COMPOUND

Compounds / Immune

VIP

Vasoactive Intestinal Peptide (28-amino-acid neuropeptide) / Aviptadil (synthetic VIP, RLF-100/Zyesami)

Immune Nasal · SubQ Investigational

28-amino-acid neuropeptide with broad anti-inflammatory, vasodilatory, and immunomodulatory effects. Two product forms:\n\n1. Aviptadil / Zyesami / RLF-100 (NeuroRx / Relief Therapeutics): investigational IV/inhaled formulation for COVID-19 ARDS and pulmonary arterial hypertension. Met phase 2b/3 primary endpoint for COVID ARDS but FDA did not grant EUA. FDA Fast Track designation.\n\n2. Compounded intranasal VIP: established off-label use in the Shoemaker protocol for Chronic Inflammatory Response Syndrome (CIRS) from mold/biotoxin exposure. Primarily used by mold-illness functional medicine practitioners.\n\nCRITICAL SEQUENCING WARNING: In Shoemaker CIRS protocol, VIP is the FINAL step, used ONLY after MARCoNS (multiple antibiotic resistant coag-negative staph) clearance, mycotoxin clearance, and prior inflammation normalization. Starting VIP before mold/MARCoNS clearance can WORSEN CIRS symptoms. CIRS itself is a controversial clinical entity outside functional medicine.

At a glance

Half-life
~3 min Plasma t½: ~2 minutes IV (extremely short). Intranasal: longer functional duration via local + CNS receptor activation. Inhaled (Zyesami): direct lung receptor binding; effect outlasts plasma clearance.
Routes
Nasal · SubQ
Vial sizes
5 mg · 10 mg
Evidence base
2 studies 2 human

Mechanism

VIP binds VPAC1 and VPAC2 receptors (GPCRs) widely distributed in immune cells, vascular endothelium, lung, GI, and CNS. Activation produces: anti-inflammatory effects (shifts Th1/Th17 → Th2/Treg balance; reduces TNF, IL-6, IFN-γ); vasodilation (especially pulmonary); bronchodilation; modulation of TGF-β1, MMP-9, C4a, VEGF (the inflammatory markers Shoemaker uses to define CIRS); neuroprotection.

Dosing

Any amounts shown here are reported from published studies only. 2 of 2 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.

Published evidence

  1. Human RCT 2021

    NeuroRx ZYESAMI Phase 2b/3 COVID-19 ARDS trial

    Youssef J, Javitt JC, et al. Press release / preliminary report

    ZYESAMI (aviptadil) met primary endpoint for recovery from respiratory failure at days 28 and 60 in critical COVID-19 with ARDS; survival benefit demonstrated. FDA did NOT grant EUA despite results (controversy over data interpretation).

  2. Human observational 2013

    Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings

    Shoemaker RC, Hudnell HK, et al. Health (Surviving Mold)

    VIP normalized inflammatory markers (TGF-β1, MMP-9, C4a, VEGF) and improved symptoms in CIRS patients post mold exposure. Foundational CIRS protocol paper.

Reported side effects

Flushing / hypotension
Occasional Moderate · Vasodilatory effect; transient. More pronounced with IV/inhaled than intranasal.
Diarrhea
Occasional Mild · GI VIP receptor activation.
Worsening of CIRS inflammation if started prematurely
Occasional Serious · CRITICAL: Shoemaker explicitly warns that VIP started before MARCoNS clearance and prior inflammation normalization can WORSEN CIRS symptoms. Sequence the protocol correctly.

Interactions

  • Cholestyramine Synergy

    Shoemaker protocol: bile acid sequestrant for mycotoxin removal precedes VIP. Required sequencing.

  • Nasal bactroban Synergy

    MARCoNS clearance precedes VIP in Shoemaker protocol. Without MARCoNS clearance, VIP can worsen symptoms.

Reconstitution and storage

Lyophilized peptide; reconstitute with BAC water at 1-2 mg/mL. Compounded intranasal: prepared by pharmacy with metered-dose pump, 50 mcg/spray typical.

Lyophilized: refrigerated, away from light. Reconstituted: refrigerated, use within 14-30 days. VIP is heat- and light-sensitive.

Open the reconstitution calculator for VIP