VIP Peptide Benefits and Side Effects: Research Data
What animal studies and small human trials report on vasoactive intestinal peptide, why the large aviptadil trials failed, what side effects were seen, and where VIP stands with regulators.
Update History ▾
Research-use-only framing applied throughout in line with Remy editorial standards.
The VIP peptide benefits most often claimed (lung protection, lower inflammation, better gut health and immune balance) come mainly from mouse models and small human studies; no VIP medicine has shown a clear benefit in a large controlled trial.[1][2][3] Aviptadil, the drug name for synthetic VIP, missed the primary endpoints of two US trials in critical COVID-19, one of them an NIH trial stopped for futility.[4][5]
VIP peptide side effects in human studies include flushing, a faster pulse and, in people with migraine, headache attacks.[6][7] Aviptadil is not FDA-approved; India authorised it for restricted emergency use in severe COVID-19 in 2022.[8][9] Remy Research supplies VIP for in-vitro laboratory research only.
What Is Vasoactive Intestinal Peptide (VIP)?
Vasoactive intestinal peptide (VIP), also called vasoactive intestinal polypeptide, is a chain of 28 amino acids ending in an asparagine amide. It is cut from a larger precursor made by the vasoactive intestinal peptide gene, which also yields a related peptide, PHM-27.[10] Sami Said and Viktor Mutt isolated it from hog small intestine in 1970 and found that it widened blood vessels, lowered blood pressure and raised cardiac output in animals.[11]
VIP belongs to the same peptide family as glucagon, GLP-1, secretin and GHRH, and is closely related to PACAP. It works in the central nervous system and in the peripheral nervous systems, where it acts as a co-transmitter released by nerve cells.[12] In the body VIP acts mainly as a short-lived local nerve signal: in volunteers it left the blood within about one minute.[6]
How VIP Acts: VIP Receptors
VIP acts through two receptors, VPAC1 and VPAC2, which bind VIP and PACAP with high affinity; a third receptor, PAC1, prefers PACAP. VIP receptors help control circadian rhythms in the brain and, in the rest of the body, the immune system, inflammation and insulin secretion.[12] Mice lacking the VPAC2 receptor lost their normal daily rest–activity rhythm, showing that the receptor is essential for the brain’s master clock.[13]
Potential VIP Peptide Benefits in Research
The table lists each claimed benefit, what was reported and the type of evidence.
| Claimed benefit | What was reported | Evidence type |
|---|---|---|
| Blood vessels | Vasodilation and lower blood pressure | Animal, small human |
| Pulmonary hypertension | Lower artery pressure in 8 patients | Human, uncontrolled |
| Anti inflammatory | Milder arthritis and colitis in mice | Animal |
| Sarcoidosis | Fewer inflammatory signals, more T regs | Human, open study |
| COVID-19 lungs | Two US trials missed primary endpoints | Human, randomised |
| Circadian rhythms | VPAC2 needed for normal daily rhythm | Animal (knockout) |
Blood Flow, Blood Pressure and Pulmonary Hypertension
VIP relaxes blood vessels: the original animal work showed lower blood pressure and higher cardiac output.[11] In 2003 a Vienna group reported a deficiency of VIP in the serum and lung tissue of patients with primary pulmonary hypertension; in eight patients studied without a control group, vasoactive intestinal peptide lowered mean pressure in the pulmonary arteries (pulmonary arterial pressure) and raised cardiac output.[2] In a 2008 study of 20 patients, a single exposure produced a small, short-lived widening of the pulmonary blood vessels, with a fall of more than 20% in vascular resistance in 6.[14] Neither study can show a lasting effect on pulmonary arterial hypertension.
Anti Inflammatory Effects and Autoimmune Diseases
In mice, VIP reduced the incidence and severity of experimental arthritis, a model of rheumatoid arthritis, by lowering both inflammatory and autoimmune immune responses.[1] In a mouse model of Crohn’s disease, a type of inflammatory bowel disease, VIP reduced colitis severity, lowered pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6, and reduced interferon gamma made by T cells, even when given after the disease began.[15] The picture is not uniform: VIP deficient mice developed milder colitis than normal mice, not worse.[16] These anti inflammatory properties have not been confirmed in a controlled human trial.
Immune Tolerance and the Lungs
In an open phase II study, 20 people with sarcoidosis were studied for four weeks. Immune cells from their lungs made less of the inflammatory cytokine TNF-α, and regulatory T cell production rose, suggesting VIP may induce immune tolerance; there was no placebo group.[3]
Circadian Rhythms and the Central Nervous System
VIP signalling is part of the brain’s master clock: mice without the VPAC2 receptor could not sustain normal circadian rhythms.[13][12] No human study has tested VIP for sleep or circadian disorders.
Clinical Trials of Aviptadil and VIP Analogues
- Critical COVID-19, 2022. 196 patients at 10 US hospitals were randomised to aviptadil or placebo. The primary endpoint, alive and free of respiratory failure at day 60, was not met; the authors highlighted a secondary survival result.[4]
- TESICO, 2023. In this NIH-funded trial of 461 patients at 28 US sites, the aviptadil comparison was stopped for futility. Recovery at day 90 did not improve, and 90-day mortality was 38% against 36% on placebo.[5]
- Hospitalised COVID-19, 2025. A double-blind trial of an aviptadil formulation in 80 patients at nine Turkish centres reported a mean time to discharge of 7.8 against 10 days and greater improvement on lung scans at day 28.[17]
A 2025 meta-analysis of aviptadil in acute respiratory distress pooled two randomised trials and found no survival difference.[18] Across all uses, ClinicalTrials.gov lists 58 records for aviptadil or vasoactive intestinal peptide, many of them studies that only measure VIP rather than clinical trials testing it.[19]
Other trials have stalled. A Vienna study of VIP in chronic obstructive pulmonary disease, with 34 participants, was completed in 2006 but has posted no results.[20] A phase 2 trial of pemziviptadil, a long-acting VIP analogue, in pulmonary arterial hypertension was terminated after 35 participants when drug supply was delayed by COVID-19, and a pemziviptadil COVID-19 trial was terminated after 54 when the company stopped pursuing the indication.[21][22]
Gut Health and VIP Blood Levels
VIP is named for the gastrointestinal tract, and the clearest human evidence on high VIP blood levels comes from VIPoma, a rare and mostly malignant tumour. Its unregulated VIP release causes watery diarrhoea, low blood potassium and a lack of stomach acid secretion.[23] Claims that VIP helps “mould illness”, or chronic inflammatory response syndrome, rest on one case report of a man with ulcerative colitis and fatigue who received VIP alongside removal from the mould exposure and other treatments, so no effect can be attributed to VIP.[24]
VIP Peptide Side Effects and Safety
- Flushing and pulse. In volunteers, raising VIP to levels seen in VIPoma caused flushing and a faster pulse.[6]
- Low blood pressure. VIP lowered blood pressure in the original animal studies.[11]
- Headache. In a 2021 Danish trial, which used the name vasoactive intestinal polypeptide, a two-hour exposure triggered migraine attacks in 15 of 21 people with migraine, against 1 after placebo.[7]
- Critical care. In TESICO, a day-5 safety composite of death, serious adverse events, organ failure or serious infection occurred in 63% on aviptadil and 56% on placebo, a difference that was not statistically significant.[5]
- Excess VIP. Sustained high levels, as in VIPoma, cause watery diarrhoea and low potassium.[23]
There are no long-term human safety data.
Is VIP FDA Approved?
- FDA approval. No. Drugs@FDA lists no aviptadil application.[8]
- Compounding. “Vasoactive Intestinal Peptide” is in Category 1 of FDA’s 503A compounding nominations, “bulk drug substances under evaluation”; that is not an approval.[25]
- India. The national drug regulator authorised aviptadil on April 29, 2022 for restricted emergency use in patients with severe COVID-19 and acute respiratory distress syndrome.[9]
- Europe and UK. Aviptadil holds an EU orphan designation for acute respiratory distress syndrome (February 2026), which EMA says does not mean it is authorised.[26] A combination with phentolamine (Invicorp) was accepted for restricted NHS Scotland use in erectile dysfunction in 2017.[27]
- Sport. VIP and aviptadil are not named on WADA’s 2027 Prohibited List.[28]
- UAE. VIP is not a registered medicine. Remy Research sells it for in-vitro laboratory research only, not for human or veterinary use.
VIP vs Other Immune and Neuropeptides
VIP is often discussed alongside other peptides studied for immune modulation and inflammation, such as thymosin alpha-1 and KPV, and alongside oxytocin as a neuropeptide. See the thymosin alpha-1 review, the KPV review and the oxytocin review.
What the Research Does Not Yet Show
- A positive large trial. Both US randomised trials in critical COVID-19 missed their primary endpoints.[4][5]
- Controlled lung-disease data. The pulmonary hypertension and sarcoidosis studies were small and had no placebo group.[2][3]
- A consistent immune picture. VIP helped in mouse arthritis and colitis models, yet mice lacking VIP had milder colitis.[1][16]
- Stability in the body. VIP leaves the blood within minutes.[6]
VIP for Laboratory Research
Remy Research supplies VIP for in-vitro research as the Genovare VIP 25mg AQ pen. The product page carries its batch testing details. For the full receptor and trial review, read the VIP research review.
Our Research Standards
This article prioritizes primary literature, trial records and regulator documents, and keeps receptor, animal and human evidence apart. Where the human record is thin, we say so directly. No therapeutic, dosing or administration guidance is given. Read our editorial policy →
VIP Peptide Benefits and Side Effects FAQ
What is VIP peptide?
What are the benefits of VIP peptide?
What are the side effects of VIP peptide?
Is VIP FDA approved?
Is VIP safe?
Is VIP the same as aviptadil?
What is the role of aviptadil in treating ARDS?
How does VIP affect the immune system?
What happens with high VIP levels?
VIPoma, a rare tumour that releases VIP, causes watery diarrhoea, low potassium and a lack of stomach acid.[23]
Sources
- Delgado M, Abad C, Martinez C, et al. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med. 2001;7(5):563-568. doi: 10.1038/87887 · PMID: 11329057 ↩
- Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003;111(9):1339-1346. doi: 10.1172/JCI17500 · PMID: 12727925 ↩
- Prasse A, Zissel G, Lützen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 2010;182(4):540-548. doi: 10.1164/rccm.200909-1451OC · PMID: 20442436 ↩
- 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. doi: 10.1097/CCM.0000000000005660 · PMID: 36044317 ↩
- Brown SM, Barkauskas CE, Grund B, et al; ACTIV-3b/TESICO Study Group. 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. doi: 10.1016/S2213-2600(23)00147-9 · PMID: 37348524 ↩
- Domschke S, Domschke W, Bloom SR, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut. 1978;19(11):1049-1053. doi: 10.1136/gut.19.11.1049 · PMID: 730072 ↩
- Pellesi L, Al-Karagholi MA, De Icco R, et al. Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial. JAMA Netw Open. 2021;4(8):e2118543. doi: 10.1001/jamanetworkopen.2021.18543 · PMID: 34357396 ↩
- U.S. Food and Drug Administration. Drugs@FDA data (openFDA drugsfda endpoint) searched for the active ingredient aviptadil, October 28, 2026: no matching application. api.fda.gov ↩
- Central Drugs Standard Control Organisation (India). List of new drugs approved in the year 2022, entry 13: aviptadil bulk and aviptadil injection, for patients with severe COVID-19 with acute respiratory distress syndrome, for restricted emergency use in light of the COVID-19 outbreak; date of issue April 29, 2022. Checked October 28, 2026. cdsco.gov.in ↩
- UniProt Consortium. UniProtKB P01282, VIP peptides (human): vasoactive intestinal peptide, residues 125–152, with a C-terminal asparagine amide; the same precursor yields PHM-27. uniprot.org/uniprotkb/P01282 ↩
- Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970;169(3951):1217-1218. doi: 10.1126/science.169.3951.1217 · PMID: 5450698 ↩
- Harmar AJ, Fahrenkrug J, Gozes I, et al. Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol. 2012;166(1):4-17. doi: 10.1111/j.1476-5381.2012.01871.x · PMID: 22289055 ↩
- 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. doi: 10.1016/s0092-8674(02)00736-5 · PMID: 12086606 ↩
- Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. doi: 10.1183/09031936.00050008 · PMID: 18978135 ↩
- Abad C, Martinez C, Juarranz MG, et al. Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn’s disease. Gastroenterology. 2003;124(4):961-971. doi: 10.1053/gast.2003.50141 · PMID: 12671893 ↩
- Abad C, Cheung-Lau G, Coûté-Monvoisin AC, et al. Vasoactive intestinal peptide-deficient mice exhibit reduced pathology in trinitrobenzene sulfonic acid-induced colitis. Neuroimmunomodulation. 2015;22(3):203-212. doi: 10.1159/000364912 · PMID: 25301381 ↩
- Esendagli D, Sarı 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. doi: 10.1159/000543773 · PMID: 39870064 ↩
- 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. doi: 10.5005/jp-journals-10071-25084 · PMID: 41368449 ↩
- ClinicalTrials.gov API search for aviptadil OR "vasoactive intestinal peptide", run October 28, 2026 (58 records, including studies that only measure VIP). clinicaltrials.gov ↩
- ClinicalTrials.gov NCT00464932. Vasoactive Intestinal Peptide in COPD (Medical University of Vienna; 34 enrolled; completed July 2006; no results posted). Checked October 28, 2026. clinicaltrials.gov/study/NCT00464932 ↩
- ClinicalTrials.gov NCT03556020. Phase 2 study of pemziviptadil (PB1046), a long-acting VIP analogue, in pulmonary arterial hypertension (PhaseBio; terminated after 35 enrolled: “Study drug resupply delayed (Covid-19)”). Checked October 28, 2026. clinicaltrials.gov/study/NCT03556020 ↩
- ClinicalTrials.gov NCT04433546. Pemziviptadil (PB1046) in hospitalised COVID-19 patients at risk of ARDS (PhaseBio; terminated after 54 enrolled: “Company no longer pursing indication”). Checked October 28, 2026. clinicaltrials.gov/study/NCT04433546 ↩
- Karele EN. All you need to know about VIPoma: Review on the latest studies. Presse Med. 2024;53(2):104222. doi: 10.1016/j.lpm.2023.104222 · PMID: 38109967 ↩
- Gunn SR, Gunn GG, Mueller FW. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue Syndrome Symptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures. Am J Case Rep. 2016;17:320-325. doi: 10.12659/ajcr.896949 · PMID: 27165859 ↩
- U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A: Categories 1–3 (“Vasoactive Intestinal Peptide” in Category 1, bulk drug substances under evaluation; updated May 14, 2026; checked October 28, 2026). fda.gov/media/94155 ↩
- European Medicines Agency. EU/3/26/3200: orphan designation of aviptadil for the treatment of acute respiratory distress syndrome (February 23, 2026); “Orphan designation does not mean the medicine is available or authorised for use.” Checked October 28, 2026. ema.europa.eu ↩
- Scottish Medicines Consortium. Aviptadil/phentolamine mesilate (Invicorp), SMC No 1284/17: accepted for restricted use within NHS Scotland for erectile dysfunction, November 10, 2017. Checked October 28, 2026. scottishmedicines.org.uk ↩
- World Anti-Doping Agency. The 2027 Prohibited List (in force January 1, 2027): vasoactive intestinal peptide and aviptadil are not named. Checked October 28, 2026. wada-ama.org ↩
For catalog details, see the Genovare VIP 25mg AQ pen. For editorial standards, continue to the editorial policy.