Overview
Vasoactive Intestinal Peptide (VIP) is a 28-amino-acid neuropeptide belonging to the secretin/glucagon superfamily. First isolated from porcine intestine in 1970, VIP is widely distributed in central and peripheral nervous tissue, gut, lung, and immune organs. It acts through two G-protein-coupled receptors, VPAC1 and VPAC2, producing potent vasodilation, bronchodilation, immunomodulation, and neuroprotection.
VIP is one of the most powerful endogenous anti-inflammatory peptides described. It shifts immune responses from Th1/Th17 toward Th2/Treg, suppresses TNF-α, IL-6, and IL-12, and increases IL-10. These properties have driven clinical interest in inflammatory and autoimmune diseases including sarcoidosis, rheumatoid arthritis, Crohn's disease, and chronic inflammatory response syndrome (CIRS) associated with mold and biotoxin exposure.
Intranasal VIP has gained popularity in functional and integrative medicine—particularly via the work of Dr. Ritchie Shoemaker—for the late stages of CIRS treatment after VIP levels have been documented as low. Clinical trials have also explored inhaled VIP for pulmonary arterial hypertension and IV/inhaled VIP for sarcoidosis, with mixed but encouraging early results.
VIP is not FDA-approved. It is available as a research peptide and through compounding pharmacies in some jurisdictions with a prescription. Quality, sterility, and dosing accuracy are major considerations.
Quick facts
- Mechanism
- VPAC1/VPAC2 receptor agonist with vasodilatory, bronchodilatory, and anti-inflammatory effects
- Primary use
- Inflammatory illness (CIRS, sarcoidosis); pulmonary hypertension research
- Evidence
- preliminary
- FDA
- Not approved
- Route
- Intranasal (most common in research); inhaled and IV used in trials
- Typical results
- Reduces pulmonary and systemic inflammation markers; symptomatic improvement reported in CIRS and sarcoidosis case series
Chemical information
Vasoactive Intestinal Peptide (C₁₄₇H₂₃₈N₄₄O₄₂S) is a neuropeptide compound with a molecular weight of 3325 g/mol. Its structural characteristics underpin its biological activity in neuropeptide signaling and neural modulation.
How Vasoactive Intestinal Peptide works
VIP binds VPAC1 and VPAC2 receptors on smooth muscle, endothelium, neurons, and immune cells, activating Gs-coupled adenylyl cyclase and increasing intracellular cAMP. cAMP elevation produces vasodilation and bronchodilation and inhibits NF-κB-driven pro-inflammatory cytokine production in macrophages, dendritic cells, and T cells. VIP also promotes regulatory T-cell differentiation and dampens Th1/Th17 effector responses.
In the lung, VIP relaxes bronchial and pulmonary vascular smooth muscle, reduces pulmonary artery pressure, and inhibits release of histamine and leukotrienes from mast cells. Clinical trials in idiopathic pulmonary arterial hypertension and sarcoidosis have used inhaled VIP to exploit local delivery and minimize systemic hypotension.
Immunologically, VIP shifts macrophage polarization toward an M2/regulatory phenotype, reduces dendritic-cell maturation, suppresses Th1/Th17 cytokines (IFN-γ, IL-17), and induces Foxp3+ regulatory T cells. These effects underlie its therapeutic rationale in autoimmune and chronic inflammatory disease.
In the CIRS framework, VIP is hypothesized to be depleted in chronic biotoxin illness; replacement therapy is reported to normalize TGF-β1, MMP-9, C4a, and VEGF and to improve exercise tolerance and neurocognitive symptoms. Evidence is limited to case series and open-label observational data.
- VPAC1/VPAC2 agonism: Increases intracellular cAMP via Gs-coupled signaling
- Anti-inflammatory: Suppresses NF-κB, TNF-α, IL-6, IL-12; raises IL-10
- Immune rebalancing: Shifts toward Th2/Treg phenotype
- Vasodilation/bronchodilation: Relaxes pulmonary vascular and bronchial smooth muscle
- Neuroprotection: Inhibits microglial activation and excitotoxicity
Pharmacokinetics
| Parameter | Value | Significance |
|---|---|---|
| Molecular Mass | 3325.8 g/mol | 28-amino-acid peptide; requires parenteral/mucosal delivery |
| Plasma half-life (IV) | 1–2 minutes | Very short systemic half-life limits IV use |
| Intranasal bioavailability | Local nasal/CNS exposure; limited systemic | Most commonly used route in CIRS protocols |
| Inhaled delivery | Local pulmonary action; minimal systemic effect | Preferred in PAH and sarcoidosis trials |
| Metabolism | Rapid proteolytic degradation (DPP-IV and other peptidases) | Drives need for frequent dosing or sustained-release formulations |
Dosing & administration
Vasoactive Intestinal Peptide dosing varies by indication and individual factors. No FDA-approved dosing exists for this compound; protocols in the literature derive from limited clinical or preclinical data and practitioner experience.
Any use should be conducted under qualified medical supervision with appropriate monitoring of safety markers.
Important: These dosing ranges are not FDA-approved. Any use should be under qualified medical supervision.
Side effects & safety
Safety data for Vasoactive Intestinal Peptide is primarily derived from preclinical studies and limited human data. Long-term effects in humans remain incompletely characterized.
Common
- • Nasal irritation or burning with intranasal use
- • Headache
- • Facial flushing
- • Mild hypotension
- • Transient diarrhea or abdominal cramping
Serious / potential risks
- • Symptomatic hypotension and syncope
- • Tachycardia
- • Bronchospasm in susceptible individuals (rare with inhaled use)
- • Allergic/hypersensitivity reactions
- • Unknown long-term effects of chronic intranasal use
Drug interactions
| Medication | Interaction | Recommendation |
|---|---|---|
| Antihypertensives and PDE5 inhibitors | Additive vasodilation and hypotension | Monitor blood pressure with initiation |
| Bronchodilators (β2-agonists) | Additive bronchodilation | Generally compatible; monitor heart rate |
| Immunosuppressants | Potential additive immunomodulation | Coordinate with treating physician |
| Diuretics | Possible additive hypotension | Monitor volume status |
Storage & handling
Lyophilized (powder)
- • Store at -20°C to 4°C (freezer or refrigerator)
- • Protect from light and moisture
- • Stable for 12–24 months when stored properly
- • Keep in original sealed container until reconstitution
Reconstituted solution
- • Refrigerate at 2–8°C after reconstitution
- • Use bacteriostatic water for multi-dose reconstitution
- • Typical stability: 14–28 days refrigerated
- • Do not freeze reconstituted solution
Cost & availability
| Source | Cost | Notes |
|---|---|---|
| Research suppliers | Varies widely | Quality and purity vary significantly between sources |
| Compounding pharmacies | Prescription required | Higher quality assurance and purity testing |
The bottom line
Vasoactive Intestinal Peptide is a neuropeptide compound with research interest in vasodilation, immune modulation, neuroprotection, circadian rhythm. While preclinical evidence is encouraging, it remains investigational and is not FDA-approved. Any use should be under qualified medical supervision.
Best for
- • Researchers studying neuropeptide signaling and neural modulation
- • Individuals interested in vasodilation under medical guidance
Not for
- • Self-administration without medical supervision
- • Pregnant or breastfeeding individuals
- • Individuals with contraindicated conditions
Related compounds
Thymosin Alpha-1
Immune-modulating peptide used in chronic infection and inflammation
KPV
α-MSH-derived anti-inflammatory tripeptide
LL-37
Cathelicidin used in chronic infection/inflammation protocols
BPC-157
Anti-inflammatory and gut-healing peptide often paired with VIP
Frequently asked questions
References
- [1] Said SI, Mutt V.. Polypeptide with broad biological activity: isolation from small intestine. Science (1970). doi: 10.1126/science.169.3951.1217 PMID: 5450698
- [2] Delgado M, Pozo D, Ganea D.. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev (2004). doi: 10.1124/pr.56.2.7 PMID: 15169926
- [3] 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). doi: 10.1172/JCI17712 PMID: 12975476
- [4] Prasse A, Zissel G, Lutzen N, et al.. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med (2010). doi: 10.1164/rccm.200909-1451OC PMID: 20167845