Humanin (HN) Dosage Guide

Evidence-based protocols for the mitochondrial-derived peptide encoded by MT-RNR2 — subcutaneous and intranasal dosing for neuroprotection, longevity, metabolic health, cardiovascular support, and stacking strategies.

Last reviewed February 24, 2026
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What Is Humanin?

Humanin (HN) is a 24-amino-acid mitochondrial-derived peptide (MDP) encoded by the MT-RNR2 gene within mitochondrial DNA. Discovered in 2001 during a screen for survival factors that protect neurons against Alzheimer's disease-related toxicity, Humanin is one of the most extensively studied MDPs alongside MOTS-c and the SHLP (small humanin-like peptide) family.

Humanin's primary mechanism is cytoprotection — it prevents programmed cell death (apoptosis) by directly binding BAX, a pro-apoptotic protein that triggers the mitochondrial death pathway. By neutralizing BAX, Humanin keeps cells alive that would otherwise self-destruct under stress. Beyond this anti-apoptotic action, Humanin binds the tripartite CNTF receptor/WSX-1/gp130 complex, activating STAT3 signaling pathways that promote cell survival, insulin sensitization, and anti-inflammatory effects.

Circulating Humanin levels decline significantly with age, and this decline correlates with the onset of age-related diseases including neurodegeneration, metabolic syndrome, and cardiovascular disease. Exogenous Humanin supplementation aims to restore these declining levels. Synthetic analogs such as HNG (S14G-Humanin), which is approximately 1,000 times more potent than native Humanin, have been developed for research use.

Use our Peptide Dosage to calculate your exact subcutaneous dose based on vial size and concentration.

Dosing information in this guide is derived from preclinical studies and community protocols — not from approved pharmaceutical labeling.

Key Characteristics:

  • Mitochondrial-derived peptide (MDP)encoded by the MT-RNR2 gene in mitochondrial DNA; 24 amino acids; one of the founding members of the MDP family discovered in 2001
  • Cytoprotective / anti-apoptoticdirectly binds BAX to prevent mitochondrial-mediated apoptosis; keeps stressed cells alive that would otherwise undergo programmed death
  • Neuroprotectiveprotects neurons against amyloid-beta toxicity, tau phosphorylation, oxidative stress, and mitochondrial dysfunction; originally discovered as an Alzheimer’s survival factor
  • Insulin-sensitizingbinds the CNTF/WSX-1/gp130 receptor complex, activating STAT3 signaling that improves glucose tolerance and peripheral insulin sensitivity
  • Age-related declinecirculating levels decrease significantly with aging, correlating with increased susceptibility to neurodegeneration, metabolic syndrome, and cardiovascular disease
  • Synthetic analogs availableHNG (S14G-Humanin) is ~1,000x more potent; HNGF6A offers enhanced stability; most current research uses HNG due to dramatically improved efficacy

For a complete overview of its mechanism and research, see our full Humanin profile. New to peptides? Start with the Beginner's Guide to Peptides.

How Humanin Dosage Is Determined

Humanin dosing is primarily informed by preclinical animal studies and limited community experience. Unlike peptides with extensive human clinical pharmacology data (such as growth hormone secretagogues), Humanin's dosing protocols are largely extrapolated from animal models of neurodegeneration, metabolic disease, and cardiovascular protection. The dose ranges below represent the best available estimates based on current research and community reports.

Original Neuroprotection Discovery

Humanin was identified in 2001 by Hashimoto et al. through a functional screen for genes that protect neurons against amyloid precursor protein (APP)-induced cell death. The discovery that a small peptide encoded within mitochondrial DNA could prevent neuronal apoptosis was groundbreaking and launched the entire field of mitochondrial-derived peptide research. Initial in vitro studies demonstrated neuroprotection at nanomolar to low micromolar concentrations.

Preclinical Dose-Response Studies

Animal studies have used Humanin doses ranging from 0.1 to 10 mg/kg administered via intraperitoneal injection, subcutaneous injection, or intracerebroventricular infusion. Studies in mouse models of Alzheimer's disease demonstrated improved spatial memory and reduced amyloid plaque burden at doses in the mg/kg range. Metabolic studies showed improved insulin sensitivity and glucose tolerance at similar dose ranges. The HNG analog (S14G-Humanin) achieves comparable effects at doses approximately 1,000-fold lower due to its dramatically enhanced potency.

CNTF/WSX-1/gp130 Receptor Binding Studies

Guo et al. characterized Humanin's binding to the tripartite CNTF receptor complex (CNTFRα/WSX-1/gp130), demonstrating that this interaction drives STAT3 phosphorylation and downstream cytoprotective and insulin-sensitizing signaling. The binding affinity and dose-response relationships from these studies support the milligram-range dosing for native Humanin and microgram-range dosing for HNG used in community protocols.

Community-Derived Protocols

Given the absence of formal human clinical dosing data, community protocols for native Humanin have converged around 1–5 mg subcutaneously once daily. This range is derived from allometric scaling of preclinical doses and refined through community experience. The range is wide because individual responses vary and the optimal dose for different goals (neuroprotection vs. metabolic health vs. general longevity) may differ.

Strength of evidence: Strong preclinical, very limited clinical. Humanin has extensive preclinical data across neurodegeneration, metabolism, and cardiovascular models, with well-characterized receptor binding and signaling pathways. However, published human clinical trials are extremely limited. Dosing protocols are based on preclinical pharmacology and community experience. This is a research peptide — not an approved therapeutic.

Standard Humanin Dosage Ranges

Humanin is primarily administered via subcutaneous injection. The optimal dose depends on the specific form used (native Humanin vs. HNG analog), the target condition, and individual response. Always verify which form you have before dosing — the difference between native Humanin and HNG potency is approximately 1,000-fold.

Native Humanin (Subcutaneous)

LevelDose per InjectionFrequencyDaily TotalNotes
Starting1 mg1x daily1 mgAssess tolerance for 1–2 weeks before increasing
Standard2–3 mg1x daily2–3 mgMost common community protocol for general cytoprotection
Higher Range5 mg1x daily5 mgUpper end of community-reported dosing; for targeted neuroprotection protocols

HNG / S14G-Humanin Analog (Subcutaneous)

LevelDose per InjectionFrequencyDaily TotalNotes
Starting1–5 mcg1x daily1–5 mcg~1,000x more potent than native HN; start very low
Standard5–10 mcg1x daily5–10 mcgEquivalent to 5–10 mg native Humanin in cytoprotective potency
Higher Range10–20 mcg1x daily10–20 mcgUpper research range; limited community data at this level

Intranasal (Experimental)

  • Dose: 1–3 mg native Humanin per administration (intranasal bioavailability data is limited)
  • Frequency: 1x daily
  • Rationale: Intranasal delivery may provide some direct CNS access via the olfactory pathway, bypassing the blood-brain barrier — particularly relevant for neuroprotective applications
  • Note: This route is the least established; subcutaneous injection remains the standard for reliable systemic delivery

Administration Routes Compared

Unlike small tripeptides that may survive oral ingestion, Humanin's 24-amino-acid structure requires parenteral (non-oral) administration for reliable delivery. Subcutaneous injection is the primary route. IV administration is used in some research settings, and intranasal is an experimental option for CNS-targeted protocols.

ParameterSubcutaneousIntravenousIntranasal
Typical Dose (Native HN)1–5 mg0.5–3 mg1–3 mg
BioavailabilityHigh (reliable)100% (direct)Variable (mucosal)
Best ForGeneral use / all goalsResearch settingsCNS-targeted protocols
CNS AccessVia systemic circulation (BBB limited)Via systemic circulation (BBB limited)Potential direct access (olfactory pathway)
Ease of UseRequires injectionRequires IV setupEasy (nasal spray)
Community PopularityMost popularRare (clinical/research only)Growing interest
Key AdvantageReliable systemic deliveryImmediate full bioavailabilityPotential BBB bypass for neuroprotection
Why intranasal is gaining interest: Humanin's neuroprotective applications are among its most compelling research areas, but the blood-brain barrier (BBB) limits how much systemically administered peptide reaches the brain. Intranasal delivery may allow some Humanin to reach the CNS directly via the olfactory nerve pathway, bypassing the BBB. While this route is still experimental with limited absorption data, it is increasingly explored in neuroprotection research. Subcutaneous injection remains the standard for reliable systemic delivery.

Calculate Your Humanin Dose

Native Humanin is typically supplied as a lyophilized (freeze-dried) powder in 5 mg or 10 mg vials. You reconstitute it with bacteriostatic water, then draw your dose using an insulin syringe. The concentration depends on how much water you add to the vial.

Worked Example (Native Humanin):

  • Vial size: 5 mg (5,000 mcg) of Humanin
  • Bacteriostatic water added: 1 mL
  • Concentration: 5 mg ÷ 1 mL = 5 mg per mL
  • Target dose: 2 mg
  • Volume to draw: 2 ÷ 5 = 0.4 mL = 40 units on an insulin syringe

Quick Reference — 5 mg Vial (Native Humanin)

Bac Water AddedConcentration1 mg Dose2 mg Dose5 mg Dose
0.5 mL10 mg/mL10 units (0.1 mL)20 units (0.2 mL)50 units (0.5 mL)
1 mL5 mg/mL20 units (0.2 mL)40 units (0.4 mL)100 units (1 mL)
2 mL2.5 mg/mL40 units (0.4 mL)80 units (0.8 mL)Full vial

Skip the Math — Use Our

Enter your vial size, water volume, and desired dose — get instant calculations with zero manual math.

Humanin Dosage by Goal

Humanin's multi-target mechanism (BAX binding, CNTF/WSX-1/gp130 receptor activation, STAT3 signaling) makes it applicable across several research areas. The optimal protocol varies depending on whether you are targeting neuroprotection, metabolic health, cardiovascular support, or general longevity.

Neuroprotection & Cognitive Support

The most extensively researched application of Humanin. Targets neuronal survival via BAX binding (preventing apoptosis), reduction of amyloid-beta toxicity, decreased tau hyperphosphorylation, and preservation of mitochondrial membrane potential in neurons. Relevant for age-related cognitive decline, Alzheimer's disease research, and general brain health.

  • Route: Subcutaneous (standard) or intranasal (experimental, for potential direct CNS access)
  • Dose: 2–5 mg native Humanin daily (SubQ) or 1–3 mg intranasal
  • Frequency: 1x daily, typically in the morning
  • Duration: 8–12 weeks minimum; neuroprotective effects build gradually
  • Stack: + Selank or Semax for synergistic neuroprotection (Humanin prevents apoptosis + Selank/Semax promote neurotrophic signaling)

Metabolic Health & Insulin Sensitization

Humanin improves insulin sensitivity via CNTF/WSX-1/gp130 receptor activation and downstream STAT3 signaling. This enhances glucose uptake, reduces hepatic glucose output, and improves peripheral insulin sensitivity. Preclinical studies have demonstrated improved glucose tolerance in diabetic and obese animal models.

  • Route: Subcutaneous injection
  • Dose: 2–3 mg native Humanin daily
  • Frequency: 1x daily
  • Duration: 8–12 weeks; monitor fasting glucose and insulin markers
  • Stack: + MOTS-c 5–10 mg 3–5x per week for comprehensive metabolic support (Humanin insulin sensitization + MOTS-c AMPK activation and glucose regulation)

Cardiovascular Protection

Humanin has demonstrated cardioprotective effects in preclinical models of myocardial ischemia-reperfusion injury, atherosclerosis, and endothelial dysfunction. It protects cardiomyocytes from apoptosis, reduces oxidative stress in vascular tissue, and improves endothelial function through STAT3-mediated signaling.

  • Route: Subcutaneous injection
  • Dose: 1–3 mg native Humanin daily
  • Frequency: 1x daily
  • Duration: 8–12 weeks
  • Stack: + SS-31 (Elamipretide) for complementary mitochondrial and cardiovascular support (Humanin anti-apoptotic protection + SS-31 cardiolipin stabilization and mitochondrial efficiency)

Longevity & Anti-Aging

The longevity application is based on the observation that Humanin levels decline with age and that this decline correlates with age-related disease. Supplementation aims to restore youthful MDP levels, providing broad cytoprotection, improved mitochondrial function, and resistance to age-related cellular stress. This is the most common community use case.

  • Route: Subcutaneous injection
  • Dose: 1–3 mg native Humanin daily
  • Frequency: 1x daily or 5 days on / 2 days off
  • Duration: Ongoing cycles of 8–12 weeks on, 4 weeks off
  • Stack: + MOTS-c + Epitalon for a comprehensive longevity protocol (mitochondrial protection + metabolic optimization + telomere maintenance)
Patience is key. Humanin's effects are fundamentally cellular and mitochondrial — it protects cells from apoptosis, improves mitochondrial function, and enhances insulin signaling at the receptor level. These are not rapid, perceptible effects like the GH pulse from a GHRP injection. Benefits accumulate gradually over weeks to months. Consistent, sustained use within a well-designed protocol is essential.

Cycling & Duration

Humanin does not act on cell-surface receptors that are known to desensitize with repeated stimulation (unlike GHS-R1a agonists such as Hexarelin). Its primary mechanisms — BAX binding and CNTF/WSX-1/gp130 receptor signaling — are not associated with the rapid tolerance development seen with some other peptide classes. However, cycling is still recommended due to limited long-term human safety data and the theoretical concern about sustained anti-apoptotic signaling.

ProtocolOn-PeriodOff-PeriodNotes
Standard8–12 weeks4 weeks offMost common community cycling pattern; allows reassessment and health monitoring
Conservative4–8 weeks4 weeks offFor first-time users or those with elevated cancer risk concerns
5/2 Schedule5 days on / 2 days off (ongoing)Built inPopular longevity approach; provides regular micro-breaks while maintaining consistent levels
Extended Longevity12–16 weeks4–6 weeks offFor experienced users with clean health monitoring; longer on-period for gradual mitochondrial benefits

When to Extend or Shorten a Cycle

  • Extend beyond 12 weeks only if health monitoring (bloodwork, screening) is clean and you have experience with Humanin. Neuroprotective benefits in particular may require extended consistent use to manifest.
  • Shorten to 4–6 weeks if you are a first-time user, have a family history of cancer, or experience any concerning symptoms during use.
  • Consider the 5/2 schedule as a balanced approach for long-term longevity protocols — it provides consistent peptide exposure with built-in recovery days.
  • Always get bloodwork before starting, at the midpoint of your cycle, and after completion to monitor metabolic markers, inflammatory markers, and general health.

Humanin Stacking Protocols

Humanin stacks well with peptides that target complementary aspects of cellular health, mitochondrial function, and neuroprotection. Its unique anti-apoptotic and insulin-sensitizing mechanisms pair naturally with metabolic peptides, mitochondrial enhancers, and neuroprotective agents. The most rational stacks combine Humanin with other mitochondrial-derived peptides (MDPs) or peptides that act through independent signaling pathways.

Humanin + MOTS-c — The MDP Longevity Stack (Most Popular)

The flagship mitochondrial-derived peptide combination. Humanin provides cytoprotection and anti-apoptotic signaling (BAX binding, STAT3 activation), while MOTS-c activates AMPK for metabolic regulation, glucose homeostasis, and exercise-mimetic effects. Both peptides are encoded in mitochondrial DNA, both decline with age, and their mechanisms are fully complementary — Humanin protects cells from death while MOTS-c optimizes their energy metabolism.

CompoundDoseRoutePurpose
Humanin1–3 mg, 1x dailySubQCytoprotection; BAX binding; anti-apoptotic; insulin sensitization via STAT3
MOTS-c5–10 mg, 3–5x per weekSubQAMPK activation; glucose regulation; exercise mimetic; metabolic optimization
Protocol note: This is the most natural peptide stack in existence — both compounds are produced by human mitochondria and decline with age. The combination aims to restore youthful MDP levels by addressing both the cytoprotective (Humanin) and metabolic (MOTS-c) arms of mitochondrial signaling simultaneously.

Humanin + SS-31 / Elamipretide (Mitochondrial Optimization)

Combines Humanin's anti-apoptotic cellular protection with SS-31's direct mitochondrial membrane stabilization. SS-31 (Elamipretide) targets the inner mitochondrial membrane, stabilizing cardiolipin and optimizing electron transport chain efficiency. While Humanin prevents cell death from mitochondrial stress, SS-31 prevents the mitochondrial stress from occurring in the first place — an upstream/downstream complementary approach.

CompoundDoseRoutePurpose
Humanin1–3 mg, 1x dailySubQAnti-apoptotic protection; BAX neutralization; cell survival signaling
SS-315–20 mg, 1x dailySubQCardiolipin stabilization; ETC optimization; mitochondrial membrane integrity

Humanin + Epitalon (Anti-Aging / Longevity)

Pairs Humanin's mitochondrial cytoprotection with Epitalon's telomerase activation and pineal gland support. Epitalon stimulates telomerase to maintain telomere length (a key biomarker of cellular aging), while Humanin protects cells from mitochondrial-driven apoptosis. This stack targets two of the major hallmarks of aging — mitochondrial dysfunction and telomere shortening — through independent mechanisms.

CompoundDoseRoutePurpose
Humanin1–3 mg, 1x dailySubQMitochondrial cytoprotection; anti-apoptotic; insulin sensitization
Epitalon5–10 mg, 1x daily (10–20 day cycles)SubQTelomerase activation; telomere maintenance; pineal gland support

Humanin + Selank or Semax (Neuroprotection Stack)

A neuroprotection-focused stack combining Humanin's anti-apoptotic neuronal protection with either Selank (anxiolytic, immunomodulatory, BDNF-enhancing) or Semax (neurotrophic, BDNF/NGF-enhancing, cognitive enhancement). Humanin prevents neurons from dying while Selank/Semax promote the growth and function of surviving neurons — protecting existing neurons and enhancing neuroplasticity simultaneously.

CompoundDoseRoutePurpose
Humanin2–5 mg, 1x dailySubQNeuronal survival; BAX binding; mitochondrial protection in CNS
Selank or Semax200–600 mcg, 1–2x dailyIntranasalBDNF/NGF upregulation; neuroplasticity; cognitive enhancement

Explore more combinations with our Peptide Stack Builder or browse the Top 10 Peptide Stacks guide.

Safety, Side Effects & Contraindications

Reported Side Effects

Generally mild based on available preclinical and community data:

  • Injection site reactions (SubQ) — minor redness, soreness, or swelling at the injection site; standard for any subcutaneous peptide injection
  • Mild headache — reported by some users, typically transient and self-resolving within the first week
  • Possible mild fatigue or drowsiness — some users report initial fatigue as mitochondrial signaling adjusts; usually resolves with continued use
  • Nasal irritation (intranasal route) — mild irritation at the nasal mucosa with intranasal administration

Critical Theoretical Concern: Anti-Apoptotic Effects and Cancer

The most important safety consideration with Humanin is its potent anti-apoptotic mechanism. By binding BAX and preventing mitochondrial-mediated apoptosis, Humanin could theoretically protect cancer cells from the programmed death signals that normally destroy them. Some preclinical studies have shown Humanin can promote survival of certain cancer cell lines in vitro.

  • Individuals with active cancer should NOT use Humanin without explicit oncologist approval
  • Those with a recent cancer history or strong genetic cancer predisposition should exercise extreme caution
  • Regular cancer screening and health monitoring is recommended during any Humanin protocol
  • Cycling with off-periods is recommended to allow normal apoptotic surveillance to resume
Nuance on the cancer concern: The relationship between Humanin and cancer is complex. While some studies show potential pro-survival effects on cancer cells, others suggest more nuanced, context-dependent interactions. Humanin is an endogenous peptide produced by all human cells — its natural role is cellular protection, not cancer promotion. However, until more research clarifies this relationship, the precautionary principle applies. This remains an active area of investigation.

Contraindications

  • Active cancer or recent cancer history — Humanin's anti-apoptotic mechanism could theoretically interfere with cancer cell destruction. Consult an oncologist before any use.
  • Pregnancy and breastfeeding — no safety data exists for Humanin during pregnancy or nursing. Anti-apoptotic effects could theoretically interfere with normal developmental apoptosis. Avoid entirely.
  • Immunocompromised individuals — those with compromised immune function should consult a healthcare provider, as altering apoptotic signaling could have complex immune system effects.
  • Children and adolescents — developmental apoptosis is critical in growing organisms. No safety data exists for pediatric use. Do not use.
  • Known hypersensitivity — discontinue use if allergic reactions occur (rash, hives, difficulty breathing).

When to Stop or Reduce Dose

  • Any signs of allergic reaction (rash, hives, swelling, difficulty breathing)
  • Persistent or worsening headache beyond the first 1–2 weeks
  • Any abnormal findings on health monitoring or bloodwork during a cycle
  • Development of unexplained lumps, masses, or changes that could indicate abnormal cell growth
  • Any symptom that feels unusual or concerning — err on the side of caution with an anti-apoptotic peptide
Regulatory Status: Humanin is not FDA-approved for human use. It is classified as a research peptide. It is not available as a dietary supplement or wellness product in most jurisdictions. Regulations vary significantly by country and state — verify your local laws before purchasing.

Common Humanin Dosing Mistakes

Avoid these common errors to get the most out of your Humanin protocol:

Frequently Asked Questions

Key Takeaways

  • Humanin is a 24-amino-acid mitochondrial-derived peptide (MDP) — encoded by MT-RNR2 in mitochondrial DNA; discovered in 2001 as an Alzheimer's disease survival factor
  • Primary mechanism: cytoprotection via BAX binding — prevents mitochondrial-mediated apoptosis; also activates STAT3 via the CNTF/WSX-1/gp130 receptor complex for insulin sensitization and anti-inflammatory effects
  • Levels decline with age — correlating with neurodegeneration, metabolic syndrome, and cardiovascular disease; supplementation aims to restore youthful levels
  • Native Humanin: 1–5 mg SubQ daily is the standard community dose range; start at 1 mg and titrate
  • HNG analog is ~1,000x more potent — verify which form you have before dosing; HNG doses are in the microgram range
  • Not orally bioavailable — subcutaneous injection is the primary route; intranasal is experimental for CNS access
  • Gold standard stack: Humanin + MOTS-c for comprehensive mitochondrial-derived peptide support (cytoprotection + metabolic optimization)
  • Cycling: 8–12 weeks on, 4 weeks off — off-periods are particularly important due to anti-apoptotic mechanism and theoretical cancer concern
  • Critical safety concern: anti-apoptotic effects and cancer — avoid with active cancer, recent cancer history, or high genetic cancer risk; get regular health monitoring
  • Not FDA-approved — classified as a research peptide. Strong preclinical data across neurodegeneration, metabolism, and cardiovascular models, but very limited human clinical data. Consult a healthcare provider.

This article is for educational and informational purposes only. See our Disclaimer.

References

  1. Hashimoto Y, et al. “A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ.” Proc Natl Acad Sci USA. 2001;98(11):6336-6341. PubMed
  2. Guo B, et al. “Humanin peptide suppresses apoptosis by interfering with Bax activation.” Nature. 2003;423(6938):456-461. PubMed
  3. Hashimoto Y, et al. “Detailed characterization of neuroprotection by a rescue factor humanin against various Alzheimer's disease-relevant insults.” J Neurosci. 2001;21(23):9235-9245. PubMed
  4. Muzumdar RH, et al. “Humanin: a novel central regulator of peripheral insulin action.” PLoS One. 2009;4(7):e6334. PubMed
  5. Yen K, et al. “The mitochondrial derived peptide humanin is a regulator of lifespan and healthspan.” Aging (Albany NY). 2020;12(12):11185-11199. PubMed
  6. Lee C, et al. “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metab. 2015;21(3):443-454. PubMed
  7. Muzumdar RH, et al. “Acute humanin therapy attenuates myocardial ischemia/reperfusion injury in mice.” Arterioscler Thromb Vasc Biol. 2010;30(10):1940-1948. PubMed
  8. Tajima H, et al. “Evidence for in vivo production of Humanin peptide, a neuroprotective factor against Alzheimer's disease-related insults.” Neurosci Lett. 2002;324(3):227-231. PubMed
  9. Cobb LJ, et al. “Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.” Aging (Albany NY). 2016;8(4):796-809. PubMed

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