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.

Correlations between resistance training-induced changes on phase angle and biochemical markers in older women.

The main purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on phase angle (PhA), inflammatory and oxidative stress biomarkers, and to evaluate whether these RT-induced adaptations are related to PhA changes. Fifty-one older women (70.6 ± 5.1 years; 26.9 ± 4.2 kg/m2 ) were randomly allocated into a training group (TG) that performed 12-week RT or a nonexercising control group (CG). The PhA (Xitron), body composition (DXA), and blood sample measurements (after a 12 hours fast) were performed before and after the intervention. The TG showed a significant (P < .05) increase in PhA (TG: +7.4±5.9% vs CG: -3.6 ± 8.8%), and interleukin-10 (IL-10; TG: +51.8 ± 71.1% vs CG: -46.6 ± 38.0%), and a decrease in tumor necrosis factor alpha (TNF-α; TG: -15.2 ± 11.1% vs CG: +6.9±17.7%), interleukin-6 (IL-6; TG: -17.9 ± 17.8% vs CG: +6.1 ± 24.8%), and C-reactive protein (CRP; TG: -24.1 ± 19.9% vs CG: +43.8 ± 31.1%). Moreover, TG upregulated catalase (TG: +11.4 ± 15.0% vs CG: -6.7 ± 10.2%). Changes in TNF-α (r = -.71), CRP (r = -.65), lower advanced oxidation protein products (r = -.55), and catalase (r = +.73) after RT were correlated with changes in PhA (P < .05). These results suggest that RT improves PhA, inflammatory and oxidative stress biomarkers, and the changes in inflammatory and oxidative damage markers are correlated with changes in PhA.

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 Increases Total Body Water in Soccer Players: a Deuterium Oxide Dilution Study.

This study aimed to evaluate changes in total body water (TBW) in soccer athletes using a deuterium oxide dilution method and bioelectrical impedance (BIA) formulas after 7 days of creatine supplementation. In a double-blind controlled manner, 13 healthy (under-20) soccer players were divided randomly in 2 supplementation groups: Placebo (Pla, n=6) and creatine supplementation (CR, n=7). Before and after the supplementation period (0.3 g/kg/d during 7 days), TBW was determined by deuterium oxide dilution and BIA methods. 7 days of creatine supplementation lead to a large increase in TBW (2.3±1.0 L) determined by deuterium oxide dilution, and a small but significant increase in total body weight (1.0±0.4 kg) in Cr group compared to Pla. The Pla group did not experience any significant changes in TBW or body weight. Although 5 of 6 BIA equations were sensitive to determine TBW changes induced by creatine supplementation, the Kushner et al. 16 method presented the best concordance levels when compared to deuterium dilution method. In conclusion, 7-days of creatine supplementation increased TBW determined by deuterium oxide dilution or BIA formulas. BIA can be useful to determine TBW changes promoted by creatine supplementation in soccer athletes, with special concern for formula choice.

Plasma malondialdehyde as biomarker of lipid peroxidation: effects of acute exercise.

The marker most frequently used to indicate the level of lipid peroxidation in the field of exercise and sports is malondialdehyde (MDA), which can be determined by many different techniques. However, there are few studies discussing differences and advantages of the methods for MDA assay in sports science field. The aim of the present study was to compare three techniques for quantification of MDA in plasma of humans subjected to acute exercise. MDA was determined by high performance liquid chromatography (MDA-HPLC), thiobarbituric acid reactive species (MDA-TBARS) and 1-methyl-2-phenylindole (MDA-MP) techniques in the plasma of 8 healthy male soccer athletes before and after acute exercise. Acute exercise significantly increased (P<0.05) plasma MDA concentration determined by MDA-HPLC (18%) and MDA-TBARS (56%) techniques. MDA-MP technique did not reveal significant differences, although it increased 25% after exercise. When correlated to the gold standard (MDA-HPLC), MDA-TBARS and MDA-MP techniques showed weak Lin concordance coefficients and non-significant correlation. Also, MDA-TBARS and MDA-MP techniques overestimated the MDA-HPLC technique by 100 and 122%, respectively. In conclusion, MDA-HPLC and MDA-TBARS are sensitive to detect change in MDA induced by acute exercise. MDA-HPLC is the most suitable technique for accurate detection of MDA in sports and exercise area due to its sensitivity and accuracy.

Oxidative stress biomarkers response to high intensity interval training and relation to performance in competitive swimmers.

AIM: Aim of the study is to investigate the modulations of oxidative stress biomarkers and some antioxidants induced by high intensity interval training bout and its relation to swimming performance. METHODS: Ten swimmers performed a set of 8 maximal swims along 100 m by style of their specialty, with 10 minute for a rest. The concentration of blood lactate ([Lac]) was determined after each swim. The lactate tolerance index (LTI) was determined by the ratio between [Lac] and the respective times of execution of the 8 swims. The time to complete first 100 m swim at maximum effort (P100) and the international point score (IPS) reached in a specific competition were considered performance parameters. Venous blood was collected before and after the anaerobic training effort. RESULTS: Mean blood lactate concentration in the eight swims was 10.9 ± 1.2 mM. Significant increases were observed for TBARS (pre: 4.1±0.7 ?mol/L; post: 4.9±1.1. ?mol/L), CK (pre: 206.4±170.7 U/L; post: 244.4±176.9. U/L), GSH (pre: 0.52±0.06; post: 0.62±0.05. mM), and ascorbic acid (pre: 0.06±0.02; post: 0.11±0.03. mg/dL) after the anaerobic training bout compared to the values obtained before it. In addition, significant correlations (P < 0.05) were detected between LTI and P100 (r = -0.87) and IPS (r = 0.64) and between variation of ascorbic acid and P100 (r = -0.60). CONCLUSION: Anaerobic training bout proposed induces oxidative stress and cell muscle damage markers as well as modulates some antioxidants of competitive swimmers. The modulation of ascorbic acid seems to play an important role in the performance of these athletes.

Blood and salivary oxidative stress biomarkers following an acute session of resistance exercise in humans.

The aim of the present study was to compare oxidative stress biomarkers determined in blood and saliva before and after acute resistance exercise. 1 week after 1 maximum repetition (1RM) test 11 healthy well-trained males completed a hypertrophy acute session of resistance training including 3 sets of 10 repetitions at 75% of the 1RM, with 90 s rest periods between sets. Venous blood and saliva samples were collected before (pre) and 10 min after (post) the resistance training session. A significant (p<0.05) rise in blood lactate accumulation (pre: 1.6+/-0.4 vs. post: 9.5+/-2.4) was found post-acute resistance training compared with baseline values. Significant increases (p<0.05) in TBARS (42%), AOPP (28%), uric acid (27%) and GSH (14%) were detected post-acute resistance training in relation to pre in blood samples. A significant increase (p<0.05) in uric acid (36%) was found in saliva post-acute resistance training as well as a significant correlation (p<0.05) between uric acid determined in blood and saliva. Statistical analysis did not reveal any other change in the salivary oxidative stress biomarkers. In conclusion, an acute session of resistance exercise induces oxidative stress in plasma of trained men after acute resistance training, which was not found in saliva samples except for uric acid.