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Peptide (natural hormone)Human trialsNot FDA approved

VIP

Vasoactive intestinal peptide

Last reviewed October 27, 2026 · 20 sources · Written for general readers · Compare with another compound →

The bottom line

VIP is a natural hormone that widens blood vessels and airways, and its lab made copy is called aviptadil. In the largest and best run trial, in people on breathing support with COVID-19, it did not improve survival or recovery. Small inhaled studies in lung disease looked hopeful but were tiny, and no aviptadil product is approved in the United States.

Where the evidence stands

What it is

VIP stands for vasoactive intestinal peptide. It is a natural signaling molecule of 28 amino acids, with the sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN, made in the gut, the nerves and elsewhere in the body.[1]

Aviptadil is the lab made copy of the same peptide. It was studied as a drip into a vein in hospital, and as an inhaled mist.[2]

Outside the United States, an injection that combines VIP with phentolamine, another blood vessel widening drug, has been used to treat erectile dysfunction.[3][4]

Name
VIP (Vasoactive intestinal peptide)
Other names
aviptadil (the synthetic form), Zyesami (trial name)
Type
Peptide (natural hormone)
Sequence
HSDAVFTDNYTRLRKQMAVKKYLNSILN

What it does in the body

VIP is a natural hormone and nerve signal made throughout the brain, the nerves and the gut. It works by switching on two receptors, called VPAC1 and VPAC2, and its best known jobs are relaxing smooth muscle, widening blood vessels and calming immune responses.[1]

This is the biology, area by area. A change measured in the body, like a higher blood level, does not always mean a person feels a benefit. The claims check below covers that.

Heart and blood vessels

Well established

VIP widens blood vessels, lowers blood pressure and makes the heart muscle squeeze harder.[1] In 20 people with high blood pressure in the lungs, one inhaled dose briefly widened lung blood vessels and raised the amount of blood pumped with each heartbeat without lowering blood pressure in the rest of the body.[5]

Lungs and airways

Measured in people

VIP relaxes the smooth muscle of the windpipe and is a strong widener of airways.[1][6] In 20 people with sarcoidosis who inhaled it for four weeks, immune cells washed out of the lungs made less of the inflammation signal TNF.[7] Given by IV drip to people with COVID-19 lung failure, it did not improve recovery or survival.[2]

Gut

Well established

VIP relaxes the muscle of the stomach and gall bladder.[1] Rare tumors that pour out VIP, called VIPomas, cause severe watery diarrhea, low blood potassium and low stomach acid, and the high VIP levels can lead to dangerous heart problems.[8][9] This shows what too much VIP does to the gut.

Immune system

Measured in people

In nerves and the brain, VIP mainly protects nerve cells and tones down immune responses.[1] In people with sarcoidosis who inhaled it, lung samples showed more regulatory T cells, the cells that keep immune attacks in check, and in lab dishes it turned immature T cells into this type.[7]

Sleep and body clock

Seen in animals

In the brain's master clock, VIP signals through the VPAC2 receptor. Mice bred without that receptor could not keep normal daily rest and activity rhythms, and clock genes in the master clock lost their daily pattern.[10] No study has shown that taking VIP changes sleep in people.

Sexual function

Measured in people

In erections, VIP mainly helps the veins of the penis trap blood.[3] Injected into the penis together with phentolamine, it worked for 59 percent of 308 men whose earlier treatments had failed.[4]

How it works

VIP relaxes smooth muscle, the kind of muscle in blood vessel and airway walls.

  • It is a strong widener of airways and blood vessels and also affects immune cells.[6]
  • For COVID-19, researchers proposed that it protects the cells that make surfactant, the slippery film that keeps the tiny air sacs open, and calms inflammation, mostly based on cell studies.[2]
  • In people with sarcoidosis who inhaled it, immune cells washed out of the lungs made less of an inflammation signal and included more regulatory T cells, which calm immune attacks.[7]
  • In erections, VIP mainly works by helping the veins trap blood, while phentolamine boosts blood flowing in.[3]

The lung protection ideas came mainly from lab work and did not hold up in the large COVID-19 trial.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Most of the groundwork was in cells rather than animals

  • The proposed COVID-19 benefits, including blocking viral replication, protecting lung cells, calming immune cells and boosting surfactant, were supported mainly by lab cell studies.[2]
  • In lab dishes, VIP turned immature T cells into regulatory T cells, the cells that keep immune attacks in check.[7]
  • Reviews describe VIP as a potent widener of airways and blood vessels with immune calming effects, which led to interest in asthma, COPD and pulmonary hypertension.[6]

Limit: Lab findings about lung cells did not predict what happened in patients.

Human studies

Large IV trials in COVID-19 found no benefit; small inhaled studies were hopeful

  • COVID-19 breathing failure, 2022: 196 critically ill patients at ten US hospitals got an IV drip of aviptadil or placebo. The main goal, being alive and free of breathing failure at 60 days, was not met. Better survival was a secondary finding that the authors said needed testing.[11]
  • COVID-19, TESICO 2023: 471 patients were randomized and the trial was stopped early for futility. At 90 days recovery did not differ, and deaths were 38 percent with aviptadil versus 36 percent with placebo.[2]
  • In TESICO, a combined measure of serious problems in the first five days happened in 63 percent on aviptadil versus 56 percent on placebo, not a significant difference but not reassuring.[2] An editorial called it plainly a negative trial.[15]
  • Inhaled, COVID-19, 2025: 80 adults in hospital at nine centers inhaled aviptadil or placebo. Time to discharge was about 7.8 versus 10 days, lung scans improved more by day 28, and deaths were 5.1 versus 12.2 percent, though the trial was too small to judge deaths. No one dropped out because of side effects.[13]
  • Review, 2025: nine studies with 665 patients, most of them uncontrolled case series, found no survival benefit in the two randomized trials.[12]
  • Sarcoidosis, 2010: 20 people inhaled VIP for four weeks without a comparison group. Lung inflammation markers fell and it was well tolerated.[7]
  • Pulmonary hypertension, 2008: 20 people inhaled a single dose during heart testing. Lung vessels widened slightly for a short time, the amount of blood pumped with each heartbeat improved, systemic blood pressure did not drop, and no side effects were reported.[5]
  • Erectile dysfunction, 2025: 308 men used VIP combined with phentolamine as a penile injection after other treatments failed. 59 percent found it effective, 22.5 percent had facial flushing and 1 man had priapism, a prolonged painful erection.[4]
  • Severe viral lung failure, India (2024): 6 people in intensive care got an aviptadil drip with usual care, with no comparison group. Average oxygen levels rose from about 88 to 93 percent after three days and chest scans looked better, with no side effects noted.[16] With six patients and no controls, this cannot show the drug caused the change.
  • Mold illness (2016): 15 patients of one clinic used a VIP nasal spray, and blood tests showed shifts in the activity of immune and energy genes. There was no comparison group and no symptom data in the report.[14]

Limit: The best evidence, from large IV trials in COVID-19, shows no benefit, and the hopeful inhaled studies were small or uncontrolled.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Saves lives in severe COVID-19 and lung failure

No benefit in trials so far

In a 471 patient trial of people on oxygen or breathing support, an IV drip of aviptadil did not improve recovery at 90 days, and 38 percent died versus 36 percent with placebo. The trial was stopped early for futility.[2] A 196 patient trial also missed its main goal.[11] A 2025 review pooling the two controlled trials found no survival benefit, with an odds ratio of 1.01.[12]

Speeds lung recovery when inhaled

Mixed results

In one placebo controlled trial of 80 adults in hospital with COVID-19, those who inhaled aviptadil went home after about 7.8 days versus 10 days, a difference just at the edge of statistical significance, and lung scans looked better at day 28.[13] This single small trial has not been confirmed.

Calms lung inflammation such as sarcoidosis

Mixed results

In a study of 20 people with active sarcoidosis who inhaled VIP for four weeks, lung immune cells made less of the inflammation signal TNF and calming regulatory T cells increased, and it was well tolerated.[7] There was no comparison group, and the study measured lab markers rather than breathing or symptoms.

Lowers high blood pressure in the lungs

Mixed results

In 20 people with pulmonary hypertension, a single inhaled dose during a heart catheter test caused a small, short lived widening of lung blood vessels, and 6 of the 20 had a drop of more than 20 percent in lung vessel resistance.[5] No long term controlled trial results were found.

Treats erectile dysfunction

Mixed results

Only as an injection into the penis combined with phentolamine. A review reported it worked in at least 80 percent of men in clinical studies.[3] In a 2025 look back at 308 men whose earlier treatments failed, 59 percent found it effective, about 23 percent had facial flushing and one man had a prolonged painful erection.[4] VIP alone, in the forms sold online, has not been tested for this.

Treats mold illness (CIRS)

Mixed results

Nasal VIP is promoted for chronic inflammatory response syndrome, an illness blamed on water damaged buildings. The only report we found was by the clinician who promotes the treatment: 15 patients using a VIP nasal spray had shifts in the activity of immune and energy genes in their blood.[14] There was no placebo group, and no symptom scores were given, so the claim is essentially untested.

Known risks and side effects

  • No proven benefit where it was tested most. The largest trial was stopped for futility and found no improvement at 90 days, and pooled trials show no survival benefit.[2][12]
  • Flushing, low blood pressure and prolonged erection. VIP widens blood vessels. Facial flushing affected about 23 percent of men using the penile injection, and about 1 in 300 had a prolonged painful erection. IV use was studied only in monitored hospital settings.[4][2]
  • Serious problems not reduced in hospital. In the TESICO trial, serious problems in the first five days were somewhat more common with aviptadil than with placebo, 63 versus 56 percent.[2]
  • Too much VIP causes severe diarrhea. People with tumors that release large amounts of VIP get severe watery diarrhea, low potassium and heart complications, which shows that high VIP levels can be dangerous.[8][9]
  • Unregulated products. No aviptadil product has a US drug label, and VIP sits only in FDA's under evaluation compounding category, so material sold online has had no FDA review of purity or sterility.[17][18]

Regulatory status

Today: There is no approved aviptadil product in the United States, and a search of the national drug label database returns no results.[17] The COVID-19 trials were run under an FDA investigational new drug protocol, not under an approval.[2] FDA lists vasoactive intestinal peptide in category 1 of its 503A bulk drug substances list, meaning it is still under evaluation for pharmacy compounding, not cleared.[18] FDA twice declined to authorize aviptadil for emergency use in COVID-19, first citing a lack of safety and efficacy data.[19] VIP is not named on WADA's 2027 Prohibited List.[20]

  1. A 196 patient US trial in critical COVID-19 misses its main goal.[11]
  2. An independent safety board recommends stopping the larger TESICO trial for futility.[2]
  3. FDA declines a second request for emergency use authorization of aviptadil in COVID-19, after an earlier refusal for lack of safety and efficacy data.[19]
  4. TESICO results show no benefit at 90 days, alongside an editorial calling it a negative trial.[2][15]
  5. An 80 person inhaled trial reports shorter hospital stays, and a review of all studies finds no survival benefit.[13][12]
  6. FDA's 503A bulks list shows vasoactive intestinal peptide in category 1, under evaluation.[18]

Sources

  1. UniProt Consortium. VIP peptides, human. UniProtKB entry P01282 (function annotation). UniProt P01282
  2. Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023;11(9):791-803. PMID 37348524
  3. Dinsmore WW, Wyllie MG. Vasoactive intestinal polypeptide/phentolamine for intracavernosal injection in erectile dysfunction. BJU Int. 2008;102(8):933-937. PMID 18485029
  4. Al-Mitwalli A, Holden F, Di Giovanni A, et al. Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction. J Sex Med. 2025;22(5):726-730. PMID 40192471
  5. Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. PMID 18978135
  6. Mathioudakis AG, Chatzimavridou-Grigoriadou V, Evangelopoulou E, Mathioudakis GA. Vasoactive intestinal Peptide inhaled agonists: potential role in respiratory therapeutics. Hippokratia. 2013;17(1):12-16. PMID 23935337
  7. Prasse A, Zissel G, Lutzen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 2010;182(4):540-548. PMID 20442436
  8. Karele EN. All you need to know about VIPoma: Review on the latest studies. Presse Med. 2024;53(2):104222. PMID 38109967
  9. Azizian A, Konig A, Ghadimi M. Treatment options of metastatic and nonmetastatic VIPoma: a review. Langenbecks Arch Surg. 2022;407(7):2629-2636. PMID 35931878
  10. Harmar AJ, Marston HM, Shen S, et al. The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei. Cell. 2002;109(4):497-508. PMID 12086606
  11. Youssef JG, Lavin P, Schoenfeld DA, et al. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Crit Care Med. 2022;50(11):1545-1554. PMID 36044317
  12. Udupa AA, Todur P, Chaudhuri S, et al. Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis. Indian J Crit Care Med. 2025;29(11):942-953. PMID 41368449
  13. Esendagli D, Sari N, Akhan S, et al. Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19. Med Princ Pract. 2025;34(2):191-200. PMID 39870064
  14. Shoemaker R. RNA-Seq on patients with chronic inflammatory response syndrome (CIRS) treated with vasoactive intestinal peptide (VIP) shows a shift in metabolic state and innate immune functions that coincide with healing. Medical Research Archives. 2016;4(7). Med Res Arch 2016
  15. Lee WL, Slutsky AS. A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure. Lancet Respir Med. 2023;11:759-760. doi 10.1016/S2213-2600(23)00218-7
  16. Sampley S, Bhasin D, Sekhri K, et al. Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study. Indian J Crit Care Med. 2024;28(1):70-74. PMID 38510776
  17. U.S. National Library of Medicine. DailyMed search for aviptadil, accessed October 2026. DailyMed, no results
  18. U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (category lists). Updated May 14, 2026. FDA 503A category lists
  19. Taylor NP. Deja vu: FDA rejects NRx filing for emergency use in COVID-19. Fierce Biotech. July 1, 2022. News report
  20. World Anti-Doping Agency. International Standard: The 2027 Prohibited List. Comes into effect 1 January 2027. WADA 2027 List
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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