foram observadas associações no grupo de idosos. Os principais alimentos contribuintes para a ingestão de ACR foram carne vermelha não processada, aves não processadas, pão e torrada, feijão e arroz. Após o ajuste para potenciais fatores de confusão, o maior consumo de ACR total para o grupo de adultos e idosos (OR = 1,89, 95 por cento IC = 1,09 - 3,27), leucina (OR = 1,93, 95 por cento IC = 1,11 - 3,35), isoleucina (OR = 2,09, 95 por cento IC = 1,23 - 3,54) e valina (OR = 1,98, 95 por cento IC = 1,17 - 3,32) foram positivamente associados com hipertensão. E o mesmo foi observado para o modelo ajustado entre o maior consumo de ACR total (OR = 2,06, 95 por cento IC = 1,18 - 3,59), leucina (OR = 2,08, 95 por cento IC = 1,20 - 3,59), isoleucina (OR = 1,93, 95 por cento IC = 1,10 - 3,39) e valina (OR = 1,98, 95 por cento IC = 1,14 - 3,42) com hipertrigliceridemia. Conclusão: Os adolescentes e os adultos foram os grupos que mais se associaram a ter a ingestão de ACR influenciada por fatores demográficos, socioeconômicos e de estilo de vida. Dentre os fatores de risco cardiometabólicos, destacaram-se a hipertensão e a hipertrigliceridemia como fatores positivamente associados com o maior consumo de ACR total, leucina, isoleucina e valina. Esses resultados reforçam a importância da investigação do limite tolerável de ingestão dos ACR, bem como sua associação nos diferentes desfechos em saúde

Introduction: Branched chain amino acids (BCAA) comprise three essential amino acids such as leucine (Leu), isoleucine (Ile) and valine (Val). These amino acids play an important role in the human body, such as energy production, protein synthesis and many neurotransmitters. There are few studies that investigate BCAA consumption and its association with cardiometabolic diseases. However, metabolic studies suggest that BCAA found in plasma may be a predictor of cardiometabolic diseases. Objectives: To evaluate the intake of branched chain amino acids (BCAA), leucine (Leu), isoleucine (Ile) and valine (Val) with demographic, socioeconomic and lifestyle factors, and to investigate the intake of BCAA with cardiometabolic risk factors. Methods: Data were obtained from the Health Survey of São Paulo, a population-based cross-sectional study with a representative sample of residents of the city of São Paulo, of both sexes and aged over 12 years. Dietary intake was evaluated by two 24-hour dietary recalls and a structured questionnaire was used to obtain socioeconomic, demographic and lifestyle information. Blood samples were collected and blood pressure, weight, height and waist circumference were measured. The analyzed analytes were fasting plasma glucose, triacylglycerols (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), C-reactive protein (PCRu), homocysteine and serum leptin (LEP). All analyses were performed with Stata®, version 13 and a p-value < 0.05 was considered statistically significant. Results: Total BCAA intake was 217.14 mg/kg.day (Leu: 97.16 mg/kg.day; Ile:56.44 mg/kg.day; Val: 63.54 mg/kg.day). BCAA intake was negatively associated with female sex in adolescents and adult groups, with no white race in adolescents, and with former smoker status in adults. Conversely, BCAA was positively associated with household per capita income in adolescents and adults. No associations were observed in the older adults group. Main food contributors to BCAA for all ages were unprocessed red meat, unprocessed poultry, bread and toast, beans and rice. For the group of adults and older adults, after adjusting for potential confounding factors, higher intakes of total BCAA (OR = 1,89, 95 per cent CI = 1,09 - 3,27), leucine (OR = 1,93, 95 per cent CI = 1,11 - 3,35), isoleucine (OR = 2,09, 95 per cent CI = 1,23 - 3,54) e valine (OR = 1,98, 95 per cent CI = 1,17 - 3,32) were positively associated with hypertension. The same was observed for the adjusted model between the highest consumption of total BCAA (OR = 2,06, 95 per cent CI = 1,18 - 3,59), leucine (OR = 2,08, 95 per cent CI = 1,20 - 3,59), isoleucine (OR = 1,93, 95 per cent CI = 1,10 - 3,39) and valine (OR = 1,98, 95 per cent CI = 1,14 - 3,42) with hypertriglyceridemia. Conclusion: Adolescents and adults were the most vulnerable to having their BCAA intake influenced by demographic, socioeconomic and lifestyle factors. Among the cardiometabolic risk, hypertension and hypertriglyceridemia were positively associated with higher intake of total BCAA, leucine, isoleucine and valine. These results reinforce the importance of investigating the tolerable limit of intake of BCAA, as well as its association in different health outcomes

Effect of respiratory syncytial virus-related pulmonary infection on endogenous metabolites in large intestinal mucosa in mice / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).</p><p><b>METHODS</b>Mice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.</p><p><b>RESULTS</b>PCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.</p><p><b>CONCLUSIONS</b>RSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.</p>

Successful domino liver transplantation in maple syrup urine disease using a related living donor

Maple syrup urine disease (MSUD) is an autosomal recessive disease associated with high levels of branched-chain amino acids. Children with MSUD can present severe neurological damage, but liver transplantation (LT) allows the patient to resume a normal diet and avoid further neurological damage. The use of living related donors has been controversial because parents are obligatory heterozygotes. We report a case of a 2-year-old child with MSUD who underwent a living donor LT. The donor was the patient's mother, and his liver was then used as a domino graft. The postoperative course was uneventful in all three subjects. DNA analysis performed after the transplantation (sequencing of the coding regions of BCKDHA, BCKDHB, and DBT genes) showed that the MSUD patient was heterozygous for a pathogenic mutation in the BCKDHB gene. This mutation was not found in his mother, who is an obligatory carrier for MSUD according to the family history and, as expected, presented both normal clinical phenotype and levels of branched-chain amino acids. In conclusion, our data suggest that the use of a related donor in LT for MSUD was effective, and the liver of the MSUD patient was successfully used in domino transplantation. Routine donor genotyping may not be feasible, because the test is not widely available, and, most importantly, the disease is associated with both the presence of allelic and locus heterogeneity. Further studies with this population of patients are required to expand the use of related donors in MSUD.

Redução do MELD em pacientes na lista de transplante hepático após o uso de aminoácidos de cadeia ramificada: relato de caso / Reduction of MELD in patients on the liver transplant list after using chain amino acids: case report

A cirrose hepática (CH) é uma doença com altas taxas de mortalidade e que apresenta, como único tratamento definitivo, o transplante hepático (TH). Infelizmente, nem todos os pacientes têm acesso ao TH e muitos acabam morrendo ainda na lista de transplante. O uso de aminoácidos de cadeia ramificada (AACR) já é amplamente conhecido como tratamento eficaz para a melhora da qualidade de vida destes pacientes. Neste relato, pela primeira vez, documentou-se uma grande melhora clínica e laboratorial em um paciente após o tratamento com AACR, que permitiu ao paciente sair inclusive da lista de transplante. Além da diminuição do escore MELD, houve reestabilização do peso corporal e melhora da qualidade de vida, documentada pelo questionário SF-36.

Liver cirrhosis (LC) is a disease with high mortality rates and its only definitive treatment is the orthotopic liver transplantation (OLT). Unfortunately, not all patients have access to OLT and many of them end up dying on the transplant waiting list. The use of branched chain amino acids (BCAA) is widely known as an effective treatment for improving the quality of life of these patients. For the first time, in this paper we documented a great improvement of clinical and laboratorial tests of a patient treated with BCAA, which allowed him to be out of the transplant waiting list. In addition to the increase of the MELD score, the patient achieved restabilization of body weight and recovery of the quality of life registered by the SF-36 questionnaire.

Consumo de aminoácido de cadeia ramificada na esclerose lateral amiotrófica: suplemento proteico ou substância neurotóxica? / Branched-chain amino acid consumption in amyotrophic lateral sclerosis: protein supplement or neurotoxic substance?

Estudos demonstraram efeito positivo principalmente no ganho ponderalem pacientes com esclerose lateral amiotrófica (ELA), suplementadoscom aminoácidos de cadeia ramificada (AACR). Achados recentes têm mostrado que o consumo excessivo e crônico de AACR pode contribuir para a progressão da doença, provavelmente devido a estes serem precursores do glutamato. O objetivo deste estudo foi avaliar a evidência acerca da utilização dos AACR por pacientes com ELA, a fim de elucidar questões pertinentes a sua ingestão. Foi feita busca em base de dados de artigos científicos relacionados ao consumo de AACR na ELA, no período de 1988 a 2013. Foram encontrados seis artigos relacionados ao consumo de AACR por pacientes com ELA. Desses, um referiu melhora da força, enquanto os outros relataram ganho ponderal ou não mostraram resultados significativosem relação aos desfechos. Além disso, foi possível observar uma estreita relação entre o consumo excessivo e crônico dos AACR com o agravamento da doença. À luz dos conhecimentos ora disponíveis, a suplementação com AACR não é recomendada devido aos possíveis efeitos nocivos. O consumo adequado de alimentos proteicos, fontes desses aminoácidos, deve ser utilizado pelos pacientes, respeitando as recomendações estabelecidas. No entanto, estudos adicionais devem ser desenvolvidos em virtude do escasso número de publicações disponíveis.

Studies have shown positive effect mainly in weight gain inpatients with amyotrophic lateral sclerosis (ALS) supplemented with branched chain amino acids (BCAA). However, recent studies have shown that excessive and chronic intake has contributed to the worsening of the disease progression, probably because the amino acids are glutamate precursors. The objective of this study was to assess the evidence about the use of BCAA by patients with ALS, with the aim to clarify pertinent issues for its intake. A search was conducted in data bases for scientific papers related to the intake of BCAA in ALS, between 1988 and 2013. For these review six articles related to the use of BCAA in ALS were found. Of these, one described strength improvement, while the remaining reported weight gain or no significant effects in relation to the outcome. Additionally, it waspossible to observe a close relationship between the excessive and chronic BCAA intake with the worsening of the disease. Considering the presente day available knowledge BCAA supplementation should not be indicated due to the possible harmful effect. The intake of appropriated protein foods should be consumed by these patients, respecting the suggested recommendation. However, more studies are necessary due to the scarce papers in this area.

Synthesis reduction of central neurotransmitter 5-hydroxytryptamine by branched chain amino acid and associated antagonists improves postoperative fatigue syndrome / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To observe the change of postoperative fatigue in rats after the effect of branched chain amino acid(BCAA) and associated antagonists on central neurotransmitter 5-HT metabolic pathway, and to investigate the role of 5-HT in the development of postoperative fatigue syndrome(POFS).</p><p><b>METHODS</b>Fifty SD rats were randomly divided into sham operation group(C group, n=10), model group(M group, n=10), L-type amino acid transporter inhibitor group(L group, n=10), 5-HT uptake inhibitor group(F group, n=10) and branched chain amino acids(B group, n=10). The rats in the C group and the M group were injected with normal saline, while other three groups were respectively injected with BCH, fluoxetine, BCAA(val:leucine:isoleucine=5:3:2), on preoperative 1 h, postoperative day 1, 2, 3, 4. The rats, except for those in the C group, underwent resection of 70% of the middle small intestine with end-to-end anastomosis. General status of the rats was observed before and after surgery. Morris water maze test, including the hidden platform test and search space test (detecting the learning ability of rats) and tail suspension test (detecting physical endurance of rats) were used to evaluate the degree of POFS from postoperative day 1 to day 7. Concentration of tryptophan(TRP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in different position of brain(hippocampus, striatum, hypothalamus) of rats were measured by high performance liquid chromatography(HPLC) at postoperative day 8.</p><p><b>RESULTS</b>As compared to the M group, other four groups showed better general condition and less fatigue. In the hidden platform test, M group showed the least time of crossing platform as compared to other four groups(all P<0.05). Meanwhile, M group and B group performed the longer incubation period than C group and L group(all P<0.05). In search space test, M group and B group showed less time of crossing platform, but there were no significant differences among the groups(all P>0.05). In tail suspension test, M group and F group showed lower score of physical strength than L group and B group(all P<0.05). Levels of TRP in the L, F, B groups were lower compared to the M group(all P<0.01) in brain tissue. The least concentration of striatum 5-HT was found in the C group but there were no significant differences among the M, L, F and B groups. Level of 5-HIAA in the M group, only in hypothalamus, was higher than that in the F group(P<0.05), but no significant differences between the M group and the L and B groups were found.</p><p><b>CONCLUSION</b>BCAA and associated antagonists (BCH, fluoxetine) can improve POFS by reducing the absorption of TRP that results in decreased synthesis of central 5-HT.</p>

Meta-analysis of branched chain amino acid-enriched nutrition to improve hepatic function in patients undergoing hepatic operation / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To perform a meta-analysis of randomized controlled trials (RCTs) assessing the benefit of providing branched chain amino acid (BCAA)-enriched nutrition to improve hepatic function in patients undergoing hepatic operation.</p><p><b>METHODS</b>The electronic databases of PubMed, Springerlink, the Chinese Biomedical Database (CBM), the Cochrane Library, and the China National Knowledge Infrastructure (CNKI) were searched for relevant RCTs using the following search terms: nutritional support, enteral nutrition, parenteral nutrition, hepatic/liver surgery, liver cirrhosis, cancer, hepatectomy, and liver transplantation. The quality of the retrieved RCTs was assessed according to the scale developed by the Cochrane Collaboration. The meta-analysis was conducted using RevMan software, version 5.2.</p><p><b>RESULTS</b>A total of 11 relevant RCTs, representing 510 patients, were included in the meta-analysis. Compared to patients in the control (normal nutrition) group, the patients in the BCAA group experienced an effective improvement in hepatic function, as evidenced by significant decreases in total bilirubin (by 0.07 mumol/L; 95% confidence interval (CI): -0.18 to 0.05, P more than 0.05]. In addition, the BCAA group showed improvements in plasma levels of albumin (weighted mean difference (WMD) = 0.07; 95% CI: 0.06, 0.24, P less than 0.05) and alanine aminotransferase (WMD = +5.61; 95% CI: -8.63 to 19.86, P more than 0.05] but neither of the changes reached the threshold of a statistically significant improvement. The BCAA group did however show significantly lower complication rate after operation (65%, 95% CI: 0.48, 0.87, P less than 0.01] and mean duration of hospital stay (4.61 days; 95% CI: -6.61, -2.61, P less than 0.01].</p><p><b>CONCLUSION</b>BCAA-enriched nutrition improves hepatic function in patients undergoing hepatic operation, thereby helping to reduce the complication risk, duration of hospital stay, and financial burden. BCAA-enriched nutrition is a safe and effective therapy and further clinical application may be beneficial.</p>

Suplementação com aminoácidos de cadeia ramificadae estado clínico-nutricional de pacientes cirróticos: série de casos / Supplementation with branched chain amino acids and clinical andnutritional status of cirrhotic patients: a case series

Introdução: a doença hepática, na forma aguda ou crônica, provocagrandes alterações no estado nutricional e no metabolismo denutrientes do doente, principalmente na utilização de aminoácidos.Mudanças no metabolismo de aminoácidos, com reduções nosníveis dos de cadeia ramificada (BCAA) e elevações nos níveis deaminoácidos aromáticos, tem função importante no aparecimentodas complicações da cirrose hepática (CH). A suplementação oralcom BCAA pode corrigir tanto transformações metabólicas quantomelhorar a desnutrição associada à cirrose.Objetivo: avaliar os efeitos da administração de suplemento deBCAA sobre o estado clínico - nutricional de pacientes com CH.Método: estudo em série de casos com pacientes cirróticos internadosno Hospital Regional da Asa Norte (HRAN), entre novembro de2012 e agosto de 2013. Foram aferidas medidas antropométricas eanalisados os resultados de exames bioquímicos antes e após 7 diasde suplementação com BCAA oral.Resultados: seis pacientes participaram do estudo, não houvemelhora da albumina.Conclusão: existe uma elevada prevalência de pacientes comdesnutrição, os valores de albumina não refletiram os efeitosda suplementação na doença hepática e sim o estado clíniconutricionaldos pacientes. Em curto prazo, o BCAA oral não foieficaz em evitar o agravo do estado nutricional nem de melhorar oquadro de desnutrição.

Introduction: Liver disease in its acute or chronic forms, causesmajor changes in nutritional status and nutrient metabolism of thepatient, especially in the use of amino acids. Changes in amino acidmetabolism, with reductions in levels of branched chain (BCAA)and elevated levels of aromatic amino acids, plays an important rolein the onset of complications of liver cirrhosis (LC). Oral supplementationwith BCAA can correct both metabolic transformationsand improve malnutrition associated with cirrhosis.Objective: To evaluate the effects of administration of BCAAsupplementation on clinical and nutritional status of patients withCH.Method: this is a series of cases study with cirrhotic patients conductedat Hospital Regional da Asa Norte (HRAN), between November2012 and August 2013. Anthropometric measurements were takenand the results of biochemical tests of albumin were analyzedbefore and after 7 days of oral supplementation with BCAA.Results: six patients participated in the study, there was no improvementin albumin.Conclusion: there is a high prevalence of malnutrition, albuminvalues did not reflect the effects of supplementation on liver diseasebut the clinical and nutritional status of patients. In the shortterm, oral BCAA was not effective in preventing the worsening ofthe nutritional status and improvement of malnutrition.

Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy. MATERIALS AND METHODS: Patients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored. RESULTS: Fifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043). CONCLUSION: Oral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.