Side-by-side · Research reference

HumaninvsTesamorelin

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

BFDA-ApprovedFlagship27/68 cited

Humanin

Mitochondrial-Derived Peptide · Cytoprotective

24-AAPeptide lengthZhu 2022

mtDNAEncoded originZhu 2022 Shahzaib 2026

Bax/BimPrimary targetZhu 2022 Morris 2021

SQ · Experimental

Tesamorelin

GHRH Analogue · FDA-Approved

2 mgDaily doseEGRIFTA® (tesamorelin for inje 2010

15–20%VAT reductionFalutz 2010

~26 minHalf-lifeEGRIFTA® (tesamorelin for inje 2010

SQ · Abdomen · Once Daily

01Mechanism of Action

Parameter

Humanin

Tesamorelin

Primary target

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

Hypothalamic GHRH receptorsEGRIFTA® (tesamorelin for inje 2010

Pathway

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

GHRH → Pituitary GH release → Liver IGF-1 synthesisFalutz 2007

Downstream effect

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

Increased GH pulsatility, elevated IGF-1, lipolysis of visceral adipose tissueFalutz 2010

Feedback intact?

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

Yes — physiological pulsatility preserved

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

Synthetic 44-AA GHRH analogue with trans-3-hexenoic-acid modification for stabilityEGRIFTA® (tesamorelin for inje 2010

Antibody development

Not reported in animal models

~50% after 26 wks (non-neutralising in most)Sévigny 2018

02Dosage Protocols

Parameter

Humanin

Tesamorelin

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 (morning or pre-sleep)

Aligns with natural GH pulse.

Duration

8–12 weeks in animal studies

12–52 weeks

VAT returns within months of stopping.

Evidence basis

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

RCT / FDA-approvedFalutz 2007 Falutz 2010

Human data

None — no clinical trials reported

—

Analog (HNG)

Gly[14]-humanin — more potent variant

Substitution at position 14 enhances cytoprotective activity.

—

Standard dose

—

2 mg / dayEGRIFTA® (tesamorelin for inje 2010

FDA-approved protocol.

Lower / starter dose

—

1 mg / dayFalutz 2010

1 mg still produces significant IGF-1 elevation.

Reconstitution

—

Sterile water per labeling

Preserved at 2–8 °C after reconstitution.

Timing

—

Empty stomach, pre-sleep preferred

Half-life

—

~26 min (plasma)EGRIFTA® (tesamorelin for inje 2010

Modified vs native GHRH (7 min t½).

03Metabolic / Fat Loss Evidence

Parameter

Humanin

Tesamorelin

Direct fat loss evidence

None

—

Mechanism overlap

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

—

Primary fat target

—

Visceral adipose tissue (VAT) — abdominal

Quantified reduction

—

15–20% VAT ↓Falutz 2010

By CT at 26 weeks (Falutz et al., NEJM).

IGF-1 impact

—

+66 ng/mL (2 mg dose) · +81% mean elevationFalutz 2007

Effect on lean mass

—

Modest lean mass preservation / slight increase

Insulin sensitivity

—

Neutral to slight impairment (monitor HbA1c)Clarke 2018

Triglycerides

—

Significant TG reduction noted in Phase 3Falutz 2010

Glucose metabolism

—

Generally neutral; 4.5% HbA1c elevation riskClarke 2018

Effect reversibility

—

VAT returns within months of stopping

Key publication

—

Falutz et al. NEJM 2007 · Falutz JCEM 2010 · FDA approval 2010Falutz 2007 Falutz 2010 EGRIFTA® (tesamorelin for inje 2010

04Side Effects & Safety

Parameter

Humanin

Tesamorelin

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)

Erythema, pruritus, redness (common)

Reproductive safety

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

—

Fluid retention / Edema

—

Peripheral edema, arthralgia, carpal tunnel (GH-axis effect)

Glucose intolerance

—

HbA1c ↑ in 4.5% vs 1.3% placebo; HbA1c ≥6.5% hazard OR 3.3Clarke 2018

IGF-1 elevation

—

Dose-dependent; supraphysiological levels = discontinue

Cancer risk

—

Contraindicated in active malignancy (GH/IGF-1 axis); theoretical tumour growth riskEGRIFTA® (tesamorelin for inje 2010

Antibody formation

—

~50% at 26 weeks; non-neutralising in most; rare hypersensitivity (<1%)Sévigny 2018

GI symptoms

—

Nausea, diarrhea (mild, transient)

Pregnancy / OB

—

ContraindicatedEGRIFTA® (tesamorelin for inje 2010

Absolute Contraindications

Humanin

·Unknown — no human data

Tesamorelin

·Active malignancy or history of treated cancer
·Pregnancy
·Hypersensitivity to tesamorelin or mannitol
·Disruption of hypothalamic-pituitary axis (trauma, tumour, radiation)

Relative Contraindications

Humanin

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

Tesamorelin

·Untreated diabetes (monitor HbA1c)
·Severe carpal tunnel syndrome
·Acute critical illness

05Administration Protocol

Parameter

Humanin

Tesamorelin

1. Route (experimental)

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

Add 2.1 mL sterile water to 2 mg lyophilised vial. Roll gently — do not shake. Solution should be clear.

2. Reconstitution

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

Subcutaneous — abdomen preferred. Rotate sites (avoid same spot within 2 cm). Avoid navel and waistband area.

3. Timing

Daily administration in animal studies. Optimal timing not characterized.

Once daily. Preferred: evening, 2–3 hrs post-meal, before sleep — aligns with natural GH secretion pulse.

4. Storage

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

Lyophilised: room temp, light-protected. Reconstituted: refrigerate 2–8 °C, use within 21 days.

5. Human use

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

27–31G, 4–8 mm insulin syringe. Pinch skin, 45° angle for lean individuals.

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

Tesamorelin

+ Ipamorelin

Strong

View Ipamorelin →

Tesamorelin (GHRH analogue) and ipamorelin (GHRP / ghrelin mimetic) act on two distinct receptor systems to amplify GH release synergistically — GHRH receptor + ghrelin receptor. This dual-axis stimulation produces a more robust, sustained GH pulse than either alone while maintaining physiological pulsatility. Ipamorelin is highly selective with minimal cortisol or prolactin elevation, making it the preferred GHRP pairing.

Tesamorelin: 2 mg SQ · evening
Ipamorelin: 200–300 mcg SQ · same injection
Frequency: Once daily, pre-sleep
Primary benefit: Maximal GH pulsatility, fat loss, recovery, sleep quality

Raun 1998