VIP
Neuropeptide / Immunomodulatory Peptideresearch (investigational for some indications)Also known as: Vasoactive Intestinal Peptide, Aviptadil, RLF-100
A 28-amino acid neuropeptide with broad immunomodulatory, vasodilatory, and anti-inflammatory effects, used in CIRS (Chronic Inflammatory Response Syndrome) protocols and researched for pulmonary conditions.
Overview
Vasoactive Intestinal Peptide (VIP) is an endogenous 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily. It is widely distributed throughout the central and peripheral nervous systems and plays roles in vasodilation, smooth muscle relaxation, immune regulation, neuroprotection, and gastrointestinal function. VIP has gained particular prominence in the mold illness and biotoxin community through Dr. Ritchie Shoemaker's CIRS (Chronic Inflammatory Response Syndrome) protocol, where it is used as a final step to restore regulatory neuropeptide levels. VIP acts through VPAC1 and VPAC2 receptors to modulate inflammatory cascades, protect pulmonary epithelium, and regulate circadian rhythms. It has also been investigated as Aviptadil (RLF-100) for COVID-19 ARDS, pulmonary hypertension, and erectile dysfunction. VIP's broad biological activity makes it one of the most versatile regulatory peptides, though its short half-life and route of administration present practical challenges.
Mechanism of Action
VIP acts through VPAC1/VPAC2 G-protein coupled receptors: (1) Activates adenylyl cyclase, increasing intracellular cAMP; (2) Potent vasodilator — relaxes vascular and bronchial smooth muscle; (3) Inhibits pro-inflammatory cytokines (TNF-α, IL-6, IL-12) while promoting anti-inflammatory IL-10; (4) Protects pulmonary surfactant-producing type II alveolar cells; (5) Modulates T-cell differentiation, promoting regulatory T-cells (Tregs); (6) Regulates circadian clock gene expression in the suprachiasmatic nucleus; (7) Stimulates water and electrolyte secretion in the gut; (8) Neuroprotective through BDNF upregulation and anti-apoptotic signaling.
Molecular Formula
C147H237N43O44S
Molecular Weight
3326.82 g/mol
Sequence
His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn-NH2
Dosage Protocols
Dose Range
50mcg – 50mcg
Frequency
4 times daily
Route
intranasal
Cycle Length
30 days minimum; ongoing as needed based on biomarkers
Shoemaker CIRS protocol: 50mcg per nostril (4 sprays) QID. Used as a final step after other CIRS markers are normalized. Monitor VIP levels, MSH, MMP-9, VEGF, and lipase. Must pass VCS (Visual Contrast Sensitivity) test and have ERMI < 2 before starting.
Source: Shoemaker CIRS protocol
Side Effects
| Effect | Severity |
|---|---|
| Nasal irritation | mild |
| Diarrhea | mild |
| Hypotension | moderate |
| Facial flushing | mild |
| Headache | mild |
Pros & Cons
Endogenous neuropeptide with broad anti-inflammatory and immunoregulatory effects
Central to CIRS/mold illness treatment protocol with demonstrated clinical benefit in this population
Intranasal delivery is non-invasive and reaches CNS effectively
Multi-system benefits: immune, pulmonary, GI, neurological, and cardiovascular
Very short half-life (~1-2 minutes in blood) requiring frequent dosing or intranasal route
Limited RCT data for CIRS use — most evidence from Shoemaker's clinical practice
Strict prerequisites in CIRS protocol — cannot be used until other markers are normalized
Compounded nasal spray availability and cost can be barriers
Research Studies
Legal Status
Not FDA-approved for CIRS use. Aviptadil has FDA Fast Track and Emergency Use designations for ARDS. Available by prescription from compounding pharmacies (nasal spray). Used off-label in CIRS/mold illness protocols.
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