The pleiotropic effects of creatine (Cr) are based mostly on the functions of the enzyme creatine kinase (CK) and its high-energy product phosphocreatine (PCr). Multidisciplinary studies have established molecular, cellular, organ and somatic functions of the CK/PCr system, in particular for cells and tissues with high and intermittent energy fluctuations. These studies include tissue-specific expression and subcellular localization of CK isoforms, high-resolution molecular structures and structure-function relationships, transgenic CK abrogation and reverse genetic approaches. Three energy-related physiological principles emerge, namely that the CK/PCr systems functions as (a) an immediately available temporal energy buffer, (b) a spatial energy buffer or intracellular energy transport system (the CK/PCr energy shuttle or circuit) and (c) a metabolic regulator. The CK/PCr energy shuttle connects sites of ATP production (glycolysis and mitochondrial oxidative phosphorylation) with subcellular sites of ATP utilization (ATPases). Thus, diffusion limitations of ADP and ATP are overcome by PCr/Cr shuttling, as most clearly seen in polar cells such as spermatozoa, retina photoreceptor cells and sensory hair bundles of the inner ear. The CK/PCr system relies on the close exchange of substrates and products between CK isoforms and ATP-generating or -consuming processes. Mitochondrial CK in the mitochondrial outer compartment, for example, is tightly coupled to ATP export via adenine nucleotide transporter or carrier (ANT) and thus ATP-synthesis and respiratory chain activity, releasing PCr into the cytosol. This coupling also reduces formation of reactive oxygen species (ROS) and inhibits mitochondrial permeability transition, an early event in apoptosis. Cr itself may also act as a direct and/or indirect anti-oxidant, while PCr can interact with and protect cellular membranes. Collectively, these factors may well explain the beneficial effects of Cr supplementation. The stimulating effects of Cr for muscle and bone growth and maintenance, and especially in neuroprotection, are now recognized and the first clinical studies are underway. Novel socio-economically relevant applications of Cr supplementation are emerging, e.g. for senior people, intensive care units and dialysis patients, who are notoriously Cr-depleted. Also, Cr will likely be beneficial for the healthy development of premature infants, who after separation from the placenta depend on external Cr. Cr supplementation of pregnant and lactating women, as well as of babies and infants are likely to be of benefit for child development. Last but not least, Cr harbours a global ecological potential as an additive for animal feed, replacing meat- and fish meal for animal (poultry and swine) and fish aqua farming. This may help to alleviate human starvation and at the same time prevent over-fishing of oceans.

https://link.springer.com/content/pdf/10.1007%2Fs00726-011-0877-3.pdf

The creatine kinase system and pleiotropic effects of creatine

There is an extensive and still growing body of the literature supporting the efficacy of creatine (Cr) supplementation. In sports, creatine has been recognized as the most effective nutritional supplement in enhancing exercise tolerance, muscle strength and lean body mass. From a clinical perspective, the application of Cr supplementation is indeed exciting. Evidences of benefits from this supplement have been reported in a broad range of diseases, including myopathies, neurodegenerative disorders, cancer, rheumatic diseases, and type 2 diabetes. In addition, after hundreds of published studies and millions of exposures creatine supplementation maintains an excellent safety profile. Thus, we contend that the widespread application of this supplement may benefit athletes, elderly people and various patient populations. In this narrative review, we aimed to summarize both the ergogenic and therapeutic effects of Cr supplementation. Furthermore, we reviewed the impact of Cr supplementation on kidney function.

In sickness and in health: the widespread application of creatine supplementation.

Intradialytic creatine supplementation: A scientific rationale for improving the health and quality of life of dialysis patients.

BACKGROUND Creatine supplementation has been proposed to alleviate muscle loss in various populations, but has not been investigated in hemodialysis (HD) patients. Thus, our objective was to evaluate whether creatine supplementation could attenuate the loss of lean body mass (LBM) and malnutrition-inflammation score (MIS) in HD patients. METHODS A randomized, placebo-controlled, double blind, parallel-design study included HD patients, of both sexes, aged 18-59 years. The patients were allocated to a Placebo Group (PG; n = 15; received maltodextrin, 1st week: 40 g/day and 2nd-4th weeks: 10 g/day) and a Creatine Group (CG; n = 15; received creatine plus maltodextrin, 1st week: 20 g/day of creatine plus 20 g/day of maltodextrin and 2nd-4th weeks: 5 g/day of creatine plus 5 g/day of maltodextrin). Pre and post the intervention, patients were evaluated for food intake, MIS, body composition and biochemical parameters. RESULTS CG group attenuated the MIS (Pre: 5.57 ± 0.72 vs. Post: 3.85 ± 0.47 score, P = 0.003) compared with PG (Pre: 5.71 ± 0.97 vs. Post: 5.36 ± 0.95 score, P = 0.317) (supplement × time P = 0.017, effect size: 0.964). The change of LBM was greater in CG than in PG (CG: Δ0.95 vs PG: Δ0.13 kg). At post-intervention, 28.6% of PG patients presented LBM loss and 71.4% remain stable. In contrast, 14.4% of CG patients had LBM loss, 42.8% remain stable and 42.8% gained. Food intake and quality of life did not change. CG increased the BMI and gait speed in post-compared to pre-moment, but no difference among the groups. CONCLUSION In HD patients, four weeks of creatine supplementation may alleviate the MIS as well as attenuate the LBM loss compared to placebo.

/pdf/short-term-creatine-supplementation-may-alleviate-the-4cr8auz9so.pdf

Short-Term Creatine Supplementation May Alleviate the Malnutrition-Inflammation Score and Lean Body Mass Loss in Hemodialysis Patients: A Pilot Randomized Placebo-Controlled Trial

The aim of this study was to determine the effects of creatine supplementation on kidney function in resistance-trained individuals ingesting a high-protein diet. A randomized, double-blind, placebo-controlled trial was performed. The participants were randomly allocated to receive either creatine (20 g/d for 5 d followed by 5 g/d throughout the trial) or placebo for 12 weeks. All of the participants were engaged in resistance training and consumed a high-protein diet (i.e., ≥ 1.2 g/Kg/d). Subjects were assessed at baseline (Pre) and after 12 weeks (Post). Glomerular filtration rate was measured by 51Cr-EDTA clearance. Additionally, blood samples and a 24-h urine collection were obtained for other kidney function assessments. No significant differences were observed for 51Cr-EDTA clearance throughout the trial (Creatine: Pre 101.42 ± 13.11, Post 108.78 ± 14.41 mL/min/1.73m2; Placebo: Pre 103.29 ± 17.64, Post 106.68 ± 16.05 mL/min/1.73m2; group x time interaction: F = 0.21, p = 0.64). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria remained virtually unchanged. A 12-week creatine supplementation protocol did not affect kidney function in resistance-trained healthy individuals consuming a high-protein diet; thus reinforcing the safety of this dietary supplement. ClinicalTrials.gov NCT01817673

/pdf/does-long-term-creatine-supplementation-impair-kidney-2mmtwyft0w.pdf

Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet?

It currently is unknown whether creatine supplementation is safe for people with or at risk of kidney disease. We report on the short-term effects of creatine supplementation on kidney function in a young man with a single kidney and mildly decreased glomerular filtration rate (GFR). A 20-year-old man who had undergone unilateral nephrectomy and presented with mildly decreased GFR without kidney damage underwent a trial with 35 days of creatine supplementation (20 g/d for 5 days followed by 5 g/d for the next 30 days) and had his kidney function monitored. After the intervention, 51 Cr-EDTA clearance (pre, 81.6 mL/min/1.73 m 2 ; post, 82.0 mL/min/1.73 m 2 ), proteinuria (protein excretion: pre, 130 mg/d; post, 120 mg/d), and electrolyte levels were unchanged. Albuminuria, serum urea level, and estimated creatinine clearance were decreased (pre, 4.6 mg/d; post, 2.9 mg/d; pre, 37 mg/d; post, 28 mg/dL; and pre, 88 mL/min/1.73 m 2 ; post, 71 mL/min/1.73 m 2 , respectively), whereas serum creatinine level was slightly increased (pre, 1.03 mg/dL; post, 1.27 mg/dL), falsely suggesting kidney function impairment. This prospective report suggests that short-term creatine supplementation may not affect kidney function in an individual with a single kidney, mild decreased GFR, and ingesting a high-protein diet (ie, 2.8 g/kg/d). This finding has great relevance considering that creatine-induced kidney disease has been a growing concern, even for healthy people. Am J Kidney Dis 55:e7-e9. © 2010 by the National Kidney Foundation, Inc.

CASE REPORT Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man With a Single Kidney

Recently, studies have suggested that creatine supplementation can modulate glucose homeostasis by increasing glucose uptake in peripheral tissues. The aim of this study was to investigate the effects of creatine supplementation on glucose tolerance, muscle and hepatic glycogen content in rats submitted or not to physical activity for four and eight weeks. Wistar rats were divided in two groups: four and eight weeks of intervention. Afterwards, each group was subdivided in four subgroups, according to supplement intake and exercise: Sedentary Control; Trained Control; Supplemented Sedentary; and Sup-plemented Trained. The animals had free access to water and chow and the supplemented groups had two % of their diet as creatine monohydrated. The exercise groups swam for 40 minutes a day, four days a week, with two to five % of their body weight attached to their chests. After four and eight weeks, oral glucose tolerance tests were performed and both hepatic and muscle glycogen were determined. No significant differences were observed between groups on glucose tolerance and glycogen content in muscle and hepatic tissue. This study shows that creatine supplementation does not influence neither glucose tolerance nor glycogen concentrations in rats submitted or not to physical activity for four and eight weeks.

Efeitos da Suplementação de Creatina na Captação de Glicose em Ratos Submetidos ao Exercício Físico Effects of Creatine Supplementation on Glucose Uptake in Rats Submitted to Exercise Training

The aim of the present study was to evaluate if the food consumption patterns and the expression of hypothalamic neuropeptides of young rats (~4 months) is modulated in response to a 12-week resistance training protocol at 80% of the previously established maximum force. For this purpose young male Wistar rats were randomly divided in two groups: sedentary control group (CON) and a trained group (TR). To compare the different treatments at each time point, we used analysis of variance (ANOVA). For the analysis of mRNA levels between trained and control groups we used the paired t test. Our results showed no

http://www.m-hikari.com/cems/cems2013/cems5-8-2013/mediciCEMS5-8-2013.pdf

Does Resistance Training Modulate Food Intake and Hypothalamic Neuropepetides mRNA Expression in Rats

Artioli, GG, Gualano, B, Franchini, E, Batista, RN, Polacow, VO, and Lancha, AH Jr. Physiological, performance, and nutritional profile of the Brazilian Olympic Wushu (kung-fu) team. J Strength Cond Res 23(X): xxx‐xxx, 2008—The purpose of the present study was to determine physiological, nutritional, and performance profiles of elite Olympic Wushu (kung-fu) athletes. Ten men and four women elite athletes took part in the study. They completed the following tests: body composition, nutritional assessment, upper-body Wingate Test, vertical jump, lumbar isometric strength, and flexibility. Blood lactate was determined at rest and after the Wingate Test. Blood lactate was also determined during a training session (combat and Taolu training). We found low body fat (men: 9.5 6 6.3%; women: 18.0 6 4.8%), high flexibility (sit-and-reach—men: 45.5 6 6.1 cm; women: 44.0 6 6.3 cm), high leg power (vertical jump—men: 37.7 6 8.4 cm; women: 32.3 6 1.1 cm), high lumbar isometric strength (men: 159 6 13 cm; women: 94 6 6 cm), moderate arm mean and peak power (Wingate Test—men: 4.1 6 0.4 and 5.8 6 0.5 Wkg 21 , respectively; women: 2.5 6 0.3 and 3.4 6 0.3 Wkg 21 , respectively), and elevated blood lactate after the Wingate Test (men: 10.8 6 2.0 mmolL 21 ; women: 10.2 6 2.0 mmolL 21 ) and during training (combat: 12.0 6 1.8 mmolL 21 ; Taolu: 7.7 6 3.3 mmolL 21 ). Men athletes consume a high-fat, low-carbohydrate diet, whereas women consume a moderate, high-carbohydrate diet. Energy consumption was markedly variable. In conclusion, Olympic Wushu seems to be a highly anaerobic-dependent combat sport. Low body fat, high flexibility, leg anaerobic power, isometric strength, and moderately high arm anaerobic power seem to be important for successful competitive performance.

Physiological ,p erformance, and nutritional profile of the brazilian olympic wushu

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CASE REPORT Effect of Short-term High-Dose Creatine Supplementation on Measured GFR in a Young Man With a Single Kidney

Efeitos da Suplementação de Creatina na Captação de Glicose em Ratos Submetidos ao Exercício Físico Effects of Creatine Supplementation on Glucose Uptake in Rats Submitted to Exercise Training

Does Resistance Training Modulate Food Intake and Hypothalamic Neuropepetides mRNA Expression in Rats

Physiological ,p erformance, and nutritional profile of the brazilian olympic wushu