What is VIP?
VIP was first isolated in 1970 by Sami Said and Viktor Mutt, who found it in extracts of pig intestine and noticed that it widened blood vessels. That is where the name comes from: vasoactive means it acts on blood vessels. It was later found throughout the nervous system, including the brain's internal clock, the lungs, the pancreas and the reproductive organs.
VIP belongs to the same peptide family as secretin, glucagon and PACAP, and it shares receptors with PACAP. Synthetic VIP is called aviptadil. Natural VIP breaks down within minutes in the blood, which limits how it can be used and is one reason researchers have tested inhaled and nasal forms.
How does VIP work?
VIP binds to receptors called VPAC1 and VPAC2, and to a lesser degree PAC1, found on smooth muscle, blood vessels, gland cells and immune cells. Activating them raises a signaling molecule called cyclic AMP inside the cell. In blood vessels and airways this tends to relax muscle, which widens vessels and opens airways. In the gut it drives water and salt secretion. In immune cells, lab and animal studies show it can dampen inflammatory signals and favor regulatory T cells, which help keep immune responses in check.
What has research looked at?
- Lung conditions
- Small studies tested inhaled aviptadil in pulmonary arterial hypertension and sarcoidosis. Early, mostly uncontrolled reports were encouraging, but a clear benefit has not been confirmed in controlled trials.
- Severe COVID-19
- Intravenous aviptadil was tested in people with COVID-19 respiratory failure. A large randomized trial in the US found no improvement in recovery or survival compared with placebo.
- Erectile dysfunction
- A combination of aviptadil and phentolamine, given by injection, has been studied for erectile dysfunction and has been used for it in some European countries.
- Autoimmune and inflammatory disease
- In mouse models of arthritis, colitis and other immune conditions, VIP reduced inflammation and tissue damage. These findings have not been confirmed in human trials.
- Brain and nerve health
- Cell and animal studies suggest VIP protects nerve cells and helps coordinate the body clock. Human evidence for brain conditions is very limited.
VIP is well understood as part of normal physiology, and animal research on inflammation is extensive. Turning that into treatment has been harder. Its short life in the blood and its effects on blood pressure complicate its use, and the largest human trial so far was negative.
Side effects and cautions
Because VIP widens blood vessels and acts on the gut, its side effects follow from those actions. In human studies, commonly reported effects were flushing, low blood pressure, a faster heartbeat and diarrhea. A rare tumor called a VIPoma, which releases large amounts of VIP, shows what sustained high levels do: severe watery diarrhea and loss of potassium. Anyone with heart, blood pressure or immune conditions should talk to a qualified clinician.
- Low blood pressure
- VIP lowers blood pressure, which can cause dizziness or fainting, especially alongside blood pressure medicines.
- Flushing and fast heartbeat
- Facial flushing, warmth and a racing pulse have been reported, mostly with infusions.
- Diarrhea and stomach upset
- VIP increases fluid secretion in the gut, so diarrhea and cramps are possible.
- Immune conditions
- Because it shifts immune activity, its effects in people with autoimmune disease or on immune-modifying drugs are not well known.
Further reading
This page summarizes the research in plain words. To read the studies yourself:
- Published studies on VIP PubMed, US National Library of Medicine
- Registered human trials of VIP ClinicalTrials.gov
