Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Humanin | SS-31 (Elamipretide) | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research 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. |
| Timing | No established timing protocol. Morning dosing suggested for neuroprotective applications. | Morning dosing preferred. No food timing restrictions. |
| Cycle Duration | Experimental — no established cycle lengths. | Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established. |
| Evidence Level | animal_plus_anecdotal | Emerging (Phase 2/3 trials) |
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.
Research indicates dosing remains experimental. Animal studies use 1-10 mcg/day equivalents. Human protocols are not established.
No established timing protocol. Morning dosing suggested for neuroprotective applications.
Experimental — no established cycle lengths.
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.
Research indicates 0.05-0.25 mg/kg daily via subcutaneous injection. Clinical trials used 4-40 mg/day IV or SC.
Morning dosing preferred. No food timing restrictions.
Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established.
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