Side-by-side · Research reference

HumaninvsTesofensine

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 3AUTO-DRAFTED10/40 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Tesofensine

SNDRI · Phase 3 obesity candidate

0.25–0.5 mgDaily doseAstrup 2008

9.2 kgWeight ↓ (24 wk)Astrup 2008

Phase 3Evidence levelAstrup 2008

Oral · Once daily morning

01Mechanism of Action

Parameter

Humanin

Tesofensine

Primary target

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

Serotonin / norepinephrine / dopamine transporters (SERT / NET / DAT)Astrup 2008

Pathway

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

Triple monoamine reuptake inhibition → ↑synaptic 5-HT, NE, DA → appetite suppression + thermogenesisAstrup 2008

Downstream effect

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

Strong appetite suppression, mild thermogenic effect, weight lossAstrup 2008

Feedback intact?

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

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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

Small molecule developed by NeuroSearch (Denmark) for CNS indications, repurposed for obesityAstrup 2008

Antibody development

Not reported in animal models

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02Dosage Protocols

Parameter

Humanin

Tesofensine

Standard experimental dose (HNG)

4 mg/kg IP (rat)

Most common dose in rodent models.

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Ex vivo bone culture

1 µg/mL

Protective against venetoclax-induced bone growth retardation.

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Frequency

Daily (IP)

Once daily, morning

Duration

8–12 weeks in animal studies

24 weeks per studied cycle

Evidence basis

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

Phase 2b + ongoing Phase 3Astrup 2008

Human data

None — no clinical trials reported

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Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

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Standard dose

—

0.25–0.5 mg / dayAstrup 2008

Lower / starter dose

—

0.125 mg / day

Form

—

Oral capsule

Timing

—

Morning to avoid sleep disruption

Half-life

—

~9 days (very long)

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Tesofensine

Direct fat loss evidence

None

—

Mechanism overlap

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

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04Side Effects & Safety

Parameter

Humanin

Tesofensine

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.

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Injection site reaction

Not reported in animal studies (IP route)

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Reproductive safety

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

—

Heart rate / BP

—

Dose-dependent ↑ HR + BPAstrup 2008

Insomnia

—

Dose-related; mitigate with morning timing

Dry mouth

—

Common

Nausea

—

Common

Mood changes

—

Anxiety / agitation possible

Cardiovascular events

—

Phase 3 trial monitoring; not yet FDA-cleared

Pregnancy / OB

—

Contraindicated

Absolute Contraindications

Humanin

·Unknown — no human data

Tesofensine

·Pregnancy / breastfeeding
·Severe cardiovascular disease
·Concurrent MAOI use

Relative Contraindications

Humanin

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

Tesofensine

·Hypertension
·Anxiety disorder
·Insomnia

05Administration Protocol

Parameter

Humanin

Tesofensine

1. Route (experimental)

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

Oral capsule (investigational; not commercial).

2. Reconstitution

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

Swallow whole with water, morning only.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

Morning to mitigate insomnia. Do not dose evening.

4. Storage

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

Room temp ≤25 °C, dry place.

5. Human use

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

Monitor BP + HR + mood. Avoid stimulants + MAOIs.

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

Tesofensine

— no documented stacks