Peptides & Biologics
Peptides & biologics target innate physiologic functions to maximize healing, repair, and recovery.
Peptides are the future of medicine: they are small powerful biological signaling molecules that can exert potent effects on cells and tissues, and they are also now being used as powerful tools for optimizing tissue repair, healing, recovery, and overall health. Peptides are designed to specifically bind to different types of cell receptors, thereby working through multiple unique mechanisms, including repairing injured cells, rebuilding structural components of tissues, making cells work better and more efficiently, replacing injured or worn out cells with new ones, modulating inflammatory responses, and increasing cell migration to an area of injury. We utilize FDA-approved peptides and biologic agents to aid recovery and tissue repair through your own natural and unique cell signaling pathways. The following summary of scientific research on a variety of peptides and their molecular mechanisms and clinical effects is for informational and educational purposes only-- there are many other peptides and biologic agents not discussed here, not all agents may be available, not all agents are FDA-approved, and the risks and benefits of peptide and biologic therapies should always be discussed with a physician who has expertise and experience prescribing these unique pharmacologic agents. The following detailed discussion covers some of the best peptides for healing, joint pain, injury repair, arthritis, inflammation, and recovery.
Unfortunately, many doctors and practitioners are still uneducated on these new therapeutic approaches and continue to use high-dose corticosteroids as a mask for pain and a shotgun approach for many orthopedic ailments even though these types of corticosteroid medications slow healing and cause atrophy of tendon, ligament, bone, and cartilage due to downregulation of collagen synthesis, thus causing worsening or recurrence of the problem and degenerative feedback cycles. It is far better to find the specific details of an injury or condition, then treat the specific underlying cause in ways that help it to heal. There are actually only a few instances where steroids (e.g., methyl-prednisolone, triamcinolone, dexamethasone, or "cortisone shots") should be used (e.g., for certain types of inflammatory processes but rarely for chronic injuries or pain) (1) (2) (3) (4) (5) (6) (7) (8). Many other options-- including peptides, biologics, and PRF-- promote connective tissue rebuilding (rather than inhibit it like steroids), as further discussed below. In other words, our ideal approach is to stop the degenerative process and promote regenerative processes that enhance tissue repair and maximize function. Peptides can also be combined in with protein hydrogels like PRF to create peptide hydrogels that further enhance tissue repair.
Peptide functions create synergistic effects on tissue healing by combining them with growth factors and self-assembling scaffolds like PRF. Dr. McMurtrey is studying peptides in advanced tissue engineering designs to aid in repair and regeneration of brain and spinal cord after stroke and traumatic spinal cord injury as well as orthopedic injuries and many other types of tissue repair (9) (10) (11) (12) (13) (14) (15) (16) (17) (18) (19a) (19b).
Sermorelin + Glycine: glycine is a single amino acid found in high levels in collagen protein (see the nutrition page), and it can help stimulate natural release of growth hormone from the pituitary gland (20). Sermorelin is a 29 amino-acid fragment of the naturally occurring human growth hormone-releasing hormone (GHRH or GRF), and it can be used for additional release of your own natural growth hormone, thereby enhancing tissue healing, anti-inflammatory, and anti-aging effects (21). Evidence also suggests that growth hormone release may enhance peripheral nerve regeneration and remyelination repair in scientific studies (22) (23) (24). In addition, your own GH can also act in concert with another natural peptide called IGF-1 to further promote connective tissue healing and repair.
Ipamorelin + CJC-1295: these two peptides act together to help you release your natural growth hormone (GH), which is an excellent stimulant of connective tissues healing, including bone, tendon, and ligament healing. CJC-1295 imitates your natural GHRH, while Ipamorelin is an analog of the natural ghrelin hormone that acts on the pituitary via a different mechanism to augment GH release: (25) (26) (27) (28) (29) (30) (31) (32). This approach may also help stimulate remyelinating nerve regeneration effects cited above. By combining other peptides with synergistic effects (e.g., BPC-157), it is also possible to upregulate GH-receptors on cells like tenocytes (tendon cells) to stimulate tendon repair and help regenerate and lay down more collagen for repair (33). This combination of peptides augments your own natural GH production, storage, and pulsatile release without the typical downsides of exogenous GH or other similar peptides (i.e., without increased cortisol, ACTH, prolactin, aldosterone, or hunger), and many people report suppressed appetite, weight loss, better sleep, and better cognitive function and mental acuity. In addition, your own GH can act in concert with another natural peptide called IGF-1 to further promote connective tissue healing and repair.
Semaglutide & Tirzepatide: these unique peptides have recently become popular for treating both diabetes and obesity, providing rapid and substantial weight loss by activating the GLP-1R signaling pathway to stimulate glucose-dependent insulin secretion via activity at the GIP receptor (GIPR) or the GLP-1R, as well as augmenting insulin secretion, inhibiting glucagon release and hepatic gluconeogenesis, improving insulin resistance, reducing adverse cardiovascular events like heart attack and stroke, and suppressing gastric emptying and appetite. However, there might also be side effects which patients should be aware of, such as potential risk of thyroid cancer but also simultaneous beneficial enhancement of anti-cancer effects by promoting tumor recognition and immunity (34).
TB-500 (Thymosin Beta 4): a derivative of the natural Thymosin Beta-4 peptide which has been studied in several clinical trials and which is produced naturally by the thymus gland and platelets and has been shown to be upregulated in acute phases of injury. TB-500 is a short bioactive peptide sequence which has also been shown to enhance wound repair, suppress inflammation, enhance collagen deposition, promote neurogenesis, and which has also been shown to play a role in recovery from traumatic brain injury, stroke, spinal cord injury, cardiac ischemic injury, peripheral neuropathy, and others. In injured neural tissue it has been shown to protect neurons, enhance neurogenesis, and promote re-myelination by oligodendrocytes. Additionally, when injected in the scalp it may also have some benefit in hair regrowth, especially when combined with PRF. Its many good effects on multiple types of tissues make it a very useful agent, but it is banned in sports as a performance enhancing drug (35) (36) (37) (38) (39) (40) (41) (42) (43) (44) (45) (46) (47) (48) (49) (50) (51) (52) (53) (54) (55) (56) (57) (58) (59)
TB4 Fragment (Ac-SDKP): a derivative of the Thymosin Beta-4 peptide, this is the shorter bioactive peptide sequence which is orally bioavailable (and can also be produced naturally in the body with enzymatic hydrolysis of innate Tβ4), and which has likewise shown several anti-inflammatory, immunomodulatory, and tissue-protective properties (60). Interestingly, evidence also suggests that Tβ4 along with Tα1 (below) may be able to induce myelin repair, neuroprotection, therapeutic effects in multiple sclerosis, as well as other inflammatory and autoimmune diseases (61). (62).
BPC-157: a pentadecapeptide fragment of a naturally-occurring peptide in gastric juice known as "body protection compound" and which is highly stable at room temperature and can thus last longer than many other injectable signaling factors. Most importantly, it demonstrates significant protective and reparative properties in tissues, including anti-inflammatory effects, enhanced cellular repair, and enhanced collagen synthesis. BPC 157 is not only protective of gut health, but when injected at an injury site it can stimulate tendon fibroblasts and upregulate growth hormone receptors in injured tissues to enhance the repair response. Altogether BPC157 has shown potent healing capabilities in muscle, tendon, and ligament injuries, particularly in achilles and knee tendons and ligaments as well as repair of non-healing bone fractures and tendon-to-bone avulsion tears and muscle strains (63) (64) (65) (66) (67) (68) (69) (70) (71) (72) (73) (74) (75) (76a) (76b). These studies also show that BPC-157 has unique anti-inflammatory effects, which avoids the unwanted degradative downsides of corticosteroids, and BPC-157 also upregulates GH-receptors and VEGF-receptors that work in concert with your own natural growth hormone and natural growth-hormone augmentation strategies for exponentially greater effects. BPC-157 may also enhance axon regeneration and repair in spinal cord injury, and because it can enhance ligament and tendon strength, it may also help spinal deformities, disc repair, and spinal instabilities when used at specific targeted sites (77) (78)
Pentosan Polysulfate: a unique agent that both stimulates cartilage matrix synthesis and inhibits cartilage breakdown, thus showing new promise as a powerful therapeutic agent for osteoarthritis. Originally designed as an intra-articular injection, it has also shown potent effects as a subcutaneous injection, and it is one of the only agents that has been shown to strengthen cartilage tissue by increasing cross-linking and polymerisation of the large molecules found in cartilage: (79) (80) (81) (82) (83) (84). It is a unique glycoasminoglycan that has potent anti-inflammatory properties, and it typically only needs to be used for just a few weeks for therapeutic effect. Furthermore, it can be combined with HA+Chondroitin treatments and/or PRF treatments and/or peptide treatments for enhanced synergistic effects-- see the osteoarthritis page for more information.
AOD 9604 (Frag 176-191): a small 15 amino-acid fragment of Growth Hormone which does not significantly activate the GH-receptor, this small fragment has been shown to have strong lipolytic (fat-burning) effects and thus is very effective for weight loss. It can also enhance cartilage repair, especially when paired with Pentosan, PRF, Hyaluronic Acid, BPC-157, and/or Ala-Glu-Asp (AED) peptide sequences. (85) (86) (87) (88) (89) (90a). (90b).
Thymosin Alpha-1 (Tα1): evidence suggests enhancement of healthy immune responses (including T-cell, dendritic cell, and antibody reponses), and this peptide has been approved in over 35 countries for its immune enhancing, immune modulating, and immune controlling effects (also known as thymalfasin), particular for treating infectious conditions like viral, fungal, and mold infections, treating autoimmune diseases like psoriatic arthritis, treating cancer and inducing tumor immunity (including hepatic, renal, and lung cancer), as well as recovery from chemotherapy-induced toxicity (91) (92). More specifically, Tα1 upregulates MHC-I expression, enhances toll-like receptor (TLR) signaling, increases NK cell number, regulates T-cells, and may provide a variety of anti-viral replication effects, anti-fungal, anti-mold, and anti-bacterial effects. In addition, new evidence has also shown powerful effects in enhancing tumor immunogenicity to help recognize and eradicate foreign agents and help provide anti-tumor and anti-cancer effects (93) (94) (95) (96) (97) (98) (99) (100) (101) (102) (103) (104). Many doctors are unaware that viral infections frequently alter the expression of toll-like receptors (TLRs) in ways that make our immune systems more susceptible to bacterial infections as well (as is seen in the critical care setting where, for example, a viral pneumonia can transition into an even worse bacterial pneumonia) (105) (106) (107) (108) (109) (110), but interestingly the Thymosin Alpha-1 peptide may enhance TLR immune responses to virus, bacteria, mold, and fungi, thereby helping fight these infections and protect against severe infectious consequences. TA1 also appears to help fight hepatitis B and C infections, and can be used as an adjunct to significantly enhance immunity for immunocompromised and immunosuppressed conditions (including cancer, transplant, and autoimmune rheumatology patients), with evidence suggesting that natural levels of Thymosin Alpha-1 are significantly depleted in auto-immune diseases and restoring TA1 levels helps to regulate T-cells and antibody responses while suppressing inappropriate inflammatory responses, thereby bringing immune reactions into balance (111) (112) (113) (114) (115) (116) (117).
Hyaluronic Acid + Chondroitin (Viscosupplementation): these molecules are not peptides but instead form some of the main constituents of cartilage matrix and can help restore joint function and mechanical properties of shock absorption, lubrication, and cartilage protection. Studies have shown a 77% reduction in pain, 78% improvement in mobility and 74% reduced consumption of analgesics with use of hyaluronic acid and chondroitin sulfate in osteoarthritis (118). Although a numbing agent like lidocaine can also be injected into the joint at the same time for temporary pain relief, there is some evidence that this actually worsens arthopathy in the long run. Thus, the ideal regenerative therapies mentioned above are better in the long run-- see the osteoarthritis page for more information.
Epithalon or Epitalon: may induce telomere elongation, induce neurogenesis, guide stem cell differentiation, prevent skin fibroblast aging, and influence other epigenetic controls that can slow aging processes (119) (120) (121) (122). Telomere length has been shown to explain most transcriptional changes observed with cellular aging in humans, and many interventions described on our aging page have been shown to counter these aging processes and restore balance to altered transcriptome profiles within aging cells (123).
Epicatechin: although not a peptide, this unique flavonoid molecule occurs naturally in small amounts in dark chocolate and green tea, and it has been shown to induce mitochondria biogenesis, promote muscle regeneration, and inhibit myostatin, thereby enhancing lean muscle mass, strength, and VO2 max (124) (125) (126) (127) (128) (129). It can therefore be used to prevent age-related or altitude-related loss of muscle mass (sarcopenia), but at least one study has found no improvement in aerobic exercise performance (130).
GHK-Cu: may enhance wound healing, glycosaminoglycan synthesis, and collagen deposition in the skin, thereby helping to regenerate and tighten the skin (131) (132) (133) (134) (135). It can also be combined with methylene blue to help enhance collagen synthesis and anti-aging effects in the skin, giving a more youthful appearance and texture (136) (137) (138).
KPV: this peptide, along with Thymosin Alpha-1, has shown effects in reducing intestinal inflammation such as that caused by ulcerative colitis and inflammatory bowel disease (IBD), and preliminary evidence in animal studies suggests it may be capable of preventing other forms of autoimmune inflammation as well as colitis-related colorectal carcinogenesis (139) (140) (141) (142).
Oxytocin: this natural neuroendocine peptide hormone can not only provide weight loss effects (143), but may also stimulate regeneration of skeletal muscle and heart cells (cardiomyocytes), including preservation of muscle mass as we age (144) (145), in addition to sexual performance benefits.
Adalimumab (Humira), Etanercept (Enbrel), or Infliximab (Remicade): biologic monoclonal antibodies used in the treatment of various autoimmune arthritides like spondyloarthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. These work by binding and sequestering TNF-alpha, which is known to cause severe degradation of joints, cartilage, and entheses. These diagnoses tend to be associated with the HLA-B27 marker but diagnosis can be complicated by the fact that many symptoms may or may not be present and no single imaging study or lab test can make the diagnosis. Because of the immunosuppressive effects of this class of biologic agents, latent infections like tuberculosis should be ruled out before starting (146) (147) (148) (149) (150) (151).
Parathyroid Hormone Analogs: Abaloparatide, Denosumab, and Teriparatide (Tymlos, Prolia, & Forteo) are peptides and biologic agents based on natural parathyroid sequences to replicate the anabolic effect of parathyroid hormone increasing bone density and calcium deposition, which can stop and reverse even severe osteoporosis (152) (153). Like the bisphosphonates, these can potentially have risks of inducing brittle bones or osteonecrosis, and the benefits tend to disappear once you stop taking them, but they can often be dosed many months apart and offer another option if other treatments are not effective enough.
Future Studies: We often combine regenerative therapies like stem cells with other synergistic agents like peptides. Due to their specific targeting capabilities, peptides are the way of the future, and many other types of peptides are under investigation for many conditions, including for organ functions, cancers, neurological injuries, and cognitive functions (e.g., semax and selank for cognition, kisspeptin for cancers, NVG-291 for spinal cord injury, P021 for Alzheimer's dementia, BIIB080 for Alzheimer's disease (actually an anti-sense nucleotide or ASO), and many others (154) (155) (156) (157) (158) (159) (160) (161) (162).
Also see additional peptides for sexual health, weight loss, and additional synergistic agents on our anti-aging, infusions, and PRF pages.
Dr. McMurtrey managed critical care units and trauma surgery services at a Level I trauma center when he began to wonder why some patients with extensive and complex injuries could sometimes recover quickly while other patients with less severe injuries would sometimes seem to fall into an unrecoverable rut of chronic degradation and endless complications. Although we are still sorting out all the answers to this complex question, one clear explanation can be found in the numerous intersecting cell signaling pathways that mediate inflammation, immunity, and tissue repair. Novel peptides are known to act directly and indirectly on many of these crucial pathways in highly targeted ways that enable us to optimize your healing based on your particular condition.
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ASOI © 2021 All Rights Reserved*Disclaimer: We seek to always provide the highest-quality evidence-based care to our patients customized for their specific conditions, injuries, and diagnoses, which may include FDA-approved therapies as well as additional investigational, alternative, or regenerative therapies. We always discuss potential risks and benefits of all these options. The information presented here is for informational use and cites the ongoing cutting-edge research and medical advancements on these relevant topics. There are many treatments, interventions, and protocols routinely practiced in medicine and surgery which the FDA has not studied nor formally approved yet which have demonstrated overwhelming evidence of efficacy and clinical benefit, while many standard treatments and common surgeries can actually have high rates of failure and complication. The FDA does not regulate the practice of medicine but rather regulates medical marketing of devices and drugs. The FDA does not conduct clinical trials or attempt to discover new treatments, but rather requires companies or other entities to fund marketing approvals. Breakthrough technologies typically require years to decades of research work to optimize the technology and collect enough data to prove efficacy and superiority, which in some cases can optionally be submitted to the FDA if there is sufficient financial backing to market a specific product or drug. Thus the FDA has not yet studied, evaluated, or formally approved many regenerative therapies currently practiced by many of the top physicians and surgeons in the United States and around the world. Some therapies, products, or interventions may still be considered investigational or "off-label" even with substantial evidence of efficacy, and many different applications of regenerative therapies continue to be researched by our institute and other top institutions around the world. The rapid evolution and advancement of medicine demands that physicians continually update their knowledge and practice techniques to adapt to future improvements and advancing technologies. These statements have not been evaluated by the FDA, and the treatments and products presented here are for informational purposes and not guaranteed to diagnose, treat, cure, or prevent any specific disease or condition. All injuries and conditions should be formally evaluated by a knowledgeable medical professional whereby standard treatments and additional therapeutic interventions may be considered with the diagnosis and treatment plan.