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 is a 28-amino-acid neuropeptide that functions as both a neurotransmitter and a hormone, with receptors (VPAC1 and VPAC2) distributed throughout the central and peripheral nervous systems, the GI tract, the respiratory tract, and the immune system. It was first isolated from porcine intestine in 1970 by Sami Said and Viktor Mutt, and its vasoactive properties (potent vasodilation and blood pressure reduction) led to its name.
VIP has attracted significant attention in two clinical contexts. First, it has been studied for its neuroprotective properties — VIP promotes neuronal survival, reduces neuroinflammation, and has shown promise in preclinical models of Parkinson's disease, Alzheimer's disease, and traumatic brain injury. Second, Dr. Ritchie Shoemaker popularized VIP as a treatment for Chronic Inflammatory Response Syndrome (CIRS), a multi-system condition associated with biotoxin exposure (particularly from mold). In the Shoemaker protocol, intranasal VIP is used as a final step to normalize dysregulated neuropeptide levels.
VIP is not FDA-approved for any indication and was placed on the Category 2 restricted list in late 2023. Its status under the February 2026 reclassification is uncertain.
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 |
Vasodilation and hypotension: VIP's primary pharmacological effect is vasodilation, which can cause transient hypotension (low blood pressure), flushing, and lightheadedness. These effects are dose-dependent and typically self-limiting but require caution in patients with baseline low blood pressure or those taking antihypertensive medications.
Diarrhea: VIP stimulates intestinal water and electrolyte secretion — this is the mechanism behind VIPoma-associated secretory diarrhea. At therapeutic doses used in CIRS protocols, diarrhea is occasionally reported.
Nasal administration: In the Shoemaker CIRS protocol, VIP is administered intranasally. Nasal irritation and rhinorrhea have been reported. Standard dosing in this context is 50 μg per nostril, 4 times daily.
Limited clinical data: Most VIP safety information comes from short-term clinical observations and the Shoemaker CIRS protocol experience rather than from formal clinical trials. Rigorous safety studies for chronic intranasal VIP use are lacking.
| 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 |