Peplens

VIP (Vasoactive Intestinal Peptide)

Limited human data

Endogenous 28-amino-acid neuropeptide / VPAC1–VPAC2 receptor agonist (synthetic form: aviptadil) · Also known as Vasoactive Intestinal Polypeptide, Aviptadil, Zyesami, RLF-100, synthetic VIP

Overview

Vasoactive Intestinal Peptide (VIP) is a naturally occurring 28-amino-acid neuropeptide with vasodilatory, anti-inflammatory and immune-modulating activity; it acts at VPAC1/VPAC2 receptors and, in the lung, protects alveolar type II cells. The synthetic form, aviptadil (brand name Zyesami / RLF-100), has been studied clinically — most prominently inhaled VIP in sarcoidosis (a 20-patient study showed reduced TNF-alpha production and increased regulatory T-cells in lung lavage) and in pulmonary arterial hypertension, plus a high-profile program in severe COVID-19 respiratory failure. That COVID program ultimately failed: the FDA twice declined Emergency Use Authorization (2021 and 2022) and the NIH ACTIV-3b trial's aviptadil arm was stopped after it did not beat placebo at interim analysis. Aviptadil holds FDA Orphan Drug and Fast Track designations for ARDS but is NOT FDA-approved for any indication.

Commonly Reported Uses

These are uses commonly discussed or marketed by users and vendors — not a list of proven or approved benefits, and not a recommendation.

  • Acute respiratory distress syndrome (ARDS) / severe COVID-19 respiratory failure (investigated as Zyesami; FDA declined EUA twice, pivotal trial failed)
  • Sarcoidosis (inhaled VIP studied in a small trial; investigational, not approved)
  • Pulmonary arterial hypertension (investigational; early studies, not approved)
  • Erectile dysfunction and general anti-inflammatory/immune support (marketed/off-label claim; not an approved use)

What to Track

Data points you and your clinician might monitor. For observation only — not a diagnostic protocol.

  • Subjective — respiratory symptoms (breathlessness, cough) for a tracked respiratory goal; flushing or diarrhea (known VIP side effects)
  • Blood pressure and heart rate — VIP is a vasodilator; transient hypotension/flushing are documented, so monitor especially with cardiovascular risk
  • Labs — hs-CRP, IL-6 or TNF-alpha if a clinician is tracking inflammation
  • WHOOP — resting heart rate, recovery and sleep trends
  • Subjective — energy and overall well-being check-ins

Sources & References

  1. [1]Inhaled Vasoactive Intestinal Peptide Exerts Immunoregulatory Effects in Sarcoidosis — American Journal of Respiratory and Critical Care Medicine
  2. [2]Inhaled ZYESAMI (Aviptadil Acetate) for the Treatment of Severe COVID-19 (NCT04360096) — ClinicalTrials.gov
  3. [3]FDA Declines Emergency Use Authorization for ZYESAMI (aviptadil) — NRx Pharmaceuticals press release

Quick Reference

Class
Endogenous 28-amino-acid neuropeptide / VPAC1–VPAC2 receptor agonist (synthetic form: aviptadil)
Evidence Level
Limited human data
Reported Uses
4 listed
Tracking Metrics
5 suggested
Citations
3 sources

Safety & legal notes

NOT FDA-approved for any indication. The synthetic form aviptadil (Zyesami) has FDA Orphan Drug and Fast Track designations for ARDS, but the FDA twice declined Emergency Use Authorization for critical COVID-19 (November 2021 and July 2022) and the NIH ACTIV-3b aviptadil arm was halted for futility. Reported side effects are mainly vasodilatory — hypotension, flushing, diarrhea. Not a primary WADA doping target, but athletes should verify current rules. Material sold outside clinical/compounding channels is generally 'research use only.' Long-term human safety for self-directed use is not established. Consult a licensed clinician.

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