Side-by-side · Research reference

CortagenvsSS-31

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

AAnimal-MechanisticHUMAN-REVIEWED11/35 cited

BPhase 3HUMAN-REVIEWED9/43 cited

Cortagen

Bioregulatory Tetrapeptide · Khavinson-School

TetrapeptideStructure

↓ LPO productsAntioxidant effectKozina 2007

AnimalEvidence level

Injectable · Animal models

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

Cortagen

SS-31

Primary target

Cerebral cortex tissue — molecular targets under investigation

Cardiolipin in inner mitochondrial membraneSzeto 2014

Pathway

Antioxidant pathway modulation — suppression of LPO cascade, reduction of protein oxidative modificationKozina 2007

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

Downstream effect

Decreased lipid peroxidation products, reduced oxidative protein damage, altered gene expression in cardiac tissueKozina 2007 Anisimov 2004

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

Feedback intact?

—

Origin

Synthetic tetrapeptide derived from amino acid analysis of natural brain cortex peptide preparation CortexinAnisimov 2004

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

Antibody development

—

02Dosage Protocols

Parameter

Cortagen

SS-31

Animal model dose (rat)

Injection protocol (dose not specified in abstracts)

Multiple injections over study period.

—

Avian model dose (chicken)

40-day injection courseKuznik 2008

Compared to epithalon in hypophysectomized and aged birds.

—

Human peripheral nerve study

Therapeutic course (protocol details not provided)

Posttraumatic recovery context — reference cited but not detailed.

—

Evidence basis

Animal mechanistic studies

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

Route

Injectable (inferred from animal protocols)

—

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

Cortagen

SS-31

Antioxidant suppression

Suppression of antioxidant activity noted alongside LPO reductionKozina 2007

Mechanism unclear — possible homeostatic adaptation.

—

Immune/hemostasis effects

No effect on immunity or hemostasis parameters in avian hypophysectomy model (unlike epithalon)Kuznik 2008

Epithalon reversed deficits; cortagen did not.

—

Human safety data

No adverse events reported in peripheral nerve recovery context

Limited detail in available abstracts.

—

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

Cortagen

—

SS-31

·Pregnancy / breastfeeding
·Hypersensitivity to peptide

Relative Contraindications

Cortagen

—

SS-31

·None established

05Administration Protocol

Parameter

Cortagen

SS-31

1. Preparation

Reconstitute lyophilised peptide with bacteriostatic water per supplier protocol. Exact volumes depend on concentration supplied.

Add bacteriostatic water per label. Light-protected handling.

2. Injection site

Subcutaneous injection typical for bioregulatory peptides — abdomen or thigh. Rotate sites.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Animal protocols used repeated dosing over weeks. Human timing not established — evening administration common in Khavinson tradition.

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

4. Storage

Lyophilised: refrigerate or freeze per supplier. Reconstituted: refrigerate 2–8 °C, use within guideline window.

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

5. Needle

—

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Cortagen

— 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