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The Peptide Effect
preclinicalImmune & Anti-Inflammatory

VIP (Vasoactive Intestinal Peptide)

Also known as: Vasoactive Intestinal Peptide, VIP, Aviptadil, PHM-27 related peptide

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily. It is distributed throughout the gut, brain, lungs, and immune system, where it acts as a potent vasodilator, anti-inflammatory, and immunoregulatory molecule. VIP has gained significant attention in integrative medicine for its role in treating Chronic Inflammatory Response Syndrome (CIRS) caused by mold and biotoxin exposure.

Key Facts

Mechanism
VIP activates two G-protein coupled receptors — VPAC1 (widely distributed) and VPAC2 (concentrated in CNS and immune cells) — triggering cAMP-mediated signaling. This results in potent vasodilation via smooth muscle relaxation, suppression of pro-inflammatory cytokines (TNF-α, IL-6, IL-12), promotion of anti-inflammatory IL-10, inhibition of macrophage activation, and regulation of T-cell differentiation toward Th2/Treg phenotypes. In the lungs, VIP acts as a bronchodilator. In the brain, it functions as a neurotransmitter involved in circadian rhythm regulation via the suprachiasmatic nucleus.
Research Status
preclinical
Half-Life
~1–2 minutes in blood
Molecular Formula
C₁₄₇H₂₃₈N₄₄O₄₃S
Primary Use
Immune & Anti-Inflammatory
Table of Contents

Benefits

  • Potent anti-inflammatory — suppresses TNF-α, IL-6, and macrophage activationmoderate
  • CIRS/mold illness symptom relief in Shoemaker protocol patientsanecdotal
  • Bronchodilation — relaxes airway smooth muscle, improves pulmonary functionmoderate
  • Neuroprotective effects — prevents neuronal cell death in ischemia and neurodegeneration modelspreliminary
  • Regulates circadian rhythms through action on the suprachiasmatic nucleuspreliminary
  • Modulates gut motility and intestinal secretion — potential for functional GI disordersmoderate

Dosage Protocols

RouteDosage RangeFrequencyNotes
Intranasal spray50 mcg per nostril2–4× dailyStandard Shoemaker CIRS protocol; titrate up slowly to assess tolerance
Nebulized inhalation50–100 mcg1–2× dailyUsed for pulmonary applications including CIRS-related respiratory symptoms
Subcutaneous injection25–75 mcgDailyLess common route; used for systemic anti-inflammatory effects when intranasal is insufficient

Medical disclaimer

Dosage information is provided for educational reference only. Always follow your prescriber's instructions and consult a qualified healthcare provider before starting any peptide protocol.

Side Effects

  • Hypotension and dizziness due to vasodilationcommon
  • Facial flushing and warmthcommon
  • Diarrhea or loose stools (VIP stimulates intestinal secretion)common
  • Nasal congestion or runny nose with intranasal usecommon
  • Tachycardia (reflex response to blood pressure drop)rare

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Frequently Asked Questions

How does VIP help with mold illness (CIRS)?
In the Shoemaker Protocol for Chronic Inflammatory Response Syndrome, VIP is used as the final step after other interventions have reduced inflammatory markers. VIP addresses residual symptoms by suppressing the chronic inflammatory cascade, improving pulmonary artery pressure, normalizing TGF-beta and MMP-9 levels, and restoring regulatory T-cell function. Dr. Ritchie Shoemaker's clinical observations suggest VIP can significantly improve quality of life in CIRS patients, though controlled clinical trials are limited.
What is the Shoemaker Protocol for VIP?
The Shoemaker Protocol is a step-by-step treatment approach for CIRS. VIP nasal spray (50 mcg per nostril, 2–4 times daily) is introduced as the final step, only after other markers (MMP-9, TGF-beta-1, VEGF) have been reduced through binders, antifungals, and environmental remediation. Starting VIP too early without addressing the underlying inflammation can worsen symptoms. The protocol requires monitoring blood pressure, lipase, and VIP levels.
Does VIP nasal spray lower blood pressure?
Yes. VIP is a potent vasodilator, so blood pressure reduction is an expected effect. Most patients experience mild, tolerable drops. However, individuals already on antihypertensive medications or those with naturally low blood pressure should start with a lower dose and titrate up gradually. Blood pressure monitoring during initial dosing is recommended. Symptoms of excessive hypotension include dizziness, lightheadedness, and fatigue.
Is VIP the same as the VIP test used for diagnosis?
VIP serves both diagnostic and therapeutic roles. A blood test measuring VIP levels is part of the CIRS diagnostic panel — low VIP levels are commonly found in CIRS patients and are associated with chronic fatigue, shortness of breath, and cognitive dysfunction. Therapeutically, exogenous VIP nasal spray is used to restore levels and reduce inflammation. The same molecule, different applications: one measures it, the other replaces it.
Can VIP be used for respiratory conditions beyond CIRS?
VIP has inherent bronchodilatory properties and has been studied for pulmonary arterial hypertension, COPD, and asthma. Aviptadil, a synthetic form of VIP, received FDA Fast Track designation for ARDS associated with COVID-19. Its ability to relax airway smooth muscle and reduce pulmonary inflammation makes it a candidate for multiple respiratory conditions, though most applications remain investigational.

References

  1. 1
    Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions(2000)PubMed ↗
  2. 2
    VIP as a potent anti-inflammatory mediator in the gut and other tissues(2006)PubMed ↗
  3. 3
    Therapeutic potential of vasoactive intestinal peptide and its receptors in autoimmune and inflammatory diseases(2007)PubMed ↗
  4. 4
    Aviptadil (VIP analog) for the treatment of COVID-19 ARDS: clinical trial results(2021)PubMed ↗

Last updated: 2026-02-14