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Holmberg, Hans-ChristerORCID iD iconorcid.org/0000-0002-3814-6246
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Publications (10 of 283) Show all publications
Skattebo, Ø., Martin-Rincon, M., Calbet, J. A. L., Hallén, J. & Holmberg, H.-C. (2026). A Review of Central and Peripheral Limitations to Endurance Exercise Performance on the Road to the Milano-Cortina 2026 Olympics. Scandinavian Journal of Medicine and Science in Sports, 36(3), Article ID e70266.
Open this publication in new window or tab >>A Review of Central and Peripheral Limitations to Endurance Exercise Performance on the Road to the Milano-Cortina 2026 Olympics
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2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 3, article id e70266Article, review/survey (Refereed) Published
Abstract [en]

Performance in endurance sports reflects a complex interplay between physiological, biomechanical, neuromuscular and psychological factors, nutrition, and environmental conditions. This review focuses on physiological factors, particularly on the determinants of maximal oxygen uptake (VO2max), its fractional utilization during competition, and examines how these interact with sport-specific demands and conditions anticipated at the Milano-Cortina 2026 Winter Olympics. We highlight that systemic O2 delivery, determined by the product of cardiac output and arterial O2 content, is the primary limiting factor of VO2max in elite athletes. However, invasive data on elite female athletes are scarce, and more research is needed. Well-developed peripheral characteristics, such as a high mitochondrial density and capillarisation, are important determinants of fractional utilization of VO2max, but also support high muscle O2 extraction, which may reach values above 95% in elite endurance athletes, including cross-country skiers. However, most values of fractional utilization of VO2max in the literature are calculated estimates based on performance determinants and race times, and more research with direct, continuous O2 uptake measurements during simulated competitions is needed. In endurance sports with undulating terrain race profiles (uphill, downhill, flats), such as cross-country skiing and biathlon, the resulting intermittent exercise intensity creates substantial fluctuations in external power output. As a result, O2 demands may reach 100%–160% of VO2max in uphill sections, facilitated by transient but profound anaerobic energy contributions. Thus, the ability to recover anaerobic energy sources in downhill sections and repeatedly use them throughout the race emerges as a critical performance determinant and an avenue for further research, as well as how these abilities influence fractional utilization of VO2max in intermittent sports. Environmental factors, including moderate altitude (Biathlon will be held in Antholz at ~1650 m) and cold temperatures, exert modest but relevant influences on performance. Understanding these integrative mechanisms is essential for optimizing training and competition strategies for endurance sports at the Winter Olympics and beyond.

Place, publisher, year, edition, pages
John Wiley and Sons Inc, 2026
Keywords
biological sex, cardiac output, elite athletes, endurance performance, limiting factors, maximal oxygen uptake, oxygen extraction, oxygen transport
National Category
Sport and Fitness Sciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116982 (URN)10.1111/sms.70266 (DOI)001720799000001 ()41845944 (PubMedID)2-s2.0-105033121211 (Scopus ID)
Note

Funder: Ministerio de Ciencia, Innovación y Universidades (PID2024- 156206OA- I00, PDC2025- 165723- I00) 

Available from: 2026-04-08 Created: 2026-04-08 Last updated: 2026-06-30Bibliographically approved
Ørtenblad, N., Holmberg, H.-C., Nybo, L. & Gejl, K. D. (2026). Carbohydrate Storage and Supplementation Strategies for Peak Performance in Cross-Country Skiing. Scandinavian Journal of Medicine and Science in Sports, 36(3), Article ID e70242.
Open this publication in new window or tab >>Carbohydrate Storage and Supplementation Strategies for Peak Performance in Cross-Country Skiing
2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 3, article id e70242Article in journal (Refereed) Published
Abstract [en]

Carbohydrates are essential for sustaining performance in most competitive exercise, fueling both anaerobic glycolysis during high-intensity efforts and aerobic metabolism during prolonged activity. Numerous factors contribute to muscle fatigue and exercise performance; still, carbohydrate and muscle glycogen contents are agreed to have an essential role in sustaining prolonged exercise at moderate-to-high intensities. To maintain consistent training and competition performance, elite athletes under certain conditions consume adequate carbohydrates between sessions to restore liver and muscle glycogen and possibly supplement during prolonged workouts to delay depletion. Effective glycogen restoration requires both sufficient carbohydrate intake and adequate recovery time. Understanding how glycogen levels fluctuate during intense or prolonged exercise, the rate at which stores are utilized, and the optimal amount and timing of carbohydrate intake for replenishment is essential. Here we examine the role of carbohydrate availability and utilization in competitive cross-country skiing, which is characterized by exceptionally high whole-body energy turnover with varying loads on the upper- and lower-body muscles as well as fluctuating physiological demands determined by course profile, snow conditions, sub-technique, and race format. This narrative review synthesizes existing evidence on the role of muscle glycogen contents and carbohydrate intake in muscle function and fatigue mechanisms, with a particular focus on cross-country skiing and herein biathlon and Nordic combined. Additionally, we explore how exercise influences glycogen metabolism, the factors regulating glycogen utilization, and training adaptation in order to clarify physiological underpinnings and practical implications for endurance athletes.

Place, publisher, year, edition, pages
John Wiley and Sons Inc, 2026
Keywords
biathlon, carbohydrate, cross- country skiing, glycogen, Nordic combined, Olympic, performance, recovery
National Category
Sport and Fitness Sciences Physiology and Anatomy
Research subject
Physiotherapy
Identifiers
urn:nbn:se:ltu:diva-116698 (URN)10.1111/sms.70242 (DOI)001703915800001 ()41755452 (PubMedID)2-s2.0-105031477839 (Scopus ID)
Funder
Novo Nordisk Foundation
Note

Full text license: CC BY;

This article also appears in:Winter Sports Science: https://onlinelibrary.wiley.com/doi/toc/10.1111/(ISSN)1600-0838.winter-sports-science

Available from: 2026-03-24 Created: 2026-03-24 Last updated: 2026-06-30Bibliographically approved
Boraxbekk, C., Supej, M. & Holmberg, H. (2026). Cognitive Neuroscience in Alpine Skiing: Introducing Computational Sports Medicine for Performance Optimization. Scandinavian Journal of Medicine and Science in Sports, 36(1), Article ID e70188.
Open this publication in new window or tab >>Cognitive Neuroscience in Alpine Skiing: Introducing Computational Sports Medicine for Performance Optimization
2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 1, article id e70188Article in journal (Refereed) Published
Abstract [en]

While sport psychology has long emphasized mental and cognitive aspects of performance, sports medicine has traditionally focused on musculoskeletal and physiological aspects, largely overlooking the brain's central role in athletic performance. This narrative review aims to bridge this gap by introducing Computational Sports Medicine, a novel framework that integrates cognitive neuroscience with established physiological and biomechanical measures. Using alpine skiing as a primary example, this review examines the critical role of working memory updating in dynamic environments, discusses how neural processes enable adaptation, and proposes Computational Sports Medicine as a unifying predictive framework. This approach moves beyond descriptive analysis to provide objective, quantifiable metrics, testable models, and the ability to simulate “what-if” scenarios for proactive intervention. Practical implications for training include developing sport-specific cognitive tasks, individualizing variability in motor and cognitive learning, and leveraging technologies like virtual reality and wearable sensors. The review primarily targets elite and sub-elite athletes, for whom cognitive and environmental demands are most pronounced. This brain-inclusive framework offers a personalized approach to performance optimization, injury prevention, and safe return-to-play decisions, positioning the brain as the central organ to the future of sports medicine.

Place, publisher, year, edition, pages
John Wiley & Sons, 2026
Keywords
athlete development, brain, predictive modeling, working memory updating
National Category
Sport and Fitness Sciences Neurosciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116095 (URN)10.1111/sms.70188 (DOI)001659147700001 ()41521369 (PubMedID)2-s2.0-105027100290 (Scopus ID)
Note

Full text license: CC BY

Available from: 2026-01-21 Created: 2026-01-21 Last updated: 2026-06-30Bibliographically approved
Sperlich, B. & Holmberg, H.-C. (2026). Endurance Training in Olympic Winter Sports: A Narrative Review of the Current Literature and Future Research Priorities. Scandinavian Journal of Medicine and Science in Sports, 36(2), Article ID e70220.
Open this publication in new window or tab >>Endurance Training in Olympic Winter Sports: A Narrative Review of the Current Literature and Future Research Priorities
2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 2, article id e70220Article, review/survey (Refereed) Published
Abstract [en]

The Milano-Cortina 2026 Winter Olympics present an opportunity to synthesize evolving paradigms in endurance training within the broader context of long-term athlete development. As Olympic winter sports span from endurance-limited events to disciplines in which aerobic fitness primarily serves as a feeder capacity, a single training model is insufficient. In this narrative review, we propose a dual framework: (1) a demand-driven, athlete-centered, data-supported model for Endurance-Limited sports (e.g., cross-country skiing, biathlon) and (2) a Feeder-Function model for sports in which endurance primarily supports recovery, training tolerance, and resilience (e.g., freestyle skiing, snowboarding, sliding sports). Within this framework, we narratively synthesize and critically evaluate the literature across key domains, including individualized volume–intensity architectures, the integration of concurrent strength training, and the strategic use of multimodal stress stacking (e.g., hypoxia, heat). We further address the operationalization of emerging performance constructs such as durability, fatigability, resilience, and repeatability. We also present a heuristic tier framework describing when endurance acts as a primary performance limiter versus a supporting capacity across Olympic winter sports. Subsequently, we examine the role of advanced technologies, from multisensor wearables and analytics to mechanistic approaches (e.g., multiomics), highlighting their potential to shift practice from passive monitoring to active, individualized modeling. Future research priorities include validating field-based operational metrics, defining minimal effective endurance doses for feeder-function sports, and developing interpretable, athlete-centered decision-support tools. By aligning sport-specific demands with individualized, evidence-informed prescription, this dual-framework approach offers a perspective to guide interpretation and future applied work for scientists, coaches, and athletes preparing for Milano-Cortina 2026 and beyond.

Place, publisher, year, edition, pages
John Wiley and Sons Inc, 2026
Keywords
adaptive phenotyping, duarability, fatgability, fatigue, load-response modeling, recovery, training responsiveness
National Category
Sport and Fitness Sciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116526 (URN)10.1111/sms.70220 (DOI)001692345800001 ()41673933 (PubMedID)2-s2.0-105029739891 (Scopus ID)
Note

Full text license: CC BY 4.0;

Available from: 2026-02-25 Created: 2026-02-25 Last updated: 2026-06-30Bibliographically approved
Edholm, P., Bouten, L. J. L., Holmberg, H.-C., Losnegard, T. & Hettinga, F. J. (2026). Mind-Muscle-Environment Interactions: Psychophysiological Determinants of Optimal Pacing in Olympic Winter Endurance Sports. Scandinavian Journal of Medicine and Science in Sports, 36(2), Article ID e70215.
Open this publication in new window or tab >>Mind-Muscle-Environment Interactions: Psychophysiological Determinants of Optimal Pacing in Olympic Winter Endurance Sports
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2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 2, article id e70215Article in journal (Refereed) Published
Abstract [en]

Pacing is a critical determinant of performance in Olympic endurance winter sports such as cross-country skiing, biathlon, and speed skating. Although the physiological (“engine”) and psychological (“operator”) determinants of pacing have frequently been examined in isolation, growing evidence highlights the need for an integrated psychophysiological perspective. This structured narrative review first outlines the defining characteristics of Olympic winter sports and, within this context, synthesizes current knowledge on the psychophysiological mechanisms governing pacing to inform optimal preparation strategies. We describe how the physiological engine, encompassing energy systems, fatigue, and afferent feedback, and the psychological operator, involving self-regulation, expectations, and cognitive-affective processes, interact to shape pacing behavior. Moreover, the distinctive demands of winter endurance events necessitate consideration of environmental factors such as head-to-head racing formats, variable weather conditions, and undulating terrain. The affordance competition hypothesis is proposed as a unifying framework for understanding pacing as a continuous decision-making process driven by dynamic mind-muscle-environment interactions. Finally, practical recommendations for athletes and coaches preparing for the Milano–Cortina 2026 Winter Olympic Games are presented, advocating a phased training approach that integrates physiological and psychological development within ecologically valid environments. Future research should prioritize real-world competition settings, neurocognitive mechanisms, and underrepresented populations, including women and para-athletes. We conclude that Olympic success in modern endurance winter sports depends on mastering an integrated psychophysiological control system, where performance is determined by both physical capacity and its effective regulation under varying environmental conditions.

Place, publisher, year, edition, pages
John Wiley and Sons Inc, 2026
Keywords
biathlon, cross-country skiing, endurance performance, pacing, psychophysiology, speed skating, winter sports
National Category
Sport and Fitness Sciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116590 (URN)10.1111/sms.70215 (DOI)001692342000001 ()41665741 (PubMedID)2-s2.0-105029779671 (Scopus ID)
Note

Full text license: CC BY 4.0;

Available from: 2026-03-05 Created: 2026-03-05 Last updated: 2026-06-30Bibliographically approved
Sperlich, B., Zoppirolli, C., Hettinga, F., Hannigan, L. S., Colyer, S., Vigh-Larsen, J. F., . . . Holmberg, H.-C. (2026). Olympic Ice Sports: A Narrative Review and Perspectives Toward Milano-Cortina 2026. Scandinavian Journal of Medicine and Science in Sports, 36(2), Article ID e70213.
Open this publication in new window or tab >>Olympic Ice Sports: A Narrative Review and Perspectives Toward Milano-Cortina 2026
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2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 2, article id e70213Article, review/survey (Refereed) Published
Abstract [en]

As the Milano-Cortina 2026 Winter Olympics approach, a consolidated understanding of performance determinants across the diverse spectrum of ice sports is crucial, yet the scientific literature remains unevenly distributed. This structured narrative review synthesizes available evidence on key performance-determining factors and contemporary training characteristics for Olympic ice sports, based on topic-driven literature searches and qualitative synthesis. Disciplines are grouped according to their primary performance demands. (1) High-volume gliding sports (long- and short-track speed skating): Performance balances biomechanical efficiency (e.g., aerodynamic posture) against physiological constraints. This necessitates high annual training volumes (900–1100 h·year−1), polarized, mixed-modal training, with short-track adding critical tactical and pack-dynamic elements. (2) Exposure-driven gravity sports (bobsleigh, skeleton, luge): Performance is overwhelmingly determined by start velocity, with the initial 15–65 m contributing disproportionately to overall race outcome. Bobsleigh and skeleton training mirrors sprint athletes, prioritizing lower-body power, while luge demands explosive upper-body strength. (3) Arena-based sports (ice hockey, figure skating, curling): These sports show varied demands. Ice hockey requires managing high-intensity intermittent efforts, with 40%–50% of on-ice distance performed at high skating speeds; figure skating hinges on the power and precision of high-value jumps (e.g., triple and quadruple rotations); and curling relies on delivery accuracy and sweeping strength-endurance. Sex-specific differences, often related to absolute power output (skating, sliding) and biomechanics, are evident, although evidence remains limited or uneven across several disciplines. Rather than providing prescriptive training models, this review identifies discipline-specific training priorities and key gaps in the current evidence base relevant to athlete preparation for Milano-Cortina 2026. 

Place, publisher, year, edition, pages
John Wiley and Sons Inc, 2026
Keywords
gliding sport, ice sport, Olympic sport, winter sport
National Category
Sport and Fitness Sciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116634 (URN)10.1111/sms.70213 (DOI)001693762100001 ()41707040 (PubMedID)2-s2.0-105030489635 (Scopus ID)
Note

Full text license: CC BY

Available from: 2026-03-04 Created: 2026-03-04 Last updated: 2026-06-30Bibliographically approved
Zoppirolli, C., Fornasiero, A., Spörri, J., Losnegard, T., Elfmark, O. A., Sandbakk, Ø. & Holmberg, H.-C. (2026). Olympic Snow Sports: Current Insights and Future Directions for Milano Cortina 2026 and Beyond. Scandinavian Journal of Medicine and Science in Sports, 36(2), Article ID e70222.
Open this publication in new window or tab >>Olympic Snow Sports: Current Insights and Future Directions for Milano Cortina 2026 and Beyond
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2026 (English)In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 36, no 2, article id e70222Article, review/survey (Refereed) Published
Abstract [en]

As the Milano Cortina 2026 Winter Olympic Games approach, a comprehensive understanding of performance determinants across Olympic snow sports is increasingly important to further evolve training and performance. However, the scientific literature remains unevenly distributed, with well-established knowledge in cross-country skiing, biathlon, and alpine skiing, and limited data in disciplines such as ski mountaineering, freestyle skiing, snowboarding, ski jumping, and Nordic combined. This narrative review synthesizes current evidence to (1) identify key performance-determining factors, (2) describe discipline-specific training characteristics, and (3) highlight critical knowledge gaps. Regarding performance determinants, Olympic snow sports can be broadly categorized into endurance-dominant disciplines (e.g., cross-country skiing, biathlon, ski mountaineering), which rely on high aerobic capacity and movement efficiency, and the gravity and technical disciplines (e.g., alpine skiing, freestyle skiing, snowboarding, ski jumping), which emphasize neuromuscular power and technical precision. Nordic combined represents a hybrid of these categories. In terms of training characteristics, elite athletes' training models reflect sport-specific demands through tailored combinations of endurance, strength–power, technical, tactical, and psychological preparation. Finally, regarding knowledge gaps, sex-specific analyses of physiological profiles, biomechanics, and training responses remain scarce, particularly in gravity and technical sports. Furthermore, standardized documentation of training structure, integration of on-snow monitoring technologies, and research on energy availability remain underdeveloped. Addressing these gaps through holistic, multidisciplinary research is essential to develop individualized, sex-informed, and evidence-based frameworks that support athlete development and performance optimization in the lead-up to Milano Cortina 2026 and future Olympic cycles.

Place, publisher, year, edition, pages
John Wiley & Sons, 2026
Keywords
athlete development, biomechanics, elite athletes, performance determinants, physiology, sex differences, training characteristics, Winter Olympic Games
National Category
Sport and Fitness Sciences
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116451 (URN)10.1111/sms.70222 (DOI)001685165000001 ()41653367 (PubMedID)2-s2.0-105029366578 (Scopus ID)
Note

Full text license: CC BY

Available from: 2026-02-19 Created: 2026-02-19 Last updated: 2026-06-30Bibliographically approved
Kalén, A., Abrahamsson, J., Kalliorinne, K., Holmberg, H.-C. & Almqvist, A. (2026). Perceptual consensus on cross-country ski–snow performance: a questionnaire study of experts and non-experts. Frontiers in Sports and Active Living, 8, Article ID 1766019.
Open this publication in new window or tab >>Perceptual consensus on cross-country ski–snow performance: a questionnaire study of experts and non-experts
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2026 (English)In: Frontiers in Sports and Active Living, E-ISSN 2624-9367, Vol. 8, article id 1766019Article in journal (Refereed) Published
Abstract [en]

Introduction: Understanding how skiers and ski technicians perceive snow conditions and ski preparation is essential for optimising glide performance in cross-country (XC) skiing. While tribological research has established how snow microstructure, water-film formation, and ski-snow interactions influence friction, comparatively little is known about how skiers and ski technicians interpret these mechanisms in practice.

Methods: We therefore conducted a nationwide questionnaire study (n = 249) to quantify perceptual consensus on ten topics related to snow type, glide determinants, ski preparation, and skier-equipment interaction. Responses were analysed using van der Eijk's agreement coefficient for ordinal data and Cliff's delta to evaluate expert (n = 20) versus non-expert (n = 229) differences.

Results: Agreement varied systematically across topics: the highest consensus was found for perceived ski speed on different snow types and structure selection, while the lowest was observed for glide determinants, paired glide tests involving skier mass, and double-poling positioning. Experts showed higher within-group agreement for perceived ski speed in skate-skiing and on moist transformed snow, and they consistently rated ski camber as more important than non-experts did.

Discussion: These findings highlight empirically developed know-how within the skiing community, such as shared heuristics for snow-type assessment and preparation, and systematic expertise-related differences in prioritising fundamental ski characteristics (e.g., camber). As such, they can be used for targeted education and to inform future applied tribology research.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2026
Keywords
agreement analysis, expertise, glide performance, perception, ski preparation, skiing, snow, tribology
National Category
Sport and Fitness Sciences Other Mechanical Engineering
Research subject
Information Systems; Machine Elements; Centre - Centre for Sports and Performance Technology (SPORTC)
Identifiers
urn:nbn:se:ltu:diva-116657 (URN)10.3389/fspor.2026.1766019 (DOI)001697590400001 ()41743256 (PubMedID)2-s2.0-105031008814 (Scopus ID)
Note

Funder: Swedish Olympic Committee (SOK);

Full text license: CC BY;

A correction is available for this publication, please see: Kalén A, Abrahamsson J, Kalliorinne et al. (2026) Correction: Perceptual consensus on cross-country ski–snow performance: a questionnaire study of experts and non experts. Front. Sports Act. Living 8,  1808795. https://doi.org/10.3389/fspor.2026.1808795

Available from: 2026-03-06 Created: 2026-03-06 Last updated: 2026-06-30Bibliographically approved
Sandbakk, Ø., Herzog, S., McGawley, K., Pyne, D. B., Talsnes, R. K., Millet, G. P., . . . Sandbakk, S. B. (2026). Perspectives of World-Class Endurance Coaches on the Evolution of Athlete Training and Performance. International Journal of Sports Physiology and Performance, 21(1), 98-105
Open this publication in new window or tab >>Perspectives of World-Class Endurance Coaches on the Evolution of Athlete Training and Performance
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2026 (English)In: International Journal of Sports Physiology and Performance, ISSN 1555-0265, E-ISSN 1555-0273, Vol. 21, no 1, p. 98-105Article in journal (Refereed) Published
Abstract [en]

Purpose: To provide insights into the key practices driving the evolution of endurance training and performance. Methods: Atotal of 78 world-class coaches (73 men, 5 women), representing 14 endurance sports, and 18 nations, participated in a digitalsurvey comprising open-ended questions about recent trends and projected future developments. Results: Qualitative thematicanalysis revealed 8 key drivers of change: (1) individualized and sport-specific training strategies, (2) precision in trainingexecution, (3) load-management procedures, (4) strategic use of environmental stressors, (5) optimized nutrition, (6) holisticrecovery practices, (7) health and injury prevention, and (8) equipment and technology-driven innovation. To provide a clearerconceptual framework, these themes were grouped into 3 overarching categories: training methodologies (themes 1–4), recoveryand health management (themes 5–7), and technological innovation (theme 8). Conclusions: World-class endurance coachesdescribe a continuing shift toward more individualized training strategies, characterized by detailed sport-specific considerations,training plans aligned with physiological profiles, greater precision in training execution, refined load management, and strategicuse of environmental stressors. In this context, advanced monitoring technologies are viewed as essential for optimizing trainingadaptations while minimizing the risk of maladaptation and injury. Coaches also emphasized the importance of enhanced healthand recovery strategies to support training adaptations, including sleep quality, stress management, life balance, and targetednutritional interventions, particularly carbohydrate availability. Finally, the rapid development of new equipment and technologies is transforming training and coaching practices, thereby contributing to improved endurance performance.

Place, publisher, year, edition, pages
Human Kinetics Publishers Inc., 2026
Keywords
endurance sports, injury prevention, monitoring technology, nutrition, recovery, training-load management
National Category
Sport and Fitness Sciences
Research subject
Physiotherapy and Health Promotion
Identifiers
urn:nbn:se:ltu:diva-116018 (URN)10.1123/ijspp.2025-0317 (DOI)001622452700001 ()41248624 (PubMedID)2-s2.0-105024966588 (Scopus ID)
Available from: 2026-01-16 Created: 2026-01-16 Last updated: 2026-06-30Bibliographically approved
Ström, K., Oskolkov, N., Karaderi, T., Kalamajski, S., Mir, B. A., Ekström, O., . . . Hansson, O. (2026). RAB3GAP2 is a regulator of skeletal muscle endothelial cell proliferation and associated with capillary-to-fiber ratio. Cell Reports, 45(2), Article ID 116961.
Open this publication in new window or tab >>RAB3GAP2 is a regulator of skeletal muscle endothelial cell proliferation and associated with capillary-to-fiber ratio
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2026 (English)In: Cell Reports, ISSN 2639-1856, E-ISSN 2211-1247, Vol. 45, no 2, article id 116961Article in journal (Refereed) Published
Abstract [en]

Skeletal muscle capillary density is correlated with physical performance and whole-body metabolic properties. Thus, we performed a genome-wide association study of skeletal muscle capillary-to-fiber ratio (C:F) (n = 603 males) and found that the rs115660502 G allele was associated (p < 5 × 10−8) with increased C:F and reduced skeletal muscle expression of RAB3 GTPase-activating non-catalytic protein subunit 2 (RAB3GAP2). The capillary-increasing G allele was more prevalent in elite endurance athletes than in power athletes and non-athlete controls in two independent cohorts. Low-muscle-expressing RAB3GAP2 expression quantitative trait locus (eQTL) alleles were associated with muscle damage in athletes. In healthy individuals, RAB3GAP2 expression was reduced by high-intensity intermittent training. RAB3GAP2 protein was not uniformly expressed in muscle but predominantly expressed in the endothelium and capillaries. RAB3GAP2 expression was lower in endurance compared with power athletes and was negatively associated with type I (oxidative) muscle fiber density. Experimental reduction of RAB3GAP2 in human endothelial cells led to (1) increased proliferation and tube formation in vitro, (2) regulation of secreted factors (e.g., CD70 and TNC) promoting angiogenesis and T cell activation, and (3) increased in vivo endothelial cell density in mice. RAB3GAP2 expression in skeletal muscle was negatively correlated with exercise-induced release of TNC in vivo in humans. In conclusion, RAB3GAP2 is expressed in the microvascular endothelium and is suggested to be a negative regulator of angiogenesis through a decrease in endothelial cell proliferation, possibly mediated by RAB18, with its low-expressing variant associated with higher muscle C:F and elite endurance performance.

Place, publisher, year, edition, pages
Cell Press, 2026
Keywords
skeletal muscle, exercise, genetics, capillary density, microvascular endothelium, angiogenesis, RAB3 GTPase-activating non-catalytic protein subunit 2, RAB3GAP2, RAB18, elite athletes
National Category
Physiology and Anatomy
Research subject
Machine Elements
Identifiers
urn:nbn:se:ltu:diva-116674 (URN)10.1016/j.celrep.2026.116961 (DOI)001698335500001 ()41678332 (PubMedID)2-s2.0-105031631246 (Scopus ID)
Note

Full text license: CC BY

Available from: 2026-03-09 Created: 2026-03-09 Last updated: 2026-06-30Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-3814-6246

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