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Vasoactive Intestinal Peptide (VIP)
Also known as: Vasoactive Intestinal Polypeptide, Aviptadil, RLF-100
Confidence
Updated 2026-03-18
VIP is an endogenous 28-amino acid neuropeptide with broad immunomodulatory, vasodilatory, and neuroprotective properties. It gained renewed attention during the COVID-19 pandemic when the synthetic form (aviptadil/RLF-100) was investigated for ARDS. VIP is also central to the Shoemaker CIRS (Chronic Inflammatory Response Syndrome) mold illness protocol, where intranasal VIP is used as the final treatment step.
Class
Immune / Neuro Modulator
Routes
Intranasal, Intravenous, Subcutaneous
Half-Life
~1–2 minutes (IV, very rapid degradation by DPP-IV and NEP). Intranasal: functional duration ~4–6 hours.
VIP binds VPAC1 and VPAC2 receptors expressed widely in the lung, brain, gut, and immune cells. It stimulates cAMP production, leading to: potent anti-inflammatory effects (inhibits TNF-alpha, IL-6, NF-kB), vasodilation (relaxes pulmonary and systemic smooth muscle), neuroprotection (blocks microglial activation), surfactant production in type II alveolar cells, and regulatory T-cell promotion. In CIRS, it is theorized to reset hypothalamic-mediated immune dysregulation.
Half-Life
~1–2 minutes (IV, very rapid degradation by DPP-IV and NEP). Intranasal: functional duration ~4–6 hours.
Bioavailability
Intranasal: variable, estimated 10–30%. IV: 100% but ultra-short half-life.
No approved indications. Research/off-label: CIRS (Shoemaker protocol), pulmonary hypertension, ARDS, neurodegenerative disease, GI inflammatory conditions.
Extensive basic science literature on VIP biology. COVID-19 ARDS trials (aviptadil/RLF-100) showed some survival benefit in early studies but Phase IIb/III results were mixed. Shoemaker CIRS protocol data is largely observational — VIP as final step in mold illness protocol has clinical followings but limited RCT data. Animal data robust for neuroprotection and anti-inflammation.
Human Studies
20
Animal Studies
150
IV: hypotension (vasodilation), diarrhea, flushing, tachycardia. Intranasal: generally well-tolerated, mild nasal irritation. Contraindicated in active cancer (VIP can promote tumor angiogenesis in some contexts). Blood pressure monitoring essential with IV administration.
Investigational for most uses. NeuroRx/Relief Therapeutics pursued EUA for COVID-19 ARDS (aviptadil). Intranasal VIP available through compounding pharmacies for CIRS protocols.
Drug Interactions: May potentiate hypotension with antihypertensives. Caution with phosphodiesterase inhibitors. Monitoring: Blood pressure, inflammatory markers (TGF-beta1, MMP-9, MSH, VIP levels in CIRS protocols). Research Gaps: CIRS protocol efficacy needs RCT validation. Optimal intranasal dosing not established. Cancer safety concern needs clarification.
Intranasal (CIRS/Shoemaker protocol)
Common Range
50 mcg per nostril (100 mcg total) 4 times daily
Timing
Throughout the day
Frequency
Four times daily
Cycling
Used as final step in Shoemaker protocol; duration individualized based on biomarker response
Important Note
NOT FDA-approved. Used off-label in CIRS protocols. Must confirm negative VIP levels before initiation per Shoemaker protocol. Compounded intranasal formulation.
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Antimicrobial Peptide
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Disclaimer: This content is for educational and informational purposes only and does not constitute medical advice. Always consult with a licensed healthcare provider before starting, stopping, or modifying any peptide therapy. PeptideSupplierMatch does not prescribe, sell, or distribute peptides.
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