Rankings / Longevity — Supplements

NDGA (nordihydroguaiaretic acid)

Longevity · Plant lignan / ITP geroprotector

Tier D

High-risk evidence profile

geroprotectoritpantioxidanthepatotoxicresearch-only
High-risk evidence profile
3.3 / 10
Tier D
Ev 3 Bn 3.5 Sf 3.5

Bottom line

Read Off Label grades NDGA (nordihydroguaiaretic acid) as D (3.3/10) based on weak evidence, low-unknown benefit magnitude, and a med-high-risk safety profile.

Its high-risk evidence profile reflects a Safety score of 3.5/10; reported benefits and harms can differ by indication, dose, route, duration, and population.

One of the NIA Interventions Testing Program's positive hits: NDGA extended median lifespan in male (not female) genetically heterogeneous mice across multiple sites (Strong et al.

Studied, labeled, or reported-use context: No established safe human dose; FDA has issued a hepatotoxicity warning for chaparral supplements — Supplement (chaparral); FDA has warned against chaparral for hepatotoxicity; not approved for any longevity use; not individualized guidance.

What the evidence says

One of the NIA Interventions Testing Program's positive hits: NDGA extended median lifespan in male (not female) genetically heterogeneous mice across multiple sites (Strong et al., Aging Cell 2008). Mechanism is debated — lipoxygenase inhibition, antioxidant activity, lower IGF-1. But the source plant (chaparral/creosote bush) has caused documented acute liver failure in humans, and the FDA has warned against chaparral supplements. No human longevity data exists. The row records a male-mouse geroprotector signal alongside documented human hepatotoxicity and absent human longevity evidence.

Mechanism

Creosote-bush (Larrea tridentata) lignan; a lipoxygenase inhibitor and antioxidant that lowers IGF-1/insulin signaling and inflammation — the proposed mechanisms behind its rodent lifespan effect

Studied, labeled, or reported dose & route

No established safe human dose; FDA has issued a hepatotoxicity warning for chaparral supplements

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about NDGA (nordihydroguaiaretic acid)'s effects?
Read Off Label rates the evidence for NDGA (nordihydroguaiaretic acid) as Weak and the benefit magnitude as low-unknown, producing an overall grade of D (3.3/10). One of the NIA Interventions Testing Program's positive hits: NDGA extended median lifespan in male (not female) genetically heterogeneous mice across multiple sites (Strong et al.
What safety findings are reported for NDGA (nordihydroguaiaretic acid)?
NDGA (nordihydroguaiaretic acid) has a med-high risk profile in the database. Med-High (hepatotoxicity — chaparral/creosote supplements have caused human liver failure; kidney cysts in animals) Legal status: Supplement (chaparral); FDA has warned against chaparral for hepatotoxicity; not approved for any longevity use.
What does the low Safety score for NDGA (nordihydroguaiaretic acid) represent?
The Safety score is 3.5/10. It records the substantial harms described for one or more use contexts; the Benefit score, indication, dose, route, duration, population, and legal status remain separate parts of the evidence profile.
What doses or routes are reported for NDGA (nordihydroguaiaretic acid)?
No established safe human dose; FDA has issued a hepatotoxicity warning for chaparral supplements This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does NDGA (nordihydroguaiaretic acid) work?
Creosote-bush (Larrea tridentata) lignan; a lipoxygenase inhibitor and antioxidant that lowers IGF-1/insulin signaling and inflammation — the proposed mechanisms behind its rodent lifespan effect

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.