Impact of collagen peptide supplementation together with long-term resistance training on maximal strength and muscle size in healthy adults – A systematic review and meta-analysis
Authors: Bischof Kevin , Moitzi Anna , König Daniel 
Published: September 2024

Introduction & Purpose
Of late, numerous studies have investigated the use of collagen peptides (CP) as an ergogenic aid to boost sports performance, although CP is frequently referred to as low-quality protein. Given the high content of glycine, proline, and hydroxyproline in collagen proteins, the current rationale behind the potential impact of CP supplementation may revolve around the incorporation of these amino acids into muscle and tendon tissues (Holwerda & van Loon, 2022). There have been reports of a notable increase in the uptake of these specific amino acids within two hours after the ingestion of 15 g gelatine, coupled with six minutes of rope skipping, as observed in human serum (Shaw et al., 2017). The combination of resistance training (RT) with immediate CP administration seems to serve as a potent stimulus for enhancing anabolic pathways such as phosphatidylinositol 3 - kinase - protein kinase B (PI3k - Akt), mitogen-activated protein kinase (MAPK) and the mechanistic target of rapamycin (mTOR) to induce myofibrillar hypertrophy and collagen synthesis (Centner et al. 2022). Some studies have already demonstrated increased muscle mass gains following CP intake together with exercise interventions (Balshaw et al., 2023), but not all (Centner et al., 2019). Since maximal strength is highly associated with muscular size (Balshaw et al., 2021) several trials have also investigated strength outcomes in various exercises accompanied with CP administration with equivocal results (Jendricke et al., 2019; Zdzieblik et al., 2021). Based on aforementioned findings and the fact that no systematic review and/or meta-analysis has examined the impact of long-term CP supplementation linked with RT on muscular adaptation and strength yet, a meta-analysis is conducted to figure out whether regular CP intake with RT is associated with improvements in maximal strength and increased muscle size.
Methods
The systematic review and meta-analysis was conducted based on PERSiST (implementing Prisma in Exercise, Rehabilitation, Sport medicine and SporTs science) guidelines. Studies investigating healthy adults (≥ 18 years of age, male & female) with a body mass index of 18.5 to 31 kg/m² were included. Both low and professional training status of subjects were suitable for inclusion. Participants had to ingest CP (as treatment group) daily at least for eight weeks, the control group a calorie or non-calorie matched placebo (PLA). Only studies with an accompanying RT of at least two times a week were included. Manuscripts had to be human randomized controlled trials (RCT). Studies adding creatine or caffeine as fortification were excluded. Literature search was carried out in March 2024 in PubMed, Scopus, CINAHL and SPORTDiscus without any restrictions. The following search string was applied in all databases: “collagen AND (peptide OR peptides OR supplement OR supplementation OR hydrolysate) AND (muscle strength OR architecture OR size) [AND (only added in Scopus)] NOT (disease OR skin OR osteoporosis OR osteoarthritis)”. References of included studies and Google Scholar were also screened (forward & backward search) and if eligible, handpicked. The following parameters of studies were chosen for each item: Muscle size: volume (cm³) of quadriceps (and also rectus femoris, vastus intermedius, lateralis and medialis alone), gluteus maximus & hamstrings; CSA (cm²) of the thighs; thickness (cm) of medial gastrocnemius, vastus lateralis, intermedius and rectus femoris. Maximal strength: maximal voluntary contraction and one-repetition maximum of both upper- and lower-body exercises. The Physiotherapy Evidence Database (PEDro) scale was used to assess risk of bias. Meta-analysis was conducted in Jamovi 2.4.11 using the standardized mean difference (SMD) of change scores (post – pre values, resulting in Δ mean and Δ SD) and a random effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach.
Results
After duplicate removal, 847 studies were screened. Seventeen seemed to meet eligibility criteria. Due to some limitations such as missing and too short training interventions as well as an insufficient control group design, nine studies, all of them being RCT’s, were included. Six records sourced from website searches and citation investigations ultimately resulted in exclusion due to reasons mentioned earlier. 385 subjects, aged ~18 – 65, participated in the included studies. CP and PLA were administered daily ranging from 5 g (n = 2) to 15 g (n = 7) for at least 8 weeks. Three and six studies supplemented either maltodextrin or a non-caloric PLA, respectively. Dietary protein intake have not changed significantly throughout the trials. Training status of subjects varied, from either untrained to resistance trained (being able to squat 100% of the individual body weight) before study commencements. All nine studies prescribed a RT regimen of three times a week. None of the included studies achieved a total score below “good” (6 - 8), which implicates low risk of bias overall. Muscle size was investigated in 175 subjects in five studies using either MRI or sonography. CP intake led to a statistical significant pooled estimate (ES = 0.35, p = 0.002, I² = 0%, CI [0.13, 0.57], Figure 1). Nine studies including 385 subjects resulted in a significantly higher maximal strength following CP supplementation (ES = 0.23, p < 0.01, I² = 0.01%, CI [0.13, 0.57], Figure 1) compared to placebo. Overall, certainty of evidence for both parameters was low due to wide confidence intervals and varying training status of subjects.
Discussion
To the best of our knowledge, this is the first systematic review and meta-analysis examining the effects of long-term CP supplementation alongside regular RT on maximal strength and muscle size in healthy adults. Our findings suggest that prolonged (≥ 2 months) CP intake may significantly improve muscle size accrual and maximal strength, albeit with a low level of evidence. Similar to leucine, a single bolus of CP has been shown to evoke a higher upregulation of key anabolic pathways (PI3K - Akt, MAPK) involved in myofibrillar protein synthesis four hours following RT (Centner et al., 2022). Additionally, an in-vitro experiment treating C2C12 cells with the dipeptide hydroxyprolyl - glycine inducing phosphorylation of p70S6k, mTOR and Akt, suggesting myogenic differentiation (Kitakaze et al., 2016). CP also positively impacted maximal strength concurrently with muscle size. Among other factors, muscle fiber composition, muscle architecture, neural activation and specific tension also contribute to muscle strength. Significantly higher evoked contractile twitch peak torque but no quadriceps tension, muscle architectural differences and lack of muscle fiber type adaptation occurred in long-term trials, thus assuming a probable adaptation of passive tissue components (Balshaw et al., 2023; Kirmse et al., 2019).
Conclusion
A several-week regimen of CP supplementation alongside RT seems to offer advantages to healthy, active adults aiming to enhance both maximal strength and muscle size. A daily intake of 15 g CP seems to induce these adaptations. Future trials are encouraged to identify the optimal CP dosage, composition, absorption and incorporation into collagenous tissues.
References
Balshaw, T. G., Funnell, M. P., McDermott, E., Maden-Wilkinson, T. M., Abela, S., Quteishat, B., Edsey, M., James, L. J., & Folland, J. P. (2023). The effect of specific bioactive collagen peptides on function and muscle remodeling during human resistance training. Acta Physiologica, 237(2), Article e13903. https://doi.org/10.1111/apha.13903
Balshaw, T. G., Maden-Wilkinson, T. M., Massey, G. J., & Folland, J. P. (2021). The human muscle size and strength relationship: Effects of architecture, muscle force, and measurement location. Medicine & Science in Sports & Exercise, 53(10), 2140–2151. https://doi.org/10.1249/MSS.0000000000002691
Centner, C., Jerger, S., Mallard, A., Herrmann, A., Varfolomeeva, E., Gollhofer, S., Oesser, S., Sticht, C., Gretz, N., Aagaard, P., Nielsen, J. L., Frandsen, U., Suetta, C., Gollhofer, A., & König, D. (2022). Supplementation of specific collagen peptides following high-load resistance exercise upregulates gene expression in pathways involved in skeletal muscle signal transduction. Frontiers in Physiology, 13, Article 838004. https://doi.org/10.3389/fphys.2022.838004
Centner, C., Zdzieblik, D., Roberts, L., Gollhofer, A., & König, D. (2019). Effects of blood flow restriction training with protein supplementation on muscle mass and strength in older men. Journal of Sports Science & Medicine, 18(3), 471–478.
Holwerda, A. M., & van Loon, L. J. C. (2022). The impact of collagen protein ingestion on musculoskeletal connective tissue remodeling: A narrative review. Nutrition Reviews, 80(6), 1497–1514. https://doi.org/10.1093/nutrit/nuab083
Jendricke, P., Centner, C., Zdzieblik, D., Gollhofer, A., & König, D. (2019). Specific collagen peptides in combination with resistance training improve body composition and regional muscle strength in premenopausal women: A randomized controlled trial. Nutrients, 11(4), Article 892. https://doi.org/10.3390/nu11040892
Kirmse, M., Oertzen-Hagemann, V., de Marées, M., Bloch, W., & Platen, P. (2019). Prolonged collagen peptide supplementation and resistance exercise training affects body composition in recreationally active men. Nutrients, 11(5), Article 1154. https://doi.org/10.3390/nu11051154
Kitakaze, T., Sakamoto, T., Kitano, T., Inoue, N., Sugihara, F., Harada, N., & Yamaji, R. (2016). The collagen derived dipeptide hydroxyprolyl-glycine promotes C2C12 myoblast differentiation and myotube hypertrophy. Biochemical and Biophysical Research Communications, 478(3), 1292–1297. https://doi.org/10.1016/j.bbrc.2016.08.114
Shaw, G., Lee-Barthel, A., Ross, M. L., Wang, B., & Baar, K. (2017). Vitamin C-enriched gelatin supplementation before intermittent activity augments collagen synthesis. The American Journal of Clinical Nutrition, 105(1), 136–143. https://doi.org/10.3945/ajcn.116.138594
Zdzieblik, D., Jendricke, P., Oesser, S., Gollhofer, A., & König, D. (2021). The influence of specific bioactive collagen peptides on body composition and muscle strength in middle-aged, untrained men: A randomized controlled trial. International Journal of Environmental Research and Public Health, 18(9), Article 4837. https://doi.org/10.3390/ijerph18094837