The Effects of Creatine Supplementation Combined with Resistance Training on Regional Measures of Muscle Hypertrophy: A Systematic Review with Meta-Analysis
Open accessAbstract
The purpose of this paper was to carry out a systematic review with a meta-analysis of randomized controlled trials that examined the combined effects of resistance training (RT) and creatine supplementation on regional changes in muscle mass, with direct imaging measures of hypertrophy. Moreover, we performed regression analyses to determine the potential influence of covariates. We included trials that had a duration of at least 6 weeks and examined the combined effects of creatine supplementation and RT on site-specific direct measures of hypertrophy (magnetic resonance imaging (MRI), computed tomography (CT), or ultrasound) in healthy adults. A total of 44 outcomes were analyzed across 10 studies that met the inclusion criteria. A univariate analysis of all the standardized outcomes showed a pooled mean estimate of 0.11 (95% Credible Interval (CrI): −0.02 to 0.25), providing evidence for a very small effect favoring creatine supplementation when combined with RT compared to RT and a placebo. Multivariate analyses found similar small benefits for the combination of creatine supplementation and RT on changes in the upper and lower body muscle thickness (0.10–0.16 cm). Analyses of the moderating effects indicated a small superior benefit for creatine supplementation in younger compared to older adults (0.17 (95%CrI: −0.09 to 0.45)). In conclusion, the results suggest that creatine supplementation combined with RT promotes a small increase in the direct measures of skeletal muscle hypertrophy in both the upper and lower body.
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Creatine, citrulline, and leucine-rich feedings are best interpreted as compounds that help maintain a permissive metabolic and signalling environment in which mechanical loading can drive nucleolar expansion.
“Creatine [166,167], citrulline [168,169], and leucine-rich feedings [111,162] are best interpreted as compounds that help maintain a permissive metabolic and signalling environment in which mechanical loading can drive nucleolar expansion.”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [166]
The Introduction (page not available) says creatine supports ATP resynthesis and influences factors that may contribute to muscle accretion during resistance training. That supports the metabolic and signalling aspect of the claim about creatine, but the paper does not connect those effects to nucleolar expansion. The citrulline and leucine portions are attributed to other citations, not this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredMeta-analytic evidence indicates that creatine supplementation combined with resistance training may provide a small additional benefit for directly measured muscle hypertrophy.
“Meta-analytic evidence indicates that creatine supplementation combined with resistance training may provide a small additional benefit for directly measured muscle hypertrophy [166]”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [166]
Among nutritional supplements, creatine has one of the strongest evidence bases for supporting resistance-training adaptations.
“Among nutritional supplements, creatine has one of the strongest evidence bases for supporting resistance-training adaptations.”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [166]
Creatine is best interpreted as a plausible indirect supporter of ribosome biogenesis, not as a proven direct activator of nucleolar output.
“creatine is best interpreted as a plausible indirect supporter of ribosome biogenesis, not as a proven direct activator of nucleolar output [166,167]”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [166]
The Introduction discusses creatine’s effects on energy availability and factors that may contribute to muscle accretion; the Discussion reports a small hypertrophy effect. Neither section addresses ribosome biogenesis or direct activation of nucleolar output (searched: “ribosome biogenesis” and “nucleolar output”). (LLM, conf=0.72)
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“Crea-tine [166,167], citrulline [168,169], and leucine-rich feedings [111,162] are best interpreted as compounds that help maintain a permissive metabolic and signalling environment in which mechanical loading can drive nucleolar expansion.”
Creatine and the plurality of its uses, with emphasis on its supplementation in sports
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Self-citationEnerji Sistemleri ile Uyumlu Kanıta Dayalı Besin Takviyesi Stratejileri
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Self-citationCreatine: Clinical Implications for Orthopedic Surgeons
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From Anecdote to Evidence: Dispelling Myths in Bodybuilding and Physique Sports
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Fat-Free Mass Accretion: Limits, Targets, and Best Practices
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Prehabilitation in Spine Surgery and Joint Arthroplasty
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Bisikletçilerde Glutamin ve Kreatin Kombine Tüketiminin Fonksiyonel Eşik Güç Üzerine Etkisi
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Creatine supplementation in sport and medicine - a review of recent reports
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Einflussnehmende Faktoren der medizinischen Trainingstherapie
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O poder da creatina: hipertrofia, força e performance
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Influencing Factors of Medical Exercise Therapy
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A critical analysis of the disconnection between science and practice in weight training
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EFEITOS DA SUPLEMENTAÇÃO DE CREATINA NO ESPORTE
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Suplementación con creatina y entrenamiento de fuerza en mujeres jóvenes: una revisión sistemática
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Effect of creatine on improving a person’s physical performance: A literature review
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Top 5 Dietary Supplements for Bodybuilders
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Should young people take creatine?
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From autophagy to mitophagy: Quality control mechanisms in skeletal muscle
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EFFECTIVENESS OF CREATINE SUPPLEMENTATION IN STRENGTH SPORTS – A REVIEW
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Egzersizle Metabolik Esnekliğin Düzenlenmesi: Substrat Kullanımı ve Antrenman Adaptasyonları
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Egzersiz Bilimi ve Metabolik Adaptasyonlar
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CREATINE USE IN SPORTS: SAFETY AND MECHANISMS OF ACTION
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Mechanisms, Dosing Strategies, and Performance Effects of 5 Leading Ergogenic Supplements
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Orthobiologics to Improve Skeletal Muscle Health After Injury and Aging
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Cardiorespiratory Fitness Indicators in Young Athletes: Analysis for Personalized Training Programs
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Creatine Supplementation in Patients With Cancer: A Systematic Review and Meta‐Analysis
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Self-citationCreatine supplementation in patients with kidney disease–harm or benefit?
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Creatine monohydrate supplementation: one tool in the toolbox for treating sarcopenia
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Self-citationIs Creatine Supplementation Safe and Effective? – A Review
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Physical activity and improvement of physiological parameters by training
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When does nutrition add value to blood flow restriction training?
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- Authors
- Burke, R., Piñero, A., Coleman, M., Mohan, A., Sapuppo, M., Augustin, F., Aragon, A. A., Candow, D. G., Forbes, S. C., Swinton, P., & Schoenfeld, B. J.
- Affiliations
- Lehman College (US)
- California State University, Northridge (US)
- University of Regina (CA)
- Brandon University (CA)
- Robert Gordon University (GB)
- Corresponding author
- Schoenfeld, Brad J.
- ORCID
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2023-04-28
- Volume
- 15
- Issue
- 9
- Pages
- 2116
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC10180745
- OpenAlex
- W4367317704
- Cited by
- 80
- References
- 45
- Citations by year
- 2026: 31 · 2025: 31 · 2024: 13 · 2023: 5
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Access Institutional Repository at Robert Gordon University (Robert Gordon University) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- creatine supplementation, resistance training, muscle hypertrophy, skeletal muscle mass, healthy adults, age differences
- MeSH terms
- Aged, Creatine, Humans, Hypertrophy, Muscles, Dietary Supplements, Resistance Training
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