Side-by-side · Research reference

DihexavsHumanin

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED7/28 cited

BAnimal-StrongHUMAN-REVIEWED14/52 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

01Mechanism of Action

Parameter

Dihexa

Humanin

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022 Lue 2021

Pathway

HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization

Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival

Downstream effect

Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models

Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022 Lue 2021 Velentza 2024

Feedback intact?

—

Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis

Origin

Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015

Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022 Shahzaib 2026

Antibody development

—

Not reported in animal models

02Dosage Protocols

Parameter

Dihexa

Humanin

Human dosing

Not established — no human trials

—

Animal studies

Mouse/rat models only — dosing not translatable to humans

—

Evidence basis

Pre-clinical / Rodent models

Animal models (rat, mouse)Huang 2025 El 2022 Velentza 2024

Clinical status

No Phase 1, 2, or 3 trials published

—

Standard experimental dose (HNG)

—

4 mg/kg IP (rat)

Most common dose in rodent models.

Ex vivo bone culture

—

1 µg/mL

Protective against venetoclax-induced bone growth retardation.

Frequency

—

Daily (IP)

Duration

—

8–12 weeks in animal studies

Human data

—

None — no clinical trials reported

Analog (HNG)

—

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

03Metabolic / Fat Loss Evidence

Parameter

Dihexa

Humanin

Direct fat loss evidence

—

None

Mechanism overlap

—

Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect

04Side Effects & Safety

Parameter

Dihexa

Humanin

Human safety data

None available — no human clinical trials

None — no clinical trials

Theoretical c-Met risks

c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile

—

Pre-clinical tolerability

Not systematically reported in available studies

—

Animal model safety

—

Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks

Theoretical fibrillation risk

—

Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.

Injection site reaction

—

Not reported in animal studies (IP route)

Reproductive safety

—

Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025

Absolute Contraindications

Dihexa

·Not approved for human use — research compound only

Humanin

·Unknown — no human data

Relative Contraindications

Dihexa

·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)

Humanin

·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)

05Administration Protocol

Parameter

Dihexa

Humanin

1. Human administration

No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.

Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.

2. Legal status

Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.

Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.

3. Timing

—

Daily administration in animal studies. Optimal timing not characterized.

4. Storage

—

Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.

5. Human use

—

No FDA approval, no IND, no clinical trials. Experimental research tool only.

06Stack Synergy

Dihexa

— no documented stacks

Humanin

+ MOTS-c

Multi-pathway

View MOTS-c →

Both are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.

Humanin: 4 mg/kg IP · daily (animal model)
MOTS-c: 5 mg/kg IP · daily (animal model)
Frequency: Once daily
Primary benefit: Mitochondrial health, metabolic efficiency, anti-apoptotic signaling