VIP (Vasoactive Intestinal Peptide)
Vasoactive Intestinal Peptide is a 28-amino-acid neuropeptide found throughout the nervous, immune, and endocrine systems. It is a potent anti-inflammatory and immune regulator, with significant research interest in CIRS (Chronic Inflammatory Response Syndrome), mast cell activation, and autoimmune conditions.
Common Dosage
50mcg intranasally 4x daily (Shoemaker CIRS protocol)
Category
Immunity
- Immune system regulation
- Anti-inflammatory signaling
- Neuroinflammation reduction
- CIRS symptom management
- Mast cell stabilization
- Improved cognitive clarity in inflammatory conditions
Vasoactive Intestinal Peptide (VIP) was first isolated in 1970 by Sami Said and Victor Mutt from porcine small intestine during a search for substances that cause vasodilation. Its name reflects its initial characterization as a vasoactive compound, though subsequent decades of research revealed VIP to be far more significant as a broad-spectrum immunoregulatory and neuroprotective agent. It is produced throughout the body — in neurons of the peripheral and central nervous system, T-lymphocytes, mast cells, and intestinal endocrine cells. The most prominent clinical application protocol was developed by Dr. Ritchie Shoemaker, who incorporated intranasal VIP as a key late-stage intervention in his Chronic Inflammatory Response Syndrome (CIRS) treatment protocol.
VIP binds to three G-protein coupled receptor subtypes: VPAC1, VPAC2, and PAC1. VPAC1 is widely expressed in immune cells, the GI tract, and the CNS; VPAC2 is more selectively expressed in T lymphocytes and the suprachiasmatic nucleus. Receptor binding increases intracellular cAMP, which drives a broad anti-inflammatory response: VIP suppresses Th1 and Th17 pro-inflammatory cytokines (TNF-α, IL-6, IL-12, IFN-γ), promotes regulatory T-cell (Treg) differentiation, stabilizes mast cells, and reduces microglial activation. In the brain, VIP acts as a circadian rhythm regulator and neuroprotective agent. Its wide tissue distribution explains why its dysregulation is implicated in conditions as diverse as CIRS, autoimmunity, inflammatory bowel disease, and pulmonary hypertension.
- CIRS (Chronic Inflammatory Response Syndrome) — final step in the Shoemaker protocol after MMP-9 and TGF-β normalization
- Mast cell activation syndrome (MCAS) — VIP stabilizes mast cells via VPAC2 receptor signaling
- Pulmonary arterial hypertension — VIP was in Phase 2 clinical trials as an inhaled therapy
- Autoimmune conditions — IBD, rheumatoid arthritis, and multiple sclerosis research models
- Neuroinflammation and microglial activation reduction
- Circadian rhythm and sleep regulation research
- Post-COVID inflammatory dysregulation — emerging research application
- Sepsis and systemic inflammatory response syndrome (SIRS) — immunomodulation research
CIRS Protocol Outcomes
In Shoemaker's CIRS treatment framework, intranasal VIP at 50mcg 4x daily is administered after confirming normalization of MMP-9 and TGF-β levels. Practitioners using this protocol report improvements in cognitive symptoms, fatigue, and inflammatory markers (NeuroQuant MRI changes) in patients who had not fully recovered with prior protocol steps. VIP is not recommended as a standalone therapy — it is part of a sequenced multi-step protocol.
Pulmonary Hypertension Trials
A Phase 2 clinical trial investigated inhaled VIP in pulmonary arterial hypertension patients and found significant improvements in exercise capacity, pulmonary vascular resistance, and quality of life measures, though a larger Phase 3 trial was not completed due to funding constraints rather than safety concerns.
Mast Cell Stabilization
Research in mast cell activation models shows VIP activates VPAC2 receptors on mast cells, inhibiting degranulation in response to IgE-mediated and non-IgE-mediated triggers. Clinicians treating MCAS alongside CIRS report that patients who respond to VIP often show concurrent improvements in histamine-related symptoms — consistent with this mechanism.
- Hypotension — VIP causes vasodilation and blood pressure can drop, particularly in individuals with existing low blood pressure; sitting/lying administration is advised
- Should not be used without first completing earlier protocol steps in Shoemaker CIRS framework — premature use may trigger symptom flares
- VIP levels should ideally be tested before initiation — very low baseline VIP correlates with CIRS but very high VIP may indicate neuroendocrine tumor and warrants investigation
- Dizziness and facial flushing, especially with initial doses
- Short half-life (approximately 2 minutes in plasma) — intranasal delivery bypasses this limitation
- Research-phase compound — not FDA-approved for any indication except as a research tool
- Significant hypotension reported in some individuals at the standard 50mcg intranasal dose — lower starting doses (25mcg) are advisable
- Dizziness
- Facial flushing
- Hypotension (blood pressure drop)
- Nausea at higher doses