A Pilot Study to Examine the Effects of an Anti-inflammatory Supplement on Eicosanoid Derivatives in Patients with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is a progressive disease with an inverse relationship between kidney function and levels of inflammation and oxidative stress. Curcumin and Boswellia serrata have been reported to exert anti-inflammatory effects on the cyclooxygenase and lipoxygenase pathways. Therefore, the purpose of this study was to study the effects of a supplement containing curcumin and B. serrata on eicosanoid derivatives in early stage CKD patients who had not initiated hemodialysis. METHODS: Sixteen patients with stage 2 and stage 3 CKD (56.0 ± 16.0 years, 171.4 ± 11.9 cm, 99.3 ± 20.2 kg) were randomized into a treatment group with curcumin and B. serrata or a placebo group. The dependent variables prostaglandin E2 (PGE2), 5-hydroxyicosatetraenoic acid, 12-hydroxyicosatetraenoic acid, 15-hydroxyicosatetraenoic acid, and 13-hydroxyoctadecadienoic acid were measured both before and after 8 weeks of supplementation. Results were analyzed by using a repeated-measures analysis of covariance for compliance and body-mass index. RESULTS: A significant group effect (p = 0.05), and a trend for Group × Time interaction (p = 0.056) were detected for PGE2. No significant differences were observed for any other variables. CONCLUSIONS: This is the first article of baseline levels of the dependent variables in early stage CKD, and the first article to show a significant effect of these supplements on PGE2 in early stage CKD. Further studies are needed to determine whether curcumin and B. serrata may be effective means to reduce inflammation in patients with CKD.

Creatine supplementation post-exercise does not enhance training-induced adaptations in middle to older aged males.

PURPOSE: The present study evaluated the effects of creatine monohydrate (CrM) consumption post-exercise on body composition and muscle strength in middle to older males following a 12-week resistance training program. METHODS: In a double-blind, randomized trial, 20 males aged between 55 and 70 years were randomly assigned to consume either CrM-carbohydrate (CHO) [20 g days(-1) CrM + 5 g days(-1) CHO × 7 days, then 0.1 g kg(-1) CrM + 5 g CHO on training days (average dosage of ~8.8 g)] or placebo CHO (20 g days(-1) CHO × 7 days, then 5 g CHO on training days) while participating in a high intensity resistance training program [3 sets × 10 repetitions at 75% of 1 repetition maximum (1RM)], 3 days weeks(-1) for 12 weeks. Following the initial 7-day "loading" phase, participants were instructed to ingest their supplement within 60 min post-exercise. Body composition and muscle strength measurements, blood collection and vastus lateralis muscle biopsy were completed at 0, 4, 8 and 12 weeks of the supplement and resistance training program. RESULTS: A significant time effect was observed for 1RM bench press (p = 0.016), leg press (p = 0.012), body mass (p = 0.03), fat-free mass (p = 0.005) and total myofibrillar protein (p = 0.005). A trend for larger muscle fiber cross-sectional area in the type II fibers compared to type I fibers was observed following the 12-week resistance training (p = 0.08). No supplement interaction effects were observed. CONCLUSION: Post-exercise ingestion of creatine monohydrate does not provide greater enhancement of body composition and muscle strength compared to resistance training alone in middle to older males.

Rhabdomyolysis and acute renal failure in a sickle cell trait athlete: a case study.

This case study reports the clinical details and pathologic mechanisms of a nonfatal case of rhabdomyolysis secondary to heat exhaustion and sickle cell trait (SCT) resulting in acute renal failure. A 19-year-old African American male college football player collapsed after running 5 intervals of 300 m during a preseason conditioning test. After 17 days of treatment, the athlete was released from the hospital to a short-term noncritical care facility for further treatment and dialysis. Scientific literature reports that at least 15 college football players with SCT have died as a result of a sickling crisis after intense physical exertion. This case study presents the clinical importance of prompt medical treatment and sustained low-efficiency dialysis in treating rhabdomyolysis and its sequelae after collapse in an SCT athlete.

Effects of Uric Acid on Lipid Levels in CKD Patients in a Randomized Controlled Trial.

BACKGROUND: Few studies have been conducted that compared lipid levels and uric acid in CKD or End-Stage Renal Disease (ESRD) patients with most using animal models. The purpose of the study was to explore effects on lipids while controlling uric acid levels in CKD patients. METHODS: Twenty-four CKD patients (N = 24) volunteered to participate in this study. The study was conducted using a double-blind, randomized, placebo controlled experimental protocol. The experimental group was prescribed 300 mg of allopurinol PO daily by their treating physician and followed prospectively for 8-weeks. The control group consumed a similar pill once a day for 8-weeks. RESULTS: ANCOVA revealed significant differences in total cholesterol (P = 0.009) and Apo B (P = 0.006) with lower levels in the allopurinol group. A trend emerged with LDL (P = 0.052) with lower levels in the allopurinol group. No significant differences were discovered in triglycerides (P = 0.403), HDL (P = 0.762) and total Cholesterol/HDL Ratio (P = 0.455). CONCLUSIONS: After statistically controlling for compliance and inflammation significant differences between groups were observed for total cholesterol and Apo B. In both instances the allopurinol group had lower concentrations than the placebo group. Similarly, a trend was observed in LDL with the allopurinol group having lower concentrations than the placebo group.

The effects of fish oil supplementation on markers of inflammation in chronic kidney disease patients.

OBJECTIVE: One prevalent characteristic of all stages of chronic kidney disease (CKD) is excessive production of proinflammatory cytokines. Fish oil (FO) supplementation has been reported to lower levels of proinflammatory cytokines. The benefits of FO for an extensive range of populations and a variety of health concerns are apparent, yet the anti-inflammatory benefits for nondialysis CKD patients are not as well documented. Therefore, the purpose of this study was to investigate the effects of the daily consumption of FO (1,400 mg eicosapentaenoic acid + 1,000 mg docosahexaenoic acid) on interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) for 8 weeks in nondialysis CKD patients. DESIGN, SETTING, AND SUBJECTS: In this double-blind, randomized, placebo-controlled intervention, the effect of 8 weeks of FO administration on IL-1ß, IL-6, and TNF-α levels in nondialysis CKD patients were evaluated. INTERVENTION: Thirty-one nondialysis CKD patients (17 = FO; 14 = placebo) randomly received either FO dietary supplementation 2.4 g/day (1,400 mg eicosapentaenoic acid + 1,000 mg docosahexaenoic acid) or placebo (safflower oil) for 8 weeks. MAIN OUTCOME MEASURES: IL-1ß, IL-6, and TNF-α were all measured as markers of inflammation. RESULTS: One-way analysis of variance revealed no significant differences in IL-6 (P = .06), IL-1ß (P = .18), and TNF-α (P = .20) between groups in pretest values. Additionally, no pretest differences existed between groups for age (P = .549), weight (P = .324), waist circumference (P = .086), gender (P = .591), and ethnicity (P = .875). Covariance was calculated using compliance, age, gender, ethnicity, body weight, and waist circumference as covariates. No significant differences were discovered between groups after FO supplementation for IL-6 (P = .453) and TNF-α (P = .242). A significant difference was discovered for IL-1ß (P = .050) with lower levels in the FO group. CONCLUSIONS: The results of this study are in agreement with some previous studies that suggest that FO supplementation has no effect on plasma proinflammatory cytokines TNF-α or IL-6, but does have an effect on IL-1ß in nondialysis CKD patients.

Differential gene expression of FoxO1, ID1, and ID3 between young and older men and associations with muscle mass and function.

BACKGROUND AND AIMS: Aging is associated with significant losses of skeletal muscle mass and function. Numerous biochemical molecules have been implicated in the development of these age-related changes, however evidence from human models is sparse. Assessment of transcript expression is useful as it requires minimal tissue and may potentially be used in clinical trials. This study aimed to compare mRNA expression of proteolytic genes in skeletal muscle of young (18-35 yrs) and older (55-75 yrs) men. METHODS: Muscle tissue was obtained from young (n=14, 21.35±1.03 yrs) and older (n=13, 63.85±1.83 yrs) men using percutaneous biopsy, and transcript expression was quantified using real-time polymerase chain reaction. Lower limb muscle mass was assessed using DEXA while concentric peak torque (PT) and power were assessed via isokinetic dynamometer. When age-related differences in mRNA expression were observed, Pearson correlation coefficients were obtained to examine the relationship of transcripts to muscle mass and function. RESULTS: Older muscle contained significantly more transcript for Forkhead Box O 1 (FoxO1, p=0.001), Inhibitor of DNA binding 1 (ID1, p=0.009), and Inhibitor of DNA Binding 3 (ID3, p=0.043) than young muscle. FoxO1 was significantly correlated with lean mass (R=-0.44, p=0.023) and PT (R=-0.40, p=0.046) while ID3 was significantly correlated with PT (R=-0.58, p=0.001) and power (R=-0.65, p<0.001). Moreover, ID1 was significantly correlated with all assessed measures of muscle function - mass (R=-0.39, p=0.046), PT (R=-0.53, p=0.005), and power (R=-0.520, p=0.005). CONCLUSION: These data suggest that FoxO1, ID1, and ID3 are potentially useful as clinical biomarkers of age-related muscle atrophy and dysfunction.

Protease supplementation improves muscle function after eccentric exercise.

UNLABELLED: Protease supplementation has been purported to reduce the damaging effects of eccentric exercise and accelerate recovery of muscle function, possibly by regulating inflammation. PURPOSE: To determine the effectiveness of protease supplementation in attenuating eccentric exercise-induced skeletal muscle damage and inflammation. METHODS: After standard physical and hemodynamic assessment and fasting venous blood samples, subjects performed isokinetic extension/flexion of the quadriceps group on a Biodex isokinetic dynamometer at 60°·s(-1), followed by VO2max testing. Subjects were randomly assigned to consume 5.83 g daily of either a cellulose placebo (N = 15; 22.27 ± 3.33 yr, 71.17 ± 2.91 inches, 179.4 ± 24.05 lb, 50.55 ± 5.66 mL·kg(-1)·min(-1)) or a proteolytic supplement containing fungal proteases, bromelain, and papain (N = 14; 22.85 ± 5.9 yr, 70.0 ± 2.67 inches, 173.11 ± 29.94 lb, 49.69 ± 6.15 mL·kg(-1)·min(-1)) for a period of 21 d. After the supplementation period, subjects donated blood samples before performing a 45-min downhill (-17.5%) treadmill protocol at 60% of VO2max. An additional four blood draws and three muscle function tests were performed during the next 48 h. Blood was analyzed using standard hematology and clinical chemistry, enzyme-linked immunosorbent assay, and bead array. Blood data were analyzed using multivariate analysis of variance (MANOVA) with repeated measures, whereas Biodex data were analyzed using a MANOVA on %Δ values. RESULTS: Significant group differences (T1-T3, P = 0.033; T1-T4, P = 0.043) and another strong trend (T1-3 h, P = 0.055) were observed for flexion (peak torque %Δ at 60°·s(-1)) indicating higher force production in the protease group. Significant group × time interactions (P < 0.05) were observed, including elevations in circulating eosinophils and basophils in the protease group coinciding with lower levels of serum cyclooxygenase 2, interleukin 6, and interleukin 12 in this group. CONCLUSIONS: Protease supplementation seems to attenuate muscle strength losses after eccentric exercise by regulating leukocyte activity and inflammation.

Effects of eccentric treadmill exercise on inflammatory gene expression in human skeletal muscle.

The present study examined the skeletal muscle expression of several genes related to the inflammatory process before and after a bout of downhill running. Twenty-nine males between the ages of 18 and 35 years performed a 45-min downhill (-17.5%) treadmill protocol at 60% of maximal oxygen consumption. Venous bloods samples and muscle biopsy samples from the vastus lateralis were donated prior to and at 3-h and 24-h postexercise, along with ratings of perceived muscle soreness. Serum creatine kinase (CK) was determined, as was skeletal muscle gene expression of interleukin (IL)-6, IL-8, IL-12 (p35), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, cyclooxygenase 2 (COX2), and nuclear factor kappa B (NFkB) (p105/p50). Gene expression was analyzed using RT-PCR and compared with a standard housekeeping gene (beta-actin). Data were analyzed for statistical differences using multivariate analysis of variance with univariate follow-up. In addition, Pearson correlations were conducted to determine if any significant relationship exists between any of these transcripts and both CK and muscle soreness. Significant (p < 0.05) up-regulations in IL-6, IL-8, and COX2 mRNA expression were observed compared with baseline, whereas no significant changes for IL-12, IL-1beta, TNF-alpha, or NFkB were noted. Significant increases in IL-6 mRNA were observed at 3 h (p < 0.001) and 24 h (p = 0.043), whereas significant increases in IL-8 (p = 0.001) and COX2 (p = 0.046) mRNA were observed at 3-h postexercise. In addition, muscle soreness was significantly correlated with IL-8 at 24 h (r = -0.370; p = 0.048), whereas CK was significantly related to NFkB at baseline (r = -0.460; p = 0.012). These data indicate that increases in the mRNA expression of IL-6, IL-8, and COX2 occur in the vastus lateralis as a result of damaging eccentric exercise in young, recreationally trained males. Further, it appears that IL-8 transcription may play some role in inhibiting postexercise muscle soreness, possibly through regulation of angiogenesis.