VIP (Vasoactive Intestinal Peptide)

1. Clinical Overview

Widely used in CIRS protocols and complex autonomic/neuroimmune dysfunction. Potent effects on anti-inflammatory signaling, bronchodilation, gut motility/absorption, autonomic regulation, and neurovascular function.

2. Mechanisms of Action

2.1 VPAC1 & VPAC2 Receptor Activation

cAMP signaling, anti-inflammatory immunity, smooth muscle relaxation, bronchodilation, enhanced mucus clearance, vasodilation.

2.2 Anti-Inflammatory Cytokine Modulation

Reduces TNF-α, IL-6, IL-1β, IL-12, NF-κB. Increases IL-10 and Treg function. Downregulates chronic systemic inflammation, restores immune balance.

2.3 Neuroimmune & Autonomic

Parasympathetic activation, heart rate variability, vagal tone, stress reactivity, neurovascular stability. Dysautonomia, POTS, CIRS-related autonomic dysfunction.

2.4 Pulmonary & Bronchodilatory

Natural bronchodilator: relaxes bronchial smooth muscle, pulmonary vasodilation, reduced airway inflammation, improved O₂ utilization. COPD, asthma, pulmonary hypertension.

2.5 Gut Motility & Secretory

Smooth muscle relaxation, gut motility, bile flow, pancreatic enzyme secretion, mucosal healing. IBS, dysmotility, gut–brain axis dysfunction.

3. Clinical Applications

3.1 CIRS

Final step in many CIRS protocols: inflammation reduction, cognitive improvement, sleep normalization, improved autonomic tone, mitochondrial biogenesis markers, reduced symptom clusters.

3.2 Autonomic Dysfunction

Heart rate variability, parasympathetic tone, stress response, neurovascular perfusion. POTS, Long-COVID dysautonomia, post-viral instability.

3.3 Pulmonary

Bronchodilation, airflow, pulmonary vascular dilation, exercise tolerance. COPD, pulmonary hypertension, asthma, chronic bronchitis.

3.4 GI Motility

Smooth muscle relaxation, intestinal secretions, motility rhythm, pancreatic enzymes. IBS, SIBO-associated dysmotility, post-infectious GI dysfunction.

3.5 Cognitive & Neuroimmune

Neuroprotective: reduced microglial activation, decreased cytokine signaling, improved neurovascular flow. Post-inflammatory cognitive dysfunction, brain fog, stress-induced neurocognitive impairment.

4. Administration & Dosing

Reconstitution

5 mg vial: 2 mL BS → 2.5 mg/mL, or 5 mL → 1 mg/mL (preferred for precision). Gently swirl — do not shake.

5. Clinical Decision Trees

Tree 1 — Candidate Selection

Tree 2 — Route Selection

6. Safety, Contraindications & Monitoring

Contraindications

• Active severe asthma attack
• Uncontrolled hypotension
• VIP hypersensitivity
• Pregnancy / Breastfeeding
• Acute infection (wait until stabilized)

Side Effects

Common: Transient flushing, lightheadedness, nasal irritation, mild headache, loose stools, temporary BP drop. Rare: Tachycardia, anxiety/jitteriness, worsened asthma in sensitive patients.

Monitoring

• Blood pressure (especially early)
• Heart rate variability
• Cognitive function
• Dyspnea scale (pulmonary)
• GI sensitivity scoring
• CIRS symptom cluster monitoring