VIP
Also known as: Vasoactive Intestinal Peptide, Vasoactive Intestinal Polypeptide, PHM-27 related
VIP (Vasoactive Intestinal Peptide) is a 28-amino acid endogenous neuropeptide with potent anti-inflammatory, immunomodulatory, neuroprotective, and vasodilatory properties. It is researched for CIRS (Chronic Inflammatory Response Syndrome), autoimmune conditions, and pulmonary hypertension.
VIP is a 3,326.8 Da research peptide. VIP (Vasoactive Intestinal Peptide) is a 28-amino acid endogenous neuropeptide with potent anti-inflammatory, immunomodulatory, neuroprotective, and vasodilatory properties. It is researched for CIRS (Chronic Inflammatory Response Syndrome), autoimmune conditions, and pulmonary hypertension.
Also called: Vasoactive Intestinal Peptide, Vasoactive Intestinal Polypeptide, PHM-27 related
3,326.8
Molecular Weight
Daltons
1
Strong Evidence
benefits
5
Studies Cited
peer-reviewed
50-50
Typical Dose
mcg per spray
Overview
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide originally isolated from porcine intestine in 1970 by Said and Mutt. Despite its name, VIP is widely distributed throughout the central and peripheral nervous systems, immune system, and virtually every organ. It belongs to the secretin/glucagon peptide superfamily and signals through two G-protein coupled receptors: VPAC1 and VPAC2. VIP functions as a neurotransmitter, neuromodulator, and immune regulator with unusually broad biological activities. It is a potent vasodilator (originally named for this property), anti-inflammatory agent, immunomodulator, neuroprotector, and bronchodilator. In clinical medicine, VIP has gained particular attention through the work of Dr. Ritchie Shoemaker for the treatment of Chronic Inflammatory Response Syndrome (CIRS); a multi-system illness triggered by biotoxin exposure (mold, Lyme disease, etc.). VIP nasal spray is used as the final step in the Shoemaker CIRS protocol to restore regulatory neuropeptide function. VIP has also been investigated for pulmonary arterial hypertension, sarcoidosis, ARDS, inflammatory bowel disease, and neurodegenerative diseases. Its extremely broad biological profile makes it one of the most multifunctional neuropeptides known.
Key Takeaways: VIP
- Strongest evidence supports VIP for potent anti-inflammatory
- Research doses typically range from 50 to 50 mcg per spray via intranasal spray (4 sprays daily = 200 mcg/day typical)
- 1 benefits with strong evidence, 4 moderate, 1 preliminary
- Half-life: ~1-2 minutes (extremely rapid degradation by neutral endopeptidase and DPP-IV)
- 5 cited research studies in this guide
Mechanism of Action
VIP signals through two class B G-protein coupled receptors: VPAC1 (widely expressed including immune cells, CNS, lung, liver, gut) and VPAC2 (prominent in CNS, smooth muscle, pancreas). Both receptors activate adenylyl cyclase, increasing intracellular cAMP which drives diverse downstream effects. Anti-inflammatory: VIP suppresses NF-κB activation in macrophages and dendritic cells, reducing production of pro-inflammatory cytokines (TNF-α, IL-6, IL-12, IL-1β) and chemokines. It promotes the generation of tolerogenic dendritic cells and regulatory T-cells (Tregs), shifting immune balance from Th1/Th17 toward regulatory phenotypes. Neuroprotective: VIP supports neuronal survival through BDNF and activity-dependent neuroprotective protein (ADNP) induction, reduces excitotoxicity, and protects against oxidative stress in neurons and glial cells. Vasodilatory: VIP relaxes smooth muscle in blood vessels and airways through cAMP-mediated mechanisms, reducing pulmonary vascular resistance (relevant to pulmonary hypertension) and bronchospasm. In the GI tract, VIP regulates secretion, motility, and blood flow. In circadian biology, VIP is essential for SCN (suprachiasmatic nucleus) clock function and synchronization of circadian rhythms. In CIRS, VIP dysfunction is proposed as a downstream consequence of chronic inflammation, with VIP replacement helping restore regulatory immune function, reduce inflammation, and improve symptoms across multiple organ systems.
Research Benefits
VIP at a Glance
VIP signals through two class B G-protein coupled receptors: VPAC1 (widely expressed including immune cells, CNS, lung, liver, gut) and VPAC2 (prominent in CNS, smooth muscle, pancreas).
Potent Anti-Inflammatory
Strong EvidenceSuppresses NF-κB signaling and pro-inflammatory cytokine production in macrophages and dendritic cells. Promotes regulatory T-cells and tolerogenic immune responses. Studied in autoimmune models including rheumatoid arthritis, colitis, and EAE.
CIRS Treatment (Shoemaker Protocol)
Moderate EvidenceUsed as the final step in the Shoemaker protocol for Chronic Inflammatory Response Syndrome. Clinical observations show improvements in inflammatory markers (TGF-β1, MMP-9, MSH), symptoms, and quality of life in CIRS patients.
Pulmonary Vasodilation
Moderate EvidencePotent pulmonary vasodilator studied for pulmonary arterial hypertension (PAH). Inhaled VIP improved pulmonary hemodynamics and exercise capacity in PAH clinical studies.
Neuroprotection
Moderate EvidenceProtects neurons against excitotoxicity, oxidative stress, and inflammation through BDNF and ADNP induction. Studied in models of Alzheimer's disease, Parkinson's disease, and stroke.
Bronchodilation
Moderate EvidenceRelaxes airway smooth muscle and reduces bronchospasm. Studied as an inhaled treatment for asthma and COPD, with bronchodilatory potency comparable to or exceeding beta-2 agonists in some studies.
Circadian Rhythm Regulation
PreliminaryEssential neuropeptide for SCN clock function. VIP deficiency disrupts circadian rhythms, and restoration may help normalize sleep-wake cycles in conditions involving circadian disruption.
Research Dosing Protocols
Research Purposes Only: All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
| Research Protocol | Dose Range | Route |
|---|---|---|
| CIRS protocol (Shoemaker intranasal) | 50–50 mcg per spray | Intranasal spray (4 sprays daily = 200 mcg/day typical) |
| Pulmonary hypertension (inhaled) | 100–200 mcg | Inhalation (nebulized), 4x daily |
| Subcutaneous research | 50–200 mcg | Subcutaneous injection |
Frequency
2-4 times daily (intranasal); 4 times daily (inhaled)
Timing
Spread throughout the day for sustained levels given short half-life
Cycle Length
CIRS: months to ongoing; pulmonary: chronic treatment; variable for other indications
Research Notes
- 1In the Shoemaker CIRS protocol, VIP is used ONLY after other steps (binder therapy, MARCoNS eradication, correcting hormones) are completed.
- 2VIP has an extremely short half-life (~1-2 minutes), intranasal delivery provides local and CNS access.
- 3Intranasal route bypasses the blood-brain barrier for direct CNS effects.
- 4Must be compounded by a specialty pharmacy — not commercially available as a finished drug.
- 5CIRS patients should have lipase levels monitored during VIP therapy (Shoemaker protocol recommendation).
- 6VIP is fragile, protect from heat and light; use within recommended timeframe.
Reconstitution Guide
Standard Reconstitution
Vial Size
5 mg
Bacteriostatic Water
2 mL
Concentration
25 mcg
per 0.1 mL (10 units)
Step-by-Step Guide
Gather Materials
VIP vial, bacteriostatic water, alcohol swabs, insulin syringes.
Equilibrate Temperature
Remove the vial from storage and allow it to reach room temperature (5-10 minutes).
Sanitize
Swab the rubber stopper of both the peptide vial and bacteriostatic water vial with alcohol.
Draw Water
Draw 2 mL of bacteriostatic water into a syringe.
Add Water to Vial
Insert the needle into the peptide vial and direct the water stream against the glass wall — not directly onto the powder.
Mix Gently
Swirl the vial gently until the powder is fully dissolved. Never shake. The solution should be clear and colorless.
Store Properly
Refrigerate at Refrigerated (2-8°C / 36-46°F) at all times after reconstitution. 14-21 days refrigerated (VIP is relatively fragile).
Storage Temperature
Refrigerated (2-8°C / 36-46°F) at all times after reconstitution
Shelf Life
14-21 days refrigerated (VIP is relatively fragile)
Important Notes
- •VIP for intranasal use is typically prepared by compounding pharmacies as a nasal spray.
- •For research preparations, reconstitute with sterile or bacteriostatic saline.
- •VIP is sensitive to degradation; keep refrigerated and protect from light.
- •Intranasal spray devices should be primed before first use.
- •Do not freeze reconstituted VIP solution.
VIP Dosing Calculator
Calculate daily intake, cycle totals, and vials needed with pre-filled protocols →
VIP Reconstitution Calculator
Calculate concentration, syringe units, and doses per vial with auto-filled values →
Safety & Side Effects
Reported Side Effects
- !Nasal irritation with intranasal use (most common, typically mild)
- !Mild headache
- !Facial flushing (vasodilatory effect)
- !Transient hypotension (especially with higher doses or IV route)
- !Watery diarrhea at high systemic doses (VIP stimulates intestinal secretion)
- !Nasal congestion
- !Tachycardia (compensatory, from vasodilation)
- !Generally well tolerated at intranasal doses used in CIRS protocol
Potential Interactions
- ⚡May potentiate the effects of antihypertensive medications (additive vasodilation).
- ⚡Caution with PDE5 inhibitors (sildenafil, tadalafil) — additive vasodilatory effect.
- ⚡May interact with medications that affect cAMP levels.
- ⚡Potential interaction with immunosuppressive drugs (VIP modulates immune function).
- ⚡Monitor with anticoagulants; VIP may affect platelet function at high doses.
- ⚡DPP-IV inhibitors may slightly extend VIP's short half-life.
Important: Side effects and interactions listed here are compiled from published research and community reports. This is not a complete list. No formal drug interaction studies have been conducted for most research peptides. Always consult a qualified healthcare provider.
Research Studies
The following studies are referenced in this profile. PubMed IDs are provided where available for independent verification.
Vasoactive intestinal peptide as a potent anti-inflammatory neuropeptide
thorough review of VIP's anti-inflammatory mechanisms including NF-κB suppression, cytokine modulation, Treg induction, and therapeutic potential in autoimmune and inflammatory diseases.
Vasoactive intestinal peptide in pulmonary arterial hypertension
Clinical study demonstrating inhaled VIP improved pulmonary hemodynamics, exercise capacity, and cardiac output in patients with pulmonary arterial hypertension without systemic side effects.
VIP as a treatment for chronic inflammatory response syndrome
Clinical observations supporting intranasal VIP use in CIRS patients, showing improvements in inflammatory markers (TGF-β1, C4a, MMP-9), pulmonary function, and symptoms following the Shoemaker stepwise protocol.
Neuroprotective effects of VIP and PACAP in neurodegeneration
Reviewed VIP's neuroprotective mechanisms including BDNF/ADNP induction, anti-oxidant and anti-apoptotic effects, and therapeutic potential for Alzheimer's, Parkinson's, and stroke.
VIP regulates the generation of tolerogenic dendritic cells and Tregs
Demonstrated VIP's ability to generate tolerogenic dendritic cells that promote regulatory T-cell differentiation, establishing the mechanism for VIP's therapeutic potential in autoimmune diseases.
Note: This is not an exhaustive list of all published research. Studies are selected for relevance and quality. Click PubMed IDs to verify sources independently. Inclusion does not imply endorsement of the peptide for any clinical use.
Frequently Asked Questions
VIP (Vasoactive Intestinal Peptide) is a naturally occurring 28-amino acid neuropeptide with anti-inflammatory, vasodilatory, neuroprotective, and immunomodulatory properties. It is used in the Shoemaker protocol for CIRS and researched for pulmonary hypertension, autoimmune conditions, and neurodegeneration.
In the Shoemaker protocol for Chronic Inflammatory Response Syndrome, VIP nasal spray is the final treatment step used to restore regulatory neuropeptide function, reduce chronic inflammation (TGF-β1, MMP-9), and improve multi-system symptoms after other interventions have been completed.
VIP has an extremely short half-life (~1-2 minutes in blood). Intranasal delivery provides direct access to the CNS by bypassing the blood-brain barrier through olfactory and trigeminal nerve pathways, and also provides local anti-inflammatory effects in the nasal/sinus passages.
No. VIP is not FDA-approved as a drug. It is available as a compounded preparation through specialty compounding pharmacies. Clinical trials have been conducted for pulmonary hypertension and other conditions, but it has not received regulatory approval.
VIP is a potent vasodilator, so transient blood pressure reduction is possible, particularly with higher doses or intravenous administration. At the intranasal doses used in CIRS protocols, clinically significant hypotension is uncommon but patients on antihypertensive medications should be monitored.
In the Shoemaker model of CIRS, chronic biotoxin exposure (mold, Lyme, etc.) triggers a sustained inflammatory cascade that ultimately depletes regulatory neuropeptides including VIP and MSH. VIP replacement is used to restore immune regulation and reduce the chronic inflammatory state after the underlying triggers have been addressed.
Research & Educational Use Only
All content is for informational and research purposes only. This site does not provide medical advice, diagnosis, or treatment. Consult a qualified healthcare professional before using any peptide or supplement.
The information presented here is compiled from published research studies and is intended for informational purposes only. Individual results may vary. Always consult with a licensed healthcare provider.