A strong plant antioxidant from the creosote bush. Its headline effect — a longer life — comes only from male mice and has never been tested in people. Other benefits rest on animal data alone. The one human effect is from a skin cream. Oral use has caused severe liver injury, sometimes needing a transplant. (Full Review)

Protocol

Dose

None established

No human study has tested oral NDGA for aging, healthspan, or metabolic outcomes

Frequency

Divided doses

Short plasma half-life (a few hours); a single daily dose is unlikely to sustain exposure

Timing

None established

Animal studies delivered NDGA continuously in food, not as timed doses

Time to effect

Skin lesions

~1 month

Topical masoprocol reduced sun-damaged skin patches over 1 month

Lifespan

Lifelong

Animal lifespan effect required lifelong exposure; no human data

Metabolic

Weeks

Animal metabolic changes emerged over weeks of continuous dosing

Benefits

High: Reduced sun-related skin lesions

Medium: Lifespan extension in male mammals

Low: Lower blood and liver triglycerides; improved insulin sensitivity; anti-inflammatory activity

Speculative: Neuroprotection; anticancer activity; antioxidant and cardiovascular effects

Contraindications

Liver disease (fatty liver, hepatitis B/C, cirrhosis, prior drug-induced liver injury)

Chronic kidney disease (eGFR <60 mL/min/1.73 m²)

Pregnancy or breastfeeding

Already taking hepatotoxic medications

Scheduled surgery

Key Interactions

Hepatotoxic drugs (acetaminophen, methotrexate, amiodarone, isoniazid, high-dose statins)

NSAIDs (ibuprofen, naproxen)

Anticoagulants and antiplatelet agents (warfarin, apixaban, clopidogrel, aspirin)

Catechol/liver-enzyme drugs (levodopa, methyldopa)

Hepatotoxic botanicals (high-dose green tea extract, kava, comfrey, pennyroyal)

Additive supplements (omega-3, berberine, glucose-lowering supplements, high-dose vitamin C/E)

Alcohol

Risk & Side Effects

High: Liver injury

Medium: Kidney toxicity

Low: Skin irritation and contact allergy; gastrointestinal upset

Speculative: Pro-oxidant and genotoxic potential; enzyme-inhibition effects

Monitoring

Marker	Target	Why
ALT	<25 U/L (men), <20 U/L (women)	Detects liver-cell injury, the main NDGA hazard
AST	<25 U/L	Complements ALT for liver injury
ALP	40–100 U/L	Flags bile-flow/liver involvement
Total bilirubin	<1.0 mg/dL	Marker of overall liver function
GGT	<25 U/L	Sensitive marker of liver and oxidative stress
Creatinine / eGFR	eGFR >90 mL/min/1.73 m²	Detects the kidney toxicity seen with chronic use
Fasting triglycerides	<80 mg/dL	Tracks the main metabolic benefit target
Fasting insulin	<6 µIU/mL	Tracks insulin sensitivity

Cadence: Liver enzymes at 4–6 weeks, then every 3 months; kidney function every 6–12 months; metabolic markers at baseline and every 3–6 months

Qualitative Assessment

Energy levels and unusual fatigue
Appetite, nausea, or right-upper-abdominal discomfort
Yellowing of skin or eyes, or darkening of urine
General well-being and, where metabolic change is the aim, waist circumference and body weight

Nordihydroguaiaretic Acid for Health & Longevity

Protocol

Benefits

Risk & Side Effects

Monitoring

Qualitative Assessment