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Research-onlyVendors pendingFacts verified · 2026-05-25

VIP

Also known as v.i.p., vasoactive intestinal peptide · Wikipedia

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide of the secretin/glucagon superfamily, widely distributed throughout the central and peripheral nervous systems and in immune cells and the gastrointestinal tract. It signals through the Gs-coupled VPAC1 and VPAC2 receptors (with secondary affinity for PAC1) to raise intracellular cAMP, producing smooth-muscle relaxation (vasodilation, bronchodilation), intestinal secretion, circadian rhythm signaling, and broad anti-inflammatory immunomodulation. The synthetic analog aviptadil (Zyesami, RLF-100) received FDA Fast Track designation for COVID-19 acute respiratory failure but failed its pivotal primary endpoint. VIP is not FDA-approved for any indication; it is used off-label in the Shoemaker CIRS protocol.

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Mechanism of action

VIP (HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2) is a 28-aa member of the secretin/glucagon peptide family that activates Gs-coupled VPAC1 and VPAC2 GPCRs (with lower affinity at PAC1), raising intracellular cAMP and PKA activity. Tissue effects include arteriolar and bronchial smooth-muscle relaxation (potent vasodilation and bronchodilation), stimulation of intestinal water and electrolyte secretion, and entrainment of circadian rhythms via suprachiasmatic-nucleus VPAC2 signaling.

VIP (HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2) is a 28-aa member of the secretin/glucagon peptide family that activates Gs-coupled VPAC1 and VPAC2 GPCRs (with lower affinity at PAC1), raising intracellular cAMP and PKA activity. Tissue effects include arteriolar and bronchial smooth-muscle relaxation (potent vasodilation and bronchodilation), stimulation of intestinal water and electrolyte secretion, and entrainment of circadian rhythms via suprachiasmatic-nucleus VPAC2 signaling. On immune cells VIP suppresses Th1/Th17 cytokines, induces regulatory T cells, and lowers TNF-alpha and IL-6, giving it a broad anti-inflammatory profile that motivated the synthetic-VIP (aviptadil) Phase III COVID-19 ARDS program (Youssef et al., PMC9555831; PMC10527239). VIP also protects pulmonary alveolar type-II cells from inflammatory and oxidative injury, a putative mechanism for its proposed pulmonary indications.

Pharmacokinetic properties

Half-life

Plasma half-life ~1-2 minutes (rapidly cleaved by dipeptidyl peptidase IV and other proteases)

Routes

intranasal · subcutaneous · intravenous · inhaled

Bioavailability

Not orally bioavailable. Intranasal is the most popular route in CIRS/mold-illness protocols (Shoemaker). The peptide is highly susceptible to peptidase degradation, which limits systemic exposure regardless of route.

Amino-acid sequence

HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2

Use & research dosing

Healthy AgingGut IntegrityGut SupportWound Healing

Research framing only. Aviptadil (synthetic VIP) was dosed in pivotal COVID-19 ARDS trials at approximately 12 pmol/kg/min as a continuous IV infusion over 12 hours for 3 consecutive days (NCT04453839 SAMICARE; PMC9555831). An inhaled formulation was evaluated at 67-100 mcg three times daily (NCT05137795). For off-label CIRS use (Shoemaker mold-illness protocol), intranasal VIP is typically dosed at 50 mcg per spray, one spray in each nostril up to four times daily after cholestyramine-based binder treatment - this protocol has no controlled efficacy data outside Shoemaker case-series literature. Gray-market subcutaneous protocols for longevity or libido lack any clinical-trial basis.

Research-use framing only. SavePeptides sells nothing for human consumption. Doses above reflect reported research / self-experimentation ranges, not clinical recommendations.

Editorial perspective

VIP is one of the most extensively studied neuropeptides but has no approved indication. The synthetic analog aviptadil (Zyesami, RLF-100) received FDA Fast Track designation for COVID-19-associated respiratory failure during the pandemic but missed its primary endpoint in randomized controlled trials (NIH ACTIV-3b/TESICO and the Relief Therapeutics pivotal program). Off-label intranasal use in the Shoemaker CIRS (mold-illness) protocol is popularized in functional-medicine communities but rests on case-series rather than controlled-trial evidence, and the CIRS diagnostic framework itself is not accepted in mainstream medicine.

— SavePeptides editorial desk · last updated 2026-05-25

Cautions & contraindications

Before researching this compound, note:

  • Pivotal IV and inhaled aviptadil Phase III COVID-19 ARDS trials missed primary endpoints; FDA EUA was not granted
  • Hypotension is the dominant dose-limiting adverse effect (observed in ~25% of IV aviptadil patients) due to potent vasodilation
  • Contraindicated in patients with low baseline blood pressure, severe aortic stenosis, or hemodynamic instability
  • Diarrhea and electrolyte loss possible due to stimulated intestinal secretion
  • Bronchoconstriction paradoxically reported in some asthma patients via reflex pathways
  • Pregnancy and breastfeeding - no human safety data
  • Pediatric use not characterized
  • Theoretical immunosuppression with chronic dosing given Th1/Th17 suppression and Treg induction; caution in active infection
  • Off-label intranasal CIRS use (Shoemaker protocol) is controversial; no controlled trial supports the protocol or the underlying CIRS diagnostic framework
  • Gray-market injectable and intranasal VIP products are unregulated; purity and sterility are not independently verified
  • Drug interactions with antihypertensives, PDE5 inhibitors, and other vasodilators can produce additive hypotension

Research foundation

The papers behind the page.

  1. [01]https://pmc.ncbi.nlm.nih.gov/articles/PMC9555831/
  2. [02]https://pmc.ncbi.nlm.nih.gov/articles/PMC10527239/
  3. [03]https://clinicaltrials.gov/study/NCT05137795
  4. [04]https://pmc.ncbi.nlm.nih.gov/articles/PMC9486780/

Facts verified

2026-05-25

Confidence

medium

What this means

  • phase-III-COVID-failed
  • cirs-off-label-controversial
  • no-fda-approval

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