VIP
Vasoactive Intestinal Peptide
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide found throughout the central and peripheral nervous systems, gut, and immune tissues, primarily used in research contexts for its potent anti-inflammatory, bronchodilatory, and immunomodulatory properties. It has gained significant interest in the context of CIRS (Chronic Inflammatory Response Syndrome) and mast cell activation disorders, where it is used to help restore immune homeostasis and reduce neuroinflammation. VIP is also under investigation for pulmonary arterial hypertension, autoimmune conditions, and post-viral syndromes including long COVID.
Mechanism of Action
VIP exerts its effects primarily by binding to VPAC1 and VPAC2 G-protein coupled receptors, activating adenylyl cyclase and increasing intracellular cAMP, which drives downstream anti-inflammatory signaling including suppression of NF-κB and reduction of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12. It promotes regulatory T-cell differentiation, inhibits mast cell degranulation, and acts as a potent vasodilator and bronchodilator by relaxing smooth muscle via cAMP-mediated pathways. In the neuroendocrine axis, VIP regulates circadian rhythms, modulates HPA axis activity, and plays a role in the restoration of NeuroQuant-quantified brain volume losses seen in biotoxin illness.
Evidence by Health Goal(18 goals)
Dosing Protocols
Approximately every 4-6 hours, spread evenly throughout waking hours
Cycle: Start with lower frequency and titrate upward over weeks; long-term use common in CIRS protocols
This is the standard Shoemaker protocol dosing for CIRS. Treatment is typically preceded by clearance of ongoing biotoxin exposure and normalization of other inflammatory markers. Compounding pharmacy preparation required. Each nostril receives 50mcg per actuation.
Subcutaneous injection, timing flexible but consistency preferred
Cycle: Research protocols vary; typically administered for 4-12 week study periods
Primarily used in clinical research settings for pulmonary arterial hypertension and autoimmune conditions. Inhaled IV formulations were used in early PAH trials. Subcutaneous use is largely investigational outside structured protocols.
Safety & Side Effects
VIP has a relatively favorable short-term safety profile at therapeutic doses, with most adverse effects being transient and dose-dependent; however, its long-term safety data in humans remains limited and largely derives from small clinical studies and case series. It is not FDA-approved as a therapeutic agent in the United States and must be obtained through compounding pharmacies under physician supervision, making unsupervised self-administration inadvisable given its potent cardiovascular and immunological activity.
Possible Side Effects
- !Facial flushing and warmth immediately following nasal administration
- !Transient hypotension and lightheadedness, particularly at higher doses
- !Nausea and gastrointestinal cramping, especially with systemic administration
- !Nasal irritation, congestion, or epistaxis with intranasal use
- !Headache following administration, typically short-lived
- !Tachycardia or palpitations at supraphysiologic doses
- !Temporary worsening of inflammatory symptoms during initial titration (herxheimer-like reaction in CIRS context)
- !Injection site reactions including erythema and mild pain with subcutaneous use
Interactions
- -Can significantly potentiate antihypertensive medications - additive blood pressure lowering effect requiring monitoring
- -May enhance effects of other vasodilators including nitrates and phosphodiesterase inhibitors (sildenafil, tadalafil)
- -Potential additive immunomodulatory effects when combined with immunosuppressants - may over-suppress immune responses
- -May alter insulin sensitivity and glucagon signaling - use caution in diabetic patients on hypoglycemic agents
- -Theoretically may reduce efficacy of vasoconstrictor medications used in septic shock or anaphylaxis management
Cost & Where to Buy
Cost is driven primarily by compounding pharmacy preparation, which varies significantly by pharmacy and formulation. Intranasal VIP at 50mcg/actuation compounded spray typically runs $150-400 per month depending on concentration and volume. Research-grade peptide from vendors is cheaper but purity and sterility are not guaranteed for human use. Physician consultation and testing add substantial additional costs in CIRS protocols.
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