How a Croatian Lab Spawned a Buzzy Peptide (BPC-157) Now Popular With MAHA

#4

My Gemini Pro (Deep Search) effort on BPC-157. To be honest, the fact that almost all the research is in mice, and comes from a single lab in Zagreb, Croatia doesn’t give me much confidence in this peptide. Basically this is a new drug that hasn’t even been through Phase 1 clinical trials (basic safety), let alone phase 2 (efficacy) human clinical trials. I hope it is a peptide that gets more research funding.

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The Wolverine Molecule: Gastric Peptide BPC-157 Challenges Conventional Healing Timelines

The therapeutic landscape of longevity and regenerative medicine is currently being disrupted by a pentadecapeptide known as BPC-157. Originally isolated from human gastric juice, this “stable gastric pentadecapeptide” has moved from the niche world of experimental gastroenterology to the forefront of biohacking due to its purported ability to accelerate the repair of avascular tissues—tendons, ligaments, and bone—at rates that mimic the hyperbolic healing of cinematic superheroes.

The Institutional Context The vast majority of BPC-157 research originates from the University of Zagreb, Croatia, led by Dr. Predrag Sikiric. The core mechanistic papers are published in journals such as Current Pharmaceutical Design (2018) and the Journal of Physiological Sciences (2019).

Impact Evaluation The impact score of Current Pharmaceutical Design is 3.1, evaluated against a typical high-end range of 0–60+ for top general science journals like Nature or Science; therefore, this is a Medium impact journal. While respected in the field of drug design, the lack of publication in high-tier general biology journals suggests that the broader scientific community remains cautious, pending large-scale human validation.

Impact & Narrative BPC-157’s novelty lies in its stability. Unlike most peptides that succumb to enzymatic hydrolysis within seconds of entering the digestive tract, BPC-157 remains stable in gastric acid for over 24 hours. Its mechanism of action is multifaceted, revolving around the upregulation of Vascular Endothelial Growth Factor (VEGF) and the modulation of the Nitric Oxide (NO) system. This dual action facilitates rapid angiogenesis—the formation of new blood vessels—which is the rate-limiting step in healing injuries where blood supply is naturally sparse, such as the Achilles tendon.

Clinically, this suggests a tool that not only heals ulcers but could fundamentally alter the recovery trajectory of sports injuries and potentially systemic microvascular aging. However, the “Big Idea” remains tethered to a significant Translational Gap, as high-powered human randomized controlled trials (RCTs) are conspicuously absent.

Part 2: The Biohacker Analysis

Study Design Specifications

  • Type: Primarily in vivo (Animal models).
  • Subjects: Wistar rats (Male/Female), N=10 to 30 per group.
  • Lifespan Analysis: There are zero longitudinal lifespan studies for BPC-157 in healthy, aging mice. The research focuses almost exclusively on “recovery” and “acute injury.”
  • Lifespan Data: N/A. Reviewing the control groups in Sikiric’s work against the Normative Mouse Lifespan (2023)suggests that while BPC-157 prevents premature death from acute toxins (like NSAID overdose), there is no evidence it extends the maximum lifespan of a healthy organism.

Mechanistic Deep Dive

  • Vascular Health (VEGF/NO): BPC-157 upregulates VEGF and promotes the FAK-paxillin pathway, essential for cell migration. This is the “angiogenesis engine.” VEGF Pathway Analysis (2014).
  • Autophagy/mTOR: There is no direct evidence that BPC-157 modulates the mTOR pathway. It may, in fact, counteract the healing-inhibition effects of certain mTOR inhibitors.
  • Organ Priorities: Gut (Cytoprotection), Tendon/Ligament (Angiogenesis), Brain (Dopamine modulation).

Novelty & Limitations

  • What we know today: BPC-157 is a “soft-modulator” of the NO system, balancing both pro- and anti-angiogenic signals depending on the tissue state.
  • Ruthless Critique: The “Sikiric Conflict.” Almost all data comes from a single group in Croatia. Independent replication in high-impact US or EU labs is severely lacking. Sample sizes are often low (N=10), and the transition from rat “Achilles transection” to human “chronic tendinopathy” is a massive leap in complexity.

Part 3: Claims Verification

Claim Evidence Level Verification Source Translational Label
Achilles Tendon Healing Level D Sikiric et al. (2003) Pre-clinical: Rat model only.
NSAID Ulcer Prevention Level B Pilot Human Trial (2012) Human Pilot: Small sample size.
Neuroprotection Level D Brain-Gut Axis Study (2016) Pre-clinical: Murine dopamine models.
Systemic Safety Level D/E Safety Profile (2017) Safety Data Absent: For chronic use (>6 months).

Part 4: Actionable Intelligence

Human Equivalent Dose (HED)

  • Animal Dose: 10 µg/kg (Standard rat dose).
  • Math: 10×(6/37)=1.62 µg/kg.
  • Result: For an 80kg human, the theoretical dose is 130 µg daily.
  • Biohacker Context: Most protocols use 250–500 µg daily, which is significantly higher than the calculated HED.

Safety & Toxicity

  • NOAEL: No Observed Adverse Effect Level was not reached in acute rat studies.
  • LD50: Not established; extremely high safety margin in acute settings.
  • Safety Check: VEGF Paradox. Chronic administration could theoretically promote the growth of existing undiagnosed tumors (angiogenesis).

Biomarker Verification Panel

  • Efficacy: Reductions in hs-CRP and IL-6. Increase in VEGF-A (though this must be monitored carefully).
  • Safety: Standard metabolic panel plus Cystatin C and ALT/AST to monitor organ-specific engagement.

Gemini Deep Search, Full Report:

BPC-157 Longevity Research Analysis.pdf (370.8 KB)

#5

To get a perspective on how BPC-157 stacks up (from an evidence perspective) against some other therapeutics we discuss here…:

Comparison: Rapamycin, SS-31 Peptide, BPC-157 Peptide

The following comparative analysis evaluates Rapamycin, Peptide SS-31 (Elamipretide), and Peptide BPC-157 for their potential as longevity therapeutics. This audit prioritizes reproduced lifespan data (ITP standards) and human clinical efficacy over mechanistic hypotheses.

Output 1: The Master Comparison Matrix

Rank Compound Evidence Score (0-100) Primary MOA Human Trials (n) Animal Consensus Est. Users Monthly Cost ($) Safety Profile
#1 Rapamycin (Sirolimus) 88 mTORC1 Inhibition ~2,000+ (Total)

(~5+ Longevity specific) 		Robust

(ITP Replicated: +23-26% Lifespan)		 >100k

(Off-label)		 ~$45–$150 Med Risk

(Dose-dependent immunosuppression)
#2 SS-31 (Elamipretide) 62 Cardiolipin Stabilization / Mitochondrial ANT ~30

(Heart Failure, Myopathy) 		Moderate

(Reverses cardiac aging; Lifespan data mixed)		 <5k ~$300–$1,000+ Low Risk

(Injection site reactions)
#3 BPC-157 35 Angiogenesis / NO Modulation (Hypothesized) <5

(Mostly withdrawn/inconclusive) 		Inconclusive

(Wound healing only; No lifespan data)		 >10k?

(Gray market)		 ~$50–$100 Unknown/Regulated

(FDA Cat. 2 Ban; WADA Prohibited)

Output 2: Detailed Evidence Profiles

1. Rapamycin (Sirolimus)

  • Evidence Audit: The current “gold standard” for pharmacological lifespan extension.
  • Animal Data: [Total Studies: >50] | Species: Yeast, Worms, Flies, Mice |
  • Replication Status: Perfect. The NIA Interventions Testing Program (ITP) confirmed median lifespan extension of 23% (males) to 26% (females) at 42 ppm dosing.
  • Human Data: [Completed Trials: ~5 Longevity-focused] | Total N: ~150 (longevity specific) | Key Result: The PEARL Trial (Phase 2, NCT04488601) demonstrated safety and modest improvements in lean muscle mass and pain scores in women, though it lacked statistical power for broad aging biomarkers over 48 weeks.
  • Bioavailability/Delivery: Oral | Absorption: Low (~14%) but improved with fatty meals or nano-formulations.
  • Critical Flaw: Immunosuppression Window. Chronic high dosing inhibits mTORC2, leading to insulin resistance and immune compromise. Longevity protocols rely on pulsed dosing (e.g., weekly) to mitigate this, but long-term human safety of pulsed dosing remains strictly observational.

2. SS-31 (Elamipretide)

  • Evidence Audit: A mitochondrial therapeutic demonstrating potent organ-specific rejuvenation (heart/skeletal muscle) but lacking robust global lifespan extension data.
  • Animal Data: [Total Studies: ~40] | Species: Mice, Rats, Dogs |
  • Replication Status: High efficacy for organ function. Reversed age-related diastolic dysfunction and restored mitochondrial redox homeostasis in old mice (University of Washington). However, it has failed to consistently extend maximum lifespan in wild-type mice.
  • Human Data: [Completed Trials: ~15] | Total N: ~800 | Key Result: Phase 3 trials for Barth Syndrome showed functional improvement, but trials for Heart Failure (HFpEF) have been mixed/failed to meet primary endpoints.
  • Bioavailability/Delivery: Subcutaneous/IV Injection | Absorption: 100% (Injection), 0% (Oral - peptide degrades).
  • Critical Flaw: Delivery Friction. It is a tetrapeptide requiring daily subcutaneous injections. Oral bioavailability is negligible, making adherence difficult for prophylactic longevity use.

3. BPC-157 (Body Protection Compound-157)

  • Evidence Audit: A “biohacker favorite” with a massive divergence between internet popularity and clinical reality.
  • Animal Data: [Total Studies: ~30] | Species: Rats (mostly) |
  • Replication Status: Niche. Strong evidence for accelerating tendon, ligament, and gastric wound healing in rodents. No evidence exists for systemic lifespan extension or slowing aging processes.
  • Human Data: [Completed Trials: 0 Verified] | Total N: N/A |
  • Key Result: No rigorous randomized controlled trials (RCTs) published in peer-reviewed journals. Most “data” consists of anecdotal logs or withdrawn studies.
  • Bioavailability/Delivery: Subcutaneous/Oral (Arg-salt) | Absorption: Variable.
  • Critical Flaw: Regulatory & Oncogenic Risk. FDA classified BPC-157 as a Category 2 Bulk Drug Substance (significant safety risks), effectively banning it from compounding pharmacies. Mechanistically, its pro-angiogenic (blood vessel growth) properties pose a theoretical risk of accelerating tumor growth in undiagnosed cancer.

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#6

If it’s a placebo, it’s the best placebo I’ve ever used.

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#7

I’ve tried three cycles of “Glow” (so named by a random med spa) with the most recent set to end in a couple weeks. A few observations:

Dosing: we are guessing here, common “Glow”
protocol simply mirrors common doses of each compound, daily or M-F:
BPC-157: 300-500mcg
TB500: 600-1000mcg
GHK-cu: 1-2mg

None of those are based on significant human studies, but they are often repeated and anecdotally positive reports (so big rock of salt with that).

TB500 (fragment) vs. TB-4 (full chain): limited data but extrapolated dosing for TB-4 would suggest dramatically higher dosing and not in context outside cardiac healing, generally for mice only. Data doesn’t support this though anecdote does.

BPC-157: dosing from mice plus a self-reported 41 person human study - not reassuring data. But positive anecdotal reports.

GHK-cu: good data and supports low risk for topical use, but limited impact topically. Injected study is minimal though many possible benefits.

KVP: some add this or replace GHK with it and call the mix Klow, I hate the names, science should not be promoted with market names derived from random med spas in 2024 when they’re just trying to sell overpriced peps they get from China.

The ontological risk of BPC and TB4 seems overstated to me, but hard to entirely discount, particularly for anyone with known risks for cancer.

My anecdote: I wish they all worked, but if they’re doing anything it’s marginal.
Wound healing is boarding on unnoticeable. Maybe a sprained wrist healed faster, maybe some good PT and strengthening would have better served me.
Skin: still more loose skin than wanted after significant weight loss. Filling in with muscle and time certainly doing the heavy work here, GHK-cu debatable impact at best.

I’ve tried a range of doses, consistently test for copper serum levels (there’s a significant risk of copper toxicity for those with Wilson’s Disease or even if heterozygous carriers), taken before and after photos, measured range of motion for sprains, recorded notes on subjective impacts … and I’m not impressed with any of the three compounds and likely won’t try another cycle. These are now just taking up space in my freezer. Might give BPC and TB500 another try if I end up with a broken bone or surgical recovery.

We all want them to work like the dramatic impacts seen from Tirz or Reta, but those well studied and successful peptides are in a wildly different league of their own while “glow” is simply not even close. In my research at least.

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#8

For anyone interested in a skeptical take on common gray market peptides, this was a nice (if surface level) podcast:

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#9

Related Thread:

#10

I think there are wonder emergent substances. I take arginine plus vit C (1 in 2 days) and creatine HCL (low dose) + iron everyday; it changed my life. I do not feel any inflammation anymore, my sport resistence improved a lot, and also mental state :slightly_smiling_face:

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#11

The dose is too low and not often enough.

Pretty simple.

BPC 500mcg + TB500 500mcg - per daily dose
GHK-cu 1.5 to 2.0 mg - per daily dose

The GHK-cu is optional for soft tissue healing. It has a benefit for skin but I don’t see enough evidence for ligaments, tendons and muscle.

For a chronic injury, one needs to inject every day until it’s healed.

This our maintenance dose :slight_smile: for the past 2.5 years. I heal like a kid.

Most people are going to find that is an expensive dosing regimen but the cure is in the dose, why waste money on a suboptimal dose that is doing nothing? Either do it right or don’t bother.

Peptides are not magic, just because one is injecting a small amount does not mean they will work like magic. They perform based on dose, and one dose does not fit all.

#12

Interesting

i havent seen that protocol (20u + 20u) every day. I was actually taking much more of TB (70u, which is 1750mcg)

how long taking 500mcg + 500mcg should i notice a difference in my sprained ankle (havent got an mri on that) or how long should i take to heal my shoulders ? (mri confirmed tendonites)

#13

Units is not the best way to refer to the dose used. Units is not the dose.

Units, a measure of liquid volume, not the dose.
mg or mcg, a measure of weight, is the dose

Depending on how you reconstitute, that can change the amount of mg/mcg in the U. I don’t bother referencing U to the dose.

In 10 Units you could have 250mcg or 25mg a hundred fold increase in dose in the same volume of water.

For example our standard “shot volume” for weight loss is 50U, we change the weight of the peptide, from 2.0mg to 15.0mg per dose (8mg to 60mg per custom filled vial) we always recon this one with 2.0mL (4 shots of 50U) it makes it easy for accurate and repeatable dosing.

As far as how long it will take you to heal using a particular dose is quite dependent on you. Not just the dose. It’s like asking how long is a rope or how deep is a hole, it depends :slight_smile:

It took 3 months to heal my old ankle (both) injuries that had not fully healed in a year.

I pulled my infraspinatus 6 weeks ago and the first time I did that 14 years ago, it took a full year to be pain free with no peptides. This time less than 3 weeks. I was amazed!

For 2.5 years I’ve been “primed” to heal by using 500+500mcg daily, with a break every couple of months.

#14

I think one of the biggest issues with these is that we don’t truly know the proper dosing. I’m not sure how we landed on the doses that the internet universally recommends.

#15

3 months of this dose everyday ?

maybe im paying too much for peptides in europe ? :slight_smile:

#16

Very true so here are a couple of PDF with animal studies, from which most of the “internet” dosing is derived.

Thymosin Beta 4 aa43 dosing use only clinical and.pdf (532.5 KB)

BPC 157 dosing use only clinical and preclinical a (1).pdf (480.3 KB)

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#17

You probably are paying too much.

Consider that my wife and I have been doing these doses regularly for 2.5 years :slight_smile:

That’s why I got into the business side of things so I could afford my peptide addiction LoL!

This morning I used,

  1. SS 31- 3.3mg - on a single dose 30 day cycle, all done this one in about 10 more days
  2. MOTS-c- 12mg x 2 times a day, on a 30 day cycle, all done this one in about 29 more days
  3. Gonadorelin - 200mcg - single dose 4 mornings a week
  4. BPC_TB+GHK - 500mcg+500mcg+2.0mg - singel dose daily
  5. KPV - 400mcg - started this on about 2 weeks ago, will stop in 2 weeks to see if it made a difference.

Tonight I will take,

  1. Ipamorelin + CJC 1295 noDAC - 400mcg+750mcg - 5 nights a week
  2. DSIP - 400mcg - 5 nights a week

Humans have a short memory for “pain”, once it stops.

I find that as I use something that may decrease pain as it heals or does what ever it does, I get used to that reduced pain state, my new normal, and don’t fully understand if it “worked” or not. When I stop something and the “pain” comes back, then I know it did have an effect.

If the pain does not come back, then I have 2 thought options,

  1. the “pain” source was going to heal any way, I then evaluate how long I had the pain.
  2. the peptide solved the root cause

Or it was the placebo effect :slight_smile:

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#18

So let’s keep in mind that Anti-angiogenic cancer therapy is a treatment strategy that starves tumors by inhibiting the growth of new blood vessels needed for them to receive oxygen and nutrients. These agents typically target vascular endothelial growth factor (VEGF) to stop tumor angiogenesis, often used alongside chemotherapy or immunotherapy.

Let that sink in before anyone thinks about using it daily and high doses, before we have long term safety and efficacy data from human studies.

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#19

It’s more than the dose. You have to be active. You have to participate in your own recovery. You can’t just take this stuff and then sit on the couch. RICE is out of date.

The shoulder is a major intersection of bones, muscle, fascia, and tendons. A knot in the rotator cuff can be transmitted all the way down to the bottom of the bicep, and the whole area can be painful at once. To work on this referral pain, I like planks, the dead hang, and a massage gun. You also need to be patient. When you have a persistent injury, it feels like it will never end. But it does.

I started taking Steve’s full-spectrum TB-4 about 10 days ago. I also found some good pressure points to hit with the percussion gun. With this treatment, plus a little luck, I was pain-free today for the first time in moths. Went out for a brisk run in the cold, but a warm-up is coming soon, and I’ll be ready for it.

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#20

Does VEGF cause cancer?

No it does not.

Tumors will themselves increase VEGF so they can grow, so increasing VEGF when you already have cancer is definitely a bad thing.

If you have cancer do not use BPC 157 and/or TB500

does VEGF cause cancer.pdf (258.3 KB)

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#21

WoW!!

Your advice on being active during the healing process is spot on.

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#22

How will you be sure you don’t have cancerous cells in your body right now? Are you sure that by increasing angiogenesis you won’t fuel their growth before the tumor immunosurveillance is able to detect and neutralize these cells?
I am providing a counterargument to your advice of taking large amounts of these compounds on chronic basis. I personally would not without robust human data. Using it for a limited time after injury makes more sense and would limit potential risk.

While there is no single, universally cited number for how many undetectable tumors an “average” person has, scientific studies suggest that the vast majority of people—particularly as they age—harbor dormant, microscopic, or indolent tumors that never cause illness.

Here are key insights based on autopsy studies and cancer research:

  • Autopsy Findings (High Prevalence): Studies on individuals who died of other causes have shown an surprisingly high prevalence of hidden cancers. For example, some studies found that nearly 100% of individuals between 50 and 70 years old had microscopic, indolent (inactive) cancers in their thyroid glands, even though the clinical incidence is very low.
  • Breast Cancer: Postmortem examinations have shown that approximately 39% of women in their 40s harbor microscopic, undetected breast cancers, despite the clinical incidence of breast cancer in this age range being only about 1%.
  • Prostate Cancer: Similarly, autopsy studies indicate that about one in three men in their 40s-50s has microscopic prostate cancer, a number that increases with age.
  • “Dormant” State: Many of these tumors remain in a dormant, non-angiogenic state (not growing new blood vessels) and can remain in the body for decades without progressing.
  • Immune System Control: The human body generally has a robust immune system that identifies and destroys or limits these abnormal cells, preventing them from becoming harmful.

Conclusion: It is highly likely that an average, asymptomatic adult has at least one, if not several, microscopic, dormant, or slow-growing tumors that are not detected by current medical screenings.

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#23

Looks like a lot of beneficial stuff increase VEGF.
BTW I do them all except Hypoxic Training and HBOT.

Interventions increasing Vascular Endothelial Growth Factor (VEGF) which signals the body to build more blood vessels:

  • Lower-Limb Resistance Training (RT): High-intensity lower-limb RT is often the most effective method for increasing VEGF in healthy adults. Dose benefits appear above 600 METs-min/week and peak around 1950 METs-min/week.
  • Blood Flow Restriction (BFR): Combining low-load resistance exercise with BFR creates a hypoxic environment that stabilizes HIF-1α, a key trigger for VEGF transcription. It is significantly more effective at boosting VEGF mRNA levels than exercise without restriction.
  • Hypoxic Training: For specific groups, such as those with obesity, combining aerobic and resistance training under hypoxic conditions (e.g., altitude-simulated environments) has shown the strongest VEGF response.
  • Ischaemic Training: Brief periods of blocking blood flow to a limb (either via a tourniquet or sustained isometric contraction) can stimulate VEGF.

Nutritional & Supplemental Supports

  • Omega-3 Fatty Acids: Daily intake of 1–2g EPA/DHA supports VEGF production and overall vascular health.
  • Vitamins & Minerals: Adequate levels of Vitamin D3 (2000–5000 IU) and Zinc (15–30mg) are vital; deficiencies in these can impair VEGF function.
  • Antioxidants: Compounds like Resveratrol (100–250mg) and Curcumin (500–1000mg with black pepper) help restore and promote normal VEGF signaling.
  • Nitric Oxide (NO) Boosters: Foods rich in nitrates, such as beetroot juice, enhance circulation and support the downstream effects of VEGF.

Medical & Other Therapies

  • Hyperbaric Oxygen Therapy (HBOT): These sessions can enhance blood vessel formation by stimulating VEGF production during the repair phase.
  • Detoxification: In cases where levels are low due to environmental toxins (like mold), supporting liver function with Glutathione or NAC may help restore normal production pathways.
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