VIP (Vasoactive Intestinal Peptide)
Endogenous neuropeptide with vasodilatory, anti-inflammatory, and immunomodulatory properties
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Suggested dose
50 mcg
Compound profile
VIP (Vasoactive Intestinal Peptide) scientific & efficacy data
Healing & Recovery
Peptide profile
Moderate human trials
VIP (Vasoactive Intestinal Peptide)
50 mcg · Once daily
Molecular formula
C147H237N43O43S
- Mol. weight
- 3325.83 Da
- CAS number
- 37221-79-7
- PubChem
- 53314964
- Developed · 1970
- Sami Said and Viktor Mutt
Uppsala University, Sweden
Amino acid sequence
HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2 (28 amino acids)Cardiovascular
Potent pulmonary vasodilator via VPAC1/VPAC2 receptor activation [9] with Phase 2 evidence of hemodynamic improvement in pulmonary hypertension [2][19]
Dosing
How much VIP (Vasoactive Intestinal Peptide) do I take?
50 mcg · twice daily (morning and evening) · subcutaneous injection
50 mcg
Twice daily (morning and evening)
| Phase | Dose | Frequency | Route |
|---|---|---|---|
| Ongoing per protocol | 50 mcg | Twice daily (morning and evening) | Subcutaneous injection |
| 12 weeks (chronic study) | 50 mcg per inhalation (200 mcg/day); 100 mcg single acute dose | Four inhalations daily | Inhaled |
| 3 consecutive days | 50 → 100 → 150 pmol/kg/hr (ascending over 3 days) | 12-hour infusion daily | Intravenous infusion |
Covers all 3 documented dose levels · 3 administration routes · timing · dose-adjustment guidance.
Suitability
Is VIP (Vasoactive Intestinal Peptide) right for me?
Best for pulmonary arterial hypertension research & ards and respiratory failure investigation
Best for
Pulmonary arterial hypertension research
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on pulmonary arterial hypertension research. [2][19] Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
ARDS and respiratory failure investigation
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on ards and respiratory failure investigation. [1] Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Anti-inflammatory therapy development
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on anti-inflammatory therapy development. [13][18] Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
Consider alternatives if
Do not use if
Use with caution if
Not sure?
Compare VIP (Vasoactive Intestinal Peptide) with similar peptides to find the best fit for your goals.
Administration
How do I use VIP (Vasoactive Intestinal Peptide)?
Intravenous infusion · Inhaled
Route
Subcutaneous injection (into the fatty tissue just under the skin)—allows for consistent absorption and can be self-administered at home after proper training
Best sites
Covers reconstitution · step-by-step technique · storage · a sample daily schedule.
Safety
Is VIP (Vasoactive Intestinal Peptide) safe?
3 common side effects · 2 serious
VIP (Vasoactive Intestinal Peptide) is a 28-amino acid endogenous neuropeptide [8] with moderate evidence from Phase 1-2 human clinical trials.
The synthetic pharmaceutical form (aviptadil/RLF-100) received FDA fast-track designation for COVID-19-associated ARDS, [24] indicating recognition of its therapeutic potential.
Critical safety considerations: VIP is a potent vasodilator that causes dose-dependent hypotension and compensatory tachycardia [6][10][11]—hemodynamic monitoring is essential during IV administration. Common side effects include facial flushing and diarrhea from its GI effects.
[6] Phase 2b/3 COVID-19 ARDS trials (196 patients) reported NO serious drug-related adverse events, [1] a favorable safety signal. However, individual responses to vasodilation vary significantly based on baseline cardiovascular status, medications, and underlying conditions.
The peptide's short plasma half-life (1-2 minutes) limits systemic accumulation. [10] Inhaled VIP shows excellent local tolerability for pulmonary applications with minimal systemic absorption [18][19].
VIP's therapeutic evidence comes from Phase 1-2 human clinical trials in pulmonary conditions and a Phase 2b/3 COVID-19 ARDS trial (NCT04703816) that showed improved 60-day survival rates.
[1] As an endogenous 28-amino-acid neuropeptide, [8] its pharmacology is well-characterized from decades of basic science research. [9] Clinical applications require IV infusion with continuous hemodynamic monitoring.
Common side effects · experienced by some users
Facial Flushing
Common cutaneous vasodilation causing temporary redness of face and trunk during systemic administration [6][10][11]
Management: Transient and self-resolving; no treatment typically required
Diarrhea
Gastrointestinal smooth muscle effects and secretory stimulation may cause watery diarrhea, especially with systemic administration [6][20][21]
Management: Usually transient; anti-diarrheal agents if needed; dose adjustment may help
Nausea
Gastrointestinal effects including nausea and occasional vomiting during or shortly after systemic administration
Management: Antiemetic medications as needed; typically improves with continued therapy
Less common
These typically resolve with continued use or dose adjustment.
Stop and seek help if
- Severe or worsening side effects that don't improve with dose adjustment or supportive care
- Signs of an allergic reaction—rash, hives, swelling, or difficulty breathing
- Your healthcare provider recommends discontinuation based on your clinical response
- Development of any new medical condition that may be contraindicated with VIP (Vasoactive Intestinal Peptide)
- Pregnancy or planning to become pregnant (unless specifically approved for use during pregnancy)
- Abnormal lab results or clinical markers that suggest adverse effects
VIP (Vasoactive Intestinal Peptide) should only be started, adjusted, or discontinued under medical supervision. This information is for educational purposes only and does not replace professional medical advice. Never stop a prescribed treatment without consulting your healthcare provider first, as abrupt discontinuation may have consequences.
With other peptides
- Safe:Prostacyclin Analogs — Complementary vasodilatory pathways may enhance pulmonary hemodynamic improvement in pulmonary hypertension
- Safe:Anti-inflammatory Peptides — Combining with other anti-inflammatory agents like KPV may provide synergistic cytokine suppression
- Safe:Neuroprotective Compounds — VPAC receptor-mediated neuroprotection complements other neuroprotective strategies in neurodegeneration research
With medications
- Caution:Antihypertensive Medications — Additive hypotensive effects may cause dangerous blood pressure drops requiring careful hemodynamic monitoring
- Caution:PDE5 Inhibitors — Combined vasodilation through different mechanisms may cause severe hypotension
- Caution:Vasoconstrictors — Pharmacological antagonism with VIP vasodilatory effects may reduce therapeutic efficacy of both agents
With supplements
- Safe:Multivitamins — Generally safe to take alongside VIP (Vasoactive Intestinal Peptide). Space doses apart if taking oral formulations to ensure optimal absorption.
- Safe:Electrolyte supplements — Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
Effectiveness
How do I know VIP (Vasoactive Intestinal Peptide) is working?
Moderate human trials · first signs acute hemodynamic response (minutes to hours)
Evidence level
Moderate human trials
(Phase 1-2)
Regulatory status
Research compound
Onset of effects
Moderate
(1-2 weeks)
How it works
VIP is a natural messaging molecule in your body made of 28 amino acids [8] that works like a chemical messenger throughout your nervous system and digestive tract.
It tells your blood vessels to relax and widen, increases blood flow, and helps regulate your stomach and intestines. [20] When VIP levels drop, it can cause problems with digestion, gut function, and blood pressure control [2].
The deeper mechanism
Vasoactive intestinal peptide (VIP) is a 28-amino acid neuropeptide that belongs to the secretin/glucagon superfamily [9] and acts as a ligand for VIP receptors (VPAC1 and VPAC2), which are G-protein coupled receptors that activate adenylyl cyclase through Gs proteins.
VIP-mediated activation of VPAC receptors increases intracellular cAMP, leading to activation of protein kinase A (PKA) and phosphorylation of CREB transcription factors.
[14] This signaling cascade produces vasodilation through relaxation of vascular smooth muscle, [8] modulation of immune cell function through upregulation of anti-inflammatory cytokines (IL-10, TGF-beta), [13][23] and regulation of gastric and pancreatic secretions.
[20] VIP is expressed in neurons of the enteric nervous system, sympathetic ganglia, and throughout the CNS, particularly in the hypothalamus and hippocampus, making it important for neuroimmune regulation and cognitive function [9].
What to expect
Acute Hemodynamic Response (Minutes to Hours)
What you might notice
- Rapid onset vasodilation, blood pressure reduction, and smooth muscle relaxation;
- immediate hemodynamic effects with IV administration
What's normal
- Initial response to VIP (Vasoactive Intestinal Peptide) is beginning at the cellular level
- Different individuals experience VIP (Vasoactive Intestinal Peptide)'s onset at different rates
- Transient systemic effects from initial VIP (Vasoactive Intestinal Peptide) exposure are common
What's next
- Maintain consistent VIP (Vasoactive Intestinal Peptide) administration as prescribed
- Document subjective effects and physical markers daily
- Schedule a check-in with your provider about initial observations
Anti-Inflammatory Phase (Days to 1 Week)
What you might notice
- Significant reduction in inflammatory cytokines (IL-6 reduction by Day 3 in clinical trials);
- improved oxygenation in respiratory conditions
What's normal
- VIP (Vasoactive Intestinal Peptide) is achieving sufficient receptor engagement
- Initial mechanism of VIP (Vasoactive Intestinal Peptide) is taking effect
- Early transient effects from VIP (Vasoactive Intestinal Peptide) administration are resolving
What's next
- Maintain consistent VIP (Vasoactive Intestinal Peptide) administration as prescribed
- Document subjective effects and physical markers daily
- Schedule a check-in with your provider about initial observations
Clinical Benefit (1-8 Weeks)
What you might notice
- Sustained immunomodulatory effects;
- improved survival outcomes in ARDS at 60-day follow-up;
- maintained hemodynamic improvement in pulmonary hypertension
What's normal
- Full therapeutic effects of VIP (Vasoactive Intestinal Peptide) are well-characterized at this point
- Maintenance of VIP (Vasoactive Intestinal Peptide)'s therapeutic effects is typical
- Tolerance patterns with VIP (Vasoactive Intestinal Peptide) are generally stable over months
What's next
- Comprehensive assessment of VIP (Vasoactive Intestinal Peptide) efficacy should be conducted
- Discuss long-term continuation, cycling, or protocol modifications
- Continue regular monitoring of relevant biomarkers or symptoms
Signs it's working
Treatment Response
- Improvement in the primary symptoms or condition being treated
- Positive changes in relevant lab values or clinical markers
- Consistent, stable response to VIP (Vasoactive Intestinal Peptide) over time
- Reduction in symptom frequency or severity
General Well-being
- Improved energy levels and daily functioning
- Better quality of life related to the treated condition
- Manageable or absent side effects indicating good tolerance
- Positive feedback from healthcare provider during check-ups
Not seeing results? Common reasons
- Not at therapeutic dose yet—initial doses are for building tolerance, not maximum effect
- Insufficient time at target dose—most compounds need several weeks to show full benefits
- Inconsistent dosing schedule—regular, consistent use is crucial for optimal results
- Individual variation in response—genetics, metabolism, and other factors affect outcomes
- Underlying conditions or medications interfering with absorption or effectiveness
- Improper storage leading to degraded product—always verify proper storage conditions
Key research
Questions
Frequently asked about VIP (Vasoactive Intestinal Peptide)
What is the difference between VIP and aviptadil?
Aviptadil (RLF-100) is the synthetic pharmaceutical formulation of naturally occurring Vasoactive Intestinal Peptide developed by NeuroRx Inc. It has the identical amino acid sequence as endogenous VIP but is produced synthetically for clinical administration. Aviptadil received FDA fast-track designation in 2020 for COVID-19-associated ARDS [24].
How did VIP perform in COVID-19 ARDS trials?
In a Phase 2b/3 multicenter randomized controlled trial (196 patients across 10 US hospitals), IV aviptadil showed a 2-fold improvement in 60-day survival (OR 2.0, p=0.035) and a 10-fold survival improvement in mechanically ventilated patients (p=0.031). While the primary endpoint was not significant, survival signals were robust with significant IL-6 reduction by Day 3 and no serious drug-related adverse events [1].
Is VIP the same as PACAP?
No, VIP and PACAP are related but distinct peptides in the same superfamily. VIP is 28 amino acids while PACAP-38 is 38 amino acids. They share VPAC1 and VPAC2 receptors but PACAP additionally activates PAC1 receptors with high selectivity. VIP has more prominent vasodilatory and GI effects, while PACAP is more focused on neuroprotection [9].
Why is VIP given by inhaler for lung conditions?
Inhaled VIP delivers the peptide directly to pulmonary vasculature and airway smooth muscle, maximizing local therapeutic effects while minimizing systemic side effects like hypotension. [19] Studies have shown that inhaled VIP at 67-300 mcg/day is well-tolerated [25][26] with minimal systemic absorption, making it an ideal route for pulmonary hypertension and sarcoidosis [2][18].
What are VIP's neuroprotective properties?
VIP provides neuroprotection primarily through VPAC2 receptor-mediated pathways including attenuation of microglial activation, shifting cytokine profiles from pro-inflammatory to anti-inflammatory, and preventing neuronal cell body degradation. [16] It has shown protective effects in animal models of Parkinson disease (MPTP/6-OHDA) and Alzheimer disease, though clinical translation is still in early stages [15][17][27].
Is VIP being developed for any other conditions?
Beyond ARDS and pulmonary hypertension, VIP is being investigated for inflammatory bowel disease, [20] type 2 diabetes (via VPAC2-mediated insulin secretion), [3] sarcoidosis, [18] pulmonary fibrosis, [22] and emerging antiviral applications. [5] VPAC2-selective agonists are also being developed as novel hypoglycemic agents for diabetes treatment [3].
Further reading
VIP (Vasoactive Intestinal Peptide) history & related research
History · since 1970
A 28-piece messenger that tells blood vessels and lungs to relax and heal
VIP is a 28-amino-acid peptide discovered in 1970 by Iraqi-American scientist Dr. Sami Said and Swedish researcher Viktor Mutt.
Read the full history of VIP (Vasoactive Intestinal Peptide)Ready for the protocol?
Every dosing tier, administration route, timing note, and dose-adjustment rule for VIP (Vasoactive Intestinal Peptide), on one page.