Vasoactive Intestinal Peptide (VIP)
PeptideThe medical_score (38) is 14 points below the community_score (52), as community users [c1, c2, c3] report subjective improvements in Long COVID and MCAS that have not yet been substantiated for these indications by controlled clinical studies [s11, s12].
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TL;DR
VIP is an endogenous neuropeptide with potent anti-inflammatory and immunomodulatory properties, investigated clinically in ARDS and pulmonary hypertension — but without EU approval. Evidence for off-label use (intranasal, subcutaneous) in Long-COVID, MCAS, or POTS rests on fewer than 30 anecdotal reports with low reproducibility. Hypotension, tachycardia, and dizziness are common side effects requiring blood pressure monitoring with every application. High costs, difficult sourcing, and the absence of controlled data make VIP unsuitable for self-medication.
Description
VIP is an endogenous 28-amino acid neuropeptide with potent anti-inflammatory, vasodilatory, and immunomodulatory effects; investigated clinically in early phases for ARDS and PAH [s5, ...
Vasoactive Intestinal Peptide (VIP) is an endogenous 28-amino acid neuropeptide from the secretin/glucagon family. It is produced by nerve fibers, immune cells, and the enteric nervous system and acts on virtually all organ systems [s5, s7]. VIP binds to G-protein-coupled receptors of the VPAC1 and VPAC2 type, activates adenylyl cyclase, and increases intracellular cAMP concentration [s7, s8]. As an endogenous peptide, VIP regulates smooth muscle (relaxation), vascular tone (vasodilation), intestinal and pancreatic secretion, and circadian rhythms in the suprachiasmatic nucleus [s5, s8]. In the immune system, it inhibits activation of macrophages and T cells, suppresses pro-inflammatory cytokines (TNF-α, IL-6, IL-12), and promotes regulatory T cells [s9, s10]. The synthetic form aviptadil (RLF-100, ZYESAMI) was investigated in Phase 2b/3 studies in critically ill COVID-19 patients with respiratory failure, with the primary endpoint (freedom from respiratory support) achieved in one Phase 2b/3 study [s11]. However, a 2025 systematic review of aviptadil in ARDS found no conclusively established survival benefit [s12]. In the biohacking and Long COVID community, intranasal VIP is used for CIRS (Chronic Inflammatory Response Syndrome), MCAS (Mast Cell Activation Syndrome), and POTS, without controlled human studies supporting these uses [c1, c2]. Neuroprotective effects (protection against β-amyloid toxicity) have been described exclusively in animal models and in vitro experiments [s13, s14].
Legal Status (DE)
{'note_regulatory': 'No EMA EPAR approval found for aviptadil/VIP as a medicinal product in the EU. Official EMA or BfArM documents could not be directly confirmed through the search. Previous sources s3 and s4 (commercial suppliers) remain the only references; an official regulatory source (EMA/BfArM) is still absent. Status: no known EU approval (as of May 2025). ', 'sources_note': 'No official EMA EPAR or BfArM decision found — gap remains open.'}
Mechanism of Action
VIP binds with high affinity to VPAC1 and VPAC2 receptors (G-protein-coupled receptors, Gs-type) on immune cells, smooth muscle cells, epithelial cells, and neurons [s7, s8]. Receptor binding activates adenylyl cyclases, increases intracellular cAMP concentration, and activates protein kinase A (PKA). PKA phosphorylates CREB and other transcription factors, leading to modulation of gene expression [s8]. Immunological: VIP inhibits the release of TNF-α, IL-6, IL-12, and NO by macrophages; it inhibits chemotaxis and activation of T cells and promotes differentiation of regulatory T cells (Treg) [s9, s10]. In models of rheumatoid arthritis, VIP shifts the Th1/Th2/Th17 balance toward anti-inflammatory profiles [s10]. Cardiovascular: VIP is a potent vasodilator in systemic and pulmonary vessels; it lowers arterial blood pressure and compensatorily increases heart rate (dose-dependent) [s5, s15]. Gastrointestinal: VIP relaxes smooth muscle of the stomach, intestine, trachea, and bronchi; stimulates bicarbonate secretion in the intestine, pancreas, and liver; inhibits gastric acid secretion [s5, s8]. Pulmonary: In lung tissue, VIP inhibits bronchoconstriction and reduces pulmonary arterial resistance — rationale for use in PAH and ARDS [s11, s12, s15]. Neuroprotective (preclinical): VIP protects neurons against β-amyloid toxicity and Parkinson-associated neurotoxins in vitro and in animal models [s13, s14]. Clinical translatability has not been established.
Dosing
CIRS / intranasale Anwendung (experimentell, unkontrolliert)
- Dose
- 50 mcg per nostril (100 mcg total)
- Frequency
- 4× täglich
- Route
- intranasal
- Duration
- Wochen bis Monate (keine kontrollierten Daten)
- Timing
- Distributed throughout the day; first dose in the morning
- With food
- optional
Subkutan – experimentelles Titrationsprotokoll
- Dose
- 50–100 mcg s.c. twice daily, titration start
- Frequency
- 2× täglich (morgens und nachmittags)
- Route
- injektion-subkutan
- Duration
- Mindestens 7 Tage Einlaufphase; keine Langzeitdaten
- Timing
- Morning and late afternoon
- With food
- optional
Intravenös – klinische COVID-19/ARDS-Studie
- Dose
- Aviptadil 50–150 mcg/kg i.v. over 12 hours (3 days)
- Frequency
- Einmalzyklus über 3 Tage unter klinischer Überwachung
- Route
- oral
- Duration
- 3 Tage (in-Hospital)
- Timing
- In a clinically monitored setting only
- With food
- optional
No officially established upper limit for extra-medical use; dose-dependent hypotension and tachycardia practically limit the dose [s15, s17]. IV doses >150 mcg/kg have not been systematically investigated in clinical studies [s11].
VIP has a biological half-life of a few minutes in blood [s8]. Intranasal and subcutaneous administration occurs outside any clinical approval. Blood pressure monitoring is strongly recommended with every application [s15, s17]. Not suitable for self-medication.
Calculate reconstitution, plan dosing, look up injection technique
Side Effects
| Side Effect | Frequency | Severity |
|---|---|---|
| Hypotonie (Blutdruckabfall) VIP is a potent systemic vasodilator; dose-dependent blood pressure reduction is the primary pharmacodynamic adverse effect, particularly with IV administration [s11, s15]. | häufig | moderat |
| Kompensatorische Tachykardie As a reflex response to VIP-induced vasodilation, a dose-dependent increase in heart rate occurs [s15, s17]. | häufig | moderat |
| Flush (Hautrötung, Wärmegefühl) Vasodilation of peripheral vessels leads to flush symptoms, particularly with IV and s.c. administration [s15, s17]. | häufig | leicht |
| Diarrhö / gastrointestinale Hypermotilität VIP stimulates intestinal secretion and relaxes intestinal smooth muscle; diarrhea and cramps may occur at higher doses [s5, s8]. | gelegentlich | leicht |
| Schwindel / Synkope Consequence of hypotension; increased risk particularly in autonomic dysfunction (POTS) [s15, s17]. | gelegentlich | moderat |
| Nasale Reizung / Brennen (intranasal) Local irritation from intranasal formulation reported in community experience reports [c1, c2]. | gelegentlich | leicht |
| Anaphylaktische Reaktion As a peptide with potential immunogenicity, an anaphylactic reaction is theoretically possible; individual case reports from clinical studies cannot be excluded [s11, s12]. | selten | schwer |
Contraindications
VIP is a potent vasodilator; in the presence of existing low blood pressure or shock, there is a risk of life-threatening hemodynamic deterioration [s15, s17].
Vasodilation can severely worsen orthostatic instability in POTS patients; use only under medical supervision [s15, s17].
No safety data for pregnancy and lactation; VIP influences uterine contractility and vascular tone [s5].
Anaphylaxis potential in cases of peptide hypersensitivity [s11].
Additive blood pressure reduction in combination with antihypertensives; increased risk of hypotension and syncope [s15].
Interactions
Synergistic
BPC-157 can synergistically enhance VIP-mediated vasodilation and cytoprotective effects in the gastrointestinal tract, as both compounds activate NO-dependent and angiogenic signaling pathways. An additive promotion of tissue healing and anti-inflammatory effects is mechanistically plausible.
VIP modulates hypothalamic GnRH secretion and can synergistically support Kisspeptin-10-induced activation of GnRH neurons, as both peptides activate converging signaling pathways in the reproductive regulatory circuit. This may result in enhanced LH/FSH release.
VIP stimulates GnRH release in the hypothalamus, potentially potentiating the effect of exogenously administered gonadorelin on gonadotropin secretion, which may result in enhanced LH and FSH release from the pituitary. This additive activation of the HPG axis is mechanistically plausible.
VIP acts as an endogenous anti-inflammatory neuropeptide that modulates similar anti-inflammatory signaling pathways as curcumin. Combined use could enhance the reduction of pro-inflammatory cytokines (e.g., TNF-α, IL-6). The combination is theoretically plausible but not directly supported by clinical evidence.
Both VIP and KPV possess gut-protective and anti-inflammatory properties in the gastrointestinal tract. A combination may act additively in inflammatory bowel diseases. Available data are predominantly from preclinical studies.
Caution
DHEA is peripherally metabolized to estrogens and androgens, which can influence VIP receptor expression (VPAC1/VPAC2) and VIP synthesis, potentially leading to unpredictable shifts in neuroendocrine and immunological VIP signaling. Mutual modulation of hormonal axes warrants caution, particularly in hormone-sensitive conditions.
Studies
Tier A — High Evidence
Tier B — Moderate Evidence
Community Evidence
Top reported benefits
- Subjective reduction of MCAS symptoms following intranasal VIP (individual case reports)
- Improvement of Long COVID fatigue reported in individual cases
- Occasional reports of improved respiratory symptoms
Top reported issues
- Flushing and dizziness frequently reported after use
- Hypotension and palpitations documented as side effects
- Lack of effect in multiple users
- High costs and difficult procurement
The total number of identifiable VIP-specific user reports is low (fewer than 30 distinct posts on VIP self-administration). VIP has minimal presence in German biohacker forums. Community data should be classified as unreliable and non-representative. Some users report using VIP in the context of the Shoemaker CIRS protocol, which itself is not supported by RCTs [c1, c2, c3].
Scientific Sources
- Inhaled and Intravenous Aviptadil versus Placebo for Acute Hypoxaemic Respiratory Failure due to COVID-19 (ACTIV-3b/TESICO): A Randomised Controlled Trial
Brown SM, Barkauskas C, Engstrom A, et al. (2023). The Lancet Respiratory MedicineADOI - Vasoactive Intestinal Peptide (VIP) FDA Review – ISEAI Compounding Access Alert
Allen L, ISEAI Board (2023). ISEAI (International Society for Environmentally Acquired Illness)BLink - The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis
Talbot J, Bhatt DL, Gonzalez-Rey E, et al. (2018). Frontiers in Immunology (PMC6092975)BLink - NeuroRx Announces ZYESAMI (aviptadil, RLF-100) Met the Primary Endpoint of Its Phase 2b/3 Clinical Trial
NeuroRx Inc. (2021). PR Newswire / NeuroRx Press ReleaseBLink - Aviptadil Therapy in Acute Respiratory Distress Syndrome Patients: A Systematic Review and Meta-analysis
PMC Authors (2025). PMC12683555ALink - Mapping the active site in vasoactive intestinal peptide to a core of four amino acids: Neuroprotective drug design
Gozes I, Divinski I, Pilzer I, et al. (2003). PNAS (PMC22434)CLink - Vasoactive intestinal peptide (VIP) prevents neurotoxicity in neuronal cultures: relevance to neuroprotection in Parkinson's disease
Offen D, Sherki Y, Melamed E, et al. (2000). Brain ResearchCLink - VIP Dosage Guide: Vasoactive Intestinal Peptide – Intranasal, SubQ & IV Protocols
PeptideWiki Editorial (2024). PeptideWikiCLink - Effect of Aviptadil, a Novel Therapy, on Clinical Outcomes of Patients with Viral-related Severe ARDS: A Retrospective Observational Study
PMC Authors (2024). PMC10949283BLink - VIP Dosage Protocol Guide – Precision Peptide Titration
Real Peptides Editorial (2024). Real PeptidesCLink - Vasoactive Intestinal Peptide – Wikipedia (English)
Wikipedia contributors (2024). WikipediaDLink - Vasoactive Intestinal Peptide (VIP) – Regulatory Status Overview
Cenexa Labs Editorial (2024). Cenexa Research LibraryCLink - Vasoactive Intestinal Peptide (VIP): Mechanism, Evidence, and Clinical Research
PeptideFox Editorial (2024). PeptideFoxCLink - Vasoaktives intestinales Peptid – Wikipedia (Deutsch)
Wikipedia-Autoren (2024). Wikipedia DEDLink - Vasoactive intestinal peptide as a new drug for treatment of pulmonary arterial hypertension
Said SI, Hamidi SA, Dickman K, et al. (2003). PMC / American Journal of PhysiologyBLink - Vasoaktives intestinales Peptid – DocCheck Flexikon
DocCheck Redaktion (2023). DocCheck FlexikonCLink - Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions
Delgado M, Ganea D (2013). PMC (Advances in Neuroimmunology / Amino Acids)BLink - Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its therapeutic potential in inflammatory disease
Gonzalez-Rey E, Chorny A, Delgado M (2007). PubMed / Current Pharmaceutical DesignBPMID:19604262
Community Sources
Storage
Unopened
Store lyophilized VIP powder at −20 °C, protected from light and moisture; shelf life per manufacturer specifications (typically 2 years).
Opened
Store reconstituted solution at 4 °C for a maximum of 24–48 hours; do not refreeze. Use intranasal formulations according to manufacturer instructions.
Notes
VIP has a very short biological half-life in blood (a few minutes) [s8]. Cold chain must be maintained during transport. No data on stability in compounded formulations available from independent sources.