DISCLOSURE STATEMENT
ChiefMedicalOfficer-IntegrativePeptides
IntegrativePeptides.com
Currently sells orally active and absorbable peptides in oral supplement form with unique delivery methods
ChiefMedicalOfficer-NationalAcademyof HypothyroidismandIntegrativeSciences(NAHIS) NAHypothyroidism.org
NAHIS is a non-profit, multidisciplinary medical society dedicated to the dissemination of new information on the diagnosis and treatment of hypothyroidism and complex conditions. NAHIS receives grants for clinical and laboratory research for novel methods in the diagnosis and treatment of hypothyroidism and chronic illnesses
Owner/CEO-HoltorfMedicalGroup
HoltorfMed.com
A multi-specialty medical group specializing in the treatment of complex endocrine dysfunction, CFS/fibromyalgia, chronic infectious diseases, immune dysfunction, neurodegenerative disease, and other complex chronic illnesses.
Important Disclaimer
All studies have limitations, and there is no perfect study. As with other studies, the studies mentioned below have limitations that should be considered when evaluating the efficacy of peptides and determining the appropriateness of peptides for consumer use. A short summary, the abstract and the entire study is provided for your review. It is strongly recommended that you read each study in its entirety to best understand the uses, risks, effects, and limitations of the data on peptides. While studies suggest that these are possible outcomes, The National Academy of Hypothyroidism does not endorse the use of peptides for any of these conditions. These are provided for educational use only.
Kent Holtorf, M.D. is the medical director of the Holtorf Medical Group and the nation-wide Holtorf Medical Group Affiliate Centers. He is the founder and medical director of the non-profit National Academy of Hypothyroidism (NAH), which is dedicated to disseminating new evidence-based information to doctors and patients on the diagnosis and treatment of hypothyroidism and advanced integrative diagnostic and treatment protocols. He is also the founder of Integrative Peptides, which is dedicated to training physicians regarding groundbreaking peptide therapies for their patients and bringing the highest quality natural bioidentical peptides as supplements with unique delivery systems to doctors.
Dr. Holtorf is an internationally known lecturer, author, and innovator in cutting edge research and treatments. He has personally trained numerous physicians across the country in the use of bioidentical hormones, thyroid replacement for complex hypothyroidism syndromes, peptide therapies, immune-modulatory strategies, stem cell, exosome and growth factor treatment, hormone replacement for complex endocrine dysfunction, and innovative treatments of chronic fatigue syndrome, fibromyalgia, Lyme disease, and other chronic infectious diseases, CIRS, neurodegenerative diseases, and many others.
He is a fellowship lecturer for the American Board of Anti-aging Medicine. He was the Endocrinology Expert for AOL Health and is a guest editor and peerreviewer for a number of medical journals, including Endocrine, Postgraduate Medicine, and Pharmacy Practice. Dr. Holtorf has published many peer-reviewed endocrine reviews on complex, multisystem, poorly understood conditions. He has demonstrated that much of the long-held dogma in endocrinology and infectious disease is inaccurate.
He has been a featured guest on CNBC, ABC News, CNN, Fox News (debated the Fox news medical A-team), Good Morning America, The Today Show, EXTRA TV, Discovery Health, The Learning Channel, Glenn Beck, Nancy Grace, Sean Hannity, and more and quoted in numerous print media including the Wall Street Journal, Los Angeles Times, US News and World Report, San Francisco Chronicle, WebMD, Forbes, among many others.
If you’ve investigated ways to improve your health, you’ve probably come across the term ‘peptide,’ and you might be wondering, what exactly is a peptide? A peptide is a compound made of two or more amino acids linked inashortchain(figure 1). By definition, if it has less than 40 amino acids, it is called a peptide. If the chain is longer than 40 amino acids, it is called a protein.
Peptides regulate most every known process and system in the body in a tissue and cell-specific manner, including hormone production, immune function, the sleep cycle, the production of inflammatory mediators, DNA replication, cell division and renewal, cancer cell destruction and apoptosis, libido and sexual arousal, weight loss, lean muscle gain, mitochondrial function, cognitive function, mood, energy and other metabolic activities, tissue healing and specific biological functioning of the brain, skin, eyes, urinaryandreproductivesystems,agingandlongevity,andmanymore.
Compared to prescription medications and hormones, they tend to be more selective and less likely to be associated with any serious adverse side effects.
Peptides are generally cell surface signaling molecules that indirectly affect cellular activity via a cascade of secondary messengers (figure 2). Hormones work on specific receptors in the nucleus, affecting protein synthesis, generally being slow on and slow off, less selective, and, in general, higher risk. Peptides have pleiotropic effects (no one effect) that are generally like supplements but more potent and selective and are quick on and quick off but can have lasting epigenetic changes. Peptides are very synergistic with other peptides, supplements, hormones, antibiotics, and most other therapies.
Figure 2
Small natural peptides have a long history of safety and effectiveness, being used in Europe for over 40 years, having hundreds of thousands of patientyears (hundreds of thousands of patients using for almost half a decade) that demonstrate their incredible safety and effectiveness. However, despite the many obvious clinical advantages, including unprecedented safety and efficacy and decades of commercial successes in Europe, the full potential of peptide therapeutics has yet to be unleashed in the United States. A major reason is that they have surpassed their patent potential, which makes them undesirable to the pharmaceutical industry here in the US. In addition, the high cost of manufacturing has been a detriment to their widespread use in theUS.
Peptides are naturally built in the body by linking together amino acid residues through peptide bonds in an end-to-end fashion (figure 3); each amino acid carries a unique functionality adding a specific property to the peptide. The different amino acid residues are like Lego blocks that target very specific physiologic effects. As a result of their being bioidentical to what the body produces, the peptides are used to target and optimize particular physiologic functioning of the body’s systems as “optimization and replacement therapies” that add back or supplement peptide levels in cases where endogenous levels are inadequate or absent. This is much like the incredible breakthrough in the 1920s, where the isolation and therapeutic use of the peptide/protein insulin was used in people with diabetes.
PeptideBond (linking 2 amino acids)
Based on their extensive track record of safety and effectiveness over decades, it has finally been realized that they have significant advantages over most medications and protein therapeutics, including their small size, which gives them the ability to penetrate cell membranes, the blood-brain barrier, biofilms, mitochondria, gastrointestinal membranes, avascular tissue, and much more. They also have high potency, specificity, activity, and affinity. They have a huge therapeutic index (the effective dose divided by thedosethatistoxic),whichismany-foldhigherthanevenover-the-counter medicationsandsupplements.
Figure 3Many commonly used peptides have been found to have no side effects even when given at doses 1000 times the usual dose, which is unheard of with any medication, or even water for that matter. They have an incredibly low likelihood of drug or supplement interactions, other than positive synergistic effects. Being small in size and water-soluble, they are naturally degraded by the body and don’t accumulate in specific organs, such as the kidney or liver, further increasing their safety profile. Many popular peptides have no known toxic level, meaning researchers could not elicit any toxicity effectsnomatterhowhighthedosage
General Classes of Peptides
Below is a selected list and classification of the most commonly used peptides. There are many ways to classify peptides, but classification by location and the main activity is the best way to fully understand how they canbebestutilized.(Table 1).
Immune modulating peptides (thymic--from thymus gland)
Thymosin Alpha 1 (TA1)
Thymogen/Vilon (Thymogen Alpha 1-A TA! Replacement)
Thymosin Beta 4 (Tβ4), TB4 Active Frag (Ac-SDKP)
Zn-thymulin
BPC-157
KPV (Fragment of Alpha-melanocyte stimulating hormone)
Delta sleep-inducing peptide (DSIP)
Pineal gland peptides (Modulate thymus, increase telomere length, modulate immunity, sleep, and the hypothalamic-pituitary-hormone axes)
Epithalon
Pinealon
Delta sleep-inducing peptide (DSIP)
Brain peptides (Improve memory, depression, anxiety, brain injury, cognitive function, etc.)
Semax
Selank
Cerebrolysin (IV and oral)
Humanin
BPC-157
TB4 Active Frag
Delta sleep-inducing peptide (DSIP)
KPV
SS-31
5-Amino-1MQ
MOTS-c
Table 1 - Classification by location of origin and main activityTable 1 (cont.)
GHRH/GHRP (Growth hormone-releasing hormones and growth hormone-releasing peptides-stimulate growth hormone production)
CJC-1295/ Ipamorelin
Tesamorelin
Hexarelin
Ibutamoren (MK-677)
Sermorelin
BPC-157
TB4 Active Frag (Ac-SDKP)
Others
Mitochondrial peptides
MOTS-c
SS-31
Humanin
Small-humanin-like peptides (SHLP)
5-Amino-1 MQ
BPC-157
TB4 Active Frag (Ac-SDKP)
Delta sleep-inducing peptide (DSIP)
T3
Gastrointestinal/Leaky Gut/Inflammatory Bowel Disease/Gut-Brain Axis***/ Disease peptides
BPC-157
TB4 Active Frag
KPV
Delta sleep-inducing peptide (DSIP)
LL-37
Tuftsin
Cerebrolysin (IV and oral)
Selank
Rejuvenation/Pain/Healing peptides
BPC-157
TB4
TB4 Active Fragment (Ac-SDKP)
Epitalon
Pinealon
DSIP
KPV
AOD-9604 (fragment of growth hormone)
GHK-CU
GHRH/GHGP
Sleep peptides/Anti-anxiety
BPC-157
TB4
TB4 Active Fragment (Ac-SDKP)
Epitalon
Pinealon
DSIP
KPV
AOD-9604 (fragment of growth hormone)
GHK-CU
GHRH/GHGP
Gut-Brain Axis
There are two key aspects of the GI system that influence health and disease pathogenesis: the microbiome effects on the neurologic system, inflammation, and health, and the brain’s influence on the microbiome and overall GI functioning (intestinal mobility, mucous secretion, secretory functions, blood flow, etc.). Additionally, a” leaky gut” means there is a “leaky brain” (the blood-brain barrier (BBB) is not able to keep out toxins, infectious agents, and inflammatory molecules and cells), and if there is gut inflamed, there is also brain inflammation due to this gutbrain connection. (Figure 4)
Numerous studies show that BPC-157, TB4 Active Frag, KPV, and DSIP reduce gut inflammation and promote healing of the gut, the brain BBB, and other tissues in the body. Additionally, TB4 Active Frag, and KPV specifically promote healing of the GI and BBB tight junctions, which are core abnormalities that result in “leaky gut” and “leaky brain,” making them a powerful combo for “leaky gut” and cognitive, mood, and neurodegenerative diseases. The power of the effectiveness of these peptides in the treatment of “leaky gut” and diseases on the central nervous system is that they have the rare ability to work on both sides of the gut-brain axis, positively affecting the gut’s health and its influence on brain health and the brain’s health and its influence on gut health, and their influence on the overall body’s inflammation and functioning via the gutbrain-immune-inflammatory connection.
Figure 4
Gut-Brain Axis
BPC-157.TB4ActiveFrag,KPV,DSIP
Protects and/or promotes healing in the liver2,3,35
Prevents and reverses inflammatory and autoimmune diseases, such as rheumatoid arthritis, Lupus and Hashimoto’s2,3,35
Modulates pain pathways2,3
Has neuroprotective and neuro-regulatory effects, particularly related to gut-brain interaction3,10,25
Repairs the gastrointestinal tract and is shown to be more effective than H2-blockers (Zantac), proton pump inhibitors (omeprazole) and gastric coating agents (sucralfate)2,3,7-10,32
Promotes muscle, tendon, and ligament healing14,15,18,24
Promotes wound healing in the corneal epithelium16,17,22,23
Accelerates bone healing and is effective for diseases such as periodontitis19,26,30
Has anti-inflammatory effects26
Is shown to increase serotonin secretion in a number of areas in the brain and is shown more effective for depression than antidepressants and is shown to help to handle chronic and acute stress38
Counteracts the damaging effects of NSAIDs on the gastrointestinal tract28
Protects against numerous toxins, including alcohol, NSAIDS, Clostridium difficile (C. diff) toxin, mycotoxins (toxins from mold) and other neurotoxins (toxins affecting the brain) and enterotoxins (gastrointestinal toxins)3,9,31,33
Shown to be effective in traumatic brain injury, Parkinson’s and multiple sclerosis10,31,32
Shown to normalize lower esophageal and pyloric sphincter pressures, which are common causes of gastric reflux40
Effective for multiple diseases of the gastrointestinal tract, including gastritis and inflammatory bowel diseases36
Enhances the healing effects of growth hormone37
Shown to be effective both orally, rectally and parenteral (injection or intravenous)10,36
BPC-157 is shown to prevent and/or reverse a wide range of stimulated arrhythmias, including A-Fib, A-V Block, ventricular tach, A-V block, premature atrial contractions and premature ventricular contractions, as well as other cardiac arrhythmias.27,35 Table 2
Improved tissue repair and healing
Improved host defense to infection
35,36,37,41
26,27,28,29,30
Reverse immunosuppression of chronic infection (Lyme)24,26,27,28,29,33,34,37
Increases antioxidant and glutathione production
26,27,28,31,28,29,63,66
Boost NK function26,35
Stimulates ligament, tendon, and muscle repair.
Prevents and reverses fibrosis
Effective in sepsis
Improves dry eye disorders
Can improve hair growth
Accelerates wound healing
Effective against fatty liver (NAFLD and NASH)
TH2-TH1 immune modulation (infections, cancer, herxheimer, autoimmune)26,27,28,30,31,33
Protect against toxins, including neuro/myco (mold), and endotoxins111
Cardiac regeneration and protection post-MI, CHF, etc.39,65,98,99,100
Neurologic protection and regeneration post-stroke, TBI, Lyme disease, Alzheimer’s, neuropathy, Parkinson‘s, etc.63,67,42
Improves memory
Stimulate stem cell activity and proliferation
32,34,36,38,40,41,42
Increases longevity89,90,91
Have almost non-existent side effects at 100-fold dose+ excess103,104
Excellent safety profile with a large therapeutic window (over 1000 fold)103,104
Boosts mitochondrial function
Reduces microglial activation (brain inflammation) to toxins and infections
Cardiac regeneration
Effective treatment of biofilms, especially smaller fragments, such as TB4 Active Fragment
Improve allergies and mast cell activation
Improves insulin resistance and prevents and reverses diabetic complications, such as kidney and heart disease and neuropathy.
Heals the tight junctions in the gastrointestinal mucosa with leaky gut and stabilize a leaky bloodbrain barrier.
Is antimicrobial against bacteria, viruses, parasites and fungi
Breaks down biofilms
Produced in the pituitary gland, Melanocyte Stimulating Hormone (MSH) helps regulate many other hormones and plays an essential role in the body’s inflammation responses to foreign pathogens, being one of the most antiinflammatory substances produced in the body. Unlike steroids, however, MSH and its analogs do not lower the body’s ability to fight infection; rather, it enhances the body’s immunological defense against invading organisms and also has potent broad-spectrum antimicrobial effects against bacteria, viruses, mold, parasites, and fungi. Thus, low levels of MSH will result in multi-system inflammation (i.e. CIRS) and an inability to fight many infections, with MARCoNS (multiple antibiotic resistant coagulase negative staph) infection of the sinuses being a specific example.
MSH and leptin have reciprocal stimulating effects on each other. Under normal conditions, an increase in leptin levels results in a corresponding increase in MSH and vice versa. However, when leptin receptors are interfered with by inflammatory cytokines, causing leptin resistance, high leptin is associated with low MSH because the leptin signal does not reach the receptors in the brain. Low levels of MSH are evident in patients with mold illness/CIRS and can remain low even after treatment. When this happens, leptin production continues to increase without a corresponding rise in MSH levels, resulting in leptin resistance and unhealthy weight gain. In healthy people, a rise in leptin levels would trigger the brain to create more MSH, which does not occur in CIRS patients.
MSH is also involved in the opening and closing of tight junctions in the intestinal tract. Diminished MSH levels can prevent tight junctions from closing properly, leading to leaky gut. In addition, research has established that approximately 80 percent of patients with low MSH levels also have MARCoNS. This creates a vicious cycle because MARCoNS produces toxins that suppress MSH production. Treating MARCoNS is therefore vitally important in order to restore return MSH levels to normal levels. The normal range for MSH is 35-81 pg/ml.
It is not practical to give MSH due to its poor bioavailability and short half-life. Commercially available MSH analogs have been developed, which include Melanotan I & II and PT-141. Melanotan I and II have been known as the “Barbie Doll” peptide because it stimulates weight loss, libido, and activation of skin melanocytes (makes you tan). The tanning portion is a double-edged sword, however, as it works well for younger individuals, but older individuals will often develop dark spots, as areas of sun damage darken. PT-141 works for erectile dysfunction in men and is FDA approved for sexual dysfunction in women. While effective, it has a significant side-effect of nausea and vomiting and can also stimulate skin melanocytes, although less than Melanotan I & II.
It has recently been found that the C-terminal tripeptide of MSH, KPV, is much more anti-inflammatory (many fold as potent) as the parent compound MSH; is orally bioavailable, which MSH is not; it promotes healing of the gut and numerous other organ systems; is organoprotective; preventing cellular stressinduced toxicity; is very effective for excess activation of mast cells, as in mast cell activation syndrome (MCAS) and activated microglia in the brain (neuroinflammation); there is no stimulation of skin melanocytes; it is very nontoxic; and has a broad spectrum of antimicrobial and antibiofilm properties, having both direct antimicrobial effects against fungi, mold, bacteria, viruses, and parasites, as well as indirect effects mediated through the immune system, even at very low (picomolar), concentrations. (LDN longevity, 56, 57, 119, 120)
“The C-terminal region (KPV) of ��-MSH demands special attention for several reasons. It exhibits in vitro and in vivo anti-inflammatory activity similar to that of parent peptide without Melanotropic effect. Moreover, this essential antiinflammatory sequence, that is, C-terminal tripeptide (KPV) of ��-MSH, is also essential for its direct antimicrobial efficacy. Therefore, this short molecule KPV appears to have tremendous potential to be developed as therapeutic agent as it is more suitable for clinical use…” ¹²⁰
1. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. Journal of applied physiology. 2010 Oct 28;110(3):774-80.
2. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Stancic Rokotov D, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S. Stable gastric pentadecapeptide
BPC 157: novel therapy in gastrointestinal tract. Current pharmaceutical design. 2011 Jun 1;17(16):1612-32.
3. Boban-Blagaic A, Blagaic V, Romic Z, Jelovac N, Dodig G, Rucman R, Petek M, Turkovic B, Seiwerth S, Sikiric P. The influence of gastric pentadecapeptide BPC 157 on acute and chronic ethanol administration in mice. The effect of N (G)-nitro-L-arginine methyl ester and L-arginine. Medical science monitor. 2005 Dec 22;12(1):BR36-45.
4. Huang T, Zhang K, Sun L, Xue X, Zhang C, Shu Z, Mu N, Gu J, Zhang W, Wang Y, Zhang Y. Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug design, development, and therapy. 2015;9:2485.
5. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Jagic V, Turkovic B, Rotkvic I, Mise S, Zoricic I, Konjevoda P. Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats. Journal of Physiology-Paris. 1997 May 1;91(3-5):113-22.
6. Sikiric P, Seiwerth S, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S, Kolenc D. Revised Robert’s cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator. Current pharmaceutical design. 2010 Apr 1;16(10):1224-34.
7. Vuksic T, Zoricic I, Brcic L, Sever M, Klicek R, Radic B, Cesarec V, Berkopic L, Keller N, Blagaic AB, Kokic N. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia) heals ileoileal anastomosis in the rat. Surgery today. 2007 Sep 1;37(9):768-77.
8. Skorjanec S, Dolovski Z, Kocman I, Brcic L, Boban AB, Batelja L, Coric M, Sever M, Klicek R, Berkopic L, Radic B. Therapy for unhealed gastrocutaneous fistulas in rats as a model for analogous healing of persistent skin wounds and persistent gastric ulcers: stable gastric pentadecapeptide BPC 157, atropine, ranitidine, and omeprazole. Digestive diseases and sciences. 2009 Jan 1;54(1):46.
9. Sikiric P, Marovic A, Matoz W, Anic T, Buljat G, Mikus D, Stancic-Rokotov D, Šeparovic J, Seiwerth S, Grabarevic Z, Rucman R. A behavioural study of the effect of pentadecapeptide BPC 157 in Parkinson’s disease models in mice and gastric lesions induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Journal of Physiology-Paris. 1999 Dec 1;93(6):505-12.
10. Kliček R, Kolenc D, Šuran J, Drmić D, Brčić L, Aralica G, Sever M, Holjevac J, Radić B, Turudić T, Kokot A. Stable gastric pentadecapeptide BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries and motor disability. Journal of physiology and pharmacology. 2013;64(5):597-612.
11. Krivic A, Anic T, Seiwerth S, Huljev D, Sikiric P. Achilles Detachment in Rat and Stable Gastric pentadecapeptide BPC 157: Promoted Tendon-to-Bone Healing and Opposed Corticosteroid Aggravation. Journal of orthopedic research. 2006 May 1;24(5):982-9.
12. Jelovac N, Sikirić P, Ručman R, Petek M, Perović D, Konjevoda P, Marović A, Seiwerth S, Sumajstorčić J, Dodig G, Perić J. A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine. Biological psychiatry. 1998 Apr 1;43(7):511-9.
13. Jelovac N, Sikirić P, Ručman R, Petek M, Perović D, Konjevoda P, Marović A, Seiwerth S, Sumajstorčić J, Dodig G, Perić J. A novel pentadecapeptide, BPC 157, blocks the stereotypy produced acutely by amphetamine and the development of haloperidol-induced supersensitivity to amphetamine. Biological psychiatry. 1998 Apr 1;43(7):511-9.
14. Staresinic M, Petrovic I, Novinscak T, Jukic I, Pevec D, Suknaic S, Kokic N, Batelja L, Brcic L, Boban-Blagaic A, Zoric Z. Effective therapy of transected quadriceps muscle in rat: gastric pentadecapeptide BPC 157. Journal of orthopedic research. 2006 May 1;24(5):1109-17.
15. Staresinic M, Sebecic B, Patrlj L, Jadrijevic S, Suknaic S, Perovic D, Aralica G, Zarkovic N, Borovic S, Srdjak M, Hajdarevic K. Gastric pentadecapeptide BPC 157 accelerates healing of transected rat Achilles tendon and in vitro stimulates tendoncytes growth. Journal of orthopedic research. 2003 Jan 1;21(6):976-83.
16. Kralj T, Kokot A, Kasnik K, Drmic D, Zlatar M, Seiwerth S, Sikiric P. Effects of pentadecapeptide BPC 157 on Experimental Rat Model of Dry Eye. The FASEB Journal. 2017 Apr 1;31(1 Supplement):993-3.
17. Lazić R, Gabrić N, Dekaris I, Bosnar D, Boban-Blagaić A, Sikirić P. Gastric pentadecapeptide BPC 157 promotes corneal epithelial defects healing in rats. Collegium antropologicum. 2005 Jun 15;29(1):321-5.
18. Chang CH, Tsai WC, Lin MS, Hsu YH, Pang JH. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration. Journal of applied physiology. 2010 Oct 28;110(3):774-80.
19. Šebečić B, Nikolić V, Sikirić P, Seiwerth S, Šoša T, Patrlj L, Grabarević Ž, Ručman R, Petek M, Konjevoda P, Jadrijević S. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. Bone. 1999 Mar 1;24(3):195-202.
20. Sikiric P, Seiwerth S, Brcic L, Blagaic AB, Zoricic I, Sever M, Klicek R, Radic B, Keller N, Sipos K, Jakir A. Stable gastric pentadecapeptide BPC 157 in trials for inflammatory bowel disease (PL-10, PLD-116, PL 14736, Pliva, Croatia). Full and distended stomach, and vascular response. Inflammopharmacology. 2006 Dec 1;14(5-6):214-21.
21. Sikiric P, Jelovac N, Jelovac-Gjeldum A, Dodig G, Staresinic M, Anic T, Zoricic I, Rak D, Perovic D, Aralica G, Buljat G. Pentadecapeptide BPC 157 attenuates chronic amphetamine-induced behavior disturbances. Acta pharmacologica Sinica. 2002 May;23(5):412-22.
22. Masnec S, Kokot A, Zlatar M, Kalauz M, Kunjko K, Radic B, Klicek R, Drmic D, Lazic R, Brcic L, Radic R. Perforating corneal injury in rat and pentadecapeptide BPC 157. Experimental eye research. 2015 Jul 1;136:9-15.
23. Gabric N, Lazic R, Dekaris I, Bosnar D, Cima I, Boban-Blagaic A, Sikiric P. Pentadecapeptide BPC 157 and its role in corneal epithelial injuries healing in rats. Investigative Ophthalmology & Visual Science. 2003 May 1;44(13):3821-
24. Cerovecki T, Bojanic I, Brcic L, Radic B, Vukoja I, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 (PL 14736) improves ligament healing in the rat. Journal of orthopaedic research. 2010 Sep 1;28(9):1155-61.
25. Jelovac N, Sikiric P, Rucman R, Petek M, Marovic A, Perovic D, Seiwerth S, Mise S, Turkovic B, Dodig G, Miklic P. Pentadecapeptide BPC 157 attenuates disturbances induced by neuroleptics: the effect on catalepsy and gastric ulcers in mice and rats. European journal of pharmacology. 1999 Aug 20;379(1):19-31.
26. Šebečić B, Nikolić V, Sikirić P, Seiwerth S, Šoša T, Patrlj L, Grabarević Ž, Ručman R, Petek M, Konjevoda P, Jadrijević S. Osteogenic effect of a gastric pentadecapeptide, BPC-157, on the healing of segmental bone defect in rabbits: a comparison with bone marrow and autologous cortical bone implantation. Bone. 1999 Mar 1;24(3):195-202.
27. Balenovic D, Bencic ML, Udovicic M, Simonji K, Hanzevacki JS, Barisic I, Kranjcevic S, Prkacin I, Coric V, Brcic L, Coric M. Inhibition of methyldigoxin-induced arrhythmias by pentadecapeptide BPC 157: a relation with NO-system. Regulatory peptides. 2009 Aug 7;156(1-3):83-9.
28. Sikiric P, Seiwerth S, Rucman R, Turkovic B, Stancic Rokotov D, Brcic L, Sever M, Klicek R, Radic B, Drmic D, Ilic S. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Current pharmaceutical design. 2013 Jan 1;19(1):76-83.
29. Hsieh MJ, Liu HT, Wang CN, Huang HY, Lin Y, Ko YS, Wang JS, Chang VH, Pang JH. Therapeutic potential of proangiogenic BPC157 is associated with VEGFR2 activation and up-regulation. Journal of Molecular Medicine. 2017 Mar 1;95(3):323-33.
30. Keremi B, Lohinai Z, Komora P, Duhaj S, Borsi K, Jobbagy-Ovari G, Kallo K, Szekely AD, Fazekas A, Dobo-Nagy C, Sikirić P. Antiinflammatory effect of BPC 157 on experimental periodontitis in rats. Journal of physiology and pharmacology. 2009 Jan 1;60(7):115-22.
31. Sikric P, Suran J, Drmic D, et al. Stable anti-ulcer gastric pentadecapeptide BPC 157 also for multiple sclerosis: Counteraction of cuprizone brain injuries and motor disability. FASEB 2013;27(1)
32. Tudor M, Jandric I, Marovic A, et al. Traumatic brain injury in mice and pentadecapeptide BPC-158 effect. Regul Pept 2010;160(13):1-3.
33. Blagaic AB, Blagaic V, Romic Z, et al. The influence of gastric pentadecapeptide BPC-157 on acute and chronic ethanol administration in mice. Eur J Pharmacol 2004;499(3):285-90.
34. Sikiric P, Separovic J, Anic T, Buljat G, Mikus D, Seiwerth S, et al. The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation. J Physiol Paris 1999; 93: 479-85.
35. Sikiric P, Seiwerth S, Grabarevic Z, Rucman R, Petek M, Jagic V, et al. Pentadecapeptide BPC 157 positively affects both nonsteroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats. J Physiol Paris 1997; 91: 113-22.
36. Sikiric P, Seiwerth S, Rucman R, et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Curr Pharm Design 2013;19(1):76-83.
37. Chang, CH, Tsai, WC, Hsu, YH, et al. Petadecapeptide BPC-157 enhances the growth hormone receptor expression in tendon fibroblasts. Molecules 2014;19:19066-19077.
38. Tohyama Y, Sikiric P, Diksic M. Effects of pentadecapeptide BPC-157 on regional serotonin synthesis in the rat brain: alpha-methylL-Tryptophan autoradiographic measurements. Life Sci 2004;76(3): 345-57.
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