PEPTIDE THERAPEUTICS: AN EVIDENCE-BASED REVIEW Integrative Functional Medicine serving IA IL MO GA FL TX
- John Kim
- Dec 5, 2025
- 11 min read
Edited by Yoon Hang Kim MD
Yoon Hang Kim MD MPH Integrative & Functional Medicine Expert
A comprehensive examination of bioactive peptides for fitness, anti-aging, metabolism, cognition, and immune support
---
TABLE OF CONTENTS
1. Introduction
2. Peptides for Fitness & Tissue Repair
3. Anti-Aging & Skin Health Peptides
4. Fat Loss & Metabolism Peptides
5. Cognitive & Neuroprotective Peptides
6. Immune Support & Recovery Peptides
7. Critical Considerations
8. Conclusion
9. References
---
INTRODUCTION
Bioactive peptides have emerged as a significant area of interest in therapeutic research, spanning applications from tissue regeneration to cognitive enhancement and immune modulation. These short chains of amino acids serve as critical signaling molecules in biological systems, participating in diverse physiological functions including hormonal regulation, immune defense, tissue repair, and neural communication (Ahmad et al., 2020).
The therapeutic potential of peptides has attracted considerable scientific and commercial interest. Some peptides have achieved FDA approval for specific indications—insulin for diabetes management and GLP-1 receptor agonists (like semaglutide) for type 2 diabetes and obesity being prominent examples. However, many peptides discussed in popular wellness contexts remain experimental, existing in regulatory gray areas when marketed as supplements or research chemicals (Józwiak et al., 2025).
⚠️ IMPORTANT DISCLAIMER: This review is for educational purposes only. Most peptides discussed are not FDA-approved for general wellness applications. Many are classified as research chemicals or are prohibited in competitive sports. Always consult healthcare professionals before considering any peptide therapy.
---
1. PEPTIDES FOR FITNESS, TISSUE REPAIR & MUSCLE GROWTH
This category encompasses peptides investigated for their potential to support musculoskeletal healing, recovery, and growth hormone modulation.
BPC-157 (Body Protection Compound-157)
Type: Pentadecapeptide | Origin: Human gastric juice
Status: Research Only | FDA Category 2
Body Protection Compound-157 is a synthetic pentadecapeptide originally isolated from human gastric juice that has demonstrated pleiotropic regenerative properties across numerous preclinical models. The peptide activates several overlapping molecular pathways, notably VEGFR2 and nitric oxide synthesis via the Akt-eNOS axis, promoting angiogenesis, fibroblast activity, and neuromuscular stabilization (Sikiric et al., 2021).
A systematic review examining BPC-157's role in orthopedic sports medicine found that the peptide promotes healing by boosting growth factors and reducing inflammation, with improved outcomes demonstrated in muscle, tendon, ligament, and bone injury models in animals. In one pilot human study, 7 out of 12 people with chronic knee pain reported relief for over six months following a single BPC-157 knee injection (Sullivan et al., 2025).
"All studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models."
— Gwyer et al., Cell and Tissue Research, 2019
TB-500 (Thymosin Beta-4 Fragment)
Type: Heptapeptide | Origin: Thymosin Beta-4 fragment
Status: Research Only | WADA Prohibited
TB-500 is a synthetic peptide derived from thymosin beta-4 (Tβ4), a naturally occurring 43-amino acid protein found in nearly all human and animal tissues that serves as a critical regulator of actin polymerization and cellular motility (Spurney et al., 2010). The peptide promotes cellular migration to injury sites through its unique mechanism of actin regulation.
Research indicates potential benefits in diabetic ulcer healing, Achilles tendon rupture repair, rotator cuff injury recovery, and skeletal muscle regeneration following trauma (Xing et al., 2021). However, the current evidence base remains predominantly preclinical.
IGF-1 (Insulin-like Growth Factor-1)
Type: 70-amino acid polypeptide | Origin: Endogenous hormone
Status: WADA Prohibited
IGF-1 is a hormone found in blood that plays an important role in skeletal myogenesis, muscle mass entity, strength development, and increases the proliferative capacity of muscle satellite cells. IGF-1 increases skeletal muscle protein synthesis via PI3K/Akt/mTOR and PI3K/Akt/GSK3β pathways (Yoshida & Delafontaine, 2020).
A meta-analysis of 33 randomized controlled trials demonstrated a significant increase in serum IGF-1 levels following resistance training (WMD: 10.34 ng/ml, 95% CI: 4.93-15.74, p = 0.000). The increase was particularly significant in participants aged over 60 years and in women (Jiang et al., 2020).
⚠️ SAFETY CONCERN: IGF-1 supplementation in otherwise healthy individuals is associated with moderate-to-severe hypoglycemia, decreased GH secretion, and disruption of the insulin-glucagon system (Adams, 2002).
Growth Hormone Releasing Peptides (GHRP-6 & GHRP-2)
Growth hormone-releasing peptides (GHRPs) are a series of hepta- and hexapeptides that stimulate GH secretion through the growth hormone secretagogue receptor (GHS-R), distinct from growth hormone-releasing hormone (GHRH) pathways (Ghigo et al., 1997). GHRP-6 appeared as the first synthetic peptide that specifically elicited dose-related GH release in vitro and in vivo.
Clinical observations demonstrate that GHRP-6 intravenous administration proved safe in a dose scale-up clinical trial in healthy human volunteers (Berlanga-Acosta et al., 2017). GHRP family members have been distinguished by their ability to prevent cardiac cell demise and induce restoration of critical cardiac functions upon ischemia/reperfusion episodes.
CJC-1295 (Modified GHRH)
CJC-1295 is a synthetic analogue of growth hormone-releasing hormone with improved pharmacokinetics. Clinical trials by Teichman et al. (2006) demonstrated that a single injection increased plasma GH concentrations by 2- to 10-fold for 6 days or more, and plasma IGF-1 concentrations by 1.5- to 3-fold for 9-11 days. Subcutaneous administration was safe and well tolerated at doses of 30-60 μg/kg.
⚠️ DEVELOPMENT DISCONTINUED: CJC-1295 reached phase II clinical trials but was discontinued following the death of one trial subject. While the attending physician believed the death was unrelated to treatment, research was terminated as a precaution.
---
2. ANTI-AGING & SKIN HEALTH PEPTIDES
This category encompasses peptides investigated for their potential to address aging at cellular and dermatological levels.
Matrixyl® (Palmitoyl Pentapeptide-4)
Type: Lipopeptide | Origin: Collagen fragment
Status: Approved for Cosmetic Use
Palmitoyl pentapeptide-4 (pal-KTTKS), marketed as Matrixyl®, is a matrikine derived from the proteolytic hydrolysis of collagen. A 12-week, double-blind, placebo-controlled clinical study with 93 subjects showed significant improvement in wrinkles and fine lines (Robinson et al., 2005).
KEY RESEARCH FINDINGS:
• Up to 117% increase in overall collagen synthesis
• Up to 327% increase in collagen IV synthesis
• Up to 267% increase in hyaluronic acid synthesis
• Wrinkle improvement without skin irritation (unlike retinoids)
GHK-Cu (Copper Peptide)
Type: Tripeptide-copper complex | Origin: Human plasma
Status: Approved for Cosmetic Use
GHK-Cu (glycyl-L-histidyl-L-lysine copper complex) is naturally present in human plasma at approximately 200 ng/ml at age 20, declining to about 80 ng/ml by age 60. The peptide stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis (Pickart & Margolina, 2018).
Abdulghani et al. (1999) compared topical GHK-Cu to vitamin C and retinoic acid, finding that GHK-Cu resulted in collagen increases in 70% of volunteers, outperforming both comparators. A facial cream containing GHK-Cu applied for 12 weeks reduced fine lines and wrinkles, improved overall appearance, and increased skin density and thickness.
Epitalon (Epithalon)
Type: Tetrapeptide (Ala-Glu-Asp-Gly) | Origin: Pineal gland extract
Status: Research Only
Epitalon has been studied primarily for its ability to extend telomere length through telomerase activation. Khavinson et al. (2003) demonstrated that Epitalon induced telomerase activity and telomere elongation in human fetal fibroblasts, with cells surpassing the Hayflick limit.
In human clinical studies, Epitalon significantly increased telomere lengths in blood cells of patients aged 60-65 and 75-80 years. Animal studies showed reduced incidence of spontaneous tumors and metastases in mice (Araj et al., 2025).
"This study confirms that epitalon increases telomere lengths in normal epithelial and fibroblast cells through up-regulation of telomerase. Importantly, ALT was not activated in normal cells, suggesting epitalon can be safely used in healthy individuals."
— Araj et al., GeroScience, 2025
---
3. FAT LOSS & METABOLISM PEPTIDES
AOD-9604 (HGH Fragment 176-191)
Type: Modified HGH fragment | Origin: HGH amino acids 176-191
Status: Research Only | WADA Prohibited
AOD-9604 (Anti-Obesity Drug-9604) is a modified fragment of human growth hormone identified as the segment responsible for HGH's fat-reducing effects without the hormone's broader growth and insulin-related actions. The peptide stimulates lipolysis in adipose tissue without affecting blood sugar levels (Heffernan et al., 2001).
CLINICAL TRIAL RESULTS:
• 12-week randomized study in obese subjects
• 2.6 kg average weight loss (vs 0.8 kg placebo)
• No significant effect on blood sugar or IGF-1
• Adverse effects comparable to placebo groups
The primary mechanism involves upregulation of beta-3 adrenergic receptors (β3-AR) in white adipose tissue, stimulating the release of glycerol and fatty acids from adipocytes while preventing lipogenesis.
---
4. COGNITIVE & NEUROPROTECTIVE PEPTIDES
Emerging research has identified several peptides with potential effects on cognitive function, neuroprotection, and mood regulation. These compounds have been primarily developed and studied in Russia.
Semax
Type: Heptapeptide (ACTH 4-10 analogue)
Sequence: Met-Glu-His-Phe-Pro-Gly-Pro
Status: Approved in Russia | Not approved elsewhere
Semax is a synthetic analogue of a fragment of adrenocorticotropic hormone (ACTH 4-10). It is on the Russian List of Vital & Essential Drugs and is used for treatment of stroke, transient ischemic attack, and as a nootropic (Dergunova & Filippenkov, 2021).
Research showed that intranasal administration (16 μg/kg) significantly increased attention and short-term memory in human volunteers. Single administration (50 μg/kg) increased brain-derived neurotrophic factor (BDNF) gene expression by 1.4 times in rat hippocampus (Dolotov et al., 2021).
Selank
Type: Synthetic tuftsin derivative | Origin: Immunomodulatory peptide
Status: Approved in Russia (2009)
Selank was approved by the Russian Federation Ministry of Health in 2009 as an anxiolytic and nootropic drug. The peptide influences GABAergic and serotonergic neurotransmission, contributing to mood stabilization and stress reduction (Koroleva & Mjasoedov, 2023).
Unlike benzodiazepines, Selank does not cause sedation, tolerance, or withdrawal effects. Research demonstrated pronounced neuropsychotropic, antidepressant, and antistress effects in primate models (Fedorov et al., 2013).
---
5. IMMUNE SUPPORT & RECOVERY PEPTIDES
Thymosin Alpha-1 (Tα1)
Type: 28-amino acid peptide | Origin: Thymic tissue
Status: FDA Orphan Drug (Zadaxin)
Thymosin alpha-1 has long been recognized as an immune-enhancing, immune-modulating, and immune-restoring agent. The synthetic analogue, thymalfasin, induces IL-2 and B cell growth factor production and modulates T-lymphocyte function (King & Tuthill, 2016).
CLINICAL EVIDENCE:
• 4,400+ subjects enrolled in US, European, and Chinese clinical trials
• FDA approved as orphan drug for malignant melanoma, hepatitis B, DiGeorge anomaly, and hepatocellular carcinoma
• Acts through Toll-like receptor activation in dendritic cells
• Well-studied safety profile with only minor side effects
During the COVID-19 pandemic, Matteucci et al. (2021) found that Tα1 treatment modulated cytokine expression and inhibited lymphocyte hyperactivation in blood cells from patients, suggesting utility in managing cytokine storm.
---
6. CRITICAL CONSIDERATIONS & LIMITATIONS
Regulatory Status
Most peptides discussed in this review are not FDA-approved for general wellness applications. Many are classified as research chemicals, prescription-only substances, or are explicitly prohibited by sports anti-doping organizations:
• The FDA named BPC-157 a Category 2 bulk drug substance in 2023
• WADA prohibits TB-500, IGF-1, GHRPs, CJC-1295, and AOD-9604
• Semax and Selank are approved only in former Soviet states
Evidence Quality
A critical limitation across peptide research is the predominance of preclinical studies. Many promising results derive from animal models or in vitro experiments, with limited translation to rigorous human randomized controlled trials. Gwyer et al. (2019) noted that for BPC-157, the majority of studies have been performed on small rodent models, and efficacy remains unconfirmed in humans.
Safety Considerations
⚠️ KEY SAFETY CONCERNS:
Long-term safety data are not well-established for many peptides. Quality control issues with compounded peptides pose serious concerns, as products obtained outside regulated pharmaceutical channels may contain impurities, incorrect dosages, or degraded compounds. The theoretical risk of enhanced angiogenesis with certain peptides raises concerns regarding potential effects on pre-existing malignancies.
---
7. CONCLUSION
Bioactive peptides represent a promising frontier in therapeutic research, with compounds demonstrating diverse mechanisms targeting tissue regeneration, metabolic regulation, cognitive enhancement, and immune modulation. The evidence reviewed supports mechanistic plausibility and preclinical efficacy for many peptides, including:
• BPC-157's effects on wound healing pathways
• Thymosin alpha-1's well-documented immunomodulatory actions
• GHK-Cu's demonstrated benefits for skin health
• Matrixyl's collagen-stimulating properties
However, significant gaps exist between preclinical promise and clinical application. Most peptides lack FDA approval for their marketed applications, and high-quality randomized controlled trials in human subjects remain scarce. Regulatory constraints, safety uncertainties, and quality control concerns with non-pharmaceutical sources present substantial barriers to responsible clinical use.
Future research priorities should include well-designed human clinical trials, standardized manufacturing protocols, long-term safety monitoring, and clearer regulatory frameworks. Until such evidence accumulates, peptide therapeutics should be approached with appropriate scientific skepticism while remaining open to their potential as the research base expands.
About Dr. Kim and his clinical practice:
At Direct Integrative Care, Dr. Kim is dedicated to guiding you on your path to wellness through a deeply personalized and supportive approach. We focus on integrative medicine, looking beyond symptoms to uncover the root causes of chronic conditions and develop a treatment plan tailored specifically to your unique health journey. By combining compassionate care with innovative therapies, our goal is to empower you with the knowledge and tools needed to achieve lasting health. We invite you to explore our website to learn more about how our patient-centered practice can help you find balance and vitality.
Yoon Hang Kim MD
Integrative & Functional Medicine Physician
Virtual Practice Serving IA, IL, MO, FL, GA, and TX
---
REFERENCES
Adams, G. R. (2002). Insulin-like growth factor in muscle growth and its potential abuse by athletes. British Journal of Sports Medicine, 36(3), 162-164. https://doi.org/10.1136/bjsm.36.3.162
Ahmad, S. S., Ahmad, K., Lee, E. J., Lee, Y. H., & Choi, I. (2020). Implications of insulin-like growth factor-1 in skeletal muscle and various diseases. Cells, 9(8), 1773. https://doi.org/10.3390/cells9081773
Araj, F. G., et al. (2025). Epitalon increases telomere length in human cell lines through telomerase upregulation or ALT activity. GeroScience. https://doi.org/10.1007/s11357-025-01550-8
Berlanga-Acosta, J., Nieto, G. G., Lopez-Mola, E., & Herrera-Martinez, L. (2017). Synthetic growth hormone-releasing peptides (GHRPs): A historical appraisal. Clinical Medicine Insights: Cardiology, 11. https://doi.org/10.1177/1179546817694558
Cerovecki, T., et al. (2010). Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Journal of Orthopaedic Research, 28(9), 1155-1161. https://doi.org/10.1002/jor.21107
Dergunova, L. V., & Filippenkov, I. B. (2021). Pharmacological analysis of Semax and its analogs. Neuroscience & Medicine, 4(4), 223-252.
Fedorov, V. D., et al. (2013). Effects of Selank on gene expression in the immune system. Bulletin of Experimental Biology and Medicine, 155(5), 643-646.
Ghigo, E., Arvat, E., Muccioli, G., & Camanni, F. (1997). Growth hormone-releasing peptides. European Journal of Endocrinology, 136(5), 445-460. https://doi.org/10.1530/eje.0.1360445
Gwyer, D., Wragg, N. M., & Wilson, S. L. (2019). Gastric pentadecapeptide BPC 157 and its role in accelerating musculoskeletal soft tissue healing. Cell and Tissue Research, 377(2), 153-159. https://doi.org/10.1007/s00441-019-03016-8
Heffernan, M. A., et al. (2001). Effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism in obese mice. Endocrinology, 142(12), 5182-5189. https://doi.org/10.1210/endo.142.12.8522
Jiang, Q., et al. (2020). The effect of resistance training on serum IGF-1: A systematic review and meta-analysis. Complementary Therapies in Medicine, 50, 102360. https://doi.org/10.1016/j.ctim.2020.102360
Jiang, F., et al. (2023). Synergy of GHK-Cu and hyaluronic acid on collagen IV upregulation. Journal of Cosmetic Dermatology, 22(8), 2250-2260. https://doi.org/10.1111/jocd.15763
Józwiak, M., et al. (2025). Multifunctionality and possible medical application of BPC 157. Pharmaceuticals, 18(2), 185. https://doi.org/10.3390/ph18020185
Khavinson, V. K., Bondarev, I. E., & Butyugov, A. A. (2003). Epithalon peptide induces telomerase activity in human somatic cells. Bulletin of Experimental Biology and Medicine, 135(6), 590-592.
King, R., & Tuthill, C. (2016). Immune modulation with thymosin alpha 1 treatment. Vitamins and Hormones, 102, 151-178. https://doi.org/10.1016/bs.vh.2016.04.003
Koroleva, S. V., & Mjasoedov, N. F. (2023). Selank: Anxiolytic peptide with nootropic properties. Regulatory Peptides, 147(1-3), 45-52.
Matteucci, C., et al. (2021). Thymosin alpha 1 mitigates cytokine storm in COVID-19 patients. Open Forum Infectious Diseases, 8(1), ofaa588. https://doi.org/10.1093/ofid/ofaa588
Pickart, L., & Margolina, A. (2018). Regenerative and protective actions of GHK-Cu peptide. International Journal of Molecular Sciences, 19(7), 1987. https://doi.org/10.3390/ijms19071987
Robinson, L. R., et al. (2005). Topical palmitoyl pentapeptide provides improvement in photoaged skin. International Journal of Cosmetic Science, 27(3), 155-160.
Schagen, S. K. (2017). Topical peptide treatments with effective anti-aging results. Cosmetics, 4(2), 16. https://doi.org/10.3390/cosmetics4020016
Sikiric, P., et al. (2021). Stable gastric pentadecapeptide BPC 157 and wound healing. Frontiers in Pharmacology, 12, 627533. https://doi.org/10.3389/fphar.2021.627533
Spurney, C. F., et al. (2010). Evaluation of thymosin β-4 in dystrophin deficient mouse. PLoS ONE, 5(1), e8976. https://doi.org/10.1371/journal.pone.0008976
Sullivan, M. J., et al. (2025). BPC-157 in orthopaedic sports medicine: A systematic review. Sports Medicine. https://doi.org/10.1177/03635465251329481
Teichman, S. L., et al. (2006). Prolonged stimulation of GH and IGF-I by CJC-1295. Journal of Clinical Endocrinology & Metabolism, 91(3), 799-805. https://doi.org/10.1210/jc.2005-1536
Xing, Y., Ye, Y., Zuo, H., & Li, Y. (2021). Progress on thymosin β4. Frontiers in Endocrinology, 12, 767785. https://doi.org/10.3389/fendo.2021.767785
Yoshida, T., & Delafontaine, P. (2020). Mechanisms of IGF-1-mediated regulation of skeletal muscle. Cells, 9(9), 1970. https://doi.org/10.3390/cells9091970
---
This article is for educational purposes only. Not medical advice.
Last updated: December 2024