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NEW FINDINGS: What is the main observation in this case? Co-administration of LGD-4033 and MK-677 increased body mass, lean mass and fat mass, while negatively impacting bone, serum lipids, liver enzymes, testosterone (total and free) and, probably, follicle-stimulating hormone. What insights does it reveal? Our cross-sectional data imply that these compounds might alter intramuscular androgenic hormone and receptor concentrations along with promoting muscular strength, when compared with previously published data from trained males. ABSTRACT: LGD-4033, a selective androgen receptor modulator, and MK-677, a growth hormone secretagogue, are being used increasingly amongst recreationally active demographics. However, limited data exist describing their effects on health- and androgen-related biomarkers. The purpose of this case study was to determine changes in body composition and biomarkers during and after continued co-administration of LGD-4033 and MK-677. We also aimed to examine muscular strength and intramuscular androgen-associated biomarkers relative to non-users. A 25-year-old male ingested LGD-4033 (10 mg) and MK-677 (15 mg) daily for 5 weeks. Blood and body composition metrics were obtained pre-, on- and post-cycle. One-repetition maximum leg and bench press, in addition to intramuscular androgens and androgen receptor content, were analysed on-cycle. We observed pre- to on-cycle changes in body composition (body mass, +6.0%; total lean body mass, +3.1%; trunk lean body mass, +6.6%; appendicular lean body mass, +4.3%; total fat mass, +15.4%; trunk fat mass, +2.8%; and appendicular fat mass, +14.8%), bone (bone mineral content, -3.60%; area, -1.1%; and bone mineral density, -2.1%), serum lipid-associated biomarkers (cholesterol, +14.8%; triglycerides, +39.2%; low-density lipoprotein-cholesterol, +40.0%; and high-density lipoprotein-cholesterol, -36.4%), liver-associated biomarkers (aspartate aminotransferase, +95.8%; and alanine aminotransferase, +205.0%) and androgen-associated biomarkers (free testosterone, -85.7%; total testosterone, -62.3%; and sex hormone-binding globulin, -79.6%); however, all variables returned to pre-cycle values post-cycle, apart from total fat mass, appendicular fat mass, bone area, total cholesterol and low-density lipoprotein-cholesterol. Follicle-stimulating hormone was below clinical reference values on- (1.2 IU/L) and post-cycle (1.3 IU/L). Intramuscular androgen receptor (-44.6%), testosterone (+47.8%) and dihydrotestosterone (+34.4%), in addition to one-repetition maximum leg press and bench press (+39.2 and +32.0%, respectively), were different in the case subject compared with non-users. These data demonstrate that LGD-4033 and MK-677 increase several body composition parameters, whilst negatively impacting bone and several serum biomarkers. Given the sparsity of data in recreationally using demographics, further research is warranted to elucidate the acute and chronic physiological effects of these anabolic agents.
Assuntos
Androgênios , Receptores Androgênicos , Masculino , Humanos , Adulto , Receptores Androgênicos/metabolismo , Estudos Transversais , Composição Corporal , Testosterona , Músculo Esquelético/fisiologia , Biomarcadores , Hormônio Foliculoestimulante , Lipoproteínas LDLRESUMO
Resistance exercise (RE) activates cell signaling pathways associated with myostatin. Decorin is located in the extracellular matrix (ECM) and can block the inhibitory effect of myostatin. This study sought to determine the impact of low-load (LL) and high-load (HL) RE on myostatin mRNA and protein expression along with changes in muscle decorin and circulating follistatin. Ten resistance-trained men performed a LL (50% 1RM) and HL (80% 1RM) RE session using the angled leg press and leg extension with load and volume equated. Venous blood samples and muscle biopsies were obtained prior to and at 3h and 24h following each RE session. Muscle myostatin mRNA expression was increased at 24h post-exercise (p = 0.032) in LL and at 3h (p = 0.044) and 24h (p = 0.003) post-exercise in HL. Muscle decorin was increased at 24h post-exercise (p < 0.001) in LL and HL; however, muscle myostatin was increased at 24h post-exercise (p < 0.001) only in HL. For muscle Smad 2/3, no significant differences were observed (p > 0.05). Serum follistatin was increased and myostatin decreased at 24h post-exercise (p < 0.001) in LL and HL. Muscle myostatin gene and protein expression increased in response to HL RE. However, serum myostatin was decreased in the presence of increases in decorin in muscle and follistatin in circulation. Therefore, our data suggest a possible mechanism may exist where decorin within the ECM is able to bind to, and decrease, myostatin that might otherwise enter the circulation for activin IIB (ACTIIB) receptor binding and subsequent canonical signaling through Smad 2/3.
Assuntos
Decorina , Exercício Físico , Miostatina , Humanos , Masculino , Decorina/genética , Decorina/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Folistatina/genética , Folistatina/metabolismo , Músculo Esquelético/fisiologia , Miostatina/genética , Miostatina/metabolismo , Treinamento Resistido , RNA Mensageiro/genética , Exercício Físico/fisiologiaRESUMO
NEW FINDINGS: What is the main observation in this case? The main observation of this case report is that blood flow-restricted exercise can cause myofibrils to have an aberrant wave-like appearance that is accompanied by irregular pockets of sarcoplasm in the intermyofibrillar space, while traditional forms of damage to the Z-discs and contractile elements are not as apparent. What insights does it reveal? Our findings indicate that blood flow restriction-mediated fluid pooling might cause alterations in skeletal muscle ultrastructure after exercise that might be directly related to myofibre swelling. ABSTRACT: The acute effects of blood flow-restricted (BFR) exercise training on skeletal muscle ultrastructure are poorly understood owing to inconsistent findings and the use of largely imprecise systemic markers for indications of muscle damage. The purpose of this study was to compare myofibrillar ultrastructure before and 30 min after normal and BFR resistance exercise using transmission electron microscopy in a single individual to evaluate the feasibility of this more nuanced approach. One apparently healthy male with 13 years of resistance exercise completed six sets of both BFR [30% of one-repetition maximum (1-RM)] and normal non-occluded (70% of 1-RM) unilateral angled leg press on the contralateral leg, as a control, after assessment of 1-RM 72 h before. Vastus lateralis muscle biopsies were collected before and 30 min after each exercise session. The lengths and widths of 250 sarcomeres and the sarcoplasmic area were assessed via 20 individual transmission electron photomicrographs. Analysis revealed that BFR training (1.769 ± 0.12 µm) increased sarcomere length when compared with normal exercise (1.64 ± 0.17 µm; P < 0.001), without differences in sarcomere width between conditions (BFR, 0.90 ± 0.26 µm; normal, 0.93 ± 0.27 µm; P = 0.172). Furthermore, there were no significant interaction (P = 0.168) or condition effects between BFR (25.98 ± 4.17%) and normal (27.3 ± 6.49%) resistance exercise for sarcoplasmic area (P = 0.229). Exercise also increased sarcoplasmic area within the myofibril (pre-exercise, 24.42 ± 5.13%; postexercise, 28.95 ± 5.92%) for both conditions (P = 0.001). This case study demonstrates a unique BFR training-induced alteration in myofibril ultrastructure that appeared wave like and was accompanied by intracellular abnormalities that appeared to be fluid pockets of sarcoplasm disrupting the surrounding myofibrils.
Assuntos
Treinamento Resistido , Humanos , Masculino , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Músculo Quadríceps , Fluxo Sanguíneo Regional/fisiologiaRESUMO
PURPOSE: Curcumin is a polyphenolic compound that is suggested to dysregulate the ubiquitin-proteasome system (UPS). This study investigated the effects of curcumin supplementation on markers of UPS activity in response to muscle damage. METHODS: Twenty-three recreationally active male and females between the ages of 18-30 were randomized into a curcumin (CUR) or placebo (PLA) group. Both groups ingested 2 g of their respective supplement and 20 mg of piperine for 11 consecutive days. Following 8 consecutive days of supplementation, participants performed a 45-minute eccentrically-biased treadmill protocol at 60% VO2max. Muscle biopsies and delayed onset muscle soreness (DOMS) assessments were performed 30 minutes prior and 3, 24, 48, and 72 hours following exercise. Skeletal muscle ubiquitin, MAFbx/Atrogin-1, ubiquitin specific peptidase 19 (USP19), and chymotrypsin-like protease concentrations were measured using ELISA. A 3-way repeated measures ANOVA with pairwise comparisons was conducted with significance set at p ≤ 0.05. RESULTS: Compared to baseline, DOMS for both groups was significantly increased (p < 0.05) at all time points except 72 hours following exercise. No significant differences were found for USP19 between groups. Ubiquitin (p=.016) and MAFbx/Atrogin-1 (p=.006) were significantly lower for CUR compared to PLA. Additionally, MAFbx/Atrogin-1 was significantly greater for females (p=.013) compared to males. In males, curcumin resulted in significant reductions (p = .049) in chymotrypsin-like protease (p = .049). CONCLUSION: While elevations in UPS activity were not observed in response to muscle damage, curcumin supplementation in humans does appear to dysregulate basal UPS activity in the presence of exercise-induced muscle damage.
Assuntos
Curcumina , Exercício Físico , Músculo Esquelético/lesões , Complexo de Endopeptidases do Proteassoma , Adolescente , Adulto , Curcumina/farmacologia , Endopeptidases , Feminino , Humanos , Masculino , Mialgia/tratamento farmacológico , Ubiquitina , Adulto JovemRESUMO
ABSTRACT: Machek, SB, Cardaci, TD, Wilburn, DT, Cholewinski, MC, Latt, SL, Harris, DR, and Willoughby, DS. Neoprene knee sleeves of varying tightness augment barbell squat one repetition maximum performance without improving other indices of muscular strength, power, or endurance. J Strength Cond Res 35(2S): S6-S15, 2021-Neoprene knee sleeves are commonly used by powerlifters and recreational users but are heavily under-researched. Furthermore, no data exist on whether knee sleeves of varying compressive tightness impact muscular performance similar to commonly used knee wraps, which are both generally effective and more so when increasingly constrictive. Fifteen resistance trained, knee sleeve naive, recreational weight lifting men (22.1 ± 4.1 years; 177.5 ± 5.9 cm; 87.8 ± 7.8 kg) visited the laboratory on 3 separate occasions one week apart, assigned in a randomized, crossover, and counterbalanced fashion to either a minimally supportive control sleeve (CS) condition, a manufacturer-recommended sizing neoprene knee sleeve ("normal" sleeve; NS), or a one size smaller (than NS) neoprene knee sleeve (tighter sleeve [TS]). On each visit, subjects sequentially completed vertical jump (countermovement and squat jumps for both peak and mean power), one repetition maximum (1RM) barbell squat, and GymAware assessments (peak power, peak velocity, and dip) at 90% (reported) and 100% (tested) 1RM as well as one-leg extension (1RM, repetitions to failure, and total volume load at 75% 1RM) tests. All data were analyzed using one-way repeated measures analysis of variance at p < 0.05. Analysis revealed a significant condition effect on barbell squat 1RM (p = 0.003; η2 = 0.339), whereby both NS (p = 0.044; 166 ± 24 kg) and TS (p = 0.019; 166 ± 21 kg) outperformed CS (161 ± 22 kg), with no difference between neoprene sleeves. Conversely, no other tested parameters differed between knee sleeve conditions (p ≥ 0.05). The present results demonstrate that neoprene knee sleeves may function independent of tightness, relative to recommended sizing and ultimately unlike knee wraps. Furthermore, the singular benefits observed on barbell squat maximal strength potentially suggests an exercise-specific benefit yet to be fully elucidated.
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Neopreno , Treinamento Resistido , Humanos , Joelho , Masculino , Força Muscular , Músculo Esquelético , Levantamento de PesoRESUMO
Objective: Pyrroloquinoline quinone (PQQ) is a novel supplement involved in processes such as mitochondrial biogenesis and cellular energy metabolism. Since endurance exercise and PQQ exhibit similar mechanisms for mitochondrial biogenesis, it is plausible that PQQ may have ergogenic value. Therefore, the purpose of this study was to examine the effects of a six-week endurance exercise training program on mitochondrial biogenesis and aerobic performance in non-endurance-trained males.Methods: Twenty-three males were randomized to consume 20 mg/day of PQQ or placebo (PLC). Both groups followed a supervised six-week endurance exercise training program. Body composition was assessed by dual-energy-x-ray-absorptiometry (DEXA). Aerobic exercise performance and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a biochemical marker for mitochondrial biogenesis, were assessed before and after the six-week endurance training/supplementation program.Results: There were no significant differences between groups in aerobic performance after endurance-training (p > 0.05). However, there were significant improvements in peak oxygen consumption (VO2peak) and total exercise test duration after endurance-training, irrespective of group (p < 0.05). The PQQ group had a significant increase in PGC-1α protein levels from baseline to post endurance training compared to PLC (p < 0.05). Furthermore, the PQQ group had higher PGC-1α protein levels after 6 weeks of endurance training compared to PLC (p < 0.05).Conclusions: Supplementation of PQQ does not appear to elicit any ergogenic effects regarding aerobic performance or body composition but appears to impact mitochondrial biogenesis by way of significant elevations in PGC-1α protein content.
Assuntos
Exercício Físico , Biogênese de Organelas , Cofator PQQ , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/sangue , Suplementos Nutricionais , Treino Aeróbico , Humanos , Masculino , Mitocôndrias , Músculo Esquelético , Consumo de Oxigênio , Cofator PQQ/farmacologiaRESUMO
Machek, SB, Hwang, PS, Cardaci, TD, Wilburn, DT, Bagley, JR, Blake, DT, Galpin, AJ, and Willoughby, DS. Myosin heavy chain composition, creatine analogues, and the relationship of muscle creatine content and fast-twitch proportion to Wilks coefficient in powerlifters. J Strength Cond Res 34(11): 3022-3030, 2020-Little data exist on powerlifting-specific skeletal muscle adaptations, and none elucidate sex differences in powerlifters. Powerlifters tend to display higher fast-twitch fiber content and phosphagen system dependence. Nevertheless, it is unknown whether fast-twitch fiber or muscle creatine content are predictive of competitive powerlifting performance (via Wilks coefficient). Twelve actively competing powerlifters (PL; n = 6M/6F; age = 21.3 ± 1.0; 3.0 ± 1.8 year competing; 7.3 ± 6.6 meets attended) and 10 sedentary controls (CON; n = 5M/5F; age = 19.4 ± 2.0 year) underwent vastus lateralis muscle biopsies and venipuncture to compare the myosin heavy chain (MHC) fiber type and creatine analogue profiles between groups of both sexes, and determine whether MHC IIa and muscle total creatine (MTC) composition predict powerlifting performance. Samples were analyzed for specific MHC isoform (I, IIa, and IIx) content via mixed homogenate SDS-PAGE, and creatine analogues (MTC, muscle creatine transporter [SLC6A8], serum total creatine [STC], and serum creatinine [CRT]). Furthermore, MHC IIa and MTC content were compared with Wilks coefficient using Pearson correlation coefficients. Male PL MHC content was 50 ± 6% I, 45 ± 6% IIa, and 5 ± 11% IIx, versus 46 ± 6% I, 53 ± 6 IIa, and 0% IIx in female PL. Conversely, male CON MHC content was 33 ± 5% I, 38 ± 7% IIa, and 30 ± 8% IIx, vs. 35 ± 9% I, 44 ± 8% IIa, and 21 ± 17% IIx in female CON. Muscle total creatine, SLC6A8, STC, and CRT did not significantly differ between groups nor sexes. Finally, neither MHC IIa content (r = -0.288; p = 0.364) nor MTC (r = 0.488; p = 0.108) significantly predicted Wilks coefficient, suggesting these characteristics alone do not determine powerlifting skill variation.
Assuntos
Desempenho Atlético/fisiologia , Fibras Musculares de Contração Rápida/fisiologia , Cadeias Pesadas de Miosina/biossíntese , Músculo Quadríceps/fisiologia , Levantamento de Peso/fisiologia , Adolescente , Adulto , Creatina/sangue , Feminino , Humanos , Masculino , Fibras Musculares Esqueléticas/fisiologia , Cadeias Pesadas de Miosina/fisiologia , Proteínas do Tecido Nervoso/sangue , Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/sangue , Isoformas de Proteínas , Fatores Sexuais , Adulto JovemRESUMO
Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with or without carbohydrate supplementation. Muscle glycogen was assessed from biopsy specimens sampled from the vastus lateralis before supplementation, immediately after exercise, and 1hr post exercise under both conditions. There was no main effect of supplement on resistance exercise performance (p = 0.18). Muscle glycogen concentration decreased across time for both groups (p < 0.001). There was an interaction in serum glucose decreasing more during exercise in the carbohydrate condition (p = 0.026). An interaction occurred showing insulin decreased during exercise in the carbohydrate condition (p = 0.003). Also, there was a main effect of insulin being elevated with carbohydrate consumption (p = 0.027). Epinephrine was decreased across all time points after carbohydrate ingestion (p = 0.023). Carbohydrate supplementation before resistance exercise did not improve leg press performance to fatigue despite increased metabolic substrate availability. These results indicate that pre-exercise dietary carbohydrate will be utilized preferentially during exercise due to decreased epinephrine, decreased serum glucose, and increased insulin concentrations. However, the increases in glycolytic substrate availability will not increase exercise performance or glycogen content following 1hr of recovery.
Assuntos
Suplementos Nutricionais , Exercício Físico/fisiologia , Maltose/administração & dosagem , Polissacarídeos/administração & dosagem , Treinamento Resistido , Glicemia/metabolismo , Estudos Cross-Over , Método Duplo-Cego , Epinefrina/sangue , Glicogênio/metabolismo , Humanos , Insulina/sangue , Masculino , Músculo Esquelético/metabolismo , Adulto JovemRESUMO
BACKGROUND: Resistance exercise training (RET) is a common and well-established method to induce hypertrophy and improvement in strength. Interestingly, fish oil supplementation (FOS) may augment RET-induced adaptations. However, few studies have been conducted on young, healthy adults. METHODS: A randomized, placebo-controlled design was used to determine the effect of FOS, a concentrated source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), compared to placebo (PL) on RET-induced adaptations following a 10-week RET program (3 days·week-1). Body composition was measured by dual-energy x-ray absorptiometry (LBM, fat mass [FM], percent body fat [%BF]) and strength was measured by 1-repetition maximum barbell back squat (1RMSQT) and bench press (1RMBP) at PRE (week 0) and POST (10 weeks). Supplement compliance was assessed via self-report and bottle collection every two weeks and via fatty acid dried blood spot collection at PRE and POST. An a priori α-level of 0.05 was used to determine statistical significance and Cohen's d was used to quantify effect sizes (ES). RESULTS: Twenty-one of 28 male and female participants (FOS, n = 10 [4 withdrawals]; PL, n = 11 [3 withdrawals]) completed the 10-week progressive RET program and PRE/POST measurements. After 10-weeks, blood EPA+DHA substantially increased in the FOS group (+109.7%, p< .001) and did not change in the PL group (+1.3%, p = .938). Similar between-group changes in LBM (FOS: +3.4%, PL: +2.4%, p = .457), FM (FOS: -5.2%, PL: 0.0%, p = .092), and %BF (FOS: -5.9%, PL: -2.5%, p = .136) were observed, although, the between-group ES was considered large for FM (d = 0.84). Absolute and relative (kg·kg [body mass]-1) 1RMBP was significantly higher in the FOS group compared to PL (FOS: +17.7% vs. PL: +9.7%, p = .047; FOS: +17.6% vs. PL: +7.3%, p = .011; respectively), whereas absolute 1RMSQT was similar between conditions (FOS: +28.8% vs. PL: +20.5%, p = .191). Relative 1RMSQT was higher in the FOS group (FOS: +29.3% vs. PL: +17.9%, p = .045). CONCLUSIONS: When combined with RET, FOS improves absolute and relative 1RM upper-body and relative 1RM lower-body strength to a greater extent than that observed in the PL group of young, recreationally trained adults.
Assuntos
Óleos de Peixe , Treinamento Resistido , Feminino , Humanos , Masculino , Composição Corporal , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Força Muscular , Músculo Esquelético , Treinamento Resistido/métodosRESUMO
The purpose of this investigation was to compare the impacts of a potential blood flow restriction (BFR)-betaine synergy on one-leg press performance, lactate concentrations, and exercise-associated biomarkers. Eighteen recreationally trained males (25 ± 5 y) were randomized to supplement 6 g/day of either betaine anhydrous (BET) or cellulose placebo (PLA) for 14 days. Subsequently, subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs (BFR [LL-BFR; 20% 1RM at 80% arterial occlusion pressure] and high-load [HL; 70% 1RM]). Toe-tip lactate concentrations were sampled before (PRE), as well as immediately (POST0), 30 min (POST30M), and 3 h (POST3H) post-exercise. Serum homocysteine (HCY), growth hormone (GH) and insulin-like growth factor-1 concentrations were additionally assessed at PRE and POST30M. Analysis failed to detect any significant between-supplement differences for total repetitions completed. Baseline lactate changes (∆) were significantly elevated from POST0 to POST30 and from POST30 to POST3H (p < 0.05), whereby HL additionally demonstrated significantly higher ∆Lactate versus LL-BFR (p < 0.001) at POST3H. Although serum ∆GH was not significantly impacted by supplement or condition, serum ∆IGF-1 was significantly (p = 0.042) higher in BET versus PLA and serum ∆HCY was greater in HL relative to LL-BFR (p = 0.044). Although these data fail to support a BFR-betaine synergy, they otherwise support betaine's anabolic potential.
Assuntos
Treinamento Resistido , Humanos , Masculino , Betaína/metabolismo , Biomarcadores/metabolismo , Terapia de Restrição de Fluxo Sanguíneo , Expressão Gênica , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ácido Láctico/metabolismo , Músculo Esquelético/metabolismo , Fluxo Sanguíneo Regional , Adulto Jovem , AdultoRESUMO
Several previous investigations have employed betaine supplementation in randomized controlled crossover designs to assess its ostensible ergogenic potential. Nevertheless, prior methodology is predicated on limited pharmacokinetic data and an appropriate betaine-specific washout period is hitherto undescribed. The purpose of the present pilot investigation was therein to determine whether a 28 day washout period was sufficient to return serum betaine concentrations to baseline following a supplementation protocol. Five resistance-trained men (26 ± 6 y) supplemented with 6 g/day betaine anhydrous for 14 days and subsequently visited the lab 10 additional times during a 28 day washout period. Participants underwent venipuncture to assess serum betaine and several other parameters before (PRE) and periodically throughout the washout timeframe (POST0, -4, -7, -10, -13, -16, -19, -22, -25 and -28). All analyses were performed at a significance level of p < 0.05. While analyses failed to detect any differences in any other serum biomarker (p > 0.05), serum betaine was significantly elevated from PRE-to-POST0 (p = 0.047; 2.31 ± 1.05 to 11.1 ± 4.91 µg·mL−1) and was statistically indistinguishable from baseline at POST4 (p = 1.00). Nevertheless, visual data assessment and an inability to assess skeletal muscle concentrations would otherwise suggest that a more conservative 7 day washout period is sufficient to truly return both serum-and-skeletal muscle betaine content to pre-supplementation levels.
Assuntos
Betaína , Suplementos Nutricionais , Biomarcadores , Humanos , Masculino , Músculo Esquelético , Projetos PilotoRESUMO
Anabolic androgenic steroids (AAS) are testosterone and testosterone-derivative compounds sporadically employed by athletes and increasingly used recreationally to acquire a competitive edge or improve body composition. Nevertheless, users are subject to undesired side effects majorly associated with tissue-specific androgen receptor (AR) binding-mediated actions. More recently, selective AR modulators (SARMs) have gained popularity towards delivering androgen-associated anabolic actions with hopes of minimal androgenic effects. While several SARMs are in preclinical and clinical phases intended for demographics subject to hypogonadism, muscle wasting, and osteoporosis, several athletic organizations and drug testing affiliates have realized the increasingly widespread use of SARMs amongst competitors and have subsequently banned their use. Furthermore, recreational users are haphazardly acquiring these compounds from the internet and consuming doses several times greater than empirically reported. Unfortunately, online sources are rife with potential contamination, despite a prevailing public opinion suggesting SARMs are innocuous AAS alternatives. Considering each agent has a broad range of supporting evidence in both human and non-human models, it is important to comprehensively evaluate the current literature on commercially available SARMs to gain better understanding of their efficacy and if they can truly be considered a safer AAS alternative. Therefore, the purpose of this review is to discuss the current evidence regarding AAS and SARM mechanisms of action, demonstrate the efficacy of several prominent SARMs in a variety of scientific trials, and theorize on the wide-ranging contraindications and potential deleterious effects, as well as potential future directions regarding acute and chronic SARM use across a broad range of demographics.
Assuntos
Anabolizantes/farmacologia , Receptores Androgênicos/efeitos dos fármacos , Antagonistas de Androgênios/farmacologia , Animais , Humanos , Masculino , Receptores Androgênicos/química , Receptores Androgênicos/metabolismoRESUMO
Research has suggested that nutrient, exercise, and metabolism-related proteins interact to regulate mammalian target of rapamycin complex one (mTOR) post-exercise and their interactions needs clarification. In a double-blind, cross-over, repeated measures design, ten participants completed four sets to failure at 70% of 1-repitition maximum (1-RM) with 45 s rest on angled leg press with or without pre-exercise maltodextrin (2 g/kg) after a 3 h fast. Vastus lateralis biopsies were collected at baseline before supplementation and 1 h post-exercise to analyze Focal Adhesion Kinase (FAK), ribosomal protein S6 kinase beta-1 (p70S6K), insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), and 5' AMP-activated protein kinase (AMPK) activation. FAK and IRS-1 activity were only elevated 1 h post-exercise with carbohydrate ingestion (p < 0.05). PI3K and p70S6K activation were both elevated after exercise in both conditions (p < 0.05). However, AMPK activity did not change from baseline in both conditions (p > 0.05). We conclude that FAK does not induce mTOR activation through PI3K crosstalk in response to exercise alone. In addition, FAK may not be regulated by AMPK catalytic activity, but this needs further research. Interestingly, carbohydrate-induced insulin signaling appears to activate FAK at the level of IRS-1 but did not enhance mTOR activity 1 h post-exercise greater than the placebo condition. Future research should investigate these interactions under different conditions and within different time frames to clearly understand the interactions between these signaling molecules.
Assuntos
Carboidratos da Dieta/farmacologia , Ingestão de Alimentos/fisiologia , Exercício Físico/fisiologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Insulina/metabolismo , Mecanotransdução Celular/fisiologia , Nutrientes/farmacologia , Transdução de Sinais/fisiologia , Fenômenos Fisiológicos da Nutrição Esportiva/fisiologia , Adulto , Carboidratos da Dieta/administração & dosagem , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Masculino , Fosfatidilinositol 3-Quinase/metabolismo , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Serina-Treonina Quinases TOR , Adulto JovemRESUMO
The purpose of this study was (1) to determine the effect of single bouts of volume- and intensity-equated low- (LL) and high-load (HL) full-body resistance exercise (RE) on AR-DNA binding, serum/muscle testosterone and dihydrotestosterone, muscle androgen receptor (AR), and AR-DNA binding; and, (2) to determine the effect of RE on sarcoplasmic and nucleoplasmic ß-catenin concentrations in order to determine their impact on mediating AR-DNA binding in the absence/presence of serum/muscle androgen and AR protein. In a cross-over design, 10 resistance-trained males completed volume- and intensity-equated LL and HL full-body RE. Blood and muscle samples were collected at pre-, 3 h-, and 24 h post-exercise. Separate 2 × 3 factorial analyses of variance (ANOVAs) with repeated measures and pairwise comparisons with a Bonferroni adjustment were used to analyze the main effects. No significant differences were observed in muscle AR, testosterone, dihydrotestosterone, or serum total testosterone in either condition (p > 0.05). Serum-free testosterone was significantly decreased 3 h post-exercise and remained significantly less than baseline 24 h post-exercise in both conditions (p < 0.05). In response to HL, AR-DNA binding significantly increased at 3 h post-exercise (p < 0.05), whereas no significant differences were observed at any time in response to LL (p > 0.05). Moreover, sarcoplasmic ß-catenin was significantly greater in HL (p < 0.05) without significant changes in nucleoplasmic ß-catenin (p > 0.05). In conclusion, increases in AR-DNA binding in response to HL RE indicate AR signaling may be load-dependent. Furthermore, despite the lack of increase in serum and muscle androgens or AR content following HL RE, elevations in AR-DNA binding with elevated sarcoplasmic ß-catenin suggests ß-catenin may be facilitating this response.