VIP (Vasoactive Intestinal Peptide) Dosage Guide
Evidence-based protocols for the 28-amino-acid neuropeptide used in the Shoemaker CIRS Protocol — intranasal, subcutaneous, and IV dosing for mold illness, pulmonary support, immune modulation, and stacking strategies.
In This Guide
What Is VIP?
VIP (Vasoactive Intestinal Peptide) is a 28-amino-acid neuropeptide originally isolated from porcine small intestine in 1970 by Sami Said and Viktor Mutt. Despite its name suggesting a gut-only role, VIP is widely distributed throughout the body — found in the central and peripheral nervous system, gastrointestinal tract, lungs, heart, and immune system. It functions as a neurotransmitter, neuromodulator, and potent immunoregulatory peptide.
VIP acts primarily through two G-protein coupled receptors: VPAC1 (widely expressed in the immune system, lungs, and liver) and VPAC2 (predominantly in the CNS, smooth muscle, and immune cells). Activation of these receptors stimulates cyclic AMP (cAMP) production, which triggers a broad cascade of anti-inflammatory, vasodilatory, bronchodilatory, and neuroprotective effects. This makes VIP one of the most physiologically versatile peptides known.
VIP is perhaps best known in the peptide community for its role in the Shoemaker Protocol for CIRS (Chronic Inflammatory Response Syndrome), also called mold illness or biotoxin illness. Dr. Ritchie Shoemaker identified VIP as the final therapeutic step in his multi-step protocol for normalizing the inflammatory markers (TGF-β1, MMP-9, C4a, VEGF) that characterize CIRS. VIP is also being developed pharmaceutically as Aviptadil (RLF-100) for pulmonary arterial hypertension and ARDS.
Use our Peptide Dosage to calculate your exact subcutaneous dose based on vial size and concentration.
Key Characteristics:
- 28-amino-acid endogenous neuropeptide — naturally produced in the body; first isolated from porcine intestine in 1970; widely distributed in the nervous system, GI tract, lungs, and immune system
- VPAC1 and VPAC2 receptor agonist — acts through G-protein coupled receptors to stimulate cAMP production, triggering anti-inflammatory, vasodilatory, bronchodilatory, and neuroprotective cascades
- Potent anti-inflammatory — suppresses TNF-α, IL-6, IL-12 production; inhibits NF-κB signaling; promotes regulatory T-cell (Treg) differentiation; shifts immune balance from Th1/Th17 toward Th2/Treg
- Central role in Shoemaker CIRS Protocol — the final step in the multi-step protocol for mold illness / biotoxin illness; normalizes TGF-β1, MMP-9, C4a, VEGF, and MSH levels
- Potent vasodilator and bronchodilator — relaxes pulmonary and systemic blood vessels; opens airways; basis for Aviptadil (RLF-100) clinical trials in pulmonary hypertension and ARDS
- Very short half-life (~1–2 minutes IV) — rapidly degraded by endopeptidases in plasma; requires frequent dosing or intranasal delivery to maintain therapeutic levels
For a complete overview of its mechanism and research, see our full VIP profile. New to peptides? Start with the Beginner's Guide to Peptides.
How VIP Dosage Is Determined
VIP dosing is informed by a combination of clinical CIRS research (primarily Dr. Shoemaker's published work), pharmaceutical clinical trials (Aviptadil for pulmonary conditions), basic science pharmacology, and community experience. VIP has substantially more clinical context than many research peptides, largely due to the Shoemaker Protocol and Aviptadil development.
Shoemaker CIRS Protocol (Intranasal)
Dr. Ritchie Shoemaker published extensively on VIP as the final step in his CIRS treatment protocol. His clinical experience with CIRS patients established the intranasal VIP dosing paradigm: 50 mcg per nostril, 4 times daily. This protocol was derived from clinical observation of biomarker normalization (TGF-β1, MMP-9, C4a, VEGF) in CIRS patients and refined over years of clinical practice. Shoemaker's published data showed significant improvement in inflammatory markers after 30 days of intranasal VIP in patients who had completed earlier protocol steps.
Aviptadil Clinical Trials (IV)
Aviptadil (synthetic VIP, branded as RLF-100) has been studied in clinical trials for pulmonary arterial hypertension, ARDS, and COVID-19-related respiratory failure. IV infusion doses in these trials range from 50–100 pmol/kg/min, administered in clinical settings with hemodynamic monitoring. These trials provide rigorous pharmacokinetic data, confirming VIP's very short plasma half-life (~1–2 minutes) and the need for continuous infusion or frequent dosing to maintain therapeutic levels.
Pharmacology & Receptor Studies
Basic science research has characterized VIP's binding affinity for VPAC1 and VPAC2 receptors, its cAMP-mediated signaling cascade, and its downstream effects on cytokine production, T-cell differentiation, and vascular smooth muscle relaxation. VIP's potency at physiological (nanomolar) concentrations supports the microgram dosing range used in intranasal and subcutaneous protocols. The receptor pharmacology also explains VIP's broad physiological effects across multiple organ systems.
Community Protocols & Practitioner Experience
Beyond Shoemaker's clinical work, a growing number of functional medicine practitioners prescribe intranasal VIP for CIRS and related conditions. Community experience has generally confirmed the Shoemaker dose ranges, with some practitioners adjusting frequency (2–4 times daily) based on patient response and biomarker monitoring. Subcutaneous VIP use is less common but reported in research contexts at doses of 50–100 mcg.
Standard VIP Dosage Ranges
VIP dosing varies significantly by route of administration. Intranasal is the most common community route (Shoemaker Protocol), subcutaneous is used in research contexts, and IV infusion is limited to clinical/hospital settings (Aviptadil). The route determines both the dose and the practical administration schedule.
Intranasal Dosing (Most Common — Shoemaker Protocol)
| Level | Dose per Administration | Frequency | Daily Total | Notes |
|---|---|---|---|---|
| Starting | 50 mcg per nostril (100 mcg total) | 1–2x daily | 100–200 mcg | Assess tolerance; monitor blood pressure for hypotension |
| Standard (Shoemaker) | 50 mcg per nostril (100 mcg total) | 4x daily | 400 mcg | Full Shoemaker Protocol dose; the most commonly cited CIRS regimen |
| Reduced Frequency | 50 mcg per nostril (100 mcg total) | 2–3x daily | 200–300 mcg | Some practitioners use lower frequency based on patient response |
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Subcutaneous Injection
| Level | Dose per Injection | Frequency | Daily Total | Notes |
|---|---|---|---|---|
| Starting | 25–50 mcg | 1x daily | 25–50 mcg | Low starting dose; monitor blood pressure carefully |
| Standard | 50–100 mcg | 1x daily | 50–100 mcg | Research dose range; less common than intranasal for CIRS |
IV Infusion (Clinical Setting Only)
- Aviptadil (RLF-100): 50–100 pmol/kg/min continuous IV infusion
- Setting: Hospital or clinical research setting with hemodynamic monitoring
- Use: Pulmonary arterial hypertension, ARDS, critical respiratory failure
- Note: IV VIP is NOT a community protocol — it requires clinical supervision and continuous blood pressure monitoring
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Administration Routes Compared
VIP's very short plasma half-life (~1–2 minutes) is the central pharmacokinetic challenge. Different routes address this challenge in different ways. Understanding the tradeoffs is critical for selecting the right protocol.
| Parameter | Intranasal | Subcutaneous | IV Infusion |
|---|---|---|---|
| Typical Dose | 50–100 mcg per nostril | 50–100 mcg | 50–100 pmol/kg/min |
| Bioavailability | Moderate (mucosal absorption) | Higher (direct systemic) | 100% (direct IV) |
| Best For | CIRS / mold illness (Shoemaker) | Research; systemic effects | Pulmonary hypertension; ARDS |
| Frequency | 2–4x daily | 1x daily | Continuous infusion |
| Ease of Use | Easy (nasal spray) | Moderate (injection) | Clinical setting only |
| Community Popularity | Most common | Uncommon | Clinical only |
| Key Advantage | Non-invasive; frequent dosing practical | Reliable systemic delivery | Precise dose control; highest efficacy |
| Key Limitation | Variable mucosal absorption | Short half-life limits duration | Requires clinical supervision |
Calculate Your VIP Dose
VIP for intranasal use is typically supplied as a lyophilized (freeze-dried) powder, commonly in 5 mg or 10 mg vials. It is reconstituted with bacteriostatic water or sterile saline and then transferred to a metered nasal spray bottle that delivers a known volume per spray (typically 0.1 mL per actuation). For subcutaneous injection, standard reconstitution math applies.
Worked Example (Intranasal Spray):
- Vial size: 5 mg (5,000 mcg) of VIP
- Bacteriostatic water added: 5 mL
- Concentration: 5,000 mcg ÷ 5 mL = 1,000 mcg per mL
- Nasal spray delivers: 0.1 mL per actuation
- Dose per spray: 1,000 × 0.1 = 100 mcg per spray
- For 50 mcg per nostril: use a spray bottle delivering 0.05 mL, or reconstitute with 10 mL to get 500 mcg/mL (50 mcg per 0.1 mL spray)
Quick Reference — 5 mg Vial (Subcutaneous)
| Bac Water Added | Concentration | 50 mcg Dose | 100 mcg Dose |
|---|---|---|---|
| 1 mL | 5,000 mcg/mL | 1 unit (0.01 mL) | 2 units (0.02 mL) |
| 2 mL | 2,500 mcg/mL | 2 units (0.02 mL) | 4 units (0.04 mL) |
| 2.5 mL | 2,000 mcg/mL | 2.5 units (0.025 mL) | 5 units (0.05 mL) |
| 5 mL | 1,000 mcg/mL | 5 units (0.05 mL) | 10 units (0.1 mL) |
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VIP Dosage by Goal
VIP's broad receptor distribution (VPAC1/VPAC2 across nervous, immune, pulmonary, and GI systems) means it has applications across multiple conditions. The optimal protocol varies based on the target condition and the clinical context.
CIRS / Mold Illness (Shoemaker Protocol) — Most Common Use
The primary community use case for VIP. In the Shoemaker Protocol, VIP is the final step to normalize persistent inflammatory markers after earlier interventions (cholestyramine binders, MARCoNS eradication, correction of low MSH, and optimization of other biomarkers) have reduced the inflammatory burden. VIP addresses residual TGF-β1, MMP-9, C4a, and VEGF elevation.
- Route: Intranasal spray
- Dose: 50 mcg per nostril (100 mcg total per administration)
- Frequency: 4x daily (morning, midday, afternoon, evening)
- Duration: Minimum 30 days; retest biomarkers at 30 days; continue until markers normalize (often 1–3 months)
- Prerequisite: Complete earlier Shoemaker Protocol steps first
- Stack: Often used alongside BPC-157 for gut repair and LL-37 for antimicrobial support in CIRS patients
Pulmonary Support & Respiratory Conditions
VIP is a potent bronchodilator and has demonstrated lung-protective properties. The Aviptadil (RLF-100) clinical trials target pulmonary arterial hypertension and ARDS. In community/research contexts, intranasal VIP may support respiratory function through bronchodilation and reduction of pulmonary inflammation.
- Route: Intranasal (community) or IV (clinical — Aviptadil)
- Intranasal dose: 50–100 mcg per nostril, 2–4x daily
- IV dose (clinical): 50–100 pmol/kg/min continuous infusion under medical supervision
- Duration: Varies by condition; clinical trials range from days (acute ARDS) to weeks (PAH)
Autoimmune & Immune Modulation
VIP promotes regulatory T-cell (Treg) differentiation and shifts the immune balance from pro-inflammatory Th1/Th17 responses toward anti-inflammatory Th2/Treg responses. This immunomodulatory effect has been studied in preclinical models of rheumatoid arthritis, multiple sclerosis, and other autoimmune conditions.
- Route: Intranasal or SubQ
- Intranasal dose: 50 mcg per nostril, 2–4x daily
- SubQ dose: 50–100 mcg, 1x daily
- Duration: 4–8 weeks; reassess based on symptoms and inflammatory markers
- Stack: + Thymosin Alpha-1 for comprehensive immune modulation (VIP for Treg promotion + Tα1 for adaptive immune enhancement)
Neuroprotection & Circadian Rhythm
VIP is a key neurotransmitter in the suprachiasmatic nucleus (SCN) — the brain's master circadian clock. It plays a role in synchronizing circadian rhythms and has demonstrated neuroprotective properties in preclinical models of neurodegeneration. This is a more experimental application with less established dosing.
- Route: Intranasal (for potential CNS delivery via olfactory pathway)
- Dose: 50 mcg per nostril, 1–2x daily
- Duration: Experimental; no established protocol
- Note: This is the least established application — preclinical only; consult a neurologist or functional medicine practitioner
GI Support & Gut Motility
VIP regulates gut motility, relaxes smooth muscle in the GI tract, and modulates intestinal secretion. It has been studied in the context of inflammatory bowel disease and gut dysmotility. For gut-specific applications, KPV (direct NF-κB inhibition) and BPC-157 (mucosal repair) may be more targeted choices, but VIP addresses the broader neuroimmune component of gut dysfunction.
- Route: Intranasal or SubQ
- Dose: Standard intranasal protocol (50 mcg per nostril, 2–4x daily)
- Stack: + BPC-157 250–500 mcg oral for gut mucosal repair + KPV 200–500 mcg oral for direct NF-κB inhibition in the gut
Cycling & Duration
VIP cycling is primarily guided by biomarker response rather than strict on/off schedules. Because VIP is an endogenous peptide (your body naturally produces it), it does not carry the same receptor desensitization concerns as synthetic GHRP peptides. However, structured assessment periods are critical to ensure the protocol is working and to adjust dosing as needed.
| Protocol | Duration | Assessment | Notes |
|---|---|---|---|
| Shoemaker CIRS (Initial) | 30 days | Retest TGF-β1, MMP-9, C4a, VEGF, MSH at day 30 | Standard initial assessment period; continue if markers improving |
| Shoemaker CIRS (Extended) | 1–3 months | Monthly biomarker retesting | Continue until biomarkers normalize; some patients require months |
| CIRS Maintenance | Ongoing at reduced frequency | Quarterly biomarker monitoring | Some patients maintain 1–2x daily after initial normalization |
| General Immune / Autoimmune | 4–8 weeks | Reassess symptoms at 4 weeks | Cycle off for 2–4 weeks; restart if symptoms recur |
| Pulmonary (Clinical) | Per clinical protocol | Hemodynamic monitoring | IV Aviptadil duration determined by treating physician |
When to Continue, Reduce, or Stop
- Continue at full dose if biomarkers are improving but not yet normalized after 30 days. Most CIRS patients require 1–3 months for full normalization.
- Reduce to maintenance (1–2x daily instead of 4x) once biomarkers have normalized. Some patients maintain a low-dose intranasal protocol long-term, especially if they live or work in environments with ongoing biotoxin exposure risk.
- Discontinue once biomarkers have been stable in normal range for at least 30 days. Monitor for symptom recurrence.
- Restart if markers elevate again after re-exposure to mold, water-damaged buildings, or other biotoxin sources. VIP can be cycled on and off as needed in response to environmental triggers.
- For non-CIRS use (autoimmune, general immune modulation), follow standard 4–8 week cycles with 2–4 week breaks and reassess symptoms and relevant lab markers at each cycle endpoint.
VIP Stacking Protocols
VIP stacks well with peptides that target complementary immune, repair, and antimicrobial pathways. In the CIRS/mold illness context, stacking is particularly relevant because the condition involves multi-system inflammation, immune dysregulation, gut dysfunction, and sometimes persistent microbial colonization (MARCoNS).
VIP + BPC-157 — CIRS + Gut/Tissue Repair
Combines VIP's broad anti-inflammatory and immunomodulatory effects with BPC-157's tissue repair capabilities. BPC-157 promotes gut mucosal healing, angiogenesis, and growth factor upregulation — addressing the gut damage that is common in CIRS patients. This stack targets both the systemic inflammatory component (VIP) and the local tissue repair needs (BPC-157).
| Compound | Dose | Route | Purpose |
|---|---|---|---|
| VIP | 50 mcg/nostril, 4x daily | Intranasal | VPAC1/VPAC2-mediated anti-inflammatory; CIRS biomarker normalization |
| BPC-157 | 250–500 mcg, 1–2x daily | Oral or SubQ | Gut mucosal repair; angiogenesis; growth factor upregulation |
VIP + KPV (Dual Anti-Inflammatory)
Pairs VIP's VPAC receptor-mediated anti-inflammatory cascade with KPV's direct NF-κB translocation inhibition. These peptides reduce inflammation through entirely different molecular pathways, creating a synergistic anti-inflammatory effect. Particularly relevant when gut inflammation coexists with systemic CIRS inflammation.
| Compound | Dose | Route | Purpose |
|---|---|---|---|
| VIP | 50 mcg/nostril, 2–4x daily | Intranasal | VPAC receptor activation; cAMP-mediated anti-inflammatory cascade |
| KPV | 200–500 mcg, 1–2x daily | Oral (for gut) or SubQ (systemic) | Direct NF-κB inhibition; gut-targeted inflammation reduction |
VIP + Thymosin Alpha-1 (Immune Modulation)
Combines VIP's Treg-promoting and anti-inflammatory effects with Thymosin Alpha-1's adaptive immune enhancement. VIP shifts the immune balance toward Th2/Treg (reducing excessive inflammation) while Tα1 enhances T-cell maturation, NK cell activity, and overall immune surveillance. This stack addresses both the overactive inflammatory arm and the underperforming adaptive immune arm commonly seen in CIRS and chronic immune conditions.
| Compound | Dose | Route | Purpose |
|---|---|---|---|
| VIP | 50 mcg/nostril, 2–4x daily | Intranasal | Treg promotion; Th1/Th17 suppression; anti-inflammatory |
| Thymosin Alpha-1 | 1.6 mg, 2–3x per week | SubQ | T-cell maturation; NK cell activation; adaptive immune enhancement |
VIP + LL-37 (CIRS Antimicrobial + Anti-Inflammatory)
Specifically relevant for CIRS patients with MARCoNS (Multiple Antibiotic Resistant Coagulase Negative Staphylococci) nasal colonization. LL-37 provides broad-spectrum antimicrobial activity and biofilm disruption, while VIP addresses the systemic inflammatory response. In the Shoemaker Protocol, MARCoNS eradication ideally precedes VIP use, but this stack may be used when both are needed concurrently.
| Compound | Dose | Route | Purpose |
|---|---|---|---|
| VIP | 50 mcg/nostril, 4x daily | Intranasal | Systemic anti-inflammatory; CIRS biomarker normalization |
| LL-37 | 50–100 mcg, 1x daily | SubQ | Antimicrobial defense; biofilm disruption; MARCoNS eradication support |
Explore more combinations with our Peptide Stack Builder or browse the Top 10 Peptide Stacks guide.
Safety, Side Effects & Contraindications
Reported Side Effects
Most common:
- Hypotension (low blood pressure) — the primary concern; manifests as dizziness, lightheadedness, or faintness; more likely with higher doses, IV administration, or in individuals already prone to low blood pressure
- Flushing — transient skin flushing due to vasodilation; generally mild and self-resolving within minutes
- Diarrhea or loose stools — VIP stimulates intestinal secretion and relaxes GI smooth muscle; this GI effect is dose-dependent and usually manageable at standard intranasal doses
- Transient tachycardia — mild increase in heart rate as a compensatory response to vasodilation-induced blood pressure drop; usually transient
- Nasal irritation (intranasal route) — mild burning or irritation of nasal mucosa; typically resolves with continued use
Less common / higher dose:
- Headache — likely related to vasodilation
- Abdominal cramping — related to VIP's effects on GI smooth muscle and secretion
- Nausea — more common with higher doses or in sensitive individuals
Contraindications
- Severe hypotension — VIP is a potent vasodilator. Individuals with severely low blood pressure (systolic <90 mmHg) or symptomatic orthostatic hypotension should not use VIP without close medical supervision.
- Concurrent use of potent vasodilators or antihypertensives — combining VIP with PDE5 inhibitors (sildenafil, tadalafil), nitrates, alpha-blockers, or other strong blood pressure-lowering agents increases the risk of dangerous hypotension. Consult your prescribing physician.
- Pregnancy and breastfeeding — no adequate safety data for VIP in pregnancy; VIP's vasodilatory effects could theoretically affect placental perfusion. Avoid entirely.
- Active VIPoma or VIP-secreting tumors — extremely rare, but patients with VIP-secreting tumors (VIPomas) already have pathologically elevated VIP levels. Exogenous VIP would be contraindicated.
- Known hypersensitivity — discontinue immediately if allergic reactions occur (severe rash, hives, angioedema, difficulty breathing).
When to Stop or Reduce Dose
- Symptomatic hypotension (persistent dizziness, lightheadedness, near-syncope) that does not improve with hydration and dose reduction
- Persistent diarrhea or GI distress that interferes with daily function
- Any signs of allergic reaction (rash, hives, swelling, difficulty breathing)
- CIRS biomarkers not improving after 30+ days of consistent use — reassess whether earlier protocol steps were adequately completed
- Development of significant tachycardia (sustained elevated heart rate) — consult your healthcare provider
- Any symptom that feels unusual or concerning — err on the side of caution and consult a healthcare provider
Common VIP Dosing Mistakes
Avoid these common errors to get the most out of your VIP protocol:
Frequently Asked Questions
Key Takeaways
- VIP is a 28-amino-acid endogenous neuropeptide with broad anti-inflammatory, vasodilatory, bronchodilatory, and immunomodulatory effects — it acts through VPAC1 and VPAC2 receptors to stimulate cAMP signaling
- Central role in the Shoemaker CIRS Protocol — VIP is the final step for normalizing TGF-β1, MMP-9, C4a, VEGF, and MSH in mold illness / biotoxin illness
- Standard CIRS dose: 50 mcg per nostril (100 mcg total) intranasal, 4 times daily per the Shoemaker Protocol
- Intranasal is the preferred route — non-invasive, practical for frequent dosing, and compensates for VIP's very short plasma half-life (~1–2 minutes)
- Aviptadil (RLF-100) = pharmaceutical-grade VIP — FDA Breakthrough Therapy designation for pulmonary conditions; administered IV in clinical settings
- Primary safety concern is hypotension — VIP is a potent vasodilator; monitor blood pressure, especially during the first week and in individuals with low baseline blood pressure
- Biomarker-driven cycling for CIRS: use for minimum 30 days, retest inflammatory markers, continue until normalized (typically 1–3 months)
- Key stacks: + BPC-157 (gut/tissue repair), + KPV (dual anti-inflammatory), + Thymosin Alpha-1 (immune modulation), + LL-37 (antimicrobial / MARCoNS)
- CIRS patients: complete earlier protocol steps first — VIP is the FINAL step in the Shoemaker Protocol and works best after binders, MARCoNS treatment, and other interventions
- Not FDA-approved for general use — prescribed off-label by CIRS-trained physicians for mold illness; research peptide for other applications. Consult a healthcare provider.
This article is for educational and informational purposes only. See our Disclaimer.
References
- Said SI, Mutt V. “Polypeptide with broad biological activity: isolation from small intestine.” Science. 1970;169(3951):1217-1218. PubMed
- Delgado M, et al. “Vasoactive intestinal peptide generates CD4+CD25+Foxp3+ regulatory T cells in vivo.” J Leukoc Biol. 2005;78(6):1327-1338. PubMed
- Gonzalez-Rey E, et al. “Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis.” Am J Pathol. 2006;168(4):1179-1188. PubMed
- Shoemaker RC, et al. “Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings.” Health. 2013;5(3):396-401.
- Javitt JC. “Perspective: the potential role of vasoactive intestinal peptide in treating COVID-19.” Authorea. 2020; preprint.
- Moody TW, et al. “VIP/PACAP, and their receptors and cancer.” Curr Opin Endocrinol Diabetes Obes. 2011;18(1):38-41. PubMed
- Abad C, et al. “Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease.” Gastroenterology. 2003;124(4):961-971. PubMed
- Delgado M, Ganea D. “Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions.” Amino Acids. 2013;45(1):25-39. PubMed
- Henning RJ, Sawmiller DR. “Vasoactive intestinal peptide: cardiovascular effects.” Cardiovasc Res. 2001;49(1):27-37. PubMed
- Said SI. “Vasoactive intestinal peptide: biologic role in health and disease.” Trends Endocrinol Metab. 1991;2(3):107-112. PubMed
Next Steps
Continue your research with these resources.
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