HNG Reconstitution Calculator

No. HNG (S14G-humanin) is a synthetic analogue of the endogenous mitochondrial-derived peptide humanin. It remains an experimental compound with no FDA approval or approved human therapeutic indication. All available efficacy data derive from preclinical models [1–3,6,7] and a handful of human observational studies evaluating endogenous humanin levels, not exogenous HNG administration.

In rodent studies, HNG is most often administered via intraperitoneal (IP) injection at 2–10 mg/kg/day. For example, 0.4 mg/kg/day IP for 16 weeks ameliorated diabetic nephropathy in rats, while 2.5 mg/kg twice daily IP improved insulin sensitivity in diet-induced obese mice. For cardiac ischemia-reperfusion, a single IV dose of 252 μg/kg given during ischemia was cardioprotective in rats. Porcine studies used 2 mg/kg IV. No human dose has been established; common community research protocols extrapolate from animal data, typically using 0.5–5 mg subcutaneously once daily (community protocol), though these are not validated.

Nearly all preclinical efficacy studies used IP or IV routes; no direct head-to-head comparisons exist. Intravenous delivery achieves rapid peak levels but requires clinical settings; IP is impractical in humans. Subcutaneous administration is the most common route in community use due to convenience, though absorption and bioavailability data are absent. For intranasal delivery, one study demonstrated that intranasal HNG improved cognition in an Alzheimer’s mouse model; however, no human nasal formulation is available. In summary, subcutaneous is currently the default for research, but its pharmacokinetics are unknown.

Yes. A stability study showed that HNG in HPLC-grade water degraded significantly at 37 °C over days, with oxidation and dimerization occurring. In a proprietary MO formulation stored at 4 °C, HNG remained >95% intact for at least 28 days. For reconstituted peptide, storage at 2–8 °C in a sterile buffer (e.g., phosphate-buffered saline) is recommended, and freezing in single-use aliquots can further extend stability (community protocol). Avoid repeated freeze-thaw cycles.

Endogenous humanin levels decline with age, and lower circulating humanin is associated with increased mortality in heart failure patients (observational). In aged mice, chronic HNG treatment (4 mg/kg twice weekly for 14 months) attenuated age-related myocardial fibrosis and apoptosis, partly via Akt/GSK-3β signaling. HNG also prevented endothelial senescence in high-glucose-challenged human cells by upregulating SIRT6. However, no interventional human data exist to support anti-aging claims. The evidence remains preclinical and correlational.

There are no human safety data for exogenous HNG. In rodent and porcine models, HNG has generally been well-tolerated at therapeutic doses, with no serious adverse events reported in short-term studies [8,10]. One study noted that HNG alone did not cause cardiac toxicity, but when combined with bortezomib in neonatal mice, bortezomib-related toxicity (mortality) was a concern, though HNG was not the causative agent. For pregnancy, animal data show HNG can cross the placenta and modulate fetal outcomes in diabetic mouse models, making use during pregnancy contraindicated.

Both are mitochondrial-derived peptides with cytoprotective properties, but they act through distinct mechanisms. HNG primarily signals via the IL-6 receptor subunit gp130/STAT3 and can also inhibit BAX-mediated apoptosis [2,3,10]. MOTS-c predominantly activates AMPK and regulates nuclear gene expression to improve metabolic homeostasis [12,15]. In a head-to-head muscle atrophy model, both prevented dexamethasone-induced myotube loss, but MOTS-c uniquely enhanced Akt phosphorylation and suppressed MURF1, while HNG blunted STAT3 activation. The choice between them depends on targeted pathway; no human comparative trials exist.