Side-by-side · Research reference

HumaninvsSermorelin

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED14/52 cited

BPhase 3HUMAN-REVIEWED14/43 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Sermorelin

GHRH 1-29 fragment · Short-acting

100–500 mcgPer doseMolteno 2013

Phase 3Evidence levelWalker 1994 Molteno 2013

~12 minHalf-lifeMolteno 2013

SQ · Pre-sleep · 1×/day

01Mechanism of Action

Parameter

Humanin

Sermorelin

Primary target

Intracellular: Bax, Bim, tBid (pro-apoptotic Bcl-2 family). Extracellular: FPRL1/2 G-protein-coupled receptorsZhu 2022 Lue 2021

Pituitary GHRH receptorWalker 1994

Pathway

Humanin binds Bax/Bim → inhibits mitochondrial outer membrane permeabilization (MOMP) → blocks cytochrome c release → prevents caspase activation → cell survival

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994

Downstream effect

Suppression of apoptosis, mitochondrial stabilization, reduced oxidative stress, preservation of germ cells and neurons under stressZhu 2022 Lue 2021 Velentza 2024

Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013

Feedback intact?

Not applicable — peptide acts as anti-apoptotic signal, not hormonal axis

Yes — short pulse preserves feedback

Origin

Encoded by short open reading frame in mitochondrial 16S rRNA gene (MTRNR2). 24-28 amino acids. 13 homologous variants (MTRNR2L1-L13) identified.Zhu 2022 Shahzaib 2026

Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994

Antibody development

Not reported in animal models

—

02Dosage Protocols

Parameter

Humanin

Sermorelin

Standard experimental dose (HNG)

4 mg/kg IP (rat)

Most common dose in rodent models.

—

Ex vivo bone culture

1 µg/mL

Protective against venetoclax-induced bone growth retardation.

—

Frequency

Daily (IP)

Once daily, pre-sleep

Duration

8–12 weeks in animal studies

8–12 weeks per cycle

Evidence basis

Animal models (rat, mouse)Huang 2025 El 2022 Velentza 2024

Phase 3 (Geref pediatric); clinical practiceWalker 1994 Molteno 2013

Human data

None — no clinical trials reported

—

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

—

Standard dose

—

100–500 mcg per injectionMolteno 2013

Lower / starter dose

—

100 mcg per dose

Reconstitution

—

Bacteriostatic water

Timing

—

Pre-sleep, fasted preferred

Half-life

—

~12 min (plasma)Molteno 2013

Shorter than tesamorelin (~26 min) — simpler GHRH analogue.

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Sermorelin

Direct fat loss evidence

None

—

Mechanism overlap

Mitochondrial health may indirectly influence metabolic efficiency, but no quantified effect

—

04Side Effects & Safety

Parameter

Humanin

Sermorelin

Animal model safety

Well-tolerated in rat and mouse studies at 4 mg/kg for 8–12 weeks

—

Human safety data

None — no clinical trials

—

Theoretical fibrillation risk

Induces amyloid-like fibrillation of Bax/BID. Long-term sequelae unknown.

—

Injection site reaction

Not reported in animal studies (IP route)

Mild erythema, transient pain

Reproductive safety

Protective in POI model (cyclophosphamide-induced), no adverse effects on fertility notedHuang 2025

—

Flushing / headache

—

Common transient effect

IGF-1 elevation

—

Modest at standard doses

Cancer risk

—

Contraindicated in active malignancy (GH/IGF-1 axis)

Pregnancy / OB

—

Avoid

Glucose handling

—

Generally neutral

Absolute Contraindications

Humanin

·Unknown — no human data

Sermorelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

Relative Contraindications

Humanin

·Active malignancy (theoretical risk of anti-apoptotic effect on tumour cells)

Sermorelin

·Untreated diabetes

05Administration Protocol

Parameter

Humanin

Sermorelin

1. Route (experimental)

Intraperitoneal (IP) in animal models. Subcutaneous route untested. No human protocols exist.

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

2. Reconstitution

Synthetic peptide reconstituted in sterile saline or PBS. No commercial formulation available.

SQ — abdomen or thigh. Rotate sites.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

Pre-sleep, fasted.

4. Storage

Lyophilised powder: -20 °C. Reconstituted: 4 °C, use within 7 days. Avoid freeze-thaw cycles.

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

5. Human use

No FDA approval, no IND, no clinical trials. Experimental research tool only.

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

Humanin

+ MOTS-c

Multi-pathway

View MOTS-c →

Both are mitochondrial-derived peptides. MOTS-c enhances metabolic efficiency and insulin sensitivity via AMPK activation, while humanin prevents mitochondrial apoptosis. Combined, they address mitochondrial function (MOTS-c) and survival signaling (humanin), supporting cellular resilience under metabolic and oxidative stress.

Humanin: 4 mg/kg IP · daily (animal model)
MOTS-c: 5 mg/kg IP · daily (animal model)
Frequency: Once daily
Primary benefit: Mitochondrial health, metabolic efficiency, anti-apoptotic signaling

Sermorelin

+ Ipamorelin

Strong

View Ipamorelin →

Sermorelin (GHRH analogue) and ipamorelin (selective GHRP) form the prototypical GHRH+GHRP dual-axis stack at the lowest cost. Both peak within 30 min and produce a sharp physiological GH pulse without cortisol/prolactin elevation.

Sermorelin: 200–300 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Raun 1998 Walker 1994