The Peptide Guide
Immune / Gut

VIP: research protocol, dosing & reconstitution

Also known as: Vasoactive intestinal peptide, Aviptadil

Quick answer

What is VIP?

VIP (vasoactive intestinal peptide) is a 28-amino-acid signalling peptide the body makes in the gut, lungs, brain and immune system. It relaxes smooth muscle and blood vessels and dials down inflammatory signalling — but it survives about a minute in blood, so research uses inhaled or intranasal routes. A pharmaceutical version, aviptadil, has been trialled in lung disease.

What VIP is

VIP was isolated from pig small intestine in 1970 by Said and Mutt, who named it for its effect on blood vessels [1]. It belongs to the same family as secretin and glucagon and acts through two receptorsReceptorA protein on or inside a cell that binds specific signaling molecules and triggers a response. Most peptides work by binding particular receptors.See glossary →, VPAC1 and VPAC2, found on smooth muscle, epithelium and immune cells.

The body uses it everywhere: to relax airway and gut muscle, to drive water and electrolyte secretion in the intestine, as a neurotransmitter, and — the reason it appears in immunology reviews — as a brake on inflammatory signalling [3]. Research-grade VIP is the same 28-residue sequence, sold as a Research Use OnlyRUO (Research Use Only)A regulatory classification meaning a product is sold strictly for laboratory research and is not approved, labeled, or intended for human or veterinary use.See glossary → compound.

Mechanism of action

VPAC receptors are G-protein-coupled and raise cyclic AMP, which relaxes smooth muscle (vasodilation, bronchodilation) and drives secretion. Human pharmacokinetics were measured in 1978: after an infusion stops, plasma VIP falls with a half-time of about one minute, and the metabolic clearance rate is roughly 9 mL/kg/min [2] — which is why any systemic protocol is, in practice, an infusion or a repeated local dose.

On the immune side, VIP suppresses pro-inflammatory cytokine output from macrophages (TNF-α, IL-6, IL-12), shifts the T-helper balance, and induces regulatory T cells [3]; that regulatory T-cell induction has been proposed as its core therapeutic mechanism in inflammatory and autoimmune models [4].

Clinically, a single 100 mcgMicrogram (mcg / µg)One millionth of a gram, or one thousandth of a milligram. Most peptide research doses are measured in micrograms.See glossary → inhaled dose of aviptadil in 20 pulmonary-hypertension patients produced a small, short-lived but significant selective pulmonary vasodilation with no side effects [5]. In a 196-patient trial of three days of IV aviptadil for critical COVID-19 respiratory failure, the primary endpoint (alive and free of respiratory failure at day 60) did not reach significance, although the authors reported a two-fold odds of survival at 60 days as a secondary finding [6].

What researchers study VIP for

  • Smooth-muscle relaxation — pulmonary and gut vasculature
  • Immune regulation: macrophage cytokines and regulatory T-cell induction
  • Gut secretion and motility (the ‘intestinal’ in its name)
  • Airway and pulmonary-vascular disease models (aviptadil)

What dose of VIP do researchers use?

Research literature commonly references doses of 50 mcg per intranasal spray, up to 4× daily (community reference); a single 100 mcg inhaled dose in clinical study. This is not a recommendation — the table below summarizes protocols as they appear in published literature and trial designs.

ContextDoseFrequencyDuration
Inhaled, acute haemodynamic study [5]100 mcg aerosolSingle doseDuring right-heart catheterisation
IV trial, critical COVID-19 [6]Weight-based infusionDaily3 consecutive days
Intranasal community reference50 mcg per sprayUp to 4× dailyCourse-based; no controlled trials

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Half-life and dosing timing

Half-life: Very short — about one minute in plasma. Route referenced in research: Intranasal, inhaled or subcutaneous (research). With a plasma half-lifeHalf-lifeHow long it takes for half of a compound to be eliminated from the body. Half-life determines how often researchers dose a compound in protocols.See glossary → near one minute [2], VIP is gone almost as soon as it arrives. Research designs work around this with local delivery — inhaled to the lung, intranasal to the airway — or continuous infusion. A subcutaneousSubcutaneous (SubQ)An injection into the fatty tissue just below the skin. The most commonly referenced administration route in peptide research literature.See glossary → bolus is the least rational route on paper, which is worth knowing before copying a protocol.

Titration: start low, go slow

The clinical trials used fixed regimens. Community intranasal protocols start at one spray daily and add sprays over a week or two because flushing and light-headedness are dose-dependent. No standard exists.

Skip the VIP math

Enter vial size, water volume, and target dose — the free calculator returns concentration, injection volume, and exact U-100 syringe units.

How is VIP reconstituted?

Vial sizeBAC waterConcentrationWorked example
5 mg2 mL2,500 mcg/mL100 mcg = 0.04 mL = 4 units — too small to measure accurately
5 mg5 mL1,000 mcg/mL100 mcg = 0.1 mL = 10 units on a U-100 syringe

Add 5 mL of bacteriostatic waterBAC water (bacteriostatic water)Sterile water containing 0.9% benzyl alcohol, which suppresses bacterial growth. It is the standard diluent used to reconstitute lyophilized peptides for multi-dose research vials.See glossary → to a 5 mg vialVialThe small sealed glass container peptides are supplied in, topped with a rubber septum that a syringe needle can pass through.See glossary →: 5 mg ÷ 5 mL = 1 mg/mL, or 1,000 mcg/mL. A 100 mcg dose is 100 ÷ 1,000 = 0.1 mL — 10 units on a U-100 syringeU-100 syringeAn insulin syringe calibrated so that 100 units equal 1 mL. The standard syringe referenced in peptide research; each unit equals 0.01 mL.See glossary →. With only 2 mL of water the same dose would be 4 units, below the accuracy of an insulin syringe; intranasal protocols dilute further still, into a metered spray bottle.

New to the process? Read the full step-by-step reconstitution guide.

How long does reconstituted VIP last?

LyophilizedLyophilizedFreeze-dried. Peptides are shipped as a lyophilized powder ('puck') because the dry form is far more stable than a solution. It must be reconstituted before use in research.See glossary →: refrigerated, dark, stable roughly 12–24 months. ReconstitutedReconstitutionThe process of mixing a freeze-dried (lyophilized) peptide powder with bacteriostatic water to create a solution of known concentration.See glossary →: 2–8°C and used within weeks; VIP is enzymatically fragile, and a nasal-spray dilution should be made fresh in small batches.

What is VIP stacked with in research?

Rarely stackedPeptide stackTwo or more peptides used together in a research protocol because their mechanisms are complementary — for example, BPC-157 with TB-500.See glossary →. Discussed alongside thymosin alpha-1 in immune-regulation contexts (VIP as the anti-inflammatory brake, Tα1 as the dendritic-cell regulator). In lung research its pharmaceutical form has been paired with a neutral-endopeptidase inhibitor to slow its breakdown.

Side effects observed in research

Flushing, a drop in blood pressure with light-headedness, and gut cramping or diarrhoea follow directly from what the peptide does — vasodilation and intestinal secretion. The inhaled 100 mcg dose caused no side effects in 20 patients [5], and the COVID trial reported no drug-related serious adverse events [6]. There is no approval for VIP in Canada or the US; aviptadil is investigational, and research-grade VIP is sold as Research Use Only.

  • Flushing
  • Drop in blood pressure / light-headedness
  • Gut cramping or diarrhoea
  • Nasal irritation (intranasal)

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Frequently asked questions

Why is VIP usually taken intranasally in research protocols?

Because it lasts about a minute in blood [2]. Local delivery to the airway avoids the bloodstream entirely and puts the peptide where the receptors of interest are. Inhaled aviptadil is the same idea in a pharmaceutical form [5].

What is aviptadil?

The pharmaceutical name for synthetic VIP. It has been trialled inhaled for pulmonary hypertension [5] and intravenously for critical COVID-19 respiratory failure, where the 2022 trial's primary endpoint did not reach significance [6]. It is not approved in Canada or the US.

What dose do research protocols reference?

Clinical data: a single 100 mcg inhaled dose [5] and three-day IV infusions in critical care [6]. Community intranasal protocols reference 50 mcg per spray up to four times daily — convention, not trial data.

Does VIP suppress the immune system?

The literature describes regulation: it reduces pro-inflammatory cytokines from macrophages and encourages regulatory T cells [3][4], which is why it is studied in inflammatory and autoimmune models rather than as an immunosuppressant.

Related research peptides

Browse all Immune / Gut peptides or start with the beginner’s guide to research peptides.

References

  1. 1.Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970. PubMed
  2. 2.Domschke S, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut. 1978. PubMed
  3. 3.Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013. PubMed
  4. 4.Gonzalez-Rey E, Delgado M. Vasoactive intestinal peptide and regulatory T-cell induction: a new mechanism and therapeutic potential for immune homeostasis. Trends Mol Med. 2007. PubMed
  5. 5.Leuchte HH, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008. PubMed
  6. 6.Youssef JG, et al. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial. Crit Care Med. 2022. PubMed