Histatin-5
Evidence: C+Antimicrobial / Innate-Defense Peptides
Evidence Snapshot
What this grade covers
Composite proposed grade: identity/discovery B; anticandidal activity (isoform-resolved) B; mechanism B; human observational association C; controlled human administration absent (no grade); safety/assay-condition evidence insufficient (empty bucket).
Regulatory Context
Endogenous human peptide; no native Histatin-5 drug product approval record identified in this review.
Research Takeaway
Histatin-5 is a 24-amino-acid histidine-rich peptide, one of a family of related peptides (Histatin-1, -3, -5) present in human parotid/submandibular saliva; it is proteolytically derived from the 32-residue Histatin-3 protein, encoded by HTN3.
Evidence boundary: Family paper -- only Histatin-5-resolved findings are used here; Histatin-1/Histatin-3 findings from the same paper do not apply to Histatin-5 without independent isoform resolution.
See all 5 evidence claims →Quick Summary
Histatin-5 is a 24-amino-acid antimicrobial peptide fragment derived from human salivary Histatin-3, showing the most potent anti-Candida activity among the major human salivary histatins via a mechanism that targets the fungal mitochondrion. No controlled human administration study of native Histatin-5 has been identified, and no primary source addressing its sensitivity to assay conditions or host-cell effects was located -- these remain open evidence gaps, not established safety findings.
Mechanism & Research Overview
Histatin-5 is a 24-amino-acid antimicrobial peptide fragment derived from human salivary Histatin-3, showing the most potent anti-Candida activity among the major human salivary histatins via a mechanism that targets the fungal mitochondrion. No controlled human administration study of native Histatin-5 has been identified, and no primary source addressing its sensitivity to assay conditions or host-cell effects was located -- these remain open evidence gaps, not established safety findings.
Evidence Claims
Individual scientific statements drawn from the sources cited below, each shown with the specific evidence boundary that statement does not establish.
Supported
Histatin-5 is a 24-amino-acid histidine-rich peptide, one of a family of related peptides (Histatin-1, -3, -5) present in human parotid/submandibular saliva; it is proteolytically derived from the 32-residue Histatin-3 protein, encoded by HTN3.
Does not establish
Evidence boundary: Family paper -- only Histatin-5-resolved findings are used here; Histatin-1/Histatin-3 findings from the same paper do not apply to Histatin-5 without independent isoform resolution.
Supported
Histatin-5 shows the most potent anticandidal (killing and germination-inhibition) activity among the major human salivary histatins (Histatin-1, -3, -5) in direct, isoform-resolved comparison assays against Candida albicans.
Does not establish
Evidence boundary: Isoform-resolved, not pooled -- this activity level does not apply to Histatin-1 or Histatin-3.
Sources: Anticandidal activity of major human salivary histatins
Supported
Histatin-5 kills Candida albicans by targeting the energized mitochondrion, causing loss of mitochondrial transmembrane potential after cellular uptake.
Does not establish
Evidence boundary: This mechanism has not been demonstrated for Histatin-1 or Histatin-3, or against organisms other than C. albicans in this specific study.
Sources: The cellular target of histatin 5 on Candida albicans is the energized mitochondrion
Supported
Lower salivary Histatin-5 levels are associated with increased oral Candida colonization in patients with Down syndrome, a population with documented elevated oral candidiasis risk.
Does not establish
Evidence boundary: Correlative, single study, specific population; does not establish causation or generalizability beyond this population.
Supported
Lower salivary Histatin-5 levels are significantly associated with vaginal candidiasis in reproductive-age women, a cross-anatomical-site correlation distinct from Histatin-5's local oral antifungal mechanism.
Does not establish
Evidence boundary: Correlative, single study, systemic/cross-site association not mechanistically explained by the local oral-cavity mechanism.
Sources: Salivary Histatin 5 Level in Women with Vaginal Candidiasis
Safety & Evidence Limitations
Considerations reported in the sources cited on this page — not a complete list of every possible risk, and not medical advice.
Safety Consideration
No study administering native Histatin-5 to human volunteers by any route has been identified in this evidence review.Safety Consideration
No primary source addressing Histatin-5's sensitivity to assay conditions (e.g. ionic strength) or its effects on human host cells was located. This absence must be stated explicitly and never used to imply either safety or unsafety.Safety Consideration
Both human observational associations (Down syndrome oral Candida; vaginal candidiasis) are correlative, single-study findings limited to specific populations.
Research Areas Being Studied
Research areas discussed on this page reflect the Antimicrobial / Innate-Defense Peptides category and the sources cited below.
Findings Reported in Studies
Educational summary only — reported in cited studies, not a claim of proven benefit.
- Salivary Histatin 5 Level in Women with Vaginal Candidiasis (2022):
- Association between Antimicrobial Peptide Histatin 5 Levels and Prevalence of Candida in Saliva of Patients with Down Syndrome (2021):
- The cellular target of histatin 5 on Candida albicans is the energized mitochondrion (1999):
- Anticandidal activity of major human salivary histatins (1991):
- Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans (1988):
Study Tables by Evidence Type
Human Studies & Clinical Data
| Title | Year | Population / Model | Dose / Duration / Finding | Safety Notes | Source |
|---|---|---|---|---|---|
| Salivary Histatin 5 Level in Women with Vaginal Candidiasis | 2022 | reproductive-age women (18-50) with vaginal candidiasis vs. controls | Lower salivary Histatin-5 levels are significantly associated with vaginal candidiasis in reproductive-age women. | ||
| Association between Antimicrobial Peptide Histatin 5 Levels and Prevalence of Candida in Saliva of Patients with Down Syndrome | 2021 | Down syndrome patients, saliva samples | Lower salivary Histatin-5 levels are associated with increased oral Candida colonization in patients with Down syndrome. | ||
| The cellular target of histatin 5 on Candida albicans is the energized mitochondrion | 1999 | human-derived Histatin-5 vs. Candida albicans, in vitro | Histatin-5 targets the energized mitochondrion in Candida albicans, causing loss of mitochondrial transmembrane potential after cellular uptake. | ||
| Anticandidal activity of major human salivary histatins | 1991 | human salivary histatins, in vitro Candida albicans assay | Histatin-5 shows the most potent anticandidal (killing and germination-inhibition) activity among Histatin-1, -3, and -5 in direct, isoform-resolved comparison. | ||
| Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans | 1988 | human parotid saliva | Discovery of the histatin family (Histatin-1, -3, -5) in human parotid secretion, with fungistatic effects on Candida albicans. |
Animal / Cell / Preclinical Data
No Animal / Cell / Preclinical Data Listed Yet
This section will be updated as sources are added.
Regulatory Documents & Official Trial Registries
No Regulatory Documents & Official Trial Registries Listed Yet
This section will be updated as sources are added.
Anecdotal Reported Patterns — Not Medical Advice
Anecdotal Reported Patterns — Not Medical Advice
Reported dosing patterns are included for educational context only. They are self-reported, unverified, not medical advice, and not instructions for human use. Community-submitted patterns are not yet available in this Phase 1 prototype; this section is a placeholder reserved for moderated, aggregated community data.
Lab Markers to Discuss With a Clinician
Educational topics only — not self-monitoring instructions.
FAQ
Disclaimer
Educational information only. This page summarizes published research on endogenous human Histatin-5 and does not constitute medical advice, a treatment recommendation, or dosing guidance for any related substance.
Educational use only. This content is provided for informational and research-summary purposes only. It is not medical advice, not a treatment recommendation, not a dosing guide, and not a substitute for care from a licensed medical professional. Nothing here is intended to diagnose, treat, cure, prevent, or mitigate disease. Reported dosing patterns, when shown elsewhere on the site, must be labeled either as Study / Trial Dosing or Anecdotal Reported Patterns — Not Medical Advice. Community reports are self-reported, unverified, and not scientific proof.
Community-reported experiences, once enabled, must be displayed only as moderated, anonymized, or aggregated data. They are anecdotal, self-reported, unverified, and should never be presented as proof of safety, efficacy, or expected results.
Content status: Published. Last updated 2026-08-29.
Follow research updates for Histatin-5
Get notified in your MitoCore account when this profile is updated, a new study is added, or its evidence grade changes.
Get updates when new studies or safety notes are added for this peptide.
Get educational updates on new studies, evidence-grade changes, and safety notes. Educational content only — not medical advice.