VIP (Vasoactive Intestinal Peptide)
Also known as: VIP, Vasoactive Intestinal Polypeptide, Aviptadil (synthetic VIP)
Grey-Market Compound. This compound is not approved by the FDA or any major regulatory authority. No established regimen exists. Products available outside of regulated channels lack standardized manufacturing, quality control, and potency verification. Consult a qualified clinician. Research-only risks apply.
Overview
Clinical Summary
Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide with potent anti-inflammatory, vasodilatory, and immunomodulatory properties. It acts through VPAC1 and VPAC2 receptors distributed widely throughout the nervous, immune, and gastrointestinal systems. In clinical practice, VIP is most recognized for its use in the Shoemaker protocol for chronic inflammatory response syndrome (CIRS), where intranasal VIP is administered as the final step in treating mold-related illness. VIP has also been studied for respiratory failure (aviptadil/Zyesami for COVID-19 ARDS), pulmonary hypertension, and autoimmune conditions. The evidence base is limited by VIP's short half-life and the difficulty of conducting large trials.
Plain Language Summary
VIP (Vasoactive Intestinal Peptide) is a natural signaling molecule in your body that reduces inflammation, relaxes blood vessels, and regulates immune function. It is best known in integrative medicine for treating chronic inflammatory response syndrome (CIRS), a condition caused by biotoxin exposure from mold. In the Shoemaker protocol, VIP nasal spray is used as a final treatment step. While the science behind VIP is promising, most of the evidence comes from small studies and animal research.
Mechanism of Action
VIP binds to two G-protein-coupled receptors: VPAC1 (widely distributed in immune cells, lungs, and intestine) and VPAC2 (predominant in smooth muscle, CNS, and pancreas). Receptor activation stimulates adenylyl cyclase, increasing intracellular cAMP. In immune cells, VIP suppresses macrophage activation, reduces production of pro-inflammatory cytokines (TNF-alpha, IL-6, IL-12), inhibits NF-kB signaling, and promotes regulatory T-cell differentiation. VIP shifts the Th1/Th17 immune profile toward Th2/Treg dominance. In smooth muscle, VIP causes vasodilation and bronchodilation. In the GI tract, VIP regulates secretion, motility, and mucosal blood flow. In the CNS, VIP acts as a neuromodulator and neuroprotectant.
Evidence Summary
Shoemaker et al. (2014) published an observational study showing that intranasal VIP improved grey matter nuclear volume on MRI and reduced inflammatory markers (TGF-beta-1, MMP-9) in CIRS patients. Delgado et al. (2004) reviewed the anti-inflammatory mechanism. Gonzalez-Rey et al. (2007) summarized preclinical evidence in autoimmune disease models. Aviptadil (synthetic VIP) was evaluated in a Phase 2/3 trial for COVID-19 ARDS with mixed results. The CIRS literature is primarily from a single investigator group (Shoemaker) and lacks randomized controlled trials.
Safety Profile
Intranasal VIP has been used clinically in the CIRS context with generally good tolerability. The most common side effects are nasal congestion, rhinorrhea, and transient flushing. VIP is a potent vasodilator and can cause hypotension, particularly with parenteral administration. Diarrhea may occur due to GI smooth muscle effects. The short half-life (approximately 1 to 2 minutes in plasma) limits systemic exposure from intranasal administration.
Contraindications
- Known hypersensitivity to VIP
- Hypotension or conditions exacerbated by vasodilation
- Active diarrheal illness (VIP promotes intestinal secretion)
- Pregnancy and breastfeeding (insufficient safety data)
Adverse Events
- Nasal congestion and rhinorrhea (intranasal route)
- Facial flushing (vasodilation)
- Hypotension (especially parenteral route)
- Diarrhea
- Headache
- Tachycardia (reflex, from vasodilation)
Interactions
- Antihypertensive medications (additive hypotension)
- Vasodilators (additive effect)
- May enhance effects of bronchodilators
- No formal drug interaction studies for intranasal formulation
Regulatory Notes
VIP is not FDA-approved as a standalone therapeutic. Aviptadil (synthetic VIP) received Emergency Use Authorization review for COVID-19 ARDS but was not granted full approval. Intranasal VIP for CIRS is used off-label, compounded by specialty pharmacies. No FDA-approved VIP nasal spray product exists. The Shoemaker protocol is not recognized by mainstream medical guidelines.
Monitoring Considerations
Blood pressure monitoring, especially during initial doses. Inflammatory markers relevant to CIRS (TGF-beta-1, MMP-9, MSH, VIP levels, C4a, VEGF) per Shoemaker protocol. Pulmonary function testing if used for respiratory indications. Symptom tracking with validated CIRS assessment tools.
These are general considerations for clinical awareness and do not constitute prescriptive monitoring recommendations for any individual patient.
Stability and Handling Notes
Compounded VIP nasal spray: store at 2 to 8 degrees C. VIP has very poor plasma stability (half-life 1 to 2 minutes). Nasal spray formulations typically use preservatives and stabilizers. Use within the beyond-use date assigned by the compounder (typically 30 to 90 days). Protect from light and heat.
References
- 1review
Vasoactive Intestinal Peptide: An Anti-Inflammatory Neuropeptide with Therapeutic Potential
Delgado M, Pozo D, Ganea D. (2004). Trends in Pharmacological Sciences
Key findings: VIP is a potent anti-inflammatory mediator that inhibits macrophage activation, reduces pro-inflammatory cytokines (TNF-alpha, IL-6), and promotes regulatory T-cell function. Acts through VPAC1 and VPAC2 receptors.
Limitations: Primarily preclinical mechanistic data. Clinical translation limited by VIP instability and short half-life.
View source - 2observational
Intranasal VIP Safely Restores Volume to Multiple Grey Matter Nuclei in Patients with CIRS
Shoemaker RC, House D, Ryan JC. (2014). Internal Medicine Review
Key findings: Intranasal VIP treatment in CIRS patients showed volumetric increases in caudate nucleus and other grey matter structures on MRI. VIP also reduced markers of inflammation including TGF-beta-1 and MMP-9.
Limitations: Open-label observational study. Single investigator group. No placebo control. Small sample size. Journal of limited impact factor.
- 3review
VIP as a Therapeutic Agent for Inflammatory and Autoimmune Diseases
Gonzalez-Rey E, Chorny A, Delgado M. (2007). Annals of the New York Academy of Sciences
Key findings: Review of VIP therapeutic potential across autoimmune conditions including rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. VIP shifts immune balance from Th1/Th17 to Th2/Treg profiles.
Limitations: Most data from animal models of autoimmune disease. Clinical trial data extremely limited.
Last reviewed: 2026-03-24 | Version: 1 | Status: Published
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