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Not medical advice. The Atlas is not a substitute for a clinician who can examine you.

VIP

Vasoactive Intestinal Peptide

Evidence grade 2 of 5, Thin. Read how the Atlas grades evidence.

VIP is a well-characterized 28-amino-acid endogenous neuropeptide, but as a therapeutic its record is thin and its highest-profile test was a failure. The pivotal TESICO trial (ACTIV-3b, NIH-run, ~461 patients) found intravenous aviptadil (Zyesami/RLF-100) was not superior to placebo on recovery at day 90 or on 90-day mortality (38% vs 36%) for COVID-19 hypoxaemic respiratory failure, and the FDA declined an Emergency Use Authorization on 4 Nov 2021 citing insufficient benefit-risk data. The only positive human signals are small, early-phase sarcoidosis studies (inhaled VIP, ~20-patient Avisarco II), and the intranasal-VIP use in Dr. Shoemaker's CIRS/mold protocol is unproven with no controlled trial support, so the honest grade is preliminary human evidence at best.

FDA
No FDA-approved VIP or aviptadil product. FDA declined Emergency Use Authorization for Zyesami (aviptadil) in critical COVID-19 on 4 Nov 2021; holds orphan-drug designation for sarcoidosis (investigational only).
WADA
Not on the WADA Prohibited List

Reference only. Not medical advice.

What can go wrong

No approved product; pivotal COVID-19 trial was negative; very short half-life complicates dosing; intranasal CIRS use is unproven and off-protocol from any regulator.

Talk to a clinician before taking this. The Atlas can tell you what has been studied about VIP. It cannot tell you how it would interact with your body, your history, or anything else you are taking, and nothing on this page is a reason to start.

A 28-amino-acid endogenous neuropeptide (VIP) produced in the GI tract, central nervous system, and immune tissue, with anti-inflammatory and vasodilatory signaling. Its synthetic form, aviptadil (Zyesami / RLF-100), was tested at scale for COVID-19 acute respiratory failure and failed the pivotal NIH TESICO trial, with the FDA declining emergency use authorization; it retains orphan-drug designation for sarcoidosis. Intranasal VIP used in Dr. Ritchie Shoemaker's CIRS/mold-illness protocol is unproven. No FDA-approved VIP product exists.

The inflammation resolver. The signature of Dr. Shoemaker's mold-illness protocol.

What people take it for

These are the reasons people give for taking it. They are not effects it has been shown to have.

  • CIRS / mold illness protocol
  • Pulmonary arterial hypertension
  • GI motility disorders

How it is supposed to work

VIP (Vasoactive Intestinal Peptide), sold synthetically as aviptadil, is a 28-amino-acid signaling peptide in the glucagon-secretin family. It is a potent vasodilator and a key messenger of the neuroendocrine-immune network, binding VPAC receptors to raise cellular cAMP. In the lung it is concentrated around the surfactant-producing cells, where it is anti-inflammatory and protective, which is the basis for most of its therapeutic interest.

VIP is a 28-amino-acid neuropeptide found naturally throughout the body, concentrated in the lungs and gut, acting on receptors that lower inflammation. Its synthetic version is aviptadil, given intravenously or by inhalation, with a very short half-life. It is known biologically for the watery diarrhea caused by a rare VIP-secreting tumor, and it is sold gray-market, often as a nasal spray.

Type
Anti-inflammatory neuropeptide
Synthetic
Aviptadil
Action
Calms lung inflammation
COVID trial
Failed
Gray-market
Mold-illness protocol
Approved
No

The Lung Peptide COVID Made Famous, Then Failed

VIP is a real anti-inflammatory peptide with a long, legitimate pedigree, and also a textbook case of how a promising early signal can collapse under a rigorous trial. For two decades its synthetic form held orphan-drug status for hard respiratory diseases, with small, encouraging studies in sarcoidosis and pulmonary hypertension, where inhaled VIP calmed inflammation. Then COVID arrived. Because VIP protects the exact lung cells the virus attacks and dampens the cytokine storm, aviptadil was rushed into trials for COVID respiratory failure, and an early open-label study suggested it helped people survive. That signal, amplified by heavy promotion and stock speculation, made it briefly famous. But the definitive test, a large randomized trial of over four hundred patients, found no benefit on any endpoint. The biology is genuine and the drug is well tolerated, but its highest-profile use did not hold up. It is not approved for these conditions, and it is separately sold gray-market, often as a nasal spray within a contested protocol for so-called mold illness, on far thinner evidence than even its failed trials had.

Safety in detail

In the TESICO phase 3 trial intravenous aviptadil did not reduce death or speed recovery, and the FDA found the benefit-risk data insufficient for authorization. Any current human use of VIP or aviptadil, including the intranasal CIRS/mold protocol, is investigational or off-label and not supported by an FDA approval.

  • As a potent vasodilator, its main effects are low blood pressure, flushing and diarrhea, especially at therapeutic intravenous doses.
  • It has been studied in serious illness under medical supervision; its broad-population safety outside trials is not established.
  • Its large COVID-19 trials did not deliver clear benefit, tempering enthusiasm.
  • Approved uses are narrow and region-specific; it is not a general wellness peptide.

Children and teenagers

VIP has no general pediatric use. It is an investigational and gray-market peptide without pediatric approval, and the contested mold-illness protocol and gray-market nasal use are inappropriate for children. Any legitimate respiratory use would belong in a supervised clinical setting.

What people get wrong

Nothing recorded here yet. There is almost certainly something people get wrong about this one, and the blank space means we have not written it down, not that the record is clean.

Who profits, and who pushes back

Nobody is named here yet, because we have not done that work on this entry. Read that as unfinished. Somebody almost certainly sells this, and somebody almost certainly disputes it. Assume both until we have checked.

VIP’s economy is split between biotech development of aviptadil for respiratory disease, including a controversial wave of COVID-era stock promotion, and gray-market vendors selling intranasal VIP for inflammation and mold-related illness. There is no approved product for these headline uses, making it largely a pedigree-and-hype-driven market rather than an evidence-driven one.

How we got here

VIP was isolated from porcine intestine by Said and Mutt in the early 1970s and named for its vasodilatory action, then found to be a widely distributed neuropeptide in the gut, lung, and nervous system. Its synthetic form was later developed as a drug: the sarcoidosis and pulmonary-hypertension work ran under academic and European programs, and around 2020 the same molecule was licensed and rebranded as RLF-100 by Relief Therapeutics and Zyesami by NeuroRx (later NRx Pharmaceuticals) for a high-profile COVID-19 acute-respiratory-failure program that ultimately failed in the NIH TESICO trial and was denied FDA emergency authorization. A separate, unrelated lineage is the compounded intranasal 'nasal VIP' popularized within Dr. Shoemaker's chronic-inflammatory-response-syndrome protocol, which shares the molecule but has no controlled-trial basis.

VIP was characterized as a 28-amino-acid anti-inflammatory neuropeptide concentrated in the lungs, and its synthetic form aviptadil earned orphan-drug status for several respiratory diseases, with small encouraging studies in sarcoidosis and pulmonary hypertension. During COVID it was rushed into respiratory-failure trials amid an early survival signal and heavy promotion, but a large randomized trial in 2022 and 2023 found no benefit. It persists as a gray-market intranasal product within a contested mold-illness protocol.

  1. 1970sVIP is characterized as an anti-inflammatory lung and gut neuropeptide.
  2. 2000s-2010sAviptadil earns orphan status and shows promise in small respiratory studies.
  3. 2020-2021It is rushed into COVID trials amid an early signal and heavy promotion.
  4. 2022-2023A large randomized COVID trial finds no benefit.
  5. ongoingGray-market intranasal use within a contested protocol persists.

The numbers behind the grade

Type
VIP (28 aa)
Drug name
Aviptadil
Action
Vasodilator, immune
Tested in
COVID-19, PAH
Approved
Narrow/regional
Wellness use
No

The people taking it

Best known from its high-profile, ultimately inconclusive COVID-19 trials, VIP is a genuine clinical-stage peptide with narrow approvals rather than a wellness compound.

VIP’s gray-market users are people with so-called mold illness following a contested protocol, the main driver, along with people seeking help for chronic inflammation, immune dysfunction or long COVID. Its legitimate context is patients with severe respiratory disease in trials or compassionate use. The thread is complex, hard-to-treat illness.

Used as the drug aviptadil for narrow indications such as pulmonary hypertension and, in low dose, erectile dysfunction, and trialed without clear success for COVID-19 lung injury. A clinical drug, not a consumer peptide.

Set against the alternatives

Against the COVID therapies that did work, like dexamethasone, which have solid trial evidence, aviptadil failed its definitive trial. Against the gray-market mold-illness protocol it is sold within, that protocol is contested and not mainstream-validated. And against other anti-inflammatory and immune peptides like thymosin alpha-1 and KPV, it shares the same broad calming biology. Its defining lesson is the gap between a small open-label signal and a large controlled result, which went against it. Its strength is genuine anti-inflammatory biology and a long safety record; its weakness is that its biggest test was negative.

What we do not know

  • Whether VIP has a real role in acute lung injury after the inconclusive COVID-19 trials.
  • Whether its strong immune-modulating biology can be harnessed for inflammatory lung disease.
  • How to manage its vasodilatory side effects therapeutically.

What could change

VIP-receptor agonistsNewer, longer-acting receptor agonists are in development.Respiratory nichesSmall interest continues in sarcoidosis and related diseases.Contested protocolGray-market mold-illness use persists without validation.Signal-versus-trial lessonIt stands as a case of early promise not surviving rigorous testing.

The market for this

What follows describes how this is bought and sold. It is not a buying guide and it is not an endorsement of any seller.

Where approved, available as a prescribed pharmaceutical (aviptadil) for specific conditions. It is not a consumer wellness peptide, and its serious-illness uses belong under medical care.

Gray-market intranasal VIP is moderately priced, and the contested protocol it is used within is an ongoing cost, while pharmaceutical-grade aviptadil remains investigational.

As aviptadil it is manufactured pharmaceutically where approved; otherwise VIP appears as research material with the usual quality caveats.

Pharmaceutical-grade aviptadilMade for trials and some compounded hospital use.Gray-market nasal spraySold intranasally for inflammation and mold-illness protocols.No approved productThere is no approved consumer formulation for these uses.

At a glance

Found in
Gut, CNS, immune system
Action
Anti-inflammatory, vasodilatory
Half-life
Minutes
Use
CIRS / mold illness

What this entry does not yet cover

What follows is unfinished work on our side, not a finding about VIP.

Nothing outstanding on this one.

Sources

The studies that matter

  • COVID-19 respiratory-failure trials2020-2022

    Aviptadil received FDA Fast Track designation and was tested in large trials for critical COVID-19 lung injury; results were mixed and it did not clearly establish benefit in the major US trials, though it gained emergency use in some countries.

  • Sarcoidosis and pulmonary hypertension2010s

    Inhaled VIP showed immunoregulatory effects in sarcoidosis, and aviptadil has approvals in some regions for pulmonary arterial hypertension.

  • Erectile dysfunctionestablished

    A low-dose aviptadil-plus-phentolamine injection is approved in some markets for erectile dysfunction, a separate and much smaller-dose use.