VIP
Also known as Vasoactive Intestinal Peptide, Vasoactive Intestinal Polypeptide, Aviptadil
VIP is a 28 amino acid neuropeptide found throughout the gut, lungs, brain and immune system that relaxes smooth muscle, widens blood vessels and calms inflammation. It is used, mostly as a nasal spray, for chronic inflammatory response syndrome from mold exposure, lung inflammation and immune regulation.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 50 mcg per spray, one spray in each nostril; 50 to 200 mcg per dosing session
- How often
- 1 to 4 times daily (nasal), starting at once daily
- Where
- Intranasal, alternating nostrils; subcutaneous use is uncommon
- Timing
- earlier in the day, since late doses can affect sleep; start with one spray daily and build up over weeks
- Effects timeline
- energy and cognitive clarity 1 to 3 weeks, inflammatory markers 4 to 8 weeks, full CIRS protocol 1 to 3 months
- Storage
- fridge 2 to 8 C once mixed, use within 2 to 3 weeks; nasal sprays kept cold and used within 30 days
- Cycle length
- 1 to 3 months at full dose
- Break between
- taper down over 2 to 4 weeks rather than stopping abruptly; some stay on a low maintenance dose
Overview
VIP was discovered in 1970 by Sami Said and Viktor Mutt in pig intestine and named for its effect on blood vessels. It turned out to be one of the most widely distributed neuropeptides in the body, acting as a neurotransmitter, a hormone and an immune signal. It relaxes smooth muscle in the gut and airways, stimulates secretion in the pancreas and intestine, and is a major regulator of the circadian clock in the hypothalamus. Its levels fall in a range of chronic inflammatory conditions.
Animal and cell studies show VIP is strongly anti-inflammatory. It shifts T cells toward regulatory and Th2 profiles, suppresses production of TNF-alpha and other inflammatory cytokines, and protects lung tissue from injury. In mouse models it reduces the severity of arthritis, colitis, sepsis and autoimmune encephalitis. It also protects nerve cells and supports gut barrier integrity. Low VIP levels have been measured in people with chronic fatigue, inflammatory bowel disease and biotoxin illness, which is the rationale for replacing it.
Human use has two main tracks. Aviptadil, the pharmaceutical form, has been trialed for pulmonary hypertension, ARDS and severe COVID-19 respiratory failure, with mixed results in the COVID trials. Separately, a compounded VIP nasal spray is used in the Shoemaker protocol for chronic inflammatory response syndrome after mold or biotoxin exposure, based on a small open label study showing normalization of inflammatory markers. That use has a devoted following but limited controlled evidence.
How it works
VIP binds two G protein coupled receptors, VPAC1 and VPAC2, found on smooth muscle, epithelial cells, neurons and most immune cell types. Binding raises intracellular cAMP, which relaxes smooth muscle, opens blood vessels and, in immune cells, suppresses NF-kB driven inflammatory gene expression. It reduces release of TNF-alpha, IL-6 and IL-12 from macrophages and dendritic cells, promotes regulatory T cell development and inhibits Th1 and Th17 responses. In the lung it protects alveolar cells and reduces pulmonary artery pressure. In the hypothalamus it synchronizes the neurons that set circadian rhythm. Because the receptors are so widespread, VIP touches nearly every system, which is both why it is interesting and why dosing needs care.
Where the research stands
Lung inflammation and pulmonary hypertensionModerate evidence
- Critical COVID-19 respiratory failure. Intravenous aviptadil improved oxygenation and survival in some patients, but the main randomized trial did not meet its primary endpoint.
- Pulmonary hypertension. Inhaled aviptadil lowered pulmonary artery pressure in animal models and small human studies; it did not progress to approval.
- Sarcoidosis and ARDS. Small open label human studies of inhaled VIP reported reduced inflammation; not confirmed in controlled trials.
Chronic inflammatory response syndrome (mold and biotoxin illness)Emerging
- CIRS symptom and lab normalization. One small open label study of nasal VIP reported improved symptoms and normalized inflammatory markers; no controlled trial exists.
- Fatigue and cognitive symptoms. Anecdotal within the Shoemaker protocol community, resting on that same single study.
Autoimmune and gut inflammationEmerging
- Arthritis, colitis and autoimmune encephalitis. Mouse models improve consistently; human data for these conditions does not exist.
- Immune regulation. In vitro work shows suppressed TNF-alpha and IL-6 release and a shift toward regulatory T cells.
Erectile dysfunctionStrong evidence
- Intracavernosal aviptadil with phentolamine. Randomized trials led to approval in several countries; this is a different route and use from anything in the peptide community.
- rodentReduced severity of collagen-induced arthritis, colitis and experimental autoimmune encephalomyelitis in mouse models.
- human pilotNasal VIP normalized inflammatory markers and improved symptoms in patients with chronic inflammatory response syndrome in a small open label study.
- human RCTIntravenous aviptadil improved oxygenation and survival in some patients with critical COVID-19 respiratory failure, though the main RCT did not meet its primary endpoint.
- in vitroSuppressed TNF-alpha and IL-6 release from activated macrophages via VPAC1 and cAMP signaling.
- human pilotProtected lung tissue and reduced pulmonary hypertension in animal models and small human studies of inhaled aviptadil.
Rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Levels over time
Modeled from the half-life. Illustrative, not measured.A half-life of 3 min against dosing every 24 h means each dose has cleared before the next. Nothing stacks; you start from zero every time, and the tissue effect is what carries over.
The plasma half-life is so short that injection produces a brief spike with blood pressure effects and little else, which is why nasal spray dosed up to four times daily is the practical route for immune regulation.
VIP dosage and protocols
The CIRS approach starts low, one 50 mcg spray daily, and titrates up over weeks to four times daily as tolerated, holds at full dose for 1 to 3 months, then tapers. It is meant to be the last step after removing exposure and correcting other markers, and starting it too early is the most common reason it goes badly.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Starting dose | 50 mcg (one spray) | once daily | Intranasal |
| Titration | 50 mcg per nostril | once daily, increasing to twice daily | Intranasal, alternating nostrils |
| Full CIRS protocol | 50 mcg per nostril (100 mcg per session) | 4 times daily, 400 mcg per day | Intranasal |
| Maintenance | 50 to 100 mcg | once or twice daily | Intranasal |
| Subcutaneous (uncommon) | 50 to 200 mcg | once daily | Subcutaneous, abdomen |
Food does not matter. Doses are spread through the day with the last one by late afternoon, because VIP is a circadian signal and evening doses can disturb sleep in some people. Blood pressure sensitive users take it seated and wait a few minutes before standing.
The CIRS nasal protocol is 50 mcg per spray, one spray in each nostril up to four times daily, giving 400 mcg daily at full dose. Community protocols often start at 50 mcg once daily and titrate. Subcutaneous use is uncommon.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 2 mg | 1 mL | 2 mg/mL | 2.5 units |
| 6 mg | 2 mL | 3 mg/mL | 1.7 units |
| 10 mg | 3 mL | 3.333 mg/mL | 1.5 units |
How to reconstitute VIP
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1 to 2
Flushing, lightheadedness or a faster heart rate right after a spray are common while finding the dose; some people feel a lift in energy, others feel worse, which is a signal to slow the titration.
- Week 3 to 6
In responders, better sleep quality, clearer thinking and less fatigue tend to show up as the dose reaches twice daily or more.
- Month 2 to 3
Inflammatory labs are rechecked here in the CIRS protocol; this is where the open label study measured normalization, and where the decision to taper is made.
Interactions and stacking
KPVcompatible
Both dampen inflammation through different pathways and are paired in mold and gut protocols, with no data on the combination.
BPC-157compatible
BPC-157 repairs gut lining while VIP calms the immune activation behind it; no known interaction.
Semaxcompatible
Both are nasal peptides, so people space them apart by an hour or more to avoid one washing the other out.
Blood pressure medicationcaution
VIP dilates blood vessels and lowers blood pressure, which adds to antihypertensives and can cause lightheadedness or fainting.
PDE5 inhibitors (sildenafil, tadalafil)caution
Both raise cyclic nucleotide signaling in smooth muscle and lower blood pressure; the combination has not been studied outside the approved intracavernosal product.
Ongoing mold exposureavoid
In the CIRS protocol VIP is not started while exposure continues or MMP-9 is markedly elevated, because it tends to make symptoms worse.
Pancreatic disease or high lipasecaution
VIP stimulates pancreatic secretion and can raise lipase; the protocol checks pancreatic markers before and during use.
Safety
- ▲Flushing, lightheadedness or rapid heart rate, especially at higher doses
- ▲Headache
- ▲Diarrhea or stomach upset from its secretory effect on the gut
- ▲Nasal irritation or runny nose
- ▲Trouble sleeping if dosed late in the day
- ▲Raised lipase on blood tests
- ▲VIP lowers blood pressure and can cause flushing, lightheadedness or rapid heart rate, especially at higher doses.
- ▲In the CIRS protocol it should not be started while still exposed to mold or with markedly elevated MMP-9, since it can worsen symptoms.
- ▲Can raise lipase; the Shoemaker protocol checks pancreatic markers before and during use.
- ▲May cause diarrhea or GI upset because of its secretory effects on the gut.
- ▲Nasal spray potency is highly dependent on cold storage and formulation quality.
- ■Blood pressure drops enough to cause fainting or near fainting
- ■Symptoms of mold illness flare and keep getting worse rather than settling with a lower dose
- ■Lipase rises above normal or there is upper abdominal pain suggesting pancreatitis
- ■Palpitations or chest discomfort after dosing
- ■Signs of an allergic reaction such as hives, swelling or trouble breathing
Community poll
Self-reported by visitors. Not clinical evidence.VIP: frequently asked
What is VIP used for in the mold illness protocol?
In the Shoemaker CIRS protocol, VIP nasal spray is the final step after removing exposure, binding toxins and correcting other inflammatory markers. It is meant to restore normal regulation of inflammation and has been reported to improve fatigue, cognitive symptoms and abnormal lab values. The evidence is a small open label study, not controlled trials.
Why nasal instead of injection?
VIP is degraded in blood within minutes, so injection gives a brief systemic spike with cardiovascular side effects. Nasal delivery provides gradual absorption through the mucosa and some direct access to the brain along olfactory pathways, with fewer blood pressure effects. It is also easier to dose multiple times daily.
Can VIP make symptoms worse?
Yes, particularly if started too early or at too high a dose. People report headache, flushing, palpitations, and in the mold context a flare of symptoms if exposure is ongoing. Starting with a single spray daily and increasing over weeks is the usual approach.
Is VIP the same as aviptadil?
Aviptadil is the international name for synthetic VIP used as a pharmaceutical. It has been trialed intravenously for COVID-19 lung failure and is approved with phentolamine as an injection for erectile dysfunction in some countries. The peptide is identical; the difference is in formulation, route and regulatory status.
References
- Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions (review). Amino Acids, 2013
- Vasoactive intestinal peptide as a novel treatment for chronic inflammatory response syndrome. Health, 2013
- Intravenous aviptadil for critical COVID-19 with respiratory failure (COVID-AIV trial). NeuroRx clinical program, 2021
- VIP and PACAP as immunomodulators (review). Nature Reviews Immunology, 2004