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Tissue Repair & Anti-Inflammatory

VIP

Potent anti-inflammatory neuropeptide used intranasally in CIRS (mold illness) protocols; small human studies only.

InvestigationalEvidence level 3 of 5: Limited human dataAlso: Vasoactive Intestinal Peptide, Aviptadil (synthetic VIP), Zyesami (investigational)

Overview

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide made by nerves throughout the brain, gut, lungs and immune system. Acting on VPAC1 and VPAC2 receptors, it relaxes smooth muscle and blood vessels, opens airways, regulates gut secretion and is one of the body's strongest natural anti-inflammatory signals, suppressing inflammatory cytokines and supporting regulatory T cells. It also helps regulate circadian rhythm and the stress-hormone axis. Intranasal VIP is best known as the final step of the Shoemaker protocol for chronic inflammatory response syndrome (CIRS) linked to mold exposure, used only after the exposure is removed and other markers are corrected. Intravenous and inhaled forms have been studied in sarcoidosis, pulmonary hypertension and COVID-19, with mixed results.

Classification
Endogenous 28-amino-acid neuropeptide (secretin/glucagon family)
Route
Intranasal (IV and inhaled in trials)
Half-life
~1–2 minutes in plasma (IV); intranasal delivery extends local effect

Mechanism of action

Primary targetVPAC1 and VPAC2 G-protein–coupled receptors
  1. Intranasal deliveryBypasses rapid blood degradation; reaches nasal mucosa and the brain.
  2. VPAC1/VPAC2 bindingActivates cAMP–PKA signaling in immune, neural, vascular and epithelial cells.
  3. Cytokine suppressionTNF-α, IL-6 and IL-12 fall; regulatory T cells expand.
  4. Vasodilation, bronchodilationSmooth muscle relaxes in blood vessels and airways.
  5. Neuroendocrine rebalancingSupports hypothalamic and circadian regulation, including MSH and ADH patterns.
Downstream effects
  • Reduced systemic inflammation
  • Improved CIRS markers
  • Bronchodilation

Researched for

  • Chronic inflammatory response syndrome (CIRS)
  • Sarcoidosis
  • Pulmonary arterial hypertension
  • COVID-19 respiratory failure
  • Autoimmune and inflammatory disease

Research notes

  • Shoemaker et al. (2013) open-label CIRS study reported symptom and biomarker improvement (C4a, TGF-β1, VEGF, MSH).
  • Prasse et al. (2010): inhaled VIP reduced inflammatory cytokines and increased regulatory T cells in 20 sarcoidosis patients.
  • IV aviptadil in COVID-19 respiratory failure missed its primary endpoint in the main RCT; EUA requests were denied.
  • Plasma half-life is only 1–2 minutes, limiting systemic delivery.

Reported side effects

  • Flushing
  • Low blood pressure or lightheadedness
  • Watery diarrhea or nausea
  • Headache
  • Worsening symptoms if used before CIRS steps are complete

Contraindications & cautions

  • Ongoing mold/biotoxin exposure or untreated MARCoNS (CIRS)
  • Symptomatic hypotension
  • Pregnancy and breastfeeding
  • Active prostatitis (theoretical)

Lab monitoring

  • CBC with differential, CMP
  • MSH, VEGF, TGF-β1, C4a (CIRS)
  • ACTH, cortisol, ADH/osmolality
  • Vitamin D (25-OH)
  • Visual contrast sensitivity (VCS) test

Dosing and pricing for VIP

Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.

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