VIP PEPTIDE
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide that binds to VPAC1 and VPAC2 receptors, mediating vasodilation, smooth muscle relaxation, and immunomodulation across gastrointestinal, cardiovascular, nervous, and immune systems.
Vasoactive Intestinal Peptide (VIP) is a naturally occurring neuropeptide widely distributed throughout the body, particularly abundant in the brain, gastrointestinal tract, and peripheral nervous system. It functions as a neurotransmitter and neuromodulator, influencing vasodilation, immune regulation, gastrointestinal motility, and neurological processes. VIP has been studied for its roles in migraine pathophysiology, inflammatory bowel conditions, and as a potential therapeutic agent for various gastrointestinal and neurological disorders.
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Research
Reported Effects
Clinical Evidence:: Strong correlation found between VIP levels and inflammatory bowel disease activity with good sensitivity (81%) and specificity (55%) as a biomarker. Migraine Research:: Clinical trials demonstrate VIP can trigger migraine-like headaches, establishing its role in headache pathophysiology but not as a therapeutic. Limited Supplement Use:: VIP is not commonly used as a direct supplement in biohacking communities; most discussion focuses on other peptides like BPC-157 rather than VIP specifically. Research vs Practice Gap:: While VIP has established physiological roles, its therapeutic application as an exogenous supplement remains experimental with limited real-world user experience
- Strong correlation found between VIP levels and inflammatory bowel disease activity with good sensitivity (81%) and specificity (55%) as a biomarker
- Clinical trials demonstrate VIP can trigger migraine-like headaches, establishing its role in headache pathophysiology but not as a therapeutic
- VIP is not commonly used as a direct supplement in biohacking communities; most discussion focuses on other peptides like BPC-157 rather than VIP specifically
- While VIP has established physiological roles, its therapeutic application as an exogenous supplement remains experimental with limited real-world user experience
VIP lung biology and immunomodulation
Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide highly concentrated in the lung, where it binds VPAC1/VPAC2 receptors on alveolar type II (ATII) cells. VIP is a potent smooth-muscle relaxant (bronchodilator, vasodilator) and anti-inflammatory mediator that upregulates surfactant, suppresses cytokine release, and blocks apoptosis of ATII cells. These properties motivated aviptadil (synthetic VIP) as a therapy for acute lung injury and COVID-19 ARDS.
- Concentrated in lung ATII cells; signals via VPAC1/VPAC2 receptors
- Bronchodilator, pulmonary vasodilator, and anti-inflammatory
- Upregulates surfactant and protects ATII cells from injury
Aviptadil clinical development
Aviptadil (RLF-100/ZYESAMI) has orphan designations for ARDS and sarcoidosis. Results in COVID-19 respiratory failure were contradictory: a sponsor-run Phase 2b/3 trial reported benefit while the larger, independent NIH ACTIV-3b/TESICO trial found none, and no approval for COVID/ARDS resulted. Inhaled aviptadil showed anti-inflammatory effects in Phase 2 sarcoidosis and pulmonary hypertension studies. The VIP-plus-phentolamine combination (Invicorp) is separately approved for erectile dysfunction.
- Conflicting COVID-19 trials: positive sponsor study, negative NIH TESICO
- Inhaled aviptadil dampened alveolar inflammation in sarcoidosis Phase 2
- Invicorp (aviptadil + phentolamine) approved for erectile dysfunction in Europe
Safety Profile
Safety Profile: VIP Peptide (Vasoactive Intestinal Peptide)
Common Side Effects
- Facial flushing and generalized vasodilation are the most common effects due to potent vasodilatory activity
- Hypotension, sometimes significant, particularly with intravenous or high-dose intranasal administration
- Tachycardia (reflex response to vasodilation)
- Diarrhea and abdominal cramping due to stimulation of intestinal secretion
- Nasal irritation and rhinorrhea with intranasal administration
- Headache secondary to vasodilation
Serious Adverse Effects
- Severe hypotension and cardiovascular collapse possible with rapid IV administration or overdose
- Watery diarrhea syndrome at supratherapeutic doses (mimics VIPoma effects)
- Cardiac arrhythmias secondary to hemodynamic changes
- Bronchodilation may mask worsening of underlying pulmonary conditions
- Limited long-term human safety data; most clinical evidence from small studies in CIRS, pulmonary hypertension, and sarcoidosis
Contraindications
- Known hypersensitivity to VIP or formulation components
- Severe hypotension or hemodynamic instability
- Active diarrheal illness (VIP stimulates intestinal water and electrolyte secretion)
- VIPoma or suspected VIP-secreting tumors
- Pregnancy and lactation (insufficient safety data; potent vasodilatory effects may compromise fetal circulation)
Drug Interactions
- Antihypertensives: Severe additive hypotension risk; close blood pressure monitoring essential
- Phosphodiesterase inhibitors (sildenafil, tadalafil): Synergistic vasodilation; dangerous hypotension possible
- Beta-blockers: May prevent reflex tachycardia, worsening hypotension
- Secretin and other GI hormones: Additive effects on intestinal secretion and motility
- Corticosteroids: VIP is sometimes used alongside steroids in CIRS protocols; monitor for additive immunomodulation
Population-Specific Considerations
- CIRS patients: Primary clinical use population (intranasal); titrate slowly and monitor blood pressure
- Elderly: Higher susceptibility to hypotension; use lowest effective dose with careful monitoring
- Pediatric: Very limited safety data; use only under specialist supervision
- Pulmonary hypertension patients: Investigational use via inhalation; requires hemodynamic monitoring
- Cardiac patients: Avoid in unstable cardiovascular disease; vasodilatory effects may precipitate ischemia
Pharmacokinetic Profile
Quick Start
- Typical Dose
- Unlike common peptides discussed in biohacking communities (BPC-157, etc.), VIP lacks established dosing guidelines for supplementation purposes
Research Indications
Approved / Marketed Uses
Aviptadil combined with phentolamine (Invicorp) is approved in the UK and parts of Europe as an intracavernosal injection for erectile dysfunction.
Investigational Respiratory Uses
IV aviptadil (synthetic VIP) tested for acute lung injury; a sponsor trial was positive but the larger independent NIH TESICO trial was negative.
Inhaled aviptadil (orphan designation) reduced alveolar inflammation and cough in Phase 2 studies.
VIP is deficient in PAH; inhaled aviptadil studied for pulmonary vasodilation.
Safety Profile
Common Side Effects
- Migraine Trigger:: VIP infusion can induce migraine-like headaches in susceptible individuals, particularly those with migraine history
- Limited Safety Data:: Minimal information exists about side effects from chronic exogenous VIP supplementation in humans
- Cardiovascular Effects:: As a vasoactive peptide, VIP influences blood vessel dilation and cardiovascular function, requiring monitoring in therapeutic contexts
- Unknown Long-term Effects:: The safety profile of prolonged VIP supplementation has not been adequately studied in healthy populations
References (11)
- [1]Gut-brain Axis and migraine headache: a comprehensive review
→ Reviews the bidirectional relationship between the gastrointestinal system and central nervous system in migraine, highlighting VIP's role in the gut-brain axis and its association with migraine pathophysiology and gastrointestinal disorders.
- [3]Effect of Vasoactive Intestinal Polypeptide on Development of Migraine Headaches: A Randomized Clinical Trial
→ A clinical trial examining VIP infusion effects on migraine development, providing evidence for VIP's role as a migraine trigger and its involvement in headache pathophysiology.
- [2]Vasoactive intestinal polypeptide plasma levels associated with migraine
→ Investigates the relationship between VIP plasma levels and migraine development, suggesting VIP may cross the blood-brain barrier and play a role in anxiety, depression, and migraine mechanisms.
- [4]Vasoactive intestinal peptide as a laboratory supplement to clinical activity index in inflammatory bowel disease
→ Demonstrates that circulating VIP levels correlate strongly with clinical activity in inflammatory bowel disease, showing sensitivity and specificity as a biomarker for gauging disease severity in UC and Crohn's disease.
- [5]Immunohistochemical study of vasoactive intestinal peptide (VIP) enteric neurons in diabetic rats supplemented with L-glutamine
→ Examines how L-glutamine supplementation affects VIP-immunoreactive neurons in diabetic rats, showing changes in cell body and nerve fiber areas that suggest modulation of enteric nervous system function.
- [6]Postprandial effect of gastrointestinal hormones and gastric activity in patients with irritable bowel syndrome
→ Investigates postprandial VIP secretion and gastric activity in IBS patients, examining the role of gut peptides in altered gut regulation characteristic of irritable bowel syndrome.
- [7]The impact of exogenous vasoactive intestinal polypeptide on inflammatory responses and mRNA expression of tight junction genes in lambs fed a high-grain diet
→ Evaluates exogenous VIP administration effects on inflammation and intestinal barrier function in lambs, demonstrating VIP's impact on gut inflammatory responses and tight junction integrity.
- [8]Domschke S, Domschke W, Bloom SR, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects Gut (1978)
→ Graded IV VIP infusions of 0.6, 1.3, and 3.3 pmol/kg/min in humans raised plasma VIP markedly; plasma half-life ~1 minute.
- [9]Morice AH, et al. Vasoactive intestinal peptide as a bronchodilator in severe asthma Peptides / PubMed (1986)
→ VIP IV infusion at 6 pmol/kg/min produced significant bronchodilation in severe asthma.
- [10]Youssef JG, Lavin P, Schoenfeld DA, et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial Critical Care Medicine (2022)
→ In this sponsor-led Phase 2b/3 trial, IV aviptadil improved the likelihood of recovery from respiratory failure and survival at 60 days versus placebo in critical COVID-19, with mild diarrhea the main adverse event.
- [11]ACTIV-3b/TESICO Study Group Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial Lancet Respiratory Medicine (2023)
→ The independent NIH-funded TESICO trial found no clinical benefit of IV aviptadil versus placebo in COVID-19-associated acute hypoxaemic respiratory failure, contrasting with the sponsor-led study.
VIP
**Vasoactive Intestinal Peptide (VIP)** is a 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily. Originally isolated from porcine small i
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