Nobiletin for Health & Longevity - Quick Reference Sheet

Nobiletin for Health & Longevity

Created on 09/23/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5.5 Audit

Nobiletin, a citrus-peel compound sold as a dietary supplement for the body's daily clock, metabolism, and brain health, shows striking animal results. Human evidence is thin: small trials of mixed citrus products suggest modest memory gains and less night-time urination. Trials link no consistent side effects, but laboratory data point to possible effects on blood clotting and on how the liver clears common medicines. Overall, low-risk but largely unproven. (Full Review)

Protocol

Trial-based dosing
3–30 mg daily
Most human trials, in mixed products; no dose-finding study exists
Time of day
After dinner in the night-time urination trial
Human optimal timing is unknown; in mice, effects differed by dosing phase
Absorption
With a fat-containing meal
Or lipid-based formulations; poorly water-soluble compound
Time to effect
Memory
16 weeks to 12 months
Multi-ingredient products in healthy older adults
Night-time urination
6 weeks
Nobiletin plus tangeretin after dinner in adults over 50
Muscle quality
12 weeks
Shiikuwasa fruit extract during stroke rehabilitation (pilot trial)

Benefits

Contraindications
  • Pregnant or breastfeeding women
  • Women with hormone receptor-positive breast cancer taking tamoxifen
  • Bleeding disorders or platelet count below 100,000/µL
  • Within 2 weeks before scheduled surgery
  • Moderate-to-severe liver impairment (Child-Pugh Class B or C)
  • Transplant recipients on tacrolimus or cyclosporine without drug-level monitoring
  • Known citrus allergy
Key Interactions
  • Drugs cleared by CYP3A4 with a small margin between effective and toxic levels (tacrolimus, cyclosporine, simvastatin, midazolam): Caution
  • Drugs cleared by CYP1A2 (theophylline, clozapine, tizanidine, caffeine): Caution
  • Drugs moved out of cells by P-gp (digoxin, dabigatran): Monitor
  • Anticoagulants and antiplatelets (warfarin, apixaban, clopidogrel, aspirin): Caution
  • Over-the-counter NSAIDs (ibuprofen, naproxen): Monitor
  • Antiplatelet supplements (fish oil, ginkgo, vitamin E, garlic): Monitor
  • Melatonin: Monitor
  • Other citrus-flavone or grapefruit products (bergamot, tangeretin, grapefruit juice): Caution
  • Additive-effect supplements (berberine, red yeast rice): Monitor
  • UVA phototherapy or tanning beds: Caution

Risk & Side Effects

  • High:
  • Medium:
  • Low: Digestive upset
  • Speculative: Altered levels of prescription drugs; increased bleeding tendency; reduced tamoxifen effectiveness; skin sensitivity to UVA light; acute stress-hormone release

Monitoring

Marker Target Why
Fasting glucose 75–90 mg/dL Glycemic response
HbA1c 4.8–5.3% 3-month glycemic trend
Fasting insulin 2–6 µIU/mL Insulin sensitivity
LDL-C Below 100 mg/dL Lipid response (conflicting evidence)
Triglycerides Below 100 mg/dL Metabolic response
ALT and AST Below 25 U/L each Liver safety
Creatinine and eGFR eGFR above 90 mL/min/1.73 m² Kidney function baseline
Platelet count 150,000–400,000/µL Bleeding risk baseline
INR (warfarin users only) Individual target set by prescriber, usually 2.0–3.0 Detect interaction
Levels of CYP-dependent drugs (tacrolimus, cyclosporine, theophylline) Prescriber's therapeutic range Detect interaction

Cadence: Baseline before starting; INR or drug levels at 1–2 weeks after starting when interacting medications are used; metabolic and liver labs at 12 weeks; then every 6–12 months while use continues

Qualitative Assessment

  • Sleep onset time, night-time awakenings, and morning alertness (sleep diary)
  • Number of night-time urinations
  • Daytime energy and consistency of daily rhythm
  • Subjective memory and mental clarity
  • Bruising or prolonged bleeding from minor cuts
  • Skin reactions after sun exposure