VIP (Vasoactive Intestinal Peptide) — Research, Dosing & Price Guide

Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide with broad physiological functions including vasodilation, immunomodulation, neuroprotection, and regulation of circadian rhythms. It is found throughout the central and peripheral nervous systems, the gastrointestinal tract, and the immune system. VIP has gained attention for its potential therapeutic applications in chronic inflammatory conditions, mast cell activation syndrome (MCAS), mold illness (CIRS), and neurodegenerative diseases.

VIP signals through two G-protein coupled receptors: VPAC1 (widely expressed in the CNS, liver, lungs, and immune cells) and VPAC2 (predominant in the CNS, pancreas, and smooth muscle). Both receptors activate adenylyl cyclase via Gsα, increasing intracellular cAMP levels and activating protein kinase A (PKA). This triggers diverse tissue-specific effects. In blood vessels, VIP is one of the most potent endogenous vasodilators, relaxing smooth muscle via cAMP-mediated inhibition of myosin light chain kinase. In the immune system, VIP is a potent anti-inflammatory mediator — it suppresses pro-inflammatory cytokine production (TNF-α, IL-6, IL-12), inhibits NF-κB activation, promotes regulatory T-cell differentiation, and shifts macrophages from M1 (inflammatory) to M2 (resolving) phenotype. In the nervous system, VIP acts as a neuroprotective agent — it enhances neuronal survival, promotes neurite outgrowth, and modulates glutamate excitotoxicity. VIP also regulates circadian rhythms through its action on the suprachiasmatic nucleus (SCN) master clock. In the context of CIRS (chronic inflammatory response syndrome), VIP normalizes dysregulated inflammatory cascades, reduces pulmonary artery pressure, and restores regulatory neuropeptide function that is often disrupted by biotoxin exposure.

• Delgado et al. (2001, Nature Medicine) demonstrated VIP's potent anti-inflammatory effects, showing it prevented lethal endotoxemia by suppressing TNF-α and IL-6 in sepsis models
• Shoemaker et al. documented VIP's efficacy in CIRS patients, showing improvement in pulmonary artery pressure, regulatory neuropeptides (MSH, VIP), and inflammatory markers (TGF-β1, MMP-9, C4a)
• Gonzalez-Rey et al. (2006, Annals of the New York Academy of Sciences) reviewed VIP's role as a neuroimmune mediator with therapeutic potential in autoimmune diseases
• VIP has shown neuroprotective effects in animal models of Alzheimer's disease, Parkinson's disease, and traumatic brain injury
• Studies demonstrate VIP promotes regulatory T-cell differentiation and immune tolerance
• Research shows VIP normalizes circadian rhythm disruption via SCN modulation

• CIRS/mold illness protocol (Shoemaker): 50 mcg intranasally 4 times daily, titrating up based on response
• Some protocols start at 25 mcg intranasally 2–3 times daily and titrate to 50 mcg 4x daily
• Research doses vary: 1–10 mcg/kg IV for acute vasodilation studies
• Intranasal is the preferred route for CNS and systemic immune effects
• Cycle: used continuously for chronic conditions (CIRS, MCAS) until inflammatory markers normalize
• Must pass VCS (visual contrast sensitivity) test and have MARCoNS (nasal staph) treated before starting VIP per Shoemaker protocol
• Some protocols use subcutaneous injection at 50–100 mcg daily as an alternative to intranasal

Known Side Effects

• Nasal irritation and rhinorrhea with intranasal administration
• Transient hypotension and facial flushing (due to potent vasodilatory effects)
• Diarrhea at higher doses (VIP stimulates intestinal secretion — it's named 'vasoactive intestinal peptide' for this reason)
• Headache related to vasodilation
• Tachycardia as a reflex response to vasodilation
• Rare: water retention and electrolyte disturbances at high systemic doses

Safety Profile

VIP is an endogenous peptide with natural biocompatibility. At intranasal doses used in CIRS protocols, systemic side effects are generally mild. The primary concern is hypotension in susceptible individuals — patients with low baseline blood pressure should start at lower doses. VIP should be used cautiously in patients with active malignancy, as it has both pro-angiogenic and immunosuppressive properties that could theoretically support tumor growth. In the Shoemaker CIRS protocol, VIP is used only after other inflammatory triggers have been addressed (mold avoidance, binders, MARCoNS treatment), as premature VIP use may be less effective or mask ongoing exposure. Not FDA-approved for any indication. Drug interactions include potential additive hypotension with antihypertensives. Not studied in pregnancy.

Week 1–2: Mild vasodilatory effects may be noticeable (facial warmth, slight blood pressure drop). Nasal irritation is common with intranasal use. Some CIRS patients report initial 'herx-like' reactions as inflammatory pathways are modulated. Week 2–4: Anti-inflammatory effects become apparent. CIRS patients may notice improved energy, reduced brain fog, and improved respiratory symptoms. Inflammatory markers (if monitored) begin trending downward. Week 4–8: Sustained improvement in CIRS symptoms. Pulmonary artery pressure normalizes. Regulatory neuropeptide levels improve. Sleep quality and circadian rhythm regulation may improve. Week 8+: Full therapeutic effects in chronic conditions. CIRS patients show normalized lab markers (TGF-β1, C4a, MMP-9). Cognitive function improves. Quality of life enhances significantly. Ongoing use may be needed for sustained benefit.

Prices sourced from peptides.gg marketplace. Prices may vary.