Unlocking The Potential Of Oral Peptide Bioregulators For Antiaging And Chronic Illness
Unlocking
the Potential of Oral Peptide Bioregulators for Antiaging and Chronic Illness with Bonus Slides
Kent Holtorf,
MD
Understand the Benefits and Limitations
Gain a clear understanding of multiple bioregulators, including limitations, dosage, protocols, combinations, interaction, expectations, and monitoring, along with patient selection
Immune Modulation, a Key to Success:
Learn how immune modulation is essential for successfully treating chronic infections, chronic illness, and age-related conditions.
Develop Strategies for Integration:
Learn how to effectively integrate these treatments into your clinical practice with other peptides, medications, supplements and cellular therapies.
Understand why thymic, pineal and vascular bioregulator supplementation serve as a core therapy where additional tissue specific bioregulators can then be added depending on the patient's unique needs & dysfunctions.
The Immune System and Health
Immune Health is Key
It's the most significant determinant of overall health and longevity.
Thymus Plays a Major
Role
Thymus involution is at the core of the Th1/Treg to Th2/Th17 shift.
Shift Worsens with Age and Environment
Toxins, stress, and poor lifestyle contribute to the shift.
Vicious Cycle of Degeneration
A worsening immune shift leads to multisystem degeneration and illness.
Kavinson, VKh, Peptides, Genome, Aging. Advances in Gerontology, 2014;4(4):337-45.
New and reactivating infections, IAOC, autoimmunity, & T-cell exhaustion.
With associated reduced autophagy SASP Increased inflammation
Cellular Senescence
Tissue, organ and cellular dysfunction
Multisystem Disease and Multiple Symptoms 1.
Thymic Decline with Age
Thymus gland, crucial for immunity, begins to decline.
Age 30
Pineal gland calcification is common, affecting hormone and immune function.
Age 40-45
The thymus involution weakens the immune system, contributing to age-related health problems like cancer, heart disease, diabetes, mortality and morbidity and a major reason patients can't recover from chronic infectious, autoimmune and inflammatory conditions.
Thymus activity is minimal, coinciding with increased risk of age-related diseases. 1.
Lewis V, et al. Circulating
Thymic Activity and Chronic Disease
According to the U.S. 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.
Low levels of thymic peptides
• Seen in primary, secondary, and tertiary immunodeficiencies
• Found in autoimmune diseases, including SLE, RA, Hashimoto's, and MS.
• Thymectomized animals and humans are highly susceptible to autoimmune diseases
Immune Shift and Mitochondrial Dysfunction
The authors found that all of the CFS patients had mitochondrial dysfunction. The degree of mitochondrial dysfunction correlated with the severity of the illness (p < 0.001)
“Only1ofthe71patients overlapsthenormalregion.”
CD4/CD8 Ratio and Thymic Function in HIV Patients
Traditional Markers
Traditional markers, like viral load and CD4 counts, have been used to monitor HIV progression. However, these may not fully capture subtle immune dysfunction in patients on effective treatment.
CD4/CD8 Ratio
The CD4/CD8 ratio is a more precise biomarker for immune health in HIV patients, providing a comprehensive assessment of overall immune dysfunction and biologic age.
Thymic Function
Disruption of thymic function, reflected by the CD4/CD8 ratio, is a key marker for premature thymus dysfunction and immune aging seen in chronically infected patients.
1. Smith CJ, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D. The Lancet 2014;384(99939):241-8.
2. McBride JA, et al. Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health? PLOS Pathogens;13(11)e1006624
CD4/CD8 Ratio, Thymic Function, Biologic Age, and Healthspan Mortality
“We recently described that thymic function failure is an independent predictor of all-cause mortality in uninfected elderly humans.”
Immunosenescence
A low CD4/CD8 ratio reflects Immunosenescence and significantly predicts a wide range of morbidities, such as autoimmunity, diabetes, CVD, stroke, cancer, frailty, chronic infections, etc.
Biologic Age
A low CD4/CD8 ratio is associated with chronic viral infections, oxidative stress, thymic dysfunction, and multiple disease states (ideal > 2.5).
1. Ferrando, et al. Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age (Dordr) 2013; 35:251–59
2. De Santis M, et al. β-thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up. Respir Res 2011; 12(1): 22
3. Muller GC, et al. The inverted CD4:CD8 ratio is associated with oxidative stress during aging. Cellular Immunology 2015;296(2):149-154.
What are Peptides and Bioregulators?
Chemical Structure
Peptides are short chains of amino acid. They are similar to proteins, but are shorter in length, typically less than 50 amino acids long.
Bioregulators are two (2) to four (4) amino acids in length.
Biologic Role
Peptides & bioregulators play vital roles, acting as the master regulators of most every known process in the body and serve to fine tune the body's processes. They can act as hormones, neurotransmitters, and metabolic and immune system regulators.
Therapeutic Potential
Due to their potent biological activities, peptides have significant therapeutic potential.
Increasing numbers of peptides and bioregulators are becoming clinically available that can safely improve, optimize or normalize specific functions of the body.
1. Khavinson V. Peptides and ageing. Neuroendocrinology Letters 2002;23(3):11-144
2. Anisimo VNN, et al. Effect of synthetic thymic and pineal peptide on biomarkers of ageing, survival and spontaneous tumor
3. incidence of female CBAmice. Mech Ageing Dev 2001;122(1):41-68.
Understanding Peptide Complexes
Peptides are isolated from young animal tissues using advanced biotechnology techniques. Extraction
Purified peptides are combined into specific complexes tailored for different physiological targets. Formulation
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The extracted peptides undergo rigorous purification processes to ensure high quality and safety.
Clinical Application
Purification The peptide complexes are administered to patients as part of comprehensive treatment programs.
Mechanism of Action
Peptides act as signaling molecules, binding to receptors on the cell surface and initiating a cascade of events that indirectly influence cellular activity, rapid onset and offset, but can lead to long-lasting epigenetic changes.
Bioregulator peptides bind to gene translation activators or inhibitors, influencing transcription patterns and affecting protein synthesis, altering transcription patterns toward a younger, healthier phenotype, with a slower onset and offset.
Safety of Peptides
Highly Specific and Targeted Control
Peptides regulate a vast array and multiple tiers of biological processes, from the nervous system to connective tissue to the cardiovascular system.
Compared to hormones, peptides exhibit more specific and targeted control, while peptide bioregulators exhibit the most specific and targeted control of metabolic processes.
Exceptional Safety Profile
Studies have shown the exceptional safety of oral peptides, with many showing no toxicity at a 100 or even 1,000 to 10,000 times the typical therapeutic dose.
Growing Availability
As the number of clinically available peptides and bioregulators continues to grow, healthcare professionals now have an increasing array of tools that can safely optimize and normalize bodily functions.
Potent at Low Doses
Peptides are highly potent and effective even in the nanogram and picogram range, which are one million to one billion-fold less than the typical milligram doses used for supplements and medications. (0.000,000,1 to 0.000,000,000,1 less than a mg)
Use of Peptides and Bioregulators Can Change Your Practice
Wide Range of Applications
Peptides and bioregulators can effectively treat a large percentage of your patients across a wide range of conditions, many who you previous had nothing for, from the sickest, multisystem patients to antiaging, HRT, fatigued, depressed, and athletic populations.
Unparalleled Safety and Efficacy
These 3rd generation, oral peptide supplements and bioregulators offer an unmatched safety and efficacy ratio compared to other therapies, with potent formulations and improved bioavailability.
Gut-Brain Axis and Beyond
Peptides and bioregulators can address both the gut-brain axis and brain-gut axis, effectively treating a huge population with gut and systemic issues that have been resistant to other treatments.
Bioregulators
Unveiling the Secret Weapon of Soviet Super Soldiers and Olympic Athletes
A Cold War Secret
Soviet Military Challenge
During the Cold War, Soviet submariners, supersonic jet fighters, and cosmonauts suffered from “premature aging effect” and physical decline.
Top Secret Mission
This alarming problem prompted the formation of a top-secret project for the USSR Ministry of Defense to find a solution.
Breakthrough Discovery
Their search led to a groundbreaking discovery with the potential to revolutionize our understanding of aging.
The Birth of Peptide Bioregulators
Soviet Discovery
Soviet scientists, led by Colonel Vladimir Khavinson, M.D., Ph.D., paired with Ivon Pavolv, made a groundbreaking discovery that specific organ extracts from fetal cows, including the pineal and thymus glands, could reverse premature aging effects in a tissue-specific manner.
Unlocking the Secrets of Peptides
This led to the isolation of ultra-short peptides, only 2-4camino acids in length, which were found to be orally bioavailable and able to enter cells and interact directly with DNA, modulating gene expression to promote youthful cellular function.
A Secret Weapon
For decades, these peptide bioregulators were a closely guarded secret, used exclusively by the Soviet military and olympic athletes to maintain peak performance.
The Cold War Discovery That Could Extend Your Lifespan
Western Discovery
It wasn't until after the fall of the Soviet Union that the West began to uncover the extensive research and incredible potential of these once-classified peptides.
High Bioavailability
Other uniquely beneficial properties of bioregulators are their resistance to enzymatic degradation in the GI tract and their ability to be transported through the intestinal and bloodbrain barriers, making them highly orally bioavailable.
Public Availability
Now, after years of research and development, these powerful peptide bioregulators are available to anyone looking to enhance their health, vitality, and longevity.
Cellular Bioavailability
They also readily pass across cell and nuclear membranes, allowing them to efficiently affect their target tissues.
The Cold War Discovery That Could Extend Your Lifespan
Longevity
With the ability to selectively activate youthful genes and suppress age-related genes, peptide bioregulators offer a way to not just slow aging but potentially reverse it, extending both lifespan and health span.
Cutting Edge of Health Science
With over twenty natural bioregulator extracts and over thirty bioregulator peptide isolates available for commercial use, these peptides represent the cutting edge of health science, providing a practical solutions for those seeking to maintain youth and vitality.
1. Khavinson V. Peptides and ageing. Neuroendocrinology Letters 2002;23(3):11-144
2. Anisimo VNN, et al. Effect of synthetic thymic and pineal peptide on biomarkers of ageing, survival and spontaneous tumor incidence of female CBAmice. Mech Ageing Dev 2001;122(1):41-68.
Longevity and Therapeutic Effects
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Lifespan Extension
Peptide bioregulators can potentially extend lifespan by regulating gene expression associated with aging processes, enhancing protein synthesis, and supporting healthy cellular function.
Senescent Cell Removal
Peptide bioregulators promote the removal of senescent cells, reduce inflammaging, and suppress SASP secretion, targeting the root causes of aging and chronic illness.
1. Khavinson V. Peptides and ageing. Neuroendocrinology Letters 2002;23(3):11-144
2. Anisimo VNN, et al. Effect of synthetic thymic and pineal peptide on biomarkers of ageing, survival and spontaneous tumor incidence of female CBAmice. Mech Ageing Dev 2001;122(1):41-68.
Oral Dermatologic Bioregulator
Effects on Skin
Oral Dermatologic Peptide
Highly Purified
Increased Hydration
Reduced Wrinkles
Orally Active
Skin Whitening
Increased Elasticity
Increased Brightness Decreased Menopausal Sx
Relative Melanin Index
Placebo Placenta Derived Skin BR
Relative Eye Wrinkle Index
Placebo Placenta Derived Skin BR
Investigators' Cumulative Relative Skin Aging Index
Placebo Placenta Derived Skin BR
Bioregulators and Aging (TAP Study)
Telomere Length and Aging
Numerous studies have shown that telomere length is closely linked to the aging process. People with shorter telomeres have a much higher chance of dying from any cause compared to people with longer telomeres.
Clinical Evidence
Studies in Russia and the United States have proven that peptide bioregulators can restore stem cell function, increase telomere length, and reverse biological aging in a broad spectrum of ways. These effects are linked to significant decreases in markers of mortality and illness.
Ongoing Russian Study
The Telomerase Activation Protocol (TAP) study gives subjects a combination of 5-7 peptide bioregulators for ten days each month, rotating through a total of 21 peptides over time.
Telomere length and biological age are measured at the start and annually.
Telomerase Activation Protocol (TAP)
Study Study Goals
The study goals are to reduce biological age by 7 years, which is associated with a 50% reduction in all-cause mortality, improve quality of life (QoL), and achieve an extended healthy lifespan.
Clinical Results
On average, participants reversed their telomere age by 22 years over three years, achieving an average of 7 years of telomere lengthening per year.
Current Status
Over 100 participants are actively involved or have achieved their telomere goals and are now on a minimal maintenance program.
The Epigenetic Methylation Analysis and Intervention Study
Study Goals
For this 3-4 year study, the goals are to determine if peptides can reverse biological aging, in addition to telomere length, at the molecular (DNA/m) level via EpiAge testing with a personalized peptide bioregulator protocol.
Study Participants
The average study participant had a baseline epigenetic age 3.5 years older than their chronological age, equating to about a 40% increased risk of mortality.
Current Status
Over 100 participants are actively involved or have achieved their telomere goals and are now on a minimal maintenance program.
Clinical Results
On average, participants reversed their telomere age by 14 years and over 5 years in EpiAge after two years. Over 90% of the telomere participants reached their telomere goal in 2 to 3 years.
Thyroid and Thyroid Axis Bioregulators Overview
Thyroid and Thyroid Axis
Bioregulators Overview
• Extracted from the thyroid glands of young animals
• Stabilizes thyroid function and thyroid hormone levels.
• Can normalize thyroid function and reverse hypo and hyperthyroidism and autoimmune thyroiditis, including Hashimoto’s and Grave’s disease.
• Reduces the size of thyroid nodules.
• Improves pineal-hypothalamic-pituitary-thyroid axis and mitochondrial function.
• Prevents stem cell aging.
• Activates telomerase and stem cell function.
• Supports the healthy functioning of the neurologic, immune, and cardiovascular systems.
• Improves hypercholesterolemia, insulin resistance, and metabolic function.
• Rejuvenates hair, nails and skin.
• Shown to improve physical performance, endurance, cognitive function, mood disorders, bone density, antioxidant activity, quality of life, and survival rate.
• Improved longevity in old and elderly patients.
• Reduced cancer rates and the incidence of chronic infections.
Thyroid Bioregulator for Primary
Hypothyroidism
1 Treatment
Study Participants
The study involved 25 patients with primary hypothyroidism, including 11 men and 14 women aged 56 to 67 years. The control group consisted of 19 patients, including 7 men and 12 women.
Patients in both groups complained of significant fatigue, poor endurance, drowsiness, memory impairment, frequent headaches, dizziness, and an increased incidence of angina. In most cases, signs of thyroid atrophy were detected by palpation.
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2 Testing
The control group was prescribed conventional therapy of T4 for three months.
Patients of the primary group received thyroid bioregulator 1-2 capsules 2 times a day before meals for three months.
The patients’ biochemical analysis of blood (serum T3 and T4) was performed along with a thyroid ultrasound and EKG examination before and after the trial.
Thyroid BioregulatorTherapy for Primary Hypothyroidism
Results
• Compared to the control group receiving T4 therapy, those receiving the Thyroid Bioregulator noted improvement in the clinical manifestations of the disease in 78% of cases, and the most significant effect was observed in persons of the older age group with pronounced signs of thyroid atrophy.
• After 20 days of treatment, the Thyroid Bioregulator group noted increased working capacity and endurance, decreased frequency and intensity of headaches, and decreased angina compared to the control group on T4 therapy.
Thyroid Hormone Levels
• After treatment with T4, the total T3 reached the low normal range, but T4 levels did not change from a pretreatment T3 level that averaged 60% below the lowest level of normal and a T4 level that was 35% below the lowest level of normal.
• On the other hand, the addition of the thyroid bioregulator resulted in a 300% increase in the T3 level from baseline and a 40% increase over T4 replacement alone, with T4 levels doubling and 60% higher than T4 alone.
• After stopping the therapy, the T4 and T3 levels in the Thyroid Bioregulator group remained in the normal range for 3-4 months.
Thyroid Hormone Levels
1. Khavinson V. Short Peptide Bioregulators in the Treatment of Hypothyroidism. Medical Center of the Northwest Department of the Russian Academy of Medical Sciences, 20052006.
Treatment of Autoimmune Thyroiditis with Thyroid vs. Thyroid-Axis Bioregulator
Mission
A 4-month study on the efficacy of thyroid vs. thyroid axis bioregulator therapy for autoimmune Thyroiditis with hypothyroidism compared to standard therapy of L-thyroxine 50 mcg/day for four months.
• Two hundred eighteen patients (218) with autoimmune thyroiditis aged between 39 and 51-years old. were randomized
Group I
Eighty-nine (89) people received standard treatment of L-thyroxine 50 mg daily for 4 months.
Group II
Forty-two (42) people received peptide thyroid bioregulator therapy in addition to the standard treatment scheme
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Group III
Eighty-seven (87) people received peptide thyroid-axis bioregulator therapy in addition to the standard treatment.
Khavinson V. Thyroid –axis Bioregulators in the Treatment of Hashimoto’s Thyroiditis. Medical Center of the Northwest Department of the Russian Academy of Medical Sciences, 2018.
Study Results
Indicators
Number of Patients -
Thyroid Axis Bioregulators
Group IV: Fifteen (15) young rats and ten (10) old hypophysectomized (pituitary removed) rats received THYROID AXIS BIOREGULATOR Alpha-24C (TAB-A24C) in group IV. 1 3 5 2 4
Experiment on the effects of Thyroid Axis Bioregulators on sixty (60) young rats (4 days old) and forty-five (45) old rats (24 months old) after undergoing hypophysectomy (pituitary removed).
Group I: Fifteen (15) young and ten (10) old rats were sham-operated with all others undergoing Hypophysectomy
Group II: Fifteen (15) young and fifteen (15) old rats in group II received physiologic saline for 40 days after having pituitary removed.
Group III: Fifteen (15) young rats and ten (10) old rats received THYROID AXIS BIOREGULATOR C44 (TABa-C44),
Longevity and Therapeutic Effects
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Thriving
The young and old rats treated with saline quickly experienced a 43% and 30% weight loss and growth retardation with sluggishness, suppressed excitement and anorexia.
While those given TAB-C44 had a 19% and 21% weight loss, and the TAB-A24C group only had a 7% and 6% weight loss, respectively.
Thyroid and Thymus Function
Normal thyroid architecture was much more consistently maintained in the TAB-C44 and ATB-A groups compared to the saline group.
TAB-C44 and TAB-A24C prevented the signs of hypothyroidism and normalized the structure and function of the thyroid gland.
TSH, T3 and T4 levels plummeted 80-90% after hypophysectomy, but the decline was significantly blunted by TAB-C44 and TAB-A24C.
Thyroid Bioregulator Axis Formula
Serving Size: 1 capsule Servings
Per Container: 60
Supplement Facts
Amount per serving Value
Purified Natural Bovine Thyroid Glandular Peptide Complex (Free of T4 & T3) with Minimum of Naturally Occurring Acetylated and Amidated 25 mg
Thyroid Bioregulator Alpha-24C > 190 mg
Thyroid Bioregulator AWG2 > 235 mcg
Thyroid Bioregulator C44 > 185 mcg
Cerebral Peptide Bioregulators
Brain Peptides and Bioregulators
Bioregulators of the cerebral cortex, such as Cortagen, Cerebrolysin and CerebroPep (the oral version of Cerebrolysin), and the subcortical area, Pinealon (CogniPep), represent a class of therapeutic brain peptides designed to mimic natural peptides that regulate brain function and have demonstrated a promising potential in managing neurodegenerative diseases, cognitive decline, brain injuries, and toxic and infectious encephalopathies (CogniPep, CerebroPep PinealPep, LongevityPep, Thymogen Alpha-1, Vilon).
Mechanisms of Action
Bioregulators support brain health by enhancing neuroplasticity and stimulating the synthesis of specific proteins that maintain the structural and functional integrity of neurons and glial cells. They promote neurogenesis, modulate neurotransmitter balance, enhance brain metabolism, and improve synaptic plasticity. And protect against oxidative stress and inflammation, stimulate neurotrophic factors, reduce glutamate-induced excitotoxicity, support mitochondrial function, modulate calcium homeostasis, and reduce inflammatory responses in the CNS.
Mechanisms of Action
Brain bioregulators have demonstrated promising potential in managing neurodegenerative diseases, cognitive decline, brain injuries, and toxic and infectious encephalopathies. They have been studied extensively for their neuroprotective effects in age-related cognitive decline, Alzheimer's disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and traumatic brain injury (TBI). Applications include stroke recovery, cerebral palsy, epilepsy, neuropsychiatric conditions, and encephalopathies.
1. Pinealon for Long-term Consequences of craniocerebral Injury. Bioreg Gerontology Russ Acad Med Sci, 2005; Fedin, AI. The efficacy of cortexin and memantinol (memantine) in the treatment of cognitive impairment in patients with chronic cerebral ischemia.
Brain Peptides and Bioregulators
Neuro-stem cell proliferation (LongevityPep), reduce apoptosis, and enhance the functional recovery of damaged neurons along with neurogenesis, neurotropic factors, synaptic plasticity, and cognitive function by regulating neurotrophic factors such as Brain-Derived Neurotrophic Factor (BDNF) (Zhang et al., 2021) (CogniPep).
Neuroprotection and Neuro-telomere Elongation: (PinealPep, CerebroPep, Thyropep, LongevityPep).
Anti-Apoptotic Effects in Neural Cells: Cerebral peptide bioregulators inhibit the expression of pro-apoptotic genes in neurons and increase anti-apoptotic factors, protecting brain cells from age-related or injuryinduced apoptosis (CogniPep, PinealPep, CerebroPep, LongevityPep, Thymogen Alpha-1, Vilon).
Mitochondrial
and
Metabolic Function and Cellular Energy:
Pinealon, Bpc-157 and other bioregulators reduce ROS production, enhance ATP synthesis, and protect mitochondrial membranes, reducing SASP, improving cellular energy metabolism similar to the mitochondrial peptides, like SS-31 (Elamipretide), MOTs-c, Humanin, small humanin-like peptides (SHLPs), (Cohen et al., 2020) (CogniPep, PinealPep, CerebroPep, ThyroPep, BPC-157, Gut Feeling, CardioPep, RenalPep).
Vascular Bioregulators: Exhibit tissue-specific regulatory effects on the vascular system, promoting repair and regeneration, normalization of vascular functions, stabilization of cell membranes, enhancement of endothelial function and vascular elasticity, improvement of nitric oxide production and microcirculation, demonstrating the ability to reverse atherosclerosis and have significant clinical utility in the treatment of cardiovascular, neurodegeneration, and metabolic conditions. Vessel BR can improve VEGF expression and improves BBB permeability, potentially reducing neurovascular dysfunction in AD. (CogniPep, PinealPep).
1. Pinealon for Long-term Consequences of craniocerebral Injury. Bioreg Gerontology Russ Acad Med Sci, 2005;
2. Fedin, AI. The efficacy of cortexin and memantinol (memantine) in the treatment of cognitive impairment in patients with chronic cerebral ischemia.
1, 2018
3. Anastasiia Ilina, et al. Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 4259-4288
Brain Peptide Bioregulators
• These peptides often exhibit a multi-target approach, addressing various aspects of AD pathophysiology, including amyloid beta (Aβ) aggregation, mitochondrial dysfunction, oxidative stress, neuroinflammation, and synaptic dysfunction (CogniPep, PinealPep).
• The peptides Pinealon and Vesugen (CogniPep) have shown promising results in reducing Aβ-induced synaptotoxicity, restoring the number of dendritic spines in hippocampal neurons, and preventing the elimination of mushroom spines in mice (AD model).
• Epitalon peptide has been found to increase the synthesis of transthyretin (TTR), a protein that cleaves amyloid and protects neurons from Aβ toxicity. This suggests a potential role in preventing Aβ accumulation. Vilon and Epitalon have been shown to regulate the expression of genes involved in mitochondrial function, suggesting their potential to mitigate mitochondrial dysfunction (CogniPep, PinealPep).
• Pancragen has been shown to regulate glucose metabolism in AD (MetabaPep).
• Epitalon and Vilon (PinealPep, CogniPep) have also been shown to modulate neuroinflammation by regulating the synthesis of cytokines like IL-1β and IL-7. 1
1. Anastasiia Ilina, et al. Neuroepigenetic Mechanisms of Action of Ultrashort Peptides in Alzheimer’s Disease. Int. J. Mol. Sci. 2022, 23, 4259-4288
Efficacy of Subcortical Brain Bioregulator (Pinealon) on Clinical Symptoms of CNS Disorders
Improvement in Cognitive and Neurological Functions with subcortical brain bioregulator, pinealon, with a marked reduction in symptoms such as headaches, dizziness, impaired memory, and emotional instability compared to the control group, which only received conventional treatment.
The frequency of these complaints decreased by 2-3 times in the treatment group.
EEG Changes from Subcortical Brain Bioregulator (Pinealon) and Clinical Symptoms with CNS Disorders
EEG Findings
EEG showed enhanced cerebral stability and activity, supporting cognitive improvement.
Cognitive Performance
Patients showed substantial improvements in cognitive test performance compared to controls.
Motor and Speech Function
Treatment led to improved speech recovery in aphasia patients and reduced muscle spasticity poststroke.
2. Treatment of nervous disease: Viderholt, VK. M Medicine 1984:545-60.
EEG
Changes with Pinealon Rx in Chronic CNS Disorders
CerebroPep (Oral Cerebrolysin)
Nootropic Peptide: CerebroPep
• Mixture of neuropeptides
• Functions as a brain immune modulator, anti-inflammatory, and mast cell inhibitor while performing a broad range of neurologic regenerative functions
• Is currently approved for use in 44 countries as a treatment for dementia and stroke
• Neuroprotective
• Neurotrophic repair properties
• Penetrates the BBB, as the active portion is less than 10,000 Daltons.
• Stimulates central and peripheral neural growth factors
• Improves cognitive function
• Has been used for TBI, Alzheimer’s and stroke patients
• Shown to be effective in autism and Asperger’s syndrome at very low doses114
• Historically given intravenously, but bioavailable orally (effective when given orally)
CerebroPep
The effects of a single oral dose of the Cerebrolysin on brain bioelectrical activity and on cognitive performance were investigated in healthy elderly people.
The present results indicate that oral Cerebrolysin influences brain functioning when administered by oral route, having positive effects on cognitive performance (improves memory and attention) and inducing an acceleration of the brain bioelectrical activity pattern (enhances alpha activity and decreases delta power). 1 3 2 4
A single oral dose of Cerebrolysin induced a progressive increase in relative alpha activity power in 1 hour and lasted 6 hours after treatment in almost all the brain electrodes in elderly control subjects
A significant improvement in memory performance was also found in elderly people taken a single dose of oral Cerebrolysin treatment; (p < 0.01).
Peptide Bioregulator Combinations and Atherosclerosis
Combinations of peptide bioregulators, such as blood vessels, pineal, subcortical brain, and liver, are shown to prevent and reverse chronic diseases of aging, such as atherosclerosis, varicose veins, osteoporosis, diabetes, Alzheimer's, etc.
The Role of Senescent Cells in Cardiovascular Pathology
Endothelial Dysfunction
The accumulation of senescent endothelial cells with shortened telomeres during aging leads to apoptosis, resulting in disturbed blood flow and endothelial dysfunction.
Vasorelaxation Impairment
These senescent cells are unable to produce adequate nitric oxide, essential for vasorelaxation, contributing to lipid peroxidation in smooth muscle cells and promoting intimal thickening a key stage in atherosclerosis development.
Proatherosclerotic Influence of SASP
SASP factors enhance proatherosclerotic activities, exacerbating plaque formation and endothelial dysfunction at vulnerable sites.
2. Treatment of nervous disease: Viderholt, VK. M Medicine 1984:545-60. \
The Role of Peptide Bioregulators in CV Health
Senescent Cell Removal
Oral thymic peptides bioregulators, including Thymogen, Vilon, and TB4 Frag are key to removing SCs via increased Th1.
Inflammaging and SASP Reduction
BPC-157, and the bioregulators KPV, oral Cerebrolysin, and the Vessel, Cardiac, Pineal, and Brain Bioregulators, function to reduce inflammaging and SASP production vital in managing the aging of the cardiovascular system.
Therapeutic Potential
Demonstrating the ability to remove SCs, reduce inflammaging and suppress SASP secretion, bioregulators can significantly prevent, reverse, and mitigate the progression of atherosclerosis, myocardial infarction, CHF, cardiac hypertrophy, diastolic dysfunction, and other cardiovascular conditions.
1. Stojhanovic, SD, et al. Senescence-induced inflammation: An important player and key target in atherosclerosis. Euro Heart J 2020;41:2983-96.
Study Design: Bioregulator Treatment of Cerebral Atherosclerosis
Group I (514 pts)
Control Group: Received standard treatment following conventional schemes for atherosclerosis, including statins.
Group II (319 pts)
Two Peptide Combination: Standard treatment enhanced with vascular peptides (vesugen) and subcortical brain bioregulator peptides (pinealon)
Group III (416 pts)
Four Peptide Combination: Group II therapies plus pineal (epitalon), and liver bioregulators.
The study involved 1,249 patients aged 55-65 with atherosclerosis, conducted at the Moscow Center of Revitalization and Health.
1. Gorgiladze, DE, et al. The Use of Peptides for the Treatment of Age-related Diseases. Aging and Antiaging-Prospects for the Development of anti-aging technologies: The World Congress of the International Assoc. of Gerontology and Geriatrics. June 23, 2013:2-10.
Peptide Complex Components and Their Functions
Vesugen (Blood Vessel)(CogniPep, PinealPep)
Regulates vascular wall cells, reduces pathological vascular changes, lowers cholesterol and lipoprotein levels, mitigates risks of vascular, neurologic, and glandular dysfunction, and inhibits SASP secretion.
Pinealon (Subcortical Brain) (CogniPep)
Targets brain tissue cells, enhances brain reserve capacity, improves resistance to hypoxia and toxins, reduces oxidative stress, and is crucial for cognitive function.
Livagen (Liver)(GIPep)
Epitalon (Pineal)(PinealPep)
Acts on liver cells, normalizing their function and restoring metabolism, prevents and treats fatty liver, NASH, and is essential for overall health and longevity.
Regulates pineal gland cells, normalizes melatonin synthesis, reverses infertility, lengthens telomeres, reduces morbidity and mortality, including the incidence of cancer, CVD, and is shown to improve the QOL, healthspan and longevity. 1 2 3 4
Methodology and Measurements
Cholesterol and Lipid Levels
Total cholesterol, VLDL, and triglycerides were measured to assess the impact of peptide complexes on lipid metabolism.
Subjective Health Evaluation
Patients' self-reported symptoms and quality of life were assessed to gauge the overall impact of the treatment on their well-being.
Treatment Duration and Dosage
During the four month study, Pineal was given once per day for two months, while the others were given two per day for three out of the four months.
Efficacy of Subcortical Brain Bioregulator (Pinealon) on Clinical Symptoms of CNS Disorders
*Statistically significant improvement compared to the standard treatment group.
"The application of our peptide complex yielded remarkable improvements in lipid metabolism and coagulation system indicators…"
"The most significant positive changes were observed in the third group, which received the comprehensive four-peptide treatment." 1. Gorgiladze, DE, et al. The
Before Treatment
ST+Vessel (V)+Subcort Brain...
Standard+V+SCB+Liver+Pineal
Standard Scheme (ST)
Bioregulators for Atherosclerosis
"Our groundbreaking study demonstrates the remarkable efficacy of peptide bioregulator complexes in treating cerebral atherosclerosis.“
"The combination of bioregulators not only improved objective markers of vascular health but also significantly enhanced patients' quality of life.“
"These peptide bioregulators showed no side effects, complications, or addiction potential, making them a safe and powerful tool in anti-aging medicine."
1. Gorgiladze, DE, et al. The Use of Peptides for the Treatment of Age-related Diseases. Aging and Antiaging-Prospects for the Development of anti-aging technologies: The World Congress of the International Assoc. of Gerontology and Geriatrics. June 23, 2013:2-10.
Combination Oral Peptide Bioregulator Therapy for Type II Diabetes
This study evaluates the effectiveness of peptide complexes in treating type II diabetes mellitus.
A cohort of 918 patients aged 52-65 were divided into three groups, receiving different treatment regimens. The research aimed to compare standard treatment with peptide-enhanced approaches. 2 3 1
1. Gorgiladze, et al. The Use of Complex Peptide Bioregulators on the Pathogenesis of Diabetes Mellitus. XX World Congress of teh International Assoc. of Gerontology and Geriatrics. Seoul, South Korea. June 23-27:2013.
Study Location Methods
The 3-month study was conducted at the Moscow office of the Center of Revitalization and Health.
Dosing
Pancreas and subcortical brain was given, two capsules per day for three months, while pineal was given one capsule per day for two months.
Patient Groups
Group 1
Three hundred twenty-nine (329) people who received standard treatment following a conventional regimen.
Group 2
Two hundred fourteen (214) people who received, in addition to the standard treatment regimen, pancreas bioregulator.
Group 3
Three hundred seventy-five (375) people who received a combination of oral peptide bioregulators, which included pancreas plus pineal and subcortical brain.
Peptide Combinations
Pancreas Bioregulator (Pancragen)
Regulates pancreatic cells, improves metabolic health, lipid utilization, and is shown to prevent and reverse metabolic syndromes, diabetes, neurologic, and cardiovascular diseases. Reduces body fat and improves endurance.
Subcortical Brain Bioregulator (Pinealon)
Regulates and protects brain cells, improving function of the nervous, endocrine, reproductive, and immune systems. It also restores lipid and carbohydrate metabolism, offering anti-atherogenic, anti-diabetic, antiautoimmune, and potent anti-cancer effects.
Epitalon (pineal)
Regulates pineal gland cells, normalizes melatonin synthesis and improves nervous, endocrine, reproductive, and immune system functioning. It restores lipid and carbohydrate metabolism, offering anti-atherogenic, anti-diabetic, anti-autoimmune, and potent anti-cancer effects.
The Effectiveness of Each Treatment (Percent Improvement in Each Marker)
Gorgiladze, DA, Pinaev, RN, Aleksandrov, VA. The Use of Complex Peptide Bioregulators on the Pathogenesis of
Glucose levels in the three groups, fasting and 2-hr glucose tolerance test before and after treatment
Traditional Scheme TT + Pancreas (P)
TT+P+Subcortical
Brain+Pineal
Combination Oral Peptide Bioregulator Therapy for Type II Diabetes
Benefits
This study evaluates the effectiveness of peptide complexes in treating type II diabetes mellitus. Long-term
Peptide treatments demonstrated longer-lasting positive effects compared to standard therapy. Efficacy of Peptide Combination
No side effects, complications, or addictions were reported with peptide treatments. Safety Profile
Advised dosage: Pancreas and Subcortical Brain (2 capsules/day, /3 months), and Pineal (1 capsule/day, 2 months).
1. Gorgiladze, DA, et al. The Use of Complex Peptide Bioregulators on the Pathogenesis of Diabetes Mellitus. World Congress of teh International Assoc. of Gerontology and Geriatrics. Seoul, South Korea. June 23-27:2013.
Methodology and Measurements
Muscle Bioregulator Action
Muscle bioregulators (MB) regulate metabolic processes in muscle tissue, increase reserve capacity, have a beneficial effect on the adaptation process in extreme conditions, restore muscle functions during intense physical activity, and positively effect biomarkers of aging.
Performance Measurement
The effectiveness of MB was determined by changes in speed and strength tests that include maximum grip strength, long jump from a standing position, the Harvard step test of endurance, and a flexibility measure.
Study Design
The study compared the performance off 17 individuals who continued with their usual training for two months between tests plus placebo compared to 22 individuals in the treatment group who took the MB for two months in addition to the usual training between tests.
1. Veretenko, AA. Biologically Active Food Supplement Gotratix and Physical Performance. The Russian Academy of Medical Sciences. 2011:28-30.
2. Lysenko, AV, et al. Arguments in Favor of teh Use of Biologically Active Peptides in teh Practice of Sports Pharmacology. Theory and Practice of Physical Culture. 2004;10:25-29.
Treatment Outcomes
1. Veretenko, AA. Biologically Active Food Supplement Gotratix and Physical Performance. The Russian Academy of Medical Sciences. 2011:28-30.
2. Lysenko, AV, et al. Arguments in Favor of teh Use of Biologically Active Peptides in teh Practice of Sports Pharmacology. Theory and Practice of Physical Culture. 2004;10:25-29.
Performance Improvement in Each Test (Two-months Apart)
Cntl Grp: Pre-Rx
Rx Grp: Pre-Rx
Cntl Grp: Post-Rx
Rx Grp: Post-Rx
1. Veretenko, AA. Biologically Active Food Supplement Gotratix and Physical Performance. The Russian Academy of Medical Sciences. 2011:28-30.
2. Lysenko, AV, et al. Arguments in Favor of teh Use of Biologically Active Peptides in teh Practice of Sports Pharmacology. Theory and Practice of Physical Culture. 2004;10:25-29.
Summary: Muscle Bioregulator and Athletic Performance and Aging Biomarkers
Improved Performance
The treatment group taking the MB noted improved performance across various tests, including grip strength, long jump, step-test, and flexibility, compared to the control group.
Reduced Fatigue
Participants in the treatment group reported experiencing less fatigue during training sessions, leading to more enjoyable workouts.
Faster Muscle Recovery
The bioregulator treatment contributed to faster muscle recovery after exercising, allowing athletes to train more effectively and efficiently.
1. Veretenko, AA. Biologically Active Food Supplement Gotratix and Physical Performance. The Russian Academy of Medical Sciences. 2011:28-30.
2. Lysenko, AV, et al. Arguments in Favor of teh Use of Biologically Active Peptides in teh Practice of Sports Pharmacology. Theory and Practice of Physical Culture. 2004;10:25-29.
Prostate Bioregulator Therapy for Prostate Disorders
Metabolic Effects
Prostate Bioregulators (PR) are shown to regulate metabolic processes in the prostate gland cells, increase their reserve capacity, improve adaptation in stressful environments, and protect against harmful ROS.
Study Design
Clinical assessment of 48 patients, aged 38-65, with the diagnosis of BPH (20) and chronic prostatitis (28) who were prescribed PB BID for 30 days, compared to 22 matched individuals who received only conventional treatment.
Assessments
The effectiveness of treatment was based on patient questionnaires, physical exams, blood and urine testing, ultrasonography, and dynamic urine flow assessment.
Treatment Results (Chronic Prostatitis)
Pain Relief
After 30 days of therapy with Prostate Bioregulator, 64% of CP patients became pain-free, and 32.7% had a significant reduction in pain, with 3.3% obtaining no benefit in pain.
Increased Libido
By the end of treatment, 37.1% of patients reported that their poor libido recovered.
Sexual Dysfunction
Forty-four percent (44%) of patients suffering with sexual dysfunction experienced significant recovery with improved quality of erection, enhanced orgasm, and increased duration of intercourse.
Treatment Results (Chronic Prostatitis)
Urination
Eighty-seven percent (87%) of treatment patients reversed their symptoms of increased frequency of urination, 80.7% no longer suffered from difficulty urinating, 15.9% noted an increased urine stream.
Ultrasound & Exam
Restoration of prostate size was noted on palpation with reduced edema on ultrasound
Secretory Actions
Restoration of prostate function was noted, with improved ejaculate with an 11.8% increase in motile spermatozoa, decreased leukocytes in ejaculate, prostate secretions, and urine.
Changes in Urodynamic Flow with Treatment (Chronic Prostatitis):
Before Treatment
After Conventional Rx
After Prostate Bioregulator Rx
Effects of PB on the Urodynamics in Patients with Benign Prostatic Hyperplasia (BPH) (after 30 days) Tests
1. Veretenko, AA. Biologically Active Food Supplement Gotratix and Physical Performance. The Russian Academy of Medical Sciences. 2011:28-30.
Effects of PB on the Urodynamics in Patients with Benign Prostatic Hyperplasia (BPH) (after 30 days)
Prostate Bioregulator for BPH
Significant improvement in urine flow dynamics was found in the treatment group. Urodynamic Testing
Structure
Reduction of prostatic fibrous and sclerotic tissue with increased elasticity of the bladder neck and subsequent improvement in urodynamic flow, dysuria, and prostate function.
Libido
Thirty-seven percent (37%) of the treatment group noted increased libido.
No side effects were reported by those in the treatment groups with chronic prostatitis patients or those with BPH.
Testes Bioregulator for "Low-T Syndrome"
Testes Bioregulator for "Low-T Syndrome"
Study Design
Clinical examination and symptom assessment with blood, urine and prostate secretion testing, including FSH, LH, and testosterone levels. Assessment 1 2 3 4
A small study of 36 men aged 47 to 65 with the diagnosis of hypogonadism.
Symptoms
Patients complained of rapid fatigue, decreased physical and mental performance, poor memory, emotional instability, increased sweating, irritability, and labile blood pressure.
Groups
Patients were divided into a treatment group, who received a testicular bioregulator (Testagen) one cap bid for 30 days compared to the placebo group.
Testes Bioregulator for "Low-T Syndrome"
Findings
• Testosterone levels increased to normal values in the treatment group with a significant improvement in well-being and leveling of psychophysiological disorders, including emotional instability, irritability, memory impairment, decreased physical and mental performance, as well as vegetative violations - increased sweating, headaches, and surges in blood pressure.
• All patients in the treatment group noted an increase in libido.
• There was a slight increase in LH, FSH, and testosterone in the control group, but remained at the lower limit of normal.
• LH, FSH, and testosterone increased by 50%, 80%, and 70% in the treatment group, respectively.
• Microscopic examination of the ejaculate demonstrated an increase in the number of sperm and sperm mobility, a decrease in the pathological forms of sperm, and a decrease in the number of leukocytes.
Safety of Peptides
Highly Specific and Targeted Control
Peptides regulate a vast array and multiple tiers of biological processes, from the nervous system to connective tissue to the cardiovascular system.
Compared to hormones, peptides exhibit more specific and targeted control, while peptide bioregulators exhibit the most specific and targeted control of metabolic processes.
Potent at Low Doses
Peptides are highly potent and effective even in the nanogram and picogram range, which are one million to one billion-fold less than the typical milligram doses used for supplements and medications.
(0.000,000,1 to 0.000,000,000,1 less than a mg)
Growing Availability
Studies have shown the exceptional safety of oral peptides, with many showing no toxicity at a 100 or even 1,000 to 10,000 times the typical therapeutic dose.
Exceptional Safety Profile
Peptides are highly potent and effective even in the nanogram and picogram range, which are one million to one billion-fold less than the typical milligram doses used for supplements and medications.
(0.000,000,1 to 0.000,000,000,1 less than a mg)
Combination Bioregulators for "Low-T Syndrome"
Study Parameters
Studied 105 men aged 38-57 years with erectile dysfunction and prolonged stress.
Patients were divided into three groups and received various combinations of adrenal, prostate, testis, and pancreas peptides for six weeks.
Outcomes
In all subjects, the quality of erections was studied, as well as indicators of glucose, insulin, cortisol, sex hormones, and insulin resistance (HOMA-R).
All patients had moderately elevated HOMA-R. The use of prostate and testicular peptides had a minimal effect on the quality of erections and was associated with an increase in total and free testosterone by 5% and 20%, respectively.
Key Findings
The use of a combination of adrenal, prostate, and testis peptides increased total and free testosterone by 54% and 24%, respectively, and had effect on the quality of erections.
The use of adrenal, prostate, testes and pancreas improved HOMA-R and cortisol level, increased free testosterone by 1.9-fold, and had a bigger impact on erectile function.
• Although patients with grossly elevated glucose or insulin levels were excluded, it appears that insulin resistance affected the activity of all the bioregulators
• Using multiple combinations of bioregulators is significantly more effective than monotherapy.
1. Gorgiladze, et al. Features of the application of gender profile peptides in middle-aged men. XXII World Congress of the International Association of Gerontology and Geriatrics. Buenos Aires, Argentina. June 12, 2022:23-25.
Treatment of Menopause and Infertility with Ovarian and Pineal Bioregulators
Treatment
of
Menopause
and Infertility with Ovarian and Pineal Bioregulators
Study the efficacy of ovary and pineal (epitalon) bioregulators in 214 women, aged 34 to 38 years old. Study Design
Therapeutics
The treatment group received ovarian bioregulator, two caps bid for four months and pineal bioregulator, one cap q 3 days for 4 months.
1. Gorgiladze, DE, et al. Assessing teh Effectiveness of Peptide Bioregulator Combinations for the treatment of Reduced Reproductive Function in Women. World Congress of the International Assoc. of Gerontology and Geriatrics. June 23, 2018:92-104. 1 2 3 4
Condition
All pts with reduced pineal-hypothalamicpituitary-estrogen/ progesterone axis dysfunction and associated age-related ovarian decline in women trying to unsuccessfully get pregnant.
Assessment
Blood testing for FSH, LH, estradiol, and AMH will be determined along with antral follicle number vis U/S before treatment and after 2 and 4 months of treatment.
Emerging Therapeutic Agents: Vascular bioregulators, with their promising potential, are paving the way for a brighter future in the treatment of cardiovascular and neurological disorders, the leading causes of morbidity and mortality globally.
Peptide-Based Interventions: Key vessel bioregulators such as Vesugen, Ventfort, Blood Vessel Bioregulator, and KED are specifically designed to enhance vascular health.
Mechanisms of Action
Tissue-Specific Regulation: Derived from natural sources, these peptides exhibit targeted effects on the vascular system.
Repair and Regeneration: Promotes repair, regeneration, and normalization of vascular functions; enhances resilience against stressors such as hypertension, hyperglycemia, and hyperlipidemia; epigenetically regulates genes related to the antioxidant system; and reduces cholesterol levels and the risk of vascular pathologies.
Cell Membrane Stability: Helps stabilize cell membranes and enhance endothelial function.
Senomorphic: KED (vessel), AEDR (cardiac), and KE (Vilon) regulate the synthesis of molecules involved in inflammaging and SASPforming cells of the cardiovascular system. This indicates the prospects for the development of drugs based on peptides for the treatment of age-associated cardiovascular pathology.
• Potential to Prevent and Reverse Atherosclerosis: Demonstrate the ability to reduce lipid peroxidation, normalize endothelin-1 expression, which is elevated in atherosclerosis and restenosis, enhance cell-tocell communication by increasing connexin expression,
• Clinical Utility: These bioregulators hold the potential for effectively managing cardiovascular, neurodegenerative, Kall and metabolic conditions.
Vascular Bioregulators
Beduction in Mortality: Administration of vascular bioregulator peptide prior to experimentally induced myocardial infarction in rats led to a threefold reduction in mortality rates compared to controls.
Observational Findings: There were substantial decreases in necrotic areas, overall residual cardiac damage, preservation of glycogen in cardiac tissue, and enhanced mitochondrial protection.
Reparative Effects: These observations underscore the peptides' capacity to foster reparative processes, enhancing cardiomyocyte metabolism and overall cardiac function.
Additive Benefits of the Vascular Bioregulator: Blood Vessel bioregulators restore vascular function, normalize expression of endothelin-1, which is associated with increased atherosclerosis and restenosis, boost the expression of connexin, which improves cell-to-cell communication, enhances SIRT1, which plays a role in cellular aging, normalizes morphological and functional aspects of the endothelium, restores nitric oxide secretion, stimulates endothelial metabolic processes, regulates the content of cholesterol and lipoproteins in the blood, and inhibits senescence and SASP secretion, all resulting in a reduced risk of vascular lesions, MI, stroke, and CVD.
Paradigm Shift in Treatment
Moving away from conventional therapies that solely compensate for dysfunctional physiological systems, the focus is now on addressing fundamental aging processes such as immunosenescence, inflammaging, and cellular senescence.
This strategic shift introduces new methods for the prevention, reversal, and treatment of severe age-related diseases, including cardiovascular diseases such as atherosclerosis, CVD, stroke, and myocardial infarction.
1. Lepakhin V.M. Clinical pharmacology and pharmacotherapy: Manual for doctors. M. Universum, 1993.-398 pages.
2. Korkushko O.V. Cardiovascular system and age. M.: Medicine, 1983.-176 pages.
3. Blood diseases in elederly people: Translated from English/Edited by M. G. Danham, I. Chanarina - M.: Medicine, 1989.
The tripeptide bioregulator
Vesugen, (Vessel Bioregulator) in combination with conventional treatment in elderly patients with atherosclerosis, was more effective than standard care alone. "
Can normalize hypertension and elevated cholesterol
"Peroral Vesugen reduces angina and decreases manifestations of cardiac arrhythmias in elderly patients with HTN."
Oral use of Vesugen led to long-term reduction remission between hypertensive crisis and a decrease in total cholesterol and VLDL."
It helped improve memory, attention, and thinking to accelerate perceptual motor reactions, increase mental capacity, and reduce neural aging."
"Vesugen stimulated the proliferation of immune and stem cells."
BPC-157: GI Peptide Origins
Body Protection Compound-157 (BPC-157) is a pentadecapeptide (15 amino acid peptide) isolated from human gastric fluid.65
It is highly stable and resistant to hydrolysis or enzymatic digestion.
Ac-BPC-157-NH2 (acetylated and amidated) is stable in gastric juice and absorbs intact with significant bioavailability.65
A vast number of studies have shown that BPC-157 can influence gene function and work through both the gut-brain axis and NO-system to improve health.5,6,1113,15,16,18,19,22,24,26,27,29-33, 3639,42,44.
Acetylated and Amidated BPC-157 vs. So-Called “Stable BPC-157” (Arginine BPC-157)
1
The majority (60-80%) of BPC-157 in the body is naturally acetylated and amidated (capped at each end) and is the most abundant, bioavailable, stable, and active natural form of the peptide. Should “Stable BPC-157” be Called “Unstable BPC-157?”
2
Such stabilization occurs with the most essential peptides and proteins, as the body uses this mechanism to protect critical peptides and proteins from breaking down in the gastrointestinal tract and serum by proteolytic enzymes.
"Ac-BPC-157 -NH2 is a very stable peptide that did not degrade after two 4 hr. incubations in human gastric juice.65”
1. Veljaca M, Chan K, Guglietta A (1995a): Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761.
Should “Stable BPC-157” be Called “Unstable BPC-157?”
Acetylated and Amidated BPC-157 vs. So-Called “Stable BPC-157” (Arginine BPC-157).
1
In contrast, an uncapped peptide salt, such as arginineBPC-157, called “Stable-BPC-157” by the manufacture, is prone to rapid degradation by enzymatic peptidases in the small intestine and the endothelial brush border lining of the gastrointestinal tract.
2
3
The arginine BPC-175 patent owners published a study that purported that the arginine salt version of BPC-157 is more stable in the stomach’s acidic environment than the acetylated version.
Their results contradict third-party studies demonstrating that N-acetylated BPC-157 (Ac-BPC-157), especially if also amidated (Ac-BPC-157-NH2), is stable in the gut for over 24 hours.
1. Veljaca M, Chan K, Guglietta A (1995a): Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761.
Should “Stable BPC-157” be Called “Unstable BPC-157?”
Acetylated and Amidated BPC-157 vs. So-Called “Stable BPC-157” (Arginine BPC-157)
To counter the poor absorption and bioavailability of “Arginine- BPC-157,” several manufacturers have resorted to adding the intestinal permeability enhancers, such as SNAC, which disrupts the endothelial lining and tight junctions.
SNAC is very controversial because it induces or worsens gastrointestinal inflammation and leaky-gut syndrome, potentially allowing harmful substances and microbes to enter the body. This has resulted in a ban of its use in numerous countries.
Additionally, the peptide salt is more polar than the naturally stable acetylated and amidated BPC-157, further hindering its ability to transverse the GI endothelial lining, limiting its bioavailability and activity.
1. Veljaca M, Chan K, Guglietta A (1995a): Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761.
2. Sikiric, P., et al., Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract. CPD, 2011. 17(16): p. 1612-1632
Administration of BPC-157
Given its origins as a gastric peptide, Ac-BPC157 has enhanced stability compared to other peptides. It is unique because it is effective regardless of the route of administration with oral administration being equipotent to systemic administration, such as IV, IM, or SQ. (oral, IV, Intraperitoneal, IM, SQ).
1. Perovic D, et al. BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery .Ortho Surg & Res 2019;14(1):199.
2. Gjurasin M, et. Al. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regulatory peptides. 2010 Feb 25;160(1-3):33-41.
3. Tudor M, et al. Traumatic brain injury in mice and BPC-157 effect. Regul Pept 2010;160(1- 3):1-3.
Treatment with BPC-157
Potential target conditions:
Infections
Inflammation
Gut-Brain Axis
Arrhythmias
Mold/EMF/entero, neuro, & mycotoxins
Post-surgical
Urinary incontinence
Skin
Bone
Stimulates stem cells
Autoimmune disease
GI inflammation
Periodontitis
Neurodegenerative Dz.
Prevents side effects
Anxiety
Thyroid disorders
Autoimmunity
Degenerative joints
Tendon/ligaments
Immunity
Cardiovascular Dz.
Leaky Gut
Anti-ageing
Depression/ neurotransmitters
Diabetes
Coagulation
Mitochondria
Liver/Kidney
Increases GH receptors
CFS/Fibromyalgia
Allergies/MCAS
H-pylori/GERD
Wound healing
Increases glutathione/ antioxidant levels
Muscle/bone
HTN and hypotension
TBI/Cognition
Pain syndromes
Anti-viral, anti-fungal, & anti-bacterial
Administration of BPC-157
Oral and systemic administration significantly improves a wide range of health issues:
Prevents and reverses a wide range of cardiac issues, including HTN, hypotension (POTS), CHF, and arrhythmias, such as A fib, V-tach, PACs and PVCs. 3,14,16,21,28,48,54,56-60,65
Improves a wide range of central and peripheral neurologic, psychiatric, neuro-inflammatory and neurodegenerative diseases via direct effects and indirectly through the gutbrain axis.11-13,15,16,18,23,26,36, 39,42-45,61 Enhances growth hormone-stimulated healing (increases GH receptors on cell surfaces).26
Stimulates musculoskeletal healing and rejuvenation, including muscles, joints, cartilage, bone, ligaments, & tendons.2,17,15,22,25,49, 50,65
Outperforms acyclovir in HSV treatment, amoxicillin for bacterial infections, and Diflucan for fungal infections at 1/1000th the dose.25
Increases tolerance to stress and improves anxiety and depression, outperforming antidepressants.5,6,12,23,44,5 3,56,62,66 Prevents and reverses mitochondria and metabolic dysfunction damage.8
Stimulates wound healing and healthy, youthful skin.4,10,55,56,64
Modulates immunity and can benefit autoimmune disease.15,18,46,49
Protects cells, tissues and mitochondria from a wide range of environmental toxins, mycotoxins, enterotoxins, neurotoxins, heavy metals, and EMFs, prevents medication side effects and overdoses, and inhibits mast cell activation (MCAS) and anaphylaxis.11,12,14,1620,27,29,30,33,43,46,53, 55,57,59,60
BPC-157: GI Peptide
Repairs the gastrointestinal tract and promotes the healing of varied GI conditions. 2-5, 8, 9, 27-37
Is more effective than many medications. 3,4, 10-14
BPC-157 and the Gut-Brain Axis
BPC-157 supports the microbiome & overall health via epigenetic modulation
Chronic infections has broad-spectrum antimicrobial effects
Prevents MCAS & anaphylaxis better than antihistamines
Acts as an antioxidant and reduces reactive oxygen species
Induces the release of serotonin, GABA, dopamine, enkephalins and endorphins, improving depression, anxiety and pain syndromes
1. Sikiric P, et al. Brain-gut axis and BPC 157: Theoretical and practical implications. Current neuropharmacology. 2016 Nov 1;14(8):857-65.]
2. Jones M , et al. Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. Current Med Chem. 2012 Apr 1;19(10):1519-29..
3. Duplancic B, et al. BPC 157 and anaphylactoid reaction iafter intravenous dextran and white egg administration. Europ J Pharm 2014;727(15):75-9
Oral BPC-157 for IBD and MS
Oral BPC-157 was tested in two experimental models for Inflammatory bowel disease and multiple sclerosis
Counteracting and/or healing both gastrointestinal and central nervous system damage.
Significant and dramatic effects were shown grossly, microscopically, functionally and behaviorally.
“Its ability to be orally administered is particularly noteworthy, as there are currently no options for concomitant treatment inflammatory bowel disease and multiple sclerosis.“ 1
and motor disability. J Physiol Pharmacol. 2013 Oct;64(5):597-61
1. Klicek R, et al. BPC 157 heals cysteamine-colitis and colon-colon-anastomosis and counteracts cuprizone brain injuries
BPC-157 and Neurologic Damage
Prevents and reverses central, spinal and peripheral neurologic damage
Axonal and neuronal necrosis & demyelination
Can also help improve mobility, resolve spasticity and improve neurologic recovery
The healing process of the transected nerve was inadequate in all control rats while the BPC-157 treated rats had consistent dramatic regeneration regardless of the route of administration (oral, intraperitoneal, local).
1. Perovic D, et al. BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats. Journal of orthopaedic surgery and research. 2019 Dec;14(1):199..
2. Gjurasin M, et. Al. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regulatory peptides. 2010 Feb 25;160(1-3):33-41.
3. Sikiric P, et al. A behavioral 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, 6tetrahydropyridine. Journal of Physiology-Paris. 1999 Dec 1;93(6):505-12.
4. Kliček R, et al. 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.
5. Tudor M, et al. Traumatic brain injury in mice and BPC-157 effect. Regul Pept 2010;160(1- 3):1-3.
BPC-157: Bone, Tendon, and Ligament Healing
BPC 157 can improve osteoarthritis-related issues, tendon-to-bone and ligament healing
1. Cerovecki T, et al. BPC 157 (PL 14736) improves ligament healing in the rat. J of orthopaedic research. 2010 Sep;28(9):1155-61.
BPC-157 and Urinary Incontinence
BPC 157 can ameliorate stress urinary incontinence
Functional and physiologic improvement in stress and urge incontinence.
Restores blood flow, prevents hypoxia, improves muscle and sphincter function.
Able to heal damaged smooth and striated musculature.
Positively affects leak point pressure.
1. Jandric l, et al. BPC 157 in two different stress urinary incontinence models in female rats. Medical science monitor basic research. 2013;19:93.
Prevents Hepatotoxicity (Alcohol & Other Substances)
Prevents and reverses portal hypertension, NASH & liver lesions
Antibiotics
Alcohol NSAIDS
1. Prkacin I, et al. Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats. Journal of Physiology-Paris. 2001 Jan 1;95(1-6):295-301.
2. Prkacin I,et al. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. Journal of Physiology-Paris. 2001 Jan 1;95(1-6):315-24.
3. Sikiric , et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Current pharmaceutical design. 2013 Jan 1;19(1):76-83.
4. Boban-Blagaic A, et al. 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 Larginine. Medical science monitor. 2005 Dec 22;12(1):BR36-45.
5. Seiwerth S, et al. Revised Robert’s cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator, Curr. Pharm. Des. 2010;16:1224–1234.
BPC-157: Counteraction of Toxic Exposures
Prevents
amphetamine overdose Mold and Mycotoxin toxicity
Inhibits mast cells activation and anaphylaxis better than antihistamines
Prevents and reverses mitochondrial damage from various toxins
Prevents induced hypercoagulation and thrombosis
1. Duplancic B, et al. BPC 157 & anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration. Europ J Pharm 2014;727(15):75-9
2. Sikiric P, et al. Toxicity by NSAIDs. Counteraction by stable gastric pentadecapeptide BPC 157. Current pharmaceutical design. 2013 Jan 1;19(1):76-83.
3. Sikiric P, et al. BPC 157: Novel therapy in gastrointestinal tract. Current pharmaceutical design. 2011 Jun 1;17(16):1612-32.
4. Sikiric P, et al. A behavioral 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, 6tetrahydropyridine. Journal of Physiology-Paris. 1999 Dec 1;93(6):505-12.
5. Kliček R, et al. 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.
6. Tudor M, et al. Traumatic brain injury in mice and pentadecapeptide BPC-158 effect. Regul Pept 2010;160(1- 3):1-3.
7. Krivic A,, et al. BPC 157: Promoted Tendon‐to‐Bone Healing and Opposed Corticosteroid Aggravation. J of Orthopedic Research. 2006 May;24(5):982-9.
8. Sikiric P, et al. Corticosteroid-impairment of healing and BPC-157 creams in burned mice. Burns. 2003 Jun 1;29(4):323-34.
9. Huang T, et al. BPC-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug design, development and therapy. 2015;9:2485.
BPC Counteracts Drug-Related Side Effects
A variety of side effects are induced by neuroleptic and prokinetic drugs, including:
BPC-17 is able to counteract side effects induced by these drugs, including catalepsy, gastric ulcers and prolonged QTc interval and serve as an antidote.
1. Sikiric P, et al. Toxicity by NSAIDs. Counteraction by BPC 157. Current pharmaceutical design. 2013 Jan 1;19(1):76-83.
2. 61.Strinic
Udovicic
Balenovic
D. BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats. Life sciences. 2017 Oct 1;186:66-79.
D, Halle ZB, Luetic K, Nedic A, Petrovic I, Sucic M, Posilovic GZ,
Intragastric administration of 100% alcohol induces a wide range of systemic effects:
Gastric lesions
Intracranial hypertension
Severe brain swelling & lesion
Intracerebral hemorrhage
Vena-caval hypertension
Aortal hypotension
Severe thrombosis
Inferior vena cava congestion
Azygos vein failure
Electrocardiogram disturbances
Myocardiac infarcts
Lung hemorrhage
Liver lesions and congestion
Kidney lesions and congestion
"BPC 157 therapy given intraperitoneally 1 min after the alcohol administration rapidly counteracted these deficits."
1. Gojkovic, S, et al. Robert’s intragastric alcohol-induced gastric lesion model as an escalated general peripheral and central syndrome, counteracted by the stable gastric pentadecapeptide BPC 157. Biomedicines 2021, 9, 1300.
BPC-157
& the Cardiovascular System
Reverses Post-MI damage, fibrosis &
cardiomyopathy
Acts as an angio-modulatory agent & educes and reverses post-MI damage.
Counteracts cardiotoxicity & arrythmias
Prevents and treats arrythmias from medication overdose, ischemia, sympathetic stimulation, & EMFs.
Hypercoagulability
Inhibits hypercoagulation, reduces bleeding time & excessive bleeding if hypocoaguable, and prevents anticoagulant induced thrombocytopenia.
Can improve high and low BP issues and CHF. Benefical in HTN, POTS & CHF
1. Bencic M, et al. Doxorubicin-Congestive Heart Failure-Increased Big Endothelin-1 Plasma Concentration: Reversal by BPC157.J Pharmacol Sci 2004;95:19-26.
2. Gojkovic, S, et al. Robert’s intragastric alcohol-induced gastric lesion model as an escalated general peripheral and central syndrome, counteracted by the stable gastric pentadecapeptide BPC -1 57. Biomedicines 2021;9:1300-24.
3. Stupnisek M, et al. BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin. Thrombosis research. 2012 May.
BPC-157 References
1. Sikiric, P., et al., Stable Gastric Pentadecapeptide BPC 157: Novel Therapy in Gastrointestinal Tract. CPD, 2011. 17(16): p. 1612-1632.
2. 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.
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.
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 enhancesalkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro. Drug design, development, and therapy. 2015;9:2485.
5. Szabo S, Yoshida M, Filakovszky J, Juhasz G. “Stress” is 80 years old: From Hans Selye original paper in 1936 to recent advances in GI ulceration. Current pharmaceutical design. 2017 Aug 1;23(27):4029-41.
6. Sikiric P, Seiwerth S, Rucman R, Drmic D, Stupnisek M, Kokot A, Sever M, Zoricic I, Zoricic Z, Batelja L, Ziger T. Stress in gastrointestinal tract and stable gastric pentadecapeptide BPC 157. Finally, do we have a solution?. Current pharmaceutical design. 2017 Aug 1;23(27):4012-28.
7. Baric M, Sever AZ, Batelja L, et al. Stable gastric pentadecapeptide BPC 157 heals rectovaginal fistula in rats. Life Sciences 2016;148:63-70.
8. Sikiric, P., Seiwerth, S., Brcic, L., Sever, M., Klicek, R., Radic, B., et al., Revised Robert’s cytoprotection and adaptive cytoprotection and stable gastric pentadecapeptide BPC 157. Possible significance and implications for novel mediator, Curr. Pharm. Des. 2010;16:1224–1234.
9. 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.
10. 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.
11. 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.
12. 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.
13. Tudor M, Jandric I, Marovic A, et al. Traumatic brain injury in mice and pentadecapeptide BPC-158 effect. Regul Pept 2010;160(1- 3):1-3.
14. Stambolija V, Stambolija T, Holjevac J, et al. BPC 157: The counteraction of succinylcholine, hyperkalemia, and arrhythmias. Eurp J Pharm 2016
15. 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.
BPC-157 References
16. Sever M, Klicek R, Radic B, Brcic L, Zoricic I, Drmic D, Ivica M, Barisic I, Ilic S, Berkopic L, Blagaic AB. Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats. Digestive diseases and sciences. 2009 Oct 1;54(10):2070-83.
17. Sikiric, Predrag, et al. "Pentadecapeptide BPC 157 after 70% liver resection in rats." (2013): 1093-26.
18. Lojo N, Rasic A, Server AZ, et al. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats. PLOS 2016;11;9:1-18
19. Veljača M, Pavić-Sladoljev D, Mildner B, Brajša K, Krnić Ž, Bubenik M, Stipaničić S, TabakSlošić M, Brnić L, Khan Z, Krznarić Ž. Safety, tolerability and pharmacokinetics of PL 14736, a novel agent for treatment of ulcerative colitis, in healthy male volunteers. InUnited European Gastroentherology Week (10; 2002) 2002 Jan 1.
20. Ruenzi M. A multicenter, randomized, double blind, placebo-controlled phase II study of PL 14736 enema in the treatment of mild-to-moderate ulcerative colitis. Gastroenterology. 2005;128:A584.
21. Mittal R, Debs LH, Patel AP, Nguyen D, Patel K, O'Connor G, Grati MH, Mittal J, Yan D, Eshraghi AA, Deo SK. Neurotransmitters: The critical modulators regulating gut–brain axis. Journal of cellular physiology. 2017 Sep;232(9):2359-72.
22. Kim HN, Yun Y, Ryu S, Chang Y, Kwon MJ, Cho J, Shin H, Kim HL. Correlation between gut microbiota and personality in adults: A cross-sectional study. Brain, behavior, and immunity. 2018 Mar 1;69:374-85.
23. Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in neuroscience. 2018 Feb 7;12:49.
24. Sikiric P, Seiwerth S, Rucman R, Kolenc D, Batelja Vuletic L, Drmic D, Grgic T, Strbe S, Zukanovic G, Crvenkovic D, Madzarac G. Brain-gut axis and pentadecapeptide BPC 157: Theoretical and practical implications. Current neuropharmacology. 2016 Nov 1;14(8):857-65.
25. Jones RM, Mercante JW, Neish AS. Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. Current medicinal chemistry. 2012 Apr 1;19(10):1519-29.
26. Sikiric P. Stable Gastric PentadecapeptideBPC 157, Somatosensory Neurons and Their Protection and Therapeutic Extensions A Survey. In Capsaicin-Sensitive Neural Afferentation and the Gastrointestinal Tract: from Bench to Bedside 2014 Jul 16. IntechOpen.
27. Perovic D, Kolenc D, Bilic V, Somun N, Drmic D, Elabjer E, Buljat G, Seiwerth S, Sikiric P. Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats. Journal of orthopaedic surgery and research. 2019 Dec;14(1):199.
28. Blagaic AB, Blagaic V, Mirt M, Jelovac N, Dodig G, Rucman R, Petek M, Turkovic B, Anic T, Dubovecak M, Staresinic M. Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats. European journal of pharmacology. 2005 Apr 11;512(2-3):173-9.
29. Sikiric P, Šeparovic J, Buljat G, Anic T, Stancic-Rokotov D, Mikus D, Marovic A, Prkacin I, Duplancic B, Zoricic I, Aralica G. The antidepressant effect of an antiulcer pentadecapeptide BPC 157 in Porsolt's test and chronic unpredictable stress in rats. A comparison with antidepressants. Journal of Physiology-Paris. 2000 Mar 1;94(2):99-104.
30. Gjurasin M, Miklic P, Zupancic B, Perovic D, Zarkovic K, Brcic L, Kolenc D, Radic B, Seiwerth S, Sikiric P. Peptide therapy with pentadecapeptide BPC 157 in traumatic nerve injury. Regulatory peptides. 2010 Feb 25;160(1-3):33-41.
BPC-157 References
31. Duplancic B, Stambolija V, Holjevac J, Zemba M, Balenovic I, Drmic D, Suran J, Radic B, Filipovic M, Blagaic AB, Brcic L. Pentadecapeptide BPC 157 and anaphylactoid reaction in rats and mice after intravenous dextran and white egg administration. European journal of pharmacology. 2014 Mar 15;727:75-9.
32. Kang EA, Han YM, An JM, Park YJ, Sikiric P, Kim DH, Kwon KA, Kim YJ, Yang D, Tchah H, Hahm KB. BPC157 as potential agent rescuing from cancer cachexia. Current pharmaceutical design. 2018 May 1;24(18):1947-56.
33. Seiwerth S, Brcic L, Batelja Vuletic L, Kolenc D, Aralica G, Misic M, Zenko A, Drmic D, Rucman R, Sikiric P. BPC 157 and blood vessels. Current pharmaceutical design. 2014 Feb 1;20(7):1121-5.
34. Sikiric P, Krstonijevic Z, Sever M, Lojo N, Drmic D, Zenko Sever A, Baric M, Starcevic N, Buljan M, Zoricic I, Rasic Z. Pentadecapeptide BPC 157 given intraarticulary counteracts knee osteoarthritis in rats (844.11). The FASEB Journal. 2014 Apr;28(1_supplement):844-11
35. 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;28(9):1155-61.
36. 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.
37. Jandric I, Vrcic H, Balen MJ, Kolenc D, Brcic L, Radic B, Drmic D, Seiwerth S, Sikiric P. Salutary effect of gastric pentadecapeptide BPC 157 in two different stress urinary incontinence models in female rats. Medical science monitor basic research. 2013;19:93.
38. Prkacin I, Aralica G, Perovic D, Separovic J, Gjurasin M, Lovric-Bencic M, Stancic-Rokotov D, Ziger T, Anic T, Sikiric P, Seiwerth S. Chronic cytoprotection: pentadecapeptide BPC 157, ranitidine and propranolol prevent, attenuate and reverse the gastric lesions appearance in chronic alcohol drinking rats. Journal of Physiology-Paris. 2001 Jan Prkacin I, Separovic J, Aralicia G, Perovic D, Gjurasin M, Lovric-Bencic M, Stancic-Rokotov D, Staresinic M, Anic T, Mikus D, Sikiric P. Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine. Journal of Physiology-Paris. 2001 Jan 1;95(1-6):315-24.
39. Sikiric P, Seiwerth S, Mise S, Staresinic M, Bedekovic V, Zarkovic N, Borovic S, Gjurasin M, Boban-Blagaic A, Batelja L, Rucman R. Corticosteroid-impairment of healing and gastric pentadecapeptide BPC-157 creams in burned mice. Burns. 2003 Jun 1;29(4):323-34.
40. Salem I, Ramser A, Isham N, et al. The gut Microbiome as a Major Regulator of the GutSkin Axis. Frontiers in Microbiology. July 10, 2018.
41. Strinic D, Halle ZB, Luetic K, Nedic A, Petrovic I, Sucic M, Posilovic GZ, Balenovic D, Strbe S, Udovicic M, Drmic D. BPC 157 counteracts QTc prolongation induced by haloperidol, fluphenazine, clozapine, olanzapine, quetiapine, sulpiride, and metoclopramide in rats. Life sciences. 2017 Oct 1;186:66-79.
42. Radevski F, Peraic P, Dretar V, Masek T, Starcevic K, Pavlov KH, Drmic D, Kralj T, Zlatar M, Seiwerth S, Sikiric P. Stable Gastric Pentadecapeptide BPC 157 in Rats Subjected to High Salt (30%) Diet for One Month Counteracts Hypertension and Compromised Optic Disc Head Circulation and Following Atrophy. The FASEB Journal. 2019 Apr;33(1_supplement):822-.
43. Zivanovic-Posilovic G, Balenovic D, Barisic I, Strinic D, Stambolija V, Udovicic M, Uzun S, Drmic D, Vlainic J, Bencic ML, Sindic A. Stable gastric pentadecapeptide BPC 157 and bupivacaine. European journal of pharmacology. 2016 Dec 15;793:56-65.
BPC-157 References
44. 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
45. 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.
46. 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)
47. 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.
48. Blagaic AB, Blagaic V, Romic Z, et al. The influence of gastric pentadecapeptide BPC-157 on acute and chronic ethanol administration n mice. Eur J Pharmacol 2004;499(3):28590.
49. Lovric-Bencir M, Sikiric P, Hanzevacki JS, et al. Doxorubicine-Congestive Heart FailureIncreased Big Endothelin-1 Plasma Concentration: Reversal by Amlodipine, Losartan, and Gastric Pentadecapeptide BPC157 in Rat and Mouse. J Pharm Sci 2004;95:19-26.
50. Jandric I, Vicic H, Balen MJ. Salutary Effect Of Gastric Pentadecapeptide Bpc 157 In Two Different Stress Urinary Incontinence Models In Female Rats. Med Sci Monitor 2013;19:93-102
51. Tohyama Y, Sikiric P, Diksic M. Effects of pentadecapeptide BPC-157 on regional serotonin synthesis in the rat brain: alpha-methyl- L-Tryptophan autoradiographic measurements. Life Sci 2004;76(3): 345-57.
52. Turkovic B, Sikric P, Seiwerth S, et al. Gastric Pentadecapeptide Bpc 157. A New Stable Peptide in Clinical Phase II for Inflammatory Bowel Disease (Pliva. PL-14736) as Therapy for HSV-1 and HSV-2 Infection. Gastroenterology 2003;124(4):A560
53. 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
54. Duzel A, Vlainic J, Antunovic M, Malekinusic D, Vrdoljak B, Samara M, Gojkovic S, Krezic I, Vidovic T, Bilic Z, Knezevic M. Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights. World journal of gastroenterology. 2017 Dec 28;23(48):8465.
55. Drmic D, Samara M, Vidovic T, Malekinusic D, Antunovic M, Vrdoljak B, Ruzman J, Perisa MM, Pavlov KH, Jeyakumar J, Seiwerth S. Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157, L-NAME and L-arginine. World journal of gastroenterology. 2018 Dec 28;24(48):5462.
56. Hrelec M, Kliček R, Brčić L, Brčić I, Cvjetko I, Seiwerth S, Sikirić P. Abdominal aorta anastomosis in rats and stable gastric pentadecapeptide BPC 157, prophylaxis and therapy. Journal of physiology and pharmacology. 2009 Jan 1;60(S7):161.
57. Sikiric P. Intestinal anastomosis and diclofenac in rats counteracted by pentadecapeptide BPC 157. HealthMED.:747.
58. Djakovic Z, Djakovic I, Cesarec V, Madzarac G, Becejac T, Zukanovic G, Drmic D, Batelja L, Sever AZ, Kolenc D, Pajtak A. Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME. World journal
BPC-157 References
59. Stupnisek M, Franjic S, Drmic D, Hrelec M, Kolenc D, Radic B, Bojic D, Vcev A, Seiwerth S, Sikiric P. Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin. Thrombosis research. 2012 May 1;129(5):652-9.
60. Kim N, Yun M, O YJ, et al. Mind-altering with the gut: Modulation of the gut-brain axis with probiotics. J Microbiology 2018;56(3):172-82.
61. Sikric P, Petek M, Rucman R, et al. A New Gastric Juice Peptide, BPC. An Overview of the Stomach-Stress-Organoprotection Hypothesis and Beneficial Effects of BPC. J Physiol Paris, 1993;87(5):313-27.
62. Rossi M, Johnson DW, Campbell KL. The Kidney-Gut Axis: Implications for Nutrition Care. Ren Nutr 2015;25(5):399-403.
63. Staresinic, et al. Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle. Biomedicines 2022;10:3221.
64. Veljaca M, Chan K, Guglietta A (1995a): Digestion of h-EGF, h-TGF alpha, and BPC-15 in human gastric juice. Gastroenterology 108:761.
Thymosins: Mechanisms of Action
Significant repairing, restoring and healing properties.
The thymus works by activating secondary messengers to affect cell function and epigenetic gene expression.
Stimulates phagocytosis and autophagy.
Stimulate stem cell activity and proliferation.
Modulate the immune system to maintain a healthy a Th1/TregTh2/Th17 as opposed to the pathogenic, inflammatory TH2/Th17/Th9 immune system. Stimulates wound healing by enhanced angiogenesis, cell migration, and promotion of stem cell differentiation.
Needed to maintain normal antimicrobial activity.
The thymus has antiinflammatory properties: decrease inflammatory cytokines
Increases antioxidant and glutathione production.
Increases nitric oxide levels
Needed to maintain healthy Gl mucosa and blood brain barrier permeability, greatly promoting the expression of tight junction proteins that maintain tight junction integrity.
Reduces microglial activation from toxins, EMFs, infections and alcohol. Binds and blocks the effects of neuro/endotoxins/electromagnetic toxins.
Boosts NK function.
Breaks down biofilms and granulomas.
Reduce IL-6 induced immune and mitochondrial dysfunction.
A combination of orally bioactive bioregulators, Immune Peptide A2 (Vilon) and Thymogen was shown to be a superior immune modulator than injectable thymosin alpha-1 and numerous other chosen parameters and endpoints. It is approximately 100 times as potent as injectable thymulin and Thymosin Alpha-1, 1-2,5,8
Thymogen Alpha 1 is a potent synergistic blend of immune-modulating bioregulator dipeptides (only two amino acids long) purified from the thymus gland and lymphoid tissues. 1,2,8
Thymogen Alpha 1 is designed to replace Thymosin Alpha 1, which has generally become unavailable.
Both Thymogen Alpha 1 and Thymosin Alpha 1 have been shown to be especially effective in support of the native and adaptive immune system, including the normalization of absolute counts of T and B lymphocytes, increase in T lymphocyte functional activity, enhanced thymus activity, normalize the CD4/CD8 ratio, increased white blood cell count, and activity, increased chemotaxis and phagocytosis, and the maturation of T-cells. 1-2,5
Both components of Thymogen Alpha 1, Thymogen (Glu-Trp) and Immune Peptide A2 (Lys-Glu), are shown to improve immunity and homeostasis associated with infections and hasten the clearance of infections with a reduced number of days with fever and the length of stay in the hospital.7
Oral Thymic Bioregulator, Thymogen
Alpha 1
A Synergist Blend of Immune Modulating, Thymosin Bioregulator Dipeptides (only two amino acids long), Immune Peptide A2 (Vilon) & Thymogen
Both components of oral Thymogen Alpha 1 are shown to be more potent immune modulators than Thymosin Alpha 1, and even more so when Immune Peptide A2 Vilon and Thymogen are combined.6
While Thymosin Alpha 1 is approved for the treatment of a variety of cancers in a number of countries around the world, the medical literature demonstrates that Thymogen and Immune Peptide A2 have more potent broad-spectrum inhibition of spontaneous and induced cancer with associated increases in survival rate. 1-5
Studies show that Immune Peptide A2 increases lifespan, physical and mental endurance, physical activity, pineal-hypothalamic-pituitaryhormone axis, sexual function, and the ability to handle stress, while also inhibiting thymic involution and improving and protecting mitochondrial function. It also optimizes coagulation hemostasis, prevents hypercoagulability, and improves insulin resistance and gastrointestinal function.
Oral Thymic Bioregulator
Combination, Thymogen Alpha 1
A Synergist Blend of Immune Modulating, Thymosin Bioregulator Dipeptides (only two amino acids long), Immune Peptide A2 (Vilon) & Thymogen
Immune peptide A2 is particularly effective at inhibiting excessive production of hTGFb, C4a, and IL-6, which are key abnormalities in mold illness and CIRS, cirrhosis, chronic Lyme disease, CFS, fibromyalgia, congestive heart failure, diabetes, chronic renal failure, aging skin, leaky gut, peripheral edema, leaky blood-brain barrier, autoimmune disease, and overall aging.
Both Thymogen and Immune Peptide A2 can effectively reverse a wide range of autoimmune, allergic, and inflammatory diseases and allergic conditions and slow the aging process.
Both are shown to reduce cellular senescence by increasing senolytic activity.
It is associated with improvements in numerous conditions, including aging, stress-related immunosuppression, inflammatory disease, chronic infections, cancer, uterine diseases, tissue repair disorders, hypercoagulation, intravascular coagulation, and autoimmune disease. 1-5
1. Morozov, VG, and Khavinson, V.K. (1997), Natural and synthetic thymic peptides as therapeutics for immune dysfunction, international Journal of Immunopharmacology 19, 501-505
2. 2. Tavelev V. et al. (Thymogen in the complex treatmerit of inflammatory diseases of the female genital system). (1992).
3. 3. Kh Khavinson, V., and Anisimov, V. (2010). The role of peptides in aging control: results and prospects of research.
4. 4. Anisimov Vn, et al. (1992) [The effect of the synthetic immunomodulator thymogen on radiation-induced carcinogenesis in rats.
5. Anisimov, V.N., Khavinson Vik. Fau-Marozov, V. G., and Morozov, V.G. (2000) (menunomodulatory synthetic dipeptide L-Glu-L-Trp slows down aging and inhibits spontaneous carcinogenesis in rats.
6. 6. Schuinf, R.S. et al. 1985. A randomized trial to evaluate the immunorestorative properties of synthetic thymosin-alpha 1 in patients with lung cancer. 1. Biol. Response Modif. 4: 147-153
Thymus Preparations vs. Polyvitamins and Mood, SOWB, Energy, Metabolism, Detoxication, Bone Density in 60-74 y.o. Patients.
1. Khavinson V. Peptides and ageing. Neuroendocrinology Letters 2002:23(3) 11-144
2. Anisimo VNN, et al. Effect of synthetic thymic and pineal peptide on biomarkers of ageing, survival and spontaneous tumor incidence of female CBAmice, Mech Ageing Dev 2001, 122(1):41-68
3. Khavinson VKh, et al. Experimental studies of the pineal gland preparation Epithalamin. The Pineal Gland and Cancer: Neuroimmunoendocrine Mechanisms in Malignancy 2001-294-306
THYMOGEN, CANCER & LIFESPAN
Seventy-six, five-month-old female rats were divided into two groups and were treated with only 5 mcg per rat of thymogen (44 rats) or saline (32 rats), 5 times per week for 12 months.
Animals were monitored up to their natural death and all the tumors discover ed were studied microscopically
The maximal life span of the thymogen-treated group was 4.6 months longer than that of the control group.
THYMOGEN, VILON, CANCER,
INFLAMMATORY DISEASE AND LIFESPAN
A year-long treatment with thymogen significantly increased lifespan in rats and reduced overall tumor incidence by 50%, malignant tumor incidence by 70%, and leukemias and lymphomas by 340%
In a second study, five-month-old female rats were exposed to radiation for 12 months; half received thymogen for 5 days per month. The animals receiving the thymogen had significantly reduced rates of radiation carcinogenesis and total cancer occurrence. The thymogen was also found to extend life span and slow the rate of aging.
In the third study, rates were exposed to a bladder carcinogen, with half also receiving Vilon. Rats taking Vilon had a 2-fold decrease in the incidence of preneoplastic and early neoplastic changes in the bladder mucosa and significantly inhibited carcinogenesis.
Thymogen is Effective for Inflammatory Conditions, Chronic Infections, & T1DM
Both thymogen and Vilon are shown to be significantly beneficial for women urogenital inflammatory conditions and inflammation. The authors note a "marked clinical effect... accompanied by more rapid correction of these disorder with a favorable clinical effect." It was shown to normalize immune dysfunction and prevent hypercoagulatory complications
"Thymogen was found to be the most effective in the complex treatment of experimental tuberculosis," increasing lifespan, reducing the index of spleen weight lung density and reversing immunosuppression. Thymogen reverses the immunodeficiency often seen in diabetic patients.
Thymogen Increases Tissue Oxygenation and increases the Healing of diabetic Foot Syndrome by 3.2-Fold
"The data obtained prove the ability of the L-Glu-L-Trp dipeptide to enhance tissue oxygenation. The positive effect of the dipeptide on oxygenation processes in tissues contributed to faster healing of soft tissue wounds, which led to a reduction in the regeneration period, the appearance of granulation tissue in the wound, the onset of marginal epithelialization or complete epithelialization in animals in the experimental group."
"Moreover, it should be noted that the rate of complete epithelialization of wounds with the introduction of dipeptide was 3.2 times higher than that in the control group."
Immune Peptide A2 (Vilon) and Suppression
of Malignancy
Adv Gerontol 2003;12:128-31.
[Combined effect of vilon and cyclophosphane on tumor transplants and lymphoid tissue explants in mice and rats of various age]
O P Barykina 1, et al. PMID: 14743610
Abstract
The experiments were performed in mice with transplanted Lewis lung carcinoma. The injections of synthetic peptide vilon at the doses 1 mg/kg significantly increased the survival of mice. So vilon has possessed the oncomodulating action on the transplanted carcinoma. The synchronous injection both of vilon and cyclophosphane at the doses 100 mg/kg decreases the survival of mice. There was also studied in spleen organotypic tissue culture the effect of vilon and cyclophosphane on the development of explants of rats of various age: 1 day and 2 years old. Vilon stimulated apoptosis both in young and old rats, but the inhibitory effect of cyclophosphane was abolished in the presence of vilon in culture media at the dose 5 ng/ml. The results obtained suggested that perspective preparate in the cancer therapyvilon and cytostatic drugs-must be used not synchronously.
Ansimov V, et al. Mechanisms of Aging and Development; 2001
THYMOGEN, VILON, AND THYMULIN
Thymic peptides are potent immune modulators, anticarcinogens, and anti-inflammatories.
Thymogen and Vilon are orally bioactive and approximately 100 times as potent as injectable thymulin.
CONCLUSIONS
The results of experimental and clinical studies reveal that thymic factors regulate immune response as Thl-cell cytokine agonists and inflammatory responses as proinflammatory cytokine antagonists.
1. Morozov VG, et al. Natural and Synthetic Thymic Peptides as Therapeutics for Immune Dysfunction. Int J Immunopharac 1997:19(9/10):501-5.
Vilon Effects on Immune Deficiency and
Coagulation
Status in Diabetic Patients and Normalized GI Function in Aged Rats
Normalizes Age and Chronic Illness-Related Immune Deficiency, Hypercoagulation, and GI Function
Peptide Bioregulators and Cancer Reduction
experimental gerontology and oncology Ann NY Acad Sci 1994,719: 483-93
1. Anisimo v V.N., et al. Twenty years of study on the effect of pineal peptide preparation: epitalon in
Vilon, Pinealon, Epitalon, Irisin and Telomeres
Irisin is 112 aa myokine protein produced during exercise. It has antiobesity, insulinsensitizing, metabolic stimulating actions, activates telomerase, and improves exercise tolerance and mental working capacity.
The data demonstrates that Vilon, Pinealon, and Epitalon all improve exercise tolerance, and mental and physical working capacity, stimulate the antioxidant system, increase telomere length, and prolong lifespan.
1
2
3 4
5 Pinealon is also shown to be a potent stimulator of serotonin production, stimulates muscle mitochondrial function, promotes and maintains a "trained status," and improves energy metabolism in athletes.
6
Experimental Bio and Med. 2016;160(3):347-9
Higher irisin concentrations are found in young subjects and are associated with a prolonged lifespan, while diminished levels are associated with the elderly, short telomeres, and cardiovascular disease.
Vilon and Pinealon increase telomerase by activating Irisin expression through the FNDC5 gene, while Epitalon induces the expression of the telomerase gene and telomerase activity, promoting telomere elongation (2.4 times) through the GDF11 gene and other mechanisms.
Vilon and Epitalon reduce the expression of the HER2/neu (breast cancer) gene by 2.0-3.6-fold in transgenic mice.
1. Khavinson VKh, et al. Short Peptides and Telomere Length Regulator Hormone Irisin. Bull
WHAT IS TB4 FRAG?
TB4 is 43 AAs long and has multiple domains (active sections) that code for different and overlapping functions HC C
TB4 Active Fragment, the four amino acid bioregulator fragment (1-4) (AcSDKP) of the 43 amino acid full-length TB4 peptide, removes the domain that stimulates mast cells, and is the workhorse of TB4, possessing the immune modulatory, angiogenic, healing, anti-inflammatory, cellular protective, and repair actions of full length TB4
1. Kanasaki M, et al. Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-pength converting enzyme inhibitors. Fibrogenesis & tissue repair. 2011 Dec:4(1):25.
WHAT IS TB4 FRAG?
Compared to full-length TB4, TB4 Frag:
is a more potent antifibrotic
has 10 times the potency of immune modulatory effects.
does not stimulate mast cell activation (segment 16-38).
is orally active (absorbs intact), while full-length TB4 needs to be injected
O... has a significantly reduced molecular weight that allows TB4 Active Frag (Ac-SDKP) to cross the blood-brain barrier and penetrate biofilms.
is a potent inhibitor of TGF-b (a potent activator of mast cells and fibrosis) and subsequent immune activation of coagulation, a vicious cycle of inflammation, immune dysfunction, mitochondrial dysfunction, pinealhypothalamic-pituitary-hormone deficiency, including low thyroid with a normal or low TSH, cognitive dysfunction, sleep disorders, pain syndromes, gastrointestinal dysfunction, and gut-brain axis issues.
1. Kanasaki M, et al. Elevation of the antifibrotic peptide N-acetyl seryl-aspartyl lysyl-proline: a blood pressure independent beneficial effect of angiotensin I-converting enzyme inhibitors. Fibrogenesis & tissue repair. 2011 Dec:4/3) 25
NATURAL ISOMER OF TB4 FRAG
(unique to IP)
It has significant clinical benefits for most chronic illnesses, chronic and acute infections, wound healing, mitochondrial dysfunction, cognitive dysfunction, neurodegenerative diseases, neuropathy, IBS, SIBO, depression, leaky gut (directly heals Gl tight junctions), CHF, chronic kidney disease, and more.
In addition, a naturally occurring isomer of TB4 Active Frag is used, having 20-60 times the half-life and significantly increased activity compared to the standard compound, despite having the same chemical formula. It is also naturally acetylated and amidated.
These properties result in a lack of enzymatic destruction in the Gl tract, improved bioavailability and transport through the lining of the gut, across the BBB, and into the cells and nuclei, increased receptor affinity and activity, and longer half-life (20-50 times). As expected, a much greater clinical benefit is seen for those using the "capped" isomer compared to standard TB4 Frag.
Peptide Fragment of Thymosin B4
Increases Hippocampal Neurogenesis and Facilitates Spatial Memory
"Taken together, these data demonstrate that TB4 frag [AcSDKP] functions as a regulator of neural proliferation and indicate that Ac-SDKP may be a therapeutic candidate for diseases characterized by neuronal loss. Ac-SDKP also increased spatial memory."
O "For the first time, we showed that ẞ-thymosin peptide active fragment, Ac-SDKP, could increase adult neurogenesis, which may be highly relevant in preventing various neurodegenerative diseases by the replenishment of damaged neurons."
1. Kim DH, et al. Peptide fragment of thymosin 4 increases hippocampal neurogenesis and facilitates spatial memory. Department of Medicinal Biotechnology, College of Natural Resources and Life Science and 2 Dong-A Anti-aging Research Center, Dong-A University, Busan 604-714, Republic of Korea
TB4 ACTIVE FRAG REVERSES RADIATIONINDUCED ENDOTHELIAL DAMAGE, AND PERIPHERAL AND CORONARY ARTERY DISEASE AND RESTORES DIMINISHED CARDIAC BLOOD FLOW
1. Sharma et al. Effects of novel peptide Ac-SDKP in radiation-induced coronary endothelial damage and resting myocardial blood flow. Cardio-Oncology 218,4(8):1-14
TB4 ACTIVE FRAG PREVENTS DIABETIC CARDIOMYOPATHY
TB4 Active Frag shows cardioprotective effects in diabetic subjects
Reduces both left ventricular interstitial and perivascular fibrosis
Improves and restores diastolic function
Reduces the expression of hTGF-β1 in myocardial tissue
More effective than Ramipril (an ACE inhibitor) but combination outperformed both compounds alone.
Orange: Control
Green: Ac-SDKP
Yellow: Ramipril
Purple Ac-SDKP + Ramipril
% of perivascular fibrosis
1. Castoldi G, et al. Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyllyryl-proline in diabetic rats. Clinical science. 2009 Nov 2:118(3):211-20,
ORAL TB4 FRAG REVERSES DM I & II KIDNEY DAMAGE
AND FIBROSIS
TB4 FRAG MAX
TB4 Active Frag Max also includes purified low molecular weight thymus peptide lysate, which is over six times as potent as a typical thymus extract.
The peptides range in weight from 1-10 kD compared to standard thymus extract, averaging 130-140kD, which have reduced efficacy due to poor bioavailability of large peptides and destruction by intestinal enzymes.
KPV - The Newest Anti-Inflammatory Peptide
KPV is an orally active C-terminal, three amino acid fragment of alpha-melanocyte stimulation hormone (alpha-MSH), but it has no melanocyte stimulation like its parent compound and other analogs such as Melanotan I & II, and PT141.
It has potent anti-inflammatory, immune-modulatory, and antimicrobial properties.
It is unique because its anti-inflammatory effects are associated with improved immunity and antimicrobial effects.
It is effective against viruses, bacteria, and fungi, being more potent against Candida than Diflucan at 1/1000th the dose and is free of side effects associated with antifungals, antibiotics, and antiparasitics, and works synergistically with the body's immune system and antibiotics.
Effectiveness with Candida vaginitis, has been demonstrated¹2 and "Its role in the cure of HIV patients has also been reported." 3 Recent studies have highlighted the antimicrobial activity of a-MSH against both planktonic and biofilm phenotype of S. aureus strains irrespective of their susceptibility to methicillin.4
When paired with antibiotics for MRSA that was strongly resistant to the antibiotics given, the MRSA lost its method of resistance and became susceptible to those antibiotics.
IP's KPV is a naturally occurring isomer that is acetylated and amidated, making it highly resistant to enzymatic degradation, dramatically increasing the half-life, bioavailability, and target tissue affinity and potency compared to standard KPV. Only available at IP.
1. Catania, et al. Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [AcCKPV 12," Journal of Peptide Research, 2005:66[1]:19-26.
2. Ji, XI, et al. The synthetic melanocortin (CKPV)2 exerts anti-fungal and anti-inflammatory effects against Candida albicans vaginitis via inducing macrophage M2 polarization, PLoS ONE, vol. 8, no. 2. Article ID e56004, 2013.
3. A Catania, Ed., Melanocortins: MultipleActions and Therapeutic Potential, Landes Biosciences and Springer Science Business Media, New York, NY, USA, 2010.
4. Shireen T, et al. Characterization of cell membrane parameters of clinical isolates of Staphylococcus aureus with varied susceptibility to alpha-MSH. Peptides, 2012;37(2) 334-9.20
5. Singh M, et al. Combination of alpha-melanocyte stimulating hormone with conventional antibiotics against methicillin resistant Staphylococcus aureus," PLoS ONE, 2013:8:Article (De73815, 2013
KPV - The Newest Anti-Inflammatory Peptide
The capped isomer has excellent oral bioavailability, being transported across the intestinal lining by the PepT1 transporter that transports a range di and tripeptides.
It is effective at nanomolar concentrations (10-9)
It works both via cell surface receptors and nuclear epigenetic gene modulation interacting directly with the DNA
It suppresses mast cell and microglial activation
It reduces airway inflammation via modulation of IgE and inflammatory cytokines and can induce tolerance to allergens KPV is smaller in size and more chemically stable than alpha-MSH.
KPV improves leaky gut by lowering gut inflammation, increasing gut transepithelial resistance, improving tight junction function and inhibiting the harmful inflammatory effects of LPS.
It can aid in weight loss by activating thermogenesis and reducing insulin and leptin resistance.
has shown to limit symptoms of skin conditions, including itchiness, dryness, redness, peeling, and more.
No study has found any associated toxicity.
It accelerates wound healing and reduces scar formation
It is shown to normalize abnormal gene expression in the hippocampus following acute stress.
The essential anti-inflammatory sequence (KPV) is also essential for its direct antimicrobial efficacy
1. Singh M, et al. Combination of alpha-melanocyte stimulating hormone with conventional antibiotics against methicillin resistant Staphylococcus aureus," PLOS ONE, 2013:8:Article IDe73815, 2013.
2. Pavlov, VA, et al. The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation. Mal Med; 2003; 9(5-8):125-34
ANTIMICROBIAL EFFECTS OF KPV
KPV (MSH 11-13) out-performed fluconazole on inhibition of C. albicans viability
Significantly antimicrobial, including against Candida albicans and Staph aureus at extremely low levels (picomolar range).
1. McManus M, Cincotta A. Advances in Integrative Medicine. Adv Integ Med 2015;2:81-89. 309
1. Khavinson V.Kh, et al. Alpha-Melanocyte Stimulating Hormone: An Emerging AntiInflammatory Antimicrobial Peptide. BioMed Research Int 2014;874610:1-10
The Cholinergic Anti-inflammatory Pathway
A Missing Link in Neuroimmunomodulation
KPV works in part through a cholinergic anti-inflammatory effect via the efferent vagus nerve. This pathway plays a critical role in controlling the inflammatory response through interaction with peripheral nicotinic acetylcholine receptors expressed on macrophages
1. Pavlov, VA, et al. The Cholinergic Anti-inflammatory Pathway: A Missing Link in Neuroimmunomodulation. Mol Med; 2003; 9(5-8): 125-34
KPV inhibits brain damage and damage via anti-inflammatory effects, a reduction of abnormal apoptosis, and suppressing abnormally activated microglial cells.
1. Pavlov, VA, et al. The Cholinergic Anti-inflammatory Pathway. A Missing Link in Neuroimmunomodulation. Mol Med; 2003; 9(5-8): 125-34
Kent Holfrof, MD
Case Studies
Holtrof Medical GROUP
Case Study #1
Massive un-rehabbed TBI, mold
"Since my concussions, I no longer felt joy or fulfillment from my hobbies and everything I do feels like a chore. I've been told this is depression, but I've tried a million pysch drugs, hormones, IASIS and many other standard and functional medicine treatment.
Since the introduction of BPC157, this has started to change. Once I added CerebroPep there was a remarkable change, which started after a few days of taking it."
"My depth perception is improving (things aren't so flat), I no longer struggle to find words, my mind is sharper, my wit
quicker, I wake up refreshed and energized and my ability to manage complex things is improving. I'm remembering to pay bills on time and am beginning to be able to plan things out like finances. My voice of reason is returning and I'm becoming the calm, controlled person I once was. I'm no longer ruled by fiery emotion. This has improved my impulsivity and knee jerk reactions. Believe it or not, I used to perform incredibly well under pressure."
"The changes I have experienced from BPC-157 and CerebroPep [oral Cerebrolysin] have been shocking. Holy cow I'm even writing better!"
Case Study #2: Harriet M, NP, ABAAHP
Integrative practitioner who suffered form 28 years of gastrointestinal disorders which included diagnoses of IBS and Crohn's disease, which began suddenly with severe intestinal bacterial infections after eating undercooked meat at restaurants.
She had seen NUMEROUS physicians (standard, Gl and immunology subspecialists, alternative, and integrative) with little improvement in
her conditions. Gl docs consideringcolon resection. She tried numerous antibiotics, biologics, immunosuppressants, herbal preparations, and more without benefit or had to stop due to significant side-effects.
"I am so happy with the new oral BPC-157, Thymosin Alpha-1, KPV, and TB4-frag/TB4-frag+. These products have significantly changed my life, as well as the lives of my patients. I started taking BPC-157 after 28 years of gastrointestinal disorders which included diagnoses of IBS and Crohn's disease, which began suddenly with severe intestinal bacterial infections after eating undercooked meat at restaurants."
"Prior to these infections I had been a competitive cyclist. I had tried multiple therapies, drug combinations, and diets for 20+ years, with limited success, as my health continued to plummet. I switched to running, frequently dropping out of races due to gut issues. Along with the gut issues came fatigue, brain fog, and memory problems."
"In 2017 I began taking oral BPC-157 from various compounding pharmacies, but the supply was limited, and the amount that I needed to repair my Gl tract was unaffordable at that time, with a bottle of 30-60 capsules costing $250. The recommended one capsule twice daily showed no efficacy. When Integrative Peptides introduced their more potent BPC-157 brand at a significantly lower price, I was finally able to take as much as I needed. The more I took, the more I improved, both in health and in fitness. I have been taking 2 capsules each morning and evening, and 2-3 capsules 1-2 hours prior to exercise."
Case Study #3
Harriet M, NP, ABAAHP
"In 2020, I added TB4-frag, thymogen alpha-1 and Cerebropep. which improved my endurance, as well as my memory. Now at age 66, I am back to doing the same highintensity cycling intervals that I was doing in my late 20's and early 30's. I'm even able to eat a large meal and go for a hard run, with no Gl distress, something I haven't been able to do since my 20's. In addition, I never get sore after a hard workout, and have never even gotten a cold in the past 2 years, no matter how hard I train."
I now have patients on the same protocol, being a great success in their lives. One example is a competitive runner who developed congestive heart
failure and had been unable to raise his ejection fraction despite multiple therapies. After 4-5 months of TB4-frag, we were able to get his EF to the mid-40s and he was able to compete in a half-marathon. Our goal is to get his EF up to 50. I believe this would also entail adding BPC, KPV and Thymogen Alpha-1.
"I am looking forward to any additional peptides that the company will be offering in the near future. Thank you Dr. Holtorf, for all the hard work that you do!"
Case Study #4
"For 7 years, I have been battling Chronic Fatigue Syndrome with CrossFit, yoga, intermittent fasting, meditation, healthy eating, and high-quality health food supplements. As a pastor, I had burn-out from care-taking others."
"The peptides gave me massive surges of energy that lasted 2-3 days, followed by great sleep. My dreams became technicolor vivid where higher beings from other dimensions tutor me on how universal wisdom operates. I thought it might be the Weber laser creating cosmic psychic intervention. However, subsequent peptide IVs without the laser did not stop the dreams. Sometimes, the dreams
Vicky Lee 47 years old, CFS are me running at full-speed for 20 hours accompanied by evolved mentors."
"How I felt in my 30s is how I am starting to feel now in my late 40s, due to oral peptide supplements (CerebroPep, BPC-157, TB4 Frag, and Thymogen Alpha 1). It seems the cells of my body are in phase of "clearing" old or past information the renewal has shifted me at a foundational level. I am experiencing a reboot. Because of this surprise that I'm getting younger instead of older, I must rethink all of my life goals."
Case Study #5 and #6
JK & Lisa (not patients at clinic)
Symptoms: Pots, racing heart, palpitations, nausea, bloated stomach, anxiety, sleep, pain, and much more
JK
"I am very pleasantly surprised how well the peptide combination, BPC157, TB4 Frag, and KPV has helped my POTS and other symptoms (not sure if one or all of them), including racing heart, palpitations, nausea, bloated stomach, anxiety, sleep, and much more. It started improving in a few days and continually improved over a few months. I am so happy!!!"
Thank you, Lisa"
Lisa
"Hi Dr. H, When I started BPC-157, my sleep and pain improved, and my POTS symptoms decreased substantially.
What a great start. Thank you, JK"
Case Study #7
Mary Lee 74 years old, gout
"For several years, I have had gout. This past year it inflamed in my shoulder, knee and feet to the point where it was so painful, I could not walk or sleep. My doctor prescribed Allopurinol 300 mg, Colchicine 0.6 mg, Indomethacin 50 mg, which made my ankles swell up like an elephant."
After a single peptide IV, Weber Laser and Meyers cocktail, the pain was gone. The same day, I celebrated a feast with my family. We had lobster, this giant crab pictured here, cheesecake and other delicious deep fried gourmet foods. No pain! No swelling!"
"In my Zumba dance class, all my friends can tell the difference. They say I look prettier. It might be my attitude. I feel lighter, younger. Before I didn't want to move and I didn't want to live. But now, I feel like my health has come back. I didn't even know that it was missing, until it returned."
"Covid had made my teeth and gums swollen. After the peptides, the swelling went down so that I can now bite and eat normally. Going up a flight of stairs, my heart is always pounding. But after the peptides, I can go up a flight stairs effortlessly with no heart issues."
Case Study #8
Sarcoidosis Patient Told to Go and Die in Hawaii
Mark, a 47 y.o. extremely sick gentleman who was sick for 21 years (mostly bedbound/housebound) with terrible multisystem symptoms. He saw about 50 "top experts" in every specialty. The Mayo Clinic told him that he had Sarcoidosis, but their treatment with prednisone made him worse, so they concluded that his body was shutting down and he must have AIDS even though his test was negative or something worse. They told him to move to Hawaii, get hospice and smoke a lot of pot and die somewhat happy.
He had symptoms of fatigue, night sweats, swollen glands (submandibular, axilla), intermittent fever, muscle pain, weakness, migrating joint pain, shooting pains and peripheral neuropathy, RLS, insomnia, post-exertional fatigue, SOB,
air hunger, very poor endurance, IBS, bloating, palpitations, chest pain (w/u neg), dry burning eyes, dx with uveitis x 1, allodynia, occasional rashes no nodules, painful soles of feet, enlarged veins, eye floaters, brain fog, orthostatic hypotension, anxiety, depression, never refreshed, severe cognitive dysfunction, anxiety, and lichen planus in mouth.
While flying to Hawaii to "die," he happen to sit next to an integrative doctor who told him to call me. He gave me a call, and I said let me guess, these are your symptoms, and rattled off 15 or so. He said, "You are creeping me out-all my doctors said they had never seen such symptoms."
Case Study #9
5 y.o. girl multi-year hx of Crohn's Nonresponsive to aggressive standard treatment-scheduled for colon resection
1 Seeking help
2
3
Numerous Gl doctors, immunologists, and alternative practitioners Medication
Steroids immunosuppressant drugs supplements high dose probiotics Reaction Non-responsive to all standard and alternative treatments Severe bloody stools Scheduled for colectomy
Case Study #9
CROHN'S DISEASE
1 PROTOCOL
We recommended oral BPC-157, oral TB4 Frag, oral KPV, Thymogen Alpha-1, and LDN, along with ozone, oral IgG, and some other theraples
2 BPC-157
Mother wanted to do one thing at a time, so we did BPC-157. Mother noted improvement of about 30%
3 FINDINGS
She was found to have low NK cell function and iron levels with a high hTGFb and C4a. She was found to have Hashimoto's with a TSH of 5.9, low normal free 13, midrange free T4, high-normal rT3, low IGF-1 and IGFBP3.
4
T3SR
She was given T3SR, 2.5-5-10-15 and TB4 frag was added along with growth hormone (did not do secretagogues
5 KPV
We then added KPV and increased T3 to 25 mcg.
6
RESULT
She ended up doing very well with very infrequent GI discomfort and extremely rare bouts of any bloody stools.
Case Study #10
Case Study of Multi-system Dysfunction 37-year-old with long hx CFS
Severe fatigue, insomnia, anxiety, cognitive dysfunction, night sweats, POTS, palpitations, interstitial cystitis, swollen legs, livedo reticularis, urinary incontinence, hari loss, irregular periods, multiple food and other allergies, and other multisystem symptoms. Mostly house and bed-bound.
Been sick for over 9 years-"has seen too many doctors to count." Dx with CFS, FM, MCAS, POTS, pre lupus, preRA, antiphospholipid syndrome (resolved), Lyme test negative.
Ended up positive for Lyme, bartonella, mold, CIRS, immune activation of coagulation, severe).
At visit three, the patient was feeling much better with T3SR, biest, progesterone, 6-8 peptides, ozone, Weber laser, a short course of antibx, NAD+, Poly MVA, PC-resolution or dramatic improvement in most all symptoms, but she continued to suffer from anxiety, insomnia and could not get NK cell function above 5 LU (nl>30).
Asked about potential EMF sources: Has Wi-Fi router in bedroom, sleeps with iPhone, TV, house alarm, smart thermostat and TV. We did not have Thymogen Alpha 1 or improved version of peptides at the time. We will see how she improves with the improved peptide formulations, add 5-amino-1 MQ, Dihexa, epitalon, high dose thymogen Alpha-1, LL-37, LDN, DSIP, mitochondrial peptides and supplements, ketamine assisted psychotherapy, and brain, vascular, and other bioregulators and consider SOT, senolytic therapy and new more potent stem celfa
Case Study #11
Recommended that she turns off her Wi-Fi at night, flip the breaker to the bedroom at night, turn the phone Wi-Fi and blue tooth off, and keep the phone outside of the bedroom at night. Pt returned several months later, noting significant improvement in insomnia (feels getting some deep sleep, which she felt she never got before). Anxiety was better and felt overall much healthier.
I asked about what she does in a typical day; she mentioned that she goes out with her husband in his Tesla. I told her to drive her gas-powered car instead, but she said she wasn't ready to drive yet. She said she'll try to not go very often with her husband. Also, added and adjusted several
Case Study of Multi-system Dysfunction 37 year old with long hx CFS therapies
and drew a set of labs.
Pt returned 3 months later, stating that her anxiety was dramatically better if she doesn't drive in the Tesla, and she was driving her gaspowered BMW.
Case Study #12
Traumatic Brain Injury
A doctor suffering from severe debilitating TBI commenting on the effects of samples of peptides and KJ BioPharm peptide cream given to him at a conference
Thanks for your response, Kent. And thanks for the miraculous treatment in Orlando!"
"Thank you, Lori; however, I was not just sending compliments. I am serious; the topical peptide cream is amazing, at least for me. With never-ending gratitude."
He sent an email to his colleagues in a doctor chat group
"Dear Colleagues,
At the ILADS conference in Orlando, Dr. Holtorf and Juan gave me peptides and a sample of a peptide serum to apply to my head for the symptoms of TBI.
It is the single most effective therapy that I have noticed. The peptides are truly a new and important component of my personal recovery."
"My name is Gina Cubero, and I am the proud mother of Jesse, a highly decorated combat war Veteran. My son served six years in the Air Force as a Special Forces Operator with multiple deployments including a combat deployment to Afghanistan. As an Air Force Combat Controller, he was involved in very intense combat, frequent extensive toxin exposure, PTSD, anxiety, depression,, fatigue, weakness, Gl dysfunction, and brain fog and significant stress and trauma. Jesse coped with the significant physical and psychological trauma from horrific combat experiences. But, on March 16, 2022, he was found on the ground unconscious with barely a pulse."
I received the call from an ER doctor that my son was in very critical condition with rhabdomyolysis, severe cardiomyopathy (heart failure) and acute kidney failure. I flew from Austin that same day to see my 28year-old son in a coma, on a ventilator and dialysis machine. His eyes were taped shut and there were tubes connecting him to 6 different machines."
Case Study #13
Special Forces Veteran
On 3/22/22 Jesse was released from the ER and sent home with some directions. Jesse was unable to communicate clearly and needed 24/7 care. On 3/25/22 Jesse collapsed again, had what was felt to be a seizure and was rushed back to ER. I was told to take him to the VA Neurology. His short term and long-term memory were not functioning. The neurologist told me that he will possibly need to be on seizure medicine for the rest of his life due to hippocampal scaring. Jesse's lower extremities were numb and weak with little functioning, making him unable to walk."
On 4/9/22 Jesse's lower extremities numbness started going away, but the numbness was now being replaced with extreme burning pain and nerve damage. The left leg that has a rod in the tibia from a military accident, causing him the excruciating pain."
Case Study #13
Special Forces Veteran
"The pain was unbearable, and he was unable to move his toes nor put any weight onto the left foot. The wind from a window blowing on his foot caused extreme pain. There was no relief from the pain that shot up to an 8 or 9 at night. I remember him saying, that if this pain continues, he would rather have his leg cut off. I was up at night with him around the clock.
I continued to contact his VA doctor for help, but nothing worked. We were finally referred to a pain specialist for the hyperesthesia that he had but was told to wait a couple more weeks and at that time a nerve
block would be inserted into his spinal cord. This was not something that Jesse nor I wanted. Jesse was not doing well mentally nor physically. The lack of sleep and depression was alarming. He was unable to eat nor care for himself."
"On 4/27/22 Jesse's MRI showed hippocampal and temporal lobe lesions. He suffered from severe memory loss, depression and anxiety. He expressed that he felt completely empty, and that life has no color. The VA neurology group just stuck with their seizure diagnosis and had little interest in the depth of his suffering."
Case Study #13 Special Forces Veteran
"The VA and numerous out of network specialist doctors were unable to do anything for Jesse. It was a dark time. We heard of Kent Holtorf through a friend and Dr. Holtorf agreed to see Jesse. The friend mentioned that Dr. Holtorf mentioned a new cream that he wanted to try. I have to say that we had little confidence that a cream would be of much help with such a severe condition. We were discouraged."
"We did not have high expectations, but we kept our appointment on 5/3/22 1 remember them putting this cream (*1) on Jesse's foot and about ten minutes later, the assistant said he was going to slap Jesse's leg. I thought he had to be kidding because he had the most severe terrible supper sensitive skin pain, allodynia, where the slightest touch would cause IMMENSE pain. But he did multiple times-I was initially horrified but couldn't believe the fact that Jesse calmly said that it didn't hurt!!! It was astonishing."
"They then told Jesse to bend his toes, which was not possible and associated with severe pain for some time. But the cream was immediate pain relief there, as well. Prior to the cream being applied Jesse was unable to move his toes nor flex his foot."
(*1) The cream was formulated about a week prior and consisted of 1054 peptides (tested via via LC/MS/MS). Many were stabilized, modified, converted to lipopeptides, and/or attached to skin penetrating peptides.
No steroids or local anesthetics were part of the cream.
Case Study #13 Special Forces Veteran
"Dr. Holtorf had squeezed us in, so he asked if we could come back in five days so he could do a more extensive workup and treatment. They gave us the cream and a lab slip for blood work and sent us on our way. We were certainly more encouraged than we had ever hoped."
"Jesse was able to finally sleep at night Pretty much within 3 days his pain level went from an to a 4 at night. If he woke up, he would apply the cream and go right back to sleep. During the day, Jesse would apply the cream and was able to move about slowly with very little pain. Life become tolerable with the cream.
On 5/8 Jesse returned for his appointment. He received oral, sublingual and injectable peptides in his legs and a small amount of exosomes (*2), IV ozone, and a number of other things. We were sent home with oral peptides, as well. He make us promise that we would get the lab work done."
Within 3 days of treatment, he was starting to walk without limping and was able to begin low impact activities. Sleep improved and he only woke maybe 2 or 3 times at night. When he woke, he put on a little cream and a couple minutes later he was again asleep. Jesse was able to stand up all day on Memorial Day (5/30) and feed his fellow veterans at the West LA VA Hospital. Jess also volunteered to bring food to some of the guys in their rooms and talk with them. So many of them just wanted to have a visitor and were so inspired with Jesse's quick transformation."
Jesse stated that the oral peptides immediately (within days) relieved his depression, anxiety (PTSD), and pain. By this time the cream has only been used maybe once before bed. Jesse now sleeps a solid 8 hours and sleeps without pain. He is now able to bend his toes completely and walk.
What would you do at this point?
KH- Patient doing well with little pain, depression and anxiety essentially gone. No benefit from treatment from a number of neurologists (they felt the most likely cause was that he had a problem with pot) Very minimal pain and almost full use of foot Did more of the same and-if relapses-consider IV ketamine/NAD. Pushing to get labs. Family is ecstatic.
(*2) Ivs Ozone, IV peptides, poly MVA, PC, IV silver, Myers, Vit C, (Argentyn), MOTSC, TB4, AOD. Weber laser. Amino acids, nutrients, vit C, Mg+,
PPEMF, told to get red light therapy and hyperbaric if possible. Also recommended rectal ozone.
Case Study #13 Special Forces Veteran
5/20/22 KH-Jesse got his labs done but took Quest slip to Labcorp so many tests were not done or done incorrectly. 5/20 labs did show (see column to right) low NK cells, low thyroid, high ACTH with low cortisol, low WBC, immune activation of coagulation, high hTGFb and C4a. + 45 kd IgG Lyme-present in about 5% of normals.
Started Jesse on IV ketamine with NAD, methylene blue, heparin, Fibrinex, and DIHEXA. Trying to get follow-up labs, labs that were not done and maybe some specialty labs, but pt and family are not very motivated because he is doing so well
Labs: TSH 3.1, high normal fT4, low normal fT3, high normal rT3, cortisol 7, ACTH 22, low WBC,
Coag: high D-dimer, TAT complex, low Pt/PTT, high fibrinogen, high SFM, abnormal protein C, activity nl protein S
High hTGFB, C4a, high platelets, high mean cell hemoglobin. Leptin11, hgA1c 4.9, 2? IgG toxic molds.
Positive 45 kd band WB. Pos Mycoplasma IgG
Started on IV ketamine with NAD. Amino acids and peptides. Nasal Ozone
Sq heparin titrated up to 5000 iu bid SQ with Fibrinex, oral IgG, spore-based probiotics, broad-spectrum binder, PQQ, MitoQ, amino acids, 20 mg melatonin strips
Ramped up T3SR 10-65 mcg
Cortisol 5-10-15-10-5-0ff with Adrenal repair. 397
Case Study #13 Special Forces Veteran
"7/24/22- Jesse is working out on a regular basis, sleep is good and his appetite is back. He has returned to working out in the gym and his brain function has improved tremendously due to the peptide treatments and IV's. He was able to travel to visit another CCT buddy and they went hiking and camping in Utah. Jesse is now reading a book a week and it so amazing considering just a couple months ago he was unable to retain anything he read and had to keep rereading."
Continue IV ketamine Q week-will pause stop in two weeks.
Doing well on orals. Pushing IV PC, aminos, glutathione, nutrients, ozone, weber laser.
Will continue to monitor
Get f/u head CT at some point and some specialty labs.
Case Study #13 Special Forces Veteran
MAJOR UPDATE: All veterans, including Jesse, were found to have massive amounts of toxins, severe immune dysregulation (Th2/Treg to Th2/Th17 shift), with low NK cell activity, most with elevated C4a and hTGFb, massive amounts of toxins, positive for borrelia and often multiple coinfections, and all have antibodies to their brains and multiple receptors, such as serotonin, dopamine, norepinephrine, GABA, (PANS).
It is not surprising why the standard treatment of antidepressants and antipsychotics don't work with the veterans. The fact that they all had a chronic borrelia and often multiple coinfections is interesting; the thought is that the likely source is fort Bragg in North Carolina where they trained in deep brush for many weeks.
An interesting study on nonresponding patients with TBI found that a frequent cause is Lyme disease. Also, chronic Lyme disease is associated with a twelve-fold risk of substance abuse, which is a major issue with veterans.
Armed with this information, directed multi-system treatment is resulting in significant and rapid benefits.
Case Study #14
42 y.o. woman thyroid patient
Complaint
inability to lose weight, ongoing depression on antidepressants, fatigue and muscle pain.
Diagnosis
fibromyalgia, bipolar depression, type II diabetes.
Medication
Metformin, Effexor, Lipitor. Vicodin for pain. Numerous antidepressants and Lyrica without benefit.
Labs
TSH of 1.2, free T4 of 1.7 (0.8-1.8), free T3 of 2.7 (2.3-4.2), positive four bands on IgG WB for Lyme.
Case Study #14
What is the chance of low thyroid levels contributing to her symptoms?
1. Overweight
• Donders, et al 36% chance
• Ford et al all obese patients
• Krotkiewski, et al 50 mcg of T3 to obese patients partially compensated for their inherent thyroid deficiency with resultant improvement in CV risk factors such as elevated cholesterol and insulin resistance
2. Chronic Dieting
• Araujo, et al-50% reduction in T4 to T3 conversion (no change in TSH) with chronic dieting
• Leibel, et al 25% lower metabolism with chronic dieting
3. Diabetes
• Pittman et al- 42% reduction in T4 to T3 conversion
4. Depression
• Kelly, et al, Posternak, et al and Star*D report - T3 is safer and more effective than antidepressants.
5. Statins
• Seth, et al- Statins artificially lower TSH, making the TSH unreliable
Case Study #14
What is the chance of low thyroid levels contributing to her symptoms?
6. Pain meds
• Pain and pain meds shown to reduce D1 (cellular T4-T3 conversion), increase D2 (increase pituitary T4-T3 conversion, lowering TSH), increase D3 (increasing rT3 with resultant decreased thyroid transport into cells (there is no rT3 produced in the pituitary)
7. CV risk
• Hak et al - low-normal thyroid is associated with higher CV risk than having high cholesterol, HTN, diabetes or smoking.
8. Positive LD
• Positive LD with many markers for Th1/Treg to Th2/Th17 shift causing mitochondrial dysfunction, excessive oxidative stress, CDR and subsequent decreased thyroid transport in peripheral cells (not the case in pituitary), suppressed D1 so reduced T4 to T3 conversion, increased D3 with subsequent increased rT3 (not in pituitary), and increased D2 so increased T4 to T3 conversion in pituitary and suppression of TSH (central hypothyroidism not detected on standard TFTs).
Case Study #14
What can be done to further evaluate her thyroid function?
Signs & Symptoms
• Low body temp (97.4) inability to lose weight, dry skin Constipation, course skin (heel & elbows).
• cold skin. & extremities
• Zulewski, et al - more than five very common symptoms have a positive predictive value of being hypothyroidism > 96.9%.
Thyroflex Test
• Visually had a slow relaxation phase of ankle reflex and confirmed with a Thyroflex test of 190ms (normal < 110ms).
• Maier, et al Shown in BMJ to be a better determinant of hypothyroidism than an elevated TSH.
RMR
• Found to have a low resting metabolic rate (RMR)-22% lower than expected for a person of her weight and gender, which is a gold standard for hypothyroidism (hypometabolic
Case Study #14
What if lab tests reveal?
• SHBG 32 mg/dl (>70): measure of tissue (liver) thyroid and estrogenlevels.
• Leptin 22 (< 12): Leptin resistance (TSH not reliable).
• Insulin 16.
• Rt3-high normal associated with decreased thyroid transport into thecell showing that this patient has low intracellular T3 levels and T4would not be optimal for this patient..
• CRP 3.2 (<1.0): Reduced T4-T3 conversion and suppressed TSH·
• D-dimer 1.8 (<0.5); PF 1 & 2, SFM and TAT complex elevated: PositiveImmune Activation of Coagulation-thyroid resistance.
• CD4/CD8 < 2.5.
• High Trig or low HDL: metabolic syndrome-decreased T4T3conversion.
• High C4a, HTGFB, or ECP or low NKC function: Significantinflammation-thyroid resistance (consider chronicinfection/Lyme/CIRS disease workup)
Diagnosis (Thyroid Labs)
Symptoms
Signs on physical exam
o Look at T3 to reverse T3 (t3/rT3) ratio(should be >12)
o Free T3 should be above 3.5
o Reverse T3 greater than the mean
o TSH greater than 2.0 is significant
o Usually low normal free T3, normalTSH, high normal free T4, and aboveaverage reverse T3
o SHBG < 70 for women; <30 for menLow WBC
o Leptin> 12 Insulin > 6
o Toxic Mold IgG
o IL-6
BMR
Reflex speed (<110ms) Thyroflex
o High C4a, ECP, HTGFB,
o Free T3/Free T4 < 3
o TPO/antithyroglobulin AB
o Iron/ferritin
o HgA1c
o Lipids
o lodine
o CRP
o Cortisol/ACTH/DHEA
o LH/FSH
o Vit D. < 60
o CD4/CD3 <2.5
o Anti-myelin AB
Body Temp
Pulse
o Testosterone (Calculate freetestosterone manually)
Resources: Non-profit National Academy of Hypothyroidism
1. On the non-profit National Academy of Hypothyroidism (NAHypothyroidism.org) there is a computerized algorithm where you can plug in the above laboratory values of your patients to determine the likelihood that they suffer from tissue or cellular hypothyroidism, despite having normal thyroid function tests (TFTs), and would likely benefit from thyroid (usually T3SR) replacement.
2. There are also copies of laboratory recs to use for your patients for different scenarios ., as well as a variety of useful articles, forms, consents, dosing sheets, patient questioners, and much more.
3. There will be a map of doctors that treat likely hypothyroid patients with normal TFTs, so please provide all your clinic information it you want to be included, as we get significant numbers of patients looking for such doctors.
4. I would recommend that you download the following papers (many being published and peer-reviewed: Thyroid Hormone Transport into Cellular Tissue; 2) Peripheral Thyroid Hormone Conversion and Its Impact on 15H and Metabolic Activity; 3) Thyroid 101 eBook; 4) Hormones in Wellness and Disease Prevention; Common Practices, Current State of the Evidence, and Questions for the Future, 5) Harmane Replacement Therapy in the Geriatric Patient: Current State of the Evidence and Questions for the Future- Estrogen, Progesterone, Testosterone, and Thyroid Hormone Augmentation in Geriatric Clinical Practice. Part 2 (Thyroid section), 6) The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol, Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions In Hormone Replacement Therapy ?, 7) A Confounding Condition: Treating chronic fatigue syndrome and Fibromyalgia requires addressing the underlying problems; 8) Diagnosis and Treatment of Hypothalamic Pituitary-Adrenal (HPA) Axis Dysfunction in Patients with Chronic fatigue Syndrome(CFS) and Fibromyalgia (FM) (with peer-reviewed published outcomes); 9) Why Doesn't My Endocrinologist Know All of This ?; and 10) Mold Illness and the Holtorf Updated Peptide Protocol for the Rapid Treatment of CIRS (HUPPRTOC).
5. These may save your butt someday
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