Review
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly marketed in sports medicine contexts, spanning both FDA-approved compounds (e.g., tesamorelin/Egrifta) and unapproved "gray market" substances (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, and others). The authors note that while many unapproved peptides show promising tissue repair and metabolic effects in animal models, rigorous human safety and efficacy data are largely absent. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses the potential for serious patient harm. Notably, the authors address the placebo effect as a possible mediator of perceived peptide efficacy and examine how social media may amplify this effect. A clinician-oriented framework is proposed to guide evidence-based patient discussions about peptide use for musculoskeletal healing and athletic performance, including consideration of alternative treatments. Key limitations include the narrative (non-systematic) review methodology and the inherently limited and heterogeneous evidence base for most compounds discussed, particularly in human populations.
Sports medicine (Auckland, N.Z.) · Apr 2026DOI ↗ ReviewPreprint
This narrative review examines the pharmacological mechanisms, safety profiles, and regulatory status of twelve peptides commonly encountered in sports medicine and athletic performance contexts, including both approved agents (e.g., tesamorelin/Egrifta, sermorelin) and unapproved "gray market" compounds (e.g., BPC-157, CJC-1295, TB-500, ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, SS-31, and thymosin beta-4). The authors note that while many unapproved peptides show promising tissue repair and metabolic outcomes in animal models, rigorous human safety and efficacy data remain scarce. The review highlights the emergence of a direct-to-consumer gray market operating outside regulatory oversight and the potential for serious patient harm. It further discusses the placebo effect as a potential mediator of perceived peptide efficacy, and how social media may amplify this effect. The authors provide a clinical framework to guide patient-provider discussions and promote evidence-based practice for musculoskeletal healing. Key limitations include the narrative (non-systematic) review design, reliance on preclinical literature for most unapproved compounds, and the absence of head-to-head human trials for the majority of agents discussed.
Unknown journal · Apr 2026DOI ↗ Review
This comprehensive narrative review examines nine therapeutic peptides with proposed applications in healthy aging and age-related conditions: tirzepatide (metabolic dysfunction), epitalon (telomere biology), GHK-Cu (dermal regeneration), BPC-157 and TB-500 (tissue repair), Semax (neuroprotection), CJC-1295 and ipamorelin (growth hormone modulation), and bremelanotide (sexual function). The authors searched PubMed, Scopus, and regulatory databases through January 2026, selecting 20 primary sources based on relevance and methodological quality. The review found that FDA-approved agents such as tirzepatide and bremelanotide have robust safety and efficacy data from large-scale trials, while investigational peptides such as epitalon, BPC-157, and TB-500 show promising signals primarily from preclinical and limited clinical studies. The authors highlight significant knowledge gaps, including the absence of long-term safety data for non-approved peptides, undefined optimal dosing regimens, unknown combination therapy effects, and lack of validated biomarkers for monitoring efficacy. The authors conclude that while therapeutic peptides offer mechanistically diverse approaches to aging hallmarks, investigational agents require rigorous clinical trial validation before clinical adoption. As a narrative review, findings are subject to selection bias and do not represent a quantitative synthesis of evidence.
Frontiers in aging · Apr 2026DOI ↗ Review
This narrative review examines the potential role of therapeutic peptides in orthopaedic care, synthesizing preclinical and mechanistic literature across several peptide classes. The authors categorize peptides by their primary proposed function: wound-healing agents (BPC-157, TB-500, GHK-Cu), growth hormone secretagogues (ipamorelin, CJC-1295, tesamorelin, sermorelin, AOD-9604), recovery-enhancing peptides (epithalon, delta sleep-inducing peptide, pinealon), and neuroactive peptides (selank, semax, dihexa). The review describes how these compounds are theorized to interact with signaling pathways—including PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK—to promote tissue regeneration, resolve inflammation, and support neuromuscular recovery. The authors acknowledge that, while preclinical evidence is promising, robust human clinical trial data are largely absent, representing a significant gap in the literature. Limitations include the review's reliance on animal and in vitro studies, the absence of a systematic search methodology, and the lack of direct clinical evidence supporting efficacy or safety in human orthopaedic populations. The authors call for future controlled trials to validate these mechanistic findings in clinical settings.
Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · Jan 2026DOI ↗ Review
This narrative review, aimed at orthopaedic and sports medicine physicians, synthesizes the existing biochemical and clinical literature on six commonly marketed injectable therapeutic peptides: BPC-157, TB-4, TB-500, CJC-1295 + ipamorelin, tesamorelin, and GHK-Cu. The authors conducted a PubMed literature search and evaluated evidence across preclinical and clinical settings. Key findings attributed to the reviewed studies include: BPC-157 showed potential in tendon and muscle repair in preclinical models, with one human case series reporting pain reduction after intra-articular knee injection, though that study had significant methodological limitations and no control group. TB-4 and TB-500 demonstrated angiogenesis and tissue repair effects in animal models, but no human orthopaedic data were identified, and both are banned in sport. CJC-1295 combined with ipamorelin improved muscle tension in a murine glucocorticoid-induced muscle loss model only. Tesamorelin holds FDA approval for HIV-associated lipodystrophy but lacks orthopaedic evidence. GHK-Cu showed wound healing and anti-inflammatory properties preclinically, with no clinical musculoskeletal data. The authors conclude that indications, safety profiles, and dosing for all these peptides remain undefined for orthopaedic use, and robust human trials are needed before clinical recommendations can be made.
The American journal of sports medicine · Jan 2026DOI ↗ ReviewPreprint
This review paper examines the pharmacological mechanisms, safety profiles, and regulatory status of both approved and unapproved peptide therapies relevant to sports medicine, musculoskeletal injury recovery, and athletic performance enhancement. The compounds reviewed span a wide spectrum — from FDA-approved agents such as tesamorelin and sermorelin, to gray-market compounds including BPC-157, TB-500, CJC-1295, Ipamorelin, AOD-9604, FS-344, GHK-Cu, MOTS-C, and SS-31. The authors note that while many unapproved peptides show promising results in preclinical and animal models — including favorable tissue repair and metabolic effects — rigorous human safety and efficacy data remain scarce. The review highlights a growing direct-to-consumer gray market operating outside regulatory oversight and discusses how social media may amplify perceived benefits through placebo-related mechanisms. The paper also offers a clinical framework to guide patient conversations and support evidence-based decision-making. Key limitations include the inherent constraints of a narrative review design, reliance on heterogeneous preclinical data for unapproved compounds, and the absence of controlled human trials for most of the highlighted peptides.
Unknown journal · Dec 2025DOI ↗ Review
This comprehensive review synthesizes research published between 2016 and 2025 on the role of tripeptides in wound healing and skin regeneration. The authors examine how these short, three-amino-acid peptides regulate critical repair processes including cell migration, proliferation, and differentiation, as well as inflammation modulation, angiogenesis promotion, and extracellular matrix (ECM) remodeling. The review highlights several specific tripeptides: GHK-based formulations (including nanoparticle conjugates, hydrogels, and clinical derivatives TriHex and TriHex 2.0) were found in cited studies to enhance fibroblast migration, collagen and elastin synthesis, ECM remodeling, and wound closure with added antimicrobial activity. KdPT was reported to mitigate hyperglycemia-induced oxidative stress and restore keratinocyte function, while KPV-loaded hydrogels reduced inflammation and combated MRSA infections. Lipotripeptides (DICAMs) were noted to inhibit and disrupt bacterial biofilms, and GPE was associated with neuroprotection via ERK and PI3K/Akt signaling. The review also addresses physicochemical comparisons with larger peptides, biomaterial scaffold integration, and emerging applications in cancer and cosmetics. As a narrative review, it does not generate new experimental data. Key limitations include inherent selection bias and the predominance of preclinical evidence in the underlying literature. The authors call for further research into stability, bioavailability, and delivery optimization.
International journal of medical sciences · Oct 2025DOI ↗ Review
This review paper examines the current state of knowledge and methodology surrounding the skin permeation of GHK-Cu (glycyl-L-histidyl-L-lysine copper tripeptide), a naturally occurring cosmetically active compound (CAC) associated with properties such as reducing fine lines and wrinkles, improving skin elasticity, and tightening skin. The authors highlight a central challenge: GHK-Cu is relatively hydrophilic, which limits its ability to penetrate the lipophilic stratum corneum, the skin's outermost barrier. The paper reviews liposomal encapsulation as a strategy to improve GHK-Cu's skin permeation potential, and surveys existing methods used to study transdermal transport of CACs—both free and liposome-encapsulated. A key finding from the literature analysis is that research specifically examining liposome-mediated transport of GHK-Cu is sparse, representing a notable gap in the field. The authors argue this gap motivates further methodological development to better assess how liposomes affect GHK-Cu trafficking through skin layers. As a review, the paper synthesizes existing literature rather than presenting original experimental data, and it does not include clinical trials or controlled human studies. Its conclusions about efficacy are therefore inferential and limited by the quality and quantity of the underlying studies reviewed.
Molecules (Basel, Switzerland) · Jan 2025DOI ↗