Educational reference only. Informational material drawn from peer-reviewed literature. Not medical advice and not a recommendation to use, dose, or modify any therapy. Decisions about hormone therapy should be made with a qualified healthcare provider.
Overview
Overview
VIP (vasoactive intestinal peptide, also vasoactive intestinal polypeptide) is a 28-amino-acid neuropeptide first isolated from porcine intestine in 1970. It belongs to the secretin/glucagon peptide family, which also includes PACAP, glucagon, GLP-1, GIP, and GHRH. The synthetic human peptide is called aviptadil.
It was first described as a gut hormone and a potent vasodilator. It is now known to act throughout the body: the digestive tract, lungs and airways, cardiovascular system, immune system, reproductive tract, and central nervous system, including the circadian clock.
The core practical problem: native VIP is broken down within about two minutes in blood. That short life has limited its clinical use to continuous infusion, inhalation, or local injection. Many "research peptide" VIP products are the same unmodified peptide.
Where it is actually used:
- Established: an intracavernosal injectable combination with phentolamine for erectile dysfunction (brand Invicorp, alias only), approved in the UK and parts of Europe
- Investigational: IV and inhaled aviptadil (RLF-100 / Zyesami, aliases only) for lung injury (ARDS, COVID-19 respiratory failure), sarcoidosis, and pulmonary hypertension
- Off-label/community: compounded intranasal VIP in CIRS / "mold illness" protocols
Forms
Available forms & half-lives
| Form | Approximate half-life |
|---|---|
| Intracavernosal injection (with phentolamine) | Plasma half-life under 2 minutes; effect is local |
| Intravenous infusion | Under 2 minutes; continuous infusion required for sustained effect |
| Inhaled / nebulized | Under 2 minutes in plasma; intended to concentrate effect in the lung |
| Intranasal (compounded, off-label) | Under 2 minutes in plasma; systemic exposure after nasal delivery is not characterized |
| Subcutaneous (community-reported) | Under 2 minutes; systemic effect after a bolus is uncertain |
What it does
Main effects
- Smooth-muscle relaxation and vasodilation in systemic and pulmonary vessels, bronchi, gut and erectile tissue; vasodilating potency estimated at roughly 50 times that of prostacyclin
- Erectile function (intracavernosal, with phentolamine): relaxes cavernosal smooth muscle and may aid veno-occlusion; efficacy similar to alprostadil injection with less injection pain
- Lung protection: at VPAC1 on alveolar type II cells it upregulates surfactant production, inhibits apoptosis, and dampens inflammatory cytokines (TNF-α, IL-6)
- Immune modulation: shifts T-cell responses toward regulatory T cells (Tregs), reduces macrophage activation, inhibits platelet-activating-factor-driven platelet activation
- Acute pulmonary vasodilation when inhaled in lung-disease-related pulmonary hypertension (single-dose hemodynamic study; no long-term benefit established)
- Neural roles: parasympathetic neurotransmitter and neuromodulator; circadian regulation via VPAC2 in the suprachiasmatic nucleus; neurotrophic effects
What to watch for
Common side effects
- Facial flushing: the most common effect with intracavernosal use
- Low blood pressure: the dose-limiting effect with IV use; hypotension occurred in about a quarter of IV-treated patients in one expanded-access cohort
- Rapid heart rate and headache
- Diarrhea (seen in IV cohorts); sustained excess VIP causes profuse watery diarrhea with potassium loss (the VIPoma picture)
- Intracavernosal route: injection pain (less than with alprostadil), bruising, priapism (rare but an emergency), penile fibrosis risk with repeated injections
- Intranasal route: nasal irritation; one report of a transient symptomless lipase elevation
- Unregulated injectable products: sterility, identity and purity risks
Key facts
Key facts worth knowing
- VIP was first isolated from porcine intestine in 1970 and belongs to the secretin/glucagon family alongside PACAP, glucagon, GLP-1, GIP and GHRH. It acts on two Gs-coupled receptors, VPAC1 and VPAC2, and binds the PACAP receptor PAC1 with much lower affinity. PMC: 3483716
- Plasma half-life is under two minutes. Continuous IV infusion or repeated inhalation is needed for any sustained systemic or lung effect, which is why longer-acting VIP analogs have been pursued. Altmeyer's encyclopedia (half-life, vasodilation potency, VIPoma/WDHA)US patent 9,700,598 background (half-life under 2 minutes, receptor tissue distribution)
- The only approved VIP product is the intracavernosal aviptadil + phentolamine combination for erectile dysfunction (first approved 1998; UK, with restricted NHS Scotland use). In an open-label crossover against alprostadil injection, efficacy was similar with fewer moderate/severe adverse events and less injection pain. Evidence grade A for this use. Scottish Medicines Consortium advice, aviptadil/phentolamine (Invicorp)NHS BLMK bulletin 284, Invicorp evidence review, 2023
- IV aviptadil in COVID-19 respiratory failure was negative. A phase 2b/3 trial of about 196 patients missed its primary endpoint, and the independent NIH ACTIV-3b TESICO trial (461 patients) showed no benefit on primary or secondary endpoints at 90 days. FDA did not grant emergency use authorization. Evidence grade B for systemic and inhaled use, mixed to negative. PMC: 9555831TESICO, Lancet Respiratory Medicine 2023PMC: 10278994
- The CIRS / "mold illness" intranasal evidence is low quality (grade C/D): single-clinic, uncontrolled observational reports, often published in patent filings or non-indexed journals, for a diagnosis that is itself contested in mainstream medicine. There are no randomized controlled trials. US patent 9,770,170 (Shoemaker; CIRS intranasal VIP data)Outliyr VIP evidence overview (CIRS evidence quality, compounding)
- VIP-secreting tumors (VIPomas) cause WDHA / Verner-Morrison syndrome: profuse watery diarrhea (1 to 10 liters per day), hypokalemia and achlorhydria. This is what sustained high VIP exposure does, and it is the physiological reason to watch for persistent diarrhea and electrolyte loss with any repeated systemic use. Altmeyer's encyclopedia (VIPoma/WDHA)Iwasaki et al. 2019, F1000Research, VIP in GI physiology and pathophysiology
Legal status
Legal status
No FDA approval for any VIP product; emergency use authorization for IV aviptadil (RLF-100 / Zyesami) in COVID-19 was not granted. Aviptadil + phentolamine (Invicorp) is approved in the UK and parts of Europe for erectile dysfunction, with restricted use in NHS Scotland. Intranasal VIP is compounded, off-label. Outside the approved erectile-dysfunction product, VIP is compounded or research-grade. Not a controlled substance.