Search

Human skeletal muscle fiber type composition varies greatly along the muscle, so one biopsy may not accurately represent the whole muscle. Recommendations on the number of biopsies and fiber counts using immunohistochemistry and whether these findings can be extrapolated to other muscles are lacking. We assessed fiber type composition in the vastus lateralis and gastrocnemius medialis muscles of 40 individuals. Per muscle, we took four biopsy samples from one incision, collecting two samples each from a proximally and distally directed needle. Based on another dataset involving 10 vastus lateralis biopsies per participant ( n = 7), we calculated 95% limits of agreement for subsets of biopsies and fiber counts compared with the 10-biopsy average. Average absolute differences in type I fiber proportions between proximal and distal, and between within-needle samples were 6.9 and 4.5 percentage points in the vastus lateralis, and 5.5 and 4.4 percentage points in the gastrocnemius medialis, respectively. The 95% limits of agreement narrowed to ±10 percentage points when 200 fibers from at least three biopsies were analyzed, with minimal improvements with greater fiber counts. Type I fiber proportions in the vastus lateralis and gastrocnemius medialis showed a moderate positive association ( r 2 = 0.22; P = 0.006; at least 200 fibers in each of three to four samples per muscle). In conclusion, three biopsies with a minimum of 200 counted fibers are required to estimate the vastus lateralis fiber type composition within ±10 percentage points. Even when using these standards, researchers should be cautious when extrapolating muscle fiber type proportions from one muscle to another. NEW & NOTEWORTHY Fiber type composition is equally variable in muscle biopsy samples taken from one incision as from multiple incisions. Hence, we propose two biopsies from a single incision-needles directed proximally and distally, and each rotated 180° for cutting a second sample-as a more feasible, less invasive alternative to three biopsies from as many incisions. In addition, we identified the gastrocnemius medialis as a slow-twitch muscle with an average of 64.7% slow fibers.

The heterogeneous fiber type composition of skeletal muscle makes it challenging to decipher the molecular signaling events driving the health- and performance benefits of exercise. We developed an optimized workflow for transcriptional profiling of individual human muscle fibers before, immediately after, and after 3 h of recovery from high-intensity interval cycling exercise. From a transcriptional point-of-view, we observe that there is no dichotomy in fiber activation, which could refer to a fiber being recruited or nonrecruited. Rather, the activation pattern displays a continuum with a more uniform response within fast versus slow fibers during the recovery from exercise. The transcriptome-wide response immediately after exercise is characterized by some distinct signatures for slow versus fast fibers, although the most exercise-responsive genes are common between the two fiber types. The temporal transcriptional waves further converge the gene signatures of both fiber types toward a more similar profile during the recovery from exercise. Furthermore, a large heterogeneity among all resting and exercised fibers was observed, with the principal drivers being independent of a slow/fast typology. This profound heterogeneity extends to distinct exercise responses of fibers beyond a classification based on myosin heavy chains. Collectively, our single-fiber methodological approach points to a substantial between-fiber diversity in muscle fiber responses to high-intensity interval exercise. NEW & NOTEWORTHY By development of a single-fiber transcriptomics technology, we assessed the transcriptional events in individual human skeletal muscle fibers upon high-intensity exercise. We demonstrate a large variability in transcriptional activation of fibers, with shared and distinct gene signatures for slow and fast fibers. The heterogeneous fiber-specific exercise response extends beyond this traditional slow/fast categorization. These findings expand on our understanding of exercise responses and uncover a profound between-fiber diversity in muscle fiber activation and transcriptional perturbations.

Background: COPD is a disease characterised by skeletal muscle dysfunction. A spatial relationship exists between satellite cells and muscle fibre capillaries, which has been suggested to be of major importance for satellite cell function. In the present study we compared the spatial relationship between satellite cells and capillaries in patients with COPD and age-matched healthy older adults., Methods: Muscle biopsies were obtained from the vastus lateralis of n=18 patients with COPD (8 female, 10 male; age 66±5 years, mild-to-severe airflow obstruction) and n=18 age-, sex- and body mass index-matched healthy control adults (8 female, 10 male; age 68±5 years). Immunohistochemistry was used to assess type I/II muscle fibre size, distribution, myonuclear content, satellite cell number and fibre capillarisation. In addition, type I/II muscle fibre satellite cell distance to its nearest capillary was assessed., Results: The percentage of type II muscle fibres was significantly greater in patients with COPD (62±10%) compared with controls (50±12%, p<0.05). Muscle fibre capillarisation was significantly lower in patients with COPD compared with controls (p<0.05). While satellite cell content was not different between groups, type I and type II satellite cell distance to its nearest capillary was significantly greater in patients with COPD (type I: 21.3±4.8 µm; type II: 26.7±9.3 µm) compared with controls (type I: 16.1±3.5 µm; type II: 22.7±5.8 µm; p<0.05)., Conclusion: Satellite cells are located at a greater distance from their nearest capillary in patients with COPD compared with age-matched controls. This increased distance could play a role in impaired satellite cell function in patients with COPD., Competing Interests: Conflict of interest: All authors report no conflict of interest., (Copyright ©The authors 2024.)

Purpose: Apnea duration is dependent on three factors: oxygen storage, oxygen consumption, hypoxia and hypercapnia tolerance. While current literature focuses on maximal apneas to improve apnea duration, apnea trained individuals use timed-repeated submaximal apneas, called "O 2 and CO 2 tables". These tables claim to accommodate the body to cope with hypoxia and hypercapnia, respectively. The aim of this study was twofold. First, to investigate the determinants of maximal apnea duration in apnea novices. Second, to compare physiologic responses to maximal apneas, O 2 and CO 2 tables., Methods: After medical screening, lung function test and hemoglobin mass measurement, twenty-eight apnea novices performed three apnea protocols in random order: maximal apneas, O 2 table and CO 2 table. During apnea, peripheral oxygen saturation (SpO 2 ), heart rate (HR), muscle (mTOI) and cerebral (cTOI) tissue oxygenation index were measured continuously. End-tidal carbon dioxide (EtCO 2 ) was measured before and after apneas., Results: Larger lung volumes, higher resting cTOI and lower resting EtCO 2 levels correlated with longer apnea durations. Maximal apneas induced greater decreases in SpO 2 (- 16%) and cTOI (- 13%) than O 2 (- 8%; - 8%) and CO 2 tables (- 6%; - 6%), whereas changes in EtCO 2 , HR and mTOI did not differ between protocols., Conclusion: These results suggest that, in apnea novices, O 2 and CO 2 tables did not induce a more profound hypoxia and hypercapnia, but a similar reduction in oxygen consumption than maximal apneas. Therefore, apnea novices should mainly focus on maximal apneas to improve hypoxia and hypercapnia tolerance. The use of specific lung training protocols can help to increase oxygen storage capacity., Competing Interests: Declarations Competing interests The authors declare that they have no competing interest. Consent to participate A written informed consent was obtained from all individual participants included in the study. Consent to publish Not applicable. Ethics approval “All procedures performed in studies involving human participants were in accordance with the ethical standards of the ethical committee of the Ghent University Hospital (EC UZG 2018/0221) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To gather information on practices and perceptions of high-performance experts regarding their athletes' muscle fiber-type composition (MFTC) and its estimation., Methods: A questionnaire on the noninvasive versus invasive estimation of MFTC was completed by 446 experts including coaches and sport-science/sports-medicine staff. Moreover, the perceived importance of MFTC for training and performance optimization was assessed. Differences between sport types (individual and team sports) were analyzed using chi-square tests., Results: Forty percent of the experts implemented MFTC assessment in pursuit of performance optimization, while 50% did not know their athletes' MFTC but expressed a desire to implement it if they would be able to assess MFTC. Ten percent did not perceive value in MFTC assessment. Only 18% of experts believed that their athletes would undergo a muscle biopsy, leading to the adoption of alternative noninvasive techniques. Experts primarily relied on their experience to estimate MFTC (65%), with experts working in individual sports using their experience more frequently than those working in team sports (68% vs 51%; P = .009). Jump tests emerged as the second-most commonly employed method for estimating MFTC (56%). When only considering experts who are currently using MFTC, 87% use MFTC to individualize training volume and 84% to individualize training intensity., Conclusions: Experts value MFTC assessment primarily to individualize training but mainly rely on noninvasive methods to estimate MFTC. Some of these methods lack scientific validity, suggesting a continuing need for education and further research in this area.

Carnosine, an MR-visible dipeptide in human muscle, is well characterized by two peaks at ~8 and ~7 ppm from C2 and C4 imidazole protons. Like creatine and other metabolites, carnosine is subject to residual dipolar coupling in the anisotropic environment of muscle fibers, but the effects have not been studied extensively. Single-voxel TE 30-32 PRESS spectra from three different 3T studies were acquired from gastrocnemius medialis and soleus muscles in the human lower leg. In these studies, carnosine T 2 values were measured, and spectra were obtained at three different foot angles. LCModel was used to fit the carnosine peaks with a basis set that was generated using shaped RF pulses and included a range of dipolar couplings affecting the C4 peak. A seven-parameter analytic expression was used to fit the CH 2 doublets of creatine. It incorporated an optimized "effective TE" value to model the effect of shaped RF pulses. The fits confirm that the triplet C4 peak of carnosine is dipolar coupled to a pair of CH 2 protons, with no need to include a contribution from a separate pool of freely rotating uncoupled carnosine. Moreover, the couplings experienced by carnosine C4 protons and creatine CH 2 protons are strongly correlated (R 2  =  0.88, P<0.001), exhibiting a similar 3cos 2 θ - 1 dependence on the angle θ between fiber orientation and B0. T 2 values for the singlet C2 peak of gastrocnemius carnosine are inversely proportional to the C4 dipolar coupling strength (R 2  = 0.97, P < 0.001), which in turn is a function of foot orientation. This dependence indicates that careful positioning of the foot while acquiring lower leg muscle spectra is important to obtain reproducible carnosine concentrations. As proton magnetic resonance spectroscopy of carnosine is currently used to non-invasively estimate the muscle fiber typology, these results have important implications in sport science., (© 2024 John Wiley & Sons, Ltd.)

Purpose: To examine the association between muscle fiber typology and match running performance in professional Australian football (AF) athletes., Methods: An observational time-motion analysis was performed on 23 professional AF athletes during 224 games throughout the 2020 competitive season. Athletes were categorized by position as hybrid, small, or tall. Athlete running performance was measured using Global Navigation Satellite System devices. Mean total match running performance and maximal mean intensity values were calculated for moving mean durations between 1 and 10 minutes for speed (in meters per minute), high-speed-running distance (HSR, >4.17 m·s-1), and acceleration (in meters per second squared), while intercept and slopes were calculated using power law. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate z score (CAZ score) to estimate muscle fiber typology. Mixed linear models were used to determine the association between CAZ score and running performance., Results: The mean (range) CAZ score was -0.60 (-1.89 to 1.25), indicating that most athletes possessed a greater estimated proportion of type I muscle fibers. A greater estimated proportion of type I fibers (ie, lower CAZ score) was associated with a larger accumulation of HSR (>4.17 m·s-1) and an increased ability to maintain HSR as the peak period duration increased., Conclusion: AF athletes with a greater estimated proportion of type I muscle fibers were associated with a greater capacity to accumulate distance running at high speeds, as well as a greater capacity to maintain higher output of HSR running during peak periods as duration increases.

Aim: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear., Methods: Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively)., Results: Our data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion., Conclusion: Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease., (© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Background: Beta-alanine (BA) supplementation increases muscle carnosine, an abundant endogenous antioxidant and pH buffer in skeletal muscle. Carnosine loading promotes exercise capacity in healthy older adults. As patients with chronic obstructive pulmonary disease (COPD) suffer from elevated exercise-induced muscle oxidative/carbonyl stress and acidosis, and from reduced muscle carnosine stores, it was investigated whether BA supplementation augments muscle carnosine and induces beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress in patients with COPD., Methods: In this double-blind, randomized, placebo (PL)-controlled trial (clinicaltrials.gov identifier: NCT02770417), 40 patients (75% male) with COPD (mean ± standard deviation: age 65 ± 6 years; FEV 1 % predicted 55 ± 14%) were assigned to 12 weeks oral BA or PL supplementation (3.2 g/day). The primary outcome, i.e. muscle carnosine, was quantified from m. vastus lateralis biopsies obtained before and after intervention. Co-primary outcomes, i.e. incremental and constant work rate cycle capacity, were also assessed. Linear mixed model analyses were performed. Compliance with and side effects of supplement intake and secondary outcomes (quadriceps strength and endurance, and muscle oxidative/carbonyl stress) were also assessed., Results: Beta-alanine supplementation increased muscle carnosine in comparison with PL in patients with COPD (mean difference [95% confidence interval]; +2.82 [1.49-4.14] mmol/kg wet weight; P < 0.001). Maximal incremental cycling capacity (VO 2 peak: +0.5 [-0.7 to 1.7] mL/kg/min; P = 0.384, Wpeak: +5 [-1 to 11] W; P = 0.103) and time to exhaustion on the constant work rate cycle test (+28 [-179 to 236] s; P = 0.782) did not change significantly. Compliance with supplement intake was similar in BA (median (quartile 1-quartile 3); 100 (98-100)%) and PL (98 (96-100)%) (P = 0.294) groups, and patients did not report side effects possibly related to supplement intake. No change was observed in secondary outcomes., Conclusions: Beta-alanine supplementation is efficacious in augmenting muscle carnosine (+54% from mean baseline value) without side effects in patients with COPD in comparison with PL. However, accompanied beneficial changes in exercise capacity, quadriceps function, and muscle oxidative/carbonyl stress were not observed., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Purpose: To examine whether the muscle typology of elite and world-class swimmers could discriminate between their best distance event, swimming stroke style, or performance level., Methodology: The muscle carnosine content of 43 male (860 [76] FINA [Fédération Internationale de Natation] points) and 30 female (881 [63] FINA points) swimmers was measured in the soleus and gastrocnemius by proton magnetic resonance spectroscopy and expressed as a carnosine aggregate Z score (CAZ score) to estimate muscle typology. A higher CAZ score is associated with a higher estimated proportion of type II fibers. Swimmers were categorized by their best stroke, distance category (sprinters, 50-100 m; middle distance, 200-400 m; or long distance, 800 m-open water), and performance level (world-class, world top 10, or elite and world top 100 swimmers outside of the world top 10)., Results: There was no significant difference in the CAZ score of sprint- (-0.08 [0.55]), middle- (-0.17 [0.70]), or long-distance swimmers (-0.30 [0.75], P = .693). World-class sprint swimmers (all strokes included) had a significantly higher CAZ score (0.37 [0.70]) when compared to elite sprint swimmers (-0.25 [0.61], P = .024, d = 0.94). Breaststroke swimmers (0.69 [0.73]) had a significantly higher CAZ score compared to freestyle (-0.24 [0.54], P < .001, d = 1.46), backstroke (-0.16 [0.47], P = .006, d = 1.42), and butterfly swimmers (-0.39 [0.53], P < .001, d = 1.70). Furthermore, within the cohort of breaststroke swimmers, there was a significant positive correlation between FINA points and CAZ score (r = .728, P = .011); however, this association was not evident in other strokes., Conclusion: While there was no clear association between muscle typology and event distance specialization, world-class sprint swimmers possess a greater estimated proportion of type II fibers compared to elite sprint swimmers, as well as breaststroke swimmers compared to freestyle, backstroke, and butterfly swimmers.

Background: Recent studies suggest that acute-combined carnosine and anserine supplementation has the potential to improve the performance of certain cycling protocols. Yet, data on optimal dose, timing of ingestion, effective exercise range, and mode of action are lacking. Three studies were conducted to establish dosing and timing guidelines concerning carnosine and anserine intake and to unravel the mechanism underlying the ergogenic effects., Methods: First, a dose response study A was conducted in which 11 men randomly received placebo, 10, 20, or 30 mg.kg -1 of both carnosine and anserine. They performed 3x maximal voluntary isometric contractions (MVC), followed by a 5 x 6 s repeated cycling sprint ability test (RSA), once before the supplement and 30 and 60 minutes after. In a second study, 15 men performed 3x MVCs with femoral nerve electrical stimulation, followed by an RSA test, once before 30 mg.kg -1 carnosine and anserine and 60 minutes after. Finally, in study C, eight men performed a high intensity cycling training after randomly ingesting 30 mg.kg -1 of carnosine and anserine, a placebo or antihistamines (reduce post-exercise blood flow) to investigate effects on muscle perfusion., Results: Study A showed a 3% peak power (p = 0.0005; 95% CI = 0.07 to 0.27; ES = 0.91) and 4.5% peak torque (p = 0.0006; 95% CI = 0.12 to 0.50; ES = 0.87) improvement on RSA and MVC, with 30 mg.kg -1 carnosine + anserine ingestion 60 minutes before the performance yielding the best results. Study B found no performance improvement on group level; however, a negative correlation (r = -0.54; p = 0.0053; 95% CI = -0.77 to -0.19) was found between carnosinase enzyme activity (responsible for carnosine and anserine breakdown) and performance improvement. No effect of the supplement on neuromuscular function nor on muscle perfusion was found., Conclusions: These studies reveal that acute ingestion of 30 mg.kg -1 of both carnosine and anserine, 60 minutes before a high intensity exercise, can potentially improve performance, such as short cycling sprints or maximal muscle contractions. Subjects with lower carnosinase activity, and thus a slower breakdown of circulating dipeptides, appear to benefit more from this ergogenic effect. Finally, neither the involvement of a direct effect on neuromuscular function, nor an indirect effect on recovery through increased muscle perfusion could be confirmed as potential mechanism of action. The ergogenic mechanism therefore remains elusive., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Purpose: We aimed to identify the underpinning physiological and speed/mechanical determinants of different types of 800-m running time trials (i.e., with a positive or negative pacing strategy) and key components within each 800-m time trial (i.e., first and final 200 m)., Methods: Twenty trained male 800-m runners (800-m personal best time (min:s): 1:55.10 ± 0:04.44) completed a maximal 800-m time trial (800MAX) and one pacing trial, whereby runners were paced for the first lap, and speed was reduced by 7.5% (800PACE) relative to 800MAX, whereas the last lap was completed in the fastest time possible. Anaerobic speed reserve, running economy, the velocity corresponding with V˙O2peak (VV˙O2peak), maximal sprint speed (MAXSS), maximal accumulated oxygen deficit, and sprint force-velocity-power profiles were derived from laboratory and field testing. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and expressed as a carnosine aggregate Z (CAZ) score to estimate muscle typology. Data were analyzed using multiple stepwise regression analysis., Results: MAXSS and vV˙O2peak largely explained the variation in 800MAX time (r2 = 0.570; P = 0.020), whereas MAXSS was the best explanatory variable for the first 200-m time in 800MAX (adjusted r2 = 0.661, P < 0.001). Runners with a higher CAZ score (i.e., higher estimated percentage of type II fibers) reduced their last lap time to a greater extent in 800PACE relative to 800MAX (adjusted r2 = 0.413, P < 0.001), whereas better maintenance of mechanical effectiveness during sprinting, a higher CAZ score and vV˙O2peak was associated with a faster final 200-m time during 800PACE (adjusted r2 = 0.761, P = 0.001)., Conclusions: These findings highlight that diversity in the physiological and speed/mechanical characteristics of male middle-distance runners may be associated with their suitability for different 800-m racing strategies to have the best chance of winning., (Copyright © 2021 by the American College of Sports Medicine.)

Purpose: To determine the influence of muscle fiber typology (MFT) on the pacing strategy of elite swimmers competing in the 200-m freestyle event., Method: The top 3 career-best performances from 25 elite 200-m freestyle swimmers were analyzed-12 women (1:58.0 [0:01.3] min:s) and 13 men (1:48.4 [0:02.5]). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus muscles and expressed as a carnosine aggregate z score (CAZ score) relative to an age- and gender-matched nonathlete control group to estimate MFT. Linear regression models were employed to examine the influence of MFT on the percentage of overall race time spent in each 50-m lap., Results: Swimmers with a higher CAZ score spent a greater percentage of race time in lap 3 compared with swimmers with a lower CAZ score (0.1%, 0.0% to 0.2%; mean, 90% confidence interval, P = .02). For every 1% increase in the percentage of race time spent in lap 1, the percentage of race time spent in lap 3 decreased by 0.4% for swimmers with a higher CAZ score (0.2% to -0.5%, P = .00, r = -.51), but not for swimmers with a lower CAZ score (-0.1%, -0.3% to 0.1%, P = .28, r = -.18). The percentage of race time spent in lap 4 decreased by 0.8% for higher-CAZ-score swimmers (-0.5% to -1.0%, P = .00, r = -.66) and by 0.9% for lower-CAZ-score swimmers (-0.6% to -1.3%, P = .00, r = -.65) when lap 1 percentage increased by 1%., Conclusion: MFT may influence the pacing strategy of swimmers in the 200-m freestyle event, which provides an avenue for maximizing individualized pacing strategies of elite swimmers.

Due to the invasiveness of a muscle biopsy, there is fragmentary information on the existence and possible origin of a sexual dimorphism in the skeletal muscle concentrations of the energy delivery-related metabolites carnosine, creatine, and carnitine. As these metabolites can be noninvasively monitored by proton magnetic resonance spectroscopy, this technique offers the possibility to investigate if sexual dimorphisms are present in an adult reference population and if these dimorphisms originated during puberty using a longitudinal design. Concentrations of carnosine, creatine, and carnitine were examined using proton magnetic resonance spectroscopy in the soleus and gastrocnemius muscles of an adult reference population of female ( n = 50) and male adults ( n = 50). For the longitudinal follow-up over puberty, 29 boys and 28 girls were scanned prepuberty. Six years later, 24 boys and 24 girls were rescanned postpuberty. A sexual dimorphism was present in carnosine and creatine, but not carnitine, in the adult reference population. Carnosine was 28.5% higher in the gastrocnemius ( P < 0.001) and carnosine and creatine were respectively 19.9% ( P < 0.001) and 18.2% ( P < 0.001) higher in the soleus of male when compared with female adults. Through puberty, carnosine increased more in male subjects compared with female subjects, both in the gastrocnemius (+10.43% and -10.83%, respectively; interaction effect: P = 0.002) and in the soleus (+24.30% and +5.49%, respectively; interaction effect: P = 0.012). No significant effect of puberty was found in either creatine (interaction effect: P = 0.307) or carnitine (interaction effect: P = 0.066). A sexual dimorphism in the adult human muscle is present in carnosine and creatine, but not in carnitine. NEW & NOTEWORTHY This is the first study to investigate sexual dimorphisms in skeletal muscle carnosine, creatine, and carnitine concentrations in a substantial adult reference population ( n = 100). A sexual dimorphism is present in both carnosine and creatine at adult age. The origin of the sexual dimorphisms is investigated using a longitudinal design over puberty in 24 males and 24 females. The sexual dimorphism in carnosine originated partly during puberty for carnosine, but not for creatine.

Chronic low-grade systemic inflammation is frequently observed in patients with chronic obstructive pulmonary disease (COPD), e.g., elevated pentameric CRP (pCRP). However, pCRP can dissociate to form monomeric CRP (mCRP) which exhibits a clear pro-inflammatory behaviour in contrast to the more anti-inflammatory properties of pCRP. Therefore, mCRP may be an informative biomarker to demonstrate chronic low-grade systemic inflammation. This was confirmed by analysing serum samples from 38 patients with COPD and 18 non-COPD control persons (NCCP). mCRP was significantly elevated in patients with COPD vs. NCCP, indicating that mCRP might be considered as a new sensitive marker of chronic low-grade systemic inflammation., Competing Interests: Ms Revathy Munuswamy and Prof. Dr. Luc Michiels report a patent EP20212664 pending to Luc Michiels, UHasselt. The authors report no other conflicts of interest in this work., (© 2021 Munuswamy et al.)

During the first half of the 20th century, extraordinary high jumping performances of East-African athletes were observed. These athletes used a specific native jumping style called Gusimbuka Urukiramende. Eye-witnesses believed that these performances could have been world-records and that these athletes could have competed at the Olympics. However, these athletes never participated in international competitions and there is no other proof to support these performance claims. We have analysed historical photos and cine sequences of these jumps, documented the movement analysis of this technique, quantified performance and compared it to contemporaneous elite performances. Our analyses demonstrate that Gusimbuka Urukiramende athletes did not jump as high as the world record. Nevertheless, even though they used a suboptimal jump technique (because they had to lift their bodies higher to cross the bar) they could cross bar heights of 188 cm or 106% body height and as such their performance still was worthy of participation to the Olympics.

Purpose: To determine the association between estimated muscle fiber typology and the start and turn phases of elite swimmers during competition., Methods: International and national competition racing performance was analyzed from 21 female (FINA points = 894 ± 39: 104.5 ± 1.8% world record ratio [WRR]) and 25 male (FINA points = 885 ± 54: 104.8 ± 2.1% WRR) elite swimmers. The start, turn, and turn out times were determined from each of the swimmers' career best performance times (FINA points = 889 ± 48: 104.7 ± 2.0% WRR). Muscle carnosine concentration was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and soleus and was expressed as a carnosine aggregate z score relative to an age- and gender-matched nonathlete control group to estimate muscle fiber typology. Linear mixed models were employed to determine the association between muscle fiber typology and the start and turn times., Results: While there was no significant influence of carnosine aggregate z score on the start and turn times when all strokes and distance events were entered into the model, the swimmers with a higher carnosine aggregate z score (ie, faster muscle typology) had a significantly faster start time in 100-m events compared with the swimmers with a lower carnosine aggregate z score (P = .02, F = 5.825). The start and turn times were significantly faster in the male compared with the female swimmers in the 100-m events compared with other distances, and between the 4 different swimming strokes (P < .001)., Conclusion: This study suggests that start times in sprint events are partly determined (and limited) by muscle fiber typology, which is highly relevant when ∼12% of the overall performance time is determined from the start time.

Exercise training is a powerful strategy to prevent and combat cardiovascular and metabolic diseases, although the integrative nature of the training-induced adaptations is not completely understood. We show that chronic blockade of histamine H 1 /H 2 receptors led to marked impairments of microvascular and mitochondrial adaptations to interval training in humans. Consequently, functional adaptations in exercise capacity, whole-body glycemic control, and vascular function were blunted. Furthermore, the sustained elevation of muscle perfusion after acute interval exercise was severely reduced when H 1 /H 2 receptors were pharmaceutically blocked. Our work suggests that histamine H 1 /H 2 receptors are important transducers of the integrative exercise training response in humans, potentially related to regulation of optimal post-exercise muscle perfusion. These findings add to our understanding of how skeletal muscle and the cardiovascular system adapt to exercise training, knowledge that will help us further unravel and develop the exercise-is-medicine concept., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objectives: Recreational runners show a large interindividual variation in spatiotemporal characteristics. This research focused on slow runners and intended: (1) to document the variance in duty factor (DF) between runners in a real-life running setting and (2) examine whether the interindividual variation in DF and stride frequency (SF) relates to differences in external loading parameters between runners., Methods: Spatiotemporal characteristics of 23 slow runners (ie, <2.6 m/s) were determined during a 5.2 km running event. To relate the interindividual variation in DF and SF to differences in external forces between runners (maximal vertical ground reaction force (FzMax), peak braking force (PBF) and vertical instantaneous loading rate (VILR)), 14 of them were invited to the lab. They ran at 1.9 m/s on a treadmill while ground reaction forces were recorded. A multiple linear regression analysis was conducted to investigate the effect of DF and SF on external force measures., Results: DF between slow runners varied from 42.50% to 56.49% in a recreational running event. DF was found to be a significant predictor of FzMax (R²=0.755) and PBF (R²=0.430). SF only improved the model for PBF, but to a smaller extent than DF (R² change=0.191). For VILR, neither DF nor SF were significant predictors., Conclusion: External forces are lower in recreational runners that run with higher DFs and slightly lower SFs. These findings may be important for injury prevention purposes, especially directed to recreational runners that are more prone to overuse injuries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: chicken meat extract is a popular functional food in Asia. It is rich in the bioactive compounds carnosine and anserine, two histidine-containing dipeptides (HCD). Studies suggest that acute pre-exercise ingestion of chicken extracts has important applications towards exercise performance and fatigue control, but the evidence is equivocal. This study aimed to evaluate the ergogenic potential of the pre-exercise ingestion of a homemade chicken broth (CB) vs a placebo soup on a short-lasting, high-intensity cycling exercise., Methods: fourteen men participated in this double-blind, placebo-controlled, crossover intervention study. Subjects ingested either CB, thereby receiving 46.4 mg/kg body weight of HCD, or a placebo soup (similar in taste without HCD) 40 min before an 8 min cycling time trial (TT) was performed. Venous blood samples were collected at arrival (fasted), before exercise and at 5 min recovery. Plasma HCD were measured with UPLC-MS/MS and glutathione (in red blood cells) was measured through HPLC. Capillary blood samples were collected at different timepoints before and after exercise., Results: a significant improvement (p = 0.033; 5.2%) of the 8 min TT mean power was observed after CB supplementation compared to placebo. Post-exercise plasma carnosine (p <  0.05) and anserine (p <  0.001) was significantly increased after CB supplementation and not following placebo. No significant effect of CB supplementation was observed either on blood glutathione levels, nor on capillary blood analysis., Conclusions: oral CB supplementation improved the 8 min TT performance albeit it did not affect the acid-base balance or oxidative status parameters. Further research should unravel the potential role and mechanisms of HCD, present in CB, in this ergogenic approach.

Purpose: The present study identified the physiological and performance characteristics that are deterministic during a maximal 1500-m time trial and in paced 1500-m time trials, with an all-out last lap., Methods: Thirty-two trained middle-distance runners (n = 21 male, VO 2peak : 72.1 ± 3.2; n = 11, female, VO 2peak : 61.2 ± 3.7 mL kg -1 min -1 ) completed a 1500-m time trial in the fastest time possible (1500 FAST ) as well as a 1500 MOD and 1500 SLOW trial whereby mean speed was reduced during the 0-1100 m by 5% and 10%, respectively. Anaerobic speed reserve (ASR), running economy (RE), the velocity corresponding with VO 2peak ( V VO 2peak ), maximal sprint speed (MSS) and maximal accumulated oxygen deficit (MAOD) were determined during additional testing. Carnosine content was quantified by proton magnetic resonance spectroscopy in the gastrocnemius and expressed as a Z-score to estimate muscle fibre typology., Results: 1500 FAST time was best explained by RE and V VO 2peak in female runners (adjusted r 2  = 0.80, P < 0.001), in addition to the 0-1100-m speed relative to V VO 2peak in male runners (adjusted r 2  = 0.72, P < 0.001). Runners with a higher gastrocnemius carnosine Z-score (i.e., higher estimated percentage of type II fibres) and greater MAOD, reduced their last lap time to a greater extent in the paced 1500-m trials. Neither ASR nor MSS was associated with last lap time in the paced trials., Conclusion: These findings suggest that V VO 2 peak and RE are key determinants of 1500-m running performance with a sustained pace from the start, while a higher carnosine Z-score and MAOD are more important for last lap speed in tactical 1500-m races.

The aim of this study was to identify markers of training stress and characteristics of middle-distance runners related to the incidence of overreaching following overload training. Twenty-four highly trained middle-distance runners [ n = 16 male, peak oxygen uptake (V̇o 2peak ) = 73.3 (4.3) mL·kg·min -1 ; n = 8 female, V̇o 2peak  = 63.2 (3.4) mL·kg·min -1 ] completed 3 wk of normal training (NormTr), 3 wk of high-volume training (HVTr; a 10%, 20%, and 30% increase in training volume each successive week from NormTr), and 1 wk of taper (TapTr; 55% exponential reduction in training volume from HVTr week 3 ). Before and immediately after each training period, an incremental treadmill-running test was performed, while resting metabolic rate (RMR), subjective fatigue responses, and various resting blood biomarkers were assessed. Muscle fiber typology of the gastrocnemius was estimated by quantification of muscle carnosine using proton magnetic resonance spectroscopy and expressed as a z -score relative to a nonathlete control group. Twelve runners were classified as functionally overreached (FOR) following HVTr [decreased running time to exhaustion (TTE)], whereas the other 12 were classified as acutely fatigued (AF; no decrease in running TTE). The FOR group did not demonstrate systematic alterations in RMR, resting blood biomarkers, or submaximal exercise responses, compared with the AF group. The gastrocnemius carnosine z -score was significantly higher in the FOR group (-0.44 ± 0.57) than in the AF group (-1.25 ± 0.49, P = 0.004, d  = 1.53) and was also negatively correlated with changes in running TTE from pre- to post-HVTr ( r  = -0.55, P = 0.005) and from pre-HVTr to post-TapTr ( r  = -0.64, P = 0.008). Muscle fiber typology is related to the incidence of overreaching and performance supercompensation following increased training volume and a taper. NEW & NOTEWORTHY Variability in the performance responses following an overload training period and subsequent taper was associated with the variation in the muscle fiber typology of the gastrocnemius. Runners with an estimated higher proportion of type I fibers (i.e., lower carnosine z -score) were able to maintain performance in response to an overload training period and subsequently achieve a superior performance supercompensation. These findings show that muscle fiber typology contributes to the variability in performance responses following training.

Introduction: Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD., Methods and Analysis: Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured., Ethics and Dissemination: Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19)., Trial Registration Number: NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC)., Competing Interests: Competing interests: FMEF reports research grants from AstraZeneca and Novartis, not related to the current projects, and personal fees for consultancies and lectures from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and TEVA. EBdV reports personal fees for consultancies and lectures from Boehringer Ingelheim, Chiesi, Mylan, Novartis, Vivisol and TEVA, not related to the current projects. FNS reports speakers fees from AstraZeneca, Chiesi, Menarini, Mundipharma and Novartis; reports consultancy fees from GSK; and reports service on an advisory board for AstraZeneca, Chiesi, GSK and Novartis, all outside the submitted work. MH reports research grants from Bastide Medical, not related to the current project; personal fees from AstraZeneca for participation to scientific lectures; financial support for congress participation from SOS Oxygène, Eole Santé, Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca; and hospitalities during local scientific meetings from ALK-Abelló, Actelion Pharmaceuticals France, Vifor Fresenius Medical Care Renal Pharma, Sanofi Aventis France, Novartis Pharma, LVL Medical Sud, Chiesi, SOS Oxygene Mediterranee. MAS reports a research grant from Netherlands Lung Foundation (grant number 5.1.18.232) for the described BASE-TRAIN and BASE-ELECTRIC study. Moreover, MAS reports other grants from Netherlands Lung Foundation, grants and personal fees from AstraZeneca, grants and personal fees from Boehringer Ingelheim, and a grant from Stichting Astma Bestrijding, all outside the submitted work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting. Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures. This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass. PUBMED and PEDro databases were searched. In all, 70 studies ( n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised. Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated. Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured. Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients. Which intervention(s) is (are) best for which subgroup of patients remains currently unknown. Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients.

Background: Muscle carnosine is related to contractile function (Ca ++ handling) and buffering of exercise-induced acidosis. As these muscular functions are altered in Multiple Sclerosis (MS) it is relevant to understand muscle carnosine levels in MS., Methods: Tibialis anterior muscle carnosine was measured in an animal MS model (EAE, experimental autoimmune encephalomyelitis, n = 40) and controls (CON, n = 40) before and after exercise training (EAE EX , CON EX , 10d, 1 h/d, 24 m/min treadmill running) or sedentary conditions (EAE SED , CON SED ). Human m. vastus lateralis carnosine of healthy controls (HC, n = 22) and MS patients (n = 24) was measured., Results: EAE muscle carnosine levels were decreased (p < .0001) by ~ 40% to ~ 64% at 10d and 17d following EAE induction (respectively) regardless of exercise (p = .823). Similarly, human MS muscle carnosine levels were decreased (- 25%, p = .03)., Conclusion: Muscle carnosine concentrations in an animal MS model and MS patients are substantially reduced. In EAE exercise therapy does not restore this., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 -8 ) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

Introduction: The contribution of reduced testosterone levels to tail suspension (TS)-induced muscle atrophy remains equivocal. The molecular mechanism by which testosterone regulates muscle mass during TS has not been investigated., Methods: Effects of TS on serum testosterone levels, muscle mass, and expression of muscle atrophy- and hypertrophy-inducing targets were measured in soleus (SOL) and extensor digitorum longus (EDL) muscles after testosterone administration during 1, 5, and 14 days of TS in male mice., Results: TS produced an increase followed by a transient drop in testosterone levels. Muscle atrophy was associated with downregulation of Igf1 and upregulation of Mstn, Redd1, Atrogin-1, and MuRF1 mRNA with clear differences in Igf1, Mstn, and MAFbx/Atrogin-1 gene expression between SOL and EDL. Testosterone supplementation did not affect muscle mass or protein expression levels during TS. Conclusions The known anabolic effects of testosterone are not sufficient to ameliorate loss of muscle mass during TS., (© 2014 Wiley Periodicals, Inc.)

Introduction: Chronic β-alanine (BA) supplementation is an increasingly popular nutritional strategy, because it can elevate muscle carnosine content and thereby enhance high-intensity exercise performance. The current study investigated 1) whether sex and body mass are determinants of BA-induced muscle carnosine loading and 2) the optimal maintenance dose for ensuring constantly elevated muscle carnosine stores., Methods: During the loading phase, 34 participants (men and women) were supplemented with 3.2 g (4 × 800 mg) BA per day for 46 d (slightly different loading strategies were applied concerning the effect of meal timing and supplementation form). Thereafter, 19 participants (men and women) continued taking free-powder BA for six more weeks (maintenance phase). The participants were matched and redivided into three groups receiving 0.4, 0.8, and 1.2 g·d(-1) BA, respectively. Muscle carnosine content was measured in the soleus and gastrocnemius muscles using proton magnetic resonance spectroscopy., Results: Body mass and sex had only minimal effect on the absolute increase in muscle carnosine. Given the lower baseline values in women, the relative increase for women was higher, indicating that women required less BA for the same relative increase. In addition, a significant negative correlation was observed between body mass and the relative increase in muscle carnosine (r = -0.45, P = 0.007). A maintenance dose of ∼1.2 g·d(-1) BA was the most effective in keeping muscle carnosine content elevated at the postsupplementation level., Conclusions: Sex and body mass did not markedly affect the absolute increase during muscle carnosine loading, although they are determinants for the relative increase. In addition, we established for the first time an effective maintenance dose of ∼1.2 g·d(-1) BA to keep muscle carnosine content elevated at 30%-50% above baseline for a prolonged period.

Despite the large variety of so-called ergogenic supplements used by the sporting community, only few of them are effectively supported by scientific proof. One of the recent evidence-based supplements that entered the market is β-alanine. β-Alanine is the rate-limiting precursor for the synthesis of the dipeptide carnosine (β-alanyl-L-histidine) in human muscle. The chronic daily ingestion of β-alanine can markedly elevate muscle carnosine content, which results in improved exercise capacity, especially in sports that include high-intensity exercise episodes. The use of β-alanine is exponentially growing in recent years. This chapter aims to (1) discuss the scientific basis and physiological background of β-alanine and its synthesis product carnosine, and (2) translate these scientific findings to practical applications in sports., (Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Carnosine (beta-alanyl-l-histidine) is present in high concentrations in human skeletal muscle. The ingestion of beta-alanine, the rate-limiting precursor of carnosine, has been shown to elevate the muscle carnosine content. We aimed to investigate, using proton magnetic resonance spectroscopy (proton MRS), whether oral supplementation with beta-alanine during 4 wk would elevate the calf muscle carnosine content and affect exercise performance in 400-m sprint-trained competitive athletes. Fifteen male athletes participated in a placebo-controlled, double-blind study and were supplemented orally for 4 wk with either 4.8 g/day beta-alanine or placebo. Muscle carnosine concentration was quantified in soleus and gastrocnemius by proton MRS. Performance was evaluated by isokinetic testing during five bouts of 30 maximal voluntary knee extensions, by endurance during isometric contraction at 45% maximal voluntary contraction, and by the indoor 400-m running time. beta-Alanine supplementation significantly increased the carnosine content in both the soleus (+47%) and gastrocnemius (+37%). In placebo, carnosine remained stable in soleus, while a small and significant increase of +16% occurred in gastrocnemius. Dynamic knee extension torque during the fourth and fifth bout was significantly improved with beta-alanine but not with placebo. Isometric endurance and 400-m race time were not affected by treatment. In conclusion, 1) proton MRS can be used to noninvasively quantify human muscle carnosine content; 2) muscle carnosine is increased by oral beta-alanine supplementation in sprint-trained athletes; 3) carnosine loading slightly but significantly attenuated fatigue in repeated bouts of exhaustive dynamic contractions; and 4) the increase in muscle carnosine did not improve isometric endurance or 400-m race time.

The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. This chapter aims to summarize the current knowledge regarding the impact muscle creatine loading can have on exercise performance and rehabilitation. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation, and the response can be further enhanced by a concomitant exercise or insulin stimulus. The elevated muscle creatine content moderately improves contractile performance in sports with repeated high-intensity exercise bouts. More chronic ergogenic effects of creatine are to be expected when combined with several weeks of training. A more pronounced muscle hypertrophy and a faster recovery from atrophy have been demonstrated in humans involved in resistance training. The mechanism behind this anabolic effect of creatine may relate to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling. An additional effect of creatine supplementation, mostly when combined with training, is enhanced muscle glycogen accumulation and glucose transporter (GLUT4) expression. Thus, creatine may also be beneficial in sport competition and training characterized by daily glycogen depletion, as well as provide therapeutic value in the insulin-resistant state.

Electrical field stimulation of isolated, incubated rodent skeletal muscles is a frequently used model to study the effects of contractions on muscle metabolism. In this study, this model was used to investigate the effects of electrically stimulated contractions on creatine transport. Soleus and extensor digitorum longus muscles of male NMRI mice (35-50 g) were incubated in an oxygenated Krebs buffer between platinum electrodes. Muscles were exposed to [(14)C]creatine for 30 min after either 12 min of repeated tetanic isometric contractions (contractions) or electrical stimulation of only the buffer before incubation of the muscle (electrolysis). Electrolysis was also investigated in the presence of the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase (SOD) and catalase. Both contractions and (to a lesser degree) electrolysis stimulated creatine transport severalfold over basal. The amount of electrolysis, but not contractile activity, induced (determined) creatine transport stimulation. Incubation with SOD and catalase at 100 and 200 U/ml decreased electrolysis-induced creatine transport by approximately 50 and approximately 100%, respectively. The electrolysis effects on creatine uptake were completely inhibited by beta-guanidino propionic acid, a competitive inhibitor of (creatine for) the creatine transporter (CRT), and were accompanied by increased cell surface expression of CRT. Muscle glucose transport was not affected by electrolysis. The present results indicate that electrical field stimulation of incubated mouse muscles, independently of contractions per se, stimulates creatine transport by a mechanism that depends on electrolysis-induced formation of ROS in the incubation buffer. The increased creatine uptake is paralleled by an increased cell surface expression of the creatine transporter.

Oral creatine supplementation can acutely ameliorate skeletal muscle function in older humans, but its value in the prevention of sarcopenia remains unknown. We evaluated the effects of lifelong creatine supplementation on muscle mass and morphology, contractility, and metabolic properties in a mouse model of muscle senescence. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 wk. Soleus and extensor digitorum longus muscles were tested for in vitro contractile properties, creatine content, and morphology at weeks 25 and 60. Both muscle types showed reduced phosphocreatine content at week 60 that could not be prevented by creatine. Accordingly, age-associated decline in muscle mass and contractility was not influenced by treatment. Aged soleus muscles had fewer and smaller fast-twitch glycolytic fibers irrespective of treatment received. It is concluded that lifelong creatine supplementation is no effective strategy to prevent sarcopenia in senescence-accelerated mice.

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.