Library / Peptides / Gut & Inflammation / VIP
Emerging evidence · Grade B

VIP

Vasoactive Intestinal Peptide (VIP)
Evidence
Emerging
Route
Intranasal or Intravenous
Frequency
Intranasal: 2-4x daily; IV: per protocol
Category
Gut & Inflammation
TL;DR
VIP is a natural signaling peptide your body makes to reduce inflammation and calm immune overactivation. In a condition called CIRS (often associated with mold or biotoxin exposure), VIP levels can drop, and intranasal VIP is used as part of a specific treatment protocol to restore these signals. While the CIRS community reports meaningful benefits, large controlled trials are lacking, and VIP should only be used under knowledgeable medical supervision as part of a structured treatment plan.
Part 01 · How it works

Mechanism.

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide naturally produced throughout the nervous system, gut, and immune tissues. It acts as a potent inflammation-modulating, smooth muscle relaxant, and neuromodulator. Synthetic VIP administered intranasally has been studied by Dr. Ritchie Shoemaker and colleagues as a treatment for Chronic Inflammatory Response Syndrome (CIRS) associated with mold/biotoxin illness, showing effects on inflammatory biomarkers and symptom resolution.

VIP is like the nervous system's universal 'calm down' signal — it tells blood vessels to relax, tells immune cells to stand down from excessive inflammation, and helps gut and brain tissue recover from inflammatory insults. In CIRS, the biotoxin essentially silences this calming signal, and supplemental VIP attempts to restore it.

Mechanism · technical
VIP binds to VPAC1 and VPAC2 receptors, which are G-protein coupled receptors coupled to adenylyl cyclase. Activation elevates cAMP, which broadly suppresses pro-inflammatory cytokine production (TNF-alpha, IL-6, IL-12), promotes regulatory T-cell function, and inhibits NF-κB activation. In the gut, VIP relaxes smooth muscle and modulates secretion. In the brain, it regulates circadian rhythm, neuroinflammation, and autonomic tone. In CIRS, low VIP levels are considered a downstream consequence of biotoxin-driven TGF-beta and other inflammatory mediators.
Part 02 · Dosing & administration

How it's taken.

Values below describe how VIP has been administered in published trials and labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Standard dose
50-100 mcg intranasal; variable IV dosing
Intranasal or Intravenous · Intranasal: 2-4x daily; IV: per protocol
Duration
Variable; CIRS protocols may be months

28-amino acid neuropeptide. Used in CIRS/mold illness protocols (Shoemaker protocol). Also studied for pulmonary hypertension and ARDS. Potent vasodilator — caution with hypotension. Not FDA-approved.

Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

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Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Reported side effects
Intranasal VIP: flushing, headache, and nasal irritation are common. At higher systemic doses: hypotension, tachycardia, and facial flushing. May worsen symptoms if cytokine storm or active infection is present. Contraindicated before completing environmental remediation in CIRS (may trigger paradoxical reactions per Shoemaker protocol).
Absolute · do not use
×
Pregnancy or breastfeeding
×
Children under 18
×
Known hypersensitivity to VIP or any component
×
Severe hypotension (VIP is a potent vasodilator)
×
History of diarrheal disorders (VIP stimulates intestinal secretion)
Interactions
Antihypertensives
VIP is a potent vasodilator; additive hypotensive effect may cause symptomatic hypotension
Major
PDE5 inhibitors (sildenafil, tadalafil)
Additive vasodilation; significant risk of hypotension
Major
Corticosteroids
VIP has inflammation-modulating properties; may potentiate or interfere with corticosteroid effects depending on context
Moderate
Immunosuppressants
VIP modulates immune function (promotes regulatory T-cells); may have additive immunosuppressive effects
Moderate
Labs to monitor
Blood Pressure
Before and after each dose initially
VIP is a potent vasodilator — hypotension risk
CMP (Comprehensive Metabolic Panel)
Baseline and every 3 months
Liver and kidney function
CRP / ESR
Baseline and monthly
Inflammation-modulating effects monitoring
CBC with Differential
Baseline and every 3 months
Immune modulation monitoring
TGF-beta, C4a, MSH (Shoemaker Panel)
Per CIRS protocol
If used for CIRS/mold illness protocol
Part 04 · Evidence

How strong is the evidence?

Scores derived from rating, indexed studies, regulatory status, and catalogued safety data for this peptide. Curated per-peptide scoring replaces this when available.

74
Grade B
Grade B. Signal is real but maturing. Treat results as directional until larger or independent replications land.
Clinical efficacy
Emerging signal across multiple indexed studies; effect sizes still firming up.
68
Study quality
3 indexed studies in our dataset. Designs vary — see Research log for per-study grades.
79
Regulatory clarity
FDA-approved for at least one indication.
90
Safety profile
Based on 5 documented contraindications, 4 interactions, 5 lab checkpoints.
84
Long-term data
Long-horizon data not yet available outside research settings.
48
Part 05 · Research log

Every study we cite.

Each study with its published finding and a plain-language note on limitations or funding.

01
2015
0
VIP as part of the Shoemaker Protocol for CIRS: observational cohort study
Shoemaker and colleagues reported that intranasal VIP (50 mcg four times daily) normalized inflammatory biomarkers (TGF-beta, MMP9, VEGF), improved NeuroQuant brain volumetrics, and improved symptom scores in CIRS patients who had completed prior protocol steps.
Non-randomized observational study. Investigator is developer of the CIRS protocol. Potential significant confirmation and reporting bias. No placebo arm.
PMID 25835398 ↗
02
2011
0
Inflammation-modulating effects of VIP in autoimmune and inflammatory disease models
Comprehensive review of preclinical and early clinical evidence confirmed VIP's broad immunosuppressive and inflammation-modulating effects via VPAC1/2 receptors in models of rheumatoid arthritis, colitis, and sepsis.
Primarily preclinical. Human clinical RCTs for these conditions are limited.
PMID 21356234 ↗
03
2010
0
VIP and pulmonary arterial hypertension: inhalation therapy trial
A small RCT showed inhaled VIP improved pulmonary vascular resistance, exercise capacity, and quality of life in pulmonary arterial hypertension patients.
Small trial (n=20). Single center. Short duration. PAH is a distinct indication from CIRS.
PMID 20463178 ↗
Part 06 · Cost & access

Where you can get it.

Regulatory status
Not FDA-approved as a pharmaceutical for CIRS or mold illness. Available only through compounding pharmacies in the US. FDA has issued warnings about unapproved compounded VIP. No IND or NDA exists for CIRS indication. Research use is legitimate.
The Peptide Column takes no affiliate commission from any source.
Part 07 · Your appointment

Questions to bring.

01
Have my VIP levels been measured, and does low VIP fit within a CIRS diagnosis framework?
02
Should VIP be used only after completing the Shoemaker Protocol (removal, binders, etc.) or earlier?
03
Are there risks to intranasal VIP administration, particularly with regard to cardiovascular effects?
04
Is compounded intranasal VIP available through a licensed compounding pharmacy, and what is the appropriate oversight?