Alzheimer’s disease (AD), the most common form of dementia in the elderly, is a global issue affecting about 24 million individuals. Because AD is a systemic pathology, dementia is not the only leading factor contributing to loss of independence in AD patients. AD may also impair skeletal muscle metabolism and function. Creatine (CR) supplementation may enhance skeletal muscle hypertrophy/mass and function in sarcopenia and muscular dystrophies, but has yet to be studied in AD. This study examined the effect of oral CR on muscle metabolism in a triple-transgenic (3xTg) AD mouse model. Twenty-four, 3×Tg AD mice (~8 month-old) were randomly assigned to control (CON) or CR (3% w/w) diet. Bodyweights and feed intakes were measured throughout the 8-week study. Lower limb (quadriceps muscle; QM and gastrocnemius; GM) and upper limb muscles (triceps; TM) were collected to analyze levels of CR, total protein, DNA, RNA, amino acids (AA), adenosine triphosphate (ATP), adenosine diphosphate (ADP), total and phosphorylated p70 ribosomal S6 kinase (p70S6K). Data (mean ± SEM) were assessed by analysis of variance (ANOVA) and Fisher’s least significant difference (LSD) post hoc test. In comparison to the CON group, CR supplementation increased CR content in both GM (p=0.002) and QM (p=0.037), with higher (p=0.032) ATP/ADP ratio in CR in comparison with CON in QM. A higher protein concentration (p<0.0001) was notable in GM of CR supplemented group vs. CON. Total branched-chain AA levels in QM increased 2-fold (p< 0.0001) in CR groups. Additionally, CR resulted in a higher (p<0.05) protein/DNA ratio; an index of muscle cell size, in both QM and GM for CR groups. The index of cell capacity for protein synthesis (RNA/DNA ratio) in GM was also higher (p=0.001) in CR groups. However, phosphorylation (activation) level of p70S6K, an integral component in protein synthesis signalling pathway, did not show any significant differences in female (p=0.161) and male (p=0.292) CR supplemented groups compared with CON. To conclude, CR supplementation is capable of inducing muscle hypertrophy/growth parameters in the 3×Tg AD mouse model, thereby enhancing protein synthesis capacity in skeletal muscles, thus possibly promoting muscle function in AD. / May 2016

The purpose of this thesis was to determine ways to maximize creatine uptake and retention during creatine supplementation. Since there are many factors that affect muscle creatine concentrations, a series of studies were performed. In the first study, the purpose was to determine if á-lipoic acid aided creatine uptake and retention. It was hypothesized that á-lipoic acid would increase creatine uptake, because it has been found to increase glucose disposal in animal studies and because creatine uptake has been found to be related to increased glucose transport. Results showed that phosphocreatine and total creatine increased following supplement intervention. In the second study, the purpose was to develop an optimal dose of creatine in order to minimize urinary excretion of creatine. It was hypothesized that individuals with more lean tissue mass would excrete less urinary creatine during consumption of the same loading dose. There was a high negative correlation between lean tissue mass and urine creatine excretion. Regression equations were developed for the relationship between lean tissue mass and urine total creatine and used to determine the amount of creatine to ingest relative to lean tissue mass that would result in minimal creatine losses in urine. Based on these results, a creatine dose of 0.22 [right arrow] 0.25 g/kg lean tissue mass/d was recommended. In the third study, the purpose was to determine if a habitual vegetarian diet resulted in lower muscle creatine and phosphocreatine concentrations compared to an omnivorous diet. A secondary purpose was to determine if creatine supplementation and weight training resulted in greater increases in muscle metabolite content, muscle fiber area, lean tissue mass, and strength in vegetarians compared to non-vegetarians. Results indicated that vegetarians had lower resting total creatine concentration, and that creatine supplementation and weight training led to greater increases in muscle phosphocreatine and total creatine in vegetarians compared to non-vegetarians (p < 0.0125). The supplement and exercise intervention eliminated the differences in intramuscular total creatine concentration that existed prior to the study. Type II muscle fiber area, lean tissue mass, total work output, and 1-RM bench press increased to a greater extent following creatine supplementation compared to placebo supplementation (p < 0.017), with no difference between vegetarians and non-vegetarians. (Abstract shortened by UMI.)

Introduction: Creatine is a nitrogen-containing compound that is found in many supplements that claim to increase muscle mass and there is increasing evidence that creatine supplementation can increase muscle mass in older individuals. Purpose: To evaluate the safety of 12-months creatine supplementation and resistance exercise in older adults by monitoring measures of kidney and liver function, complete blood count, and reports of adverse events. Methods: Older adults (n=70, males 50 years of age or older (39), and post-menopausal females (31) who were not performing resistance exercise were recruited for the study and randomized by computer to creatine (32; 18 males, 14 females) or placebo (38; 21 males, 17 females) groups. Other exclusionary criteria were: presence/history or kidney impairments, consumption of creatine supplement/bone altering drugs, and the presence of fragility fractures. Participants were given creatine or placebo (0.1g/kg/day) consumed before and after resistance training on exercise days and with a meal on non-exercise days. The study used a double-blind, placebo-controlled design. Blood and urine were collected to assess complete blood cell count, liver function indicators (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and Bilirubin), and creatinine clearance (kidney function) at baseline, 4 months, 8 months, and 12 months. A mixed ANOVA was used to determine differences in the kidney and liver measures within and between groups, and chi-square analysis was used to determine if the frequency counts for liver, kidney, and other adverse events were different between groups.

No description available.

A betaína é um trimetil derivado do aminoácido glicina. Os seus principais efeitos fisiológicos são atuar como um osmólito e como doador de radicais metil. Especulase que a betaína possa contribuir para a síntese de creatina no músculo esquelético pelo fornecimento de grupos metil, resultante da conversão de betaína em dimetilglicina, para a remetilação de homocisteína em metionina. Os efeitos da suplementação de creatina sobre o desempenho são conhecidos e relacionam-se principalmente ao aumento na ressíntese de fosforilcreatina (PCR). Autores de estudos recentes têm atribuído seus resultados positivos em relação ao aumento de força muscular a um possível efeito da betaína sobre as concentrações de PCR. Essa variável, entretanto, não foi avaliada, de maneira que os mecanismos responsáveis pelo aumento de força advindo da suplementação de betaína ainda são inexplorados em humanos. Diante disso, este estudo teve como objetivo investigar os efeitos da suplementação de betaína, combinada ou não com a suplementação de creatina, sobre as concentrações intramusculares de PCR, e a produção de força e potência muscular em indivíduos não treinados em força. Além disso, as respostas fisiológicas e ergogênicas da suplementação de betaína e creatina foram comparadas e avaliados os possíveis efeitos aditivos desses suplementos. Foi conduzido um estudo duplo-cego, randomizado, controlado por placebo. Trinta e quatro sujeitos foram divididos em quatro grupos: Betaína (BET; 2 g/dia), Creatina (CR; 20 g/dia), Betaína + Creatina (BET + CR; 2 + 20 g/dia) e Placebo (PL). No período basal (PRÉ) e após 10 dias de suplementação (PÓS), os indivíduos submeteram-se a avaliações do consumo alimentar e da composição corporal, a testes de força e potência muscular e à quantificação intramuscular de PCR. Após a intervenção, as concentrações intramusculares de PCR foram maiores nos grupos CR e BET + CR, quando comparados ao grupo PL (p = 0,004 e p = 0,006, respectivamente). Não houve diferenças significativas entre os grupos BET e PL (p = 0,78) e CR e BET + CR (p = 0,99). Os grupos CR e BET + CR apresentaram maior produção de potência muscular no exercício de agachamento, quando comparados ao grupo PL (p = 0,003 e p = 0,041, respectivamente). Resultados similares foram encontrados para o exercício de supino. Os grupos CR e BET + CR também demonstraram aumento significativo de força muscular (teste de 1-RM) do teste PRÉ para o teste PÓS nos exercícios de supino e agachamento (CR: p = 0,027 e p 0,0001; BET + CR: p = 0,03 e p 0,0001 para membros superiores e inferiores, respectivamente). Não houve diferenças significativas para os testes de força e de potência muscular entre os grupos BET e PL e os grupos CR e BET + CR. Também não houve diferença significativa entre os grupos para a composição corporal. O consumo alimentar permaneceu inalterado ao longo do estudo. Os resultados permitem concluir que a suplementação de betaína, combinada ou não com a suplementação de creatina, não aumenta o conteúdo intramuscular de PCR e não afeta o desempenho de força e de potência muscular / Betaine is a trimethyl derivative of the amino acid glycine. The main physiological functions of betaine are to act as an organic osmolyte and as a donor of methyl radicals. It is speculated that betaine may contribute to the synthesis of creatine in skeletal muscle through the donation of a methyl group, resulting from the conversion of betaine to dimethylglycine, to homocysteine to form methionine. The effects of creatine supplementation on performance are well known and are related primarily to an increase in fosforilcreatina resynthesis (PCR). Authors of recent studies have attributed its positive results regarding the increase of muscle strength to a possible effect of betaine on the concentrations of PCR. However, this variable was not assessed, so that the mechanisms responsible for the increase in muscle strength coming from betaine supplementation in humans are still unexplored. In light of this, the aim of this study was to investigate the effect of betaine supplementation combined or not with creatine supplementation on muscle PCR content, muscle strength and power output in non-resistance trained subjects. Additionally, we compared the ergogenic and physiological responses to betaine versus creatine supplementation. Finally, we also tested the possible additive effects of creatine and betaine supplementation. A randomized, double-blind, placebo-controlled study was conducted. Thirty and four subjects were assigned into four groups: Betaine (BET; 2 g/day), Creatine (CR; 20 g/day), Betaine + Creatine (BET + CR; 2 + 20 g/day) or Placebo (PL). At baseline (PRE) and after 10 days of supplementation (POST) body composition, food intake, muscle strength and power and muscle PCR were assessed. The CR and BET + CR groups presented greater increase in muscle PCR content than PL (p = 0.004 and p = 0.006, respectively). PCR content was comparable between BET versus PL (p = 0.78) and CR versus BET + CR (p = 0.99). CR and BET + CR presented greater muscle power output than PL in the squat exercise following supplementation (p = 0.003 and p = 0.041, respectively). Similarly, bench press average power was significantly greater for the CR-supplemented groups. CR and BET + CR groups also showed significant pre- to post-test increase in 1-RM squat and bench press (CR: p = 0.027 and p 0.0001; BET + CR: p = 0.03 and p 0.0001 for upper- and lower-body assessments, respectively). No significant differences for 1-RM strength and power were observed between BET versus PL and CR versus BET + CR. Body composition did not differ between the groups. Dietary intake was unchanged throughout the study. Thus, we concluded that betaine supplementation does not augment muscle PCR content and betaine supplementation combined or not with creatine supplementation does not affect strength and power performance in non-resistance trained subjects

A betaína é um trimetil derivado do aminoácido glicina. Os seus principais efeitos fisiológicos são atuar como um osmólito e como doador de radicais metil. Especulase que a betaína possa contribuir para a síntese de creatina no músculo esquelético pelo fornecimento de grupos metil, resultante da conversão de betaína em dimetilglicina, para a remetilação de homocisteína em metionina. Os efeitos da suplementação de creatina sobre o desempenho são conhecidos e relacionam-se principalmente ao aumento na ressíntese de fosforilcreatina (PCR). Autores de estudos recentes têm atribuído seus resultados positivos em relação ao aumento de força muscular a um possível efeito da betaína sobre as concentrações de PCR. Essa variável, entretanto, não foi avaliada, de maneira que os mecanismos responsáveis pelo aumento de força advindo da suplementação de betaína ainda são inexplorados em humanos. Diante disso, este estudo teve como objetivo investigar os efeitos da suplementação de betaína, combinada ou não com a suplementação de creatina, sobre as concentrações intramusculares de PCR, e a produção de força e potência muscular em indivíduos não treinados em força. Além disso, as respostas fisiológicas e ergogênicas da suplementação de betaína e creatina foram comparadas e avaliados os possíveis efeitos aditivos desses suplementos. Foi conduzido um estudo duplo-cego, randomizado, controlado por placebo. Trinta e quatro sujeitos foram divididos em quatro grupos: Betaína (BET; 2 g/dia), Creatina (CR; 20 g/dia), Betaína + Creatina (BET + CR; 2 + 20 g/dia) e Placebo (PL). No período basal (PRÉ) e após 10 dias de suplementação (PÓS), os indivíduos submeteram-se a avaliações do consumo alimentar e da composição corporal, a testes de força e potência muscular e à quantificação intramuscular de PCR. Após a intervenção, as concentrações intramusculares de PCR foram maiores nos grupos CR e BET + CR, quando comparados ao grupo PL (p = 0,004 e p = 0,006, respectivamente). Não houve diferenças significativas entre os grupos BET e PL (p = 0,78) e CR e BET + CR (p = 0,99). Os grupos CR e BET + CR apresentaram maior produção de potência muscular no exercício de agachamento, quando comparados ao grupo PL (p = 0,003 e p = 0,041, respectivamente). Resultados similares foram encontrados para o exercício de supino. Os grupos CR e BET + CR também demonstraram aumento significativo de força muscular (teste de 1-RM) do teste PRÉ para o teste PÓS nos exercícios de supino e agachamento (CR: p = 0,027 e p 0,0001; BET + CR: p = 0,03 e p 0,0001 para membros superiores e inferiores, respectivamente). Não houve diferenças significativas para os testes de força e de potência muscular entre os grupos BET e PL e os grupos CR e BET + CR. Também não houve diferença significativa entre os grupos para a composição corporal. O consumo alimentar permaneceu inalterado ao longo do estudo. Os resultados permitem concluir que a suplementação de betaína, combinada ou não com a suplementação de creatina, não aumenta o conteúdo intramuscular de PCR e não afeta o desempenho de força e de potência muscular / Betaine is a trimethyl derivative of the amino acid glycine. The main physiological functions of betaine are to act as an organic osmolyte and as a donor of methyl radicals. It is speculated that betaine may contribute to the synthesis of creatine in skeletal muscle through the donation of a methyl group, resulting from the conversion of betaine to dimethylglycine, to homocysteine to form methionine. The effects of creatine supplementation on performance are well known and are related primarily to an increase in fosforilcreatina resynthesis (PCR). Authors of recent studies have attributed its positive results regarding the increase of muscle strength to a possible effect of betaine on the concentrations of PCR. However, this variable was not assessed, so that the mechanisms responsible for the increase in muscle strength coming from betaine supplementation in humans are still unexplored. In light of this, the aim of this study was to investigate the effect of betaine supplementation combined or not with creatine supplementation on muscle PCR content, muscle strength and power output in non-resistance trained subjects. Additionally, we compared the ergogenic and physiological responses to betaine versus creatine supplementation. Finally, we also tested the possible additive effects of creatine and betaine supplementation. A randomized, double-blind, placebo-controlled study was conducted. Thirty and four subjects were assigned into four groups: Betaine (BET; 2 g/day), Creatine (CR; 20 g/day), Betaine + Creatine (BET + CR; 2 + 20 g/day) or Placebo (PL). At baseline (PRE) and after 10 days of supplementation (POST) body composition, food intake, muscle strength and power and muscle PCR were assessed. The CR and BET + CR groups presented greater increase in muscle PCR content than PL (p = 0.004 and p = 0.006, respectively). PCR content was comparable between BET versus PL (p = 0.78) and CR versus BET + CR (p = 0.99). CR and BET + CR presented greater muscle power output than PL in the squat exercise following supplementation (p = 0.003 and p = 0.041, respectively). Similarly, bench press average power was significantly greater for the CR-supplemented groups. CR and BET + CR groups also showed significant pre- to post-test increase in 1-RM squat and bench press (CR: p = 0.027 and p 0.0001; BET + CR: p = 0.03 and p 0.0001 for upper- and lower-body assessments, respectively). No significant differences for 1-RM strength and power were observed between BET versus PL and CR versus BET + CR. Body composition did not differ between the groups. Dietary intake was unchanged throughout the study. Thus, we concluded that betaine supplementation does not augment muscle PCR content and betaine supplementation combined or not with creatine supplementation does not affect strength and power performance in non-resistance trained subjects

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / By definition Traumatic brain injury (TBI) is a common involvement in all societies and covers the entire set of processes that alone or in combination can damage the brain. In children and adolescents TBI is an interruption in their normal development, with estimates ranging from 200 to 500 cases per 100,000 per year. Most cases are characterized as mild, with few long-term consequences, however, a significant portion of young people suffer more serious injuries. Furthermore, Juvenile TBI is the major cause of death and disability in children and adolescents. An important factor is that the sports and youth have always been closely related. In this sense, it called attention traumas, especially for young people during practice of contact sports such as martial arts, football, ice hockey, baseball. Because of the wide variety of conditions associated with TBI, there is considerable interest in the development and subsequent application of biochemical markers that relate the severity of brain damage with the development of neurological problems such as memory and learning deficits. In this context, this study aimed, at first, to see if the young animals subjected to TBI had cognitive impairment fifteen days after the injury and whether creatine supplementation has protective effect by changing the activity of CK enzyme, modulating the expression of AMPK protein, CREB, p-CREB and BDNF involved in cognitive impairment and histological damage generated by TBI To this end the present study used young male Wistar rats at 35 days of life subjected to TBI or subjected to all processes except TBI were divided into four groups which were randomized to receive the Cr supplementation (300 mg / kg po) was suspended in 0.5% CMC or vehicle (CMC) twice daily for a period of 14 days. it was shown that animals on submitted to TBI showed a reduction in cognitive functions evaluated by 15 days object recognition task after TBI. The animals that received creatine supplementation did not have their compromised functions. Our biochemical data revealed that the activity of the enzyme creatine kinase was increased fifteen days after trauma, in the same period the TBI did not alter the expression of AMPK however creatine supplementation increased its expression, suggesting a connection between CK and AMPK after TBI, since the creatine supplementation was effective in raising the activity of CK while increased expression of AMPK also caused a significant increase in the ratio of CREB and p-CREB in animals that were supplemented. We also note the participation of BDNF, whose expression this increases the animals submitted to the TBI and were supplemented with creatine, protection evidenced by creatine in lesion volume induced by the TBI. / Por definição o Traumatismo Cranioencefálico (TCE) é um acometimento comum em todas as sociedades e abrange todo o conjunto de processos que sozinhos ou em combinação podem danificar o encéfalo. Em crianças e adolescentes o TCE representa uma interrupção em seu desenvolvimento normal, com estimativas que variam de 200 a 500 casos para cada 100.000 ao ano. A maioria dos casos é caracterizada como leve, com poucas consequências a longo prazo, entretanto, uma porção significativa de jovens sofrerá ferimentos mais graves. Além disso, o TCE juvenil é a principal causa de morte e incapacidade em crianças e adolescente. Neste sentido, chama-se a atenção traumas sofridos, principalmente por jovens durante pratica de esportes de contato como as artes marciais, o futebol americano, hóquei no gelo, baseball. Devido a grande variedade de condições associadas ao TCE, há um considerável interesse no desenvolvimento e posterior aplicação de marcadores bioquímicos que relacionem a gravidade do dano cerebral com o desenvolvimento de problemas neurológicos, como déficits de memória e aprendizado. Neste contexto, o presente trabalho teve como objetivo, verificar se o se os animais jovens submetidos ao TCE apresentavam déficit cognitivo quinze dias após a lesão e se a suplementação com creatina possui efeito protetor, alterando a atividade da enzima CK, modulando a expressão das proteínas AMPK, CREB, p-CREB e BDNF envolvidas no déficit cognitivo e no dano histológico gerado pelo TCE. Para tal o presente estudo utilizou ratos Wistar jovens machos aos 35 dia de vida submetidos ao TCE ou submetido a todos os processos exceto o TCE, foram divididos em quatro grupos onde foram aleatoriamente separados, para receber a suplementação com Cr (300 mg / kg, p.o), suspensa em CMC a 0,5% ou veículo (CMC) duas vezes ao dia por um período de 14 dias. Foi evidenciado que os animais submetidos ao TCE apresentaram uma redução nas funções cognitivas avaliadas pela tarefa de reconhecimento de objeto 15 dias após o TCE. Já os animais que receberam a suplementação com creatina não tiveram suas funções comprometidas. Nossos dados bioquímicos revelaram que a atividade da enzima creatina quinase estava aumentada quinze dias pós-trauma, no mesmo período o TCE não alterou a expressão de AMPK porem a suplementação com creatina aumentou sua expressão, sugerindo uma conexão entre CK e AMPK após o TCE, uma vez que a suplementação com creatina foi efetiva em elevar a atividade da CK ao mesmo tempo que elevou a expressão de AMPK, também causou um aumento significativo na razão entre CREB e p-CREB nos animais que foram suplementados. Observamos também a participação do BDNF, cuja expressão esta aumenta nos animais que foram submetidos ao TCE e foram suplementados com creatina, na proteção evidenciada pela creatina no volume da lesão induzida pelo TCE.