Link: https://youtu.be/_DfqnpSbMfE

Duration: 168 min

Transcript: Download plain text

Short Summary

Dr. Abu Bakri, an internal medicine physician specializing in peptides, hormones, and circadian biology, joins Andrew Huberman to discuss the rapidly evolving peptide therapeutics landscape, covering BPC-157's healing potential and regulatory challenges, EDR and thymus peptides for longevity and immune function, and GLP-1 drugs enabling 50-100 lbs weight loss in clinical practice. The episode emphasizes that without foundational health basics in place, peptide therapies offer limited benefit, and that the $5-10 billion gray market peptide industry urgently requires proper clinical trials to establish safety and efficacy for millions of users.

Key Quotes

1. "We don't naturally make BPC157. That's what you'll commonly hear online. We make BBC the big uh protein." (00:07:17)
2. "LD50 is is the dose of which would kill 50% of the animals if it was administered to them. So we don't even know what that is." (00:20:23)
3. "Everything's from China." (00:35:34)
4. "The API for all these active pharmaceutical ingredients comes from China. There are no such thing as Americanmade peptides." (00:35:30)
5. "There's no signal from the animal literature on BPC57 for for you know cancers. Now that all that literature comes from one group." (00:43:03)

Detailed Summary

Huberman Lab Podcast: Peptide Therapeutics with Dr. Abu Bakri

Episode Overview

This Huberman Lab episode features Dr. Abu Bakri, a 33-year-old internal medicine physician specializing in peptides, hormones, and circadian biology, who provides an extensive clinical and research perspective on peptide therapeutics. The discussion covers BPC-157, EDR (formerly Pinealon), thymus peptides, GLP-1 drugs, and the broader peptide landscape, emphasizing both the promise and regulatory challenges of these compounds. The episode emphasizes that without foundational health basics in place, peptide therapies offer limited benefit, and that the $5-10 billion gray market peptide industry urgently requires proper clinical trials to establish safety and efficacy for millions of users.

BPC-157 Discovery and Origins

BPC-157 (Pentadecapeptide BPC) is a 15-amino-acid peptide fragment derived from a larger 40,000-dalton protein called BPC, which humans do not naturally produce. Croatian researchers discovered the peptide in 1991 by investigating Ivan Pavlov's earlier work on gastric juices, theorizing that the gut must contain protective compounds since stress damages the gut lining. The researchers named BPC-157 an "anti-stress compound" based on their observations of its effects in animal models, with Dr. Cric holding one of the patents on the compound.

• BPC-157 was discovered by Croatian researchers in 1991 building on Pavlov's work on gastric juices
• The peptide is a 15-amino-acid fragment derived from a larger 40,000-dalton protein humans do not naturally produce
• Researchers theorized that the gut must contain protective compounds since stress damages the gut lining
• The compound was named an "anti-stress compound" based on observations in animal models
• Dr. Cric, a Croatian researcher, holds one of the patents on BPC-157

BPC-157 Mechanism of Action

BPC-157 accelerates healing of tendon, ligament, and nerve pathways in animal studies, including effects on the central nervous system where nerves typically do not regenerate. The peptide increases VEGF (vascular endothelial growth factor) signaling to promote blood vessel formation and modulates nitric oxide synthesis for wound healing through blood vessel dilation and cell recruitment. Unlike typical corticosteroids that slow wound healing, BPC-157 continues or improves healing when administered with corticosteroids.

• BPC-157 increases VEGF (vascular endothelial growth factor) signaling to promote blood vessel formation
• The peptide modulates nitric oxide synthesis for wound healing through blood vessel dilation and cell recruitment
• In tendon models, BPC-157 increased growth hormone receptors, theoretically allowing more growth hormone to dock and cause tendon outgrowth
• Unlike corticosteroids that slow wound healing, BPC-157 continues or improves healing when administered with corticosteroids
• Animal studies show accelerated healing of tendon, ligament, and nerve pathways, including effects in the CNS where nerves typically do not regenerate

BPC-157 Animal Research and Clinical Trials

Researchers injected BPC-157 at 1000x normal dose in animals with no observed adverse effects, though the LD50 remains unknown, preventing FDA approval. Small Phase 1 and Phase 2 trials on rectal BPC-157 enemas for ulcerative colitis were conducted by the Croatian research group in the early 2000s involving approximately 40 patients, showing positive signals. A Phase 2 trial for hamstring injuries is currently underway in the United States by an orthopedic group on the East Coast, while Chinese research groups replicated ulcerative colitis work using 80mg enemas compared to typical human injection doses of 100-200 micrograms daily.

• Researchers injected BPC-157 at 1000x normal dose in animals with no observed adverse effects
• The LD50 remains unknown, which is a key factor preventing FDA approval
• Small Phase 1 and Phase 2 trials on rectal BPC-157 enemas for ulcerative colitis involved approximately 40 patients in the early 2000s
• Chinese research groups replicated ulcerative colitis work using 80mg enemas compared to typical human injection doses of 100-200 micrograms daily
• A Phase 2 trial for hamstring injuries is currently underway in the United States by an orthopedic group on the East Coast
• In mice studies, BPC-157 demonstrates a homeostatic mechanism preventing intoxication from alcohol or methamphetamine and preventing withdrawal symptoms

BPC-157 Regulatory Status and Gray Market

In late 2024, BPC-157 and approximately 20 other peptides were moved to FDA Category 2 compounding list (do not compound), but it was removed from that category in April 2025, leaving it in regulatory limbo. Peptaibrate (PDA/Pentadecapeptide Arginate) is essentially BPC-157 with a slightly different formulation that sellers use to circumvent regulations. BPC-157 is available as an oral supplement in the US because it has never been approved as a medication, creating a legal gray area similar to how creatine is treated as a supplement. The gray market peptide industry represents an estimated $5-10 billion market in 2025 and is projected to grow.

• BPC-157 was moved to FDA Category 2 compounding list in late 2024 but removed in April 2025, leaving it in regulatory limbo
• Peptaibrate (PDA/Pentadecapeptide Arginate) is essentially BPC-157 with a slightly different formulation used to circumvent regulations
• BPC-157 is available as an oral supplement in the US because it has never been approved as a medication
• The gray market peptide industry represents an estimated $5-10 billion market in 2025
• All active pharmaceutical ingredients (API) for peptides, including semaglutide, originate from China
• Gray market vendors like Peptide Sciences sold products labeled "for research purposes only" with customers paying via Venmo or Zelle with ever-changing account names
• Standard pharmaceutical manufacturers like Novo Nordisk and Eli Lilly produce the most stringently tested peptides, while compounding pharmacies vary in quality

BPC-157 Clinical Experiences and Physician Perspectives

An internal medicine physician who works on hospital wards from ER to ICU admitted to using BPC-157 through a compounding pharmacy and personally experienced healing of a grade 2 tricep tear in 3-4 weeks instead of the typical 3-month recovery period. The physician noted systemic transfer effects from local injection—his shoulder improved from an elbow injection. Physicians risk license revocation for prescribing non-FDA approved peptides in hospital settings, and no malpractice provider covers physicians for such prescriptions except high-risk providers.

• Dr. Abu Bakri personally experienced healing of a grade 2 tricep tear in 3-4 weeks instead of the typical 3-month recovery using compounded BPC-157 through a pharmacy
• Systemic transfer effects were observed from local injection—his shoulder improved from an elbow injection
• Physicians risk license revocation for prescribing BPC-157 instead of standard medication in hospital settings
• No malpractice provider will cover physicians for prescribing non-FDA approved peptides except high-risk providers
• Speaker 2 expressed skepticism that 250 micrograms (the dosage some orthopedic groups use) is sufficient, suggesting online peptide sites influence dosing without data support

EDR (Formerly Pinealon): Soviet Peptide Research

Dr. Vladimir Khavinson, a Soviet researcher tasked with protecting soldiers' eyes from supposed US laser attacks and counteracting accelerated aging in submariners and astronauts, discovered Pinealon (renamed EDR). EDR appears to bind to DNA promoter regions and assist transcription factors in accessing DNA, effectively turning on genetic programs. Cavson researched pinealon extensively in the 1970s Soviet Union on neuronal tissue, animal studies, and athletes but never studied REM sleep because sleep tracking technology didn't exist. When taken at the beginning of the night, EDR reduces deep slow-wave sleep and significantly increases REM sleep.

• Dr. Vladimir Khavinson discovered Pinealon (renamed EDR) while working for the Soviet military
• Khavinson was tasked with protecting soldiers' eyes from supposed US laser attacks and counteracting accelerated aging in submariners and astronauts
• EDR appears to bind to DNA grooves, exposing promoter regions and acting like a transcription factor to modulate gene expression
• EDR activates PPAR alpha, PPAR gamma, and iris pathways, modulating GDF11, SOD1, SOD2 to improve brain metabolism and neuronal oxidative state
• When taken at the beginning of the night, EDR reduces deep slow-wave sleep and significantly increases REM sleep
• Used approximately 3 times per month, EDR produces lingering effects that improve REM percentage on nights without injection
• Oral EDR dosages range from 0.5mg to 3mg; Russian formulations are 200 micrograms
• Vivid dreams with unusual color and quality are a notable effect, especially at higher doses

Thymus Peptides and Immune Function

The thymus secretes hormones and develops T cells, which travel from bone marrow to get trained in the thymus to recognize foreign invaders and cancer cells while not attacking self-tissue. Thymic involution is the process where the thymus slowly shrinks from puberty until death, with the majority of shrinkage occurring in the 20s and 30s under pressure of androgens, estrogens, progesterones, and corticosteroids. Thymosin alpha 1 was FDA approved as Zidaxin for children born without or with malfunctioning thymuses, and is approved in other countries for hepatitis B, hepatitis C, and certain cancers.

• The thymus develops T cells that recognize foreign invaders and cancer cells while not attacking self-tissue
• Thymic involution begins at puberty with the majority of shrinkage occurring in the 20s and 30s under pressure of androgens, estrogens, progesterones, and corticosteroids
• At age 15, a person produces 10 to the eth magnitude of naive T cells every day, decreasing dramatically with age
• T cells live somewhere between 10 and 15 years, which relates to when the mortality window kicks in for various disorders
• Thymosin alpha 1 was FDA approved as Zidaxin for children born without or with malfunctioning thymuses
• Thymosin alpha 1 is approved in other countries for hepatitis B, hepatitis C, and certain cancers
• Thymosin beta 4 is a 43 amino acid peptide that helps regulate the actin cytoskeleton in cells, enabling immune cells to reorganize quickly
• Thymulin is a nine amino acid peptide that serves as the main thymus hormone, is zinc-dependent, and decreases dramatically with age

Thymus Involution, Biomarkers, and Clinical Implications

Thymic atrophy occurs after every infection, not just with age; modern stressed people who get sick repeatedly never get full thymus rejuvenation. The lymphocyte-to-monocyte ratio on a CBC ($3 lab test) serves as a practical thymic score and general immune health indicator, yet the speaker estimates zero out of 100 randomly pulled physicians in the US know about this metric. Removing thymus tissue leads to a mortality signal within the first 5 years after open heart surgery, with higher rates of cancers and autoimmune diseases. A 2026 Nature paper using MRI imaging found that people with higher thymic scores had less mortality from cardiovascular disease and cancer across every condition studied.

• Thymic atrophy occurs after every infection, not just with age; repeatedly sick people never get full thymus rejuvenation
• The lymphocyte-to-monocyte ratio on a CBC ($3 lab test) serves as a practical thymic score and general immune health indicator
• Zero out of 100 randomly pulled physicians in the US know about the lymphocyte-to-monocyte ratio's clinical significance
• Low lymphocyte-to-monocyte ratio is associated with poor outcomes across cardiovascular disease, cancer, and diabetes
• Removing thymus tissue leads to a mortality signal within the first 5 years after open heart surgery, with higher rates of cancers and autoimmune diseases
• A 2026 Nature paper found that people with higher thymic scores had less mortality from cardiovascular disease and cancer
• Dr. Abu Bakri self-administers thymosin alpha 1 twice weekly at 2.5mg as a prophylactic, reporting no flu, colds, or infections during the current year on hospital wards
• Peptide interventions (e.g., growth hormone secretagogues) have produced measurable improvements in lymphocyte-to-monocyte ratios, with documented cases of ratios increasing from 4:1 to 8:1

Growth Hormone and Secretagogues

Growth hormone is released in a large pulse during the first 90 minutes of slow-wave sleep; missing this pulse results in only small pulses throughout the day. Growth hormone is thymoregenerative, stimulating regrowth of the aged involuted thymus gland based on Dr. Fee's work. However, growth hormone and GHRPs cause insulin insensitivity, raise A1C levels, and animal models suggest the somatopause may actually be protective from a longevity perspective—chihuahuas (lower IGF-1) live much longer than Great Danes (higher IGF-1). Tesamorlin combined with Epamorlin creates IGF-1 levels in the 380s-390s (puberty levels) with higher fidelity and fewer side effects than other GHRPs.

• Growth hormone is released in a large pulse during the first 90 minutes of slow-wave sleep
• Missing the first 90 minutes of sleep results in only small pulses throughout the day
• Growth hormone is thymoregenerative, stimulating regrowth of the aged involuted thymus gland
• Growth hormone and GHRPs cause insulin insensitivity and raise A1C levels
• Chihuahuas (lower IGF-1) live much longer than Great Danes (higher IGF-1), illustrating growth hormone's inverse relationship with longevity
• IGF-1 decreases dramatically from age 18 to 30 to 50
• Tesamorlin combined with Epamorlin creates IGF-1 levels in the 380s-390s (puberty levels) with higher fidelity and fewer side effects
• MK-677 is not a peptide; it is a non-peptide GHRP (growth hormone-releasing peptide)
• The debate on growth hormone for aging centers on whether its properties as a growth factor could promote existing cancer growth, though no mutagenic effect has been demonstrated

Epitalon and Khavinson's Longevity Research

Khavinson conducted a 15-year longevity study with nursing home patients using epithalamine (pineal gland extract) and the thymus peptide thyolin, where participants received a 10 or 20 day course of peptides per year and showed significantly lower mortality from cardiovascular disease, infectious risk, and cancers. Epitalin has shown neuroprotective effects in mouse studies for retinitis pigmentosa and glaucoma-related downstream neurodegeneration. The theory is that epitalon works by upregulating melanopsin levels, potentially making morning sunlight more effective, with animal studies showing 5 days of pure darkness dramatically increasing melanopsin levels.

• Khavinson conducted a 15-year longevity study with nursing home patients using epithalamine and thyolin
• Study participants received a 10 or 20 day course of peptides per year and showed significantly lower mortality from cardiovascular disease, infectious risk, and cancers
• Epitalin increases expression of clock genes in lymphocytes and peripheral tissues, creating a more rhythmic circadian pattern with higher morning cortisol
• Epitalin has shown neuroprotective effects in mouse studies for retinitis pigmentosa and glaucoma-related downstream neurodegeneration
• The theory is that epitalon works by upregulating melanopsin levels, potentially making morning sunlight more effective
• Animal studies show 5 days of pure darkness dramatically increases melanopsin levels
• Brennan Henry translated thousands of Russian peptide research papers into English, making Russian longevity literature accessible

GHK-Copper Peptide

GHK-CU was discovered in type 1 collagen fibers by Dr. Lauren Pickard in the mid-70s; serum levels reach up to 200 nanograms in youth. GHK-CU upregulates both collagen synthesis AND breakdown, allowing proper tissue remodeling rather than just accumulation or degradation. Pickard's studies compared GHK-CU to retinol and vitamin C creams with positive effects on skin. A Chinese group is studying GHK-CU for lung regeneration in COPD, smokers, and long COVID patients, while GHK-CU topical has human data showing aesthetic outcomes, especially when combined with red light therapy for collagen repair.

• GHK-CU was discovered in type 1 collagen fibers by Dr. Lauren Pickard in the mid-70s
• Serum levels reach up to 200 nanograms in youth
• GHK-CU upregulates both collagen synthesis AND breakdown, allowing proper tissue remodeling rather than just accumulation or degradation
• Pickard's studies compared GHK-CU to retinol and vitamin C creams with positive effects on skin
• GHK-CU is not better than minoxidil for hair but may work as an adjunct with other hair loss agents
• A Chinese group is studying GHK-CU for lung regeneration in COPD, smokers, and long COVID patients
• GHK-CU topical has human data showing aesthetic outcomes, especially when combined with red light therapy for collagen repair

GLP-1 Drugs: Origins and Mechanisms

GLP-1 was originally discovered in the saliva of Gila monsters and was initially too short-acting to be clinically useful on its own. Pharmaceutical companies developed longer-acting versions with extended serum half-lives, enabling therapeutic applications. GLP-1 acts as a "don't eat" signal to the brain, modulating pathways involving GIP, glucagon, insulin, testosterone, and estrogen. Zach Knight (UCSF Howard Hughes investigator) reported that older diabetic GLP-1 drugs increased GLP ~2-4x, while newer drugs like Mounjaro, Zepbound, and Retatrutide increase GLP ~1000x.

• GLP-1 was originally discovered in the saliva of Gila monsters and was initially too short-acting for clinical use
• Pharmaceutical companies developed longer-acting versions with extended serum half-lives
• GLP-1 acts as a "don't eat" signal to the brain, modulating pathways involving GIP, glucagon, insulin, testosterone, and estrogen
• Bodybuilders began using GLP-1 drugs in the late 2010s
• Older diabetic GLP-1 drugs increased GLP ~2-4x, while newer drugs like Retatrutide increase GLP ~1000x
• GLP-1 medications are credited with driving the overall peptide popularity explosion
• Weight regulation follows set point or settling point theory—the brain integrates hormonal signals daily to decide whether to eat
• GLP-1 receptors exist on neurons in the brain and may affect the leptin-melanocortin pathway

GLP-1 Clinical Results and Weight Loss

Previous weight loss drugs achieved 5-10% body weight reduction; GLP-1s now achieve 10-20%, with emerging data showing up to 30% reduction. The speaker prescribed GLP-1 drugs to veterans weighing 300 lbs at a VA clinic before FDA approval for weight loss; patients lost 50-100 lbs. 18-19 year olds on 5mg Retatrutide have lost 30-40 lbs, though it's unclear if they must stay on the drug for life to maintain weight. GLP-1 drugs have created a "post-GLP1 world" where downstream effects influence health practices and prescribing patterns for clinicians and health enthusiasts.

• Previous weight loss drugs achieved 5-10% body weight reduction; GLP-1s now achieve 10-20%, with emerging data showing up to 30% reduction
• Zepbound is the FDA-approved version of tirzepatide specifically for weight loss
• The speaker prescribed GLP-1 drugs to veterans weighing 300 lbs at a VA clinic before FDA approval for weight loss; patients lost 50-100 lbs
• 18-19 year olds on 5mg Retatrutide have lost 30-40 lbs, though it's unclear if they must stay on the drug for life
• Retatrutide hits not just the GLP pathway but also GIP and glucagon pathways
• Retatrutide is predicted to become a trillion dollar industry because Eli Lilly will find additional therapeutic uses to protect patent investment
• To qualify as a biologic requiring longer patent protection (15 years vs 5-7 years), a drug must have 40+ amino acids; retatrutide has exactly 39 amino acids

GLP-1 Fertility Effects and Pricing

GLP-1 drugs improve fertility in overweight/obese women by modulating leptin status—both low leptin (starvation) and leptin resistance impair fertility. Leptin hitting a certain threshold signals the onset of puberty in females, as body fat signals sufficient energetic resources for reproduction. The Trump administration is pressuring Eli Lilly and Novo Nordisk to reduce GLP-1 drug prices, with monthly Tirzepatide costs dropping from $1500 to around $300. Orforglipron is a non-peptide GLP-1 agonist costing approximately $150/month.

• GLP-1 drugs improve fertility in overweight/obese women by modulating leptin status
• Both low leptin (starvation) and leptin resistance impair fertility
• Leptin hitting a certain threshold signals the onset of puberty in females, as body fat signals sufficient energetic resources for reproduction
• The Trump administration is pressuring Eli Lilly and Novo Nordisk to reduce GLP-1 drug prices
• Monthly Tirzepatide costs have dropped from $1500 to around $300
• Orforglipron is a non-peptide GLP-1 agonist costing approximately $150/month
• People taking GLP-1 medications commonly share prescriptions, obtain them from alternative sources, and use lower dosages than prescribed

Clinical Recommendations and Future Directions

Dr. Abu Bakri recommends obtaining peptides through physician-led options and monitored telehealth services rather than self-sourcing, with more clinician options expected within 6-24 months. Without foundational health basics (morning sunlight, sleep, good diet) in place, there is no point in taking peptides. Physicians are now in a "peptide era" and need to get educated on peptides to serve their patients properly. Peptide interventions are often used in stacks: "Wolverine stack" (TB500 and BPC157), "Glow stack" (adds GHK-CU), and "Trinity stack" (GLP-1 + growth hormone/GHR modulation + androgen modulation).

• Dr. Abu Bakri recommends obtaining peptides through physician-led options and monitored telehealth services rather than self-sourcing
• More clinician options for peptide prescribing are expected within 6-24 months
• Without foundational health basics (morning sunlight, sleep, good diet) in place, peptide therapies offer limited benefit
• Peptide stacking is increasing average order value (AOV) from research peptide websites
• "Wolverine stack" includes TB500 and BPC157; "Glow stack" adds GHK-CU; "Trinity stack" combines GLP-1 + growth hormone/GHR modulation + androgen modulation
• Patients commonly stack GLP-1s with ADHD medications and peptide stimulants, creating compounding effects
• RFK stated peptides are supplements not medications and FDA won't regulate them as meds
• The term "peptide" is too general and lacks functional definition; what matters is which receptor a compound touches

Research Gaps and Concerns

Speakers identified three problematic outcomes if BPC-157 research isn't conducted: it works but isn't researched properly, it's harmful, or adverse events cause it to be abandoned without understanding if problems were from the compound, misuse, or dissolution factors. No literature exists on animal or human data relating BPC-157 or other peptides to endometriosis or fibroids. There are no case reports or studies on CNS effects of BPC-157 or similar peptides. From 1910s to 1940s, children's thymuses were irradiated to prevent SIDS, considered gold standard medicine at the time; at least 10,000 children died from cancers due to this practice.

• Three problematic outcomes identified if BPC-157 research isn't conducted: improper research, harm, or abandonment due to adverse events without proper understanding
• No literature exists on animal or human data relating BPC-157 or other peptides to endometriosis or fibroids
• There are no case reports or studies on CNS effects of BPC-157 or similar peptides
• Russian studies exist on TBI using cortexin and cerebralin, compounds that would likely never be available in the United States
• From 1910s to 1940s, children's thymuses were irradiated to prevent SIDS; at least 10,000 children died from cancers due to this practice
• Mad cow disease cases in the early 2000s dramatically set back animal-derived peptide research
• Thymosin research fell out of favor in recent decades despite promising findings from the Goldstein lab
• More clinical data is urgently needed for BPC-157 to determine proper dosing, safety, and efficacy before millions of people continue using it