VIP (Vasoactive Intestinal Peptide): Research Overview, Mechanisms, and Current Evidence
Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide found throughout the nervous, digestive, and immune systems, where it acts on VPAC1 and VPAC2 receptors. Its synthetic form, aviptadil, has been studied in preclinical and clinical research for lung protection and immune modulation, including randomized trials in COVID-19 respiratory failure. The information below summarizes published research for educational and research purposes only. It is not medical advice and is not guidance for use in humans.
The linked product is a VIP plus BPC-157 combination tablet. Available for research use from our preferred vendor, Project Zero. For laboratory research use only.
How It Works (Preclinical Mechanisms)
In preclinical models, VIP has been reported to bind VPAC receptors and influence pathways linked to lung homeostasis, inflammation, and vascular tone.
- Binds VPAC1 and VPAC2 receptors, including on alveolar type II cells in the lung.
- Reported to support surfactant production and protect alveolar cells in lung-injury models.
- Investigated as a regulator of pro-inflammatory cytokines, with reductions in markers such as IL-6 reported in clinical studies.
- Studied for vasodilatory and smooth-muscle relaxing effects, which underlie earlier interest in pulmonary hypertension.
Areas of Research Interest
Published studies have examined VIP and synthetic aviptadil in the following research contexts, ranging from preclinical models to randomized clinical trials.
Acute respiratory failure
Studied in randomized COVID-19 trials of intravenous and inhaled aviptadil for effects on recovery and survival.
Lung protection and surfactant
Investigated in models where VIP supports alveolar type II cells and surfactant production.
Inflammation and immune modulation
Examined for effects on cytokine release and immune signaling in inflammatory lung conditions.
Pulmonary vascular tone
Studied historically for vasodilatory effects relevant to pulmonary arterial hypertension research.
Reported Study Parameters
For laboratory research use only. The table below reports the doses and routes used in specific published studies, with sources. It describes what researchers administered in these models and is not a protocol, recommendation, or guidance for use in humans or animals. Animal-study doses are expressed per kilogram of body weight.
| Research Model | Dose and Route Reported | Source |
|---|---|---|
| COVID-19 respiratory failure (Phase III RCT, intravenous aviptadil) | Daily 12-hour IV infusion for 3 days, targeting 600 pmol/kg on day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3 | Brown 2023·DOI |
| COVID-19 at high ARDS risk (RCT protocol, inhaled aviptadil) | 67 ug inhaled three times a day for 10 days | Boesing 2022·DOI |
| Human research (critical COVID-19, Phase II RCT) | 3-day IV aviptadil infusion in a 196-patient trial; mixed results and no validated regimen established | Youssef 2022·DOI |
Products are supplied as lyophilized powder or tablets requiring preparation. For reconstitution concentration math, use the Peptide Calculator.
Latest Research (2022 to 2023)
Recent peer-reviewed literature indexed on PubMed has focused on synthetic VIP (aviptadil) in COVID-19 respiratory failure, with results that clarify both its biological effects and its limits.
Intravenous aviptadil (Phase III RCT)
A 2023 randomized, placebo-controlled trial in 461 patients with COVID-19 hypoxaemic respiratory failure reported that intravenous aviptadil did not significantly improve clinical outcomes at day 90 compared with placebo, and the trial was stopped for futility. PubMed·DOI
Intravenous aviptadil (Phase II RCT)
A 2022 multicenter trial in 196 patients reported that the primary endpoint was not met, but described a statistically significant improvement in 60-day survival and reduced IL-6 cytokine release, with an acceptable safety profile. PubMed·DOI
Inhaled aviptadil (trial protocol)
A 2022 protocol described a randomized trial of inhaled aviptadil at 67 ug three times daily for patients hospitalized with COVID-19 at high risk of ARDS, reasoning that inhalation could achieve higher lung-tissue concentrations than intravenous dosing. PubMed·DOI
Mechanism in lung tissue
A 2022 case report described rapid clinical recovery in a critically ill pregnant patient given escalating IV VIP infusions (50, 100, then 150 pmol/kg/hr), consistent with the proposed role of VIP in protecting alveolar type II cells. PubMed·DOI
Research Questions
What is VIP?
VIP is a naturally occurring 28-amino-acid neuropeptide active in the nervous, digestive, and immune systems. Its synthetic counterpart, aviptadil, has been the focus of clinical research in respiratory failure.
What is the current state of human evidence?
Human research centers on COVID-19 respiratory failure. The largest Phase III trial did not show significant benefit, though smaller trials reported survival and cytokine signals. No regimen is validated for general use.
What does the available safety literature suggest?
Clinical trials reported aviptadil to have an acceptable safety profile without drug-related serious adverse events, but the data set is limited and efficacy remains unproven.
Referenced Citations
Literature indexed on PubMed.
- Brown, S.M., et al. (2023). Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO). Lancet Respir. Med., 11(9), 791-803. PubMed·DOI
- Youssef, J.G., et al. (2022). The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure. Crit. Care Med., 50(11), 1545-1554. PubMed·DOI
- Boesing, M., et al. (2022). Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol. Trials, 23(1), 790. PubMed·DOI
- Youssef, J.G., et al. (2022). Rapid clinical recovery from critical COVID-19 with respiratory failure in a pregnant patient treated with IV vasoactive intestinal peptide. Crit. Care Explor., 4(1), e0607. PubMed·DOI
- Lythgoe, M.P., et al. (2016). Why drugs fail in clinical trials in pulmonary arterial hypertension, and strategies to succeed in the future. Pharmacol. Ther., 164, 195-203. PubMed·DOI
PeptideInfo.org provides information strictly for educational and research purposes. All referenced products are intended for laboratory and research use only and are not approved for human consumption, medical use, or self-administration. Nothing on this page constitutes medical advice. Research summaries reference literature indexed on PubMed.