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
Intravenous infusion
Route
3 recommended
Sites
Once daily
Frequency
Preparation
VIP (Vasoactive Intestinal Peptide) vial (lyophilized powder or solution)
Bacteriostatic water or sterile sodium chloride for reconstitution
Alcohol swabs for cleaning vial tops and injection sites
Appropriately sized syringes with fine-gauge needles (27-30 gauge)
Sharps disposal container
Pro tip
Prepare all supplies on a clean surface before you begin. Having everything ready makes the process smoother and more sterile.
Mixing
Wash your hands thoroughly with soap and water. Gather all supplies on a clean, flat surface.
Remove the plastic cap from the peptide vial and wipe the rubber stopper with an alcohol swab. Let it air dry.
Draw the appropriate amount of bacteriostatic water into a sterile syringe.
Insert the needle into the vial at an angle, aiming at the inside wall of the vial. Slowly push the plunger to let the water trickle down the glass wall -- do NOT squirt directly onto the powder.
Once all water is added, gently swirl the vial in a slow circular motion. Never shake the vial, as this can damage the peptide bonds.
Continue swirling until the powder is completely dissolved and the solution is clear. If particles remain, let the vial sit for a few minutes and swirl again.
Label the vial with the date of reconstitution, the peptide name, and the concentration (e.g. 250mcg per 0.1mL).
Example calculation
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.
Dose calculation
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.
Pro tip
Always add the bacteriostatic water slowly, letting it run down the side of the vial. Never shake the vial -- swirl gently to avoid damaging the peptide.
Location
Site 01
Abdomen
Pinch the skin 2 inches from navel. Avoid the area directly around the belly button. Rotate between left and right sides.
Site 02
Outer Thigh
Middle third of the outer thigh. Keep at least 4 inches above the knee and below the hip. Alternate legs each injection.
Site 03
Upper Arm
Back or outer area of the upper arm. This site may require assistance from another person for proper technique.
Rotate between 3 sites to prevent tissue buildup and ensure consistent absorption.
Pro tip
Rotate your injection sites with each dose to prevent lipohypertrophy (buildup of fatty tissue). Keep a simple log of where you last injected.
Step by step
Wash your hands thoroughly with soap and water before handling supplies
Clean the injection site with an alcohol swab and let it air dry completely
Pinch a fold of skin at the chosen injection site
Insert the needle at a 45-90 degree angle (depending on needle length and body composition)
Inject the medication slowly and steadily over 5-10 seconds
Release the skin fold and remove the needle, applying gentle pressure with a clean swab
Rotate injection sites to prevent tissue irritation or lipodystrophy
Dispose of the needle safely in a sharps container—never recap or reuse needles
Pro tip
This peptide uses subcutaneous injection (into the fatty tissue just under the skin)—allows for consistent absorption and can be self-administered at home after proper training. Inject at a 45-90 degree angle into pinched skin. Aspirate before injecting to ensure you haven't hit a blood vessel.
Timing
Optimal timing
Best time
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.
With food?
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.
Stacking notes
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.
Sample daily schedule
As prescribed (once daily)
As prescribed by your healthcare provider injection
Site: Intravenous infusion—rotate sites if applicable
Maintain a consistent schedule for optimal results with VIP (Vasoactive Intestinal Peptide). Set reminders if needed. If you miss a dose, follow your healthcare provider's instructions—do not double up on doses to compensate.
Dosing tiers
Dose
50 mcg
Frequency
Twice daily (morning and evening)
Duration
Ongoing per protocol
Common research/community practice dose for systemic/peripheral effects (approx., not from a controlled trial).
Dose
50 mcg per inhalation (200 mcg/day); 100 mcg single acute dose
Frequency
Four inhalations daily
Duration
12 weeks (chronic study)
Inhaled aviptadil in primary pulmonary hypertension: 4 inhalations/day; single 100 mcg dose used for acute vasoreactivity testing [7].
Dose
50 → 100 → 150 pmol/kg/hr (ascending over 3 days)
Frequency
12-hour infusion daily
Duration
3 consecutive days
Aviptadil (ZYESAMI) dose-escalation regimen in critical COVID-19 respiratory failure trials [6]. Hospital/investigational only.
Preservation
Before mixing
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.
After mixing
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.
Shelf life after mixing
Use within the timeframe specified on product labeling (typically 14-28 days refrigerated)
Signs of degradation
Discard the vial immediately if you notice any of these:
Solution appears cloudy, discolored, or contains visible particles (should be clear)
Product has been exposed to temperatures outside the recommended storage range
Product has been frozen (unless specifically designed for freeze-thaw stability)
Expiration date has passed or reconstituted solution has exceeded its use-by date
Unusual odor, color change, or visible contamination
Important
When to stop
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.
Clean technique checklist
Wash hands thoroughly with soap and water before handling supplies
Swab vial tops and injection site with alcohol and let dry
Never touch the needle tip or allow it to contact non-sterile surfaces
Use a new syringe and needle for each injection
Dispose of used sharps in a proper sharps container
Store reconstituted peptides according to the storage instructions above
Published research
Youssef JG, et al. · 2022
Aviptadil (synthetic VIP) showed two-fold odds of improved survival in COVID-19 respiratory failure patients at day 60 versus placebo. Respiratory distress improved and interleukin-6 cytokine release was reduced by day 3.
Petkov V, et al. · 2003
Vasoactive intestinal peptide treatment decreased pulmonary artery pressure, increased cardiac output by 40%, and improved mixed venous oxygen saturation. VIP deficiency was documented in patient plasma and lung tissue.
Hou X, et al. · 2022
VIP stimulates glucose-dependent insulin secretion by binding VPAC2 receptors on pancreatic beta cells and promotes beta-cell proliferation. VPAC2-selective agonists show potential as novel hypoglycemic drugs.
White CM, et al. · 2010
No abstract available for comprehensive analysis.
He Y, 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.
NeuroRx Inc. / Relief Therapeutics; ClinicalTrials.gov · 2020
Petkov V, Mosgoeller W, Ziesche R, et al. · 2003
Said SI, Mutt V · 1970
Original isolation of VIP from hog small intestine. The peptide has 28 amino acid residues and is chemically distinct from the kinins, substance P, glucagon and secretin. Its actions include systemic vasodilation, hypotension, increased cardiac output, respiratory stimulation and hyperglycemia.
Harmar AJ, Fahrenkrug J, Gozes I, et al. · 2012
VIP and PACAP belong to a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, GIP and GHRH. They act through three class B GPCRs: PAC1, VPAC1 and VPAC2. PAC1 is selective for PACAP, whereas VPAC1 and VPAC2 respond to both VIP and PACAP with high affinity. The peptides have roles in the CNS and in the control of immunity, inflammation and pancreatic insulin secretion.
Domschke S, Domschke W, Bloom SR, et al. · 1978
Graded IV VIP infusions in healthy volunteers. After the infusions plasma VIP fell by first-order kinetics with an average disappearance half-time of one minute. During the highest dose the pulse rate and the amplitude of blood pressure were increased and cutaneous flushing occurred.
Unwin RJ, Reed T, Thom S, Calam J, Peart WS · 1987
Intravenous VIP (6 pmol/kg/min) in healthy male volunteers produced cutaneous flushing, increased heart rate and plasma renin activity, and decreased forearm vascular resistance. The measured cardiovascular responses to VIP infusion in man are probably direct.
Smitherman TC, Popma JJ, Said SI, Krejs GJ, Dehmer GJ · 1989
Intravenous VIP in men lowered coronary, systemic and pulmonary vascular resistances and significantly raised myocardial oxygen uptake. Intracoronary VIP reduced coronary vascular resistance by up to 46% without an increase in myocardial oxygen uptake, indicating both direct and indirect effects.
Leceta J, Gomariz RP, Martinez C, Abad C, Ganea D, Delgado M · 2000
VIP and PACAP inhibit production of TNF-alpha, IL-6, IL-12 and nitric oxide and stimulate IL-10 in macrophages. Effects on TNF-alpha, IL-10, IL-12 and NO are mostly mediated through VPAC1, with VPAC2 also participating; IL-6 inhibition runs mainly through PAC1 and PKC.
Delgado M, Munoz-Elias EJ, Gomariz RP, Ganea D · 1999
VIP/PACAP enhance IL-10 production in LPS-stimulated macrophages through VPAC1, with cAMP as the major second messenger. The neuropeptides increase nuclear CRE-binding complexes with CREB as the major active component; a protein kinase A inhibitor abolishes both IL-10 stimulation and the increase in CRE binding.
Delgado M, Ganea D · 2003
In the MPTP mouse model of Parkinson disease, VIP treatment significantly decreased dopaminergic neuronal loss in the substantia nigra pars compacta and nigrostriatal nerve-fiber loss, and prevented MPTP-induced microglial activation and expression of iNOS, IL-1beta and TNF-alpha.
Olson KE, Kosloski-Bilek LM, Anderson KM, et al. · 2015
A VPAC2-selective agonist produced the most pronounced reduction in microglial responses and increased neuronal sparing in MPTP-intoxicated mice, with reduced pro-inflammatory cytokine release (IL-17A, IL-6, IFN-gamma) and a shift from effector to regulatory T cells. VPAC2 activation attenuates microglial activation and slows degradation of neuronal cell bodies and termini.
Song M, Xiong JX, Wang YY, Tang J, Zhang B, Bai Y · 2012
VIP increased microglial phagocytosis of fibrillar Abeta42 and suppressed TNF-alpha and nitric oxide release from activated microglia. VIP overexpression in the hippocampus of APPsw/PS1 transgenic mice significantly reduced amyloid load in this Alzheimer disease model.
Prasse A, Zissel G, Lutzen N, et al. · 2010
Open phase II study of nebulized VIP for 4 weeks in 20 patients with active pulmonary sarcoidosis. VIP inhalation was safe, well tolerated, and significantly reduced TNF-alpha production by bronchoalveolar lavage cells while increasing regulatory T cells.
Leuchte HH, Baezner C, Baumgartner RA, et al. · 2008
Twenty patients with pulmonary hypertension inhaled a single 100 microgram dose of aviptadil during right-heart catheterisation. The aerosol caused selective pulmonary vasodilation with improved stroke volume and mixed venous oxygen saturation, did not cause any side-effects and did not affect systemic blood pressure.
Iwasaki M, Akiba Y, Kaunitz JD · 2019
Review of VIP as a gut peptide originally reported as a vasodilator in 1970, with effects on neuronal, epithelial and endocrine cell function that regulate ion secretion, nutrient absorption, gut motility, glycemic control, immune responses and circadian rhythms. Genetic ablation of the peptide and its receptors in mice informs the pathogenesis of related diseases, including colitis.
Karele EN · 2023
VIP-secreting tumours are characterised by watery diarrhea, hypokalemia and achlorhydria caused by the non-regulated increased secretion of VIP.
Duan JX, Guan XX, Yang HH, et al. · 2021
VIP overexpression attenuated bleomycin-induced lung tissue destruction, reduced extracellular matrix deposition and suppressed TGF-beta1-induced epithelial-mesenchymal transition in alveolar epithelial cells, supporting inhaled long-acting VIP as a candidate anti-fibrotic drug for pulmonary fibrosis.
Fraccaroli L, Grasso E, Hauk V, et al. · 2015
VIP increased the frequency of CD4+CD25+FoxP3+ regulatory T cells and of CD4+IL10+ and CD4+TGF-beta+ cells; the increase in regulatory T cells was prevented by an anti-TGF-beta antibody, indicating a mechanism involving TGF-beta1.
NeuroRx, Inc. / RELIEF THERAPEUTICS Holding AG · 2020
Announced 24 June 2020: the FDA awarded Fast Track Designation to NeuroRx for the investigation of RLF-100 (Aviptadil) for the treatment of acute lung injury / acute respiratory distress syndrome associated with COVID-19. RLF-100 (Aviptadil) is described as a synthetic form of human Vasoactive Intestinal Peptide.
NRx Pharmaceuticals / Relief Therapeutics; ClinicalTrials.gov · 2020
Phase 2/3 study of inhaled aviptadil dosed at 100 micrograms three times daily by mesh nebulizer (300 micrograms per day).
Relief Therapeutics / NeuroRx; ClinicalTrials.gov · 2020
Phase 2 study of nebulized aviptadil dosed at 67 micrograms three times a day for ten days.
Korkmaz OT, Ay H, Ulupinar E, Tuncel N · 2012
In 6-OHDA-lesioned rats, systemically administered VIP significantly increased the number of tyrosine-hydroxylase-immunostained neurons in the substantia nigra pars compacta and the spine density of striatal medium spiny neurons; earlier work from the group showed VIP reversing motor deficits and decreasing neuronal cell death in the same model.
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