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VIP vs LL-37 side-by-side

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VIPLL-37

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Property	VIP	LL-37
Category	Immune	Immune
Also known as	Vasoactive Intestinal Peptide, Aviptadil	Cathelicidin, CAP18
FDA approved	No	No
Clinical status	Clinical Trials - Multiple indications Pre Preclinical I Phase I II Phase II III Phase III IV Phase IV FDA FDA approved	Investigational; source notes clinical trials for wound healing and FDA Category 2 restricted status due to limited safety data and immunogenicity concerns. Pre Preclinical I Phase I II Phase II III Phase III IV Phase IV FDA FDA approved
What to expect	Autoimmune conditions, CIRS/mold illness, inflammation	Antimicrobial, infections, biofilm disruption, wound healing
How it works	VIP is reported to act through VPAC1 and VPAC2 receptors. The supplied mechanism evidence links receptor activation to increased cyclic AMP, relaxation of smooth muscle, dilation in vascular and airway tissues, and dampening of inflammatory pathways. The same evidence connects immune effects with reduced NF-kB activity and lower TNF-alpha signaling. Because VPAC receptors are distributed across immune cells, the gut, blood vessels, and the brain, the source characterizes VIP as a broad signaling hormone rather than a narrowly targeted agent.	LL-37 is described as a positively charged, amphipathic host-defense peptide that can associate with negatively charged microbial membranes and disrupt them. Beyond direct antimicrobial effects, the source reports signaling roles that include neutralizing bacterial LPS, shaping inflammatory activity, recruiting immune cells to sites of injury or infection, and supporting epithelial repair. The source notes production in epithelial tissues such as skin, gut, and lung, as well as immune cells including neutrophils.
Typical dosing	50-100 mcg intranasal daily · 1-2x daily, intranasal · intranasal	100-200 mcg daily · Once daily
Research dosing	50-100 mcg IV for acute conditions · Variable by indication · IV infusion, inhaled, or intranasal	100-200 mcg subcutaneous · Variable by protocol · Subcutaneous injection or topical
Typical duration	Variable by indication	Variable by protocol
Administration	IV infusion, inhaled, or intranasal	Subcutaneous injection or topical
Timing	Morning or as directed With or without food	Morning With or without food
Evidence level	Clinical Trials	Clinical Trials
Possible side effects	Nausea and diarrhea Injection site reactions Headache +4 more Dizziness Facial flushing Blood pressure decrease Short-lived effects due to instability	Injection-site reactions (Reported as common in the source.) Skin toxicity (Source examples include ulcers and burning.) Allergic reactions (Reported by the source without severity grading.) +4 more Histamine release (Source flags caution for MCAS or histamine sensitivity.) Possible contribution to autoimmune conditions (Reported as a potential concern, not established causality.) High-dose toxicity concerns (Source flags concern at higher doses.) Limited long-term safety data (Source notes uncertainty around longer-term safety.)
Research summary	The source describes most human evidence for VIP as coming from aviptadil, a synthetic analog. It cites a randomized trial in about 196 critically ill COVID-19 patients with respiratory failure, published in Critical Care Medicine in 2022, where intravenous aviptadil did not meet the 60-day primary endpoint of survival without respiratory failure, although exploratory findings were noted. It also reports that larger and inhaled approaches were evaluated in the ACTIV-3b/TESICO program, with mixed overall results. Outside pulmonary disease, the source mentions rheumatoid arthritis, pulmonary arterial hypertension, and other inflammatory conditions as areas of mechanistic or early-stage study. The supplied evidence explicitly does not support anti-aging, longevity, or general wellness claims.	The source presents LL-37 as a well-studied endogenous component of human innate immunity, with literature support for broad antimicrobial activity, membrane disruption, and distribution across epithelial and immune tissues. It also reports exploratory research on LL-37 or related mimics in laboratory anticancer models, Helicobacter pylori host-defense research, and ocular-surface pathogen contexts. The evidence described is strongest for LL-37 as a natural immune peptide; deliberate administration remains experimental in the supplied source, and the source flags that LL-37 may worsen inflammation in some disease settings.
References	Source Source +2 more Source Source	Peptibase peptides Peptibase peptides +3 more Peptibase peptides Peptibase peptides Peptibase peptides
Full profile	View Details	View Details

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Educational use only. This information is aggregated from public research and community reports. It is not medical advice, and dosing details are descriptive, not recommendations. Always consult a qualified healthcare professional.

Property

VIP

LL-37

Category

Immune

Also known as

Vasoactive Intestinal Peptide, Aviptadil

Cathelicidin, CAP18

FDA approved

Clinical status

Clinical Trials - Multiple indications

Pre
Preclinical
I
Phase I
II
Phase II
III
Phase III
IV
Phase IV
FDA
FDA approved

Investigational; source notes clinical trials for wound healing and FDA Category 2 restricted status due to limited safety data and immunogenicity concerns.

Pre
Preclinical
I
Phase I
II
Phase II
III
Phase III
IV
Phase IV
FDA
FDA approved

What to expect

Autoimmune conditions, CIRS/mold illness, inflammation

Antimicrobial, infections, biofilm disruption, wound healing

How it works

VIP is reported to act through VPAC1 and VPAC2 receptors. The supplied mechanism evidence links receptor activation to increased cyclic AMP, relaxation of smooth muscle, dilation in vascular and airway tissues, and dampening of inflammatory pathways. The same evidence connects immune effects with reduced NF-kB activity and lower TNF-alpha signaling. Because VPAC receptors are distributed across immune cells, the gut, blood vessels, and the brain, the source characterizes VIP as a broad signaling hormone rather than a narrowly targeted agent.

LL-37 is described as a positively charged, amphipathic host-defense peptide that can associate with negatively charged microbial membranes and disrupt them. Beyond direct antimicrobial effects, the source reports signaling roles that include neutralizing bacterial LPS, shaping inflammatory activity, recruiting immune cells to sites of injury or infection, and supporting epithelial repair. The source notes production in epithelial tissues such as skin, gut, and lung, as well as immune cells including neutrophils.

Typical dosing

50-100 mcg intranasal daily · 1-2x daily, intranasal · intranasal

100-200 mcg daily · Once daily

Research dosing

50-100 mcg IV for acute conditions · Variable by indication · IV infusion, inhaled, or intranasal

100-200 mcg subcutaneous · Variable by protocol · Subcutaneous injection or topical

Typical duration

Variable by indication

Variable by protocol

Administration

IV infusion, inhaled, or intranasal

Subcutaneous injection or topical

Timing

Morning or as directed

With or without food

Morning

With or without food

Evidence level

Clinical Trials

Possible side effects

Nausea and diarrhea
Injection site reactions
Headache

+4 more

Dizziness
Facial flushing
Blood pressure decrease
Short-lived effects due to instability

Injection-site reactions (Reported as common in the source.)
Skin toxicity (Source examples include ulcers and burning.)
Allergic reactions (Reported by the source without severity grading.)

+4 more

Histamine release (Source flags caution for MCAS or histamine sensitivity.)
Possible contribution to autoimmune conditions (Reported as a potential concern, not established causality.)
High-dose toxicity concerns (Source flags concern at higher doses.)
Limited long-term safety data (Source notes uncertainty around longer-term safety.)

Research summary

The source describes most human evidence for VIP as coming from aviptadil, a synthetic analog. It cites a randomized trial in about 196 critically ill COVID-19 patients with respiratory failure, published in Critical Care Medicine in 2022, where intravenous aviptadil did not meet the 60-day primary endpoint of survival without respiratory failure, although exploratory findings were noted. It also reports that larger and inhaled approaches were evaluated in the ACTIV-3b/TESICO program, with mixed overall results. Outside pulmonary disease, the source mentions rheumatoid arthritis, pulmonary arterial hypertension, and other inflammatory conditions as areas of mechanistic or early-stage study. The supplied evidence explicitly does not support anti-aging, longevity, or general wellness claims.

The source presents LL-37 as a well-studied endogenous component of human innate immunity, with literature support for broad antimicrobial activity, membrane disruption, and distribution across epithelial and immune tissues. It also reports exploratory research on LL-37 or related mimics in laboratory anticancer models, Helicobacter pylori host-defense research, and ocular-surface pathogen contexts. The evidence described is strongest for LL-37 as a natural immune peptide; deliberate administration remains experimental in the supplied source, and the source flags that LL-37 may worsen inflammation in some disease settings.

References

Source Source

+2 more

Source Source

Peptibase peptides Peptibase peptides

+3 more

Peptibase peptides Peptibase peptides Peptibase peptides

Full profile

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