Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents.

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.

Sex- and tissue-dependent creatine uptake in response to different creatine monohydrate doses in male and female Sprague-Dawley rats.

Sprague-Dawley rats (n = 32) underwent 8-weeks of creatine monohydrate (CM) supplementation (0, 2.5, 5, and 10 g/L). Total creatine (TCr) concentrations in female white fibre-dominant gastrocnemius (WGAS) and cardiac muscle (HRT) were significantly higher compared with males (p < 0.05). CM supplementation increased TCr concentrations in female WGAS (p < 0.05) and HRT (p < 0.01) and in male red fibre-dominant gastrocnemius muscle (RGAS) (p < 0.05). Future research should further investigate sex-differences in basal levels of TCr and the response to CM supplementation. Novelty: There is a sex- and tissue-dependant response to CM supplementation in rats.

Creatine in Health and Disease.

Although creatine has been mostly studied as an ergogenic aid for exercise, training, and sport, several health and potential therapeutic benefits have been reported. This is because creatine plays a critical role in cellular metabolism, particularly during metabolically stressed states, and limitations in the ability to transport and/or store creatine can impair metabolism. Moreover, increasing availability of creatine in tissue may enhance cellular metabolism and thereby lessen the severity of injury and/or disease conditions, particularly when oxygen availability is compromised. This systematic review assesses the peer-reviewed scientific and medical evidence related to creatine's role in promoting general health as we age and how creatine supplementation has been used as a nutritional strategy to help individuals recover from injury and/or manage chronic disease. Additionally, it provides reasonable conclusions about the role of creatine on health and disease based on current scientific evidence. Based on this analysis, it can be concluded that creatine supplementation has several health and therapeutic benefits throughout the lifespan.

Pharmacokinetics and hemorheology of phosphocreatine and creatine in rabbits: A directly comparative study between parent drug and active metabolite.

This study is to investigate pharmacokinetics (PK) and hemorheology (HR) of exogenous phosphocreatine (PCr), a cardio-protective agent, and its active metabolite creatine (Cr), with particular focus on the PK and PD comparison between PCr and Cr. A specific ion-pair reversed-phase HPLC-UV assay was used to simultaneously measure PCr, Cr and ATP concentrations in plasma and red blood cells (RBC) samples of rabbits. PK and HR parameters were calculated based on concentration-time (C-T) curves and effect-time (E-T) curves, respectively, obtained after i.v. dosing. Meanwhile the apparent pharmacological activity ratio (Rapp) and real pharmacological activity ratio (Rreal) of Cr to PCr were calculated. The PCr disappeared from plasma rapidly and in a biphasic manner; plasma PCr was converted to Cr fast and largely with the elimination rate limited metabolite disposition in vivo (Km < K). The i.v. administration of PCr led to a markedly elevated and long-lasting ATP level in RBC. After i.v. administration of preformed Cr, plasma Cr displayed similar elimination kinetics behaviors to that of Cr generated metabolically after i.v. PCr. The Cr could also raise ATP level in RBC, but to less extent than PCr. Approximately 43% of PCr-derived ATP came from Cr-derived ATP in RBC. PCr could significantly reduce whole blood viscosity and RBC osmotic fragility and Cr could do so, but weakly with estimated Rapp of 0.53-0.68 and Rreal of 0.38-0.48. PCr also inhibited platelet aggregation significantly, as opposed to Cr. The PCr-caused improvement of HR is related to the rise in ATP level in RBC. Cr is likely to partially mediate HR effect of PCr.

Creatine supplementation exacerbates ethanol-induced hepatic damage in mice.

OBJECTIVE: The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. METHODS: Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. RESULTS: Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P < 0.05). CONCLUSION: Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

Simultaneous quantitative analysis of phosphocreatine, creatine and creatinine in plasma of children by HPLC-MS/MS method: Application to a pharmacokinetic study in children with viral myocarditis.

A simple and rapid HPLC-MS/MS method was developed and validated for simultaneous measurement of phosphocreatine and its metabolites creatine and creatinine in children's plasma. A 50 µL aliquot of plasma was prepared by protein precipitation with acetonitrile-water (1000 µL, 1:1, v/v) followed by separation on a Hypersil Gold C18 column (35°C) with gradient mobile phase consisting of 2 mm ammonium acetate aqueous solution (pH 10) and methanol at a flow rate of 0.3 mL/min and analyzed by mass spectrometry in both positive (phosphocreatine) and negative (creatine and creatinine) ion multiple reaction monitoring mode. Good linearity (r > 0.99) was obtained for the three analytes. The intra-day and inter-day values of CV were <5.46% (-13.09% ≤ RE ≤ 2.57%). The average recoveries of the three analytes were 70.9-97.5%. No obvious impact was found for the quantitation of three analytes in normal, hemolyzed and hyperlipemic plasma. In the end, this method was successfully applied to a pharmacokinetic study of phosphocreatine in children (six cases) with viral myocarditis of children after intravenous infusion of 2 g of the test drug. The pharmacokinetc parameters of phosphocreatine/creatine were as follows: t1/2 0.24/0.83 h, Tmax 0.49/0.55 h, Cmax 47.34/59.29 µg/mL, AUClast 17.07/59.63 h µg/mL, AUCinf 17.16/79.01 h µg/mL and MRT 0.29/0.67 h.

Strong Relation Between Muscle Mass Determined by D3-creatine Dilution, Physical Performance, and Incidence of Falls and Mobility Limitations in a Prospective Cohort of Older Men.

BACKGROUND: Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass. METHODS: Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 years). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 m); and dual x-ray absorptiometry (DXA) lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls. RESULTS: Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (odds ratio [OR] Q1 vs Q4: 2.49, 95% confidence interval [CI]: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95% CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend < .001 for all. Results for incident recurrent falls were in the similar direction (p = .156). DXA lean mass had weaker associations with the outcomes. CONCLUSIONS: Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility, and incident injurious falls in older men.

Metabolic Syndrome and the Iodine-Dose/Creatinine Clearance Ratio as Determinants of Contrast-Induced Acute Kidney Injury.

BACKGROUND: Finding patients at risk of developing contrast-induced acute kidney injury (CI-AKI) is important because of its associated complications. In the present study, the contribution of different variables, such as the presence of metabolic syndrome (MetS), the volume creatinine clearance (V/CrCl) ratio, the iodine-dose (I-dose)/CrCl ratio, or hypertension, to CI-AKI was evaluated. METHODS: A total of 255 patients undergoing elective coronary angiography with or without intervention were enrolled and divided into a MetS and a control group. All patients were assessed for the development of CI-AKI after the procedures. RESULTS: CI-AKI occurred in 39.23% (51 of 130) of the MetS patients and 14.4% (18 of 125) of the control group (p < 0.001). The multivariable regression model showed that male sex and the use of statins decreased the risk of CI-AKI, and high triglyceride levels, I-dose/CrCl > 0.52, MetS, CrCl ≤60 mL/min, and age ≥70 years increased the risk of CI-AKI, independent of confounding factors. The difference in the mean V/CrCl ratio was statistically significant between patients who developed CI-AKI and those who did not show renal impairment (2.36 ± 1.35 vs. 1.43 ± 0.89, respectively; p < 0.001). The ROC curve analysis of I-dose/CrCl determined the best cutoff value for patients with and those without MetS as 0.51 and 0.63, with a sensitivity value of 68 and 72% and a specificity value of 73 and 74%, respectively. CONCLUSIONS: We showed that MetS is a strong risk factor for CI-AKI in nondiabetic patients undergoing elective coronary interventions; and the I-dose/CrCl ratio is a strong predictor of CI-AKI in these patients. We suggest that clinicians identify MetS patients and calculate their I-dose/CrCl ratio before coronary interventions.

Dilution of oral D3 -Creatine to measure creatine pool size and estimate skeletal muscle mass: development of a correction algorithm.

BACKGROUND: Muscle mass can be measured directly in vivo by isotope dilution, using Creatine-(methyl-d3 ) monohydrate (D3 -Cr) by mouth followed by measurement of the steady-state enrichment of D3 -creatinine (D3 -Crn) in urine. Isotope dilution methods require knowledge of the amount of tracer delivered to the pool of interest. In a subset of human subjects, a small amount of orally administered D3 -Cr 'spills' into urine after absorption and prior to transport into skeletal muscle cells. The objectives were to develop a method to correct for spillage to compare the estimate of muscle mass by D3 -Cr dilution to other assessments of fat-free mass. METHODS: Subjects (19 males, 23-81 years old; 20 females, 20-77 years old) ingested a single dose of 60 mg D3 -Cr and urine was collected prior to and daily for 4 days following the dose. Fasting morning urine samples was assessed for D3 -Cr, total Cr, D3 -Crn, and total Crn concentrations, as well as isotopic enrichments of D3 -Crn, by LC/MS. The 24-h urine collections over 3 days after the dose of D3 -Cr were also performed to determine D3 -Cr spillage. Total body water, fat mass, and fat-free mass were assessed by bioelectrical impedance spectroscopy (BIS). RESULTS: Spillage of D3 -Cr in the urine was greater in women than men. D3 -Crn enrichment and the ratio of Cr/Crn were used in an algorithm to calculate Cr pool size and muscle mass. Specifically, an algorithm was developed for the estimation of spillage based on the relationship between the fasting Cr/Crn ratio and the cumulative proportion of the D3 -Cr dose excreted over 3 days based on 24-h urine collections. Muscle mass corrected using the algorithm based on fasting urine levels correlated (r = 0.9967, P < 0.0001) with that corrected by measuring D3 -Cr dose excreted. Muscle mass measured by D3 -Crn enrichment also correlated (r = 0.8579, P < 0.0001, algorithm corrected) with that measured by 24-h Crn excretion. Muscle mass measured by D3 -Cr dilution method correlated with intracellular water by BIS, whether using spillage corrected by the algorithm (r = 0.9041, P < 0.0001) or measured by 3 day D3 -Cr losses (r = 0.91, P < 0.0001) and similarly correlated with fat-free mass by BIA (r = 0.8857 and 0.8929, P < 0.0001, respectively). CONCLUSIONS: The D3 -Cr dilution method is further validated here as a non-invasive, easy-to-use test for measuring muscle mass. The technical issue of D3 -Cr spillage can be corrected for with a simple algorithm based on fasting spot urine samples. Muscle mass by Cr dilution potentially has broad applications in clinical and research settings.

Comparison of muscle/lean mass measurement methods: correlation with functional and biochemical testing.

DXA-measured lean mass is often used to assess muscle mass but has limitations. Thus, we compared DXA lean mass with two novel methods-bioelectric impedance spectroscopy and creatine (methyl-d3) dilution. The examined methodologies did not measure lean mass similarly and the correlation with muscle biomarkers/function varied. INTRODUCTION: Muscle function tests predict adverse health outcomes better than lean mass measurement. This may reflect limitations of current mass measurement methods. Newer approaches, e.g., bioelectric impedance spectroscopy (BIS) and creatine (methyl-d3) dilution (D3-C), may more accurately assess muscle mass. We hypothesized that BIS and D3-C measured muscle mass would better correlate with function and bone/muscle biomarkers than DXA measured lean mass. METHODS: Evaluations of muscle/lean mass, function, and serum biomarkers were obtained in older community-dwelling adults. Mass was assessed by DXA, BIS, and orally administered D3-C. Grip strength, timed up and go, and jump power were examined. Potential muscle/bone serum biomarkers were measured. Mass measurements were compared with functional and serum data using regression analyses; differences between techniques were determined by paired t tests. RESULTS: Mean (SD) age of the 112 (89F/23M) participants was 80.6 (6.0) years. The lean/muscle mass assessments were correlated (.57-.88) but differed (p < 0.0001) from one another with DXA total body less head being highest at 37.8 (7.3) kg, D3-C muscle mass at 21.1 (4.6) kg, and BIS total body intracellular water at 17.4 (3.5) kg. All mass assessment methods correlated with grip strength and jump power (R = 0.35-0.63, p < 0.0002), but not with gait speed or repeat chair rise. Lean mass measures were unrelated to the serum biomarkers measured. CONCLUSIONS: These three methodologies do not similarly measure muscle/lean mass and should not be viewed as being equivalent. Functional tests assessing maximal muscle strength/power (grip strength and jump power) correlated with all mass measures whereas gait speed was not. None of the selected serum measures correlated with mass. Efforts to optimize muscle mass assessment and identify their relationships with health outcomes are needed.

Creatine ( methyl-d3) dilution in urine for estimation of total body skeletal muscle mass: accuracy and variability vs. MRI and DXA.

A noninvasive method to estimate muscle mass based on creatine ( methyl-d3) (D3-creatine) dilution using fasting morning urine was evaluated for accuracy and variability over a 3- to 4-mo period. Healthy older (67- to 80-yr-old) subjects ( n = 14) with muscle wasting secondary to aging and four patients with chronic disease (58-76 yr old) fasted overnight and then received an oral 30-mg dose of D3-creatine at 8 AM ( day 1). Urine was collected during 4 h of continued fasting and then at consecutive 4- to 8-h intervals through day 5. Assessment was repeated 3-4 mo later in 13 healthy subjects and 1 patient with congestive heart failure. Deuterated and unlabeled creatine and creatinine were measured using liquid chromatography-tandem mass spectrometry. Total body creatine pool size and muscle mass were calculated from D3-creatinine enrichment in urine. Muscle mass was also measured by whole body MRI and 24-h urine creatinine, and lean body mass (LBM) was measured by dual-energy X-ray absorptiometry (DXA). D3-creatinine urinary enrichment from day 5 provided muscle mass estimates that correlated with MRI for all subjects ( r = 0.88, P < 0.0001), with less bias [difference from MRI = -3.00 ± 2.75 (SD) kg] than total LBM assessment by DXA, which overestimated muscle mass vs. MRI (+22.5 ± 3.7 kg). However, intraindividual variability was high with the D3-creatine dilution method, with intrasubject SD for estimated muscle mass of 2.5 kg vs. MRI (0.5 kg) and DXA (0.8 kg). This study supports further clinical validation of the D3-creatine method for estimating muscle mass. NEW & NOTEWORTHY Measurement of creatine ( methyl-d3) (D3-creatine) and D3-creatinine excretion in fasted morning urine samples may be a simple, less costly alternative to MRI or dual-energy X-ray absorptiometry (DXA) to calculate total body muscle mass. The D3-creatine enrichment method provides estimates of muscle mass that correlate well with MRI, and with less bias than DXA. However, intraindividual variability is high with the D3-creatine method. Studies to refine the spot urine sample method for estimation of muscle mass may be warranted.

Creatine monohydrate ingestion-related placebo effects on brief anaerobic exercise performance. A laboratory investigation / Efectos placebo de la ingestión de monohidrato de creatina sobre el rendimiento breve del ejercicio anaeróbico. Una investigación de laboratorio / Efeitos de placebo relacionados com a ingestão de monohidrato de creatina no desempenho de exercício anaeróbico breve. Uma investigação laboratorial

People’s thoughts influence their action that led researchers to investigate the placebo effect in exercise performance. In the current study the placebo effects of creatine monohydrate on a one-minute anaerobic step-exercise performance were examined in a double blind laboratory inquiry. University students (n = 79, 64.5% women) were randomly assigned to one of three experimental conditions: 1) intervention (ingestion of 80 mg/kg dissolved creatine monohydrate, n = 26), 2) placebo (ingestion of dissolved corn starch, thought to be creatine, n = 26), and 3) no-intervention control (ingestion of drinking water only, n = 27). After a baseline measurement, participants have consumed their respective drinks and 40 minutes later the 1-minute exercise was repeated. While analysis of variance revealed no group level differences in actual and perceived change in performance, the latter was linked to participants’ expectations regarding performance on the second exercise test in the correlation analysis. Two thirds of the participants in the current study believed that their performance would improve in the actual test-exercise. However, these expectations were not linked to creatine ingestion. These findings suggest that (1) a single dose of creatine monohydrate does not affect anaerobic performance, (2) in low-challenge and low-subjective-importance 'artificial' research conditions sufficient expectations could not be evoked, and probably due to the lack of creatine-related expectations the placebo effects did not emerge (AU)

La influencia de los pensamientos de las personas sobre sus acciones, llevó a los investigadores a investigar el efecto placebo sobre el rendimiento en el ejercicio. En el presente estudio se analiza el efecto placebo de la creatina monohidrato sobre el rendimiento en un ejercicio anaeróbico de un minuto de duración en laboratorio mediante el método de doble ciego. Los participantes fueron estudiantes universitarios (n = 79, 64,5% mujeres) que se asignaron aleatoriamente a una de las tres condiciones experimentales: 1) intervención (ingestión de creatina monohidrato disuelta, n = 26); 2) placebo (ingestión de almidón de maíz disuelto, creyendo que es creatina , n = 26); y 3) grupo control sin intervención (ingestión de agua potable solamente, n = 27). Después de establecer la línea base, los participantes tomaron sus respectivas bebidas y 40 minutos más tarde se repitió el ejercicio de 1 minuto de duración. Si bien el análisis de varianza no reveló diferencias entre los grupos entre el rendimiento real y el percibido, este último se vinculó, mediante análisis de correlación, a las expectativas de los participantes en relación con el rendimiento en la segunda prueba realizada. Dos tercios de los participantes consideraron que su rendimiento mejoraría en la prueba de ejercicio real, sin embargo, estas expectativas no estuvieron relacionadas con la ingesta de creatina. Los resultados sugieren que: (1) una dosis única de creatina monohidrato no afecta al rendimiento anaeróbico; (2) en la condición de bajo desafío y baja importancia subjetiva, no emergió el efecto placebo debido, probablemente, a la falta de expectativas evocadas sobre los efectos de la creatina (AU)

A influência dos pensamentos das pessoas sobre suas ações, levou os pesquisadores a investigar o placebo efeito sobre o desempenho do exercício. No presente estudo, a creatina mono-hidrato de placebo no desempenho no exercício anaeróbio de um minuto no laboratório pelo método de efeito duplo-cego é analisada. Os participantes eram estudantes universitários (n = 79, 64,5% mulheres) que foram atribuídos aleatoriamente a uma de três condições experimentais atribuída: 1) intervenção (ingestão de creatina monohidratada dissolvida, n = 26); 2) placebo (amido de milho dissolvido ingestão, acreditando que a creatina, n = 26); e 3) grupo de controlo sem intervenção (apenas ingestão de água potável, n = 27). Depois de estabelecer a linha de base, os participantes tomaram suas bebidas e 40 minutos depois do exercício de 1 minuto de duração repetido. Enquanto a análise de variância não revelou diferenças entre os grupos de entre o desempenho real e percebidos, a última foi ligada por análise de correlação, as expectativas dos participantes em relação ao desempenho no segundo teste realizado. Dois terços dos participantes sentiram que seu desempenho iria melhorar no teste de esforço real, no entanto, essas expectativas não foram relacionados com a ingestão de creatina. Os resultados sugerem que: (1) uma única dose de mono-hidrato de creatina não afecta o desempenho anaeróbio; (2) a condição sob desafio e menor importância subjetiva, surgiu o efeito placebo, provavelmente devido à falta de expectativas evocado sobre os efeitos da creatina (AU)

Ayudas ergogénicas en el deporte / Ergogenic aids in sport

Introducción: muy pocos suplementos nutricionales han demostrado científicamente su eficacia como ayuda ergogénica. Esta revisión analizará el monohidrato de creatina (MC), el β-hidroxi-β-metilbutirato (HMB), el bicarbonato sódico (BS), la β-alanina y la cafeína. Objetivos: analizar la eficacia, mecanismos de acción, dosis, efectos adversos y algunos deportes que se pueden beneficiar de su consumo. Métodos: búsqueda en la base de datos PubMed de revisiones bibliográficas de los últimos 15 años y artículos originales de los últimos 5 años de las sustancias estudiadas. Resultados: dosis de MC de 20 g/día durante 4-7 días son eficaces para mejorar la fuerza y la potencia muscular y el rendimiento en sprints cortos y repetidos. El HMB en dosis de 3 g/día durante un mínimo de 2 semanas contribuye al aumento de la masa magra y de la masa libre de grasa. La ingesta de 0,3 g/kg de BS mejora el rendimiento en pruebas de 400-1.500 m de atletismo y en sprints intermitentes. Por su parte, dosis de 80 mg/kg/día de β-alanina durante 4-10 semanas pueden mejorar el rendimiento en ejercicios intermitentes de alta intensidad. Finalmente, la cafeína en dosis de 2 mg/kg mejora la capacidad de reacción y en dosis de 3-6 mg/kg mejora el rendimiento en pruebas de resistencia aeróbica. Conclusiones: los suplementos revisados presentan una demostrada eficacia en el rendimiento físico, pero hay que tener en cuenta que la mayoría de los estudios se han realizado con deportistas de nivel recreativo. Generalmente, la mejora del rendimiento físico con estos suplementos es menor cuanto mejor es el nivel deportivo del individuo; sin embargo, un incremento de apenas un 1% permite a veces avanzar varios puestos en una final. Finalmente, se debe llamar la atención sobre la importancia de optimizar la alimentación antes de plantearse la introducción de suplementos deportivos, especialmente en niños y jóvenes. Las sustancias que hemos analizado poseen una base científica que respalda su efecto ergogénico. Todas ellas se pueden encontrar en el mercado con Certificado de Calidad y Pureza (AU)

Introduction: Very few nutritional supplements have scientifically demonstrated their effectiveness as an ergogenic aid. This review will examine creatine monohydrate (MC), the β-hydroxy-β-methylbutyrate (HMB), sodium bicarbonate (BS), the β-alanine and caffeine. Objectives: To analyze the efficacy, mechanisms of action, dose, side effects and some sports that can benefit from their consumption. Methods: Searching in PubMed bibliographic database reviews from the last 15 years and original articles from the last 5 years of the studied substances. Results: Doses of 20 mg/day for 4-7 days are effective in improving strength and muscular power and performance in short and repeated sprints. HMB at doses of 3 g/day for at least 2 weeks contributes to increased lean mass and fat-free mass. The intake of 0.3 g/kg of BS improves performance on tests of 400-1,500 meters in athletics and intermittent sprints. Meanwhile, doses of 80 mg/kg/day of β-alanine for 4-10 weeks may improve performance in high-intensity intermittent exercise. Finally, caffeine at doses of 2 mg/kg improves responsiveness and 3-6 mg/kg improves performance in endurance tests. Conclusions: The revised supplements have shown their efficacy in physical performance, but it is needed to keep in mind that most studies have been conducted with recreational-level athletes. Generally, the better the individual´s fitness level is the less improvement in physical performance the supplement shows. However, an increase of only 1% may sometimes allow the athlete to advance several positions in a final. Finally, we should draw attention to the importance of optimizing nutrition before considering the introduction of sports supplements, especially in children and youth. All analyzed substances have scientific basis supporting its ergogenic effect. All of them can be found in the market with Certificate of Quality and Purity (AU)

Plasma Creatine Kinetics After Ingestion of Microencapsulated Creatine Monohydrate with Enhanced Stability in Aqueous Solutions.

Creatine monohydrate represents one of the largest sports supplement markets. Enhancing creatine (CRE) stability in aqueous solutions, such as with microencapsulation, represents innovation potential. Ten physically active male volunteers were randomly assigned in a double-blind design to either placebo (PLA) (3-g maltodextrin; n = 5) or microencapsulated CRE (3-g creatine monohydrate; n = 5) conditions. Experimental conditions involved ingestion of the samples in a 70-mL ready-to-drink format. CRE was delivered in a novel microencapsulation matrix material consisting entirely of hydrolyzed milk protein. Three hours after ingestion, plasma creatine concentrations were unchanged during PLA, and averaged ∼45 µM. During CRE, plasma creatine concentration peaked after 30 min at 101.6 ± 14.9 µM (p < 0.05), representing a 2.3-fold increase over PLA. Thereafter, plasma creatine concentration gradually trended downwards but remained significantly elevated (∼50% above resting levels) 3 hr after ingestion. These results demonstrate that the microencapsulated form of creatine monohydrate reported herein remains bioavailable when delivered in aqueous conditions, and has potential utility in ready-to-drink formulations for creatine supplementation.

The effects of creatine supplementation on thermoregulation and physical (cognitive) performance: a review and future prospects.

Creatine (Cr) is produced endogenously in the liver or obtained exogenously from foods, such as meat and fish. In the human body, 95 % of Cr is located in the cytoplasm of skeletal muscle either in a phosphorylated (PCr) or free form (Cr). PCr is essential for the immediate rephosphorylation of adenosine diphosphate to adenosine triphosphate. PCr is rapidly degraded at the onset of maximal exercise at a rate that results in muscle PCr reservoirs being substantially depleted. A well-established strategy followed to increase muscle total Cr content is to increase exogenous intake by supplementation with chemically pure synthetic Cr. Most Cr supplementation regimens typically follow a well-established loading protocol of 20 g day(-1) of Cr for approximately 5-7 days, followed by a maintenance dose at between 2 and 5 g day(-1) for the duration of interest, although more recent studies tend to utilize a 0.3-g kg(-1) day(-1) supplementation regimen. Some studies have also investigated long-term supplementation of up to 1 year. Uptake of Cr is enhanced when taken together with carbohydrate and protein and/or while undertaking exercise. Cr supplementation has been shown to augment muscle total Cr content and enhance anaerobic performance; however, there is also some evidence of indirect benefits to aerobic endurance exercise through enhanced thermoregulation. While there is an abundance of data supporting the ergogenic effects of Cr supplementation in a variety of different applications, some individuals do not respond, the efficacy of which is dependent on a number of factors, such as dose, age, muscle fiber type, and diet, although further work in this field is warranted. Cr is increasingly being used in the management of some clinical conditions to enhance muscle mass and strength. The application of Cr in studies of health and disease has widened recently with encouraging results in studies involving sleep deprivation and cognitive performance.

Exploratory studies of the potential anti-cancer effects of creatine.

Two experiments were performed, in which male Wistar Walker 256 tumor-bearing rats were inoculated with 4 × 10(7) tumor cells subcutaneously and received either creatine (300 mg/kg body weight/day; CR) or placebo (water; PL) supplementation via intragastric gavage. In experiment 1, 50 rats were given PL (n = 22) or CR (n = 22) and a non-supplemented, non-inoculated group served as control CT (n = 6), for 40 days, and the survival rate and tumor mass were assessed. In experiment 2, 25 rats were given CR or PL for 15 days and sacrificed for biochemical analysis. Again, a non-supplemented, non-inoculated group served as control (CT; n = 6). Tumor and muscle creatine kinase (CK) activity and total creatine content, acidosis, inflammatory cytokines, and antioxidant capacity were assessed. Tumor growth was significantly reduced by approximately 30 % in CR when compared with PL (p = 0.03), although the survival rate was not significantly different between CR and PL (p = 0.65). Tumor creatine content tended to be higher in CR than PL (p = 0.096). Tumor CK activity in the cytosolic fraction was higher in CR than PL (p < 0.0001). Blood pCO2 was higher in CT and CR than PL (p = 0.0007 and p = 0.004, respectively). HCO3 was augmented in CT compared to PL (p = 0.03) and CR (p = 0.001). Plasma IL-6 was lower and IL-10 level was higher in CR than PL (p = 0.03 and p = 0.0007, respectively) and TNF-alpha featured a tendency of decrease in CR compared to PL (p = 0.08). Additionally, total antioxidant capacity tended to be lower in CT than PL (p = 0.07). Creatine supplementation was able to slow tumor growth without affecting the overall survival rate, probably due to the re-establishment of the CK-creatine system in cancer cells, leading to attenuation in acidosis, inflammation, and oxidative stress. These findings support the role of creatine as a putative anti-cancer agent as well as help in expanding our knowledge on its potential mechanisms of action in malignancies.

Creatine supplementation as a possible new therapeutic approach for fatty liver disease: early findings.

Over the last few years, consistent data have demonstrated that creatine (Cr) supplementation prevents the accumulation of fat in rat liver as well as the progression of fatty liver disease in different situations. Studies have demonstrated that Cr is effective and prevents fatty liver in high-fat and choline-deficient diets and in hepatoma cells in vitro. Because Cr synthesis is responsible for a considerable consumption of hepatic methyl groups, studies have tested the idea that Cr supplementation could modulate phospholipid formation and VLDL secretion. Studies have also demonstrated Cr is able to modulate the expression of key genes related to fatty acid oxidation in hepatocyte cell culture and in rat liver. However, to date, the mechanism by which Cr exerts protective effects against fatty liver is poorly understood. Therefore, the present review aims to summarize the studies involving the therapeutic use of Cr supplementation on fatty liver disease and to explore the mechanisms involved in one-carbon and fatty acid metabolism for the preventive effects of Cr supplementation on fat liver accumulation. Although a small number of studies have been conducted to date, we consider Cr as a new and promising therapeutic strategy to control fat accumulation in the liver as well as the progression of fatty liver disease.

Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats.

The purpose of this study was to investigate (1) the impact of tumor growth on homocysteine (Hcy) metabolism, liver oxidative stress and cancer cachexia and, (2) the potential benefits of creatine supplementation in Walker-256 tumor-bearing rats. Three experiments were conducted. First, rats were killed on days 5 (D5), 10 (D10) and 14 (D14) after tumor implantation. In experiment 2, rats were randomly assigned to three groups designated as control (C), tumor-bearing (T) and tumor-bearing supplemented with creatine (TCr). A life span experiment was conducted as the third experiment. Creatine was supplied in drinking water for 21 days (8 g/L) in all cases. Tumor implantation consisted of a suspension of Walker-256 cells (8.0 × 10(7) cells in 0.5 mL of PBS). The progressive increase (P < 0.05) in tumor mass coincided with a progressively lower body weight and higher hepatic oxidative stress; plasma Hcy concentration was 80 % higher (P < 0.05) by 10 days of tumor implantation. Impaired Hcy metabolism was evidenced by decreased hepatic betaine-homocysteine methyltransferase (Bhmt), glycine N-methyltransferase (Gnmt) and cystathionine beta synthase (CBS) gene expression. In contrast, creatine supplementation promoted a 28 % reduction of tumor weight (P < 0.05). Plasma Hcy (C 6.1 ± 0.6, T 10.3 ± 1.5, TCr 6.3 ± 0.9, µmol/L) and hepatic oxidative stress were lower in the TCr group compared to T. Creatine supplementation was unable to decrease Hcy concentration and to increase SAM/SAH ratio in tumor tissue. These data suggest that creatine effects on hepatic impaired Hcy metabolism promoted by tumor cell inoculation are responsible to decrease plasma Hcy in tumor-bearing rats. In conclusion, Walker-256 tumor growth is associated with progressive hyperhomocysteinemia, body weight loss and liver oxidative stress in rats. Creatine supplementation, however, prevented these tumor-associated perturbations.

Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice.

Recent evidence obtained from a rodent model of birth asphyxia shows that supplementation of the maternal diet with creatine during pregnancy protects the neonate from multi-organ damage. However, the effect of increasing creatine intake on creatine homeostasis and biosynthesis in females, particularly during pregnancy, is unknown. This study assessed the impact of creatine supplementation on creatine homeostasis, body composition, capacity for de novo creatine synthesis and renal excretory function in non-pregnant and pregnant spiny mice. Mid-gestation pregnant and virgin spiny mice were fed normal chow or chow supplemented with 5 % w/w creatine for 18 days. Weight gain, urinary creatine and electrolyte excretion were assessed during supplementation. At post mortem, body composition was assessed by Dual-energy X-ray absorptiometry, or tissues were collected to assess creatine content and mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT) and the creatine transporter (CrT1). Protein expression of AGAT and GAMT was also assessed by Western blot. Key findings of this study include no changes in body weight or composition with creatine supplementation; increased urinary creatine excretion in supplemented spiny mice, with increased sodium (P < 0.001) and chloride (P < 0.05) excretion in pregnant dams after 3 days of supplementation; lowered renal AGAT mRNA (P < 0.001) and protein (P < 0.001) expressions, and lowered CrT1 mRNA expression in the kidney (P < 0.01) and brain (P < 0.001). Creatine supplementation had minimal impact on creatine homeostasis in either non-pregnant or pregnant spiny mice. Increasing maternal dietary creatine consumption could be a useful treatment for birth asphyxia.

Novel insights on intake of meat and prevention of sarcopenia: all reasons for an adequate consumption / Nuevos conocimientos sobre el consumo de carne en la prevención de la sarcopenia: todos los motivos de un consumo adecuado

Introducion: sarcopenia is defined as a syndrome characterized by progressive and generalized loss of muscle mass and strength. The main cause of sarcopenia is the alteration of protein metabolism, in which the proteolytic processes are not accompanied by an appropriate protein synthesis and muscle cells lose progressively the sensitivity to the anabolic stimulus. The most rational approach to delay the progression of sarcopenia and counteract the anabolic resistance is proper nutrition. Meat contains biologically active compounds, such as creatine, carnitine, Conjugated Linoleic Acid (CLA) which have significant impacts upon human protein metabolism. Methods: we performed a narrative literature review to evaluate the till-now evidence regarding: 1. adequate intake of meat in elderly as a topic for prevention of sarcopenia; 2. the correct intake of biologically active compounds contain in meat, which have significant impacts upon human protein metabolism and so have beneficial effects on prevention of sarcopenia. This review included 62 eligible studies. Results: the results demonstrated that in elderly the optimum diet therapy for the sarcopenia prevention and treatment, which must aim at achieving specific metabolic goals, must recommend the consumption of 113 g of meat (220 kcal; 30 g protein) five time a week. Conclusion: in a varied and balanced diet, for preventing sarcopenia, it is recommended to assume meat 4-5 times a week (white meat 2 times per week, lean red meat less than 2 times per week, processed meat less than 1 time per week), as suggested in the diet pyramid for elderly (AU)

Introducción: la sarcopenia se define como un síndrome caracterizado por la pérdida progresiva y generalizada de la masa muscular y de la fuerza. La principal causa de la sarcopenia es la alteración del metabolismo de las proteínas, en la que los procesos proteolíticos no van acompañados de una síntesis de proteínas y células musculares adecuadas, con lo que se pierde progresivamente la sensibilidad al estímulo anabólico. El enfoque más racional para retrasar la progresión de la sarcopenia y contrarrestar la resistencia anabólica es una nutrición adecuada. La carne contiene compuestos biológicamente activos, tales como creatina, carnitina y ácido linoleico conjugado (CLA) que tienen impactos significativos sobre el metabolismo de la proteína humana. Métodos: se realizó una revisión de la literatura narrativa para evaluar la evidencia hasta ahora, en relación con: 1. ingesta adecuada de carne en ancianos como prevención de la sarcopenia; 2. la ingesta correcta de compuestos biológicamente activos que contiene la carne, que tienen impactos significativos sobre el metabolismo de la proteína humana y para así obtener efectos beneficiosos en la prevención de la sarcopenia. Esta revisión incluyó 62 estudios elegibles. Resultados: los resultados demostraron que en personas de edad avanzada la terapia óptima con dieta para la prevención y tratamiento de la sarcopenia, que debe apuntar al logro de los objetivos metabólicos específicos, debe recomendar el consumo de 113 g de carne (220 kcal; 30 g de proteínas) cinco veces a la semana. Conclusión: en una dieta variada y equilibrada, para prevenir la sarcopenia, se recomienda consumir la carne 4-5 veces a la semana (carne blanca 2 veces por semana, carne roja magra menos de 2 veces por semana, carne procesada menos de 1 vez por semana), como se sugiere en la pirámide de la dieta para personas mayores (AU)