Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Dihexa | FOXO4-DRI | |
|---|---|---|
| Category | Peptides | Peptides |
| Standard Dose | Research indicates 10-20 mg daily via oral or sublingual administration. | Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly. |
| Timing | Morning dosing preferred. Can be taken with or without food (orally active). | No established timing protocol. |
| Cycle Duration | 2-4 week cycles with equal rest periods. Long-term safety data is extremely limited. | Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established. |
| Evidence Level | animal_plus_anecdotal | animal_plus_anecdotal |
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.
FOXO4-DRI is a D-retro-inverso peptide that selectively targets the FOXO4-p53 protein-protein interaction in senescent cells. In senescence, FOXO4 binds p53's disordered transactivation domain (TAD2) in the nucleus, preventing p53 from translocating to mitochondria where it would trigger apoptosis. FOXO4-DRI competitively disrupts this interaction, causing nuclear exclusion of p53 and its redirection to mitochondria, selectively inducing apoptosis in senescent cells while sparing healthy cells. The D-retro-inverso configuration provides protease resistance.
Research indicates dosing remains experimental. Mouse studies used 5 mg/kg IV, three times weekly.
No established timing protocol.
Mouse studies used intermittent dosing (3x/week for several weeks). Human protocols not established.
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