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Peptides: Unlock the Secret to Longevity

Peptides: Unlock the Secret to Longevity

Kent Holtorf, MD

Peptides saved my life, and I have seen them do the same for so many of my patients. I have always been drawn to complex patients that have not seen improvement as expected with standard therapies, excited to look for that missing piece that could change a patient’s life. This feeling may indeed have stemmed from the fact that I was that patient. In medical school, I suffered from terrible fatigue, barely able to function. I was told by numerous specialists that I was depressed or stressed like every other medical student, or that I needed to get more sleep and exercise more. Standard tests revealed nothing abnormal, and yet, nothing seemed to help me.

After spending a year investigating potentially beneficial therapeutics for my condition, I implemented multi-system therapies that resolved my most severe symptoms and was able to get part of my life back. Seeing these positive results first-hand, I knew there were many others suffering the same way I had. As a result, I left my residency and opened a center treating patients with similar issues, the ones who had seen countless physicians only to be told that nothing was wrong with them, yet they felt horrible. I opened 22 centers around the country and set up a franchise program with an extensive physician training program.

Unfortunately during this time I went through a stressful divorce which resulted in a flare of my symptoms, leaving me mostly bedbound for months with severe fatigue, anxiety, panic attacks, severe sleep disorder, profuse sweating, neuropathy, inability to handle stress, and more. I then went into heart failure and intermittent a-fib. I could not stand upright or walk upstairs, and I developed an autoimmune kidney disease and antiphospholipid syndrome.

After extensive testing, it was discovered that I had Lyme disease, Babesia, and Bartonella, along with a number of reactivated viruses and mold toxicity. Initially, tried massive doses of antibiotics, including four to seven intravenous antibiotics simultaneously at the maximal doses. And yet, no improvement. My immune system was barely functioning (natural killer cell function ran between 0 and 3 LU (normal is > 30 LU).

I then decided to travel around the world, albeit feeling horrible as part of my quest to find a therapy that could help me. I felt I had no choice, as I knew the infections were killing me. While many treatments were somewhat helpful, I still struggled to get out of bed each day and remained in heart failure. While in Europe, a life-changing event happened. I discovered peptides, which I did not know at the time, would save my life. After trying peptides for a few weeks, I felt different, and by the six-month mark, I was a different person.

To the astonishment of my cardiologist, I walked into his office and was shown to have a normal cardiac function test less than a year later after he said that I could maybe improve 10% in 10 years. I also found several therapies that were very synergistic with the peptides, including additional peptides, T3, ozone, and ultimately SOT.

**What are Peptides?

If you have investigated improving your health, you have 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 in a chain. Essentially, they are short chains of amino acids linked together. If the chain is longer than 50 amino acids (AAs), it is called a protein. If it has less than 50 AAs, it is called a peptide. You may also hear the term oligopeptide, which is a term occasionally used for short peptides with less than 20 AAs. The simplest peptides are dipeptides (two AAs), followed by tripeptides (three AAs), tetrapeptides (four AAs), and so on, and so forth. Meanwhile, a polypeptide is a long, continuous unbranched peptide chain.

Peptides regulate most known processes and systems in the body in a tissue and cell-specific manner. Compared to medications and hormones, they tend to be more selective and less likely to be associated with serious adverse side-effects. Many 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.

Peptides generally have high potency, being very active on their target receptor. They are often naturally occurring and naturally degraded in the body, further adding to their safety profile. They typically have a vast therapeutic window, meaning that there can be a considerable variation in the doses utilized, depending on the desired effect. Many popular peptides have no known toxic level, meaning researchers could not elicit any toxicity effects no matter how high the dosage.

Peptides’ ability to control and modulate most systems in the body also includes hormone production, immune function, the sleep cycle, 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, urinary and reproductive systems, aging and longevity, and many more.

General Class of Peptides

Below is a selected list and classification of the most 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 can be best utilized.

Immune aging or immunosenescence is a known component of aging, contributing to the progressive inability to defend against infectious diseases, cancer development, autoimmunity, inflammation, cardiovascular, and neurodegenerative diseases. A significant cause of immunosenescence is the progressive involution of the thymus from about age ten until it functions at less than 10% in your 40s. The immune system is usually balanced between the division that fights intracellular infections, called Th1, along with the division that enables self-tolerance, called Treg, with the division that fights extracellular infections and induces inflammation, called Th2 and Th17 (see figure 2).

This is called a Th1/Treg to Th2/Th17 shift, which is primarily caused by the lack of thymus function and thymic peptides, but it is exacerbated by any chronic illness, aging, stress, obesity, depression, anxiety, chronic infections, and toxins. It has been found to severely shift in autoimmune disease, chronic fatigue syndrome (CFS), neurodegenerative diseases, diabetes, obesity, cardiovascular disease, gastrointestinal (GI) dysfunction (due to the gut-brain-immune axis), hypothyroidism, mast cell dysfunction, and neurodegenerative diseases.

This establishes a vicious cycle of cause and effect with chronic illness—the abnormal immune balance promotes diseases and aging, and the diseases of aging promote the abnormal immune balance, causing progressive illness and deterioration rather than reverting to a repair and rejuvenation mode. According to the US Center for Disease Control (CDC), approximately 80% of aged individuals are afflicted with at least one chronic disease as a result of a declination of thymic related immune function.73 73. Gui J, Mustachio LM, Su DM, et al. Thymus Size and Age-related Thymic Involution: Early Programming, Sexual Dimorphism, Progenitors and Stroma. Aging Dis 2012;3(3):280-90

Knowing this, one would not think it would be a big leap to assume, “why not give back the missing thymic peptides that occur with age and cause or contribute to almost all of the diseases of aging?” That is precisely what doctors are doing that practice integrative, functional, or precision medicine. Such supplementation can reverse this immunosenescence, which has been assumed to be an inevitable part of aging with resultant disease and degeneration.

There are several thymic peptides that modulate immunity to establish a healthy Th1/Treg immune system, however, it is important to note that they do have differing effects. Thymosin Alpha-1 (TA1) is approved in over 30 countries for various infections and cancer therapy. It is FDA approved as an orphan drug in the US, making it unavailable at standard pharmacies, making it available at compounding pharmacies or in some cases, available as a supplement with strict manufacturing and regulatory requirements. A broad overview of thymic peptides is to think of TA1 as increasing Th1/Treg, Thymosin Beta 4 (TB4) as increasing Th1/Treg and reducing Th2/Th17 along with providing additional rejuvenating properties, while BPC-157 (not a thymic peptide) reduces Th2/Th17 with additional healing, rejuvenating and anti-aging effects, acting directly on tissues and also through the gut-brain-immune axis. Thymulin is similar to TB4 but has more anti-inflammatory effects than full-length TB4.

TB4 Active Fragment (Ac-SDKP) is a small part of the TB4 peptide that provides the majority of healing and immune-modulatory effects and removes a part (domain) of TB4 that can have a negative impact of stimulating mast cells, which cause inflammation. The full-length TB4 is 43 amino acids long, so it cannot absorb orally, while TB4 Active Fragment (Ac-SKDP) is only four amino acids in length and orally bioavailable, being absorbed intact. It is also approximately ten times as potent per weight as the full-length TB4 and available as a supplement.

Thymic Peptide Effects: • Improved tissue repair and healing35,36,37,41 • Improved host defense to infection26,27,28,29,30 • Reverse immunosuppression of chronic infection (Lyme)24,26,27,28,29,33,34,37, • Increases antioxidant and glutathione production26,27,28,31,28,29,63,66 • 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 • 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 blood-brain barrier. • Is antimicrobial against bacteria, viruses, parasites and fungi • Breaks down biofilms  References-AARM 2020 45 min x 2 (119)

The bioidentical thymic peptide, thymalin, was injected into mice staring at the age of 3.5 months prolonged mean life span by 28%, decreased rate of cancer 2.8-fold (10. Morozov, V.G. and V.K. Khavinson, Natural and synthetic thymic peptides as therapeutics for immune dysfunction. International. Journal of Immunopharmacology, 1997. 19(9-10): p. 501-505.)

Body Protection Compound (BPC-157)

BPC-157 is a naturally occurring peptide in human gastric fluid. It has enhanced stability compared to other peptides, being resistant to enzymatic hydrolysis (breakdown) and is orally bioavailable, which is surprising due to its size (15 amino acids in length). BPC-157 has a wide range of healing, rejuvenating, and antiaging effects. Effects include the up-regulation of growth factors and genes involved with healing, proangiogenic effects (stimulates capillary formation to deliver more oxygen and nutrients to tissues), modulation of nitric oxide (NO) synthesis, modulation of the serotonergic and dopaminergic systems, as well as exerting significant beneficial effects on leaky gut, the gut-brain axis, and the microbiome. It has similar effects as TB4 and TB4 Active Fragment, but it has a different mechanism. This makes them very synergistic for a powerful antiaging combination.

Oral BPC-157 is considered a gut-healing peptide by most physicians, and demonstrates protective and healing effects for a wide range of both gastrointestinal and systemic tissues and organs. Oral BPC-157 or injectable is equally effective for systemic disorders.

BPC-157 reduces inflammation and promotes healing in most tissue and systems in the body, including the gut, the brain (mood, cognitive function, traumatic brain injury), skin, muscle, degenerative joints, the heart (prevents and treats arrhythmia, heart failure, and Lyme myocarditis), peripheral nerves (neuropathic pain), the bladder (incontinence), the immune system (inflammatory conditions, mast cell activation, and autoimmunity) and is protective against neuro, myco (mold) and endotoxins, improves insulin resistance, and is antimicrobial, outperforming the antiviral acyclovir for the herpes class of viruses at 1/1000th the dose.

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 role in determining the microbiome by influencing GI function and environment (intestinal mobility, mucous secretion, secretory functions, blood flow, etc.). Additionally, leaky gut means 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 inflammation, there is brain inflammation due to this gut-brain connection. Numerous studies show that BPC-157 reduces gut inflammation and promotes gut healing , brain, and other tissues in the body. TB4 active Frag promotes healing of the GI mucosal and BBB tight junctions, as well as promoting healing of tissues throughout the body. Making them a powerful combo for “leaky gut”.

BPC-157 Effects • Protects and 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 several 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 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

Pineal Peptides (Epitalon and Pinealon)

Epithalon is a four AA peptide isolated from Pineal gland 22. Epitalon is shown to restore impaired, aged and damaged neurologic, immune and cardiovascular system, neuroendocrine and immune regulation and prevent multiple age-related diseases, such as hypertension, memory loss, cancer, osteoarthritis and overall mortality and morbidity in humans and animals23,24,25,55,56,57,58. Additionally, it increases mean and maximal life span in humans and animals,57,58, and to inhibit spontaneous and induced carcinogenesis24,25,58

Epitalon stimulates the synthesis of serotonin and melatonin as well as telomerase activity. Human cells grown in tissue cultures are only able to divide approximately 34 times, after which they age and die. This limit to cellular replication, secondary to the shortening of the cells’ telomere length with each replication, is known as the Hayflick Limit. Increased telomerase stimulated by epitalon lengthens the telomeres, allowing cells to continue to divide and function, decreasing cellular biologic aging.

Epithalon slows down aging of the reproductive system and has been shown to be able to restore the menstrual cycle and fertility in older female mice 58. It increases thyroid hormone secretion and increases T4 to T3 conversion 58, and improves glucose tolerance (reduces insulin resistance and insulin and triglyceride levels), but it can also improve insulin production in old primates with insulin deficiency compared to young primates.

Epitalon is shown to reverse the reduced gene expression and protein synthesis in target tissues 66 as well as reversing age and illness associated mitochondrial energy production. 70. Epitalon restores melatonin production in elderly patients to the levels in young healthy patients.68


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  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.
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  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.
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  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.
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  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.
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