Tailoring the second bout of exercise to individual strength losses after initial muscle-damaging exercise: effects on recovery and damage markers

Tailoring the second bout of exercise to individual strength losses after initial muscle-damaging exercise: effects on recovery and damage markers | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Tailoring the second bout of exercise to individual strength losses after initial muscle-damaging exercise: effects on recovery and damage markers Carsten Schwiete, Christine Heinrich, Kevin Happ, Joachim Mester, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7372578/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background: Interindividual variability in response to standardized eccentric exercise presents a major challenge for load management in both research and applied sports settings. The repeated bout effect (RBE) is known to attenuate symptoms in response to exercise-induced muscle damage (EIMD), but it remains unclear whether an individualization of the RBE based on EIMD-markers can reduce the interindividual variability. Methods : Thirty trained males (25.4 ± 2.8 years) completed two bouts of high-speed eccentric hamstring exercise, separated by 14 days. The volume of the repeated bout was individualized based on the peak torque reductions at 48 hours after the first bout. Absolute (Pitman-Morgan test) and relative (coefficient of variation) variance, as well as mean changes (linear mixed models) of neuromuscular function (peak torque, MVC, jumps), muscle tissue changes (elastography, TMG, Myoton), creatine kinase levels, and soreness were assessed pre- and post-exercise up to 96 hours. Results: The individualized repeated bout resulted in significantly lower absolute and relative variance most prominently after 72 hours, in peak torque ( p = 0.04), MVC ( p = 0.02), CK ( p = 0.04), and soreness ( p < 0.001). Conclusion: Individualizing the repeated bout based on peak torque losses of the initial bout reduced the absolute and relative variance of EIMD. This approach could help with load management and recovery strategies in elite sports settings. Trial registration date: 04/07/2023 Trial registration number: DRKS00031644 Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction An individual's response to exercise or treatment is one of the most important areas in sports medical research (Ross et al., 2019 ). In healthy populations, great interindividual variability in response to standardized exercise is well established (Bouchard & Rankinen, 2001 ). This variance is magnified in elite sports settings, where pronounced interindividual variability in load response are documented in tennis (Pluim & Drew, 2016 ), soccer (Hader et al., 2019 ), 3 x 3 basketball (Willberg et al., 2022 ), or rugby (Hulin et al., 2016 ). In soccer, for instance, data reveal that weekly variations in external loads and accelerometer metrics vary substantially across playing positions (Nobari et al., 2023 ), leading to a heterogeneous load exposure within a team. This might be critical for match performance as we also know that training load manipulation within micro cycles can profoundly affect how well athletes balance stress and recovery (Owen et al., 2024 ). From a practitioner's perspective, it is essential to adequately understand individual load responses to enhance performance and minimize injury risk (Bourdon et al., 2017 ). A critical manifestation of this variability is the degree of exercise-induced muscle damage (EIMD), typically experienced as strength loss and muscle soreness lasting several days (Markus et al., 2021 ). The substantial variability in EIMD symptoms across individuals following identical loading challenges of ‘one-size-fits-all’ training prescriptions. While strength loss (Paulsen et al., 2012 ) or CK activity (T. Chen, 2006 ) are used retrospectively to describe this variability, proactive strategies to tailor upcoming training dose based on current individual responses remain scarce. The repeated bout effect (RBE) offers a promising, athlete-centered solution. The RBE describes the establishment of intrinsic protective mechanisms after a first bout of EIMD, substantially blunting damage from subsequent bouts of muscle-damaging exercise. While the exact mechanisms of the RBE are still unclear, there are three main contributors considered, ranging from neural shifts in motor unit recruitment to structural remodeling of the muscle-tendon units and adaptations of the extracellular matrix (Hyldahl et al., 2017 ). The processes are suggested to be set within the first few days of recovery, providing significant protection for up to 6 months (Nosaka et al., 2001 ). Recognizing that different athletes may vary in their initial response to EIMD implies the idea of using individualized repeated bouts to account for the interindividual variance of the damage response. Early force losses are one of the most valid, reliable, and practical indices of EIMD (Byrne et al., 2004 ; Paulsen et al., 2012 ). Further, previous research has shown a significant relationship between the torque variability during and the force losses after EIMD (Skurvydas et al., 2010 , 2011 ), with the authors concluding that prolonged symptoms of EIMD are closely related to intraindividual variability. However, to date, it remains unclear whether individual responses to an initial bout of exercise-induced muscle damage (EIMD) can be effectively used to tailor the load of a subsequent bout to reduce interindividual variability. Such an approach would aim to align the physiological strain across individuals, despite differences in initial damage susceptibility. Using this individualized strategy, the volume and intensity of the repeated bout are adjusted based on post-exercise strength loss as a proxy for EIMD severity. Accordingly, the present study aimed to evaluate a novel, exploratory approach to tailor the repeated bout based on individual post-exercise strength losses of after an initial bout of EIMD. We hypothesized that this would result in a reduction in variance independently from the mean changes, leading to an overall smaller interindividual variability across the damage markers. Methods Study design & individualization of the repeated bout This study was approved by the local ethics committee and conducted following the ethical standards set by the Declaration of Helsinki (DRKS00031644). The methodology was performed in adherence with the CONSORT guidelines. Participants performed two maximal, high-speed eccentric training protocols for the hamstrings on an isokinetic dynamometer (ISOMED 2000, D. & R. Ferstl GmbH, Hemau, Germany). Between bouts, there was a two-week resting interval. Prior to the intervention, all participants were familiarized with the measurements, and anthropometric data were collected using a 3D body scanner (Scaneca GmbH, Berlin, Germany). The initial eccentric exercise bout consisted of five sets of 15 maximal eccentric seated hamstring curls with one-minute rest intervals between sets and an eccentric contraction speed of 210°/s, and a passive, concentric contraction speed of 50°/s. Participants were seated with an 85° trunk flexion; knee joint range of motion was individualized based on the anthropometric characteristics in a range of 0° to 100° knee flexion (Schwiete, Roth, Skutschik, et al., 2023 ). Room temperature was set to 23 C° throughout the intervention via air conditioning. The repeated bout was individualized based on their decrements in eccentric peak torque 48 hours post-exercise, where force losses typically peak after EIMD (Paulsen et al., 2012 ). Accordingly, the following formula was established, where the training volume of the repeated bout ( V 2 ) was scaled directly to the force losses at 48 hours post-exercise ( \(\:\varDelta\:\%eccP{T}_{48h}\) ) after the initial bout ( V 1 ): $$\:{V}_{2}=\:{V}_{1}\left(1-\varDelta\:\%\frac{eccPT48h}{100}\right)$$ Neuromuscular assessments (eccentric peak torque, MVC, jumps), muscle contractility (Myoton, TMG), muscle stiffness (shear-wave elastography), and soreness (VAS) were performed before (pre) and after the intervention (post) as well on the consecutive four days (24–96 hours post). Creatine kinase was measured pre and 24–96 hours post (see Fig. 1 ). Participants 30 male participants (25.4 ± 2.8 years, 81.5 ± 8.6 kg, 180.6 ± 7.4 cm) were included in this project that employed a repeated measures, within-subject design. Approval was obtained from the local ethics committee, and each participant provided written informed consent for study participation. Inclusion criteria required participants to be male, between 18 and 35 years of age, free of injuries in the lower extremities, take no regular medications, and to train at least twice per week. Participants with lower body injuries, regular medication, and less than two training sessions per week were excluded from study participation. On average, participants performed 2.2 ± 2.5 hours of resistance training, 1.1 ± 1.1 hours of endurance training, and 1.5 ± 2.1 hours of other recreational sports (soccer, squash, badminton etc.) per week. Study Parameters Eccentric Peak Torque & MVC Eccentric peak torque and MVC were evaluated on the ISOMED 2000. Participants began with a five-minute general warm-up on a stationary bike at 100 Watts (60–70 rpm), followed by two eccentric warm-up sets on the isokinetic dynamometer. After securing the participants on the ISOMED, the lever arm was adjusted to ensure the axis of rotation was correctly aligned with the knee, providing clean and comfortable contact throughout the movement. MVC was measured at 90° knee flexion (Oakley et al., 2013 ) during a single, five-second maximal isometric hold. After a three-minute rest, eccentric peak torque was tested in one set of five maximal eccentric contractions at the intervention speed (210°/s). Shear-wave elastography Shear-wave speed was used to assess the muscle stiffness of the participants in all three hamstring muscles. An ACUSON Redwood (Siemens Healthineers, Erlangen, Germany) with a 10L4 linear probe was used by the same experienced investigator. The probe was aligned in the longitudinal direction of the muscle with minimal pressure, and three consecutive measurements were performed at each location. A 6 x 10 mm region of interest was placed beneath the fascial sheath, and within this region of interest, two 10 mm diameter measurement circles were placed vertically. Real-time feedback on the reliability of the measurements was provided by a color‐coded confidence map. The measurement locations were adopted from Kawama et al. ( 2022 ), including two sites on the m. biceps femoris (50% segment length & 10 cm distal), the m. semitendinosus (40% segment length & 10 cm distal), and the m. semimembranosus (60% segment length & 10 cm distal). Based on the shear wave speed of the individual locations, the ultrasound software calculated a stiffness main score including all measurement sites, which was used for the final data analysis. Creatine Kinase Capillary blood samples were collected and immediately centrifuged (Universal 320 R, Andreas Hettich GmbH, Tufflingen, Germany) for 10 minutes at 3000 revolutions per minute. Afterwards, 10 µl of blood plasma was drawn using a reusable pipette (Eppendorf Research Plus, Eppendorf, Hamburg, Germany) and analyzed in a point-of-care-testing system (DRI-CHEM Analyzer FDC NX500, Fujifilm Europe, Duesseldorf, Germany). Post-exercise samples were manually diluted in the form of a dilution series (1:2; 1:4; 1:8; 1:16; 1:32; 1:64), using a concentrated 0.9% sodium chloride solution. The value of the lowest dilution was used for the final data analysis. Tensiomyography & Myoton TMG measurements (TMG-BMC Ltd., Ljubljana, Slovenia) were conducted at the same measurement locations as used for elastography. A TMG cushion was placed below the participants' shin to create a 5° knee flexion (Schwiete et al., 2023 ). Two self-adhesive dura‐stick electrodes (50 × 50 mm) were attached to the skin with a 5 cm inter‐electrode distance (Piqueras-Sanchiz et al., 2020 ), and each placement was marked using a water‐resistant pen. Three measurements per site were performed at 100 mA, separated by a 30‐second rest interval. In keeping with the elastography protocol, a main radial displacement (D m ) score was calculated across all measurement sites for the final data analysis. Passive muscle stiffness (S, N/m) was assessed in multiscan mode using the Myoton device (Myoton Ltd., Tallinn, Estonia). CMJ, SJ, and DJ Jumping performance was evaluated using an opto-electronic measurement system (OptojumpRX10, MicroGate, Bolzano, Italy). Participants were familiarized with correct jump execution during two introductory sessions before the intervention. All jumps were performed with hands placed on the hips, and three jumps were completed with a minimum of 30 seconds’ rest between attempts. For squat jumps (SJs), participants were instructed to hold a 90° knee flexion for at least one second, and for drop jumps (DJs), a 30 cm box was used. Muscle Soreness Muscle soreness was measured using a 100 mm visual analog scale (VAS), ranging from “no pain at all” to “worst pain imaginable”. Participants were instructed following the procedure described by Schwiete et al. ( 2021 ) to ensure proper application of the scale. Statistical Analysis For statistical analyses, IBM SPSS Statistics (version 28.0), Jamovi (version 16.44), and GraphPad Prism (version 10.3) were utilized. To assess interindividual variability, the Pitman-Morgan test, a paired t-test of squared residuals, was used to compare absolute variances between two related conditions. Based on our directional hypothesis that individualization would reduce variability, one-tailed p-values were reported. In addition, the coefficient of variation (CV = SD/mean x 100) was calculated to evaluate relative variability, allowing for an interpretation regarding interindividual differences in proportion to the mean response (Lavender & Nosaka, 2006 ). For general comparisons between bouts, linear mixed-effects models (LMMs) were fitted separately for each dependent variable to examine changes over multiple time points and between experimental bouts. In each model, time, condition, and their interaction were tested as fixed effects. Covariates included baseline measures (PT, MVC, D m , SWE), average resistance training volume (RTave), total repetitions in bout 2 (RepsB2), maximal perceived exertion in bout 1 (BORGmax), and average total work and PT decreases (%TWdrop, %PTdrop) in bout 1. A random intercept for each participant was included to account for within-subject correlation arising from repeated measures. Model fit was assessed via log-likelihood, AIC, and BIC, and both marginal (fixed effects only) and conditional (fixed plus random effects) R² values were reported to gauge explanatory power. Statistical significance was evaluated at an alpha level of 0.05, and, where applicable, significant main or interaction effects were further explored using Bonferroni-corrected post-hoc comparisons. Assumptions of linearity and normality of residuals were checked through diagnostic plots, and data were screened for outliers before final model estimation. Results Peak torque, MVC & jumps For peak torque, model fit revealed that fixed effects explain 45% (marginal R 2 = 0.45) of the variance and random effects account for 25% (ICC = 0.25). There was a significant time x condition effect ( p < 0.001), with larger force decreases after bout 1 compared to bout 2 at 24 h to 96 h post (all p < 0.05) (Fig. 2 ). Among covariates, baseline PT ( p < 0.001), RepsB2 ( p = 0.004), and RTave ( p = 0.021) were all positively associated with higher post-exercise PT. The Pitman-Morgan results showed that the interindividual variability for PT was significantly lower after the repeated bout compared to bout 1 after 72 h post-exercise ( p = 0.049). Additionally, CVs showed lower relative variability after the repeated bout (16.25%) compared to bout 1 (27.7%). The model fit for MVC showed that 39% of the variability is explained by fixed effects (marginal R 2 = 0.39) and 17% is between individuals’ intercept (ICC = 0.17). There were no significant time x condition effects ( p = 0.28), but both time and condition had significant main effects (both p < 0.001). Higher baseline MVC ( p = 0.004) and PT ( p = 0.037), as well as RepsB2 ( p = 0.025) predicted lower MVC decreases post-exercise. Similar to PT, the variance in MVC was significantly lower after the repeated bout after 72 h ( p = 0.015; CV: 32.9 vs. 19.1%), but also after 96 h ( p = 0.024; CV: 29.8 vs. 18.9%). While for CMJ ( p = 0.001) and SJ ( p = 0.021), significant time effects were revealed, DJ differed significantly between bouts ( p < 0.001). Additionally, no differences in variance were present for any jump at any time point. CK & muscle soreness There was a significant time x condition interaction for CK (p = 0.002), showing higher CK increases after bout 1 compared to bout 2 after 72 ( p = 0.018) and 96 h ( p < 0.001). There were no significant changes in CK after bout 2 (Fig. 3 ). The overall model showed that fixed effects explained 24% of the variance (marginal R 2 = 0.24) and between-subject variability was 4% (ICC = 0.04). While higher baseline D m was associated with higher post-exercise CK ( p = 0.014), a higher repetition count in bout 2 was linked to lower CK responses ( p < 0.001). The results of the Pitman-Morgan test showed a significantly lower absolute variability for CK after 72 h ( p = 0.04) and 96 h ( p = 0.04). Additionally, CVs for bout 2 were smaller compared to bout 1 at 72 h (196.7 vs. 113.8%) and 96 h (205.2 vs. 83%). There was a significant time x condition interaction for VAS ( p = 0.002), with greater muscle soreness after bout 1 compared to bout 2 from 24 h post onwards (all p < 0.05). Fixed effects explained 43% of the variance, and 11% was from between-person differences (ICC = 0.114). Similar to CK, more repetitions during bout 2 were linked to a lower response in muscle soreness ( p < 0.001). Pitman-Morgan test results revealed a significantly lower absolute variability after the repeated bout at the 24 h ( p = 0.02), 48 h ( p = 0.003), 72 h ( p < 0.001), and 96 h ( p = 0.001). Contrary, relative variability was consistently higher after the repeated bout compared to bout 1 at these time points (24 h: 84 vs. 89.14%; 48 h: 69.9 vs. 93.65%; 72 h: 89.1 vs. 116.7%; 96 h: 115.5 vs. 126.1%). Muscle stiffness & muscle contractility There was no significant time x condition effect for elastography ( p = 0.34); however, time and condition (both p < 0.001) both show significant main effects. The overall model showed that 28% of the variance is explained by fixed effects (marginal R 2 = 0.28) and 58% is from between-subject variability (ICC = 0.58). Among covariates, baseline contractility ( p = 0.02) and peak torque ( p = 0.006) significantly affected muscle stiffness. No time x condition interaction ( p = 0.78) was found for D m , but time ( p = 0.09) and condition ( p = 0.02) were significant. Covariates did not significantly affect D m . For Myoton, no significant effects were found. Neither absolute nor relative variance decreased for muscle stiffness or muscle contractility. Discussion The present study investigated whether tailoring a repeated bout - based on the magnitude of post-exercise peak torque loss - could reduce interindividual variability in markers of EIMD. Importantly, variability was assessed both in absolute terms (via the Pitman-Morgan test) and relative to the group mean (via the coefficient of variation, CV), thus enabling a more nuanced interpretation of group-level response heterogeneity. Our findings support this approach: several key markers - namely peak torque, MVC, CK activity, and perceived muscle soreness - showed substantially lower absolute and relative variability in the repeated bout. The largest reductions in CV were observed at 72 hours post-exercise. This suggests that individualized loading not only reduces the magnitude of damage for some individuals but also contributes to a more consistent physiological strain across the group. Changes in variability The main finding of our study is that tailoring a repeated bout based on individual force losses after 48 h of the initial bout can effectively reduce the absolute and relative variance in EIMD markers. The variability in our study was notably reduced for peak torque, MVC, CK, and muscle soreness at different time points between 24 and 96 h post-exercise. The greatest differences in variance between both bouts were observed at 72 hours post-exercise. When comparing relative variability (CVs), we did not consistently find a smaller variance compared to standard RBE studies. For instance, in studies of Chen et al. ( 2025 ) and Nikolaidis et al. ( 2007 ), CVs for peak torque and MVC were smaller at the same time post-exercise. These studies involved maximal eccentric contractions for the knee flexors and were separated by 2 or 3 weeks, respectively. Relative variability after 72 h for peak torque (Nikolaidis et al.: 7.5%) and MVC (Chen et al.: 6.61%) was substantially lower in these studies than in ours (PT 72h: 16.25%; MVC 72h: 19.1%). On the other hand, our results show lower relative variance in peak torque and MVC compared to studies of Da Silva et al. ( 2023 ) and Howatson et al. ( 2007 ). For example, Howatson et al. ( 2007 ), who investigated the RBE in the elbow flexors, found relative variability in MVC after 96 h was higher in their study compared to our tailored RB (26.5% vs. 18.9%). Additionally, in the study of (Da Silva et al., 2023 ), who performed unilateral eccentric contractions with the knee flexors, peak torque variance was higher after 24 h (27.5%) than in our study (18.9%). Variability in CK activity and soreness was even more pronounced. Absolute CK variance was significantly lower after the individualized repeated bout at 72 and 96 h post-exercise. However, when comparing the relative variance to standard RBE studies (Chen et al., 2018 , 2025 ; Nikolaidis et al., 2007 ), our interindividual variability is substantially higher, possibly due to our higher absolute variance. While our participants reached maximum CK above 80000 U/L, the CK response in comparable studies by Nikolaidis et al. ( 2007 ) and Chen et al. ( 2025 ) peaked at 2200 U/L and 9000 U/l, respectively. Similar to CK, soreness variability was greatly reduced at all time points from 24 to 96 h post. However, the relative variance in soreness was substantially higher in our study compared to regular RBE studies (Chalchat et al., 2022 ; T. C. Chen et al., 2023 ; Deyhle et al., 2016 ). These differences in absolute and relative variance among the different damage markers can partly be explained by our LMM models and the influence of random intercepts. Our results show moderately high ICCs for peak torque and MVC (PT: 0.25; MVC: 0.17), indicating that a significant amount of variability was due to stable between-individual differences (e.g., baseline strength, etc). Accordingly, even when adjusting the load of the repeated bout, a substantial portion of this stable variance remains, limiting the extent to which variability could be reduced. This might also explain the missing differences in stiffness and contractility variance, as ICCs were even higher in these markers (SWE: 0.58; Dm: 0.33), showing that most of the variability is explained by stable individual differences rather than time or condition effects. In contrast, the low ICCs for CK (0.04) and soreness (0.1) suggest that most of the variance was affected by modifiable training variables like condition, reps, etc. Therefore, the tailoring of the repeated bout was much more effective in reducing the absolute and relative variance in the EIMD markers. Overall changes between bout 1 & 2 Beyond the differences in variability, the overall comparison between the initial and repeated bout demonstrates the typical features of a RBE. Across our study population, attenuated changes in damage markers were observed regarding force production (peak torque, MVC), CK activity, and muscle soreness following the tailored repeated bout. For peak torque, our LMM revealed a significant time x condition interaction (p < 0.001), indicating a smaller reduction in peak torque after the repeated bout. The covariates revealed a positive association between the post-exercise force levels and baseline peak torque, average resistance training volume, and number of repetitions in bout 2. In comparison to this, MVC changes showed a different pattern with no significant interaction (p = 0.28), but with main effects for both time and condition independently (p < 0.001). Similar to the peak torque model, baseline strength levels and number of repetitions in bout 2 significantly affected the damage response to the repeated bout. Our findings show that baseline strength, training background, and exercise volume significantly affect the response to EIMD, which is in line with the findings of Vincent & Vincent ( 1997 ) and Ertel et al. ( 2020 ). They found that individuals with a more extensive training background experience less severe muscle damage compared to untrained participants. All of these results reemphasize the consistent exposure to resistance training in elite sports to attenuate EIMD, possibly because of reduced z-band streaming (Damas et al., 2016 ). For both CK and muscle soreness, there was a significant time x condition interaction. After the initial bout, CK rose until 96 h post, whereas there were no significant increases after the repeated bout. The interaction shows that the differences in CK are mainly present at the 72 h ( p = 0.013) and 96 h ( p < 0.001) timepoints, which does not come surprisingly as we know that CK activity commonly peaks 3–6 days after the initial eccentric stimulus (Clarkson & Hubal, 2002 ). The results from our study yet again confirm the large interindividual variability of CK responses Chen ( 2006 ), with values ranging between 169 and 83776 U/L at the 96 h post-time point after the initial bout. Interestingly, our data suggest no matching between the CK responses between bout 1 and 2, meaning that high responders after bout 1 were not high responders after bout 2, contrary to the reports of Chen ( 2006 ). Rather, the repeated bout led to a disproportionately larger attenuation in CK among high responders from bout 1. For instance, the two highest responders from bout 1 (83776 U/L and 67543 U/L) dropped to 306 and 890 U/L at the same time point (96 hours post) after bout 2 (Fig. 4 ). This reinforces that tailoring the repeated bout was especially effective in suppressing CK response. For soreness, VAS scores differ from 24 h post onwards, with higher muscle soreness after the first bout and peaking after 48 h. For both CK and soreness, the number of repetitions in bout 2 emerged as a key predictor of the post-exercise response. In contrast, jumping performance (CMJ, SJ, and DJ) as well as muscle stiffness and contractility were less affected by the tailoring of the repeated bout. While shear-wave speed showed a significant time and condition (both p < 0.001) effect, the other parameters did not change. These findings likely indicate the more multifactorial nature of these measures, including training history, central motor control, or even tendon properties. This range of influencing variables makes these parameters less sensitive to adaptations in eccentric muscle contractions solely. Limitations While the findings of this study offer promising insights into individualized load management, several limitations should be acknowledged. First, the sample was limited to young, active males, which restricts generalizability to other populations such as female athletes, older adults, or elite performers. Future research should examine whether similar effects on variability and recovery can be observed across diverse cohorts with different training backgrounds and physiological profiles. Second, the study focused exclusively on the hamstring muscle group using a seated isokinetic protocol. Responses may differ in other muscle groups or under more sport-specific or functional loading conditions. Additionally, while the volume of the repeated bout was individualized based on early torque losses — a functional and practical marker — other variables such as soreness, CK, or stiffness were not used to further refine the individualization process. A more multidimensional individualization strategy could potentially enhance the precision and efficacy of the intervention. Finally, the study was limited to short-term responses (up to 96 hours post-exercise). Longitudinal research is needed to evaluate whether reduced variability in acute responses translates to improved performance outcomes, injury prevention, or training adaptations over time. These considerations highlight the need for continued investigation into individualized loading strategies, with the goal of optimizing both short- and long-term outcomes across broader athletic and clinical populations. Conclusion In conclusion, our study highlights that tailoring a repeated bout based on individual force losses after 48 hours can reduce variability in muscle damage markers, including peak torque, MVC, CK activity, and muscle soreness. Notably, our results show reduced variability in both absolute and relative terms. The greatest reductions in variability were observed at 72 hours post-exercise, with variability in CK and soreness showing the most significant decrease. However, when comparing the relative variability in our study to other regular RBE studies, the results were inconsistent. In some cases, our variability was smaller, while in others, it was larger, particularly in soreness and CK activity. Despite these inconsistencies, our results showed that the tailored repeated bout was more effective in reducing variance in CK and soreness than in other markers, such as peak torque and MVC, where baseline strength and training background played a larger role. While we observed some beneficial effects of individualizing the repeated bout, these findings are not entirely conclusive. The variability across studies and time points limits our ability to definitively conclude that our tailored repeated bout reduces interindividual variability more effectively than a standard repeated bout. Future research is needed to clarify the potential advantages of individualized approaches in muscle damage recovery and the factors that contribute to these differences. Declarations Funding: No fundings were received for this study. Conflicts of interest: The authors declare no conflicts of interest. Availability of data: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics approval: This study was reviewed and approved by the Ethics Committee Department 05, Goethe University (no.; 2023 - 35). This study was performed in line with the principles of the Declaration of Helsinki. Consent to participate: The participants gave informed written consent to the main study and to receive invitations to sub-studies. Consent for publication: not applicable. Author’s contribution: CS wrote the first draft of the manuscript. CS, HB, and MB were responsible for planning the study and for the study design. 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Exercise-Induced Muscle Damage in Humans: American Journal of Physical Medicine & Rehabilitation , 81 (Supplement), S52–S69. https://doi.org/10.1097/00002060-200211001-00007 Da Silva, F., Monjo, F., Gioda, J., Blain, G. M., Piponnier, E., Corcelle, B., & Colson, S. S. (2023). Knee position sense and knee flexor neuromuscular function are similarly altered after two submaximal eccentric bouts. European Journal of Applied Physiology , 123 (2), 311–323. https://doi.org/10.1007/s00421-022-05063-6 Damas, F., Phillips, S. M., Libardi, C. A., Vechin, F. C., Lixandrão, M. E., Jannig, P. R., Costa, L. A. R., Bacurau, A. V., Snijders, T., Parise, G., Tricoli, V., Roschel, H., & Ugrinowitsch, C. (2016). Resistance training‐induced changes in integrated myofibrillar protein synthesis are related to hypertrophy only after attenuation of muscle damage. The Journal of Physiology , 594 (18), 5209–5222. https://doi.org/10.1113/JP272472 Deyhle, M. R., Gier, A. M., Evans, K. C., Eggett, D. L., Nelson, W. B., Parcell, A. C., & Hyldahl, R. D. (2016). Skeletal Muscle Inflammation Following Repeated Bouts of Lengthening Contractions in Humans. Frontiers in Physiology , 6 . https://doi.org/10.3389/fphys.2015.00424 Ertel, K., Hallam, J., & Hillman, A. (2020). The effects of training status and exercise intensity on exercise-induced muscle damage . 60 (3), 449–455. https://doi.org/10.23736/S0022-4707.19.10151-X Hader, K., Rumpf, M. C., Hertzog, M., Kilduff, L. P., Girard, O., & Silva, J. R. (2019). Monitoring the Athlete Match Response: Can External Load Variables Predict Post-match Acute and Residual Fatigue in Soccer? A Systematic Review with Meta-analysis. Sports Medicine - Open , 5 (1), 48. https://doi.org/10.1186/s40798-019-0219-7 Howatson, G., Van Someren, K., & Hortobágyi, T. (2007). Repeated Bout Effect after Maximal Eccentric Exercise. International Journal of Sports Medicine , 28 (7), 557–563. https://doi.org/10.1055/s-2007-964866 Hulin, B. T., Gabbett, T. J., Lawson, D. W., Caputi, P., & Sampson, J. A. (2016). The acute:chronic workload ratio predicts injury: High chronic workload may decrease injury risk in elite rugby league players. British Journal of Sports Medicine , 50 (4), 231–236. https://doi.org/10.1136/bjsports-2015-094817 Hyldahl, R. D., Chen, T. C., & Nosaka, K. (2017). Mechanisms and Mediators of the Skeletal Muscle Repeated Bout Effect. Exercise and Sport Sciences Reviews , 45 (1), 24–33. https://doi.org/10.1249/JES.0000000000000095 Kawama, R., Yanase, K., Hojo, T., & Wakahara, T. (2022). Acute changes in passive stiffness of the individual hamstring muscles induced by resistance exercise: Effects of contraction mode and range of motion. European Journal of Applied Physiology , 122 (9), 2071–2083. https://doi.org/10.1007/s00421-022-04976-6 Lavender, A. P., & Nosaka, K. (2006). Changes in fluctuation of isometric force following eccentric and concentric exercise of the elbow flexors. European Journal of Applied Physiology , 96 (3), 235–240. https://doi.org/10.1007/s00421-005-0069-5 Markus, I., Constantini, K., Hoffman, J. R., Bartolomei, S., & Gepner, Y. (2021). Exercise-induced muscle damage: Mechanism, assessment and nutritional factors to accelerate recovery. European Journal of Applied Physiology , 121 (4), 969–992. https://doi.org/10.1007/s00421-020-04566-4 Nikolaidis, M. G., Paschalis, V., Giakas, G., Fatouros, I. G., Koutedakis, Y., Kouretas, D., & Jamurtas, A. Z. (2007). Decreased Blood Oxidative Stress after Repeated Muscle-Damaging Exercise. Medicine & Science in Sports & Exercise , 39 (7), 1080–1089. https://doi.org/10.1249/mss.0b013e31804ca10c Nobari, H., Praça, G. M., Da Glória Teles Bredt, S., González, P. P., Clemente, F. M., Carlos-Vivas, J., & Ardigò, L. P. (2023). Weekly variations of accelerometer variables and workload of professional soccer players from different positions throughout a season. Scientific Reports , 13 (1), 2625. https://doi.org/10.1038/s41598-023-29793-5 Nosaka, K., Sakamoto, K., Newton, M., & Sacco, P. (2001). How long does the protective effect on eccentric exercise-induced muscle damage last?: Medicine & Science in Sports & Exercise , 33 (9), 1490–1495. https://doi.org/10.1097/00005768-200109000-00011 Oakley, E. T., Pardeiro, R. B., Powell, J. W., & Millar, A. L. (2013). The Effects of Multiple Daily Applications of Ice to the Hamstrings on Biochemical Measures, Signs, and Symptoms Associated With Exercise-Induced Muscle Damage. Journal of Strength and Conditioning Research , 27 (10), 2743–2751. https://doi.org/10.1519/JSC.0b013e31828830df Owen, A., Weston, M., & Clancy, C. (2024). Between-microcycle variability of external soccer training loads through the evaluation of a contemporary periodisation training model ‘CUPs’. International Journal of Sports Science & Coaching , 19 (5), 2067–2077. https://doi.org/10.1177/17479541241251424 Paulsen, G., Mikkelsen, U. R., Raastad, T., & Peake, J. M. (2012). Leucocytes, cytokines and satellite cells: What role do they play in muscle damage and regeneration following eccentric exercise? 56. Piqueras-Sanchiz, F., Martín-Rodríguez, S., Pareja-Blanco, F., Baraja-Vegas, L., Blázquez-Fernández, J., Bautista, I. J., & García-García, Ó. (2020). Mechanomyographic Measures of Muscle Contractile Properties are Influenced by Electrode Size and Stimulation Pulse Duration. Scientific Reports , 10 (1), 8192. https://doi.org/10.1038/s41598-020-65111-z Pluim, B. M., & Drew, M. K. (2016). It’s not the destination, it’s the ‘road to load’ that matters: A tennis injury prevention perspective. British Journal of Sports Medicine , 50 (11), 641–642. https://doi.org/10.1136/bjsports-2016-095997 Ross, R., Goodpaster, B. H., Koch, L. G., Sarzynski, M. A., Kohrt, W. M., Johannsen, N. M., Skinner, J. S., Castro, A., Irving, B. A., Noland, R. C., Sparks, L. M., Spielmann, G., Day, A. G., Pitsch, W., Hopkins, W. G., & Bouchard, C. (2019). Precision exercise medicine: Understanding exercise response variability. British Journal of Sports Medicine , 53 (18), 1141–1153. https://doi.org/10.1136/bjsports-2018-100328 Schwiete, C., Franz, A., Roth, C., & Behringer, M. (2021). Effects of Resting vs. Continuous Blood-Flow Restriction-Training on Strength, Fatigue Resistance, Muscle Thickness, and Perceived Discomfort . 12 , 663665. https://doi.org/10.3389/fphys.2021.663665 Schwiete, C., Roth, C., Braun, C., Rettenmaier, L., Happ, K., Langen, G., & Behringer, M. (2023). Sensor location affects skeletal muscle contractility parameters measured by tensiomyography. PLOS ONE , 18 (2), e0281651. https://doi.org/10.1371/journal.pone.0281651 Schwiete, C., Roth, C., Skutschik, C., Möck, S., Rettenmaier, L., Happ, K., Broich, H., & Behringer, M. (2023). Effects of muscle fatigue on exercise-induced hamstring muscle damage: A three-armed randomized controlled trial. European Journal of Applied Physiology . https://doi.org/10.1007/s00421-023-05234-z Skurvydas, A., Brazaitis, M., & Kamandulis, S. (2010). Prolonged Muscle Damage Depends on Force Variability. International Journal of Sports Medicine , 31 (02), 77–81. https://doi.org/10.1055/s-0029-1241213 Skurvydas, A., Brazaitis, M., & Kamandulis, S. (2011). Repeated Bout Effect is not Correlated With Intraindividual Variability During Muscle-Damaging Exercise. Journal of Strength and Conditioning Research , 25 (4), 1004–1009. https://doi.org/10.1519/JSC.0b013e3181d68563 Vincent, H., & Vincent, K. (1997). The effect of training status on the serum creatine kinase response, soreness and muscle function following resistance exercise . 18 (6), 431–437. https://doi.org/10.1055/s-2007-972660 Willberg, C., Wieland, B., Rettenmaier, L., Behringer, M., & Zentgraf, K. (2022). The relationship between external and internal load parameters in 3 × 3 basketball tournaments. BMC Sports Science, Medicine and Rehabilitation , 14 (1), 152. https://doi.org/10.1186/s13102-022-00530-1 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 29 Oct, 2025 Reviews received at journal 15 Oct, 2025 Reviewers agreed at journal 12 Oct, 2025 Reviewers agreed at journal 10 Oct, 2025 Reviews received at journal 09 Sep, 2025 Reviewers agreed at journal 25 Aug, 2025 Reviewers invited by journal 25 Aug, 2025 Editor assigned by journal 25 Aug, 2025 Editor invited by journal 21 Aug, 2025 Submission checks completed at journal 20 Aug, 2025 First submitted to journal 20 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7372578","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":505455357,"identity":"c819b873-39e1-4cf7-a8dc-f90b29bfc296","order_by":0,"name":"Carsten Schwiete","email":"data:image/png;base64,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","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":true,"prefix":"","firstName":"Carsten","middleName":"","lastName":"Schwiete","suffix":""},{"id":505455360,"identity":"ce7d0da8-d47d-4317-8d68-ca5871df0899","order_by":1,"name":"Christine Heinrich","email":"","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Christine","middleName":"","lastName":"Heinrich","suffix":""},{"id":505455362,"identity":"be1d4588-f427-4d2a-9335-4e7366638ff8","order_by":2,"name":"Kevin Happ","email":"","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"","lastName":"Happ","suffix":""},{"id":505455364,"identity":"adbe5541-232b-4dd0-8686-cccb9e80153b","order_by":3,"name":"Joachim Mester","email":"","orcid":"","institution":"German Research Centre of Elite Sport, German Sport University Cologne","correspondingAuthor":false,"prefix":"","firstName":"Joachim","middleName":"","lastName":"Mester","suffix":""},{"id":505455365,"identity":"619c48cc-a4bc-4daa-abde-e58eab6b7349","order_by":4,"name":"Holger Broich","email":"","orcid":"","institution":"Medical School Hamburg","correspondingAuthor":false,"prefix":"","firstName":"Holger","middleName":"","lastName":"Broich","suffix":""},{"id":505455367,"identity":"0ceaf26d-0da7-438b-8d75-4efa195b5801","order_by":5,"name":"Michael Behringer","email":"","orcid":"","institution":"Goethe University Frankfurt","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Behringer","suffix":""}],"badges":[],"createdAt":"2025-08-14 10:17:36","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7372578/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7372578/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90410849,"identity":"f81596eb-1f4f-4e6a-b381-75316cc94a77","added_by":"auto","created_at":"2025-09-02 12:10:28","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":118415,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eStudy design using an individualized repeated bout based on force losses after bout 1. This figure was designed with BioRender.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7372578/v1/333cd8d11c605d345673dd7a.png"},{"id":90410850,"identity":"b3299df8-3512-45eb-9e62-9cd02d22a66f","added_by":"auto","created_at":"2025-09-02 12:10:28","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95051,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eMean changes in relative peak torque and MVC after bout 1 \u0026amp; 2. (*) = significant difference between bout 1 \u0026amp; 2.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7372578/v1/c7c05bedf70754b9000cd07d.png"},{"id":90411177,"identity":"7122a11b-c289-4410-9388-b11fd819f7f5","added_by":"auto","created_at":"2025-09-02 12:18:28","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":79327,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eMean changes in muscle soreness and CK levels after bout 1 \u0026amp; 2.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7372578/v1/2a8f07be2095dc9d5ece5764.png"},{"id":90410853,"identity":"70155f9b-915b-4ce0-aba6-6f09823f3902","added_by":"auto","created_at":"2025-09-02 12:10:28","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":53058,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eMatched CK response after bout 1 \u0026amp; 2.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7372578/v1/4e92d5528de7091af6d3fa5c.png"},{"id":90413156,"identity":"91bc0585-c437-4a10-bf63-2a9621459cf7","added_by":"auto","created_at":"2025-09-02 12:42:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1010465,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7372578/v1/8c7a47b9-8c99-42db-9a03-f110e2c56c2e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Tailoring the second bout of exercise to individual strength losses after initial muscle-damaging exercise: effects on recovery and damage markers","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAn individual's response to exercise or treatment is one of the most important areas in sports medical research (Ross et al., \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). In healthy populations, great interindividual variability in response to standardized exercise is well established (Bouchard \u0026amp; Rankinen, \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). This variance is magnified in elite sports settings, where pronounced interindividual variability in load response are documented in tennis (Pluim \u0026amp; Drew, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2016\u003c/span\u003e), soccer (Hader et al., \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2019\u003c/span\u003e), 3 x 3 basketball (Willberg et al., \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), or rugby (Hulin et al., \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). In soccer, for instance, data reveal that weekly variations in external loads and accelerometer metrics vary substantially across playing positions (Nobari et al., \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), leading to a heterogeneous load exposure within a team. This might be critical for match performance as we also know that training load manipulation within micro cycles can profoundly affect how well athletes balance stress and recovery (Owen et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). From a practitioner's perspective, it is essential to adequately understand individual load responses to enhance performance and minimize injury risk (Bourdon et al., \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eA critical manifestation of this variability is the degree of exercise-induced muscle damage (EIMD), typically experienced as strength loss and muscle soreness lasting several days (Markus et al., \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). The substantial variability in EIMD symptoms across individuals following identical loading challenges of \u0026lsquo;one-size-fits-all\u0026rsquo; training prescriptions. While strength loss (Paulsen et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2012\u003c/span\u003e) or CK activity (T. Chen, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2006\u003c/span\u003e) are used retrospectively to describe this variability, proactive strategies to tailor upcoming training dose based on current individual responses remain scarce.\u003c/p\u003e\u003cp\u003eThe repeated bout effect (RBE) offers a promising, athlete-centered solution. The RBE describes the establishment of intrinsic protective mechanisms after a first bout of EIMD, substantially blunting damage from subsequent bouts of muscle-damaging exercise. While the exact mechanisms of the RBE are still unclear, there are three main contributors considered, ranging from neural shifts in motor unit recruitment to structural remodeling of the muscle-tendon units and adaptations of the extracellular matrix (Hyldahl et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). The processes are suggested to be set within the first few days of recovery, providing significant protection for up to 6 months (Nosaka et al., \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Recognizing that different athletes may vary in their initial response to EIMD implies the idea of using individualized repeated bouts to account for the interindividual variance of the damage response. Early force losses are one of the most valid, reliable, and practical indices of EIMD (Byrne et al., \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2004\u003c/span\u003e; Paulsen et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Further, previous research has shown a significant relationship between the torque variability during and the force losses after EIMD (Skurvydas et al., \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e2010\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2011\u003c/span\u003e), with the authors concluding that prolonged symptoms of EIMD are closely related to intraindividual variability. However, to date, it remains unclear whether individual responses to an initial bout of exercise-induced muscle damage (EIMD) can be effectively used to tailor the load of a subsequent bout to reduce interindividual variability. Such an approach would aim to align the physiological strain across individuals, despite differences in initial damage susceptibility. Using this individualized strategy, the volume and intensity of the repeated bout are adjusted based on post-exercise strength loss as a proxy for EIMD severity.\u003c/p\u003e\u003cp\u003eAccordingly, the present study aimed to evaluate a novel, exploratory approach to tailor the repeated bout based on individual post-exercise strength losses of after an initial bout of EIMD. We hypothesized that this would result in a reduction in variance independently from the mean changes, leading to an overall smaller interindividual variability across the damage markers.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design \u0026amp; individualization of the repeated bout\u003c/h2\u003e\u003cp\u003e This study was approved by the local ethics committee and conducted following the ethical standards set by the Declaration of Helsinki (DRKS00031644). The methodology was performed in adherence with the CONSORT guidelines. Participants performed two maximal, high-speed eccentric training protocols for the hamstrings on an isokinetic dynamometer (ISOMED 2000, D. \u0026amp; R. Ferstl GmbH, Hemau, Germany). Between bouts, there was a two-week resting interval. Prior to the intervention, all participants were familiarized with the measurements, and anthropometric data were collected using a 3D body scanner (Scaneca GmbH, Berlin, Germany). The initial eccentric exercise bout consisted of five sets of 15 maximal eccentric seated hamstring curls with one-minute rest intervals between sets and an eccentric contraction speed of 210\u0026deg;/s, and a passive, concentric contraction speed of 50\u0026deg;/s. Participants were seated with an 85\u0026deg; trunk flexion; knee joint range of motion was individualized based on the anthropometric characteristics in a range of 0\u0026deg; to 100\u0026deg; knee flexion (Schwiete, Roth, Skutschik, et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Room temperature was set to 23 C\u0026deg; throughout the intervention via air conditioning. The repeated bout was individualized based on their decrements in eccentric peak torque 48 hours post-exercise, where force losses typically peak after EIMD (Paulsen et al., \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Accordingly, the following formula was established, where the training volume of the repeated bout (\u003cem\u003eV\u003c/em\u003e\u003csub\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sub\u003e) was scaled directly to the force losses at 48 hours post-exercise (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\varDelta\\:\\%eccP{T}_{48h}\\)\u003c/span\u003e\u003c/span\u003e) after the initial bout (\u003cem\u003eV\u003c/em\u003e\u003csub\u003e\u003cem\u003e1\u003c/em\u003e\u003c/sub\u003e):\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:{V}_{2}=\\:{V}_{1}\\left(1-\\varDelta\\:\\%\\frac{eccPT48h}{100}\\right)$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eNeuromuscular assessments (eccentric peak torque, MVC, jumps), muscle contractility (Myoton, TMG), muscle stiffness (shear-wave elastography), and soreness (VAS) were performed before (pre) and after the intervention (post) as well on the consecutive four days (24\u0026ndash;96 hours post). Creatine kinase was measured pre and 24\u0026ndash;96 hours post (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003e30 male participants (25.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 years, 81.5\u0026thinsp;\u0026plusmn;\u0026thinsp;8.6 kg, 180.6\u0026thinsp;\u0026plusmn;\u0026thinsp;7.4 cm) were included in this project that employed a repeated measures, within-subject design. Approval was obtained from the local ethics committee, and each participant provided written informed consent for study participation. Inclusion criteria required participants to be male, between 18 and 35 years of age, free of injuries in the lower extremities, take no regular medications, and to train at least twice per week. Participants with lower body injuries, regular medication, and less than two training sessions per week were excluded from study participation. On average, participants performed 2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 hours of resistance training, 1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 hours of endurance training, and 1.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1 hours of other recreational sports (soccer, squash, badminton etc.) per week.\u003c/p\u003e\n\u003ch3\u003eStudy Parameters\u003c/h3\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eEccentric Peak Torque \u0026amp; MVC\u003c/h2\u003e\u003cp\u003eEccentric peak torque and MVC were evaluated on the ISOMED 2000. Participants began with a five-minute general warm-up on a stationary bike at 100 Watts (60\u0026ndash;70 rpm), followed by two eccentric warm-up sets on the isokinetic dynamometer. After securing the participants on the ISOMED, the lever arm was adjusted to ensure the axis of rotation was correctly aligned with the knee, providing clean and comfortable contact throughout the movement. MVC was measured at 90\u0026deg; knee flexion (Oakley et al., \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2013\u003c/span\u003e) during a single, five-second maximal isometric hold. After a three-minute rest, eccentric peak torque was tested in one set of five maximal eccentric contractions at the intervention speed (210\u0026deg;/s).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eShear-wave elastography\u003c/h3\u003e\n\u003cp\u003eShear-wave speed was used to assess the muscle stiffness of the participants in all three hamstring muscles. An ACUSON Redwood (Siemens Healthineers, Erlangen, Germany) with a 10L4 linear probe was used by the same experienced investigator. The probe was aligned in the longitudinal direction of the muscle with minimal pressure, and three consecutive measurements were performed at each location. A 6 x 10 mm region of interest was placed beneath the fascial sheath, and within this region of interest, two 10 mm diameter measurement circles were placed vertically. Real-time feedback on the reliability of the measurements was provided by a color‐coded confidence map. The measurement locations were adopted from Kawama et al. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e), including two sites on the m. biceps femoris (50% segment length \u0026amp; 10 cm distal), the m. semitendinosus (40% segment length \u0026amp; 10 cm distal), and the m. semimembranosus (60% segment length \u0026amp; 10 cm distal). Based on the shear wave speed of the individual locations, the ultrasound software calculated a stiffness main score including all measurement sites, which was used for the final data analysis.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCreatine Kinase\u003c/h2\u003e\u003cp\u003eCapillary blood samples were collected and immediately centrifuged (Universal 320 R, Andreas Hettich GmbH, Tufflingen, Germany) for 10 minutes at 3000 revolutions per minute. Afterwards, 10 \u0026micro;l of blood plasma was drawn using a reusable pipette (Eppendorf Research Plus, Eppendorf, Hamburg, Germany) and analyzed in a point-of-care-testing system (DRI-CHEM Analyzer FDC NX500, Fujifilm Europe, Duesseldorf, Germany). Post-exercise samples were manually diluted in the form of a dilution series (1:2; 1:4; 1:8; 1:16; 1:32; 1:64), using a concentrated 0.9% sodium chloride solution. The value of the lowest dilution was used for the final data analysis.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTensiomyography \u0026 Myoton\u003c/h3\u003e\n\u003cp\u003eTMG measurements (TMG-BMC Ltd., Ljubljana, Slovenia) were conducted at the same measurement locations as used for elastography. A TMG cushion was placed below the participants' shin to create a 5\u0026deg; knee flexion (Schwiete et al., \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Two self-adhesive dura‐stick electrodes (50 \u0026times; 50 mm) were attached to the skin with a 5 cm inter‐electrode distance (Piqueras-Sanchiz et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2020\u003c/span\u003e), and each placement was marked using a water‐resistant pen. Three measurements per site were performed at 100 mA, separated by a 30‐second rest interval. In keeping with the elastography protocol, a main radial displacement (D\u003csub\u003em\u003c/sub\u003e) score was calculated across all measurement sites for the final data analysis. Passive muscle stiffness (S, N/m) was assessed in multiscan mode using the Myoton device (Myoton Ltd., Tallinn, Estonia).\u003c/p\u003e\n\u003ch3\u003eCMJ, SJ, and DJ\u003c/h3\u003e\n\u003cp\u003eJumping performance was evaluated using an opto-electronic measurement system (OptojumpRX10, MicroGate, Bolzano, Italy). Participants were familiarized with correct jump execution during two introductory sessions before the intervention. All jumps were performed with hands placed on the hips, and three jumps were completed with a minimum of 30 seconds\u0026rsquo; rest between attempts. For squat jumps (SJs), participants were instructed to hold a 90\u0026deg; knee flexion for at least one second, and for drop jumps (DJs), a 30 cm box was used.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eMuscle Soreness\u003c/h2\u003e\u003cp\u003eMuscle soreness was measured using a 100 mm visual analog scale (VAS), ranging from \u0026ldquo;no pain at all\u0026rdquo; to \u0026ldquo;worst pain imaginable\u0026rdquo;. Participants were instructed following the procedure described by Schwiete et al. (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) to ensure proper application of the scale.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eFor statistical analyses, IBM SPSS Statistics (version 28.0), Jamovi (version 16.44), and GraphPad Prism (version 10.3) were utilized. To assess interindividual variability, the Pitman-Morgan test, a paired t-test of squared residuals, was used to compare absolute variances between two related conditions. Based on our directional hypothesis that individualization would reduce variability, one-tailed p-values were reported. In addition, the coefficient of variation (CV\u0026thinsp;=\u0026thinsp;SD/mean x 100) was calculated to evaluate relative variability, allowing for an interpretation regarding interindividual differences in proportion to the mean response (Lavender \u0026amp; Nosaka, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). For general comparisons between bouts, linear mixed-effects models (LMMs) were fitted separately for each dependent variable to examine changes over multiple time points and between experimental bouts. In each model, time, condition, and their interaction were tested as fixed effects. Covariates included baseline measures (PT, MVC, D\u003csub\u003em\u003c/sub\u003e, SWE), average resistance training volume (RTave), total repetitions in bout 2 (RepsB2), maximal perceived exertion in bout 1 (BORGmax), and average total work and PT decreases (%TWdrop, %PTdrop) in bout 1. A random intercept for each participant was included to account for within-subject correlation arising from repeated measures. Model fit was assessed via log-likelihood, AIC, and BIC, and both marginal (fixed effects only) and conditional (fixed plus random effects) R\u0026sup2; values were reported to gauge explanatory power. Statistical significance was evaluated at an alpha level of 0.05, and, where applicable, significant main or interaction effects were further explored using Bonferroni-corrected post-hoc comparisons. Assumptions of linearity and normality of residuals were checked through diagnostic plots, and data were screened for outliers before final model estimation.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePeak torque, MVC \u0026amp; jumps\u003c/h2\u003e\u003cp\u003eFor peak torque, model fit revealed that fixed effects explain 45% (marginal R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.45) of the variance and random effects account for 25% (ICC\u0026thinsp;=\u0026thinsp;0.25). There was a significant time x condition effect (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), with larger force decreases after bout 1 compared to bout 2 at 24 h to 96 h post (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Among covariates, baseline PT (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), RepsB2 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004), and RTave (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021) were all positively associated with higher post-exercise PT. The Pitman-Morgan results showed that the interindividual variability for PT was significantly lower after the repeated bout compared to bout 1 after 72 h post-exercise (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049). Additionally, CVs showed lower relative variability after the repeated bout (16.25%) compared to bout 1 (27.7%).\u003c/p\u003e\u003cp\u003eThe model fit for MVC showed that 39% of the variability is explained by fixed effects (marginal R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.39) and 17% is between individuals\u0026rsquo; intercept (ICC\u0026thinsp;=\u0026thinsp;0.17). There were no significant time x condition effects (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.28), but both time and condition had significant main effects (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Higher baseline MVC (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) and PT (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.037), as well as RepsB2 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.025) predicted lower MVC decreases post-exercise. Similar to PT, the variance in MVC was significantly lower after the repeated bout after 72 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015; CV: 32.9 vs. 19.1%), but also after 96 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.024; CV: 29.8 vs. 18.9%).\u003c/p\u003e\u003cp\u003eWhile for CMJ (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) and SJ (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021), significant time effects were revealed, DJ differed significantly between bouts (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Additionally, no differences in variance were present for any jump at any time point.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eCK \u0026amp; muscle soreness\u003c/h2\u003e\u003cp\u003eThere was a significant time x condition interaction for CK (p\u0026thinsp;=\u0026thinsp;0.002), showing higher CK increases after bout 1 compared to bout 2 after 72 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018) and 96 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). There were no significant changes in CK after bout 2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The overall model showed that fixed effects explained 24% of the variance (marginal R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.24) and between-subject variability was 4% (ICC\u0026thinsp;=\u0026thinsp;0.04). While higher baseline D\u003csub\u003em\u003c/sub\u003e was associated with higher post-exercise CK (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), a higher repetition count in bout 2 was linked to lower CK responses (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The results of the Pitman-Morgan test showed a significantly lower absolute variability for CK after 72 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04) and 96 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). Additionally, CVs for bout 2 were smaller compared to bout 1 at 72 h (196.7 vs. 113.8%) and 96 h (205.2 vs. 83%).\u003c/p\u003e\u003cp\u003eThere was a significant time x condition interaction for VAS (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), with greater muscle soreness after bout 1 compared to bout 2 from 24 h post onwards (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Fixed effects explained 43% of the variance, and 11% was from between-person differences (ICC\u0026thinsp;=\u0026thinsp;0.114). Similar to CK, more repetitions during bout 2 were linked to a lower response in muscle soreness (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Pitman-Morgan test results revealed a significantly lower absolute variability after the repeated bout at the 24 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02), 48 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), 72 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and 96 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Contrary, relative variability was consistently higher after the repeated bout compared to bout 1 at these time points (24 h: 84 vs. 89.14%; 48 h: 69.9 vs. 93.65%; 72 h: 89.1 vs. 116.7%; 96 h: 115.5 vs. 126.1%).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eMuscle stiffness \u0026amp; muscle contractility\u003c/h2\u003e\u003cp\u003eThere was no significant time x condition effect for elastography (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.34); however, time and condition (both \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) both show significant main effects. The overall model showed that 28% of the variance is explained by fixed effects (marginal R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.28) and 58% is from between-subject variability (ICC\u0026thinsp;=\u0026thinsp;0.58). Among covariates, baseline contractility (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) and peak torque (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006) significantly affected muscle stiffness. No time x condition interaction (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.78) was found for D\u003csub\u003em\u003c/sub\u003e, but time (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.09) and condition (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.02) were significant. Covariates did not significantly affect D\u003csub\u003em\u003c/sub\u003e. For Myoton, no significant effects were found. Neither absolute nor relative variance decreased for muscle stiffness or muscle contractility.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe present study investigated whether tailoring a repeated bout - based on the magnitude of post-exercise peak torque loss - could reduce interindividual variability in markers of EIMD. Importantly, variability was assessed both in absolute terms (via the Pitman-Morgan test) and relative to the group mean (via the coefficient of variation, CV), thus enabling a more nuanced interpretation of group-level response heterogeneity.\u003c/p\u003e\u003cp\u003eOur findings support this approach: several key markers - namely peak torque, MVC, CK activity, and perceived muscle soreness - showed substantially lower absolute and relative variability in the repeated bout. The largest reductions in CV were observed at 72 hours post-exercise. This suggests that individualized loading not only reduces the magnitude of damage for some individuals but also contributes to a more consistent physiological strain across the group.\u003c/p\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eChanges in variability\u003c/h2\u003e\u003cp\u003eThe main finding of our study is that tailoring a repeated bout based on individual force losses after 48 h of the initial bout can effectively reduce the absolute and relative variance in EIMD markers. The variability in our study was notably reduced for peak torque, MVC, CK, and muscle soreness at different time points between 24 and 96 h post-exercise. The greatest differences in variance between both bouts were observed at 72 hours post-exercise. When comparing relative variability (CVs), we did not consistently find a smaller variance compared to standard RBE studies. For instance, in studies of Chen et al. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) and Nikolaidis et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), CVs for peak torque and MVC were smaller at the same time post-exercise. These studies involved maximal eccentric contractions for the knee flexors and were separated by 2 or 3 weeks, respectively. Relative variability after 72 h for peak torque (Nikolaidis et al.: 7.5%) and MVC (Chen et al.: 6.61%) was substantially lower in these studies than in ours (PT 72h: 16.25%; MVC 72h: 19.1%). On the other hand, our results show lower relative variance in peak torque and MVC compared to studies of Da Silva et al. (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2023\u003c/span\u003e) and Howatson et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2007\u003c/span\u003e). For example, Howatson et al. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), who investigated the RBE in the elbow flexors, found relative variability in MVC after 96 h was higher in their study compared to our tailored RB (26.5% vs. 18.9%). Additionally, in the study of (Da Silva et al., \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2023\u003c/span\u003e), who performed unilateral eccentric contractions with the knee flexors, peak torque variance was higher after 24 h (27.5%) than in our study (18.9%).\u003c/p\u003e\u003cp\u003eVariability in CK activity and soreness was even more pronounced. Absolute CK variance was significantly lower after the individualized repeated bout at 72 and 96 h post-exercise. However, when comparing the relative variance to standard RBE studies (Chen et al., \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2018\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Nikolaidis et al., \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), our interindividual variability is substantially higher, possibly due to our higher absolute variance. While our participants reached maximum CK above 80000 U/L, the CK response in comparable studies by Nikolaidis et al. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2007\u003c/span\u003e) and Chen et al. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2025\u003c/span\u003e) peaked at 2200 U/L and 9000 U/l, respectively. Similar to CK, soreness variability was greatly reduced at all time points from 24 to 96 h post. However, the relative variance in soreness was substantially higher in our study compared to regular RBE studies (Chalchat et al., \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2022\u003c/span\u003e; T. C. Chen et al., \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Deyhle et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThese differences in absolute and relative variance among the different damage markers can partly be explained by our LMM models and the influence of random intercepts. Our results show moderately high ICCs for peak torque and MVC (PT: 0.25; MVC: 0.17), indicating that a significant amount of variability was due to stable between-individual differences (e.g., baseline strength, etc). Accordingly, even when adjusting the load of the repeated bout, a substantial portion of this stable variance remains, limiting the extent to which variability could be reduced. This might also explain the missing differences in stiffness and contractility variance, as ICCs were even higher in these markers (SWE: 0.58; Dm: 0.33), showing that most of the variability is explained by stable individual differences rather than time or condition effects. In contrast, the low ICCs for CK (0.04) and soreness (0.1) suggest that most of the variance was affected by modifiable training variables like condition, reps, etc. Therefore, the tailoring of the repeated bout was much more effective in reducing the absolute and relative variance in the EIMD markers.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eOverall changes between bout 1 \u0026amp; 2\u003c/h2\u003e\u003cp\u003eBeyond the differences in variability, the overall comparison between the initial and repeated bout demonstrates the typical features of a RBE. Across our study population, attenuated changes in damage markers were observed regarding force production (peak torque, MVC), CK activity, and muscle soreness following the tailored repeated bout.\u003c/p\u003e\u003cp\u003eFor peak torque, our LMM revealed a significant time x condition interaction (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), indicating a smaller reduction in peak torque after the repeated bout. The covariates revealed a positive association between the post-exercise force levels and baseline peak torque, average resistance training volume, and number of repetitions in bout 2. In comparison to this, MVC changes showed a different pattern with no significant interaction (p\u0026thinsp;=\u0026thinsp;0.28), but with main effects for both time and condition independently (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similar to the peak torque model, baseline strength levels and number of repetitions in bout 2 significantly affected the damage response to the repeated bout. Our findings show that baseline strength, training background, and exercise volume significantly affect the response to EIMD, which is in line with the findings of Vincent \u0026amp; Vincent (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e1997\u003c/span\u003e) and Ertel et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). They found that individuals with a more extensive training background experience less severe muscle damage compared to untrained participants. All of these results reemphasize the consistent exposure to resistance training in elite sports to attenuate EIMD, possibly because of reduced z-band streaming (Damas et al., \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2016\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFor both CK and muscle soreness, there was a significant time x condition interaction. After the initial bout, CK rose until 96 h post, whereas there were no significant increases after the repeated bout. The interaction shows that the differences in CK are mainly present at the 72 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013) and 96 h (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) timepoints, which does not come surprisingly as we know that CK activity commonly peaks 3\u0026ndash;6 days after the initial eccentric stimulus (Clarkson \u0026amp; Hubal, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2002\u003c/span\u003e). The results from our study yet again confirm the large interindividual variability of CK responses Chen (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2006\u003c/span\u003e), with values ranging between 169 and 83776 U/L at the 96 h post-time point after the initial bout. Interestingly, our data suggest no matching between the CK responses between bout 1 and 2, meaning that high responders after bout 1 were not high responders after bout 2, contrary to the reports of Chen (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2006\u003c/span\u003e). Rather, the repeated bout led to a disproportionately larger attenuation in CK among high responders from bout 1. For instance, the two highest responders from bout 1 (83776 U/L and 67543 U/L) dropped to 306 and 890 U/L at the same time point (96 hours post) after bout 2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). This reinforces that tailoring the repeated bout was especially effective in suppressing CK response.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFor soreness, VAS scores differ from 24 h post onwards, with higher muscle soreness after the first bout and peaking after 48 h. For both CK and soreness, the number of repetitions in bout 2 emerged as a key predictor of the post-exercise response.\u003c/p\u003e\u003cp\u003eIn contrast, jumping performance (CMJ, SJ, and DJ) as well as muscle stiffness and contractility were less affected by the tailoring of the repeated bout. While shear-wave speed showed a significant time and condition (both p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) effect, the other parameters did not change. These findings likely indicate the more multifactorial nature of these measures, including training history, central motor control, or even tendon properties. This range of influencing variables makes these parameters less sensitive to adaptations in eccentric muscle contractions solely.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eWhile the findings of this study offer promising insights into individualized load management, several limitations should be acknowledged. First, the sample was limited to young, active males, which restricts generalizability to other populations such as female athletes, older adults, or elite performers. Future research should examine whether similar effects on variability and recovery can be observed across diverse cohorts with different training backgrounds and physiological profiles. Second, the study focused exclusively on the hamstring muscle group using a seated isokinetic protocol. Responses may differ in other muscle groups or under more sport-specific or functional loading conditions. Additionally, while the volume of the repeated bout was individualized based on early torque losses \u0026mdash; a functional and practical marker \u0026mdash; other variables such as soreness, CK, or stiffness were not used to further refine the individualization process. A more multidimensional individualization strategy could potentially enhance the precision and efficacy of the intervention. Finally, the study was limited to short-term responses (up to 96 hours post-exercise). Longitudinal research is needed to evaluate whether reduced variability in acute responses translates to improved performance outcomes, injury prevention, or training adaptations over time. These considerations highlight the need for continued investigation into individualized loading strategies, with the goal of optimizing both short- and long-term outcomes across broader athletic and clinical populations.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study highlights that tailoring a repeated bout based on individual force losses after 48 hours can reduce variability in muscle damage markers, including peak torque, MVC, CK activity, and muscle soreness. Notably, our results show reduced variability in both absolute and relative terms. The greatest reductions in variability were observed at 72 hours post-exercise, with variability in CK and soreness showing the most significant decrease. However, when comparing the relative variability in our study to other regular RBE studies, the results were inconsistent. In some cases, our variability was smaller, while in others, it was larger, particularly in soreness and CK activity. Despite these inconsistencies, our results showed that the tailored repeated bout was more effective in reducing variance in CK and soreness than in other markers, such as peak torque and MVC, where baseline strength and training background played a larger role.\u003c/p\u003e\u003cp\u003eWhile we observed some beneficial effects of individualizing the repeated bout, these findings are not entirely conclusive. The variability across studies and time points limits our ability to definitively conclude that our tailored repeated bout reduces interindividual variability more effectively than a standard repeated bout. Future research is needed to clarify the potential advantages of individualized approaches in muscle damage recovery and the factors that contribute to these differences.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e No fundings were received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data:\u003c/strong\u003e The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e This study was reviewed and approved by the Ethics Committee Department 05, Goethe University (no.; 2023 - 35). This study was performed in line with the principles of the Declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e The participants gave informed written consent to the main study and to receive invitations to sub-studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003enot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor’s contribution:\u003c/strong\u003e CS wrote the first draft of the manuscript. CS, HB, and MB were responsible for planning the study and for the study design. CS, CH, and KH conducted the study. CS analyzed and interpreted the data. CS, JM, HB, and MB revised the manuscript. The corresponding author attests that all listed authors meet authors hip criteria and that no others meeting the criteria have been omitted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBouchard, C., \u0026amp; Rankinen, T. (2001). Individual differences in response to regular physical activity: \u003cem\u003eMedicine and Science in Sports and Exercise\u003c/em\u003e, \u003cem\u003e33\u003c/em\u003e(Supplement), S446\u0026ndash;S451. https://doi.org/10.1097/00005768-200106001-00013\u003c/li\u003e\n \u003cli\u003eBourdon, P. C., Cardinale, M., Murray, A., Gastin, P., Kellmann, M., Varley, M. C., Gabbett, T. J., Coutts, A. J., Burgess, D. 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Prolonged Muscle Damage Depends on Force Variability. \u003cem\u003eInternational Journal of Sports Medicine\u003c/em\u003e, \u003cem\u003e31\u003c/em\u003e(02), 77\u0026ndash;81. https://doi.org/10.1055/s-0029-1241213\u003c/li\u003e\n \u003cli\u003eSkurvydas, A., Brazaitis, M., \u0026amp; Kamandulis, S. (2011). Repeated Bout Effect is not Correlated With Intraindividual Variability During Muscle-Damaging Exercise. \u003cem\u003eJournal of Strength and Conditioning Research\u003c/em\u003e, \u003cem\u003e25\u003c/em\u003e(4), 1004\u0026ndash;1009. https://doi.org/10.1519/JSC.0b013e3181d68563\u003c/li\u003e\n \u003cli\u003eVincent, H., \u0026amp; Vincent, K. (1997). \u003cem\u003eThe effect of training status on the serum creatine kinase response, soreness and muscle function following resistance exercise\u003c/em\u003e. \u003cem\u003e18\u003c/em\u003e(6), 431\u0026ndash;437. https://doi.org/10.1055/s-2007-972660\u003c/li\u003e\n \u003cli\u003eWillberg, C., Wieland, B., Rettenmaier, L., Behringer, M., \u0026amp; Zentgraf, K. (2022). The relationship between external and internal load parameters in 3 \u0026times; 3 basketball tournaments. \u003cem\u003eBMC Sports Science, Medicine and Rehabilitation\u003c/em\u003e, \u003cem\u003e14\u003c/em\u003e(1), 152. https://doi.org/10.1186/s13102-022-00530-1\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-sports-science-medicine-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssmr","sideBox":"Learn more about [BMC Sports Science, Medicine and Rehabilitation](http://bmcsportsscimedrehabil.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ssmr/default.aspx","title":"BMC Sports Science, Medicine and Rehabilitation","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7372578/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7372578/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eInterindividual variability in response to standardized eccentric exercise presents a major challenge for load management in both research and applied sports settings. The repeated bout effect (RBE) is known to attenuate symptoms in response to exercise-induced muscle damage (EIMD), but it remains unclear whether an individualization of the RBE based on EIMD-markers can reduce the interindividual variability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: Thirty trained males (25.4 ± 2.8 years) completed two bouts of high-speed eccentric hamstring exercise, separated by 14 days. The volume of the repeated bout was individualized based on the peak torque reductions at 48 hours after the first bout. Absolute (Pitman-Morgan test) and relative (coefficient of variation) variance, as well as mean changes (linear mixed models) of neuromuscular function (peak torque, MVC, jumps), muscle tissue changes (elastography, TMG, Myoton), creatine kinase levels, and soreness were assessed pre- and post-exercise up to 96 hours.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe individualized repeated bout resulted in significantly lower absolute and relative variance most prominently after 72 hours, in peak torque (\u003cem\u003ep\u003c/em\u003e = 0.04), MVC (\u003cem\u003ep\u003c/em\u003e = 0.02), CK (\u003cem\u003ep\u003c/em\u003e = 0.04), and soreness (\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eIndividualizing the repeated bout based on peak torque losses of the initial bout reduced the absolute and relative variance of EIMD. This approach could help with load management and recovery strategies in elite sports settings.\u003c/p\u003e\n\u003cp\u003eTrial registration date: 04/07/2023\u003c/p\u003e\n\u003cp\u003eTrial registration number:\u003cstrong\u003e \u003c/strong\u003eDRKS00031644\u003c/p\u003e","manuscriptTitle":"Tailoring the second bout of exercise to individual strength losses after initial muscle-damaging exercise: effects on recovery and damage markers","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-02 12:10:24","doi":"10.21203/rs.3.rs-7372578/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-10-29T12:32:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-15T19:51:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"278587127261267992847163920815861499077","date":"2025-10-12T12:03:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66540990318077772508540254375540590610","date":"2025-10-10T16:03:02+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-09T05:20:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"196798515238626841942898571001958600375","date":"2025-08-25T12:08:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-25T06:49:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-25T06:43:39+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-21T06:02:43+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-20T16:12:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Sports Science, Medicine and Rehabilitation","date":"2025-08-20T16:09:48+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-sports-science-medicine-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ssmr","sideBox":"Learn more about [BMC Sports Science, Medicine and Rehabilitation](http://bmcsportsscimedrehabil.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ssmr/default.aspx","title":"BMC Sports Science, Medicine and Rehabilitation","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"64886158-124c-4cf2-8eb0-930751f100b7","owner":[],"postedDate":"September 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-09-02T12:10:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-02 12:10:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7372578","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7372578","identity":"rs-7372578","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}