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NDGA (nordihydroguaiaretic acid; masoprocol) — the principal lignan/polyphenol antioxidant of the creosote bush (chaparral, Larrea tridentata), a 5-lipoxygenase inhibitor with a real but male-only mouse-lifespan signal AND a serious, FDA-documented hepatotoxicity/liver-failure record
NDGA (nordihydroguaiaretic acid; masoprocol) is the main lignan/polyphenol antioxidant of the creosote bush (chaparral, Larrea tridentata) and a classic 5-lipoxygenase inhibitor. It draws longevity interest for a GENUINE, REPLICATED finding: in the NIA's Interventions Testing Program (ITP), NDGA extended lifespan of genetically heterogeneous MALE mice (Strong 2008; first-cohort interim Miller 2007) — which is why it appears in some longevity stacks. But that is an ANIMAL result, in males only, and a later ITP-stock analysis found NO significant lifespan effect (Flurkey 2010). There are essentially NO human trials supporting longevity use. The CRITICAL fact is harm: NDGA / chaparral is HEPATOTOXIC and nephrotoxic — chaparral herbal products caused acute hepatitis, cirrhosis and fulminant liver failure requiring transplant, prompting an FDA warning against chaparral supplements in the 1990s (Sheikh 1997). Animal work also shows it lowers triglycerides and glucose (Scribner 2000), and it has anticancer/anti-inflammatory preclinical interest, but none of that is established human benefit. This is an informational, harm-reduction entry only — NOT a recommendation: a male-mouse-only longevity signal against a serious, documented human liver-injury record.
Research compound — not a dietary supplement
NDGA (Nordihydroguaiaretic acid) is a research compound, not a regulated dietary supplement. It is sold for research or off-label use. The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
Most NDGA (Nordihydroguaiaretic acid) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from mixed-quality randomised trials published 1991–2014.
Based on 7 studies · 1 RCT
Confidence
Low confidenceBy outcome
NDGA (nordihydroguaiaretic acid / masoprocol), the main antioxidant lignan and 5-lipoxygenase inhibitor of the creosote bush (chaparral, Larrea tridentata), draws longevity interest from a genuine, replicated ANIMAL finding: in the NIA Interventions Testing Program (ITP), NDGA extended lifespan of genetically heterogeneous MALE mice (Strong 2008; interim Miller 2007). But that is mouse data, in males only, and a later ITP-stock analysis found NO significant lifespan effect (Flurkey 2010). There are essentially NO human trials supporting longevity use. Against that, the dominant human-relevant signal is serious harm: chaparral/NDGA is HEPATOTOXIC and nephrotoxic — chaparral supplements caused acute hepatitis, cirrhosis and fulminant liver failure requiring transplant, prompting an FDA warning (Sheikh 1997). Animal metabolic work (triglyceride/glucose lowering, Scribner 2000) and mechanistic antioxidant/Nrf2/5-LOX data (Hernández-Damián 2014) are real but preclinical. With an animal-only, male-only, inconsistent efficacy signal, no human longevity evidence, and a documented liver-failure hazard, the score sits low.
No trials currently enrolling · 5 completed on ClinicalTrials.gov
1 of the completed trials have posted results
Registered trials show research momentum for NDGA (Nordihydroguaiaretic acid), not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Nordihydroguaiaretic acid (NDGA), also known as masoprocol, is the principal lignan and polyphenol of the creosote bush (chaparral, Larrea tridentata), a desert shrub long used in folk medicine.
Pharmacologically NDGA is a potent free-radical/reactive-oxygen-species scavenger and a classic inhibitor of lipoxygenases (notably 5-lipoxygenase), and it also activates the endogenous Nrf2/ARE antioxidant response; in tumour cells it can be pro-apoptotic (Hernández-Damián 2014).
The reason NDGA appears in longevity discussions — and in some longevity stacks such as Bryan Johnson's Blueprint — is a genuine, replicated geroscience result: in the National Institute on Aging's Interventions Testing Program (ITP), a rigorous multi-site mouse-lifespan program using genetically heterogeneous mice, NDGA significantly increased the lifespan of MALE mice.
The first-cohort interim analysis reported significantly improved male survival (Miller 2007), and the fuller analysis confirmed NDGA (and aspirin) increased male lifespan when data were pooled across the three sites, though without a clear effect on maximum lifespan and with no effect in females, possibly reflecting sex differences in drug disposition (Strong 2008).
Importantly, the honest counterpoint is also in the literature: a later analysis using the same UM-HET3 heterogeneous stock found NO significant lifespan effect from NDGA, with only N-acetyl-cysteine extending male lifespan (Flurkey 2010) — so even the mouse signal is not unconditional.
Beyond lifespan, NDGA has real preclinical metabolic activity: as masoprocol it lowered serum triglycerides and glucose and reduced hepatic triglyceride secretion in rodent models of hypertriglyceridemia and type 2 diabetes (Scribner 2000), and it has anti-inflammatory and anticancer preclinical interest.
None of this constitutes established human benefit — there are essentially no human trials supporting longevity, metabolic or other use of NDGA as a supplement. The decisive fact for any human considering it is harm. NDGA and chaparral are HEPATOTOXIC and nephrotoxic.
A review of adverse-event reports to the FDA found that chaparral ingestion was associated with serious liver injury — predominantly a toxic/drug-induced cholestatic hepatitis presenting with jaundice weeks to months after use, with progression to cirrhosis in some and acute fulminant liver failure requiring liver transplantation in others — leading the FDA to warn against chaparral supplements in the early 1990s (Sheikh 1997).
NDGA has also been linked to renal toxicity (cystic nephropathy in animal studies). It is not an approved medicine for longevity, not a dietary supplement this library endorses, and the dose, purity and identity of grey-market NDGA/chaparral products are not assured.
The evidence score sits low and the level is 'Emerging' because the only strong efficacy signal is in male mice (and is not even fully consistent across ITP analyses), there is no supporting human longevity evidence, and the dominant human-relevant signal is a serious, documented hepatotoxicity hazard.
This is an informational, harm-reduction entry: the responsible conclusion is that NDGA is an antioxidant/5-LOX-inhibitor lignan with an intriguing male-mouse lifespan result and a serious liver-injury record in humans — not a supported longevity intervention, and not something this library recommends taking.
NDGA is a classic inhibitor of lipoxygenases — notably 5-lipoxygenase, which generates pro-inflammatory leukotrienes — and a potent scavenger of reactive oxygen species. These actions underlie its anti-inflammatory and antioxidant preclinical activity. Lipoxygenase inhibition by NDGA has been characterised across many cell models (Hernández-Damián 2014); it is mechanistic/in-vitro evidence, not proof of human benefit.
Beyond direct radical scavenging, NDGA activates the endogenous Nrf2/antioxidant-response-element pathway, upregulating cytoprotective antioxidant genes in non-tumour cells. This is one proposed route for its protective effects in preclinical models. It is also 'paradoxical': in tumour cells NDGA is instead pro-apoptotic and can impair mitochondrial function (Hernández-Damián 2014).
As masoprocol, NDGA lowered serum triglycerides and glucose and reduced hepatic triglyceride secretion and liver triglyceride content in rodent models of fructose-induced hypertriglyceridemia and type 2 diabetes (Scribner 2000) — consistent with the creosote bush's folk use for diabetes. This is an animal mechanism for its metabolic effects; it has NOT been established as a human benefit.
In the NIA Interventions Testing Program, NDGA increased lifespan of genetically heterogeneous MALE mice across multiple test sites (Strong 2008; interim Miller 2007), the basis for its longevity reputation. The mechanism is unsettled and the effect is male-only, did not clearly extend maximum lifespan, and was not reproduced in a later UM-HET3 analysis (Flurkey 2010). It is an animal geroscience signal, not human evidence.
How NDGA (Nordihydroguaiaretic acid) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid — the lifespan benefit is in MALE MICE only, was not reproduced in a later analysis, and there is NO human longevity evidence; against this sits a documented record of acute hepatitis, cirrhosis and fulminant liver failure. The risk-benefit is unfavourable.
Avoid entirely — chaparral/NDGA is hepatotoxic and has caused liver failure; it must not be added to an already-stressed liver.
Avoid — NDGA carries a nephrotoxicity signal (cystic nephropathy in animals) and is taken with no renal monitoring.
Avoid — additive liver injury risk on top of a known hepatotoxin.
Avoid entirely — no human safety data and a documented hepatotoxin.
NDGA/chaparral is itself a documented hepatotoxin that has caused fulminant liver failure; combining it with other drugs that stress the liver compounds the risk of serious, potentially irreversible liver injury.
Heavy or regular alcohol use is hepatotoxic; layering it on chaparral/NDGA — which causes cholestatic hepatitis and has progressed to cirrhosis and liver failure — markedly increases the risk of severe liver damage.
As a polyphenol/lignan that affects oxidative enzymes, NDGA can plausibly alter drug metabolism; with liver injury already a risk, any narrow-therapeutic-index co-medication (such as warfarin) becomes harder to manage and less predictable.
NDGA lowered glucose and triglycerides in animals; combined with antidiabetic or lipid drugs it could in principle add to those effects, but this is unstudied in humans and is overshadowed by the hepatotoxicity hazard rather than being a useful interaction.
Tip: This is the defining hazard of chaparral/NDGA and can be irreversible. Jaundice appeared 3-52 weeks after starting in FDA case reports (Sheikh 1997). There is no validated dose that avoids it — the only protection is not to take it; any jaundice, dark urine or right-upper-quadrant pain after use is a medical emergency.
Tip: Some chaparral cases progressed to cirrhosis, and others to acute fulminant liver failure requiring liver transplantation (Sheikh 1997). This is a life-threatening, irreversible outcome — stop use at the first sign of liver trouble and seek urgent care; better, do not use the compound.
Tip: NDGA produced cystic kidney changes in animals and renal involvement appears in chaparral reports. Grey-market use involves no kidney-function monitoring; anyone with renal impairment should avoid it entirely.
Tip: Reported with chaparral ingestion; can also be an early sign of liver involvement, so it should not be dismissed — stop use and check liver chemistry if it occurs.
NDGA (Nordihydroguaiaretic acid) has an evidence score of 3/10 — emerging evidence based on 7 indexed studies. NDGA (nordihydroguaiaretic acid; masoprocol) is the main lignan/polyphenol antioxidant of the creosote bush (chaparral, Larrea tridentata) and a classic 5-lipoxygenase inhibitor. It draws longevity interest for a GENUINE, REPLICATED finding: in the NIA's Interventions Testing Program (ITP), NDGA extended lifespan of genetically heterogeneous MALE mice (Strong 2008; first-cohort interim Miller 2007) — which is why it appears in some longevity stacks. But that is an ANIMAL result, in males only, and a later ITP-stock analysis found NO significant lifespan effect (Flurkey 2010). There are essentially NO human trials supporting longevity use. The CRITICAL fact is harm: NDGA / chaparral is HEPATOTOXIC and nephrotoxic — chaparral herbal products caused acute hepatitis, cirrhosis and fulminant liver failure requiring transplant, prompting an FDA warning against chaparral supplements in the 1990s (Sheikh 1997). Animal work also shows it lowers triglycerides and glucose (Scribner 2000), and it has anticancer/anti-inflammatory preclinical interest, but none of that is established human benefit. This is an informational, harm-reduction entry only — NOT a recommendation: a male-mouse-only longevity signal against a serious, documented human liver-injury record. Representative study: PMID 18631321.
The commonly studied dose of NDGA (Nordihydroguaiaretic acid) is There is no established or endorsed human dose for NDGA/chaparral as a longevity supplement, and this library does NOT provide a dosing protocol. NDGA's only strong efficacy data are in mice (the ITP lifespan studies dosed NDGA in the diet at ~2500-5000 ppm) and its metabolic data are in rodents (masoprocol ~10-80 mg/kg twice daily orally in rats; Scribner 2000) — neither is a human recommendation. The decisive consideration is harm: chaparral/NDGA has caused acute hepatitis, cirrhosis and fulminant liver failure requiring transplant in humans (Sheikh 1997), with no safe dose established and serious injury at doses people actually self-administered. Grey-market NDGA powder and chaparral products are of unverified identity, purity and dose, taken with no liver- or kidney-function monitoring.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take NDGA (Nordihydroguaiaretic acid) is with meals. Take it with food. There is no human dosing protocol this library endorses — NDGA/chaparral has a documented hepatotoxicity/liver-failure record and no human efficacy evidence.
NDGA (Nordihydroguaiaretic acid) should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are acute liver injury / cholestatic hepatitis (jaundice, dark urine, fatigue, abdominal pain), progression to cirrhosis or fulminant liver failure (transplant required), nephrotoxicity / renal injury. Use caution if any of these apply to you: Any human use as a longevity or health supplement — NDGA/chaparral is HEPATOTOXIC and nephrotoxic, has caused fulminant liver failure requiring transplant, and has NO human efficacy evidence; it is a research compound, NOT a recommended dietary supplement; Anyone with any liver disease, hepatitis, elevated liver enzymes, or a history of drug-induced liver injury — chaparral causes acute and chronic liver damage; Anyone with kidney disease or impaired renal function — NDGA carries a nephrotoxicity signal (cystic nephropathy in animals).
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 7 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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