VIP (Vasoactive Intestinal Peptide): the basics
What is it?
A natural chain of 28 amino acids made by nerve and immune cells. It relaxes smooth muscle, widens blood vessels and calms some immune responses.
Research paper 1 ↗Research paper 2 ↗Research paper 3 ↗What do people claim it helps with?
Healing damaged lungs, treating COVID-19, calming inflammation throughout the body and improving erections.
What has research actually shown?
A large NIH-funded trial found that intravenous VIP (aviptadil) did not help people with severe COVID-19. A VIP-phentolamine injection did help erections in a placebo-controlled trial.
Research paper 1 ↗Research paper 2 ↗Research paper 3 ↗Has this been demonstrated in people?
Hospital trials in COVID-19 and older erectile-dysfunction trials, plus a lot of laboratory and animal research on inflammation.
Research paper 1 ↗Research paper 2 ↗Research paper 3 ↗What side effects, risks and unknowns should I understand?
Facial flushing is common with injections. In COVID-19 trials, serious problems were frequent in both groups because patients were very ill. Long-term effects of unsupervised use are unknown.
Research paper 1 ↗Research paper 2 ↗Is it an approved medicine?
No FDA-approved medicine contains VIP or aviptadil. A VIP-phentolamine injection is used for erectile dysfunction in some other countries, which is not U.S. approval.
FDA briefing ↗Approval here means U.S. FDA approval and applies to a particular product, formulation and use. This is a starting overview, not a complete side-effect list. Sources checked 10 October 2026; independent scientific review pending.
How is it used or studied?
Studied as an intravenous drip, an inhaled spray and, with phentolamine, an injection for erectile dysfunction. There is no FDA-approved U.S. product.
Different routes and formulations can have different effects. A study of one product does not validate every product with the same peptide name.
A common misunderstanding
VIP is not the same as PACAP or other peptides that share its receptors, and erectile-dysfunction results for the two-drug combination do not apply to VIP alone.
What should I ask a clinician?
- What diagnosis or goal are we trying to address, and what established options are available?
- Was the expected benefit shown in people like me, using this exact product?
- How could my medicines, health conditions or pregnancy plans affect the risks?
- What monitoring is needed, and what would tell us the treatment is helping or should be stopped?
What do the research words mean?
- Peptide
- A short chain of amino acids, the building blocks of proteins.
- Preclinical
- Research in cells, tissues or animals before dependable treatment evidence in people.
- Controlled trial
- A study comparing a treatment with another treatment or a placebo to help separate its effects from other explanations.
- Biomarker
- A measurement, such as a hormone level. A change does not necessarily mean someone feels better or lives longer.
VIP (Vasoactive Intestinal Peptide) Evidence & Clinical Profile
Human Study Limits
VIP (Vasoactive Intestinal Peptide) has been investigated in clinical contexts. Patient outcomes must be evaluated against study size, design, and control cohorts.
Laboratory & In Vivo Assays
Cellular and animal disease models examine receptor binding affinities and signaling cascades, which require human confirmation.
What is VIP (Vasoactive Intestinal Peptide)?
Vasoactive Intestinal Peptide (aviptadil) is A 28-amino-acid neuropeptide made by nerves and immune cells that relaxes smooth muscle and dampens inflammation. Its synthetic form, aviptadil, was tested intravenously for COVID-19 respiratory failure; an NIH-funded phase 3 trial found no benefit. Combined with phentolamine as an injection (Invicorp), it is used for erectile dysfunction outside the U.S. No VIP product is FDA approved. Aliases include: Aviptadil, Vasoactive intestinal polypeptide, RLF-100, Zyesami, Invicorp (aviptadil with phentolamine).
- Sequence (one-letter)
- HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2
- Molecular formula
- C147H238N44O42S
- Molecular weight
- 3325.8 g/mol
- CAS Number
- 40077-57-4
- UNII Code
- A67JUW790C
- PubChem CID
- 16140438
Identifiers checked against PubChem and FDA's Global Substance Registration System on 13 October 2026. FDA substance record ↗ · PubChem record ↗ See all names and codes in the peptide name index.
Clinical Trials & Human Cohorts
Human research can examine tolerability, symptoms or patient outcomes. The design and comparator determine what each result can establish.
Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial [1]
What was reported
No improvement in 90-day recovery (odds ratio 1.11). Deaths to day 90 were 38% with aviptadil and 36% with placebo. The monitoring board stopped the aviptadil comparison for futility.
What limits the conclusion
Tested only intravenous aviptadil in severe COVID-19; it says nothing about other uses or routes.
The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial [2]
What was reported
The primary endpoint (alive and free of respiratory failure at day 60) was not met. The authors highlighted a secondary survival difference.
What limits the conclusion
Primary endpoint missed; positive findings are secondary or subgroup analyses and were not confirmed by the larger TESICO trial.
Treating men with predominantly nonpsychogenic erectile dysfunction with intracavernosal vasoactive intestinal polypeptide and phentolamine mesylate in a novel auto-injector system: a multicentre double-blind placebo-controlled study [3]
What was reported
Erections suitable for intercourse were reported far more often with the VIP-phentolamine injection than with placebo. Facial flushing was the main side effect.
What limits the conclusion
Tests a two-drug combination injected into the penis, not VIP alone; the trial is more than 25 years old.
Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction [4]
What was reported
59% resumed penetrative sex; facial flushing affected 22.5% and one man (0.3%) had priapism.
What limits the conclusion
Retrospective, no control group and no validated erectile-function questionnaire.
How the compound may work
Mechanisms describe how VIP (Vasoactive Intestinal Peptide) may affect biological processes. Laboratory findings and patient outcomes answer different questions.
VPAC1 and VPAC2 receptors
VIP acts on two G-protein-coupled receptors, VPAC1 and VPAC2, which it shares with the related peptide PACAP. These receptors take part in immune, nerve, pancreatic and smooth-muscle signalling. [5]
Immune regulation
VIP is released by neurons and immune cells and has anti-inflammatory and immune-regulating effects in laboratory and animal models. These effects have not translated into a proven treatment. [6]
Areas Being Studied
These research topics reflect active areas of scientific exploration, distinct from unverified commercial marketing claims.
COVID-19 respiratory failure
Intravenous aviptadil did not improve recovery or survival in the phase 3 TESICO trial. [1]
Erectile dysfunction
An injected VIP-phentolamine combination outperformed placebo in a 1999 trial and is used in some clinics outside the U.S. [3]
Inflammatory and autoimmune disease
Studied for immune-regulating effects, mostly in cell and animal models. [6]
Compare the study designs.
| Study | Design / sample | Outcome type | Key limitation |
|---|---|---|---|
| TESICO (COVID-19) · 2023 [1] | Randomized placebo-controlled trial (NIH ACTIV-3b platform) n = 461 |
Clinical endpoint evaluation | Tested only intravenous aviptadil in severe COVID-19; it says nothing about other uses or routes. |
| IV aviptadil (COVID-19) · 2022 [2] | Multicentre placebo-controlled RCT (2:1 randomization) n = 196 |
Clinical endpoint evaluation | Primary endpoint missed; positive findings are secondary or subgroup analyses and were not confirmed by the larger TESICO trial. |
| Erectile dysfunction (with phentolamine) · 1999 [3] | Multicentre double-blind placebo-controlled trial n = 236 |
Clinical endpoint evaluation | Tests a two-drug combination injected into the penis, not VIP alone; the trial is more than 25 years old. |
| Refractory ED clinic series · 2025 [4] | Retrospective single-centre cohort n = 308 |
Clinical endpoint evaluation | Retrospective, no control group and no validated erectile-function questionnaire. |
Regulatory Status & Clinical Safety
Regulatory Classification
Not FDA approved in any form; Drugs@FDA lists no aviptadil or VIP product. VIP is in FDA's 503A bulk-substance category 1 (under evaluation; list updated May 14, 2026), which is not drug approval. An aviptadil-phentolamine injection (Invicorp) is used for erectile dysfunction outside the U.S.
Safety Realities & Impurities
Safety depends on the molecule, formulation, route and evidence. A laboratory purity measurement alone cannot establish safety for human use.
Clinical Trials Registry Records
Official registry records from ClinicalTrials.gov. Study registration does not imply government endorsement or guaranteed efficacy.
ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 [8]
- Planned enrollment
- 473 (patients)
- Posted results
- Available
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Last updated
- 2025
Intravenous Aviptadil for Critical COVID-19 With Respiratory Failure [9]
- Planned enrollment
- 203 (patients)
- Posted results
- Available
- Sponsor
- APR Applied Pharma Research s.a.
- Last updated
- 2023
Inhaled ZYESAMI™ (Aviptadil Acetate) for the Treatment of Severe COVID-19 [10]
- Planned enrollment
- 144 (patients)
- Posted results
- Pending in registry
- Sponsor
- APR Applied Pharma Research s.a.
- Last updated
- 2023
WADA & Anti-Doping Regulations
WADA Anti-Doping Status
VIP (Vasoactive Intestinal Peptide) is not prohibited under current World Anti-Doping Agency (WADA) regulations. However, athletes must ensure unregulated preparations or unverified vendor products do not violate Section S0 (Non-approved substances). Last verified: October 2026.
Research Timeline
-
1970
Isolated from intestine
Said and Mutt isolate a 28-amino-acid peptide with broad effects, including widening blood vessels, from pig small intestine. [7]
-
1999
Erectile dysfunction trial
A placebo-controlled trial tests a VIP-phentolamine injection for erectile dysfunction. [3]
-
2022
IV aviptadil trial reported
A COVID-19 respiratory failure trial misses its primary endpoint. [2]
-
2023
TESICO phase 3 result
NIH-funded trial finds no benefit of intravenous aviptadil in COVID-19 respiratory failure. [1]
-
2026
U.S. compounding status
VIP remains in FDA's 503A category 1 (under evaluation), which is separate from drug approval. [11]
What Researchers Still Don't Know
Long-term safety profiles
Multi-year observational data in broader heterogeneous cohorts remains uncharacterized.
Optimal dose-response thresholds
Comparative trials optimizing minimal effective exposure versus adverse event rates.
Formulation bioavailability
Differences between oral, subcutaneous, and modified peptide delivery vehicles.
References
Primary sources verified against PubMed / NLM and regulatory databases.
- Randomized controlled trial
- Randomized controlled trial
- Randomized controlled trial
- Retrospective cohort
- Pharmacology review
-
Narrative review
Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions ↗ (external website)
-
Discovery paper
Polypeptide with broad biological activity: isolation from small intestine ↗ (external website)
-
Registry Record
NCT04843761 ACTIV-3b: Therapeutics for Severely Ill Inpatients With COVID-19 ↗ (external website)
- Registry Record
- Registry Record
- FDA compounding category list