RESUMO
Post-transplantation hypomagnesemia is common and predicts diabetes. Magnesium improves glycemic control in diabetics and insulin sensitivity in insulin resistant subjects. We aimed to assess the effectiveness of oral magnesium for improving glycemic control and insulin sensitivity at 3 months post-transplantation. We conducted a single-center, open-label, randomized parallel group study. We included adults with serum magnesium <1.7 mg/dl within 2 weeks after kidney transplantation. We randomized participants to 450 mg magnesium oxide up to three times daily or no treatment. The primary endpoint was the mean difference in fasting glycemia. Secondary endpoints were the mean difference in area under the curve (AUC) of glucose during an oral glucose tolerance test and insulin resistance measured by Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR). Analyses were on intention-to-treat basis. In patients randomized to magnesium oxide (N = 27) versus no treatment (N = 27), fasting glycemia on average was 11.5 mg/dl lower (95% CI 1.7 to 21.3; P = 0.02). There was no difference between the two groups neither for 2 h AUC, where the mean value was 1164 mg/dl/min (95% CI -1884 to 4284; P = 0.45) lower in the treatment group nor for HOMA-IR. Magnesium supplements modestly improved fasting glycemia without effect on insulin resistance. Higher baseline glycemia among patients in the control group may have driven the positive outcome (ClinicalTrials.gov number: NCT01889576).
Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Resistência à Insulina , Transplante de Rim , Deficiência de Magnésio/tratamento farmacológico , Óxido de Magnésio/uso terapêutico , Complicações Pós-Operatórias/tratamento farmacológico , Estado Pré-Diabético/sangue , Adulto , Idoso , Área Sob a Curva , Glicemia/análise , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Inibidores de Calcineurina/uso terapêutico , Diarreia/induzido quimicamente , Feminino , Teste de Tolerância a Glucose , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Resistência à Insulina/fisiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/cirurgia , Magnésio/fisiologia , Deficiência de Magnésio/etiologia , Óxido de Magnésio/administração & dosagem , Óxido de Magnésio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Receptor de Insulina/fisiologia , Índice de Gravidade de Doença , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Tacrolimo/uso terapêuticoRESUMO
In developing countries, prenatal lipid-based nutrient supplements (LNSs) were shown to increase birth size; however, the mechanism of this effect remains unknown. Cord blood hormone concentrations are strongly associated with birth size. Therefore, we hypothesize that LNSs increase birth size through a change in the endocrine regulation of fetal development. We compared the effect of daily prenatal LNSs with multiple micronutrient tablets on cord blood hormone concentrations using a randomized, controlled design including 197 pregnant women from rural Burkina Faso. Insulin-like growth factors (IGF) I and II, their binding proteins IGFBP-1 and IGFBP-3, leptin, cortisol, and insulin were quantified in cord sera using immunoassays. LNS was associated with higher cord blood leptin mainly in primigravidae (+57%; P = 0.02) and women from the highest tertile of BMI at study inclusion (+41%; P = 0.02). We did not find any significant LNS effects on other measured cord hormones. The observed increase in cord leptin was associated with a significantly higher birth weight. Cord sera from small-for-gestational age newborns had lower median IGF-I (-9 µg/L; P = 0.003), IGF-II (-79 µg/L; P = 0.003), IGFBP-3 (-0.7 µg/L; P = 0.007), and leptin (-1.0 µg/L; P = 0.016) concentrations but higher median cortisol (+18 µg/L; P = 0.037) concentrations compared with normally grown newborns. Prenatal LNS resulted in increased cord leptin concentrations in primigravidae and mothers with higher BMI at study inclusion. The elevated leptin concentrations could point toward a higher neonatal fat mass.
Assuntos
Peso ao Nascer , Dieta , Suplementos Nutricionais , Desenvolvimento Fetal , Leptina/sangue , Fenômenos Fisiológicos da Nutrição Materna , Cuidado Pré-Natal , Tecido Adiposo , Adolescente , Adulto , Índice de Massa Corporal , Burkina Faso , Países em Desenvolvimento , Feminino , Número de Gestações , Hormônios/sangue , Humanos , Hidrocortisona/sangue , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Micronutrientes/administração & dosagem , Obesidade/complicações , Gravidez , População Rural , Somatomedinas/metabolismo , Cordão Umbilical/metabolismo , Adulto JovemRESUMO
INTRODUCTION: Beta-alanine (BA) is a popular ergogenic supplement because it can induce muscle carnosine loading. We hypothesize that, by analogy with creatine supplementation, 1) an inverse relationship between urinary excretion and muscle loading is present, and 2) the latter is stimulated by carbohydrate- and protein-induced insulin action. METHODS: In study A, the effect of a 5-wk slow-release BA (SRBA) supplementation (4.8 g · d(-1)) on whole body BA retention was determined in seven men. We further determined whether the coingestion of carbohydrates and proteins with SRBA would improve retention. In study B (34 subjects), we explored the effect of meal timing on muscle carnosine loading (3.2 g · d(-1) during 6-7 wk). One group received pure BA (PBA) in between the meals; the other received PBA at the start of the meals, to explore the effect of meal-induced insulin release. Further, we compared with a third group receiving SRBA at the start of the meals. RESULTS AND CONCLUSION: Orally ingested SRBA has a very high whole body retention (97%-98%) that is not declining throughout the 5-wk supplementation period, nor is it influenced by the coingestion of macronutrients. Thus, a very small portion (1%-2%) is lost through urinary excretion, and equally only a small portion is incorporated into muscle carnosine (≈ 3%), indicating that most ingested BA is metabolized (possibly through oxidation). Second, in soleus muscles, the efficiency of carnosine loading is significantly higher when PBA is coingested with a meal (+64%) compared with in between the meals (+41%), suggesting that insulin stimulates muscle carnosine loading. Finally, the chronic supplementation of SRBA versus PBA seems equally effective.
Assuntos
Carnosina/metabolismo , Músculo Esquelético/efeitos dos fármacos , beta-Alanina/administração & dosagem , Adolescente , Adulto , Suplementos Nutricionais , Feminino , Humanos , Masculino , Refeições , Músculo Esquelético/metabolismo , Adulto JovemRESUMO
PURPOSE: Enhanced carnosine levels have been shown to be ergogenic for high-intensity exercise performances, although the role of carnosine in the control of muscle function is poorly understood. Therefore, the aim of this study was to investigate the effect of long-term supplementation with increasing doses of carnosine and beta-alanine on muscle carnosine, anserine, and taurine levels and on in vitro contractility and fatigue in mice. METHODS: Male Naval Medical Research Institute mice (n = 66) were control fed or supplemented with either carnosine (0.1%, 0.5%, or 1.8%) or beta-alanine (0.6 or 1.2%) in their drinking water for 8-12 wk. Soleus and extensor digitorum longus (EDL) were tested for in vitro contractile properties, and carnosine, anserine, and taurine content were measured in EDL and tibialis anterior by high-performance liquid chromatography. RESULTS: Only supplementation with 1.8% carnosine and 1.2% beta-alanine resulted in markedly higher carnosine (up to +160%) and anserine levels (up to +46%) compared with control mice. Beta-alanine supplementation (1.2%) resulted in increased fatigue resistance in the beginning of the fatigue protocol in soleus (+2%-4%) and a marked leftward shift of the force-frequency relation in EDL (10%-31% higher relative forces). CONCLUSION: Comparable with humans, beta-alanine availability seems to be the rate-limiting step for synthesis of muscle histidine-containing dipeptides in mice. Moreover, muscle histidine-containing dipeptides loading in mice moderately and muscle dependently affects excitation-contraction coupling and fatigue.
Assuntos
Carnosina/farmacologia , Suplementos Nutricionais , Contração Muscular/efeitos dos fármacos , Fadiga Muscular/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/farmacologia , beta-Alanina/farmacologia , Animais , Anserina/metabolismo , Biomarcadores/metabolismo , Carnosina/administração & dosagem , Carnosina/metabolismo , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Masculino , Camundongos , Músculo Esquelético/metabolismo , Taurina/metabolismo , beta-Alanina/administração & dosagemRESUMO
Chronic oral beta-alanine supplementation can elevate muscle carnosine (beta-alanyl-L-histidine) content and improve high-intensity exercise performance. However, the regulation of muscle carnosine levels is poorly understood. The uptake of the rate-limiting precursor beta-alanine and the enzyme catalyzing the dipeptide synthesis are thought to be key steps. The aims of this study were to investigate the expression of possible carnosine-related enzymes and transporters in both human and mouse skeletal muscle in response to carnosine-altering stimuli. Human gastrocnemius lateralis and mouse tibialis anterior muscle samples were subjected to HPLC and qPCR analysis. Mice were subjected to chronic oral supplementation of beta-alanine and carnosine or to orchidectomy (7 and 30 days, with or without testosterone replacement), stimuli known to, respectively, increase and decrease muscle carnosine and anserine. The following carnosine-related enzymes and transporters were expressed in human and/or mouse muscles: carnosine synthase (CARNS), carnosinase-2 (CNDP2), the carnosine/histidine transporters PHT1 and PHT2, the beta-alanine transporters TauT and PAT1, beta-alanine transaminase (ABAT) and histidine decarboxylase (HDC). Six of these genes showed altered expression in the investigated interventions. Orchidectomy led to decreased muscle carnosine content, which was paralleled with decreased TauT expression, whereas CARNS expression was surprisingly increased. Beta-alanine supplementation increased both muscle carnosine content and TauT, CARNS and ABAT expression, suggesting that muscles increase beta-alanine utilization through both dipeptide synthesis (CARNS) and deamination (ABAT) and further oxidation, in conditions of excess availability. Collectively, these data show that muscle carnosine homeostasis is regulated by nutritional and hormonal stimuli in a complex interplay between related transporters and enzymes.
Assuntos
Dipeptidases/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Músculo Esquelético/enzimologia , Peptídeo Sintases/metabolismo , Transcrição Gênica , Adulto , Animais , Carnosina/metabolismo , Dipeptidases/genética , Dipeptídeos/biossíntese , Feminino , Histidina Descarboxilase/genética , Histidina Descarboxilase/metabolismo , Humanos , Masculino , Proteínas de Membrana Transportadoras/genética , Camundongos , Músculo Esquelético/metabolismo , Orquiectomia , Peptídeo Sintases/genética , Testosterona/metabolismo , beta-Alanina/metabolismo , beta-Alanina-Piruvato Transaminase/metabolismoRESUMO
A polymorphism in the carnosine dipeptidase-1 gene (CNDP1), resulting in decreased plasma carnosinase activity, is associated with a reduced risk for diabetic nephropathy. Because carnosine, a natural scavenger/suppressor of ROS, advanced glycation end products, and reactive aldehydes, is readily degraded in blood by the highly active carnosinase enzyme, it has been postulated that low serum carnosinase activity might be advantageous to reduce diabetic complications. The aim of this study was to examine whether low carnosinase activity promotes circulating carnosine levels after carnosine supplementation in humans. Blood and urine were sampled in 25 healthy subjects after acute supplementation with 60 mg/kg body wt carnosine. Precooled EDTA-containing tubes were used for blood withdrawal, and plasma samples were immediately deproteinized and analyzed for carnosine and ß-alanine by HPLC. CNDP1 genotype, baseline plasma carnosinase activity, and protein content were assessed. Upon carnosine ingestion, 8 of the 25 subjects (responders) displayed a measurable increase in plasma carnosine up to 1 h after supplementation. Subjects with no measurable increment in plasma carnosine (nonresponders) had â¼2-fold higher plasma carnosinase protein content and â¼1.5-fold higher activity compared with responders. Urinary carnosine recovery was 2.6-fold higher in responders versus nonresponders and was negatively dependent on both the activity and protein content of the plasma carnosinase enzyme. In conclusion, low plasma carnosinase activity promotes the presence of circulating carnosine upon an oral challenge. These data may further clarify the link among CNDP1 genotype, carnosinase, and diabetic nephropathy.
Assuntos
Carnosina/administração & dosagem , Dipeptidases/sangue , Administração Oral , Adulto , Cromatografia Líquida de Alta Pressão , Nefropatias Diabéticas/genética , Dipeptidases/genética , Dipeptidases/urina , Feminino , Humanos , Masculino , beta-Alanina/sangueRESUMO
Carnosine is found in high concentrations in skeletal muscles, where it is involved in several physiological functions. The muscle carnosine content measured within a population can vary by a factor 4. The aim of this study was to further characterize suggested determinants of the muscle carnosine content (diet, gender and age) and to identify new determinants (plasma carnosinase activity and testosterone). We investigated a group of 149 healthy subjects, which consisted of 94 men (12 vegetarians) and 55 women. Muscle carnosine was quantified in M. soleus, gastrocnemius and tibialis anterior using magnetic resonance proton spectroscopy and blood samples were collected to determine CNDP1 genotype, plasma carnosinase activity and testosterone concentrations. Compared to women, men have 36, 28 and 82% higher carnosine concentrations in M. soleus, gastrocnemius and tibialis anterior muscle, respectively, whereas circulating testosterone concentrations were unrelated to muscle carnosine levels in healthy men. The carnosine content of the M. soleus is negatively related to the subjects' age. Vegetarians have a lower carnosine content of 26% in gastrocnemius compared to omnivores. In contrast, there is no difference in muscle carnosine content between omnivores with a high or low ingestion of ß-alanine. Muscle carnosine levels are not related to the polymorphism of the CNDP1 gene or to the enzymatic activity of the plasma carnosinase. In conclusion, neither CNDP1 genotype nor the normal variation in circulating testosterone levels affects the muscular carnosine content, whereas vegetarianism, female gender and increasing age are the factors associated with reduced muscle carnosine stores.
Assuntos
Carnosina/sangue , Dipeptidases , Músculos/química , Adolescente , Adulto , Fatores Etários , Dieta , Dieta Vegetariana/efeitos adversos , Suplementos Nutricionais , Dipeptidases/sangue , Dipeptidases/genética , Feminino , Expressão Gênica , Genótipo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético , Fatores Sexuais , Testosterona/sangue , Adulto Jovem , beta-Alanina/análiseAssuntos
Tolerância ao Exercício/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Nitratos/administração & dosagem , Consumo de Oxigênio/efeitos dos fármacos , Preparações de Plantas/administração & dosagem , Administração Oral , Adulto , Beta vulgaris , Bebidas , Ciclismo , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Exercício Físico , Hemoglobinas/metabolismo , Humanos , Masculino , Contração Muscular , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Nitratos/sangue , Oxiemoglobinas/metabolismo , Raízes de Plantas , Espectroscopia de Luz Próxima ao Infravermelho , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: To test the hypothesis that L-arginine (the substrate for nitric oxide synthase [NOS]) administration slows the VO2 kinetics at the onset of moderate-intensity exercise in humans. METHODS: Seven physically active males were randomly assigned to receive either placebo (lactose) or L-arginine hydrochloride capsules (7.2 g x d(-1)) for 14 d in a double-blind crossover design, with a 7-d washout period between the two conditions. On day 11 and day 14 of each condition, the subjects completed two consecutive 6-min bouts of cycle exercise at 80% of the ventilatory threshold with a 12-min rest interval. VO2 was measured on a breath-by-breath basis, and VO2 kinetics were determined with a single exponential model from the averaged data derived from four repetitions. Capillary and venous blood samples were taken to determine plasma [La] and serum [arginine], respectively. RESULTS: There were no differences in circulating lactate either before or during exercise. However, serum [arginine] was higher (P < 0.05) in the arginine condition at rest (119.0 +/- 12.6 vs 103.6 +/- 15.7 micromol x L(-1) in the control condition) and after exercise (113.3 +/- 26.0 vs 103.8 +/- 12.6 micromol x L(-1) in the control condition). With regard to the pulmonary VO2 kinetics, no significant difference was observed in the time at which the phase II response emerged or in the phase II amplitude between the two conditions. However, contrary to our hypothesis, the time constant was significantly reduced after arginine administration (i.e., 13.9 +/- 3.1 vs 15.8 +/- 2.6 s in the control condition, P < or = 0.014). CONCLUSION: Exogenous L-arginine administration speeds the phase II pulmonary VO2 response by 12% at the onset of moderate-intensity exercise in humans.
Assuntos
Arginina/administração & dosagem , Suplementos Nutricionais , Consumo de Oxigênio/efeitos dos fármacos , Esforço Físico/fisiologia , Método Duplo-Cego , Teste de Esforço , Humanos , Cinética , Masculino , Óxido Nítrico , Troca Gasosa Pulmonar , Adulto JovemRESUMO
BACKGROUND: Specific guanidino compounds have been described as uraemic toxins and their concentrations are increased in renal failure due to dimished glomerular filtration, whereas the guanidino compound creatine is used as a performance-enhancing substance in athletes. The present study investigates the effects of creatine supplementation on plasma guanidino compounds in a chronic haemodialysis population. METHODS: Twenty male haemodialysis patients were included in a placebo-controlled cross-over trial. Patients were treated with creatine (2 g/day) or placebo during two treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma guanidino compounds and routine biochemical parameters were determined, as well as the prognostic inflammatory and nutritional index (PINI). RESULTS: Upon creatine supplementation, guanidinoacetate concentrations decreased by 15%, due to inhibition of creatine synthesis. Concentrations of alpha-keto-delta-guanidinovaleric acid increased three-fold and argininic acid concentrations doubled. Guanidinosuccinate concentrations did not change, but correlated inversely with CRP (r = -0.736; P = 0.001), PINI-score (r = -0.716; P = 0.002) and correlated positively with plasma urea concentration (r = 0.54; P = 0.02). CONCLUSIONS: Creatine supplementation in haemodialysis patients significantly altered the concentration of specific guanidino compounds. Guanidinosuccinate correlated positively with plasma urea and negatively with inflammation markers.
Assuntos
Arginina/análogos & derivados , Creatina/uso terapêutico , Glicina/análogos & derivados , Guanidinas/sangue , Inflamação/sangue , Insuficiência Renal/sangue , Succinatos/sangue , Administração Oral , Idoso , Arginina/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Creatina/administração & dosagem , Creatina/farmacocinética , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Seguimentos , Glicina/sangue , Humanos , Masculino , Nefelometria e Turbidimetria , Prognóstico , Diálise Renal , Insuficiência Renal/terapia , Índice de Gravidade de Doença , Resultado do Tratamento , Ureia/sangueRESUMO
BACKGROUND: Hyperhomocysteinemia is present in the majority of chronic hemodialysis patients. Treatment with folic acid, vitamin B12, and vitamin B6 cannot fully normalize plasma homocysteine concentrations (tHcy). Previously we have demonstrated the tHcy-lowering effect of creatine supplementation in an animal model of uremia (Kidney Int 64:1331-1337, 2003). The present study investigates the effects of creatine supplementation on tHcy in a vitamin-repleted chronic hemodialysis population. METHODS: Forty-five hemodialysis patients receiving folic acid and vitamin B6 and B12 were included. Patients were treated with creatine (2 g/day) or placebo during 2 treatment periods of 4 weeks, separated by a washout of 4 weeks. Plasma tHcy, creatine, Kt/V(urea), folic acid, vitamin B12, and routine biochemistry were determined, as well as the prognostic inflammatory and nutritional index. RESULTS: All patients had elevated tHcy concentrations (21.2 +/- 5.6 micromol/L). Creatine treatment resulted in increased plasma and red blood cell creatine levels, documenting uptake of creatine. Creatine did not affect tHcy concentrations. There was no relationship between plasma creatine concentrations and tHcy concentrations. No changes in body weight, routine biochemistry, nutritional status, folic acid, or vitamin B12 were observed during the study. CONCLUSION: Creatine supplementation at a rate of 2 g/day does not further decrease tHcy concentrations in chronic dialysis patients already treated with high dose folic acid, vitamin B6, and B12 supplementation.
Assuntos
Creatina/administração & dosagem , Homocisteína/sangue , Hiper-Homocisteinemia/tratamento farmacológico , Falência Renal Crônica/complicações , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Creatina/sangue , Estudos Cross-Over , Feminino , Ácido Fólico/administração & dosagem , Ácido Fólico/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/etiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Avaliação Nutricional , Vitamina B 12/administração & dosagem , Vitamina B 12/sangue , Vitamina B 6/administração & dosagem , Vitamina B 6/sangueRESUMO
BACKGROUND: Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is thought to contribute to the excess cardiovascular mortality and morbidity. Creatine is synthesized by methylation of guanidinoacetate with formation of S-adenosylhomocysteine and subsequently, homocysteine (Hcy). Creatine supplementation down-regulates its endogenous synthesis and, thus, may reduce Hcy production. The present study investigates the effect of creatine supplementation on Hcy concentrations in an animal model of uremia. METHODS: Male Wistar rats were either sham-operated and received a control diet (N = 8) or a 2% creatine-supplemented diet (N = 8), or underwent subtotal nephrectomy and received a control diet (N = 10) or a 2%-supplemented creatine diet (N = 10). After 2 weeks of treatment, total plasma Hcy, creatine, creatinine, folate, and vitamin B12 were determined, as well as hepatic folate and vitamin B12 concentrations. RESULTS: Plasma creatinine concentrations were higher in nephrectomized animals, but similar in creatine-supplemented and control diet-fed animals. Plasma Hcy was higher in nephrectomized animals but lower in creatine-supplemented nephrectomized animals compared to nephrectomized control diet-fed animals (12.1 +/- 2.4 micromol/L vs. 15.4 +/- 1.7 micromol/L; P < 0.01). Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals. CONCLUSION: Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.
Assuntos
Creatina/farmacologia , Homocisteína/antagonistas & inibidores , Homocisteína/sangue , Uremia/sangue , Animais , Biometria , Ácido Fólico/sangue , Ácido Fólico/metabolismo , Fígado/metabolismo , Masculino , Nefrectomia , Concentração Osmolar , Ratos , Ratos Wistar , Uremia/metabolismo , Uremia/patologia , Vitamina B 12/sangue , Vitamina B 12/metabolismoRESUMO
effect of oral creatine supplementation (CR; 5 g/day) in conjunction with exercise training on physical fitness was investigated in men between 55 and 75 yr of age (n = 46). A double-blind randomized placebo-controlled (PL) trial was performed over a 6-mo period. Furthermore, a subgroup (n = 20) completed a 1-yr follow-up. The training program consisted of cardiorespiratory endurance training as well as moderate resistance training (2-3 sessions/wk). Endurance capacity was evaluated during a maximal incremental bicycle ergometer test, maximal isometric strength of the knee-extensor muscles was assessed by an isokinetic dynamometer, and body composition was assessed by hydrostatic weighing. Furthermore, in a subgroup (PL: n = 13; CR: n = 12) biopsies were taken from m. vastus lateralis to determine total creatine (TCr) content. In PL, 6 mo of training increased peak oxygen uptake rate (+16%; P < 0.05). Fat-free mass slightly increased (+0.3 kg; P < 0.05), whereas percent body fat slightly decreased (-1.2%; P < 0.05). The training intervention did not significantly change either maximal isometric strength or body weight. The responses were independent of CR. Still, compared with PL, TCr was increased by approximately 5% in CR, and this increase was closely correlated with initial muscle creatine content (r = -0.78; P < 0.05). After a 1-yr follow-up, muscle TCr was not higher in CR than in PL. Furthermore, the other measurements were not affected by CR. It is concluded that long-term creatine intake (5 g/day) in conjunction with exercise training does not beneficially impact physical fitness in men between 55 and 75 yr of age.
Assuntos
Creatina/administração & dosagem , Suplementos Nutricionais , Educação Física e Treinamento , Aptidão Física , Administração Oral , Idoso , Composição Corporal , Creatina/sangue , Creatina/metabolismo , Creatina/urina , Método Duplo-Cego , Teste de Esforço , Seguimentos , Histocitoquímica , Humanos , Contração Isométrica , Joelho , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Resistência Física , Fatores de Tempo , Levantamento de PesoRESUMO
BACKGROUND: Creatine is widely used as an ergogenic substance among athletes. Safety of prolonged creatine intake has been questioned, based upon case reports and animal data. We investigated the effect of prolonged creatine ingestion on renal function in animals with normal kidney function or pre-existing kidney failure, respectively. METHODS: Male Wistar rats were randomly allocated to four experimental groups: (i) sham-operated, control diet; (ii) sham-operated, creatine-supplemented diet (2% w/w (0.9+/-0.2 g creatine/kg body weight/day)); (iii) two-thirds nephrectomized, control diet; and (iv) two-thirds nephrectomized, creatine supplemented diet. Glomerular filtration rate was determined using inulin and creatinine clearance, together with albumin excretion, urea clearance, muscle and serum creatine and serum cystatin C concentrations. RESULTS: In contrast to previous reports, no detrimental effects of creatine supplementation on the renal function indices were observed in two-thirds nephrectomized or sham-operated animals. No differences were observed in inulin (0.28+/-0.08 vs 0.25+/-0.08 ml/min/100 g; P=NS) or creatinine clearance rates. Serum cystatin C concentration, urinary protein excretion, and albumin and urea clearance were comparable between creatine-supplemented and control-diet fed animals in both sham-operated and two-thirds nephrectomized animals. Serum creatine and intramuscular total creatine concentrations were higher in creatine-supplemented groups (P<0.05). CONCLUSIONS: Creatine supplementation at a dosage of 2% w/w for 4 weeks does not impair kidney function in animals with pre-existing renal failure or in control animals.