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.
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.
What the research shows
- 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.
Evidence labels: 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.
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.
Dosing and protocol
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.
1-3 months at full dose, then taper. In the CIRS protocol it is the final step after other markers are addressed.
Start with one spray daily and increase slowly. Some people find late doses affect sleep, so earlier in the day is common.
| 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 |
Lyophilized: freezer or fridge, away from light. Reconstituted: fridge 2-8C, use within 2-3 weeks. Nasal sprays should be kept cold and used within 30 days.
Cautions
- ▲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.
Commonly stacked with
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