On Peptides

Distorted Risk Calculation

Recently, a lovely post-menopausal 50-year-old patient of mine came in with iron deficiency anemia and significant hesitation about scheduling her first colonoscopy. At the same visit, she wanted my opinion on peptides.

That contrast is worth examining.

She was anxious about a standard, evidence-based diagnostic procedure recommended in general at age 45 (but also for her evaluation of her anemia), yet comparatively open to compounds that are largely unregulated, inconsistently manufactured, and in many cases supported more by marketing than by meaningful human data.

A Common Inversion of Risk

This is not unusual in clinical practice. Patients are often more apprehensive about familiar medical procedures than about newer, less regulated interventions that are presented as natural and cutting-edge.

A colonoscopy is not trivial (although I am proud to say that I did my prep while seeing patients all day), but it is a known entity. It is performed in a controlled setting, with established indications, standardized protocols, trained specialists, and a clear framework for interpreting the findings. The unapproved peptide market is fundamentally different. It often asks patients to accept uncertainty at every level: uncertain efficacy, uncertain safety, uncertain sourcing, uncertain purity, and uncertain dosing.

The central problem is that many of these products borrow the language of science without meeting the standards of science. Approximately 54% of drugs entering late-stage clinical development fail, most commonly because they lack efficacy or reveal safety concerns. Preclinical success (i.e. animal studies) is not especially reassuring on its own, because animal toxicology has only limited predictive value for human outcomes. History is full of compounds that looked promising before failing in human use. In 1993, a medication called Fialuridine was developed to treatment chronic hepatitis B and herpes infections. It was found to be safe in animal trials and even short human trials. After 9–13 weeks of extended dosing, 7/15 patients developed severe hepatotoxicity. 5 died, 2 required emergency liver transplants. The toxicity was human-specific and required chronic exposure to manifest. In 2006, a medication developed to treat B-cell leukemia was found to be completely safe in monkeys at 500x the human dose. All six healthy volunteers in the first human trial were critically ill within 90 minutes due to cytokine storm and multiorgan failure.

A Brief Review of the Peptide Landscape

BPC-157 is widely promoted to “heal everything” but the human data are remarkably limited. Among hundreds of published items, there was only one small human study, and that study was methodologically weak, retrospective, and uncontrolled. It also looked at BPC-157 injections directly into painful knee joints rather than the intramuscular uses of this peptide. There are also theoretical concerns related to angiogenesis (the growth of new blood vessels) that should not be dismissed casually.

TB-500 / Thymosin Beta-4 is similarly attractive in theory and poorly grounded in human evidence. There is interest based on preclinical work, but meaningful orthopedic human data are lacking. It is also banned by World Anti-Doping Agency, which should give people pause before treating it like a fancy injectable multivitamin.

CJC-1295 and Ipamorelin at least have some early human data, which is more than can be said for many peptides in this space. But they remain unapproved, and chronic manipulation of the growth hormone axis is not benign. When humans produce growth hormone, the levels ebb and flow. We don’t know the effects of consistently elevated growth hormone levels. Possible risks include insulin resistance, high cholesterol levels and cardiovascular strain.

AOD-9604 is especially instructive because it actually progressed into formal clinical development. There it failed to demonstrate efficacy in Phase II/III obesity trials. That should have ended the conversation, but instead it continues to be marketed online as though failed clinical development were somehow irrelevant.

GHK-Cu is often discussed as though all forms and routes of administration are interchangeable. They are not. There may be support for topical cosmetic use, but that is not the same as evidence for injectable musculoskeletal or systemic applications.

Selank, Semax, and Epitalon tend to be promoted with references to use outside the United States (mainly in Russia), but geographic availability is not a substitute for rigorous evidence. These compounds lack the kind of Western clinical trial data, independent replication, and long-term safety information that should precede broad clinical enthusiasm. Come on, do you really trust Putin?

The Quality Problem Is Not Theoretical

Even if one were unusually optimistic about possible benefits, the manufacturing and sourcing issues alone should give any clinician and patient pause.

Online products show purity as low as 5% to 75%, contamination with heavy metals including arsenic and lead, and compounded products associated with 5- to 20-fold dosing errors leading to hospitalizations. These are not minor regulatory concerns.

What I Told My Patient

I told her that her anxiety about having a colonoscopy was understandable. Many patients are apprehensive about it, particularly the first time. But fear does not determine risk, and familiarity does not determine safety. I also told her that propofol was quite delightful and gave me the best nap of my life.

I advised her that iron deficiency anemia at age 50 deserves a real evaluation (especially since she was no longer menstruating). I reminded her that she was five years overdue regardless, and early onset colon cancer is rising at an alarming rate in the United States. Finally, I let her know that I was dying to be the cool hip doctor recommending peptides over a colonoscopy, but my Hippocratic just wouldn’t allow it.

P.S. She got her colonoscopy which revealed some benign internal hemorrhoids. She is now taking fiber but no peptides.