Side-by-side comparison of mechanisms, dosing, interactions, and stacking potential.
| Humanin | Semax | |
|---|---|---|
| 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 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril). |
| Timing | No established timing protocol. Morning dosing suggested for neuroprotective applications. | Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery. |
| Cycle Duration | Experimental — no established cycle lengths. | 10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns. |
| Evidence Level | animal_plus_anecdotal | moderate_human |
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.
Semax (Met-Glu-His-Phe-Pro-Gly-Pro) is a synthetic heptapeptide analog of the ACTH(4-10) fragment that rapidly upregulates brain-derived neurotrophic factor (BDNF) and its signaling receptor TrkB in the hippocampus (1.4-fold BDNF protein increase, 3-fold exon III BDNF mRNA increase). It activates dopaminergic and serotonergic brain systems, enhances neurotrophin gene expression (BDNF, NGF), and modulates intracellular calcium dynamics in brain neurons. Semax lacks ACTH's corticotropic activity, acting purely as a nootropic/neuroprotective agent.
Research indicates 200-600 mcg daily via intranasal administration (0.1% solution, 2-3 drops per nostril).
Morning and early afternoon dosing (avoid evening — may cause stimulation/insomnia). Intranasal preferred for rapid CNS delivery.
10-14 day cycles with equal rest periods. Some protocols use 3-5 day on / 2 day off patterns.
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