Sometimes the body doesn’t just get inflamed — it forgets how to turn inflammation off. That’s the premise behind vasoactive intestinal peptide, or VIP, a naturally occurring neuropeptide that regulates immune tone, vascular flow, and circadian rhythm. As a nasal spray, VIP is being explored as a precision modulator for chronic inflammatory and environmental illness — from mold exposure to autonomic dysfunction. It’s not a stimulant. It’s a reset signal for systems stuck in survival mode.
What Is VIP Nasal Spray?
VIP (vasoactive intestinal peptide) is a 28–amino acid peptide produced in the gut, brain, and immune cells. It binds to VPAC1 and VPAC2 receptors found throughout the body — in the lungs, heart, hypothalamus, and immune system — orchestrating anti-inflammatory and vasodilatory effects. Intranasal delivery brings the peptide directly into circulation and central signaling pathways, bypassing digestive breakdown.
Approval & Indications
VIP is FDA-approved in injectable form for pulmonary arterial hypertension (as aviptadil, brand name Zyesami®) in critical-care settings, but VIP nasal spray for chronic use remains compounded and off-label. Clinicians use it under medical supervision for post-inflammatory syndromes, mold-related biotoxin illness, chronic fatigue, and dysautonomia. Research is ongoing into its immune-modulating and neuroprotective potential.
Clinical Pharmacology Snapshot
VIP binds GPCR (G-protein–coupled) receptors VPAC1 and VPAC2, triggering cyclic AMP (cAMP) signaling cascades that relax smooth muscle, modulate immune cells, and improve oxygen delivery. Nasal absorption is rapid, with detectable systemic levels within minutes. It’s cleared by enzymatic degradation in plasma and tissues, with a short plasma half-life but long biologic ripple through second-messenger systems.
Clinical Uses and Benefits
Clinicians use VIP spray to reduce inflammation, improve autonomic balance, and enhance oxygen utilization in conditions marked by neuroimmune dysregulation. Patients often describe better energy, clearer thinking, and less reactivity to environmental stressors. In biotoxin illness protocols (like the Shoemaker protocol), VIP is used near the end — once detox pathways are clear — to restore immune equilibrium.
Evidence in Brief
Clinical studies are limited but growing. Small trials and case series show VIP normalizes inflammatory markers (C4a, TGF-β1), improves pulmonary function, and enhances quality-of-life scores in chronic inflammatory response syndrome (CIRS). Animal studies confirm neuroprotective and vasodilatory properties. The peptide’s safety profile is favorable, with few systemic side effects even at higher doses.
How It Works (Mechanism)
VIP acts like the body’s “rest and repair” messenger. It suppresses pro-inflammatory cytokines (TNF-α, IL-6) and boosts regulatory T-cell activity, bringing immune tone back to baseline. It also relaxes vascular smooth muscle via cAMP, enhancing oxygen and nutrient delivery to tissues under stress. In the brain, VIP helps regulate circadian rhythm and the hypothalamic–pituitary–adrenal (HPA) axis, stabilizing energy and sleep-wake patterns.
Upstream and Downstream Effects
Upstream, VIP interacts with the autonomic nervous system — reducing sympathetic overdrive and cortisol spikes. Downstream, this shows up as steadier heart-rate variability, normalized inflammatory markers, improved cognition, and reduced reactivity to environmental triggers. Because it supports endothelial nitric oxide production, tissue oxygenation and microcirculation improve too.
Where Biomarkers Fit
VIP therapy is often guided by labs such as C4a, TGF-β1, VEGF, MMP-9, and ADH/osmolality ratios — key markers in CIRS and systemic inflammation. More general markers like CRP, cortisol, and DHEA help track global stress–inflammation balance. Mitochondrial function tests or lactate levels can also reveal improved cellular oxygen efficiency.
Biomarkers to Monitor
Baseline: CRP, C4a, TGF-β1, VEGF, MMP-9, cortisol, DHEA, and electrolytes. Follow-up every 4–8 weeks shows whether immune tone and vascular function normalize. Additional markers like thyroid, ferritin, and vitamin D support broader metabolic context.
Safety Monitoring
Monitor blood pressure, electrolytes, and symptom changes. In rare cases, hypotension or mild flushing can occur from vasodilation.
Timing & Follow-Up
Most clinicians start low (one spray per nostril daily) and titrate upward. Effects may appear within days for energy and clarity, with full anti-inflammatory effects unfolding over 4–6 weeks. Labs and symptom diaries help personalize dose and timing.
Dosing and Administration
Typical compounded concentration: 50 mcg/mL. Starting dose: one spray per nostril daily, titrating to two or three as tolerated. Administer at consistent times, often morning to support circadian signaling.
How to Take It
Gently blow nose, tilt head back slightly, and spray once into each nostril. Avoid sniffing hard afterward to let the peptide absorb through mucosa. Store refrigerated and use within the pharmacy’s recommended time frame.
Onset and Reassessment
Many users notice calmer autonomic tone and improved sleep within two weeks. Full lab normalization can take 1–3 months. Clinicians reassess inflammatory panels and symptoms every 6–8 weeks.
Side Effects and Safety
VIP’s safety record is reassuring. Adverse effects are rare and typically mild.
Common Effects
Temporary nasal congestion, mild flushing, or slight headache after dosing.
Serious Risks
Very rare hypersensitivity or hypotension in sensitive individuals. Discontinue and seek medical attention for dizziness, shortness of breath, or swelling.
Who Should Be Cautious
Pregnant individuals, those with severe hypotension, or patients using high-dose vasodilators should exercise caution. Safety in children and during pregnancy remains unstudied.
Drug–Drug Interactions
Minimal systemic interactions. Theoretical additive vasodilation with PDE5 inhibitors or antihypertensives.
Clinical Evidence Highlights
In CIRS cohorts, VIP therapy normalized multiple inflammatory and hormonal markers, improved neurocognitive testing, and restored endothelial function. Pulmonary studies show improved oxygenation and decreased cytokine burden. Animal research supports neuroprotection via reduced microglial activation.
Strengths and Limitations
Strengths: multi-system regulation, anti-inflammatory precision, excellent tolerability. Limitations: compounded status, limited large-scale trials, and cost variability.
How It Compares
Compared to systemic steroids or immunosuppressants, VIP rebalances rather than suppresses immunity. Versus nootropics, it acts at a deeper physiologic level — restoring rhythm before performance. For inflammatory syndromes rooted in dysregulation, VIP is more signal than symptom management.
Choosing Between Options
The right choice depends on the goal: immune modulation (VIP), detoxification (cholestyramine or binders), or mitochondrial support (NAD+, CoQ10). Often, these therapies work sequentially — VIP comes last, to lock balance in place.
Next Steps & Monitoring with Superpower Biomarker Testing
Inflammation isn’t invisible — it shows up in your labs before your body feels better. Superpower’s biomarker testing tracks CRP, cortisol, DHEA, cytokine activity, and oxidative stress so progress isn’t guesswork. Register with Superpower to take control of your inflammation recovery and watch your data confirm your reset in real time.