VIP Nasal Spray

VIP, vasoactive intestinal peptide, is an endogenous messenger of 28 amino acids. It was isolated from the small intestine in 1970 but turns up throughout the body: in nerve fibres of the gut, the airways and the nasal lining, in the brain and in immune cells. Structurally it belongs to the secretin-glucagon family, its closest relative being PACAP. As a drug substance VIP is called aviptadil.

This variant is the finished nasal spray: 10mg of VIP dissolved in 5ml of saline (NaCl) plus 0.4ml of bacteriostatic water, 5.4ml in total, which gives 1.85mg per ml. The pump delivers 0.1ml per spray, so about 185mcg of VIP (0.185mg). On paper the bottle holds 54 sprays, after priming the pump roughly 50 remain. No mixing, no syringe, no maths: the spray is made fresh after you order and ships as an express item. If you prefer the vial and syringe, the VIP vial entry has the calculator.

The reason VIP is so often taken nasally lies in its pharmacokinetics: in blood the peptide is broken down within about a minute. A subcutaneous shot therefore delivers only a brief pulse, while the spray places the peptide where the body already uses it, on the nasal mucosa.

This information is for research and educational purposes only. No medical advice.

VIP binds two G-protein-coupled receptors, VPAC1 and VPAC2, class B receptors that signal into the cell through cAMP. They sit on the smooth muscle of vessels and bronchi, on gland cells and on many immune cells, which explains the broad profile: vessels widen, bronchi relax, glands secrete and the immune system receives a calming signal.

The immune side is what most of the research is about. The review by Delgado and colleagues (Pharmacological Reviews 2004) describes VIP as a messenger that curbs the production of TNF-alpha, IL-6 and IL-12 in activated macrophages, tilts the T-cell response from Th1 towards Th2 and promotes regulatory T cells. Prasse and colleagues showed in 2010 that nebulized VIP leaves exactly this footprint in humans: less TNF-alpha from lung cells, more regulatory T cells in the lavage fluid. VIP is therefore not an immune stimulant but an immune regulator that turns down exaggerated responses.

In the nose itself VIP is on home turf. Baraniuk and colleagues (Journal of Clinical Investigation 1990) found VIP-containing nerve fibres in human nasal mucosa concentrated around the glands, binding sites on glands, epithelium and small arteries. In tissue explants VIP stimulated the release of lactoferrin from serous gland cells. That is why the spray can briefly produce a runny or slightly stuffy nose: it is the mechanism, not a faulty product. Because of the very short half-life (Domschke and colleagues, Gut 1978: about one minute in blood), every dose is a short impulse rather than a steady level.

The nasal mucosa is thin and richly perfused, so small peptides can partly cross into the blood there, while the rest is broken down by mucosal peptidases or carried into the throat with the secretions. For VIP this means part of the dose acts locally on glands, vessels and immune cells of the lining, a smaller part reaches the circulation. Even that is degraded within minutes.

The popular idea that nasal VIP goes straight to the brain comes from a rat model. Dufes and colleagues (International Journal of Pharmaceutics 2003) found about 0.11 percent of the dose intact in the brain after nasal delivery, mainly in the olfactory bulbs, midbrain and cerebellum, while VIP in the blood was completely degraded. That only worked with a purpose-built formulation at acidic pH with albumin and an absorption enhancer. A plain saline solution like this spray is not optimised for it. What holds up is this: the nose is a sensible way to apply VIP locally and without a needle, not a way to flood the brain on purpose.

In practice: before first use, pump 2 to 3 times into the air until a fine mist appears. Gently clear your nose first, keep your head upright, point the nozzle slightly outward towards the nasal wall rather than at the septum, breathe in calmly and do not sniff hard. Avoid blowing your nose for 10 to 15 minutes afterwards. Each spray delivers 0.1ml; two sprays in quick succession into the same nostril tend to run down the back rather than work twice as hard.

The best human evidence comes from Freiburg. Prasse and colleagues (American Journal of Respiratory and Critical Care Medicine 2010) gave 20 patients with biopsy-proven, active sarcoidosis nebulized VIP for four weeks. Inhalation was safe and well tolerated. TNF-alpha production by cells recovered from lung lavage fell significantly, while the number of regulatory T cells in the lavage fluid rose. In the dish, VIP converted naive T cells into FoxP3-positive regulatory T cells. It is the first demonstration of an immune-regulating effect of VIP in humans, but an open study without a placebo group and with laboratory endpoints rather than clinical improvement.

The groundwork is laid by the review from Delgado and colleagues (Pharmacological Reviews 2004), which recasts VIP from a vasodilating hormone into an immune modulator with the features of a type 2 cytokine: a brake on inflammatory messengers from macrophages, a shift in the T-cell response, protection in animal models of chronic inflammation. For the nose itself, Baraniuk and colleagues (1990) describe VIP as part of the parasympathetic nerve supply of the mucosa, acting on glands and vascular tone.

The nasal spray as such rests on thin data. The case series by Shoemaker and colleagues (Health 2013) reports on 20 patients with chronic inflammatory response syndrome after mould exposure (CIRS) who used VIP nasal spray for at least 18 months, with improved symptoms and lab markers according to the authors. It is the origin of the scene protocols, but it is open-label, has no control group, appeared in a journal of little standing and was written by proponents of the concept. Useful as a hint, not as proof. And as a damper on expectations: the large randomised TESICO trial (Lancet Respiratory Medicine 2023) of intravenous aviptadil in severe COVID-19 found no benefit over placebo. A different application, but it shows how far hope and evidence can drift apart with VIP.

• Circulation: VIP is a potent vasodilator. In the infusion study by Domschke and colleagues (1978) the highest dose produced skin flushing, a faster pulse and a wider blood pressure amplitude. Far less reaches the blood nasally, yet warmth, flushing, palpitations or dizziness remain possible, especially with low baseline blood pressure.
• Nose: burning, sneezing, a runny nose or a briefly stuffy feeling. VIP stimulates the mucosal glands and widens their vessels, the mechanism described by Baraniuk and colleagues. Pause if irritation persists or the nose bleeds.
• Digestion: VIP increases water and electrolyte secretion in the gut. An excess of VIP in the blood presents as watery diarrhoea. Unlikely at 1 to 2 sprays, but loose stools or diarrhoea are a signal to reduce.
• Metabolism: in the infusion study blood glucose, free fatty acids and calcium rose slightly. Probably irrelevant nasally, still worth knowing for diabetics.
• Interactions: combined with blood pressure medication, nitrates or PDE-5 inhibitors (sildenafil, tadalafil) the vasodilating effects can add up, making dizziness and a drop in blood pressure more likely. Decongestant nasal sprays (xylometazoline) also change mucosal blood flow and with it uptake, do not use them at the same time.
• Immune system: VIP dampens inflammatory responses. Anyone with an acute infection, on immunosuppression or with an autoimmune condition is interfering with a running system and belongs in medical hands with that question.
• Long-term data: the only longer observation in humans is an open case series of 20 people. There are no data for pregnancy or breastfeeding.

The spray belongs in the fridge (2 to 8 degrees), not in the freezer and not in the door compartment where the temperature swings every time it opens. Protect it from light by leaving the bottle in its outer packaging or box. A few hours at room temperature, in the post or in a bag, do the solution no harm, but it should not sit warm for long.

Once opened, the solution keeps for several months in the fridge. VIP in solution is more delicate than many robust peptides, so using it up promptly beats hoarding it. At 1 to 2 sprays a day the bottle is empty after 3 to 7 weeks anyway, so the question resolves itself.

Wipe the nozzle with a clean tissue after each use and put the cap back on so nothing dries in and no germs migrate into the bottle. A bottle is personal, do not share it. If the solution turns gel-like, lumpy or smells different, stop using it. Slight cloudiness on its own is not a reason.