Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Dihexa | SS-31 (Elamipretide) | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates 10-20 mg daily via oral or sublingual administration. | 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. Can be taken with or without food (orally active). | Morning dosing preferred. No food timing restrictions. |
| Cycle Duration | 2-4 week cycles with equal rest periods. Long-term safety data is extremely limited. | Clinical trials ranged from single dose to 48 weeks. Optimal cycle length not established. |
| Evidence Level | animal_plus_anecdotal | Emerging (Phase 2/3 trials) |
Dihexa (N-hexanoic-Tyr-Ile-(6)-aminohexanoic amide) is an orally active, blood-brain barrier-permeable oligopeptide derived from angiotensin IV. It binds hepatocyte growth factor (HGF) with high affinity, inhibiting HGF dimerization and synergistically promoting c-Met receptor phosphorylation and signaling. Activation of HGF/c-Met drives procognitive effects through increased dendritic arborization, spinogenesis, and synaptogenesis via the PI3K/AKT signaling pathway. Research indicates it is approximately 10 million times more potent than BDNF for new synapse formation.
Research indicates 10-20 mg daily via oral or sublingual administration.
Morning dosing preferred. Can be taken with or without food (orally active).
2-4 week cycles with equal rest periods. Long-term safety data is extremely limited.
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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