Humanin vs SS-31 (Elamipretide)

Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.

✅ Stacking Partners — These compounds are commonly used together and may have synergistic effects.
HumaninSS-31 (Elamipretide)
CategoryPeptidesPeptides
Standard DoseResearch indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.
TimingNo established timing protocol. Morning dosing suggested for neuroprotective applications.Morning dosing preferred. No food timing restrictions.
Cycle DurationExperimental — no established cycle lengths.Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.
Evidence Levelanimal_plus_anecdotalEmerging (Phase 2/3 trials)
A

Humanin

Peptides

Mechanism

Humanin is a 24-amino acid mitochondrial-derived peptide encoded by the 16S rRNA gene of mitochondrial DNA. It binds IGFBP-3 with high affinity (via Phe-6), interfering with IGFBP-3 binding to importin-beta and suppressing IGFBP-3-mediated apoptosis. It also inhibits the pro-apoptotic protein Bax (Bcl-2 family), preventing mitochondrial outer membrane permeabilization and intrinsic apoptosis. Humanin and IGFBP-3 synergistically protect neurons from amyloid-beta-induced apoptosis, and it activates the STAT3 and ERK1/2 pathways for cytoprotection.

Standard Dosing

Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.

Timing

No established timing protocol. Morning dosing suggested for neuroprotective applications.

Cycle Duration

Experimental — no established cycle lengths.

Side Effects

  • Limited data on side effects in humans
  • Theoretical: interference with normal apoptotic processes

Contraindications

  • Active cancer (anti-apoptotic effects could support tumor survival)
  • Pregnancy and breastfeeding

Best Stacking Partners

MOTS-cEpitalonSS-31

Mechanism

SS-31 (D-Arg-Dmt-Lys-Phe-NH2, also known as elamipretide/Bendavia) is a cell-permeable tetrapeptide that localizes to the inner mitochondrial membrane and binds cardiolipin via electrostatic interactions. This stabilizes cardiolipin against oxidative damage, preserving cristae integrity, reducing ROS production, and maintaining mitochondrial ATP production. SS-31 interacts with proteins in two functional groups: oxidative phosphorylation complexes and 2-oxoglutarate metabolic enzymes — all known cardiolipin binders. It restores mitochondrial function without acting as a direct antioxidant.

Standard Dosing

Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.

Timing

Morning dosing preferred. No food timing restrictions.

Cycle Duration

Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.

Side Effects

  • Injection site reactions
  • Headache
  • Diarrhea (in clinical trials)
  • Nausea

Contraindications

  • Pregnancy and breastfeeding
  • Severe renal impairment (peptide clearance concern)
  • Not commercially available
  • Clinical trial participants only

Best Stacking Partners

MOTS-cHumaninEpitalon

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