VIP

Quick Facts

• Full Name: Vasoactive Intestinal Peptide
• Aliases: VIP, PHM-27 (related peptide)
• Category: Immune Health / Anti-Inflammatory / Gut Health / MCAS / Neuroprotection
• Sequence: 28 amino acids (endogenous neuropeptide/hormone)
• Molecular Weight: 3326.8 Da
• Administration: Intranasal / Subcutaneous / Inhaled
• Typical Dose: 50–200 mcg/day (intranasal most common); varies by condition
• Half-Life: 1–2 minutes in plasma (rapid degradation); intranasal extends CNS action
• Status: Research Only for peptide therapy; Aviptadil (synthetic VIP) has FDA orphan designation for ARDS
• WADA Status: Not listed

What It Does

VIP is a 28-amino-acid neuropeptide and hormone produced throughout the body — in the nervous system, gut, immune cells, and lungs. It is a master anti-inflammatory regulator, promoting immune tolerance, reducing cytokine storms, and protecting mucosal surfaces. VIP is critically relevant in MCAS (Mast Cell Activation Syndrome), CIRS (Chronic Inflammatory Response Syndrome), long COVID, and inflammatory gut conditions. Aviptadil (synthetic VIP) demonstrated survival benefit in critical COVID-19/ARDS patients.

Mechanism of Action

1. VPAC1/VPAC2 receptor activation: Binds VIP receptors on immune cells, smooth muscle, epithelial cells, and neurons → cAMP-mediated anti-inflammatory signaling
2. Mast cell stabilization: Reduces mast cell degranulation → critical for MCAS management; reduces histamine, tryptase, prostaglandin release
3. Cytokine suppression: Reduces TNF-α, IL-6, IL-12, IL-17; increases IL-10 (anti-inflammatory); regulates Th1/Th2/Treg balance
4. Bronchodilation and vasodilation: Smooth muscle relaxation → pulmonary vasodilation; relevant in pulmonary hypertension and ARDS
5. Gut motility and secretion: Regulates intestinal secretion, blood flow, and peristalsis; anti-inflammatory in IBD contexts
6. Neuroprotection: CNS VIP receptors → neuronal survival, neuroinflammation reduction
7. Circadian clock regulation: VIP from SCN neurons is essential for circadian rhythm coordination

Dosing Protocols

MCAS / CIRS Protocol

• Dose: 50 mcg intranasal, 2x daily
• Frequency: BID (morning and evening)
• Duration: Weeks to months; often used continuously in chronic CIRS
• Protocol: Shoemaker CIRS protocol uses intranasal VIP as a capstone therapy
• Source: The Peptides Bible, Shoemaker CIRS protocol

Anti-Inflammatory Protocol

• Dose: 100–200 mcg/day (divided doses) SubQ or intranasal
• Duration: 4–8 week cycles

Stacks Well With

• LL-37 + SS-31 – immune modulation + mitochondrial anti-inflammatory synergy
• BPC-157 – gut healing and systemic anti-inflammatory complement
• KPV – anti-inflammatory gut-specific synergy
• Thymosin Alpha-1 – immune regulation complement

Use Cases

• MCAS (Mast Cell Activation Syndrome) — mast cell stabilization
• CIRS (Chronic Inflammatory Response Syndrome / mold illness)
• Long COVID — cytokine storm modulation, lung protection
• ARDS — Aviptadil clinical data
• IBD (Crohn's, ulcerative colitis)
• Pulmonary Hypertension
• Neuroprotection and neuroinflammation
• Autoimmune conditions (immune tolerance induction)
• Circadian Rhythm support

Contraindications & Safety

• Hypotension — vasodilatory; monitor blood pressure
• Severe cardiovascular instability — vasodilation risk
• Pregnancy — insufficient data; avoid unless indicated
• Common side effects: Facial flushing, mild hypotension, nasal irritation (intranasal route)
• Very short plasma half-life → intranasal route preferred for maintained CNS/mucosal levels
• Generally well-tolerated; used in clinical CIRS practices

Storage

• Lyophilized: -20°C long-term; 2–8°C for weeks; avoid freeze-thaw cycles
• Reconstituted / intranasal solution: 2–8°C; use within 2 weeks; protect from light
• Solvent: Sterile saline (intranasal); bacteriostatic water (SubQ)

PubMed Research

Studies

• PMID-22139413 – Vasoactive intestinal peptide a neuropeptide with pleiotrop | PubMed 22139413
  • Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions.
• PMID-40449484 – Nociceptor neurons suppress alveolar macrophage-induced Sigl | PubMed 40449484
  • Nociceptor neurons suppress alveolar macrophage-induced Siglec-F+ neutrophil-mediated inflammation.
• PMID-11862320 – Vasoactive intestinal peptide in the immune system potentia | PubMed 11862320
  • Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases.
• PMID-25422088 – The neuropeptide vasoactive intestinal peptide direct effec | PubMed 25422088
  • The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases.
• PMID-36302761 – Targeting vasoactive intestinal peptide-mediated signaling e | PubMed 36302761
  • Targeting vasoactive intestinal peptide-mediated signaling enhances response to immune checkpoint therapy.

Sources

• The Peptides Bible – Immune and inflammatory peptides
• Peptide Protocols Master Bible – MCAS and CIRS protocols
• Shoemaker R. — CIRS VIP protocol
• Aviptadil FDA orphan drug data

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