Peptide bioavailability: why oral, subcutaneous, and nasal routes have different evidence bases

Insulin is a peptide. Your insulin shot is a shot, not a pill. The reason is the same reason most peptides under discussion in the longevity and performance markets are injections, sprays, or some other route that bypasses the gut.

The stomach and small intestine exist to break protein into amino acids. They are very good at it. A peptide swallowed in a capsule has to survive an acid bath, a wave of pepsin, a small-intestinal cocktail of trypsin and chymotrypsin, and a gut-wall layer evolved to absorb single amino acids rather than chains of them. Most peptides do not survive that trip in any meaningful quantity. Oral bioavailability for an unprotected peptide is typically under one percent — and often closer to zero.

That single fact reorganises the entire peptide-evidence conversation. The route a study used to deliver the molecule is rarely just a procedural detail. It is what makes the study’s result mean what it means.

The three routes most peptides actually use

For the peptides that show up in the longevity and recovery markets, three routes do the work: oral, subcutaneous, and intranasal. Each one asks a different question of the molecule.

Oral is the consumer’s preferred route — pills are easier to take than needles — and the route most peptides simply cannot survive at useful concentrations. The exceptions are cyclic peptides (with the ends joined into a ring, resisting the enzymes that cleave from either end) and peptides built with D-amino acids or unusual backbone modifications that the gut’s enzymes do not recognise as substrate. A handful of approved drugs work this way (oral semaglutide is the most famous). The peptides marketed for performance and recovery typically are not in that category.

Subcutaneous — a small injection just under the skin — is the default research route for almost everything else. It bypasses the gut entirely. Absorption from the subcutaneous tissue is slow and relatively predictable, which means a peptide that gets cleared from plasma quickly can still deliver a useful therapeutic window when injected this way. Most GLP-1 analogs, most growth-hormone-axis peptides, and insulin itself use subQ as the production route. The evidence base for these compounds is built primarily on subQ dosing.

Intranasal is the third route that matters here, and the one most underrepresented in Western peptide writing. The nasal mucosa has a high-density vasculature and, in places, a direct path to the central nervous system via the olfactory and trigeminal nerve routes. Small peptides delivered intranasally can reach the brain at concentrations the bloodstream would not allow without much higher systemic doses. Bioavailability across the nasal mucosa is variable — often single-digit percent — but for centrally acting peptides the relevant metric is brain exposure rather than plasma concentration.

The Russian neuropeptide research tradition leans heavily on intranasal dosing for exactly that reason.

What this looks like for BPC-157

BPC-157 is the cleanest example of the route-mismatch problem. The compound is marketed both as an oral capsule and as a subcutaneous injection. The published animal-model evidence is almost entirely intraperitoneal or oral-via-gavage in rats — that is, either injected directly into the abdominal cavity (a route no human ever uses) or delivered as a controlled volume directly into the stomach (which approximates the oral product more closely but is still a controlled-laboratory delivery rather than a capsule survival test).

The 2025 Pharmaceuticals literature and patent review by Józwiak and colleagues surveys the breadth of that animal evidence — and the human pharmacokinetic record is essentially absent from the review. There is no published human PK study of BPC-157 by any route. The single published human safety data point is Lee and Burgess (2025, Altern Ther Health Med) — an intravenous-infusion pilot in two healthy adult volunteers across three days, with no adverse effects, no biomarker changes, and no efficacy endpoint. That is the only published human exposure to BPC-157, and it is two people receiving IV infusion in a low-impact journal.

The oral marketing claim rests on the assumption that the animal-model oral-gavage results transfer to a human swallowing a capsule. That transfer is not characterised in any published human study. The subcutaneous marketing claim rests on the assumption that intraperitoneal results in rats transfer to subcutaneous dosing in humans. That transfer is also not characterised. Both are reasonable hypotheses. Neither is confirmed.

What this looks like for selank and semax

Selank and semax are the other side of the route-and-evidence puzzle. Both peptides are Russian-tradition compounds dosed intranasally in clinical use. Both share the Pro-Gly-Pro stabilising extension that extends half-life from minutes to hours — the molecular feature that makes intranasal dosing practical at all.

The 2008 selank anxiolytic paper in Zh Nevrol Psikhiatr is the foundational Russian clinical paper, dosing intranasally. Gusev and colleagues (1997) is the foundational Russian stroke trial of semax, also intranasal. Russian clinical use of both compounds is consistently nasal-spray delivery. The 1999 Russian Ministry of Health authorisation of semax for stroke is for that specific route.

The catch on the consumer side is whether the products sold to Western buyers match that route discipline. Some do — Russian-sourced spray formulations are available. Others are sold as injectable lyophilised powders for subcutaneous reconstitution, which is a different route than the one the Russian clinical evidence was generated on. The intranasal-to-subcutaneous transfer is not characterised in published controlled trials, and the central-nervous-system effects that are the marketing case may not survive a route change that skips the direct nose-to-brain pathway.

The route-and-evidence question is the question on the consumer file

For each of these compounds, the route the buyer is using is often not the route the evidence base was generated on. Sometimes the route shift is reasonable (subQ to subQ across populations); sometimes it requires assumptions that have not been verified (oral capsule replacing rodent gavage; subcutaneous injection replacing intranasal spray).

Mendias and Awan (2026, Sports Medicine) places all three compounds in the broader sports-medicine context: non-approved peptides operating outside FDA-recognised drug-application frameworks, with scarce Western controlled data and essentially absent human pharmacokinetic characterisation.

The regulatory state matches that picture. BPC-157 is on the July 23, 2026 FDA Pharmacy Compounding Advisory Committee docket for ulcerative colitis. Semax is on the July 24 docket for cerebral ischemia, migraine, and trigeminal neuralgia. Selank is on neither wave. Whether the PCAC review will produce route-specific compounding guidance — or only molecule-level guidance — is one of the open questions the committee’s deliberations will answer. We covered how PCAC reviews actually work in What is the PCAC.

What would actually close the route-and-evidence question?

For BPC-157, a published human pharmacokinetic study comparing oral capsule, subcutaneous injection, and (if anyone still cares) intravenous infusion across the same dose range, with plasma and tissue concentrations measured against an explicit therapeutic window. That study does not exist; the Lee and Burgess two-person IV pilot is the entire available human file.

For intranasal Russian-tradition peptides, controlled comparisons between intranasal and subcutaneous administration in human subjects, with central nervous system effects (cognition, mood, evoked potentials, or imaging biomarkers) measured directly rather than inferred from animal models. That work has not been published in the Western literature.

For the broader category, a controlled trial that establishes which route the consumer product is actually delivered by — survival through gut, mucosal absorption, plasma concentrations measured against in-vitro effective ranges — and whether the route the marketing implies is the route the buyer is actually receiving.

None of those studies are scheduled. The route the evidence base was generated on, and the route the product is sold under, are not always the same molecule’s story — and the gap between them is one of the most underexamined parts of the consumer peptide question.

Wolverine Health is being built around the version where the prescribing physician reads both the molecule’s file and the route-of-administration file before signing the script, and the dispensing pharmacy is US-licensed against an indication and route the FDA has actually reviewed. Join the waitlist for a note the day any of those gaps actually closes.