VIP
Vasoactive intestinal peptide, Aviptadil, Zyesami
A 28 amino acid signalling peptide that reached a randomised trial in critical COVID and narrowly missed its endpoint, now sold as a nasal spray for an entirely different set of claims.
Human trials
Not FDA-approved. The synthetic form aviptadil was studied under an investigational new drug application with fast track designation and received emergency or compassionate use authorisation in some countries. Nasal formulations are supplied by compounding pharmacies.
What it is
Vasoactive intestinal peptide is a naturally occurring 28 amino acid neuropeptide found throughout the gut, lungs and nervous system. It dilates blood vessels, relaxes smooth muscle, drives intestinal secretion and has broad anti-inflammatory activity.
Its concentration in the lung is the reason it became a COVID drug candidate. VIP is highly expressed in alveolar type 2 cells, the cells that produce surfactant and that SARS-CoV-2 preferentially infects.
The trial and what it actually showed
Aviptadil, synthetic VIP, was tested in a randomised placebo-controlled trial in 196 patients with critical COVID-19 respiratory failure, randomised two to one, with a primary endpoint of being alive and free from respiratory failure at day 60.
It missed. The odds ratio was 1.6 with a confidence interval from 0.86 to 3.11, which crosses one. The authors reported a survival benefit in secondary analysis and noted the trial was underpowered because mortality during the enrolment period ran higher than projected.
That is a real trial with a real negative primary result and a suggestive secondary one. It is more evidence than most peptides on this site have, and it did not establish efficacy.
The gap between that trial and what is sold
Enormous, and worth stating explicitly.
The trial delivered VIP by continuous intravenous infusion over three days to intubated patients in intensive care with monitoring of blood pressure. What is sold is a nasal spray, used at home, several times daily, for chronic inflammatory conditions, mould illness and fatigue syndromes that were not studied at all.
Nothing about the COVID trial supports those uses. The nasal route has not been characterised for absorption, dose or duration, and the conditions it is marketed for have no trial evidence involving this peptide.
Practical notes
- The two minute half-life shapes everything. VIP is degraded almost immediately in circulation, which is why the trials used continuous infusion rather than injections. Intermittent dosing of a peptide with this pharmacokinetic profile is a design nobody has validated.
- Vasodilation is the dose-limiting effect. Flushing and low blood pressure are not incidental; they are the most reliable thing this peptide does.
- Chronic inflammatory response syndrome is where most nasal VIP use comes from. That framework is contested within mainstream medicine, and the peptide protocols attached to it have not been tested in controlled trials.
Side effects and warning signs
Commonly reported
- Flushing, from vasodilation, which is the peptide's most reliable pharmacological effect
- Diarrhoea, since VIP drives intestinal secretion
- Hypotension
- Nasal irritation with the intranasal route
Stop and get medical help
- Low blood pressure or lightheadedness, since VIP is a potent vasodilator and this is dose-related
- Persistent watery diarrhoea, which is the defining feature of VIPoma, the tumour syndrome caused by excess VIP
- Any use in place of assessment for a diagnosed respiratory or inflammatory condition
Sources
From the community
Discussion for this compound concentrates in r/Peptides.
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