ISRIB for Health & Longevity - Quick Reference Sheet

ISRIB for Health & Longevity

Created on 09/04/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 Audit

ISRIB releases a cellular brake on protein production. In rodents it reversed memory loss from ageing and head injury and awakened dormant egg cells. No person has taken it in a registered trial. Harms — impaired protein clearance, tumour and infection effects, egg-reserve loss, heart effects — are reasoned from mechanism or animals. It sits at the far speculative end. (Full Review)

Protocol

Human dosing standard
None exists
No validated human protocol. ISRIB is not approved anywhere, has no prescribing information, and no clinic has published a dosing standard.
Preclinical reference regimen
0.1–2.5 mg/kg, 2–3 doses
Rodent efficacy studies dosed by injection into the abdominal cavity. No validated conversion of that dose to humans has been published.
Single versus split dosing
Untested in humans
Rodent work used single injections rather than divided doses, and poor water solubility makes oral absorption erratic.
Time to effect
Memory change (rodent)
Within days
In rodents, memory changes appeared within days of a two-to-three-dose course.
Persistence (rodent)
At least 3 weeks
Effects persisted for at least three weeks after dosing stopped.
Human time course
Does not exist
No human time course exists, so the rodent figure cannot be transferred.

Benefits

Contraindications
  • Proteasome inhibitors (bortezomib, carfilzomib, ixazomib)
  • Active or recent malignancy, or within five years of treatment for a solid tumour
  • Amyotrophic lateral sclerosis or a known SOD1 mutation
  • Active viral or bacterial infection until fully resolved
  • Pregnancy, breastfeeding, attempting conception, or wishing to preserve ovarian reserve
  • Congenital long QT syndrome, or corrected QT above 470 ms in men or 480 ms in women
  • Moderate or severe liver impairment (Child-Pugh Class B or C), or estimated glomerular filtration rate below 45 mL/min/1.73 m²
  • Under 18 years of age
Key Interactions
  • Platinum chemotherapy (cisplatin, carboplatin, oxaliplatin)
  • Tyrosine kinase inhibitors (imatinib, ponatinib, dasatinib)
  • Macrolide antibiotics (azithromycin, clarithromycin, erythromycin)
  • QT-prolonging medicines (amiodarone, sotalol, citalopram, ondansetron)
  • Over-the-counter analgesics (high-dose paracetamol, ibuprofen, naproxen)
  • Chemical chaperone supplements (TUDCA, 4-phenylbutyrate)
  • Translation-promoting supplements (leucine, creatine, essential amino acid blends)
  • Stress-pathway-activating botanicals (high-dose curcumin, resveratrol, berberine)
  • Rapamycin and other mTOR inhibitors
  • Extended fasting, protein restriction and ketogenic diets

Risk & Side Effects

  • High: [risks_high]
  • Medium: [risks_medium]
  • Low: [risks_low]
  • Speculative: Impaired clearance of damaged proteins; accelerated motor neuron loss; altered response to infection; altered tumour behaviour; accelerated depletion of ovarian reserve; cardiovascular effects seen with close analogues; harm from long-term suppression of a protective pathway

Monitoring

Marker Target Why
ALT 10–26 U/L Detects liver injury from a compound with unpublished human clearance
AST 10–26 U/L Confirms and localises any ALT rise
Lipase 10–60 U/L Screens for pancreatic irritation, the toxicity that ended PERK-inhibitor development
Fasting glucose 75–86 mg/dL Stress-pathway signalling governs glucose handling and transporter expression
HbA1c 4.9–5.3% Captures glucose drift that a single fasting value misses
hs-CRP <0.5 mg/L Tracks the inflammatory tone this pathway both responds to and drives
eGFR >90 mL/min/1.73 m² Kidney clearance matters when elimination routes are unpublished
Anti-Müllerian hormone Above the 50th centile for age; any fall over 12 months is the signal Detects depletion of the dormant ovarian follicle pool
Corrected QT interval <440 ms in men, <450 ms in women Screens for the cardiac effect that ended the closest analogue's development
Cognitive battery score No established target; track change against the individual's own two baseline sessions Measures the claimed benefit rather than a proxy for it

Cadence: Full baseline panel before any exposure, with a repeatable cognitive battery administered twice. Electrocardiogram plus liver and pancreatic enzymes at two weeks and four weeks. Full panel at three months, then every three to six months during continued use. Anti-Müllerian hormone repeated at six months.

Qualitative Assessment

  • Ease of recalling names, appointments and where objects were placed
  • Speed of picking up genuinely new material rather than rehearsing familiar material
  • Mental clarity in the late afternoon, when age-related decline is most noticeable
  • Sleep quality and dream recall, since the pathway is engaged by sleep loss
  • Absence of new palpitations, unexplained fatigue, upper abdominal pain, or reduced exercise tolerance