A 28-amino-acid neuropeptide with wide-ranging effects on vasodilation, smooth muscle relaxation, immune modulation, and circadian rhythm. Used in functional medicine for chronic inflammatory response syndrome (CIRS) and increasingly studied for autoimmune and neuroinflammatory conditions.
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide first isolated from porcine intestine in 1970 by Sami Said and Viktor Mutt. Despite its name, VIP is widely distributed throughout the body — brain, lungs, GI tract, immune cells, and blood vessels — and acts as both a neurotransmitter and an immune modulator.
VIP gained significant attention in functional medicine through Dr. Ritchie Shoemaker's protocol for chronic inflammatory response syndrome (CIRS), where it is used as a nasal spray to reduce neuroinflammation and restore immune regulation in patients with biotoxin illness (mold exposure).
VIP signals through two receptors: VPAC1 (widely expressed, dominant in immune modulation) and VPAC2 (dominant in smooth muscle relaxation and circadian rhythm). Both are Gs-coupled GPCRs that increase cAMP. In the immune system, VIP's cAMP increase promotes regulatory T cell (Treg) differentiation and suppresses pro-inflammatory Th1/Th17 responses — essentially resetting an overactive immune system toward tolerance.
| Pathway | Effect | Significance |
|---|---|---|
| Vasodilation | Relaxes vascular smooth muscle via cAMP-mediated calcium reduction | Increases blood flow, reduces blood pressure |
| Immune regulation | Promotes Treg differentiation, suppresses Th1/Th17 | Shifts from pro-inflammatory to anti-inflammatory immune state |
| Bronchodilation | Relaxes airway smooth muscle | Investigated for asthma and COPD |
| Neuroprotection | Promotes neuronal survival via BDNF upregulation | Protects against excitotoxicity and neuroinflammation |
| Circadian regulation | VPAC2 in suprachiasmatic nucleus | Modulates circadian clock and sleep-wake cycles |
| Study | Design | Findings | Level |
|---|---|---|---|
| CIRS/mold illness | Clinical protocol (Shoemaker) | Nasal VIP improved inflammatory markers (TGF-beta1, MMP9, MSH) and symptoms in CIRS patients | Level II-III |
| Pulmonary hypertension | Case series + pilot trials | Inhaled VIP reduced pulmonary artery pressure and improved exercise tolerance | Level II-III |
| Autoimmune arthritis | Preclinical + pilot | VIP reduced joint inflammation in animal models of RA. Small human studies showed promise. | Preclinical + Level III |
| Sepsis | Preclinical | VIP reduced mortality and organ damage in animal sepsis models by suppressing inflammatory cytokine storm | Preclinical |
| Sarcoidosis | Case reports | Some improvement in pulmonary sarcoidosis with inhaled VIP | Level IV |
Transient hypotension: VIP is a potent vasodilator. Blood pressure drop is the most common side effect, especially with IV administration.
Facial flushing: Vasodilation-mediated flushing is common and transient.
Nasal spray tolerability: Nasal VIP is generally well-tolerated. Mild nasal irritation possible.
Short half-life: VIP has a very short half-life (< 2 minutes in plasma), requiring frequent dosing or nasal/inhaled routes for sustained effect.
| Jurisdiction | Status |
|---|---|
| FDA | Not approved for any indication. |
| Functional medicine | Used in Shoemaker CIRS protocol (off-label compounding) |
| Research | Active research in autoimmune, pulmonary, and neuroinflammatory conditions |