VIP (Vasoactive Intestinal Peptide)

What it is

VIP stands for vasoactive intestinal peptide. It is a chain of twenty-eight amino acids that the human body produces on its own, found in the gut, the lungs, and the nervous system, where it widens blood vessels and dampens inflammatory signalling. It was pulled out of pig intestine and described by Said and Mutt in 1970, and the original paper is worth knowing about because it names what the compound does most reliably: it is a strong, long-lasting vasodilator. [1]

The manufactured version of the same molecule is called aviptadil. When a clinical trial, a regulatory filing, or a research supplier refers to aviptadil, it is referring to synthetic VIP. The two names sit on either side of the same compound, and vendor pages use them more or less interchangeably.

The approval question, stated precisely

This is the fact most commonly mangled on VIP pages, in both directions, so it is worth being exact about. VIP is not approved by the FDA for any indication in the United States. It went through emergency use consideration for COVID-19 respiratory failure during the pandemic and did not obtain approval, and the trials behind that effort are described below.

It is also not true that VIP has never been approved anywhere. Aviptadil combined with phentolamine mesilate is licensed under the brand name Invicorp as an injection for erectile dysfunction. We could verify that licence in the United Kingdom, where the NHS appraises it as a treatment option for men who have failed oral therapy, and in Sweden, Denmark, Norway and Finland, where it is marketed by Evolan Pharma. [6] [7] Longer country lists circulate on vendor pages and we could not confirm them, so this page names only the countries we could check. That is a different product at a different dose by a completely different route, injected directly into penile tissue, and it says nothing about any other use of the compound. But a page claiming VIP has no approval anywhere in the world would be wrong, and so would a page implying that an approval exists for the uses people are actually interested in.

What the good evidence actually studied

VIP is unusual on this site. Most research peptides suffer from having almost no human data. VIP has the opposite problem: there is a substantial, well-run clinical literature, it involves hundreds of patients, and on the primary endpoints it mostly did not work.

• Intravenous aviptadil in critical COVID-19, 196 patients A multicentre, placebo-controlled randomized trial across ten United States hospitals gave three days of intravenous aviptadil to patients in respiratory failure. The primary endpoint, being alive and free from respiratory failure at day 60, did not reach statistical significance. Several secondary measures did move: sixty-day survival, the respiratory distress ratio, and interleukin-6 by day three. No drug-related serious adverse events were reported. [2] The authors' own conclusion contains both halves of that result, and marketing copy tends to quote only the survival sentence.
• The larger trial, and the one that settled it TESICO was a randomized, placebo-controlled trial of intravenous aviptadil across twenty-eight United States sites, and it is the largest study of this compound. In 461 participants who received at least a partial infusion, the odds of landing in a better category of the day-90 outcome scale were essentially unchanged versus placebo, at an odds ratio of 1.11. Deaths by day 90 were 38 percent on aviptadil and 36 percent on placebo. The independent safety monitoring board stopped the aviptadil arm in May 2022 for futility, meaning it had become clear the trial would not show a benefit if it ran to completion. [3] The Lancet Respiratory Medicine ran an accompanying comment titled, plainly, a negative trial. [4]
• Inhaled VIP in sarcoidosis, 20 patients Twenty people with biopsy-confirmed active sarcoidosis inhaled nebulized VIP for four weeks. It was safe and well tolerated, reduced TNF-alpha production by cells taken from lung lavage, and increased regulatory T cells in the same samples. The authors describe it as the first demonstration of an immune-regulating effect of VIP in humans. [5] This is the study quoted most often in wellness marketing, and it is open label, twenty patients, with no control group. It is a real and interesting mechanism finding. It is not evidence of clinical benefit, and the difference matters.

What people actually buy it for

Almost none of the above describes how VIP is used on the research market. There, it is overwhelmingly bought as an intranasal spray, generally for chronic inflammatory response syndrome, sometimes described as mold illness, and often for the brain fog and fatigue that go with it. That use traces back to a protocol developed outside the peer-reviewed literature this page otherwise cites.

So the honest summary is not that we do not know whether VIP works. It is narrower and more specific than that: the substantial evidence is about intravenous and inhaled VIP in respiratory disease, and it is largely negative on its primary endpoints, while the thing people are buying is a different route for a different condition that this literature does not speak to at all. Anyone weighing the compound should notice that the trial record and the market have almost no overlap, and should not treat the size of the former as reassurance about the latter.

One related history worth knowing, because it sometimes gets cited as though it were ongoing: inhaled VIP was also investigated in pulmonary arterial hypertension. Early small studies looked encouraging, but a Phase II randomized controlled trial in 56 patients found no significant benefit on haemodynamics or exercise capacity, and later aviptadil work moved to other conditions. [8]

Safety, kept separate from efficacy

The tolerability signal in the trial record is genuinely favourable and deserves stating on its own. The 196-patient intravenous trial reported no drug-related serious adverse events. [2] The inhaled sarcoidosis study reported the compound as safe and well tolerated over four weeks. [5] Vasodilation is the expected effect of the molecule, so blood pressure and flushing responses are the predictable things to watch, and they are dose and route dependent.

Tolerated is not the same as effective, and the two belong in separate paragraphs. A compound can be comfortably given to hundreds of critically ill patients and still fail to help them, which is close to what the record here shows. None of the human safety data covers the intranasal route, ongoing daily use, or healthy people.

Typical research parameters

Related research notes