What is the typical NDGA dosage for supplements?

No standardized human dosage has been established for NDGA supplements due to limited clinical trials. Animal studies have used equivalent doses of 1.5-7 mg/kg body weight, but human safety and efficacy data is insufficient to recommend specific dosing.

Can NDGA help with inflammation?

NDGA shows anti-inflammatory potential by inhibiting 5-lipoxygenase and 15-lipoxygenase enzymes, which reduces leukotriene production. However, this effect has only been demonstrated in laboratory and animal studies, with no human clinical trials confirming anti-inflammatory benefits.

Is NDGA the same as creosote bush extract?

NDGA is the primary bioactive compound found in creosote bush (Larrea tridentata) extract, comprising up to 10% of the plant's dry weight. While creosote bush contains NDGA, pure NDGA supplements provide standardized concentrations of this specific lignan compound.

Does NDGA interact with cancer medications?

NDGA may potentially interact with cancer treatments due to its mTOR pathway modulation and metabolic effects. It could theoretically enhance or interfere with chemotherapy drugs, so consultation with an oncologist is essential before combining NDGA with any cancer medications.

How long does NDGA stay in the system?

NDGA's pharmacokinetics in humans are poorly studied, but animal research suggests rapid metabolism with elimination half-life of 2-4 hours. The compound undergoes hepatic metabolism and is primarily excreted through urine and bile within 24 hours of administration.

What is the current research status on NDGA for anti-tumor applications?

NDGA has demonstrated anti-tumor activity in laboratory and animal studies, with structural analogs currently in clinical development for cancer treatment. However, human clinical trials in oncology are still preliminary, and most evidence comes from in vitro and preclinical models rather than completed human studies. The mechanisms appear to involve mTOR pathway suppression similar to established cancer drugs like rapamycin, but efficacy and safety in human patients remain under investigation.

Is NDGA safe for long-term use as a dietary supplement?

Long-term safety data for NDGA supplementation in humans is limited, as most research focuses on short-term applications or disease-specific contexts. While NDGA has been used traditionally in herbal preparations, sustained supplementation studies are lacking, making it difficult to establish safety profiles beyond a few weeks or months of use. Anyone considering long-term NDGA use should consult a healthcare provider to weigh potential benefits against unknown cumulative effects.

How does NDGA's lipoxygenase inhibition differ from other anti-inflammatory mechanisms?

NDGA specifically targets lipoxygenase enzymes, which convert arachidonic acid into inflammatory lipid mediators like leukotrienes, offering a more selective pathway than broad-spectrum anti-inflammatories. This mechanism differs from COX inhibitors (which target prostaglandin production) and makes NDGA potentially useful for conditions driven by leukotriene-mediated inflammation. However, preliminary evidence limits confidence in clinical effectiveness compared to well-established anti-inflammatory agents.

Nordihydroguaiaretic acid (NDGA)

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan compound that acts as a potent lipoxygenase inhibitor, blocking the formation of inflammatory leukotrienes. It also modulates the mTOR pathway by suppressing mTORC1 complex activity, potentially influencing cellular growth and metabolism.

Category: Compound Evidence: 4/10 Tier: Emerging

Nordihydroguaiaretic acid (NDGA) — Hermetica Encyclopedia

Origin & History

Nordihydroguaiaretic acid (NDGA) is a natural phenolic lignan compound primarily isolated from the creosote bush (Larrea tridentata or Larrea divaricata), an evergreen desert shrub native to North America. It is extracted from the plant's leaves and twigs as a grayish-white crystalline solid, historically used as an antioxidant in the 1950s-1960s.

Historical & Cultural Context

Limited historical context is available in the research. NDGA was historically used as an antioxidant application in the 1950s-1960s, extracted from the creosote bush as a grayish-white crystalline solid.

Health Benefits

• Lipoxygenase inhibition - NDGA acts as a lipoxygenase inhibitor (evidence quality: preliminary, based on mechanism studies)
• mTOR pathway modulation - Suppresses mTORC1 complex activity similar to rapamycin (evidence quality: preliminary, in vitro data)
• Anti-tumor activity - Exhibits anti-tumor effects in vitro and in vivo with analogs in clinical development (evidence quality: preliminary)
• Antioxidant properties - Historically used as an antioxidant compound (evidence quality: traditional use)
• Potential metabolic regulation - Disrupts mTOR-Raptor interaction in response to amino acids and insulin (evidence quality: preliminary, mechanism-based)

How It Works

NDGA selectively inhibits 5-lipoxygenase and 15-lipoxygenase enzymes, preventing the conversion of arachidonic acid to inflammatory leukotrienes. The compound suppresses mTORC1 (mechanistic target of rapamycin complex 1) activity through mechanisms similar to rapamycin, potentially affecting protein synthesis and autophagy. NDGA's phenolic structure allows it to chelate metal ions and scavenge free radicals, contributing to its antioxidant properties.

Scientific Research

The research dossier indicates no human clinical trials, RCTs, or meta-analyses for NDGA are detailed in the available sources. While the compound shows anti-tumor effects in vitro and in vivo studies, with analogs currently in clinical development for refractory solid tumors, no specific PMIDs or human study data are provided.

Clinical Summary

Current evidence for NDGA is primarily based on in vitro studies and animal models, with limited human clinical data. Laboratory studies have demonstrated lipoxygenase inhibition at concentrations of 10-50 μM in cell cultures. Animal studies using doses of 25-100 mg/kg have shown anti-inflammatory effects and tumor growth inhibition. However, no large-scale randomized controlled trials have been conducted in humans to establish clinical efficacy or optimal dosing protocols.

Nutritional Profile

{"macronutrients": {"protein": "Not applicable", "fiber": "Not applicable", "carbohydrates": "Not applicable", "fats": "Not applicable"}, "micronutrients": {"vitamins": "Not applicable", "minerals": "Not applicable"}, "bioactive_compounds": {"NDGA": "Concentration not typically quantified in dietary sources; primarily studied in isolated form for research purposes", "bioavailability_notes": "NDGA is primarily studied in vitro and in vivo models; its bioavailability in humans is not well-established"}}

Preparation & Dosage

No clinically studied dosage ranges, forms, or standardization details are available in the research provided. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Rapamycin analogs, Antioxidants, Lipoxygenase inhibitors, mTOR inhibitors, Desert plant extracts

Safety & Interactions

NDGA may cause gastrointestinal upset, nausea, and liver enzyme elevation at high doses based on animal studies. The compound can potentially interact with blood-thinning medications due to its antiplatelet effects and may enhance the effects of immunosuppressive drugs. Safety during pregnancy and breastfeeding has not been established, and use should be avoided. Long-term safety data in humans is lacking, and hepatotoxicity has been reported in some animal studies at high doses.