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Insufficient 25-hydroxyvitamin D [25(OH)D] levels are associated with high resting blood pressure (BP). However, the relationship between 25(OH)D and the peak systolic BP (SBP) response to exercise, a predictor of future hypertension, has yet to be investigated. We sought to examine the relationship among serum 25(OH)D and the peak SBP response to a graded exercise stress test (GEST) among a large sample (n = 417) of healthy men (49%) and women (51%) over a broad age range (20-76 years; mean age: 44.1 ± 0.8 years). We hypothesized that individuals with clinically insufficient 25(OH)D would have a greater peak SBP response to a GEST compared to individuals with sufficient 25(OH)D levels. Fasting serum 25(OH)D, anthropometrics, resting BP, and peak exercise SBP were obtained at the baseline visit of a larger clinical trial (STOMP; NCT01140308). Mean 25(OH)D levels were 36.1 ± 0.7 ng/ml, with â¼35% of individuals classified as insufficient (<30 ng/ml). Average resting BP was 119 ± 13 mmHg/75 ± 10 mmHg, with 52.3% considered to have normal BP, while 25.2% had elevated BP and 22.5% had established hypertension. The peak SBP response to a GEST was similar between individuals with sufficient (48 ± 19 mmHg) versus insufficient (48 ± 18 mmHg) 25(OH)D (p = 1.000). One unexpected finding emerged such that individuals with sufficient 25(OH)D had higher resting SBP (120 ± 14 mmHg vs. 117 ± 13 mmHg; p = .020) than individuals with insufficient 25(OH)D. In contrast to our hypothesis, 25(OH)D levels were not associated with the peak SBP response to a GEST. Baseline 25(OH)D levels were positively correlated with resting SBP; however, the magnitude of this effect is likely not clinically meaningful.
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Pressão Sanguínea , Exercício Físico , Vitamina D/análogos & derivados , Adulto , Idoso , Teste de Esforço , Feminino , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Descanso , Vitamina D/sangue , Adulto JovemRESUMO
BACKGROUND: Interleukin-15 (IL-15) is a myokine associated with muscle strength, possibly by attenuating protein breakdown. A variant in the alpha-receptor (IL-15Rα 1775 A>C, rs2228059) partially modulates the muscle strength and size response to resistance training. We examined if this polymorphism associated with habitual physical activity among European-American adults. METHODS: Men (n = 240, 23.7 ± 0.3 year, body mass index [BMI] 25.3 ± 0.3 kg/m2 ) and women (n = 292, 23.2 ± 0.3 year, 24.0 ± 0.3 kg/m2 ) were genotyped. Physical activity phenotypes were derived from the Paffenbarger Physical Activity Questionnaire. Analysis of covariance (ancova) tested log-transformed differences between the IL-15Rα genotype and physical activity phenotypes by gender with age and BMI as covariates. RESULTS: Men with the IL-15Rα 1775AA genotype spent more time in light intensity physical activity (39.4 ± 2.4 hr/week) than men with the CC genotype (28.6 ± 2.3 hr/week, (p = .009). CONCLUSION: Further research is needed to confirm our finding and determine the possible mechanisms by which the IL-15Rα variant modulates light intensity physical activity.
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Exercício Físico/fisiologia , Subunidade alfa de Receptor de Interleucina-15/genética , Adulto , Alelos , Composição Corporal , Índice de Massa Corporal , Feminino , Frequência do Gene/genética , Variação Genética/genética , Genótipo , Humanos , Interleucina-15/genética , Subunidade alfa de Receptor de Interleucina-15/fisiologia , Masculino , Força Muscular/genética , Músculo Esquelético/anatomia & histologia , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Estados Unidos , População Branca/genéticaRESUMO
Exertional (exercise-induced) rhabdomyolysis is a potentially life threatening condition that has been the subject of research, intense discussion, and media attention. The causes of rhabdomyolysis are numerous and can include direct muscle injury, unaccustomed exercise, ischemia, extreme temperatures, electrolyte abnormalities, endocrinologic conditions, genetic disorders, autoimmune disorders, infections, drugs, toxins, and venoms. The objective of this article is to review the literature on exertional rhabdomyolysis, identify precipitating factors, and examine the role of the dietary supplement creatine monohydrate. PubMed and SPORTDiscus databases were searched using the terms rhabdomyolysis, muscle damage, creatine, creatine supplementation, creatine monohydrate, and phosphocreatine. Additionally, the references of papers identified through this search were examined for relevant studies. A meta-analysis was not performed. Although the prevalence of rhabdomyolysis is low, instances still occur where exercise is improperly prescribed or used as punishment, or incomplete medical history is taken, and exertional rhabdomyolysis occurs. Creatine monohydrate does not appear to be a precipitating factor for exertional rhabdomyolysis. Healthcare professionals should be able to recognize the basic signs of exertional rhabdomyolysis so prompt treatment can be administered. For the risk of rhabdomyolysis to remain low, exercise testing and prescription must be properly conducted based on professional standards.
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Exercício Físico , Esforço Físico , Rabdomiólise , HumanosRESUMO
Glucocorticoid receptor (NR3C1) polymorphisms associate with obesity, muscle strength, and cortisol sensitivity. We examined associations among four NR3C1 polymorphisms and the muscle response to resistance training (RT). European-American adults (n = 602, 23.8±0.4yr) completed a 12 week unilateral arm RT program. Maximum voluntary contraction (MVC) assessed isometric strength (kg) and MRI assessed biceps size (cm2) pre- and post-resistance training. Subjects were genotyped for NR3C1 -2722G>A, -1887G>A, -1017T>C, and +363A>G. Men carrying the -2722G allele gained less relative MVC (17.3±1.2vs33.5±6.1%) (p = 0.010) than AA homozygotes; men with -1887GG gained greater relative MVC than A allele carriers (19.6±1.4vs13.2±2.3%) (p = 0.016). Women carrying the -1017T allele gained greater relative size (18.7±0.5vs16.1±0.9%) (p = 0.016) than CC homozygotes. We found sex-specific NR3C1 associations with the muscle strength and size response to RT. Future studies should investigate whether these associations are partially explained by cortisol's actions in muscle tissue as they interact with sex differences in cortisol production.
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Força Muscular , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiologia , Receptores de Glucocorticoides/genética , Treinamento Resistido , Adulto , Feminino , Humanos , Masculino , Contração Muscular , Polimorfismo de Nucleotídeo Único , Adulto JovemRESUMO
The purpose of this study was to examine relationships between objective and self-report measures of physical activity and muscle strength among healthy adults ranging in age from 20 to 91 years. Participants (n = 412) were mostly Caucasian men (48 %) and women (52 %) 43.9 ± 16.1 year of age with a body mass index (BMI) of 26.4 ± 4.8 kg/m(2). Physical activity was measured objectively with an accelerometer and by self-report with the Paffenbarger Physical Activity Questionnaire. Upper and lower body muscle strength were measured with an isokinetic dynamometer and handgrip strength with a static dynamometer. Multivariate regression assessed relationships between physical activity and muscle strength. The strongest correlates of upper body strength including handgrip strength were gender (r = -0.861 to -0.716), age (r = -0.445 to -0.241), BMI (r = 0.134-0.397), and physical activity (r = 0.093-0.186). The strongest correlates of lower body strength were gender (r = -0.772 to -0.634), age (r = -0.663 to -0.445), BMI (r = 0.160-0.266), and physical activity (r = -0.139 to 0.151). The strongest correlates of muscle strength were gender (explaining 40-74 % of the variance), age (6-44 %), and BMI (2-16 %), while physical activity correlations were weaker (1-3 %). Conflict surrounding the influence of a physically active lifestyle on muscle strength with age may be due to the stronger influences of other factors that supersede those of physical activity whether measured objectively or by self-report methods.
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Pericytes are skeletal muscle resident, multipotent stem cells that are localized to the microvasculature. In vivo, studies have shown that they respond to damage through activation of nuclear-factor kappa-B (NF-κB), but the downstream effects of NF-κB activation on endothelial cell proliferation and cell-cell signaling during repair remain unknown. The purpose of this study was to examine pericyte NF-κB activation in a model of skeletal muscle damage; and use genetic manipulation to study the effects of changes in pericyte NF-κB activation on endothelial cell proliferation and cytokine secretion. We utilized scratch injury to C2C12 cells in coculture with human primary pericytes to assess NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) secretion from pericytes and C2C12 cells. We also cocultured endothelial cells with pericytes that expressed genetically altered NF-κB activation levels, and then quantified endothelial cell proliferation and screened the conditioned media for secreted cytokines. Pericytes trended toward greater NF-κB activation in injured compared to control cocultures (P = 0.085) and in comparison to C2C12 cells (P = 0.079). Second, increased NF-κB activation in pericytes enhanced the proliferation of cocultured endothelial cells (1.3-fold, P = 0.002). Finally, we identified inflammatory signaling molecules, including MCP-1 and interleukin 8 (IL-8) that may mediate the crosstalk between pericytes and endothelial cells. The results of this study show that pericyte NF-κB activation may be an important mechanism in skeletal muscle repair with implications for the development of therapies for musculoskeletal and vascular diseases, including peripheral artery disease.
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This study determined the contribution of extracellular matrix (ECM) remodeling to the protective adaptation of human skeletal muscle known as the repeated-bout effect (RBE). Muscle biopsies were obtained 3 hours, 2 days, and 27 days following an initial bout (B1) of lengthening contractions (LCs) and 2 days following a repeated bout (B2) in 2 separate studies. Biopsies from the nonexercised legs served as controls. In the first study, global transcriptomic analysis indicated widespread changes in ECM structural, deadhesive, and signaling transcripts, 3 hours following LC. To determine if ECM remodeling is involved in the RBE, we conducted a second study by use of a repeated-bout paradigm. TNC immunoreactivity increased 10.8-fold following B1, was attenuated following B2, and positively correlated with LC-induced strength loss (r(2) = 0.45; P = 0.009). Expression of collagen I, III, and IV (COL1A1, COL3A1, COL4A1) transcripts was unchanged early but increased 5.7 ± 2.5-, 3.2 ± 0.9-, and 2.1 ± 0.4-fold (P < 0.05), respectively, 27 days post-B1 and were unaffected by B2. Likewise, TGF-ß signaling demonstrated a delayed response following LC. Satellite cell content increased 80% (P < 0.05) 2 days post-B1 (P < 0.05), remained elevated 27 days post-B1, and was unaffected by B2. Collectively, the data suggest sequential ECM remodeling characterized by early deadhesion and delayed reconstructive activity that appear to contribute to the RBE.
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Adaptação Fisiológica , Matriz Extracelular/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Adaptação Fisiológica/genética , Adulto , Colágeno/genética , Matriz Extracelular/genética , Feminino , Expressão Gênica , Humanos , Laminina/genética , Masculino , Contração Muscular/genética , Músculo Esquelético/anatomia & histologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Tenascina/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Adulto JovemRESUMO
BACKGROUND: Little information exists regarding the psychometric properties of question 8 (Q8) of the Paffenbarger Physical Activity Questionnaire (PPAQ) to assess exercise. Thus, we conducted 2 studies to assess the validity and test-retest reliability of Q8 among adults. METHODS: Study 1 participants (n = 419) were 44.1 ± 16.1 years of age. Validity was determined by comparing self-reported hr·d-1 in sedentary, light, moderate, and vigorous intensity physical activity (PA) and MET-hr·wk-1 on Q8 at baseline to accelerometer and health/fitness measurements using Spearman rank-order correlations. Study 2 participants (n = 217) were 44.7 ± 16.3 years of age and completed Q8 at baseline, 3 months, and 6 months. Test-retest reliability was determined using repeated measures analysis of covariance, intraclass correlations (ICCs), and standard error of the measurement (SEM). RESULTS: Q8 displayed good criterion validity compared with accelerometer measurements (r = .102 to .200, P < .05) and predictive validity compared with health/fitness measurements (r = -.272 to .203, P < .05). No differences were observed in self-reported hr·d-1 in any of the PA categories at baseline, 3 months, and 6 months (ICC: 0.49 to 0.68; SEM: 1.0 to 2.0; P > .05), indicating good reliability. CONCLUSION: Q8 demonstrates adequate criterion validity, acceptable predictive validity, and satisfactory test-retest reliability and can be used in conjunction with other components of the PPAQ to provide a complete representation of exercise.
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Teste de Esforço , Exercício Físico , Aptidão Física , Autorrelato , Inquéritos e Questionários , Acelerometria , Adulto , Composição Corporal , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Psicometria , Reprodutibilidade dos TestesRESUMO
Statins are the most widely prescribed and effective medication for reducing low density lipoprotein cholesterol. Statins may also lower resting blood pressure (BP); however, results are inconsistent. We sought to determine if the maximum dose of atorvastatin reduces resting BP and the peak systolic BP (SBP) achieved on a graded exercise stress test (GEST) among a large sample of 419 healthy men (48%) and women (52%). Subjects (419, 44.1 ± 0.8 yr) were double-blinded and randomized to 80 mg·d(-1) of atorvastatin (n = 202) or placebo (n = 217) for 6 mo. Among the total sample, there were no differences in resting BP (SBP, P = 0.30; diastolic BP [DBP], P = 0.69; mean arterial pressure (P = 0.76); or peak SBP on a GEST (P = 0.99)) over 6 mo, regardless of drug treatment group. However, among women on atorvastatin, resting SBP/DBP (3.7±1.5 mmHg, P = 0.01/3.2±0.9 mmHg, P = 0.02) and peak SBP on a GEST (6.5±1.5 mmHg, P = 0.04) were lower versus men. Atorvastatin lowered resting BP 3-4 mmHg and peak SBP on a GEST ~7 mmHg more among women than men over 6 mo of treatment. The inconsistent findings regarding the antihypertensive effects of statins may be partially explained by not accounting for sex effects.
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Genome-wide association studies have identified thousands of variants that are associated with numerous phenotypes. One such variant, rs13266634, a nonsynonymous single nucleotide polymorphism in the solute carrier family 30 (zinc transporter) member eight gene, is associated with a 53% increase in the risk of developing type 2 diabetes (T2D). We hypothesized that individuals with the protective allele against T2D would show a positive response to short-term and long-term resistance exercise. Two cohorts of young adults-the Eccentric Muscle Damage (EMD; n = 156) cohort and the Functional Single Nucleotide Polymorphisms Associated with Muscle Size and Strength Study (FAMuSS; n = 874)-were tested for association of the rs13266634 variant with measures of skeletal muscle response to resistance exercise. Our results were sexually dimorphic in both cohorts. Men in the EMD study with two copies of the protective allele showed less post-exercise bout strength loss, less soreness, and lower creatine kinase values. In addition, men in the FAMuSS, homozygous for the protective allele, showed higher pre-exercise strength and larger arm skeletal muscle volume, but did not show a significant difference in skeletal muscle hypertrophy or strength with resistance training.
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Proteínas de Transporte de Cátions/genética , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Treinamento Resistido , Transportador 8 de ZincoRESUMO
We investigated the existence of contralateral repeated bout effect and tested if the attenuation of nuclear factor-kappa B (NF-κB; an important regulator of muscle inflammation) induction following eccentric exercise is a potential mechanism. Thirty-one healthy men performed two bouts of knee extension eccentric exercise, initially with one leg and then with the opposite leg 4 wk later. Vastus lateralis muscle biopsies of both exercised and control legs were taken 3 h postexercise. Knee extension isometric and isokinetic strength (60°/sec and 180°/sec) were measured at baseline, pre-exercise, immediately postexercise, and 1/day for 5 days postexercise. Serum creatine kinase (CK) activity and muscle soreness were assessed at baseline and 1/day for 5 days postexercise. NF-κB (p65) DNA-binding activity was measured in the muscle biopsies. Isometric strength loss was lower in bout 2 than in bout 1 at 24, 72, and 96 h postexercise (P < 0.05). Isokinetic strength (60°/s and 180°/s) was reduced less in bout 2 than in bout 1 at 72 h postexercise (P < 0.01). There were no significant differences between bouts for postexercise CK activity or muscle soreness. p65 DNA-binding activity was increased following eccentric exercise (compared with the control leg) in bout 1 (122.9% ± 2.6%; P < 0.001) and bout 2 (109.1% ± 3.0%; P < 0.05). Compared with bout 1, the increase in NF-κB DNA-binding activity postexercise was attenuated after bout 2 (P = 0.0008). Repeated eccentric exercise results in a contralateral repeated bout effect, which could be due to the attenuated increase in NF-κB activity postexercise.
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Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , NF-kappa B/metabolismo , Adulto , DNA/genética , Regulação para Baixo/genética , Exercício Físico , Humanos , Masculino , NF-kappa B/genética , Esforço Físico , Ligação Proteica/fisiologiaRESUMO
BACKGROUND: The present study examined if increases in creatine kinase (CK) levels during high-dose atorvastatin treatment are associated with changes in skeletal muscle function and symptoms. METHODS: The Effect of Statins on Muscle Performance study (STOMP) investigated the effects of atorvastatin 80 mg daily for 6 months on muscle performance, exercise capacity, and the incidence of statin-associated muscle complaints in healthy adults. RESULTS: CK levels increased with atorvastatin (n = 202) from 132.3 ± 120.9 U/L (mean ± SD) at baseline to 159.7 ± 170.4 and 153.1 ± 139.4 U/L at 3 and 6 months, respectively (P ≤ 0.002 for both). Changes in CK with atorvastatin treatment were not associated with changes in muscle function or the incidence of myalgia. More subjects on atorvastatin (n = 24) compared to placebo (n = 12 of 217) doubled their CK level at 6 months (P = 0.02). No differences in muscle function or physical activity were observed between atorvastatin-treated subjects who did or did not double their CK. CONCLUSIONS: Results of the present investigation extend the findings of STOMP by demonstrating that greater increases in CK levels with high-dose atorvastatin treatment did not deleteriously impact skeletal muscle function or predict skeletal muscle complaints. This study was registered at ClinicalTrials.gov (NCT00609063).
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Creatina Quinase/metabolismo , Ácidos Heptanoicos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Pirróis/efeitos adversos , Adulto , Atorvastatina , Método Duplo-Cego , Exercício Físico , Feminino , Ácidos Heptanoicos/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Músculos/efeitos dos fármacos , Músculos/fisiologia , Mialgia/induzido quimicamente , Pirróis/química , Resultado do TratamentoRESUMO
INTRODUCTION: Skeletal muscle regeneration following damage relies on proliferation and differentiation of muscle precursor cells (MPCs). We recently observed increased NF-kB activity in vascular-associated muscle resident pericytes following muscle damage in humans. We determined how altered NF-kB activity in human primary pericytes (HPPs) affects their myogenic differentiation (cell-autonomous effects), as well as proliferation and differentiation of co-cultured MPCs (non-cell-autonomous effects). METHODS: HPPs were transfected with vectors that increased or decreased NF-kB activity. Transfected HPPs were co-cultured with C2 C12 myoblasts under differentiation conditions, and HPP fusion to myotubes was measured. We also co-cultured HPPs with C2 C12 myoblasts and measured proliferation and myotube formation. RESULTS: Inhibition of NF-kB activity increased HPP fusion to C2 C12 myotubes. Moreover, enhanced NF-kB activity in HPPs suppressed differentiation and enhanced proliferation of co-cultured myoblasts. CONCLUSIONS: NF-kB activity acts cell-autonomously to inhibit HPP myogenic differentiation and non-cell-autonomously to promote MPC proliferation and suppress MPC differentiation in vitro.
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Fibras Musculares Esqueléticas/fisiologia , Mioblastos/fisiologia , Subunidade p50 de NF-kappa B/fisiologia , Pericitos/fisiologia , Regeneração/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Células Cultivadas , Técnicas de Cocultura , Humanos , Desenvolvimento Muscular/fisiologia , Fibras Musculares Esqueléticas/citologia , Mioblastos/citologia , Pericitos/metabolismoRESUMO
PURPOSE: An osteopontin (OPN; SPP1) gene promoter polymorphism modifies disease severity in Duchenne muscular dystrophy, and we hypothesized that it might also modify muscle phenotypes in healthy volunteers. METHODS: Gene association studies were carried out for OPN (rs28357094) in the FAMuSS cohort (n = 752; mean ± SD age = 23.7 ± 5.7 yr). The phenotypes studied included muscle size (MRI), strength, and response to supervised resistance training. We also studied 147 young adults that had carried out a bout of eccentric elbow exercise (age = 24.0 ± 5.2 yr). Phenotypes analyzed included strength, soreness, and serum muscle enzymes. RESULTS: In the FAMuSS cohort, the G allele was associated with 17% increase in baseline upper arm muscle volume only in women (F = 26.32; P = 5.32 × 10), explaining 5% of population variance. In the eccentric damage cohort, weak associations of the G allele were seen in women with both baseline myoglobin and elevated creatine kinase. The sexually dimorphic effects of OPN on muscle were also seen in OPN-null mice. Five of seven muscle groups examined showed smaller size in OPN-null female mice, whereas two were smaller in male mice. The query of OPN gene transcription after experimental muscle damage in mice showed rapid induction within 12 h (100-fold increase from baseline), followed by sustained high-level expression through 16 d of regeneration before falling to back to baseline. CONCLUSION: OPN is a sexually dimorphic modifier of muscle size in normal humans and mice and responds to muscle damage. The OPN gene is known to be estrogen responsive, and this may explain the female-specific genotype effects in adult volunteers.
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Músculo Esquelético/anatomia & histologia , Osteopontina/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Adulto , Análise de Variância , Animais , Biomarcadores/sangue , Feminino , Estudos de Associação Genética , Marcadores Genéticos , Técnicas de Genotipagem , Voluntários Saudáveis , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Knockout , Força Muscular/genética , Músculo Esquelético/fisiologia , Mioglobina/sangue , Treinamento Resistido , Fatores SexuaisRESUMO
PURPOSE: The purpose of the study was to examine the relation between serum 25-hydroxy vitamin D (25(OH)D) levels and muscle strength in 419 healthy men and women over a broad age range (20-76 yr). METHODS: Isometric and isokinetic strength of the arms and legs was measured using computerized dynamometry, and its relation to vitamin D was tested in multivariate models controlling for age, gender, resting HR, systolic blood pressure, diastolic blood pressure, body mass index, maximal oxygen uptake (VO(2max)), physical activity counts, and season of vitamin D measurement. RESULTS: Vitamin D was significantly associated with arm and leg muscle strength when controlling for age and gender. When controlling for other covariates listed previously, vitamin D remained directly related to both isometric and isokinetic arm strength but only to isometric leg strength. CONCLUSION: These data suggest that there may be a differential effect of vitamin D on upper and lower body strength. The mechanism for this difference remains unclear but could be related to differences in androgenic effects or to differences in vitamin D receptor expression. Our study supports a direct relation between vitamin D and muscle strength and suggests that vitamin D supplementation be evaluated to determine whether it is an effective therapy to preserve muscle strength in adults.
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Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Vitamina D/análogos & derivados , Adulto , Idoso , Braço , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Contração Isométrica/fisiologia , Perna (Membro) , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Dinamômetro de Força Muscular , Vitamina D/sangueRESUMO
BACKGROUND: Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. METHODS AND RESULTS: The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). CONCLUSIONS: These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.
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Ácidos Heptanoicos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Músculo Esquelético/efeitos dos fármacos , Dor Musculoesquelética/induzido quimicamente , Pirróis/efeitos adversos , Adulto , Atorvastatina , Creatina Quinase/sangue , Método Duplo-Cego , Teste de Esforço , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Ácidos Heptanoicos/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Placebos , Pirróis/administração & dosagem , Adulto JovemRESUMO
UNLABELLED: The objective of the study was to investigate the absorption of quercetin aglycone in 18 healthy human subjects administered via the following oral carrier systems: suspension of quercetin (quercetin QU995 powder in Tang(®) and spring water), nutritional bars (First Strike™), and chews (RealFX™ Q-Plus™). Subjects were divided into 3 groups of 6 individuals each receiving 500 mg quercetin in one of the aforementioned formulations. Blood levels were monitored immediately pre- and for 32 h postadministration. The concentration of total quercetin in blood samples was determined by solid phase extraction followed by high-performance liquid chromatography analysis. Pharmacokinetic parameters were determined by noncompartmental modeling using Kinetica software. The C(max) of quercetin was highest with RealFX™ Q-Plus™ Chews (1051.9 ± 393.1 µg/L) achieved within 3.3 h as compared to that for First Strike™ Bars (698.1 ± 189.5 µg/L in 2.3 h) and Tang(®) suspension (354.4 ± 87.6 µg/L in 4.7 h). The results showed no statistically significant difference in quercetin absorption among groups due to high variability within groups receiving quercetin from same dosage form. This study represents the first comprehensive evaluation of quercetin absorption from quercetin fortified oral food products at doses commonly used for quercetin supplementation. PRACTICAL APPLICATION: The current study describes for the first time, comprehensive evaluation of quercetin PK in humans from quercetin fortified oral food products at doses commonly used for quercetin supplementation. Owing to quercetin's potent antioxidant and anti-inflammatory actions, quercetin is widely being used as a nutritional supplement. In order to maximize the bioavailability of quercetin for its use in efficacy studies, it is important to determine its ideal oral carrier system and route for its delivery. The current research unveils vital information about quercetin supplementation to the international community, especially to soldiers, athletes, and the dietary supplement industry.
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Suplementos Nutricionais , Quercetina/administração & dosagem , Quercetina/farmacocinética , Administração Oral , Adolescente , Adulto , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Calibragem , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Masculino , Pós/química , Quercetina/sangue , Adulto JovemRESUMO
The flavonoid quercetin is purported to have potent antioxidant and anti-inflammatory properties. This study examined if quercetin supplementation attenuates indicators of exercise-induced muscle damage in a double-blind laboratory study. Thirty healthy subjects were randomized to quercetin (QU) or placebo (PL) supplementation and performed 2 separate sessions of 24 eccentric contractions of the elbow flexors. Muscle strength, soreness, resting arm angle, upper arm swelling, serum creatine kinase (CK) activity, plasma quercetin (PQ), interleukin-6 (IL-6), and C-reactive protein (CRP) were assessed before and for 5 d after exercise. Subjects then ingested nutrition bars containing 1,000 mg/d QU or PL for 7 d before and 5 d after the second exercise session, using the opposite arm. PQ reached 202 ± 52 ng/ml after 7 d of supplementation and remained elevated during the 5-d postexercise recovery period (p < .05). Subjects experienced strength loss (peak = 47%), muscle soreness (peak = 39 ± 6 mm), reduced arm angle (-7° ± 1°), CK elevations (peak = 3,307 ± 1,481 U/L), and arm swelling (peak = 11 ± 2 mm; p < .0001), indicating muscle damage and inflammation; however, differences between treatments were not detected. Eccentric exercise did not alter plasma IL-6 (peak = 1.9 pg/ml) or CRP (peak = 1.6 mg/L) relative to baseline or by treatment. QU supplementation had no effect on markers of muscle damage or inflammation after eccentric exercise of the elbow flexors.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Alimentos Especializados , Miosite/prevenção & controle , Quercetina/uso terapêutico , Treinamento Resistido/efeitos adversos , Fenômenos Fisiológicos da Nutrição Esportiva , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/sangue , Antioxidantes/efeitos adversos , Antioxidantes/análise , Braço , Biomarcadores/sangue , Método Duplo-Cego , Edema/etiologia , Edema/prevenção & controle , Feminino , Alimentos Especializados/efeitos adversos , Humanos , Masculino , Força Muscular , Mialgia/etiologia , Mialgia/prevenção & controle , Miosite/sangue , Miosite/etiologia , Miosite/fisiopatologia , Quercetina/efeitos adversos , Quercetina/sangue , Lanches , Adulto JovemRESUMO
Ankyrin repeat domain 6 (ANKRD6) is a ubiquitous protein that associates with early development in mammals and is highly expressed in the brain, spinal cord, and heart of humans. We examined the role of 8 ANKRD6 single-nucleotide polymorphisms (SNPs) on muscle performance and habitual physical activity (PA). Single-nucleotide polymorphisms were 545 T>A (rs9362667), 485 M>L (rs61736690), 233 T>M (rs2273238), 128 I>L (rs3748085), 631 P>L (rs61739327), 122 Q>E (rs16881983), 197805 G>A (rs9344950), and 710 L>X (NOVEL). This study consisted of 922 healthy, untrained, European-derived American men (n = 376, 23.6 ± 0.3 years, 25.0 ± 0.2 kg·m(-2)) and women (n = 546, 23.2 ± 0.2 years, 24.0 ± 0.2 kg·m(-2)). Muscle strength (maximum voluntary contraction [MVC] and 1 repetition maximum [1RM]) and size (cross-sectional area [CSA]) were assessed before and after 12 weeks of unilateral resistance training (RT). A subsample (n = 536, 23.4 ± 0.2 years, 24.6 ± 0.2 kg·m(-2)) completed the Paffenbarger Physical Activity Questionnaire. Associations among ANKRD6 genotypes and muscle phenotypes were tested with repeated measure analysis of covariance (ANCOVA) and PA phenotypes with multivariate ANCOVA, with age and body mass index as covariates. ANKRD6 122 Q>E was associated with increased baseline biceps CSA. ANKRD6 545 A>T and ANKRD6 710 L>X were associated with increased 1RM and MVC in response to RT, respectively. ANKRD6 631 P>L was associated with increased biceps CSA response to RT and time spent in moderate-intensity PA among the total sample and women. ANKRD6 genetic variants were associated with the muscle size and strength response to RT and habitual PA levels. Further research is needed to validate our results and explore mechanisms for the associations we observed.