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Efficacy of L-carnitine supplementation for improving lean body mass and physical function in patients on hemodialysis: a randomized controlled trial.
Maruyama, T, Maruyama, N, Higuchi, T, Nagura, C, Takashima, H, Kitai, M, Utsunomiya, K, Tei, R, Furukawa, T, Yamazaki, T, et al
European journal of clinical nutrition. 2019;(2):293-301
Abstract
BACKGROUND Carnitine deficiency is common in patients on hemodialysis. However, the efficacy of L-carnitine supplementation for improving lean body mass (LBM) and physical function has not yet been evaluated. METHODS In this multicenter, prospective, parallel, randomized, controlled trial, 91 patients on hemodialysis who developed carnitine deficiency were randomly assigned to receive injections of 1,000 mg L-carnitine 3 times per week after each hemodialysis session (L-carnitine group) or no injections (control group) with monitoring for 12 months. RESULTS The data for 84 of the 91 patients were available for analysis (L-carnitine group, n = 42; control group, n = 42). Dry weight and body mass index did not significantly change in the L-carnitine group, but significantly decreased in the control group. Arm muscle area (AMA) did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean AMA between the groups was 6.22% (95% confidence interval [CI] 1.90-10.5; P = 0.037). Hand grip strength did not change significantly in the L-carnitine group, but decreased significantly in the control group. The difference in change in hand grip strength between the groups was 4.27% (95% CI 0.42-8.12; P = 0.030). Furthermore, LBM did not change significantly in the L-carnitine group but decreased significantly in the control group; the difference in mean LBM between the groups was 2.92 % (95% CI 1.28-4.61; P = 0.0007). CONCLUSIONS L-carnitine supplementation is useful in patients who develop carnitine deficiency on hemodialysis because it maintains physical function and LBM.
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The Effect of Myopenia on the Inflammatory Response Early after Colorectal Surgery.
Smeets, BJJ, Brinkman, DJ, Horsten, ECJ, Langius, JAE, Rutten, HJT, de Jonge, WJ, Luyer, MDP
Nutrition and cancer. 2018;(3):460-466
Abstract
BACKGROUND Myopenia (low skeletal muscle mass) is associated with an increased risk of complications following colorectal surgery, however, the underlying mechanism is poorly understood. This study investigates the effect of myopenia on the early postoperative systemic inflammatory response. MATERIALS AND METHODS In 78 patients undergoing colorectal surgery, the presence of myopenia was preoperatively assessed using computed tomography images of the third lumbar vertebra. Interleukin-8 (IL-8) and soluble tumor necrosis factor receptor-1 (TNFRSF1A) were measured in plasma before and 4 h after start of surgery as part of a randomized controlled trial investigating the effect of perioperative gum chewing on the inflammatory response. Multivariable linear regression analysis was performed to assess the effect of myopenia on inflammatory markers while correcting for possible confounders. RESULTS Four hours after start of surgery, IL-8 was higher in patients with myopenia than in patients without myopenia (352 ± 268 vs. 239 ± 211 pg/ml, P = 0.048), while TNFRSF1A was similar between groups. After adjusting for sex and the intervention with perioperative gum chewing, myopenia remained associated with higher postoperative IL-8 concentrations (P = 0.047). CONCLUSION Myopenia may affect IL-8 early after colorectal surgery. However, more studies are needed to validate these findings.
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Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study.
Cho, L, Rocco, M, Colquhoun, D, Sullivan, D, Rosenson, RS, Dent, R, Xue, A, Scott, R, Wasserman, SM, Stroes, E
Cardiovascular drugs and therapy. 2016;(3):297-304
Abstract
PURPOSE Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905). METHODS GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS. RESULTS Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion. CONCLUSION Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.
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The efficacy of a supervised and a home-based core strengthening programme in adults with poor core stability: a three-arm randomised controlled trial.
Chuter, VH, de Jonge, XA, Thompson, BM, Callister, R
British journal of sports medicine. 2015;(6):395-9
Abstract
BACKGROUND Poor core stability is linked to a range of musculoskeletal pathologies and core-strengthening programmes are widely used as treatment. Treatment outcomes, however, are highly variable, which may be related to the method of delivery of core strengthening programmes. We investigated the effect of identical 8 week core strengthening programmes delivered as either supervised or home-based on measures of core stability. METHODS Participants with poor core stability were randomised into three groups: supervised (n=26), home-based (n=26) or control (n=26). Primary outcomes were the Sahrmann test and the Star Excursion Balance Test (SEBT) for dynamic core stability and three endurance tests (side-bridge, flexor and Sorensen) for static core stability. The exercise programme was devised and supervised by an exercise physiologist. RESULTS Analysis of covariance on the change from baseline over the 8 weeks showed that the supervised group performed significantly better on all core stability measures than both the home-based and control group. The home-based group produced significant improvements compared to the control group in all static core stability tests, but not in most of the dynamic core stability tests (Sahrmann test and two out of three directions of the SEBT). CONCLUSIONS Our results support the use of a supervised core-strengthening programme over a home-based programme to maximise improvements in core stability, especially in its dynamic aspects. Based on our findings in healthy individuals with low core stability, further research is recommended on potential therapeutic benefits of supervised core-strengthening programmes for pathologies associated with low core stability. TRIAL REGISTRATION NUMBER ACTRN12613000233729.
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Effect of a carbohydrate-protein multi-ingredient supplement on intermittent sprint performance and muscle damage in recreational athletes.
Naclerio, F, Larumbe-Zabala, E, Cooper, R, Jimenez, A, Goss-Sampson, M
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2014;(10):1151-8
Abstract
Carbohydrate-protein-based multi-ingredient supplements have been proposed as an effective strategy for limiting the deleterious effects of exercise-induced muscle damage. This study compares the effects of a commercially available carbohydrate-protein supplement enriched with l-glutamine and l-carnitine-l-tartrate to carbohydrate alone or placebo on sprint performance, muscle damage markers, and recovery from intermittent exercise. On 3 occasions, 10 recreationally trained males ingested a multi-ingredient, a carbohydrate supplement, or a placebo before, during, and immediately after a 90-min intermittent repeated sprint test. Fifteen-metre sprint times, creatine kinase, myoglobin, and interleukin-6 were assessed before (pre), immediately after (post), 1 h after (1h), and 24 h after (24h) exercise. Total sprint time measured during the intermittent protocol was not different between conditions. Fifteen-metre sprint time was slower (p < 0.05) at post, 1h and 24h compared with pre without differences between conditions (p > 0.05). Creatine kinase at 24h was lower (p < 0.05) in the multi-ingredient (461.8 ± 271.8 U·L) compared with both carbohydrate and placebo (606 ± 314.5 U·L and 636 ± 344.6 U·L, respectively). Myoglobin increased (p < 0.05) in all 3 conditions at post and 1h compared with pre, showing lower values at 1h (p < 0.05) for the carbohydrate and a trend (p = 0.060) for multi-ingredient compared with the placebo condition (211.4 ± 127.2 ng·mL(-1) and 239.4 ± 103.8 ng·mL(-1) vs. 484.6 ± 200.0 ng·mL(-1), respectively). Interleukin-6 increased at both post and 1h compared with pre (p < 0.05) with no differences between conditions. In conclusion, ingesting a multi-ingredient supplement before, during, and immediately after a 90-min intermittent sprint test resulted in no effects on performance and fatigue while the accumulation of some biomarkers of muscle damage could be attenuated.
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A randomized trial of coenzyme Q10 in patients with statin myopathy: rationale and study design.
Parker, BA, Gregory, SM, Lorson, L, Polk, D, White, CM, Thompson, PD
Journal of clinical lipidology. 2013;(3):187-93
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Abstract
BACKGROUND Statins are the most commonly prescribed and effective medications for reducing low-density lipoprotein levels. Some patients experience myopathic symptoms during statin treatment. The etiology is not known, but depletion of mevalonate pathway metabolites, including coenzyme Q10 (CoQ10), has been suggested. Despite a lack of conclusive evidence supporting its utility, CoQ10 supplementation has been recommended to patients who experience myalgic symptoms. OBJECTIVE The Co-Enzyme Q10 in Statin Myopathy study is designed to examine the effect of CoQ10 supplementation on the extent and intensity of muscle pain during treatment with simvastatin. METHODS We will recruit patients with a documented history of myalgia during statin treatment. The presence of statin-related myalgia will be confirmed in a crossover run-in trial during which the presence and absence of symptoms will be documented during statin and placebo treatment, respectively. Individuals experience myalgic symptoms while taking statins but not placebo will be randomized to receive simvastatin 20 mg daily plus either 600 mg daily of CoQ10 or placebo. Muscle pain intensity will be documented during weekly phone calls via use of the Brief Pain Inventory, Short Form. Treatment will continue for 8 weeks or until muscle symptoms are reported continuously for 1 week or become intolerable, and then subjects will crossover to the alternative treatment (CoQ10 or placebo). RESULTS This study is an ongoing clinical trial. CONCLUSIONS This study will determine the utility of CoQ10 for reducing pain intensity in myalgic patients and will provide guidance for clinicians treating patients with hypercholesterolemia who are intolerant to statins.
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HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment.
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European heart journal. 2013;(17):1279-91
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AIMS: Niacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. METHODS AND RESULTS Prior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ~1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6-7.5; P < 0.0001]; 7 vs. 5 were rhabdomyolysis. Any myopathy (definite or incipient) was more common among participants in China [138 (0.66%/year) vs. 27 (0.13%/year)] than among those in Europe [17 (0.07%/year) vs. 11 (0.04%/year)]. Consecutive alanine transaminase >3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants. CONCLUSION The risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ~1 month, three-quarters continued to take it for ~4 years.
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Efficacy and tolerability of once-weekly rosuvastatin in patients with previous statin intolerance.
Kennedy, SP, Barnas, GP, Schmidt, MJ, Glisczinski, MS, Paniagua, AC
Journal of clinical lipidology. 2011;(4):308-15
Abstract
BACKGROUND Many patients who could benefit from hydroxymethylglutaryl coenzyme-A reductase inhibitors (statins) are unable to take statins because of myalgias while taking previous statin therapy. OBJECTIVE The primary objective was to assess the efficacy and tolerability of once-weekly rosuvastatin in patients with documented myalgias on statins who were not currently taking a statin and not at low-density lipoprotein (LDL) goal. METHODS In this randomized, double-blind, placebo-controlled crossover study we enrolled a total of 17 Clement J. Zablocki Veterans Affairs (VA) primary care patients with a diagnosis of hyperlipidemia and a history of myalgias on statin therapy who were not currently on a statin and not at LDL goal. Two 8-week treatment phases consisted of rosuvastatin 5 mg once-weekly or matching placebo, with a dose titration to 10 mg once-weekly if not at LDL goal at week 4. The primary efficacy outcome was the difference in the mean percentage change in LDL from baseline between rosuvastatin and placebo. RESULTS A significant difference in the mean percentage change in LDL from baseline for rosuvastatin vs. placebo was identified (12.2% reduction vs. 0.4% reduction, respectively; P = .002). Two of the 17 patients (11.8%) in the placebo treatment phase and three of the 15 patients (20%) in the rosuvastatin treatment phase experienced myalgias requiring cessation of therapy. In addition, three patients (20%) were able to attain LDL goal on rosuvastatin compared with zero patients (0%) on placebo. CONCLUSION Once-weekly low-dose rosuvastatin is an effective and well-tolerated lipid-lowering therapy option for patients not at LDL goal and previously unable to tolerate statins because of a history of myalgias.
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Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia.
Young, JM, Florkowski, CM, Molyneux, SL, McEwan, RG, Frampton, CM, George, PM, Scott, RS
The American journal of cardiology. 2007;(9):1400-3
Abstract
Myalgia is the most frequently reported adverse side effect associated with statin therapy and often necessitates reduction in dose, or the cessation of therapy, compromising cardiovascular risk management. One postulated mechanism for statin-related myalgia is mitochondrial dysfunction through the depletion of coenzyme Q(10), a key component of the mitochondrial electron transport chain. This pilot study evaluated the effect of coenzyme Q(10) supplementation on statin tolerance and myalgia in patients with previous statin-related myalgia. Forty-four patients were randomized to coenzyme Q(10) (200 mg/day) or placebo for 12 weeks in combination with upward dose titration of simvastatin from 10 mg/day, doubling every 4 weeks if tolerated to a maximum of 40 mg/day. Patients experiencing significant myalgia reduced their statin dose or discontinued treatment. Myalgia was assessed using a visual analogue scale. There was no difference between combined therapy and statin alone in the myalgia score change (median 6.0 [interquartile range 2.1 to 8.8] vs 2.3 [0 to 12.8], p = 0.63), in the number of patients tolerating simvastatin 40 mg/day (16 of 22 [73%] with coenzyme Q(10) vs 13 of 22 [59%] with placebo, p = 0.34), or in the number of patients remaining on therapy (16 of 22 [73%] with coenzyme Q(10) vs 18 of 22 [82%] with placebo, p = 0.47). In conclusion, coenzyme Q(10) supplementation did not improve statin tolerance or myalgia, although further studies are warranted.
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Rofecoxib and tramadol do not attenuate delayed-onset muscle soreness or ischaemic pain in human volunteers.
Loram, LC, Mitchell, D, Fuller, A
Canadian journal of physiology and pharmacology. 2005;(12):1137-45
Abstract
We assessed the effect of rofecoxib, a cyclo-oxygenase-2 inhibitor, and tramadol, a centrally acting analgesic, on both delayed-onset muscle soreness (DOMS) and experimentally induced ischaemic pain. We induced DOMS in 10 male and 5 female healthy volunteers by downhill running for 30 min at a 12% decline and a speed of 9 km x h(-1). We also induced ischaemic pain by finger movements with an arterial tourniquet around the arm. In a randomized, double-blind crossover format, we administered rofecoxib (50 mg, daily), tramadol (50 mg, 3 times per day), and a placebo (orally for 3 days), starting immediately after exercise. A 100 mm visual analogue scale (VAS) and McGill pain questionnaire were used to describe muscle soreness and ischaemic forearm pain 24 h after the exercise. The pressure pain threshold (PPT) in the thigh and ischaemic pain tolerance in the forearm were measured before exercise and 24 and 72 h after exercise. PPT decreased 24 h after exercise, compared with pre-exercise values (ANOVA, p < 0.05), but neither drug had any significant effect on the PPT. Neither rofecoxib nor tramadol had any effect on time of ischaemia tolerated or amount of finger activity during ischaemia. The VAS and pain-rating index, for both muscle soreness and experimental ischaemic pain, were not affected significantly by either drug. Both DOMS and ischaemic pain share peripheral and central mechanisms, yet neither are attenuated by rofecoxib or tramadol.