VIP

What is VIP?

Vasoactive intestinal peptide (VIP) is a 28-amino-acid peptide made by nerve cells throughout the body. It was discovered in 1970 by Sami Said and Viktor Mutt, who isolated it from pig intestine and named it for its ability to widen blood vessels. It was later found in the brain, lungs, eyes, heart and immune tissue, where it acts mainly as a nerve signal rather than a circulating hormone.⁶

A synthetic version, aviptadil, has been tested as an intravenous or inhaled drug for lung diseases, most prominently in critical COVID-19 respiratory failure. It is not FDA approved for any use. In some European countries, aviptadil combined with phentolamine is licensed as an injection for erectile dysfunction.

In US integrative and functional medicine, compounded intranasal VIP has been promoted for chronic inflammatory response syndrome (CIRS), a condition some practitioners attribute to mold exposure. That diagnosis is not widely accepted, and the evidence for VIP in it is limited to small studies from a few clinicians.

How VIP works

VIP is a relaxing signal. Released from nerve endings, it tells smooth muscle to loosen. In blood vessels that means wider vessels and lower blood pressure. In the airways it means easier breathing, since VIP is one of the most potent natural bronchodilators known.⁸ In the gut it prompts the intestine to secrete water and salts. It also tends to calm immune cells, shifting them away from inflammatory signaling.

These effects explain both its therapeutic appeal and its side effects. A tumor that releases large amounts of VIP, called a VIPoma, causes severe watery diarrhea, dehydration and low potassium.⁶

In more precise terms, VIP belongs to the secretin-glucagon family and acts through two G protein-coupled receptors, VPAC1 and VPAC2, which raise intracellular cyclic AMP. It is processed from a 170-amino-acid precursor that also yields a related peptide, PHI, released in roughly equal amounts.¹ In the gut, VIP is the primary transmitter of non-cholinergic secretomotor neurons and a secondary transmitter of inhibitory motor neurons.⁵ In the eye it is found in nerves supplying the choroid, where it likely regulates blood flow.⁴ It is also among the parasympathetic neuropeptides implicated in migraine.³ Circulating VIP is cleared within a minute or two, which limits its use as a drug.

What the research shows on VIP

The largest controlled trial tested intravenous aviptadil in 196 patients with critical COVID-19 respiratory failure at ten US hospitals, randomized two to one against placebo for three days of infusion. The primary endpoint, being alive and free of respiratory failure at day 60, was not met. The authors reported better 60-day survival as a secondary result, along with lower interleukin-6 levels and benefit in some subgroups.⁷ Because the main endpoint failed, those secondary findings are hypothesis-generating rather than proof. The FDA did not authorize aviptadil for COVID-19.

Earlier work in lung disease was smaller. VIP's ability to relax airway muscle and its reduced activity in inflamed airways made it a candidate in asthma research, but that did not translate into an approved treatment.⁸ Small pilot studies of inhaled aviptadil have been reported in sarcoidosis and pulmonary hypertension, without confirmatory trials.

VIP has also been studied as one of several brain peptides that influence sleep, mostly in animals.² Its role in migraine is an area of active research, but the interest there is in blocking VIP-related signaling, not adding more of it.³

For CIRS, published support consists of small, uncontrolled studies from practitioners who promote the diagnosis. No large randomized trial has tested intranasal VIP for this or any other chronic condition.

Studied for: Respiratory failure research, Chronic inflammatory response syndrome, Sarcoidosis research.

VIP reference data

VIP dosage in published research

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How VIP is used in practice

In the US, VIP is used mainly in two settings. In hospitals, aviptadil has been given only within clinical trials or expanded access programs. In outpatient functional medicine, VIP is compounded as a nasal spray and prescribed in courses lasting weeks to months, usually for CIRS or mold-related illness, often after other steps such as removing mold exposure.

Online research-chemical vendors also sell VIP as a powder, often alongside instructions for making nasal sprays. Buyers cannot verify purity, and a peptide this short-lived is easily degraded by poor storage. Nasal sprays made at home from such powder add risks of contamination and wrong dosing.

Dosing in CIRS protocols comes from the clinicians who developed them, not from dose-finding trials. Some protocols require specific lab results before starting, but those requirements are not standardized, and many patients obtain VIP without that workup.

VIP risks and side effects

Because VIP relaxes blood vessels, the most common side effects are flushing, a drop in blood pressure, lightheadedness and a fast heart rate. Diarrhea is also common, reflecting VIP's effect on gut secretion. Intranasal use can irritate the nose. In the COVID-19 trial, the authors reported no drug-related serious adverse events.⁷

People with low blood pressure, or who take drugs that lower it, should be cautious. That includes nitrates, other vasodilators and PDE5 inhibitors such as sildenafil and tadalafil, which could add to the drop. There is no safety data in pregnancy. Long-term effects of daily intranasal use over months are unknown. Children and people with heart rhythm problems were not well represented in the trials that exist.

As with other gray-market peptides, product quality is a real risk: wrong dose, degraded peptide, bacterial contamination and mislabeling.

Reported side effects

Alternatives to VIP

For acute respiratory failure, supportive care such as oxygen, high-flow nasal oxygen and ventilation remains the standard. For COVID-19 specifically, approved treatments include antivirals and, in severe cases, dexamethasone and other immune-modulating drugs.

For sarcoidosis, corticosteroids are first line, with methotrexate and other immunosuppressants as steroid-sparing options. For symptoms attributed to mold exposure, removing the exposure and evaluating for asthma, allergy and other diagnoses has better evidence than peptide therapy. For erectile dysfunction, PDE5 inhibitors are first line.

Questions for a clinician

• What evidence applies to my situation, and at what level?
• What established alternatives should I consider first?
• What monitoring would be necessary, and how often?
• Can this be prescribed at all where I live, or only sold for research?