Side-by-side · Research reference

DihexavsSS-31

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

BPhase 3HUMAN-REVIEWED9/43 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

SS-31

Cardiolipin-binding · Mitochondrial protective

40 mgDaily doseSzeto 2014

Phase 3Evidence levelSzilagyi 2009 Szeto 2014

~3 hrHalf-life

SQ · Abdomen · Once daily

01Mechanism of Action

Parameter

Dihexa

SS-31

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

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

Cardiolipin binding → cristae stabilisation → ETC integrity → reduced ROS + preserved ATP synthesisSzeto 2014 Szilagyi 2009

Downstream effect

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

Mitochondrial bioenergetic preservation; cardio-, neuro-, and reno-protective effects in animal + clinical studiesSzeto 2014

Feedback intact?

—

Origin

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

Synthetic tetrapeptide D-Arg-Dmt-Lys-Phe-NH₂; cell-permeable, mitochondrial-selectiveSzeto 2014

Antibody development

—

02Dosage Protocols

Parameter

Dihexa

SS-31

Human dosing

Not established — no human trials

—

Animal studies

Mouse/rat models only — dosing not translatable to humans

—

Evidence basis

Pre-clinical / Rodent models

Multiple Phase 3 trials (Barth, AMD, ischemia-reperfusion)Szeto 2014 Szilagyi 2009

Clinical status

No Phase 1, 2, or 3 trials published

—

Standard dose

—

40 mg / day SQ (clinical trials)Szeto 2014

Anecdotal community range 5-10 mg/day. Phase 3 trials use 40 mg.

Frequency

—

Once daily

Lower / starter dose

—

5 mg / day (anecdotal)

Duration

—

Indefinite for mitochondrial disease; cycled for healthspan use

Reconstitution

—

Bacteriostatic water

Timing

—

Morning fasted preferred; pre-workout for exercise-induced mitochondrial stress

Half-life

—

~3 h plasma; tissue uptake longer

04Side Effects & Safety

Parameter

Dihexa

SS-31

Human safety data

None available — no human 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

—

Injection site reaction

—

Erythema, mild pruritus

GI symptoms

—

Nausea (uncommon)

Headache

—

Reported in some Phase 3 trials

Cardiovascular

—

Cardio-protective in studies; no signal of harm

Long-term safety

—

Phase 3 data over 24+ months; no major safety signalsSzeto 2014

Pregnancy / OB

—

Avoid — insufficient data

Absolute Contraindications

Dihexa

·Not approved for human use — research compound only

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Dihexa

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

SS-31

·None established

05Administration Protocol

Parameter

Dihexa

SS-31

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.

Add bacteriostatic water per label. Light-protected handling.

2. Legal status

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

SQ — abdomen or thigh. Rotate sites.

3. Timing

—

Morning fasted; pre-workout for exercise-augmented mitochondrial stress.

4. Storage

—

Lyophilised: refrigerate, light-protected. Reconstituted: refrigerate ≤30 days.

5. Needle

—

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Dihexa

— no documented stacks

SS-31

+ MOTS-c

Moderate

View MOTS-c →

SS-31 and MOTS-c address mitochondrial decline through complementary axes. SS-31 protects existing mitochondrial structure (cardiolipin binding, cristae stabilisation). MOTS-c upregulates AMPK/PGC-1α, triggering biogenesis of new mitochondria. Together they pair preservation with renewal — anecdotally favoured in healthspan and post-cardio-event recovery protocols.

SS-31: 5–10 mg SQ · daily morning
MOTS-c: 5 mg SQ · 2× per week pre-workout
Primary benefit: Mitochondrial preservation + biogenesis