Healing & recovery
A natural peptide messenger that relaxes airways and blood vessels and calms inflammation — studied for lung and immune conditions.
Start here
VIP (vasoactive intestinal peptide) is a natural messenger molecule your body already makes, with wide-ranging jobs: relaxing blood vessels, calming inflammation, and regulating the gut and lungs. As an experimental therapy it is studied in serious lung conditions; a Phase 2b/3 trial reported a 2-fold survival improvement in COVID-19 ARDS (severe lung failure), and it has shown circulation improvements in pulmonary hypertension (high blood pressure in the lungs). It is a research compound, not FDA approved, given by IV infusion, inhalation, or injection.
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.
Vasoactive intestinal peptide (VIP) is a neuropeptide (a signaling protein made by nerve cells) of 28 amino acids (protein building blocks). It belongs to the secretin/glucagon superfamily (a related group of hormones) 9. It binds VIP receptors (VPAC1 and VPAC2, docking points on cells that work through G proteins, which relay signals inside the cell) and switches on adenylyl cyclase (an enzyme) through Gs proteins. When VIP activates VPAC receptors, it raises cAMP (a messenger molecule) inside cells. That switches on protein kinase A (PKA, an enzyme) and adds phosphate tags to CREB (a protein that turns genes on). 14 This chain of events relaxes the smooth muscle in blood vessel walls, which widens the vessels. 8 It also adjusts immune cell activity by raising anti-inflammatory signals (IL-10, TGF-beta), 1323 and it regulates stomach and pancreas secretions. 20 VIP is found in nerve cells of the gut's nervous system, in sympathetic ganglia (clusters of nerve cells outside the spinal cord), and throughout the brain and spinal cord, especially the hypothalamus (the brain region that runs your hormone system) and hippocampus. This makes it important for coordinating the nervous and immune systems and for thinking and memory 9.
Evidence check
Some human studies
It has been tested in people, but only in small or early-stage studies. Promising, but not yet proven the way an approved medicine is.
Every numbered marker on this page links to one of the 27 sources at the bottom.
Heart and Blood Vessels
Strongly widens the blood vessels of the lungs by activating VPAC1 and VPAC2 receptors (docking points on cells), with Phase 2 evidence of better blood flow and pressure in pulmonary hypertension (high blood pressure in the lungs)
Anti-Inflammatory
Lowers TNF-α and IL-6 (inflammatory immune signals) through VPAC receptors (docking points on cells), with Phase 2b/3 evidence of lower IL-6 in COVID-19 ARDS (severe lung failure)
Brain protection
VPAC2-dependent neuroprotective effects documented in Parkinson and Alzheimer disease models with microglial modulation
The most-asked question
The research-reported range is 50 mcg, once daily. Studies used different doses for different situations — find yours:
General research use, Self-administered protocols
50 mcg
Common research/community practice dose for systemic (affecting the whole body)/peripheral effects (approx., not from a controlled trial).
Pulmonary hypertension research, Local pulmonary delivery
50 mcg per inhalation (200 mcg/day); 100 mcg as a single short-term dose
Inhaled aviptadil in primary pulmonary hypertension: 4 inhalations/day; single 100 mcg dose used for acute vasoreactivity testing 7.
Critical respiratory failure research, Inpatient/ICU setting
50 → 100 → 150 pmol/kg/hr (raised step by step over 3 days)
Aviptadil (ZYESAMI) dose-escalation regimen in critical COVID-19 respiratory failure trials 6. Hospital/investigational only.
The ceiling: 300 mcg/day 25 (as determined by your healthcare provider based on individual response and tolerance)
Reconstitution, in plain words
Peptides usually arrive as a freeze-dried powder in a small vial. “Reconstitution” just means adding sterile water back in so you can measure a dose. Here's how it works for VIP (Vasoactive Intestinal Peptide):
Add the recommended volume of bacteriostatic water to the VIP (Vasoactive Intestinal Peptide) vial. Gently swirl (do not shake) until the powder is fully dissolved. The resulting solution should be clear. Calculate your individual dose based on the concentration and your prescribed amount.
Your dose of VIP (Vasoactive Intestinal Peptide) is determined by your healthcare provider. Using an insulin syringe marked in units, draw up the exact amount prescribed. For example, if the reconstituted concentration is 1mg/mL and your dose is 0.5mg, draw up 0.5mL (50 units on an insulin syringe). Always double-check calculations before injection.
Three quick questions — your vial, your water, your dose — and it tells you the exact syringe mark. “Find dose amount” is preloaded with VIP (Vasoactive Intestinal Peptide)'s recorded schedule.
Injection sites & technique
Injection into the fatty layer just under the skin—it is absorbed steadily, and you can give it yourself at home after proper training
Timing
VIP (Vasoactive Intestinal Peptide) is administered intravenously in a clinical setting. 1 Timing is determined by your healthcare provider based on the treatment protocol and your medical needs.
IV administration of VIP (Vasoactive Intestinal Peptide) is not dependent on meal timing. Your healthcare team will provide specific instructions regarding food and fluid intake around treatment sessions.
VIP (Vasoactive Intestinal Peptide) should be used as directed by your healthcare provider. If combining with other medications or supplements, discuss potential interactions with your provider. Avoid combining with compounds that have overlapping mechanisms unless specifically guided by a medical professional.
The honest list
These show up most often. They usually fade as your body adjusts.
Common widening of the skin's blood vessels, causing temporary redness of the face and upper body during body-wide (systemic (affecting the whole body)) administration 61011.
What to do Transient and self-resolving; no treatment typically required
Gastrointestinal smooth muscle effects and secretory stimulation may cause watery diarrhea, especially with systemic (affecting the whole body) administration 62021
What to do Usually transient; anti-diarrheal agents if needed; dose adjustment may help
Gastrointestinal effects including nausea and occasional vomiting during or shortly after systemic (affecting the whole body) administration
What to do Antiemetic medications as needed; typically improves with continued therapy
Worth knowing about, but most people never see these.
Transient decrease in blood pressure due to potent vasodilatory (widening blood vessels) properties, particularly with intravenous administration 68
What to do Monitor blood pressure and blood flow during the IV infusion; slow the infusion rate; give fluids if needed.
The heart beats faster to make up for the drop in blood pressure that comes from widened blood vessels 61011.
What to do Usually self-limiting compensatory response; monitor during infusion; resolves after treatment completion
Positive inotropic and chronotropic effects on the heart 81012 with potential ECG changes during IV administration
What to do Cardiac monitoring during IV infusion; use inhaled route for patients with cardiac concerns
Rare, but if any of these happen, stop and contact a medical professional.
A VIP infusion through the bloodstream can cause large drops in blood pressure because blood vessels relax and widen 68. In susceptible people this can lead to fainting or circulatory collapse (the heart and blood vessels failing to keep blood flowing).
What to do Monitor blood pressure continuously during administration; use cautiously in people with low blood pressure; keep vasopressors (drugs that raise blood pressure) on hand; slow the infusion if blood pressure drops significantly.
Can cause dramatic facial flushing and temporary redness of the skin (erythema (skin redness)) because VIP strongly widens the blood vessels in the skin 61011.
What to do Inform patient about expected flushing; reduce infusion rate; monitor skin temperature; ensure adequate hydration.
Week by week
Is it right for you?
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.
Their blood-pressure-lowering effects add together and may cause dangerous drops in blood pressure, so blood flow and pressure need close monitoring
Both widen blood vessels in different ways, which together may cause severe low blood pressure (hypotension)
These drugs work against VIP's vessel-widening effect, which may make both less effective
Both widen blood vessels in different ways, which may improve blood flow and pressure in the lungs in pulmonary hypertension (high blood pressure in the lung arteries)
Combining with other anti-inflammatory agents like KPV may lower inflammation signals (cytokines (immune signaling molecules)) more than either alone
VIP protects nerve cells by switching on VPAC receptors (docking points on cells), which complements other nerve-protecting approaches in research on diseases where nerve cells slowly die
Generally safe to take alongside VIP (Vasoactive Intestinal Peptide). Space doses apart if taking oral formulations to ensure optimal absorption.
Helpful if experiencing any GI side effects that could lead to dehydration. Safe to combine.
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on pulmonary arterial hypertension research. 219 Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
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.
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on anti-inflammatory therapy development. 1318 Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
VIP (Vasoactive Intestinal Peptide) is particularly well-suited for individuals focused on neuroprotection (protecting brain cells) studies. 1516 Research and clinical experience suggest meaningful benefits in this area when used as part of a comprehensive treatment approach.
VIP (Vasoactive Intestinal Peptide) is a 28-amino acid endogenous (made naturally by your body) 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 (widening blood vessels) that causes dose-dependent hypotension and compensatory tachycardia (a racing heart rate) 61011—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 (affecting the whole body) accumulation. 10 Inhaled VIP shows excellent local tolerability for pulmonary applications with minimal systemic absorption 1819.
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 (made naturally by your body) 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.
Keeping it good
Store VIP (Vasoactive Intestinal Peptide) in the refrigerator at 36-46°F (2-8°C) in its original packaging. Protect from light and moisture. Do not freeze. Check the expiration date before use. Some formulations may be stored at room temperature for limited periods—check your specific product labeling.
Once reconstituted, VIP (Vasoactive Intestinal Peptide) should be kept refrigerated at 36-46°F (2-8°C) and used within the timeframe specified on your product labeling (typically 14-28 days). Label the vial with the reconstitution date. Do not use if the solution appears cloudy, discolored, or contains particles.
Not our opinion — the published record
2022
Aviptadil (man-made VIP) showed two-fold odds of improved survival at day 60 compared with placebo in patients with respiratory failure from COVID-19. Respiratory distress improved and release of interleukin-6 (an inflammation signal) was reduced by day 3.
Youssef JG, et al.
2003
Treatment with vasoactive intestinal peptide lowered pulmonary artery pressure (blood pressure in the lung arteries), raised cardiac output (the amount of blood the heart pumps) by 40%, and improved mixed venous oxygen saturation (the oxygen level in blood returning to the heart). VIP deficiency was documented in patients' blood plasma and lung tissue.
Petkov V, et al.
2022
VIP triggers insulin release only when blood sugar is high, by binding VPAC2 receptors (docking points) on pancreatic beta cells (the cells that make insulin), and it promotes beta-cell growth. VPAC2-selective agonists (drugs that switch on only that receptor) show potential as new blood-sugar-lowering drugs.
Hou X, et al.
2010
No abstract available for comprehensive analysis.
White CM, et al.
2022
VIP demonstrates potent antiviral and anti-inflammatory properties against SARS-CoV-2, HIV, RSV, and other viruses. Its peptide-based nature offers high efficacy with low toxic side effects.
He Y, et al.
2020
NeuroRx Inc. / Relief Therapeutics; ClinicalTrials.gov
2003
Petkov V, Mosgoeller W, Ziesche R, et al.
1970
Original isolation of VIP from hog small intestine. The peptide has 28 amino acids (protein building blocks) and is chemically different from kinins, substance P, glucagon and secretin (other signaling molecules). Its actions include widening of blood vessels throughout the body, low blood pressure, increased cardiac output (more blood pumped by the heart), stimulated breathing and hyperglycemia (high blood sugar).
Said SI, Mutt V
2012
VIP and PACAP belong to a superfamily (a related group) of peptide hormones that also includes glucagon, glucagon-like peptides, secretin, GIP and GHRH. They act through three class B GPCRs (a family of docking points on cell surfaces): PAC1, VPAC1 and VPAC2. PAC1 responds mainly to PACAP, whereas VPAC1 and VPAC2 respond strongly to both VIP and PACAP. The peptides play roles in the brain and spinal cord and in controlling immunity, inflammation and insulin release from the pancreas.
Harmar AJ, Fahrenkrug J, Gozes I, et al.
If this isn't the right fit
Your questions
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 (made naturally by your body) VIP but is produced synthetically for clinical administration. Aviptadil received FDA fast-track designation in 2020 for COVID-19-associated ARDS 24.
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.
No. VIP and PACAP are related but different peptides from the same family. VIP is 28 amino acids long, while PACAP-38 is 38. They share VPAC1 and VPAC2 receptors (docking points on cells), but PACAP also strongly activates PAC1 receptors. VIP has stronger blood-vessel-widening and gut effects, while PACAP focuses more on protecting nerves 9.
Inhaled VIP delivers the peptide directly to pulmonary vasculature and airway smooth muscle, maximizing local therapeutic effects while minimizing systemic (affecting the whole body) side effects like hypotension. 19 Studies have shown that inhaled VIP at 67-300 mcg/day is well-tolerated 2526 with minimal systemic absorption, making it an ideal route for pulmonary hypertension and sarcoidosis 218.
VIP protects nerves mainly through the VPAC2 receptor (a docking point on cells). It calms microglia (the brain's immune cells), shifts immune signals from inflammatory to anti-inflammatory, and prevents nerve cell bodies from breaking down 16. It has shown protective effects in animal models of Parkinson disease (MPTP/6-OHDA models) and Alzheimer disease, though use in people is still at an early stage 151727.
Beyond ARDS (severe lung failure) and pulmonary hypertension (high blood pressure in the lungs), VIP is being studied for inflammatory bowel disease 20, type 2 diabetes (through VPAC2-driven insulin release) 3, sarcoidosis (inflamed clumps of immune cells, often in the lungs) 18, pulmonary fibrosis (lung scarring) 22, and emerging antiviral uses 5. Drugs that selectively switch on VPAC2 are also being developed to lower blood sugar in diabetes 3.
27 sources
Every numbered marker on this page points to one of these. Same sources, same numbering as the VIP (Vasoactive Intestinal Peptide) research profile on Peptide Initiative.
Want the deep science?
Every claim on this page traces back to the research database behind Peptide Initiative — studies, citations, clinical trial data, and the technical detail we deliberately left out here.
Open the research profileThis guide is education, not medical advice. VIP (Vasoactive Intestinal Peptide) is a research compound that is not FDA-approved for human use. Talk to a clinician before taking anything.
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