Peptide Therapies

New technology for Optimal Heath Peptide Therapies

Peptide therapies are only used within the context of the doctor/patient relationship and is based upon the comprehensive needs of each patient. Dr. Harlan Bieley’s practice at Healthy Living & Longevity Medical Center incorporates peer review medical literature about peptide therapies. Results from treatment with peptides discussed below are not representative for all patients. Be curious and explore the transformative power of peptide therapies in the paragraphs below.

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Frequently Asked Questions

If interested, please schedule a visit with Dr. Harlan Bieley to explore peptide therapy solutions.

What are peptides? 

Peptides are molecules that consist of between two to fifty amino acid sequence. The word peptide, is derived from the Greek word meaning , "to digest". The first commercial peptide therapy used was insulin (1923) but now is used for hormone optimization, weight loss, sexual enhancement and function, as well as overall healing and repair.

What are peptide therapies? 

Fundamentally, peptide therapies give cells the ability to change cell behavior and to handle stress better. Peptide therapies are natural modulators of cell signaling. The cell changes behavior and can adjust to stress, aging, etc… and can manipulate the genome with signals going from the mitochondria (where energy is made by the cell) to the nucleus through MOTS-C.  There are 7,000 natural peptides in the body. There are countless clinical trials and FDA-approved peptides in clinical use . This once burgeoning field of medicine is now fully embraced as an additional mainstay treatment for acute and chronic illness.  Peptides help reclaim the efficiency of receptor sites so they work better (and you won’t need as much hormone to get the effects you seek).

Peptide therapies have a variety of applications such as immune enhancement; accelerates injury repair to muscles, reverses sarcopenia (loss of muscle), tendons, bones, nerves; progressive fat loss and improved bone mineral density, increase in Testosterone by increasing pulse size and frequency, decrease inflammation in the brain and the rest of the body, natural release of growth hormone, improves sleep. Peptide therapy plus Bio-Identical hormones = Synergy. It’s easiest to think about peptides in these easy to remember ways. Here is how: 

1. Hormone optimization

2. Weight loss

3. Sexual Functioning

4. Healing and Repair.

This means you cannot neglect other aspects of your health including:

• No smoking or forget doing peptides.

• Adequate sleep and rest.

• Only PROTEIN within 30 minutes of taking injections.  No fat, or carbs.

• Do periodic fasts.

• Exercise and stretching regularly for best peptide therapy results. (Read more below)

Where do I begin?

You can get started and just use a growth hormone releasing peptide (GHRP), eg, Ipamorelin by itself without spending a lot of money to see if your sleep improves and bone density improves. Use a GHRP together with bio-identical hormones and get great results. 

How can I get the most out of peptide therapies?

As mentioned, exercise will help get the best results.

1 hour before: Take supplements like Phosphatidic acid to increase mTOR signaling.

During: Supplement orange juice with L-glutamine,  D-Ribose.

1 hour after: Take a supplement with the amino acid Leucine .

Other well-known key amino acids:

Creatine: drives tissue anabolism. Great for older people who lack muscle mass.

Arginine: helps make growth hormone (take with Vitamin C) by suppressing somatostatin secretion. Do not take with exercise. You will not make additional growth hormone.

Glutamine: supports GI mucosal integrity, cellular repair, and healing. Supports growth hormone levels.

Sources of information: A4M lectures and International Peptide Society lectures.

What is the purpose of Peptide Optimization? 

The cell has less oxygen consumption, with more ATP produced (cellular energy), and low ROS (reactive oxygen species) generated. Simply put, this gives you more energy. Here are the potential benefits:

1. Hormone Optimization and Growth Hormone Secretagogues: CJC-1295 without DAC, Ipamorelin, Tesamorelin, GHRP-2, GHRP-6

2. Weight Loss options: Semaglutide, GH-191, GHRP, GHRH/GHRP, AOD-9064, Melanotan II, Frag 176-191 (an AOD knockoff, not effective), Thymosin Alpha-1, Cerebrolysin, DSIP, PEPCK, GLP 1R agonist. 

3. Sexual Enhancement and Function: Melanotan II and PT-141.

4. Healing and Repair: GHK-Cu, BPC-157, Thymosin Beta-4, AOD +HA, LL-37, GHRH, MGF and PEG-MGF.

How do peptide therapy treatments affect my hormones?

Peptides, as signaling substances, help reclaim efficiency of hormone receptor sites. In other words, if you take some thyroid medicine, eg, T3 (active thyroid hormone), and you don’t see improvement in the labs, it may be that the receptor site is not working properly. Peptides and certain other nutrients can help improve the functionality of the receptor so that the hormones we give work as intended. Importantly, peptide therapy works best in the background of great nutrition, cortisol balance, and the removal of environmental toxins.

The melanocortin system incudes Melanotan II and Bremelanotide (PT-141). Melanotan II increases melanogenesis for photoprotection and increased tanning, plays a role in improving autoimmune disease, eg, Lyme disease. Plays a role in sexual dysfunction and can improve libido (increases sexual arousal) and erectile dysfunction in men (and sexual desire in females) through the CNS, and not through the Cardiovascular System which is the way medicines like Cialis, and Viagra work. Has significant anti-inflammatory disease. Works through the vagal /cholinergic response and affect the immune system.   Can affect appetite and cause weight loss. Works well with intermittent fasting. Activation of the vagus nerve leads to cholinergic signaling and inhibits tumor necrosis factor (TNF) and other pro-inflammatory cytokines overproduction (Cholinergic anti-inflammatory pathway). This pathway is activated by Melanocortin 3R and 4R receptors. This pathway is critical and is significant in anti-inflammation in the brain. This plays a role in neuroprotection and is also cardioprotective, too. The melanocortin system peptides can be used with Thymosin alpha-1 to balance Th1 and Th2 issues. This can also be used with DSIP with Glycine where you can upregulate glutathione peroxidase and superoxide dismutase. This gives us new approaches to autoimmune diseases. Immune cells have melanocortin receptors 1,3,5. Melanocortin receptor 3,4 is in the brain. Melanocortin receptor 4 plays a role in appetite control. The adrenal cortex is melanocortin 2. Alpha melanin-stimulating hormone reacts with all 5 receptors. Melanotan receptor 1 is on the endothelial cell. Melanotan 1 does not cross the blood-brain barrier. Melanotan 2 crosses the blood-brain barrier. Melanotan 1 will not give you sexual desire effects but will give you tanning and is responsible for melanogenesis. Melanotan 2 gives you both tanning (sunless tanning) and sexual desire. In women, they can increase pigmentation and more freckles than with men.   Nota bene: The face and hands may get darker than the rest of the body. The use of Melanotan 1 is an art, follow the skin pigmentation to determine dosing adjustments. It has the cosmetic effect of tightening the collagen in the face. Melanotan 1 and Melanotan 2 are effective for autoimmune conditions like Hashimoto’s thyroiditis (may also use Thymosin alpha-1). Psoriasis may also be treated by Melanotan 2, but when treatment is stopped, the disease will come back. Melanotan 2 works through the vagus nerve through the cholinergic anti-inflammatory pathway. Can be useful for Seasonal Allergy because of the anticholinergic effects. Can be used on a daily, or regular basis vs. PT-141 (bremelanotide) which should only be used twice weekly to prevent desensitization. Melanotan 2 is neuroprotective, as well as plays a role in decreasing opioid addiction and ethanol consumption. Melanotan 2 improves libido and erectile dysfunction in men. Melanotan 2 plays a role in appetite and metabolism.

***Caveat emptor (Buyer beware)! Swiss Analytic Labs claims to have tested most if not all peptides advertised on the internet. They say that approximately 80% of these peptides are either adulterated or fake. Be particularly skeptical of marketing for very inexpensive peptide therapies. It simply is impossible for reputable companies to manufacture these products and make money at very low prices. ***

What are the most common peptide therapies you offer?

AOD 9064 stands for Anti-Obesity Drug and is a peptide fragment found within Growth Hormone (the last 15 amino acids),  that is responsible for the substantial weight loss effects that are seen when using Growth Hormone. Growth Hormone causes weight loss of both visceral (deep) fat and retroperitoneal fat, whereas Testosterone and exercise are responsible for the superficial fat loss. Affects lipid metabolism (women greater than men). Best for weight loss of 20-30 pounds.  Promotes chondrocyte production of collagen and proteoglycan. Enhances hyaluronic acid.  The success rate for weight loss improved with work-outs or fasting. It also helps prevent fat build up and increases the NAD+/ NADH ratio, great for the cells and for stem cell renewal. It is best used for weight loss in combination with a Growth Hormone Releasing Hormone (GHRH), and a Growth Hormone Releasing Peptide (GHRP). AOD with HA (hyaluronic acid) useful for cartilage regeneration in knee, hip, shoulder, ankle, and tendinopathies. AOD with HA- also good for trigger point injections.

Examples of GHRH’s include Sermorelin, GRF 1-29, modified GRF 1-29 (CJC-1295 without DAC) (makes the pituitary follow the natural pulsatile release to increase Growth Hormone, promotes muscle growth and fat burning and may help with sleep), CJC-1295 with DAC (the DAC-drug affinity complex- increases the half-life of the product by several days and elevates Growth Hormone and IgF1 levels after a single administration), Tesamorelin. Examples of GHRP’s include GHRP-2 (reduces atrophy in muscle, potent stimulator of Growth Hormone secretion, with minimal stimulation of Prolactin and Cortisol, increases growth velocity in children, and improves appetite with weight gain in patients with anorexia ), GHRP-6 (actively increases ghrelin in the stomach, restores Growth Hormone secretion in obesity, and improves phase 2 sleep), Ipamorelin (plays a role in nitrogen retention, the mildest of the group and with large doses does not produce prolactin or cortisol elevations, but does give a large release of Growth Hormone without desensitization side effects ), and Hexarelin (has cardioprotective effects, and the strongest of the group, and gives the biggest pulse of Growth Hormone, but there may be an elevation of prolactin and cortisol transiently, and desensitization can occur regardless of dose so use sparingly).  MK-0677 is fraught with side effects such as involution of receptor sites in the brain and irreversible neurologic damage. It also elevates cortisol and increases depression and anxiety.

The GHRH’s regulate Growth Hormone production and release, the neurochemical regulation of sleep, and much more. The GHRP’s antagonize the release of Somatostatin, and enhances the release of GHRH and increases Growth Hormone release. The GHRP’s also have stress protective benefits, anti-anxiety & anti-depression effects and can stimulate to the production of Nitric Oxide (NO) from endothelial cells. Also has muscle repair function and anti-inflammatory effects.

BPC-157 (Body Protection Compound-157)  by itself does nothing which makes it very safe to use at recommended doses. It helps the body to achieve homeostasis.  It is a powerful cell signaling messenger that decreases inflammation and accelerate healing (muscle, brain, bone, tendon, nerve, ligament, cornea, intestines, as examples). It increases fat loss, improved immune function, wellbeing, and bone mineral density.  Some patients claim that their chronic pain has been substantially reduced. BPC-157 can help you heal faster from injury to bone, muscle, ligament, tendon, nerve, brain, teeth, intestine, cornea via cell signaling. This peptide responds specifically to injury. It also has an influence on neurotransmitters related to stress, anxiety, mood, and behavior via its effects on the serotonergic, dopaminergic, GABAergic and opioid systems. May help with depression.  It has effects on the GI tract via its anti-ulcer, cytoprotective effects. It improves GI mucosal integrity (anecdotal info for healing leaky gut 500mcg, orally, twice daily).  It improves nitric oxide (NO). Useful in weaning patients off Proton Pump Inhibitors (PPI’s) with zinc carnosine over a period of a month. Induces F-actin formation. Can be used after initial use of steroids for acute anti-inflammatory purposes thus prevents the long-term adverse effects of steroid use. Decreases neuroinflammation. Ameliorates alcohol and opioid withdrawal symptoms (may be combined with DSIP), and opposes alcohol intoxication. Helps with homeostasis of dopaminergic and serotoninergic systems.  Improves nerve (axonal and myelin sheath) regeneration. It rapidly and permanently counteracts QTc prolongation of the heart caused by neuroleptic medicines (Haldol, etc) and prokinetics. Intranasal use for Lyme and Mold brain fog.

Mechanism of Action • Orally stable pentadecapeptide in human gastric juice, with no toxicity being reported. • Active in multiple cell types- gut, heart, muscle, connective tissue, skin, brain,… • So effective because of the multiple pathways that are stimulated at the same time! • Some of the most relevant pathways stimulated: • Increase F-actin formation in fibroblasts • Increases phosphorylation of Paxillin and FAK proteins - cell migration, embryonic development, immune surveillance and wound healing • Enhanced extracellular matrix (collagen) formation • Enhances eNOS signaling pathway improving angiogenesis, endothelial migration (via VEGFR2) and NO generation • Enhances cellular growth hormone receptors in fibroblasts. Ref:Abid Husain, MD.

Filaretova LP, Takeuchi K (eds): Cell/Tissue Injury and Cytoprotection/Organoprotection in the Gastrointestinal Tract: Mechanisms, Prevention and Treatment. Front Gastrointest Res. Basel, Karger, 2012, vol 30, pp 191–201 Molecules 2014, 19, 19066-19077; doi:10.3390/molecules191119066.

BPC-157 Applications:

Oral health: peridontitis; reduced both plasma extravasation, histological alterations and alveolar bone resorption, but does not alter blood circulation in healthy gingiva ● Ulcers : Esophagus, stomach, duodenum, and intestinal ○ gastric ulcers that fail to heal ●

GERD: Increasing lower esophageal sphincter while decreasing pyloric sphincter pressure ● Eosinophilic Esophagitis ● Fistulas: Heals the intestinal anastomosis, gastro-cutaneous, duodenocutaneous and colocutaneous fistulas ○

NO, angiogenic and actin/collagen effects ●

IBD - counteracts complications of IBD and improves healing of the intestinal anastomosis. ○ It increases adaptive capability of the remaining intestine in all intestinal layers, ●

Pancreas and Liver: Counteract the effects of common bile duct ligation ( pancreatitis ), hepatomegaly, and fatty liver in rodent study Filaretova LP, Takeuchi K (eds): Cell/Tissue Injury and Cytoprotection/Organoprotection in the Gastrointestinal Tract: Mechanisms, Prevention and Treatment. Front Gastrointest Res. Basel, Karger, 2012, vol 30, pp 191–201 BPC-157 : GI Applications ● Intestinal protection via reduction of inflammatory mediators ○ Treats all phases - acute, subacute and chronic inflammation ○

Counteracts the effects of acute and chronic alcohol exposure by attenuating direct liver lesions, gastric lesion & portal hypertension ○

Counteract the effects of NSAID and Paracetamol toxicity ○ Nullified the harmful effect of systemic corticosteroid therapy ○ Maintains and restores gut barrier integrity. Ref: Abid Husain, MD.

Filaretova LP, Takeuchi K; Cell/Tissue Injury and Cytoprotection/Organoprotection in the Gastrointestinal Tract: Mechanisms, Prevention and Treatment. Front Gastrointest Res. Basel, Karger, 2012, vol 30, pp 191–201

Enhances eNO system: counteracts the ulcerogenic effect of NO-synthase which causes reduction / dysfunction • Acts as free radical scavenger • Modulatory effect in regulating bleeding and thrombosis • NO directly benefits GI health independent of improved vascular effects Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway. Ref: Abid Husain, MD.

Scientific Reports. 10. 17078. 10.1038/s41598-020-74022-y. Seiwerth S, Milavic M; Stable Gastric Pentadecapeptide BPC 157 and Wound Healing; frontiersin.org/article/10.3389/fphar.2021.627533

Musculoskeletal: muscle, tendon, ligament and bone, arthritis •

Neurologic: Neuro-protective, TBI, Nerve crush injuries •

Cardiovascular: myocardial tissue , membrane stabilization, digoxin toxicity • Immune system: modulating effect •

Generalized: anti-inflammatory . Abid Husain, MD.

Seiwerth S, Milavic M; Stable Gastric Pentadecapeptide BPC 157 and Wound Healing; frontiersin.org/article/10.3389/fphar.2021.627533 BPC-157 • Dosing: • Oral- 500mcg PO BID • SQ- 500mcg SQ • Topical Cream- apply BID to TID to affected area.

Cerebrolysin is ( NO LONGER AVAILABLE Feb 2022) a neuro-regenerative and neuroprotective peptide. It has neurotrophic repair properties similar to Nerve Growth Factor (NGF) and Brain-Derived Nerve Growth Factor (BDNF). It is a low molecular weight peptide that can cross the blood-brain barrier. Can be used for Traumatic Brain Injury (TBI) and Ocular Migraine Headaches, TIA’s, Stroke, Post Stroke Recovery, and Mood Dysregulation. It can be used to increase memory and learning and can improve synaptic function and synaptic density. Protects nerves from free radicals and oxidative stress damage and improves the metabolic activity of neurons, and protects neurons from neurotoxic effects of glutamate. Improves synaptic functioning.   Enhances cognitive function, memory, learning, creativity, and motivation. It can cross the blood-brain barrier and decreases beta-amyloid formation and deposition as well as Tau protein phosphorylation. It has a positive effect on behavior and neurotrophic stimulation. It can also be used for mood dysregulation, traumatic brain injury (TBI), concussion, stroke, trans-ischemic attacks (TIA), Alzheimer’s disease. In dementia, improves neuronal cytoarchitecture which results in improved cognitive and behavioral performance. Consider doing a trial in those with Apo E 4 (3/4, or 4/4) with cognitive impairment. This can help mitigate the continued cognitive impairment. Significant improvement was seen in those with mild to moderate dementia. 

Deep (or Delta) Sleep Inducing Peptide (DSIP) This peptide not only helps regulate sleep by way of improving the circadian function of sleep (mostly stage 4, slow wave sleep, when growth hormone is released) and decreasing wake ups throughout the night. It is not a sedative drug. It is also neuroprotective (prevents neuronal death) prevents excitotoxicity,  and increases glutathione peroxidase and Superoxide dismutase (SOD) in the brain which increases oxidative phosphorylation in the brain, and hence, improves mitochondrial function and LH release which can boost Testosterone levels by 100-200 points. There are no significant side effects from treatment. Oxidative stress in the brain causes an age-associated decrease in Testosterone. DSIP improves this process in the brain, where it can also help lower feelings of stress by lowering ACTH. DSIP has also been shown to decrease alcohol and opioid withdrawal and decreases chronic pain. It has a growth hormone releasing response in a physiologic way.

Epithalon literature is mostly from Ukraine and Russia. It regulates the cell cycle to upregulate polymerase activity. The peptide is from the pineal gland, improves the sensitivity of the hypothalamus, and normalizes the function of the anterior pituitary.  It is an anti-aging peptide for short-term use (up to 10 days a year or twice a year). 33% increase in telomere length by inducing telomerase activation and elongation and also prevents chromosome fusion. It is able to overcome the Hayflick limit of cell divisions (by 10 more divisions). Human studies for 12 years, showed decreased mortality by 28%, and a two-fold decrease in cardiovascular mortality. It also has tumor suppression activities. Epithalon combined with Thymalin over a 6 year period decreased the mortality rate 4.1 times that of the control group. In human elderly studies, Epithalon has been shown to increase SOD and Glutathione peroxidase (just like DSIP, and Kisspeptin), complete normalization of antioxidant indices, reduction of lipid peroxide oxidation products, improved melatonin and immunity (both cellular and humoral). Other studies in the elderly showed: increased glucose utilization, increased insulin sensitivity, increased HDL, lowered LDL, lower BP with decreased peripheral resistance, and improved tissue repair. In other human cancer trials: restored cellular immunity, and decreased recurrence and metastasis for 10 years. In breast cancer, patients showed partial or complete tumor regression, improved leukopenia and immune function, and prolonged patient lives.

GHK-Cu (GHK-copper) modulates copper into cells. Can accelerate change from inflammation to a healing phase via decreasing TNF alpha and beta, and decreasing IL-6.   It increases SOD (copper and zinc-dependent) and that leads to a decrease in Reactive Oxygen Species (ROS). Decreases ulcers and infections. Decreases fibrinogen and metastasis of cancer.  Increases myelin and cell regeneration and increase nerve density.  Plays a role in cosmesis and also has been shown to boost self-confidence.

IGF-1 (Insulin-like Growth Factor 1), aka, Somatomedin C.  It’s very similar to insulin. In the brain, it plays a role in neural development and myelination. It is anti-inflammatory. In the heart, it has vasodilatory effects. In muscle, plays a role in muscle development and helps rebuild muscle in a more efficient way. It mediates the effects of Human Growth Hormone. It improves muscle, bone and cartilage tissue. It helps improve connective tissue healing. It plays a role in adipocyte differentiation and regulation. It improves the anti-oxidant defense system. Utility: Conditions needing soft tissue enhancement- muscle, tendon, ligament repair from sports injuries. Looks for specific results over short periods of time. It doesn’t stop the amount of scar tissue made, however (use with TB-4, which decreases scarring). Useful for Diabetes I and Insulin Resistance. It improves insulin sensitivity. Useful for weight loss and metabolic syndrome. Improves bone density. Decreases neural-inflammation.  Low level is associated with CV events and increased mortality rate. It can play a role in those susceptible to cancer so use for short-term, specific uses. High levels are associated with cancer risks (breast -premenopausal-, prostate, colorectal). We are trying to use it in physiological levels only for best results.

Ipamorelin is a Growth Hormone Releasing Peptide (GHRP), anti-depressant, anti-anxiety, protective of stress, potentially neurologically protective.

Kisspeptin 10 was developed in Hershey, PA. (home of the Hershey kiss). This peptide increases Testosterone for men with primary hypogonadism and men who lose Testosterone from the aging process. This peptide works by increasing the pulse frequency and pulse size of LH. Testosterone levels may rise 100-250 points. Kisspeptin 10 has also been shown to be better than HCG for increasing testicular size. There is no feedback inhibition. There is physiologic Growth Hormone release, too.

Lazarotide-AT1001

8 amino acid peptide that antagonizes Zonulin pathway, derived from the zonula occludens toxin secreted by Vibrio cholera

● Zonulin as the only human protein discovered to date that is known to reversibly regulate intestinal permeability by modulating intercellular tight junctions ○ Under physiological circumstances there is tight control of mucosal antigen sampling that, in concert with specific immune cells, chemokines and cytokines lead to mucosal tolerance & immune competence. ○ The inappropriate increase of zonulin causes a loss of barrier function, with subsequent inappropriate and uncontrolled antigen trafficking instigates an innate immune response by the submucosal immune compartment. ○ If this process continues, an adaptive immune response is mounted causing production of pro inflammatory cytokines, including IFN-γ and TNF-α that cause further opening gap junctions to allow the passage of antigens and LPS, creating a vicious cycle. Abid Husain, MD.

Intestinal Permeability and its Regulation by Zonulin: Diagnostic and Therapeutic Implications, Alessio Fasano , M.D, Hepatol. 2012 Oct; 10(10): 1096–1100. Published online 2012 Aug 16. doi: 10.1016/j.cgh.2012.08.012 Clin Gastroenterol

Prevents zonulin mediated gut permeability ●

Restores small intestinal barrier and reduces migration of immune cells to colon, making it effective treatment option for colitis. ● ∼50% of T1D patients have increased serum zonulin levels, some of them showing these changes in the pre-diabetic phase of the disease. ○ May contribute to decreased barrier integrity, “sterile” leaky gut and gut dysbiosis in T1D ● In rat studies corrected the gut barrier defect and reduced the incidence of diabetes. Abid Husain, MD

Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384

• Serum zonulin has been shown to be increased in T2D patients and it has been suggested, through multivariate analysis, that the relationship between insulin sensitivity and serum zonulin may be modulated through IL-6. • serum zonulin was increased in obese children with non-alcoholic fatty liver disease (NAFLD) compared to obese children without NAFLD

• FDA approval for treatment in celiac disease Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384.

LL-37 is an antimicrobial peptide classified as a Cathelicidin and is involved with our innate immune system of defense against bacterial invasion, antiviral and antifungal activity on mucous membranes, increases epithelial stiffness and decreases permeability to bacterial invasion; can improve treatment of Cystic Fibrosis. Also, improve treatment for Respiratory Syncytial Virus (RSV) and Influenza A via damaging viral envelope and disruption of viral particles. Has antifibrotic effects and inhibits pro-inflammatory responses of NF kappa beta from LPS (via decrease TNF alpha, and IL-6). Interestingly, it decreases gut permeability via improved tight junctions (claudin, occludins). Can help protect against pathogen-mediated intestinal inflammation. Powerful anti-microbial and anti-inflammatory. Useful in Crohn’s and Ulcerative Colitis. In the Diabetic gut, it improves tight junctions and microflora. With C. difficile, it can decrease inflammation (IL-6).

The sole human cathelicidin - type of anti-microbial peptide • Stored in neutrophil granules as inactive precursors and are released as mature peptides when required • Primary role of LL-37 is to exterminate the pathogens from the mucus layers across the organism • Expressed in gastrointestinal tract ( mouth, tongue, esophagus, and colon ), urinary tract, lungs and skin

Meihua Zhang,a,b Weiwei Liang, ; Critical ReviewsTM in Immunology, 39(2):83–92 (2019) LL-37 :

Applications • Anti-bacterial properties • Maintaining colon microbiota balance and supports mucosal homeostasis • Anti-viral and anti-fungal properties • Cyto-protective for colon • Anti-inflammatory • Supports small intestinal & colon barrier integrity • Reduces systemic LPS exposure • Reduces colon scarring. Abid Husain, MD.

Normal intestinal microbiota inhabits the colon mucus layer without penetrating an inner layer to trigger undesirable inflammatory responses. The inner layer of the mucus is densely packed and firmly attached to the epithelium normally “free” of bacteria. The outer layer of the mucus is movable with an expanded volume and colonized by bacteria.

• Deficiency of LL37 complex is associated with thinner and discontinuous mucus layer with severe disruptions and therefore more easily colonized and penetrated by pathologic microbes. Abid Husain, MD

• Antimicrobial peptides are major players in maintaining microbiota balance in the gut. Meihua Zhang,a,b Weiwei Liang, ; Critical ReviewsTM in Immunology, 39(2):83–92 (2019)

• Strong anti-inflammatory effects such as neutralization of TLR4 activation by LPS

• Down-regulation of inflammatory cytokine responses, and preventing invasion and inflammatory responses to pathogenic bacteria

. • Inhibits the binding of LPS to CD14 on mononuclear phagocytes preventing the expression of tumor necrosis factor (TNF)-alpha

• Prevents the LPS-induced apoptosis of endothelial cells by suppressing the assembly of the LPS receptor complex

Meihua Zhang,a,b Weiwei Liang, ; Critical ReviewsTM in Immunology, 39(2):83–92 (2019) LL-37 :

Colon • Reduces incidence of chemically induced ulcerative colitis in rat models • Reduces incidence of colorectal and gastric adenoma by up-regulating apoptosis in colon ca cells. Abid Husain, MD.

• Reduces colon scarring from inflammation by down-regulating colonic fibroblasts Meihua Zhang,a,b Weiwei Liang, ; Critical ReviewsTM in Immunology, 39(2):83–92 (2019)

GLP-1 may aid intestinal absorption by increasing the mucosa area

• Multiple animal studies have reported increased intestinal weights following GLP-1 mimetic treatment in rodents

• GLP-1 mimetics have been shown to affect gut permeability in rats and induce barrier protective effects • Moderate the enteric immune response by reducing the production of pro-inflammatory cytokines, downregulate NF-κB phosphorylation and nuclear translocation,

• systemic anti-inflammatory effects on the liver, vascular system, heart, brain, kidney, lung, testis and skin.

GLP 1 and Intestinal Disease; Hunt E H, Holst J J; Biomedicines 2021, 9(4), 383; https://doi.org/10.3390/biomedicines9040383 1 GLP 1 R

• Ameliorates the course of chemically induced colitis, most likely by altering genes involved in immune regulation, epithelial protection and repair but can be limited with excess weight loss. • Currently, there is one published case report exploring GLP-1 treatment in a patient with ulcerative colitis. • In this case, administration of daily subcutaneous liraglutide injections (0.6 mg titrated to 3.0 mg) resulted in full remission of colitis symptoms with minimal adverse effects ( mild nausea associated with dose titration ). GLP 1 and Intestinal Disease; Hunt E H, Holst J J; Biomedicines 2021, 9(4), 383; https://doi.org/10.3390/biomedicines9040383 1 GLP 1 R Agonist • During mucositis, GLP-1 has been suggested to restore the intestinal absorptive capacity through the restoration of the mucosal layer. Abid Husain, MD.

• GLP-1 levels was increased following mucositis chemotherapy in humans • May have a protective role GLP 1 and Intestinal Disease; Hunt E H, Holst J J; Biomedicines 2021, 9(4), 383; https://doi.org/10.3390/biomedicines9040383 1

MGF (mechanical-growth factor) is a peptide in development. It is an isoform of IGF-1 called IGF-1Ec. It is produced locally.  It is activated in the heart and the brain by ischemia to activate mRNA coding for the isoform IGF1-Ec. This acts locally to increase anabolism, increase stem cell pool, stimulates satellite cells to make new cells, not grow them as skeletal muscle fibers are unable to divide. MGF expression is significantly increased following mechanical stimuli to muscle, bone, and tendon.  Resistance exercise and skeletal muscle stretch/overload, both contribute to increases in IGF-1Ec. In response to stretching and damage to muscle, MGF is vital for protein synthesis, mRNA transcription, and activation and proliferation of satellite cells. Satellite cells are signaled to replicate by MGF. Satellite cells are prevented from going forward until they fuse with muscle fibers and when they adopt a myogenic program. It’s rapid induction followed by fall of in a couple of days in response to stretching or damage to the muscle, or by ischemia in the brain or heart. This works as a proliferator of cells. This works in concert with Growth Hormone. MGF promotes endothelial cell growth. MGF has been shown to improve cardiac function post-MI (myocardial infarction commonly know as a heart attack). It prevents a decrease in left ventricular ejection fraction, reduces post-infarct expansion by inhibiting post-infarct apoptosis (cell death). Helps with the development and repair of neurons. It decreases oxidative stress in the brain as well as NMDA-expressed excitotoxicity. It is also expressed in osteoblasts in response to mechanical stress. MGF reverses sarcopenia. Applications are seen in conditions needing anabolic enhancement, soft tissue repair of ligaments, tendons, muscles from injury; muscle growth; cardiac ischemia problems, brain neuroprotection/ ischemia; age-related sarcopenia. MGF and all IGF’s decline with aging. PEG-MGF is pegylation of MGF and is a peptide in development. It is an attachment of polyethylene glycol to the peptide. The pegylation process acts as a protective coating and stabilizes the MGF molecule.  It protects the MGF molecule from enzymatic and receptor inhibition and increases PEG-MGF half-life to several days (48-72 hours). PEG-MGF is useful in muscle repair or hypertrophy (specific training). The PEG is inert and doesn’t bind to other substances in the body and has rapid urinary excretion. For effects upon muscle, use MGF 600 mcg injected SQ to muscles three times a week to increase proliferation of muscle. The day after the workout you may wish to use IGF1-LR3 (100 mcg/ three times a week) that works on the recovery state of muscle. Stay below 2mg total per week.  Don’t use for more than 10 days consecutively and be cautious with hypoglycemia.

Melanotan II is a melanocortin. It works through the brain/ CNS where it causes tanning and naturally makes a woman and a man sexually aroused. Improves libido and erectile dysfunction in men. Caution: may raise blood pressure and may lead to priapism (sustained erection for over an hour) with high doses, and may cause GI upset which may be prevented by coffee, or Xantac.

PT-141 (Bremelanotide) is a melanocortin receptor agonist. Has a high affinity for melanocortin 4 receptors. Improves sexual experiences for men and for women. Improves female sexual dysfunction and erectile dysfunction in males. It acts on the CNS and elicits a more desirous sexual response. GI effects are not as pronounced as with Melanotan 2, but it has been shown that if you do experience nausea, you can use Xantac 150mg, or drink a cup of coffee prophylactically to prevent nausea, or use a lower starting dose prevents nausea. They can also develop some freckles (reversible), even though they are not supposed to become tan with this product (more pronounced in women). Caution: may raise blood pressure, and cause tachycardia, and may cause GI upset.

PEPCK stands for phosphoenolpyruvate carboxykinase. It is an enzyme used in the Krebs Cycle that converts OAA to PEP.  It is involved in the production of gluconeogenesis in the liver and brown and white fat. It plays a role in fat loss, improved performance, and endurance.  If you are trying to improve preformance, you are going to have to improve and adjust lactate threshold and PEPCK helps do this. PEPCK provides a mechanism to control lactate. If you are going to improve the NAD+/NADH ratio of the cell, you are going to increase the efficiency of the cell. PEPCK, fasting, ketone esters, GHRH’s and GHRP’s also improves the NAD+/NADH ratio. This ratio is the ultimate efficiency to evaluate cell function. PEPCK increases glycogen in muscles, decreases muscle fatigue, and increases lactate threshold.

N-Acetyl Semax is a fragment from ACTH. It is not a melanocortin. It is neuroprotective and inhibits histamine release (through its Proline-Glycine-Proline ending sequence). It also reduces vascular permeability.  Nasal spray or SQ. It elevates BDNF in the hippocampus and in the cerebral cortex. It acts as an antidepressant and anxiolytic and attenuates chronic stress. It is a potential melanocortin antagonist (3 and 4 receptors). Other medical uses: Stroke, TIA, Memory, Cognitive Disorders, Boosts Immune System, Peptic Ulcers, Optic Nerve issues. Acts as a brain anti-oxidant. It counteracts the inhibition of learning and memory occurring from toxic heavy metals and counteracts neurotoxic effects. It promotes the survival of neurons secondary to hypoxemia and glutamate neurotoxicity. It contributes to mitochondria stability when under stress. It increases the amount and mobility of immune cells. It can be alternated or mixed with Selank.

Selank shows a variety of effects such as decreased histamine response from mast cells, decreased vascular permeability,  ulcer control meaning increased ulcer healing (from alcohol or stress), allows you to relax and concentrate, helps modulate IL-6, increases brain-derived nerve growth factor (BDNF) in the hippocampus, increases neuroplasticity and stem cell differentiation, has anti-depressant, anxiolytic effects that come on quickly, useful for Generalized Anxiety Disorder (GAD) and shows no sedation/addiction/cognitive loss. has anti-viral activity, regulates inflammation and decreases tumors in breast cancer, helps balance the sleep-wake cycle. Useful to transition from Growth Hormone to using a GHRH/GHRP as it decreases anxiety.

Tesamorelin is a growth hormone releasing hormone (GHRH). It stimulates the release of growth hormone and increases the amplitude of the pulse. It is a fragile peptide so it needs to be refrigerated after being reconstituted and used immediately. Tesamorelin is a good peptide to use if you transition from the use of Growth Hormone to a GHRH (best used with a GHRP, such as Ipamorelin). It has been successfully used to treat HIV + lipodystrophy, as well as to increase lipid metabolism, improve vascular health, control inflammation, and more.

Thymulin, nee thymosin alpha-1 modulates innate immunity boosting Natural Killer cells, and that means it autocorrects the immune system. If you get sore throats and colds multiple times each year, this peptide can help you. This peptide can be used for autoimmune issues in general. It stimulates T cell production, decreases the production of pro-inflammatory cytokines, Improves Th1 response, balances Th1/Th2. It dampens immunity (by upregulating IL-10). Enhances dendritic cells, and antibody responses. It has anti-tumor effects and decreases oxidative damage. It improves tolerance to stress. It increases anti-oxidant and glutathione production. It improves microcirculation as well as tissue repair and healing. Inhibits viral replication. Applications: improves autoimmune disease, chemical sensitivity, allergies, cancers, Hepatitis B and C, HIV/AIDS, Malignant Melanoma, and other (particularly stressful situations, eg, air travel, that bring out Shingles, and Seasonal Allergy). Also, Lyme disease, Chronic Fatigue, Fibromyalgia. Adjuvant to Flu vaccinations in Geriatrics, sepsis, Dysbiosis (along with BPC-157). Best use for Hashimoto’s Thyroiditis is to use daily to lower antibodies (600 mcg/day) instead of every 3 days as used for other conditions. Works well to decrease brain fog of chemo patient (along with BPC-157, and DSIP). There are no documented adverse effects to date (10/20/18).

Thymosin beta4 (TB4) addresses inflammation, immune dysregulation, and reactive oxygen species that underlie chronic illness and age-related decline. Promotes healing via upregulation of G-actin formation. Increases cells involved in healing. Improves cell migration to the site of injury. It decreases scar tissue fibrosis (reduces levels of myofibroblasts). Anti-inflammatory. Promotes angiogenesis and differentiation of endothelial cells. Increases collagen deposition, and is cytoprotective. Improves hair growth. Useful for stroke, and traumatic brain injury (TBI) when used with BPC-157. Also supports immunity and is neuroprotective. Useful for soft tissue repair: tendons, ligaments, muscles, also post-infarction of the myocardium and decreases sarcopenia.  Applications for venous ulcers, and ischemic strokes. Cardioprotective, and useful in Non-Alcoholic Fatty   Liver Disease (NAFLD) by decreasing hepatic fibrosis and decreases proinflammatory factors and oxidative stress. Can be used with BPC-157. Prevents adhesions & fibrous band formation in injured tissue. Protects and restores neurons post-TBI. Works like BPC-157 in that it is a cell-to-cell signaling molecule. Used for patients with sepsis in ICU’s.