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Overview
What is VIP?
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide with potent anti-inflammatory, immunomodulatory, and neuroprotective properties. Acting through VPAC1 and VPAC2 receptors, VIP regulates immune function, vascular tone, circadian rhythms, and neurological health. It has been extensively studied for chronic inflammatory response syndrome (CIRS), pulmonary conditions, autoimmune diseases, and most recently COVID-19 respiratory failure. The injectable form (Aviptadil/Zyesami) received FDA Fast Track designation for COVID-19 ARDS.
Key Benefits
Immune regulation and reduced inflammation, neuroprotection and circadian rhythm support, respiratory health improvement, direct CNS delivery bypassing BBB, correction of CIRS inflammatory markers, potential cognitive and mood benefits.
Mechanism of Action
VIP binds to VPAC1 and VPAC2 receptors coupled to Gαs proteins, activating adenylate cyclase and increasing cAMP/PKA signaling. This leads to anti-inflammatory effects through inhibition of pro-inflammatory cytokines (IL-6, TNF-α), modulation of T helper cell differentiation, and regulation of innate and adaptive immune responses. Intranasal delivery allows direct brain access via olfactory and trigeminal pathways.
Molecular Information
Weight
3326.8 Da
Length
28 amino acids
Type
Linear neuropeptide
Amino Acid 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
* C-terminal amidation for stability
Pharmacokinetics
Research Indications
Chronic Inflammatory Response Syndrome (CIRS)
VIP nasal spray is the final step in the Shoemaker Protocol for CIRS from mold/biotoxin exposure. Corrects inflammatory markers (TGF-β1, C4a, MMP9) refractory to other therapies.
Autoimmune Conditions
Research shows VIP downregulates both inflammatory and autoimmune disease components. Studied in rheumatoid arthritis, Crohn's disease, and multiple sclerosis models.
Respiratory Inflammation
VIP has bronchodilatory and anti-inflammatory effects in airways. Studied for asthma, COPD, and pulmonary sarcoidosis.
Research Protocols
Disclaimer
These are commonly discussed research protocols and not medical advice. Consult a healthcare provider before use.
Timing
VIP has a very short plasma half-life (1-2 minutes IV), but intranasal delivery provides more sustained local and CNS effects. Multiple daily doses maintain therapeutic levels. Morning dosing aligns with natural circadian VIP rhythms.
Peptide Interactions
How to Reconstitute
Important
Always use bacteriostatic water (BAC). Sterile technique is essential.
VIP nasal spray is typically supplied pre-formulated by compounding pharmacies
Store in refrigerator at 2-8°C
Clear nasal passages before administration
Prime spray bottle before first use (2-3 pumps)
Insert nozzle into nostril, aim slightly outward
Spray while gently inhaling
Alternate nostrils between doses
Do not blow nose immediately after spraying
Quality Indicators
Clear Solution
Compounded VIP nasal spray should be clear and colorless with no particles or cloudiness.
Proper Spray Function
Spray bottle should deliver consistent, fine mist with each actuation.
Licensed Compounding Pharmacy
Source from accredited compounding pharmacy with Certificate of Analysis and proper quality controls.
Temperature During Shipping
VIP is temperature-sensitive. Ensure cold chain was maintained during shipping.
Cloudiness or Particles
Any visible particles, cloudiness, or precipitation indicates degradation.
Discoloration
Any yellow or brown coloration indicates oxidation or contamination.
What to Expect
- Days 1-7: May experience mild nasal irritation initially
- Week 1-2: Potential improvement in energy and sleep quality
- Week 2-4: Reduction in inflammatory symptoms
- Week 4-8: Progressive improvement in CIRS markers if applicable
- Month 2+: Continued correction of inflammatory and neurological parameters
- Note: Full benefits in CIRS may take several months of consistent use
Side Effects & Safety
- First dose should be administered under medical supervision with lab monitoring
- Pre-VIP labs: TGF-β1, Lipase (baseline)
- Post-VIP 15 min labs: TGF-β1, Lipase (to assess response and safety)
- Stop immediately if abdominal pain develops or lipase elevates above range
- Not FDA-approved as nasal spray - compounded off-label
- CIRS patients: Complete Shoemaker Protocol steps 1-11 before starting VIP
- Ensure MARCoNS eradicated and environment safe before VIP therapy
- Monitor blood pressure - VIP can cause vasodilation
- Not recommended during pregnancy or breastfeeding
References
IV Aviptadil in Critical COVID-19 Respiratory Failure - Phase 2b/3 RCT (2022)
Multicenter randomized controlled trial across 10 U.S. hospitals. Aviptadil showed 2-fold increased odds of 60-day survival (OR 2.0, p=0.035). Mechanically ventilated patients showed 10-fold increased survival odds. Significant reduction in IL-6 inflammatory marker.
View Study (opens in new tab) →VIP Corrects Chronic Inflammatory Response Syndrome (CIRS) (2013)
Study demonstrating VIP nasal spray corrects CIRS acquired from water-damaged buildings. Showed correction of proteomics, transcriptomics, and gray matter nuclear atrophy refractory to other therapies.
View Study (opens in new tab) →IUPHAR Review: VIP and PACAP Receptor Pharmacology (2012)
Definitive pharmacological review of VIP receptors. Details mechanism of action through Gαs/cAMP/PKA pathway, physiological functions in CNS and periphery, and therapeutic potential for neurodegenerative, inflammatory, and autoimmune diseases.
View Study (opens in new tab) →Quick Start Guide
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Community Insights
Self-reported by PepPedia users. Not clinical evidence. Health changes reflect all users, including those taking multiple compounds.
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