Healing & Repair

VIP (Vasoactive Intestinal Peptide)

Evidence

What is VIP?

VIP stands for vasoactive intestinal peptide, historically also called vasoactive intestinal polypeptide. It is a naturally occurring 28-amino-acid neuropeptide found throughout the nervous system, gastrointestinal tract, lungs and other tissues.

Human sequence: HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH₂

The FDA substance record identifies aviptadil as the synthetic human VIP peptide and lists the same 28-residue amidated sequence. FDA also states that having an FDA UNII substance record does not mean a substance is FDA approved.

VIP has broad biological effects involving:

• vascular tone
• pulmonary blood vessels
• airway smooth muscle
• gastrointestinal secretion
• neuronal signaling
• circadian biology
• immune-cell signaling
• inflammatory signaling
• epithelial biology

It acts primarily through the VPAC1 and VPAC2 receptors. VIP has real human evidence, but that evidence depends heavily on the exact route, formulation, indication and dose.

What is aviptadil?

Aviptadil is synthetic human VIP. Its identity relationship is cleaner than for many peptides: unlike TB-500 versus full-length thymosin beta-4, or GHK-Cu versus AHK-Cu, aviptadil is intended to reproduce the human 28-amino-acid VIP sequence. The FDA substance database recognizes aviptadil as an ingredient substance corresponding to human VIP.

Identity does not solve the route problem

These are very different clinical exposures:

• continuous IV aviptadil
• inhaled or nebulized aviptadil
• intranasal VIP spray
• intracavernosal aviptadil plus phentolamine
• community subcutaneous (SC) VIP
• modified or extended-duration VIP analogues

Containing or deriving from the same 28-amino-acid peptide does not make their doses interchangeable.

Evidence by route

Intravenous VIP / aviptadil. Real human pharmacology and randomized clinical-trial evidence exists, including classic pharmacokinetic studies, physiologic infusion research, acute respiratory-distress programs and randomized COVID-19 trials.

Inhaled / nebulized VIP / aviptadil. Real human evidence exists in pulmonary hypertension, sarcoidosis, COVID-19 pneumonia and other pulmonary conditions. The findings are route and disease specific.

Intranasal VIP. Human evidence exists but is much weaker. The best-known literature is a small 20-patient open-label CIRS-WDB clinic study, not a large randomized intranasal development program.

Subcutaneous VIP. This is the major evidence gap. Community sites publish SC protocols of roughly 50-200 mcg per administration, but no completed human SC dose-finding program has established the optimal dose, frequency, pharmacokinetics, clinical benefit, maximum dose or long-term safety of ordinary unmodified SC VIP.

IV, inhaled, intranasal and intracavernosal human evidence cannot be converted into a subcutaneous wellness protocol.

How well studied is VIP / aviptadil?

Overall evidence strength: meaningful human evidence exists, but it is highly route- and indication-specific. VIP has real human research, yet it has no clinically validated general immune, CIRS or wellness SC protocol.

Areas with human evidence

• Pulmonary vascular effects: small human studies show that inhaled VIP can acutely alter pulmonary vascular resistance and pulmonary arterial pressure.
• Pulmonary hypertension: small pilot research reported improvements in pulmonary hemodynamics and exercise capacity with inhaled VIP.
• Sarcoidosis: a small open-label study showed measurable immunologic changes in the lungs after inhaled VIP.
• COVID-19 pneumonia: randomized human research exists by both IV and inhaled routes, with results that differ substantially by study and route.
• Erectile dysfunction: aviptadil has an authorized regional pharmaceutical use when combined with phentolamine and injected intracavernosally.

What is not established

VIP / aviptadil has not been clinically established as a general SC treatment for:

• chronic inflammation
• "immune balancing"
• autoimmune disease
• CIRS
• mold illness
• fatigue
• brain fog
• circadian optimization
• gut healing
• anti-aging
• athletic recovery
• general respiratory support
• neuroprotection
• infection prevention
• longevity

Controlled human research has also not established that 50 mcg, 100 mcg or 200 mcg SC produces predictable systemic clinical benefits.

Pulmonary hypertension

2003 primary pulmonary hypertension pilot. Eight patients with severe primary pulmonary hypertension were studied. A single 100 mcg inhaled VIP dose reduced mean pulmonary arterial pressure by about 10 mmHg and improved cardiac output. Patients then received 200 mcg/day inhaled VIP in four divided inhalations. After about 12 weeks the investigators reported:

• lower pulmonary arterial pressure
• increased cardiac output
• substantially lower pulmonary vascular resistance
• improved six-minute walk distance, by about 113 meters at 12 weeks, which remained substantial at longer follow-up

Limitations: only eight patients, uncontrolled, not blinded, conducted in an older pulmonary-hypertension treatment era, and not an SC trial. This is a strong physiologic signal in a tiny uncontrolled inhaled human study. It does not prove that VIP is an established PAH treatment.

2008 pulmonary-hypertension study. Twenty patients with different forms of pulmonary hypertension each inhaled 100 mcg aviptadil once during right-heart catheterization. The study found a small, temporary but statistically significant selective pulmonary vasodilator effect. Only 6 of 20 patients showed a greater than 20% reduction in pulmonary vascular resistance.

This later result is more modest than the 2003 pilot. Inhaled VIP has shown acute pulmonary vasodilatory activity in humans, with larger clinical signals in a very small early pilot and more modest acute effects in later pulmonary-hypertension research. The literature does not show that VIP reliably produces major pulmonary improvement.

Sarcoidosis

A 2010 open-label Phase II study treated 20 patients with histologically confirmed active sarcoidosis using nebulized VIP, 50 mcg four times daily for 28 days. The investigators reported:

• reduced spontaneous TNF-alpha production by bronchoalveolar cells
• increased regulatory T-cell activity
• altered macrophage activation markers
• improvement in cough or dyspnea reported by many participants
• no major severe safety signal

This is real human evidence that inhaled VIP can alter pulmonary immune-cell behavior. It does not establish that VIP treats autoimmune disease broadly, "resets immune tolerance", treats CIRS, should be injected SC, should be used indefinitely or prevents inflammatory disease.

Evidence classification: small open-label, route-specific human immunologic study.

VIP is more than an "immune tolerance peptide"

Some community material claims the name "vasoactive intestinal peptide" is misleading and that VIP is "really" an immune-tolerance orchestrator. That framing is too strong. VIP has important immunomodulatory effects, and it also:

• dilates blood vessels
• alters pulmonary vascular tone
• relaxes smooth muscle
• stimulates intestinal secretion
• affects cardiac physiology
• acts in the nervous system
• contributes to circadian signaling

VIP is a pleiotropic neuropeptide with important vascular, gastrointestinal, pulmonary, neuronal, circadian and immune functions. No single function is its one "real" biological purpose.

COVID-19 evidence

Online summaries often cite only one trial. The full picture includes three studies.

2022 randomized IV aviptadil trial. A multicenter trial enrolled 196 patients with critical COVID-19 respiratory failure, randomized about 2:1 to aviptadil or placebo. Aviptadil was given over three days as escalating 12-hour IV infusions of 50, 100 and 150 pmol/kg/hour. The primary endpoint, alive and free from respiratory failure at day 60, did not reach statistical significance. The authors reported favorable secondary signals in 60-day survival, respiratory-distress measures and IL-6 changes, including a survival advantage in secondary analysis. This is mixed randomized evidence: encouraging secondary signals, with the primary endpoint not met.

2023 NIH TESICO trial. The modified intention-to-treat aviptadil comparison included 461 participants (231 aviptadil, 230 placebo). By day 90, 38% of aviptadil participants had died versus 36% on placebo (hazard ratio 1.04, 95% CI 0.77-1.41, p=0.78). The investigators concluded that IV aviptadil did not significantly improve clinical outcomes through day 90. The prespecified early composite safety outcome occurred in 63% of aviptadil participants versus 56% on placebo, a difference that was not statistically significant (OR 1.40, 95% CI 0.94-2.08, p=0.10). The largest randomized IV evidence is negative for overall clinical efficacy.

Was TESICO a "route failure"? Some community pages argue the result should be dismissed because VIP's half-life is too short and IV was the wrong route. That is an interpretation, not an established finding. The IV protocol used long continuous infusions specifically because VIP is cleared rapidly; it did not give one IV bolus and let it disappear. The result may prompt fair research questions about route, pulmonary targeting and timing, but it was a properly controlled IV study using prolonged infusions designed around VIP pharmacology.

2025 randomized inhaled aviptadil study. A multicenter, randomized, double-blind, placebo-controlled study evaluated inhaled aviptadil in 80 hospitalized COVID-19 patients across nine centers. Average time to discharge was 7.8 ± 4.0 days with aviptadil versus 10 ± 5.0 days with placebo (p=0.049). The investigators also reported better day-7 dyspnea scores, greater improvement in CT lung-damage score at day 28, and no treatment dropout because of adverse effects. The death rate was 5.1% with aviptadil versus 12.2% with placebo, but the study was too small for that difference alone to establish a mortality benefit.

This is a positive randomized inhaled signal in a modest-sized study. It does not prove that inhaled VIP works for ARDS generally, that inhalation is superior to IV, that nasal spray is equivalent to nebulization, that SC VIP works, or that VIP treats chronic pulmonary disease broadly.

Inhaled versus IV. The large randomized IV trial was negative overall; the smaller randomized inhaled trial showed a positive recovery and radiographic signal. These trials differed in population, disease stage, formulation, route, size, endpoints and study period. Inhaled administration has encouraging route-specific evidence, but no head-to-head trial shows inhaled or intranasal VIP to be clinically superior to IV aviptadil.

Intranasal VIP and CIRS

Much of the nasal-spray community protocol comes from a 2013 open-label study of 20 patients described as having refractory chronic inflammatory response syndrome associated with water-damaged buildings (CIRS-WDB), with no randomized placebo group. Participants self-administered 50 mcg VIP by nasal aerosol four times daily initially. Treatment continued for at least 18 months, with later individual titration down and back up according to symptoms.

The investigators reported improvements in symptom counts, quality of life, C4a, TGF-beta1, MMP-9, VEGF, sex-hormone measures, vitamin D, exercise pulmonary artery pressure and regulatory T cells.

Limitations:

• only 20 participants
• no placebo group
• no blinding
• a highly selected refractory clinic cohort
• multiple prior sequential treatments
• historical comparisons
• extensive protocol-specific diagnostic assumptions
• investigators directly involved in the treatment model

Evidence classification: small uncontrolled clinic-derived intranasal human study. It is neither randomized Phase 2 proof of intranasal VIP nor validation of CIRS as a general VIP indication.

The study's 50 mcg four-times-daily nasal regimen was one clinic protocol. It does not establish that 50 mcg is optimal, that four sprays a day is optimal, that eight sprays is better, that nasal VIP should be used indefinitely, or that the protocol applies to other inflammatory conditions. Certainty of generalizable efficacy is very low.

CIRS and sarcoidosis are different evidence categories

The two should not be presented as equal-strength Phase II evidence.

Expected results timeline

Six evidence categories to keep separate

The same peptide has been studied across many routes, which makes evidence mixing tempting.

1. Human IV VIP / aviptadil: real pharmacology and randomized clinical evidence, including a large negative COVID trial.
2. Human inhaled / nebulized VIP: real pulmonary human evidence in pulmonary hypertension, sarcoidosis and COVID pneumonia.
3. Intranasal VIP: small clinic-derived human evidence. The CIRS literature is weaker than the pulmonary randomized evidence.
4. Intracavernosal aviptadil combination: authorized regional drug-product evidence for aviptadil plus phentolamine, specific to that route and combination.
5. Community SC VIP: where the 50 mcg, 100 mcg and 200 mcg once-daily, twice-daily and five-days-weekly protocols sit. These are not validated human SC regimens.
6. Mechanistic / preclinical VIP: a large literature on immune signaling, pulmonary protection, circadian biology, neurobiology and autoimmune models. It supports biological plausibility but does not establish a wellness protocol.

Research at a glance

Evidence strength

Overall rating: meaningful human evidence with major route- and indication-specific limitations.

Stronger evidence for:

• VIP physiology
• human vascular effects
• very rapid human IV clearance
• pulmonary vasodilation
• systemic intestinal effects
• VPAC receptor biology
• inhaled pulmonary activity
• short-term IV human exposure

Limited human evidence for:

• pulmonary hypertension
• sarcoidosis
• inhaled COVID recovery
• intranasal CIRS

Weak or unestablished evidence for:

• SC immune therapy
• SC CIRS treatment
• SC circadian optimization
• 50-200 mcg SC dosing
• twice-daily superiority
• morning-timing superiority
• long-term SC use
• receptor cycling
• generic autoimmune treatment
• generalized "immune tolerance reset"

Community claims checked

Protocol logic check

Bottom line

VIP / aviptadil has substantially more legitimate human research than many compounds sold through peptide communities. VIP is an endogenous 28-amino-acid human neuropeptide and aviptadil is its synthetic pharmaceutical form. The main complication is route.

Researchers have given VIP intravenously, by nebulized inhalation, by nasal aerosol and directly into erectile tissue, and each route produces a different clinical exposure. A tiny 2003 pulmonary-hypertension pilot produced striking hemodynamic and exercise signals; a later 20-patient study confirmed acute selective pulmonary vasodilation with a more modest effect; a 20-patient sarcoidosis study showed pulmonary immune-cell changes after four weeks of inhaled VIP. These findings show that VIP is biologically active in humans. They do not establish a generalized SC protocol.

The COVID literature is mixed. The 196-patient IV trial missed its primary endpoint but reported favorable secondary findings. The larger NIH TESICO trial (461 participants, day-90 mortality about 38% with aviptadil versus 36% with placebo) found no significant improvement in clinical outcomes, and it used prolonged 12-hour infusions precisely because VIP is cleared so quickly. A later 80-patient inhaled trial was associated with shorter time to discharge and favorable day-7 dyspnea and day-28 CT findings. Route-specific evidence is mixed and still developing.

The intranasal CIRS protocol (50 mcg four times daily, followed for at least 18 months in 20 patients) is real, but the study was open-label, uncontrolled, highly selected and embedded in a larger clinic-specific sequential treatment framework. The lipase finding was one transient elevation without abdominal pain that resolved without stopping VIP, with no overall cohort increase.

Classic human IV research found VIP disappears from plasma with an average half-time of about one minute. That number does not provide a human SC half-life, so the argument "VIP lasts one minute, so inject it twice daily" does not follow.

VIP / aviptadil is a biologically well-characterized human neuropeptide with meaningful route-specific clinical research. Its strongest evidence comes from controlled or direct human IV and inhaled studies. Intranasal CIRS evidence exists but is small and uncontrolled. A general 50-200 mcg SC wellness or immune protocol has not been clinically validated, and the very short IV plasma half-life cannot be used to set an SC frequency without human SC pharmacokinetic data.

Dosing evidence

Route warning: IV, inhaled, intranasal, intracavernosal and SC VIP are not interchangeable dosing systems. A dose studied by one route should not be copied into another route because the peptide identity is the same.

Dose at a glance

FDA-approved standalone VIP dose

None. There is no FDA-approved standalone VIP / aviptadil drug with a general U.S. prescribing schedule. FDA's May 14, 2026 503A list places vasoactive intestinal peptide in Category 1: Bulk Drug Substances Under Evaluation. Category 1 does not mean FDA approved, proven safe, proven effective, or approved for SC use, CIRS or wellness.

Human SC protocol: not established

No completed human SC dose-finding program has established a starting dose, therapeutic dose, maximum dose, once-daily schedule, twice-daily schedule, maintenance schedule or clinical cycle for unmodified VIP. The clinically validated SC dose is: none.

Community SC protocols

Community protocol pages describe the following. These are not FDA-approved SC dosing schedules and have not been validated in human trials; both sources below acknowledge this.

• PeptideFox: about 50-200 mcg SC with morning-timed protocols, and about 50-100 mcg intranasal.
• Peptide Dosing Protocols: 50 mcg once daily; 100 mcg one to two times daily; 200 mcg one to two times daily; or 200 mcg five times weekly, depending on the protocol tier. A separate nasal protocol follows the CIRS clinic model.

Community protocol-page range: about 50-200 mcg per SC administration, with frequencies ranging from once daily to twice daily to five days weekly.

Human inhaled study doses

These are legitimate study doses. They are not SC dose recommendations.

• Pulmonary hypertension, 2003: acute test 100 mcg inhaled VIP; chronic treatment 200 mcg/day divided across four inhalations. Eight patients.
• Pulmonary hypertension, 2008: 100 mcg inhaled aviptadil once during invasive hemodynamic assessment. Twenty patients.
• Sarcoidosis, 2010: 50 mcg inhaled four times daily (200 mcg/day) for 28 days in 20 patients with active sarcoidosis.
• Inhaled COVID study protocol: one randomized European program studied 67 mcg inhaled three times daily for 10 days or until discharge.

Human IV study doses

Classic human physiology: VIP has been given by continuous IV infusion to healthy humans at graded pmol/kg/min rates. The classic 1978 pharmacokinetic study involved only four healthy subjects and found very rapid disappearance after the infusion stopped.

COVID-19 Phase 2b/3 program: the 196-patient randomized study used three successive 12-hour infusions: day 1 at 50 pmol/kg/hour, day 2 at 100 pmol/kg/hour, day 3 at 150 pmol/kg/hour. These were ICU continuous-infusion protocols. They do not support converting 50 pmol/kg/hour IV into 50 mcg SC or any other route.

Intracavernosal product dose (Invicorp)

Aviptadil is part of an authorized intracavernosal erectile-dysfunction combination in some European jurisdictions: 25 mcg aviptadil with 2 mg phentolamine per intracavernosal administration. The BNF lists a maximum frequency of once daily and three times weekly. This is real clinical product dosing, but intracavernosal aviptadil plus phentolamine is not standalone systemic VIP. It does not validate standalone VIP injection, SC VIP, nasal VIP, IV wellness use, immune protocols or CIRS protocols.

Frequency and timing

Duration and cycles

Duration in human research has varied widely by indication: one inhaled dose; four weeks of inhaled therapy; about 12 weeks in pulmonary-hypertension research; three days of IV ICU treatment; ten days of inhaled COVID treatment; 18 months or longer in the small CIRS nasal study. There is no universal VIP cycle.

Community sources often describe continuous use, and some discuss 4, 8 or 12 weeks or ongoing maintenance. A human SC cycle has not been established.

Receptor reset: no evidence. VIP acts mainly through VPAC receptors, but there is no validated receptor-reset cycle, weekend break, 5-on / 2-off requirement, washout period or resensitization schedule.

Mechanism

VPAC1 and VPAC2

The principal VIP receptors are VPAC1 and VPAC2, class B G-protein-coupled receptors. Both can activate adenylyl cyclase and raise cAMP, with downstream signaling that varies by cell type. Receptor expression differs among blood vessels, airway tissue, gastrointestinal tissue, immune cells, the central nervous system and endocrine tissues. VIP has no single "immune receptor": it sends similar molecular signals into very different tissues, with effects that depend on where the receptor is located.

PAC1 is primarily a receptor for PACAP. VIP can interact with PAC-family signaling under some circumstances, but VPAC1, VPAC2 and PAC1 are not three equivalent primary VIP receptors. The primary VIP receptors are VPAC1 and VPAC2.

Vascular effects

VIP is a potent vasodilator. Classic human infusion studies showed effects on vascular tone, blood pressure, heart rate and circulation. This is why systemic exposure can produce flushing, reduced blood pressure, reflex increases in heart rate and lightheadedness.

Pulmonary effects

VIP can influence pulmonary vascular resistance, airway smooth muscle, epithelial signaling, surfactant-related biology and pulmonary immune cells. Human pulmonary-hypertension research confirms that at least some pulmonary vascular effects occur in living humans.

Gastrointestinal effects

VIP stimulates intestinal fluid and electrolyte secretion. Excess endogenous VIP is classically associated with severe watery diarrhea, which is consistent with the diarrhea seen during systemic VIP administration. Its gastrointestinal actions are substantial.

Immune effects

VIP can influence macrophages, dendritic cells, T cells, regulatory T-cell biology and inflammatory cytokine production. The sarcoidosis study provides direct human evidence of pulmonary immune-cell changes. Broader claims about autoimmune disease treatment, infection tolerance or an "immune reset" are still largely extrapolated from preclinical immunology.

Circadian biology

VIP plays an important role in neuronal communication within the suprachiasmatic nucleus and in circadian-network synchronization. That supports a mechanistic link with circadian biology, but it does not establish an exogenous "morning VIP optimization protocol" for humans.

Human pharmacokinetics

Plasma half-life: VIP is very short-lived in human plasma. The classic 1978 healthy-volunteer IV study reported first-order disappearance after the infusion ended, with an average disappearance half-time of about 1 minute. The accurate statement is: human IV plasma disappearance half-time of about one minute in a small classic infusion study. It is not a half-life that applies to every route.

A plasma half-life measured after IV infusion does not describe absorption from nasal mucosa, SC absorption rate, tissue residence, pulmonary deposition, local receptor exposure or the duration of downstream signaling. The one-minute figure does not mean "inject every hour" or that twice-daily SC dosing is scientifically required.

Human SC half-life: not established. No dedicated human SC pharmacokinetic study of ordinary unmodified VIP has established absorption half-life, Tmax, Cmax, bioavailability or elimination profile. The IV one-minute number cannot serve as an SC dosing interval.

Does SC VIP make pharmacokinetic sense? SC absorption could create a different exposure curve than IV dosing, but that has to be measured. No controlled human SC PK program shows that 50, 100 or 200 mcg produces therapeutically meaningful systemic exposure. SC is a pharmacologically plausible route that is clinically inadequately characterized.

Contraindications

Formal contraindications

There is no FDA-approved standalone VIP label, so there is no official universal contraindication list. The cautions below are mechanism-based or trial-specific and are not official labeling.

The authorized aviptadil/phentolamine intracavernosal product (Invicorp) has its own indication, contraindications, injection-specific risks and dosing restrictions. Those rules apply to that combination product and do not carry over automatically to nasal or SC standalone VIP.

Low blood pressure and other vasodilators

Because VIP is a potent vasodilator, extra caution is biologically reasonable in people with low baseline blood pressure, people taking medications that substantially lower blood pressure, and people using other strong vasodilators. This is a mechanism-based caution; specific interactions and magnitudes depend on product and route.

Severe diarrheal illness

The TESICO protocol excluded severe diarrhea because VIP itself can worsen intestinal secretion, a trial-specific decision consistent with known physiology. Existing significant diarrhea is a practical caution for systemic use; it is not an FDA-labeled universal contraindication.

Pregnancy and breastfeeding

No standalone VIP safety program establishes safety for elective systemic or wellness use during pregnancy or breastfeeding. Safety is insufficiently established.

Children and adolescents

There is no established pediatric wellness or SC protocol. Dose and safety are not established.

Cancer and tumor biology

VIP receptors are expressed in many tissues, and experimental VIP biology can influence cell signaling, angiogenesis, immune regulation and growth-related pathways. That raises mechanistic questions in active malignancy. There is no human clinical evidence that ordinary exogenous VIP causes cancer or accelerates all tumors. This is a theoretical, disease-specific caution and not a formal universal contraindication.

Side effects

IV and systemic effects

Known physiologic and clinical concerns include:

• hypotension
• flushing
• tachycardia
• diarrhea
• fluid and electrolyte consequences if diarrhea is severe

These are consistent with VIP's established human vascular and intestinal pharmacology.

Hypotension: systemic VIP can lower blood pressure. This has been seen in classic healthy-volunteer infusion research, ARDS programs and ICU aviptadil programs. It is an established pharmacologic effect whose degree depends on infusion rate, clinical status, route and concurrent medications.

Tachycardia: heart-rate increases can occur secondary to systemic vasodilation and hemodynamic changes. Known systemic pharmacologic effect.

Diarrhea: VIP stimulates intestinal secretion, and higher systemic exposure can produce watery diarrhea. The NIH TESICO protocol identified hypotension and diarrhea as the primary treatment-intolerance concerns during aviptadil infusion.

Flushing: facial or generalized flushing can occur because of cutaneous vasodilation. Known pharmacologic effect.

Intranasal safety

The small CIRS study reported good overall tolerability during long-term use, but a 20-person uncontrolled study cannot establish the incidence of uncommon or serious adverse effects. Possible route-specific effects include local nasal irritation, congestion and transient systemic vasodilatory symptoms. Actual incidence is not well defined.

SC safety

Not adequately characterized. Community reports and mechanistic expectations include flushing, dizziness, injection-site effects, diarrhea and headache, but there is no human SC adverse-event database that allows reliable incidence estimates.

Lipase and the pancreatitis claim

Some community protocol pages state that pancreatitis is VIP's main documented safety risk and that lipase monitoring is universally mandatory. The 2013 CIRS study did monitor lipase, and it reported that:

• lipase did not rise across the cohort
• one patient had a transient rise in lipase
• that patient had no abdominal pain
• the elevation resolved without stopping VIP

Lipase monitoring has been part of some intranasal CIRS protocols. The study does not establish that pancreatitis is VIP's principal toxicity, that VIP commonly causes pancreatitis, that lipase monitoring is an evidence-based requirement across all routes, or that an isolated high lipase result equals pancreatitis.

Compatibility

Commonly paired with

No controlled combination study shows synergy for any of these pairings, so they are listed as commonly paired, not synergistic.

• BPC-157: community sources sometimes pair it with VIP for gut-related goals, inflammatory goals and recovery. Community combination; no controlled human trial establishes VIP plus BPC-157 synergy.
• Selank: PeptideFox suggests Selank as a complementary autonomic and circadian pairing. Community and mechanistic combination; no controlled human VIP plus Selank protocol shows superior efficacy.
• KPV: may appear in immune or inflammation-focused stacks. Community combination with no controlled human protocol.
• Thymosin alpha-1: both have immune-related research but act through very different pathways. No validated "immune stack" dose exists.
• NAD+, glutathione and other wellness compounds: may appear alongside VIP in clinic or community protocols. Concurrent use does not establish pharmacologic synergy.

Same-vial and same-syringe compatibility

Being used in the same protocol does not show that two peptides are chemically compatible, physically compatible, stable at the same pH, protected from degradation or safe to combine in one vial. Compatibility requires evidence for the exact formulation.

Storage

Formulation and stability

VIP is a relatively fragile, rapidly degraded 28-amino-acid peptide, which makes stability an important problem. There is no FDA-approved standalone injectable VIP product that provides one validated vial concentration, diluent, pH, reconstitution method, refrigerated lifetime, 14-day rule or 28-day rule. There is no basis for saying all VIP lasts 28 days after reconstitution; stability depends on the exact formulation.

Nasal spray is not a reconstituted SC vial

A pharmacy-prepared nasal formulation can differ in concentration, excipients, pH, sterility requirements, container, spray volume and preservative system. A 50 mcg nasal aerosol dose cannot be converted into 50 mcg SC because the numerical mass is the same.

Regulatory status

U.S. FDA approval

Standalone VIP / aviptadil drug: not FDA approved. FDA's orphan-drug database lists aviptadil as designated for sarcoidosis and shows it as not FDA approved for the orphan indication. An orphan designation is not drug approval.

FDA 503A status

As of FDA's May 14, 2026 update, vasoactive intestinal peptide is listed under Category 1: Bulk Drug Substances Under Evaluation. This means FDA is evaluating the nominated bulk substance within the 503A compounding framework. It does not mean FDA approval, an FDA-approved SC dose, an FDA-approved CIRS indication, or FDA-established efficacy or safety.

FDA substance identity record

FDA has a validated aviptadil substance identity record, UNII A67JUW790C, with the human VIP sequence. FDA states that UNII availability does not imply regulatory review or approval. The record confirms molecular identity, not approval status.

Orphan designations

FDA has granted aviptadil orphan-drug designation for certain investigational indications, including sarcoidosis, and its database distinguishes designation from approval. There is no FDA-approved aviptadil orphan drug.

The EMA records a European orphan designation for aviptadil in sarcoidosis and explains that orphan designation is not a marketing authorization: quality, safety and efficacy must still be demonstrated before approval.

Invicorp regional approval

Separate from standalone aviptadil development, aviptadil is used in the authorized combination aviptadil plus phentolamine for erectile dysfunction in some European jurisdictions, given by intracavernosal injection.

Sources

1. U.S. Food and Drug Administration. Global Substance Registration System: aviptadil (UNII A67JUW790C). precision.fda.gov/uniisearch/srs/unii/a67juw790c
2. U.S. Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A: categories list, updated May 14, 2026. fda.gov/media/94155/download
3. U.S. Food and Drug Administration. Orphan drug designations and approvals: aviptadil (sarcoidosis). accessdata.fda.gov orphan designation record
4. European Medicines Agency. EU/3/07/473: orphan designation of aviptadil for the treatment of sarcoidosis. ema.europa.eu orphan designation EU/3/07/473
5. British National Formulary (NICE). Aviptadil with phentolamine mesilate. bnf.nice.org.uk/drugs/aviptadil-with-phentolamine-mesilate
6. Classic human VIP infusion pharmacokinetic study in healthy subjects, 1978. PubMed Central. pmc.ncbi.nlm.nih.gov/articles/PMC1412244
7. Petkov V, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003. jci.org/articles/view/17500
8. Leuchte HH, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-94. PubMed 18978135
9. Prasse A, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med. 2010;182(4):540-8. PubMed 20442436
10. Boesing M, et al. Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial. Trials. 2022;23(1):790. PubMed 36127739
11. ClinicalTrials.gov. NCT04311697: intravenous aviptadil for critical COVID-19 with respiratory failure. clinicaltrials.gov/study/NCT04311697
12. Youssef JG, 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. Crit Care Med. 2022;50(11):1545-1554. PubMed 36044317
13. Brown SM, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023;11(9):791-803. PubMed 37348524
14. Esendagli D, et al. Inhaled aviptadil is a new hope for recovery of lung damage due to COVID-19. Med Princ Pract. 2025;34(2):191-200. PubMed 39870064
15. Shoemaker RC, et al. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health. 2013. scirp.org full text
16. PeptideFox. Vasoactive intestinal peptide (community protocol page). peptidefox.com/content/vasoactive-intestinal-peptide
17. Peptide Dosing Protocols. VIP community protocol page.