Nordihydroguaiaretic Acid for Health & Longevity - Quick Reference Sheet
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Nordihydroguaiaretic Acid for Health & Longevity

Created on 09/10/2026 – Quick Reference based on Evidence Review created using AI4L / Opus 5 – Audit

A desert-plant antioxidant with a mixed record. The one controlled human benefit, clearing sun-damaged skin patches, came from a cream no longer sold. Lifespan, blood fat, blood sugar and inflammation claims rest on animals and cells. Prolonged oral intake of the parent plant has caused severe liver injury; rats reliably develop kidney cysts. (Full Review)

Protocol

No established longevity protocol
None exists
No human dosing regimen exists for healthspan or lifespan purposes; every regimen below comes from an oncology, dermatology or traditional context
Oral regimen used in oncology research
2000 mg daily
Administered orally in three divided doses, continued in 28-day cycles until progression or toxicity; the only published oral human regimen
Historical topical regimen
10% cream, twice daily
Applied to affected skin for 14 to 28 days, with response assessed a month after the final application; the cream was withdrawn in 1996
Time to effect
Topical form
About 2 months
The topical trial assessed lesion counts one month after a 14-to-28-day course
Oral form
3 cycles of 28 days
Oral oncology dosing used three 28-day cycles before any interim assessment, so effects are not measured in days

Benefits

Contraindications
  • Chronic liver disease (Child-Pugh Class B or C cirrhosis), or baseline alanine aminotransferase above twice the upper limit of normal
  • Prior episode of drug-induced or herb-induced liver injury
  • Reduced kidney filtration (estimated glomerular filtration rate below 60 mL/min/1.73 m²), polycystic kidney disease or a solitary kidney
  • Narrow-therapeutic-index drugs cleared by CYP2C9 or CYP3A4, or any anticoagulant
  • Other hepatotoxic prescription drugs (methotrexate, isoniazid, amiodarone)
  • Pregnancy or breastfeeding
  • Prior allergic contact dermatitis to the topical form
    •
Key Interactions
  • CYP2C9 substrates (warfarin, phenytoin, glipizide)
  • CYP3A4 substrates (tacrolimus, cyclosporine, simvastatin, midazolam)
  • CYP1A2 and CYP2D6 substrates (theophylline, tizanidine, metoprolol, codeine)
  • Acetaminophen and other over-the-counter analgesics
  • Over-the-counter non-steroidal anti-inflammatory drugs (ibuprofen, naproxen)
  • Supplements with liver signals (green tea extract, kava, garcinia, comfrey)
  • Supplements with additive lipoxygenase or anti-inflammatory action (boswellia, curcumin, fish oil)
  • Antiplatelets (aspirin, clopidogrel)
  • Alcohol and other interventions
    •

Risk & Side Effects

  • Medium: Drug-induced liver injury; contact dermatitis and local irritation from the topical form; gastrointestinal and neurologic adverse events at gram-level oral doses
  • Low: Cystic kidney disease
    •
  • Speculative: Increased tumour burden and bleeding, conflicted; reactive quinone formation

Monitoring

Marker Target Why
ALT Men 10–26 U/L; women 8–22 U/L Primary signal of liver-cell injury
AST 10–26 U/L Confirms hepatocellular pattern alongside ALT
ALP 40–90 U/L Detects the cholestatic pattern typical of chaparral injury
GGT Men below 25 U/L; women below 20 U/L Confirms a biliary source and flags glutathione turnover
Total bilirubin 0.3–1.0 mg/dL Jaundice was the presenting sign in reported cases
Creatinine with eGFR eGFR above 90 mL/min/1.73 m² Tracks the filtration function the rodent lesion destroys
Cystatin C 0.6–0.9 mg/L Filtration marker independent of muscle mass
Urinalysis (protein and blood) Negative for both Detects tubular injury before filtration falls
Platelet count with INR Platelets 150–400 ×10⁹/L; INR 0.9–1.1 Covers the bleeding signal seen in long-term rodent dosing and liver synthetic function
Fasting triglycerides Below 100 mg/dL Tests the rodent metabolic claim directly
Fasting glucose with HbA1c Glucose 75–86 mg/dL; HbA1c 4.8–5.4% Second axis of the claimed metabolic effect
hs-CRP Below 0.5 mg/L Tracks the anti-inflammatory claim

Cadence: Liver chemistry at 4 weeks, at 8 weeks, then every 3 months while intake continues; kidney markers and urinalysis every 6 months; metabolic and inflammatory markers every 6 to 12 months; kidney imaging beyond a year.

Qualitative Assessment

  • Appetite loss, nausea or right-sided abdominal discomfort, which preceded jaundice in reported liver injury cases
  • Darkened urine or pale stools, which indicate impaired bile flow before yellowing of skin or eyes appears
  • Unusual fatigue disproportionate to sleep and training load
  • Easy bruising or prolonged bleeding from minor cuts
  • For topical use, escalating redness, itching or spreading rash beyond the treated area, distinguishing allergy from expected irritation
  • Cognitive clarity, given the single reported instance of cognitive disturbance at gram-level oral dosing
Not medical advice. Educational distillation of a single evidence review. Confirm any decision with a qualified clinician, especially in the presence of prescription drugs or chronic conditions.