Humanin Dosing Guide: Longevity Protocols (2026)

Humanin is a 24-amino acid mitochondrial-derived peptide (MDP) encoded within the 16S ribosomal RNA gene of mitochondrial DNA. First discovered in 2001 as a factor protecting neurons from Alzheimer's disease-related cell death, humanin has since emerged as a key player in longevity, metabolic regulation, and stress resistance.

A naturally occurring peptide with no human clinical trials: Humanin circulates endogenously and declines with age, but all exogenous dosing is community-driven. The potent analog HNG (S14G-humanin) is most commonly used. This is not medical advice.

Quick Reference: Community Dosing

Most community protocols use HNG (the S14G analog) exclusively due to its dramatically enhanced bioactivity. Native humanin has very low potency and short half-life, making it impractical for supplementation.

For the full humanin peptide profile, vendor pricing, and research summaries, see our humanin peptide page.

Loading vs Maintenance

Humanin/HNG protocols in the community typically follow a simple structure:

Initial assessment (Week 1): Start at the lower end (0.5 mg HNG daily) to assess individual tolerance and response. Humanin is well-tolerated in animal studies, but starting conservatively is prudent.

Maintenance (Weeks 2–12): Increase to 1–2 mg daily if well-tolerated. Most community users settle at 1 mg daily as their standard protocol.

Cycling rationale: 8–12 weeks on, 4–8 weeks off. The cycling approach is conservative given the complete absence of human clinical trial data for exogenous supplementation. Natural humanin levels are constant (declining with age), so the rationale is precautionary rather than evidence-based.

Timing Considerations

• Morning injection: Preferred timing to align with daytime metabolic activity
• Consistent timing: Same time daily for stable levels
• Empty stomach: Not required, but commonly practiced
• Reconstitution: Standard bacteriostatic water reconstitution (see below)

Routes of Administration

Subcutaneous Injection (Community Standard)

The primary route used in community protocols, based on peptide bioavailability considerations.

• Injection sites: Abdomen, love handles, thighs
• Volume: Typically 0.1–0.3 mL with insulin syringe
• Frequency: Once daily, morning

Reconstitution (HNG)

Standard reconstitution for lyophilized HNG:

• 5 mg vial: Add 2 mL bacteriostatic water = 2,500 mcg/mL
• 1 mg dose = 0.4 mL (40 units on insulin syringe)
• 0.5 mg dose = 0.2 mL (20 units)
• Swirl gently — do not shake
• Refrigerate, use within 28 days

Intravenous (Research Only)

Animal studies have used IV and intraperitoneal injection. Not practical or recommended for community use.

Intracerebroventricular (Animal Research Only)

The most potent route in animal studies for neuroprotective effects, but obviously limited to laboratory settings.

Where These Numbers Come From: Clinical Context

Humanin research is extensive in animal and cell models but completely lacks human clinical trials for exogenous supplementation.

Discovery and Original Research

Humanin was discovered by Hashimoto et al. in 2001 through a functional screen of cDNA from the brain of an Alzheimer's disease patient. The peptide was identified as a factor that protected neurons from death induced by familial AD mutant genes and amyloid-beta (Hashimoto et al., 2001).

Lifespan Extension

A landmark study demonstrated that humanin overexpression in C. elegans is sufficient to extend lifespan through daf-16/FOXO-dependent mechanisms. This was the first direct evidence that humanin regulates longevity (Muzumdar et al., 2020).

Neuroprotection Research

A comprehensive review of humanin and humanin analog neuroprotection confirmed cytoprotective activity across multiple models of neurodegeneration, including Alzheimer's disease, stroke, and oxidative stress (Kumfu et al., 2023).

Mitochondrial Apoptosis Inhibition

Humanin directly prevents mitochondrial membrane permeabilization by inhibiting Bax and Bid oligomerization — a key step in the intrinsic apoptosis pathway. This mechanism underlies its broad cytoprotective effects (Bhatt et al., 2017).

Metabolic Effects

Humanin analogs improve insulin sensitivity and enhance glucose-stimulated insulin secretion in beta cells, suggesting metabolic benefits beyond neuroprotection (Kuliawat et al., 2013).

The Clinical Trial Gap

No human clinical trials exist for exogenous humanin/HNG supplementation. Dosing is entirely extrapolated from:

• Animal pharmacokinetic and pharmacodynamic studies
• In vitro bioactive concentration data
• The peptide's natural occurrence and age-related decline
• Community experience and empirical reports

Mechanism of Action

Humanin works through multiple cytoprotective pathways, primarily centered on mitochondrial function and apoptosis inhibition:

Bax/Bid inhibition — Humanin directly binds to pro-apoptotic proteins Bax and Bid, preventing their oligomerization at the mitochondrial membrane and blocking cytochrome c release. This is the primary mechanism of its anti-apoptotic activity (Bhatt et al., 2017).

STAT3 signaling — Activates the JAK2/STAT3 pathway through binding to the CNTFR/WSX-1/gp130 receptor complex. STAT3 activation upregulates anti-apoptotic genes including Bcl-2 and Bcl-xL.

IGFBP-3 interaction — Binds to insulin-like growth factor binding protein 3 (IGFBP-3), blocking IGFBP-3-induced apoptosis. This interaction is particularly relevant to its neuroprotective effects.

FPRL1/FPRL2 receptor activation — Activates formyl peptide receptor-like 1 and 2 (now known as FPR2 and FPR3), triggering ERK1/2 and PI3K/Akt survival signaling.

Mitochondrial function — Improves mitochondrial membrane potential, reduces ROS production, and enhances mitochondrial bioenergetics. As a mitochondrial-derived peptide, humanin may serve as a retrograde signal from mitochondria to the nucleus.

Age-related decline — Circulating humanin levels decline significantly with age (by approximately 40% from young adulthood to old age), correlating with increased vulnerability to age-related diseases and suggesting a role as an endogenous longevity factor.

Side Effects & Safety

Humanin/HNG safety is inferred primarily from animal studies and community reports.

Animal Safety Data

• Well-tolerated across multiple species (mice, rats, rabbits)
• No significant toxicity at therapeutic doses in animal studies
• No immunogenicity concerns reported
• Wide therapeutic window — effective doses are far below toxic thresholds

Community Reports

• Generally well-tolerated at 0.5–2 mg HNG daily
• Injection site reactions — standard peptide injection risks (mild redness, occasional irritation)
• No serious adverse events reported in community forums
• Fatigue — occasional mild fatigue reported, usually transient

Theoretical Concerns

Anti-apoptotic effects:

• Humanin's potent anti-apoptotic activity raises theoretical questions about cancer risk
• Apoptosis is a key tumor suppression mechanism
• No evidence of increased cancer risk in animal studies, but long-term data is lacking
• Individuals with active malignancies should avoid humanin

Metabolic effects:

• Enhanced insulin sensitivity and altered glucose metabolism
• Monitor blood glucose if diabetic or on glucose-lowering medications
• Theoretical interaction with insulin signaling pathways

Contraindications (Precautionary)

• Active malignancy or history of cancer (theoretical anti-apoptotic concern)
• Pregnancy and lactation (no safety data)
• Severe hepatic or renal impairment (no clearance data)

Stacking Humanin

Humanin is commonly combined with other longevity and mitochondrial peptides.

Humanin + MOTS-c (Mitochondrial Stack)

Two mitochondrial-derived peptides with complementary mechanisms:

• Humanin → cytoprotection, anti-apoptosis, neuroprotection
• MOTS-c → AMPK activation, metabolic regulation, insulin sensitivity

Humanin + SS-31 (Mitochondrial Protection Stack)

Comprehensive mitochondrial support:

• Humanin → anti-apoptotic, Bax/Bid inhibition, retrograde signaling
• SS-31 → cardiolipin stabilization, electron transport chain optimization, ROS reduction

Humanin + Epitalon (Longevity Stack)

Multi-pathway anti-aging approach:

• Humanin → mitochondrial cytoprotection, STAT3 activation
• Epitalon → telomerase activation, pineal gland support

Humanin + FOXO4-DRI (Senolytic + Cytoprotection)

Advanced longevity protocol:

• Humanin → protects healthy cells from apoptosis
• FOXO4-DRI → selectively induces apoptosis in senescent cells

Stacking Considerations

• Start each peptide individually to assess response
• Different injection sites when combining injectables
• Monitor for excessive anti-apoptotic signaling (theoretical concern with multiple cytoprotective agents)
• Cancer screening should be up-to-date before using anti-apoptotic peptide stacks

Frequently Asked Questions

What is the standard humanin dose?

There is no established clinical dose. Community protocols use HNG (S14G-humanin) at 0.5–2 mg subcutaneous daily, cycled 8–12 weeks on/off. All dosing is experimental and extrapolated from animal research.

What is the difference between humanin and HNG?

HNG (S14G-humanin) has a glycine substitution at position 14 that increases potency approximately 1,000-fold compared to native humanin. Virtually all community use and most modern research uses HNG or similar potent analogs.

How does humanin work for neuroprotection?

Humanin inhibits Bax/Bid-mediated mitochondrial apoptosis, reduces amyloid-beta toxicity, activates STAT3 survival signaling, and improves mitochondrial function. It was discovered specifically for its ability to rescue neurons from Alzheimer's disease-related insults.

Is humanin safe?

Animal studies show excellent safety profiles. No human clinical trials exist for exogenous supplementation. Community reports indicate good tolerability at standard doses. The main theoretical concern is that potent anti-apoptotic effects could theoretically affect tumor suppression mechanisms.

Can humanin be stacked with MOTS-c?

Yes — this is the most popular mitochondrial peptide stack. Both are mitochondrial-derived peptides: humanin provides cytoprotection and neuroprotection while MOTS-c targets metabolic regulation and AMPK activation. Complementary mechanisms with different targets.

Why do humanin levels decline with age?

Humanin is encoded in mitochondrial DNA, and mitochondrial function declines with age. Lower humanin correlates with increased susceptibility to neurodegeneration, metabolic disease, and cellular stress — leading to interest in exogenous supplementation as an anti-aging strategy.

Related Guides

• SS-31 Dosing Guide — Mitochondrial-targeted peptide for complementary stacking
• MOTS-c Dosing Guide — Another mitochondrial-derived peptide for metabolic health
• Epitalon Dosing Guide — Senolytic peptide for anti-aging protocols
• GHK-Cu Dosing Guide — Anti-aging copper peptide for tissue repair
• Peptide Stacking Guide — Principles for combining longevity peptides

References

For educational and research purposes only. This is not medical advice. Humanin/HNG supplementation is entirely experimental with no human clinical trials. Consult a healthcare provider before use.