A 28-amino-acid gut and nerve peptide that relaxes blood vessels and calms inflammation; approved only in an erectile dysfunction injection.
Also called Vasoactive intestinal peptide, Vasoactive intestinal polypeptide, Aviptadil, Invicorp (with phentolamine), Zyesami (investigational IV aviptadil), RLF-100
Vasoactive intestinal peptide is a 28-amino-acid peptide made by nerve cells throughout the gut, lungs, brain and blood vessel walls. It relaxes smooth muscle, widens blood vessels, makes the gut and pancreas secrete water and bicarbonate, and dampens immune cells through the VPAC1 and VPAC2 receptors. The synthetic drug version is called aviptadil. In the blood it lasts about one minute.
Its one approved use is narrow: Invicorp, an injection of 25 micrograms aviptadil plus 2 mg phentolamine into the penis for erectile dysfunction, licensed in the UK and Denmark. Its high-profile failure was COVID-19. After a 196-patient trial missed its main endpoint, the NIH-run TESICO trial gave IV aviptadil to 461 critically ill patients and stopped for futility: deaths by day 90 were 38% on aviptadil and 36% on placebo. Small studies of inhaled VIP in sarcoidosis (20 patients, open-label) and pulmonary hypertension (20 patients, single dose) showed lab and blood-flow changes but no proven clinical benefit.
Most people searching for VIP find it through the mold-illness and CIRS community, where a nasal spray is prescribed through compounding pharmacies. That use rests on a 20-patient open-label study from the clinic that developed the CIRS protocol, with no placebo group. FDA lists VIP in Category 1 (still under evaluation) for 503A compounding, which is why compounded nasal VIP is available in the US. The known side effects come straight from what VIP does: flushing, low blood pressure, fast heart rate and watery diarrhea. Tumors that over-produce VIP (VIPomas) cause severe secretory diarrhea, which shows what too much VIP does to the gut.
What it binds to, and what happens inside the body after that, step by step.
VIP binds two G-protein receptors, VPAC1 and VPAC2, found on smooth muscle, gut lining, airway cells and immune cells. Both raise cAMP. In blood vessels and the penis that relaxes smooth muscle and widens vessels; in the gut it drives water and chloride secretion; on macrophages and T cells it lowers TNF-alpha and IL-6 and promotes regulatory T cells. It is broken down by peptidases within minutes, which limits it as a drug.
Human results and animal results are kept apart below. A result in rats tells you a mechanism is plausible. It does not tell you what happens in a person.
Humans: placebo-controlled trials exist for erectile dysfunction (positive, licensed in Europe) and IV use in severe COVID-19 (negative in the larger NIH trial). Inhaled VIP for sarcoidosis and pulmonary hypertension has only small open-label or single-dose studies. The nasal-spray use for mold illness/CIRS rests on one 20-patient uncontrolled study from the protocol's own clinic. Most of the anti-inflammatory and neuroprotective claims come from cell and animal work.
461 hospitalized adults with COVID-19 respiratory failure, 28 US sites
Stopped for futility: deaths by day 90 were 38% on aviptadil vs 36% on placebo (HR 1.04); diarrhea, flushing, fast heart rate and low blood pressure were more common on aviptadil.
Read the study196 patients with critical COVID-19 at 10 US hospitals, 2:1 randomization
Missed its primary endpoint (OR 1.6, 95% CI 0.86 to 3.11); diarrhea occurred in 32.8% on aviptadil vs 1.5% on placebo.
Read the study308 men in London who had failed or not tolerated alprostadil injections
59% overall resumed penetrative sex (76% of men who stopped alprostadil for pain, 36% of those who failed its maximum dose); 22.5% had facial flushing, 1 man (0.3%) had priapism.
Read the study20 patients with active pulmonary sarcoidosis, 4 weeks of nebulized VIP
Lung lavage cells made less TNF-alpha and regulatory T cells increased; well tolerated, but no placebo group and no clinical endpoint.
Read the study20 patients with pulmonary hypertension during right-heart catheterization
A single 100 microgram inhaled dose caused a small, short-lived drop in lung vessel resistance; 6 of 20 had more than a 20% reduction.
Read the study20 patients with CIRS attributed to water-damaged buildings, no control group
Authors report symptoms and markers (C4a, TGF-beta-1, MMP9) returning to control levels over at least 18 months of nasal VIP; uncontrolled and from the protocol developer's clinic.
Read the study4 healthy volunteers, IV infusion
Plasma VIP fell with a half-time of about 1 minute after infusion; the highest dose caused flushing, faster pulse and a small rise in blood sugar.
Read the studyNo preclinical studies are listed as key studies here. The human data above carries the evidence.
These are questions the published research has not answered.
No FDA-approved VIP product exists. FDA has not approved IV aviptadil for COVID-19 respiratory failure; the NIH TESICO trial stopped it for futility in 2022. Invicorp is licensed in the UK (current marketing authorisation dated April 21, 2015) and Denmark, where it launched in 2006, and a 2007 company release also listed approval in New Zealand; it is used as a second-line injection after oral ED tablets fail. VIP is not named on the WADA Prohibited List, and because aviptadil is an approved drug in Europe it falls outside the S0 catch-all; check with your anti-doping agency.
How much of VIP (Vasoactive Intestinal Peptide) is left after a single dose
Simple first-order model from the published half-life. Real clearance varies with dose, route, kidney and liver function and formulation. This is not a dosing schedule.
This table records the doses that trials and approved labels used, with the source for each row. It is a record of research, not a recommendation, and it is open to free members.
Which symptoms are expected and which mean stop and get help: side effects and red flags.
Tap a claim to see what the studies found.
The support is one 20-patient open-label study with no placebo group, from the clinic that created the CIRS protocol. That design cannot separate drug effect from time, other treatment steps or expectation.
The company-run 196-patient trial missed its primary endpoint, and the NIH TESICO trial in 461 patients stopped for futility with 38% vs 36% deaths by day 90.
VIP lowers TNF-alpha and boosts regulatory T cells in cells, animals and one 20-patient sarcoidosis study. Whether that changes any disease outcome in humans has not been shown, and it lasts about a minute in blood.
Injected into the penis with phentolamine it is a licensed second-line ED treatment in the UK and Denmark. That applies to the injection, not to nasal or other routes.
VIP is a gut nerve signal, but its main gut effect is secretion of water and salt. Excess VIP from VIP-secreting tumors causes severe watery diarrhea. No trial has shown it repairs the gut lining in people.
These pairings come up often. Almost none have been tested together in a trial, and the evidence note on each says so plainly.
In the Shoemaker protocol for CIRS, nasal VIP is added last, after removing mold exposure and earlier treatment steps, for patients with low measured VIP and ongoing symptoms.
EvidenceThe sequence and the VIP step are supported only by uncontrolled reports from the protocol's developer. No randomized trial has tested any part of the stack.
Discussed online as an anti-inflammatory gut combination.
EvidenceNever studied together. BPC-157 and KPV have no human efficacy trials, and VIP itself increases intestinal fluid secretion.
No US-labeled product exists. Invicorp is supplied as ready-made ampoules; follow its product information. No published stability data cover research-grade VIP powder.
Compounded nasal sprays carry pharmacy-assigned beyond-use dates and refrigeration instructions; no published stability study covers them.
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