Nordihydrocapsaicinguaiaretic acid

Other Names

1,2-Benzenediol, 4,4'-(2,3-dimethyl-1,4-butanediyl)bis-1,4-Bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane2,3-Bis(3,4-dihydroxyphenylmethyl)butane4,4'-(2,3-Dimethyl-1,4-Butanediyl)bis(pyrocatechol)4,4'-(2,3-Dimethyl-1,4-butanediyl)bis-1,2-benzenediol4,4'-(2,3-Dimethyltetramethylene)dipyrocatechol4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diolButane, 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethyl-Dihydronorguaiaretic acidDinorguaiaretic acid, dihydro-MasoprocolNDGANordihydroguaiaretic acidNordihydroguairaretic acidNorguaiaretic acid, dihydro-NSC 4291Pyrocatechol, 4,4'-(2,3-dimethyltetramethylene)di-β,γ-Dimethyl-α,δ-bis(3,4-dihydroxyphenyl)butane

Synopsis

Nordihydroguaiaretic Acid (NDGA)

1. Identity and Chemical Character

Names and Classification

Nordihydroguaiaretic acid (NDGA), also called masoprocol, has the IUPAC name 4-[4-(3,4-dihydroxyphenyl)-2,3-dimethylbutyl]benzene-1,2-diol and is a phenolic lignan mainly extracted from the five plant species that constitute the genus Larrea. Other names of NDGA are 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane, 4,4′-(2,3-dimethyltetramethylene)dipyrocatechol, and masoprocol.

NDGA is a classic lignan, a phenylpropane dimer linked by a bond between positions C8 and C8′, as opposed to a neolignan. As a lignan, it is a member of one of the major classes of phytoestrogens. It is a polyphenol bearing an o-dihydroxy (catechol) structure and possesses four phenolic hydroxyl groups. Structurally, the molecule consists of two catechol rings joined by a dimethylbutane carbon bridge, a configuration central to both its antioxidant potency and its biological reactivity.

Botanical Source and Geographic Distribution

A general source of NDGA is the leaves of Larrea tridentata, also known as "chaparral," "creosote bush," and "gobernadora," which is abundant in the deserts of Mexico and southwest USA. Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Formally, the plant is Larrea tridentata (Sesse and Moc. ex DC) Coville, belonging to the family Zygophyllaceae.

It is abundant in the desert areas of the Mexican states such as San Luis Potosi, Coahuila, Chihuahua, Durango, Sonora, Zacatecas, Baja California Norte and Sur, and in the southwest states of the United States such as Arizona, California, Nevada, Texas, and New Mexico. Similar species are found in arid zones of South America, mostly in Argentina and Bolivia.

Concentration in Plant Material

NDGA accounts for approximately 10% of the leaves' dry weight of L. tridentata and 80% of all flavonoids and lignans that are found in the resin of this plant. The resin that covers the leaves of creosote bush yields 19 flavonoids as well as several lignans. The major lignan in chaparral is nordihydroguaiaretic acid (NDGA), which is a derivative of guaiaretic acid and is a catechol having two hydroxyl groups on each of the two phenol rings.

Preparations and Commercial Forms

Although the pure form of NDGA is not available commercially, chaparral (extract of the creosote bush) is sold as herbal supplements in aqueous extract, tea bags, capsules, and tablets. The major lignan from L. tridentata, nordihydroguaiaretic acid (NDGA), has been used commercially in the United States as an antioxidant in foods. The FDA removed NDGA, formerly used as a food additive in low concentrations, from its "Generally Recognized as Safe" (GRAS) substances list. Masoprocol, a topical cream containing NDGA for the treatment of actinic keratoses, was withdrawn from the US market in June 1996.

2. Traditional and Historical Use

Indigenous North American Use

NDGA is a plant lignan obtained from creosote bush, Larrea tridentata, and is used in traditional medicine in North America and Mexico. This shrub has a long history of traditional medicinal use for a variety of health problems by the Native Americans and Mexicans. Chaparral tea has been used in folk medicine for the treatment of more than 50 ailments including infertility, tuberculosis, arthritis, diabetes, kidney and gallbladder stones, pain, and inflammation.

The Tohono O'odham use L. tridentata for a variety of indications related to childbirth. A powder made from dried leaves is used as an antiseptic to be applied to the navels of newborn children. Additionally, an infusion of dried powdered leaves is applied to the breasts of new mothers to help start the flow of milk.

Aqueous extracts of creosote leaves and twigs have been used medicinally by indigenous North American tribes to treat over 50 health disorders, ranging from colds to cancer.

Traditional Mexican Use

Although controversial, creosote bush, Larrea tridentata, is used to treat a variety of illnesses including infertility, rheumatism, arthritis, diabetes, gallbladder and kidney stones, pain, and inflammation. Recently, it has been used as a nutritional supplement. Chaparral tea was described in American pharmacopeia as a treatment for tuberculosis, arthritis, and cancer.

Food Preservation Use

NDGA was widely used during the 1950s as a food preservative and to preserve natural fibers. Later it was banned after reports of toxicity during the early 1960s. NDGA was once classified as "generally recognized as safe" by the Federal Food and Drug Administration and used as an antioxidant food additive. This classification was withdrawn after studies in rats showed that NDGA produced serious kidney toxicity and other pathologies, including stunted growth and internal hemorrhages.

NDGA has been utilized in traditional healing practices for many years in a wide range of remedies, but at present its application in clinical settings is limited due to reported toxicity in isolated cases.

3. Key Constituents and Active Compounds

NDGA as the Primary Active Lignan

In terms of natural product chemistry, creosote bush is best known for the large amount of the lignan or pure compound NDGA, also known as masoprocol. It is estimated that NDGA composes approximately 5 to 10% of the leaves' dry weight; this corresponds to 80% of all phenolics in the resin. While the full phytochemical profile of L. tridentata is broad — including 19 flavonoids and several other lignans — NDGA is the compound to which most studied pharmacological activity has been attributed.

Structural Features Relevant to Activity

NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals, and this may explain part of its therapeutic action. On the other hand, the oxidation of the catechols to the corresponding quinones may elicit alterations in proteins and DNA that raise safety concerns. This dual nature — potent antioxidant on one hand, potentially reactive quinone-forming species on the other — underlies much of the scientific debate surrounding NDGA.

4. Mechanisms of Action

Lipoxygenase Inhibition

NDGA is a dicatechol and phytochemical polyphenolic antioxidant and an established inhibitor of human arachidonic acid (AA) 5-lipoxygenase (LOX) and 15-LOX. NDGA has been proven to selectively inhibit arachidonic acid 5-lipoxygenase activity, which reduces leukotriene and prostaglandin synthesis, thus leading to a reduction of inflammatory pathways. It is a redox-type inhibitor of 5-lipoxygenase. The inhibition of the lipoxygenase (LOX) pathway is widely considered the compound's best-established and most pharmacologically significant molecular action.

Antioxidant and NRF2 Pathway Activation

The best-characterized effects of NDGA include: the ROS scavenging nature of NDGA, which decreases the pro-oxidant effects of inflammation; the inhibitory effects on lipoxygenase (LOX) activity, leading to the reduction of lipid hydroperoxides; and the activation of endogenous antioxidant responses mediated by NRF2. NDGA activates the antioxidant pathway Nrf2/heme oxygenase-1 (HO-1) in cerebellar granule neurons and protects them against H₂O₂ or 3-nitropropionic acid-induced neurotoxicity.

The direct ROS scavenging capacity and induction of antioxidant enzymes via the Nrf2 pathway may be involved in the mechanism by which NDGA exerts its protective effect.

Inhibition of Growth Factor Receptors

Certain anti-cancer properties in breast cancer cells can be attributed to the ability of NDGA to directly inhibit the function of two receptor tyrosine kinases (RTKs), the insulin-like growth factor receptor (IGF-1R) and the c-erbB2/HER2/neu receptor. In MCF-7 human breast cancer cells, low micromolar concentrations of NDGA inhibited activation of the IGF-1R, and downstream phosphorylation of both the Akt/PKB serine kinase and the pro-apoptotic protein BAD.

NDGA can also inhibit the platelet-derived growth factor receptor and the protein kinase C intracellular signalling family, which both play an important role in proliferation and survival of cancers.

Induction of Apoptosis and Cell Cycle Arrest

NDGA had no inhibitory effect on growth and survival signals such as tyrosine phosphorylation of the epidermal growth factor receptor or basal and growth factor-stimulated activities of extracellular signal-regulated kinase 1/2, p70^s6k, and AKT, but selectively inhibited expression of cyclin D1 in cancer cells. In addition, treatment with NDGA led to a disruption of the filamentous actin cytoskeleton in human pancreatic and cervical cancer cells, accompanied by the activation of Jun-NH₂-terminal kinase and p38^mapk. These results suggest that NDGA induces anoikis-like apoptosis as a result of disruption of the actin cytoskeleton in association with the activation of stress-activated protein kinases.

Cyclooxygenase Inhibition and Neuroprotection

NDGA also has considerable inhibitory activity against cyclooxygenase, resulting in an inhibitory effect on arachidonic acid metabolism, and limited N-methyl-D-aspartate (NMDA, a subclass of glutamate receptor)-induced neuronal toxicity.

PPARα Agonism and Metabolic Effects

NDGA functions as a potent ligand or proligand for and activator of PPARα (either directly or indirectly through its actions as a lipoxygenase inhibitor), suggesting it most likely stimulates lipid metabolism pathways by a mechanism similar to that employed by other PPARα agonists.

Epigenetic Regulation: p300 Inhibition and Autophagy

NDGA robustly increases lifespan in flies and mice, and has been reported to be an inhibitor of the epigenetic regulator p300. NDGA inhibits p300 acetyltransferase activity in vitro and suppresses acetylation of a key p300 target in histones (i.e., H3K27) in cells. In agreement with recent findings indicating that p300 is a potent blocker of autophagy, NDGA treatment induces autophagy. These findings identify p300 as a target of NDGA and provide mechanistic insight into its role in longevity.

Anti-Biofilm Activity

The natural product NDGA is effective as a curlicide in E. coli. NDGA prevents CsgA polymerization in vitro in a dose-dependent manner. NDGA selectively inhibits cell-associated curli assembly and inhibits uropathogenic E. coli biofilm formation.

Skin Barrier and PAR2 Antagonism

NDGA inhibits the PAR2-mediated signal pathway and plays a role in skin barrier recovery in atopic dermatitis. Specifically, NDGA reduces the mobilization of intracellular Ca²⁺ in HaCaT keratinocytes by down-regulating inflammatory mediators, such as interleukin-8, thymus and activation-regulated chemokine, and intercellular cell adhesion molecule-1.

5. Scientific Evidence by Health Area

5.1 Dermatology — Actinic Keratosis (Masoprocol / Actinex)

The most clinically advanced application of NDGA in human medicine has been the topical treatment of actinic keratoses (pre-malignant sun-damaged skin lesions) under the pharmaceutical name masoprocol. Masoprocol received FDA approval for the topical treatment of actinic keratosis (AK). The brand name product was Actinex cream. A pivotal controlled human study was a double-blind, vehicle-controlled trial evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck, published in the Journal of the American Academy of Dermatology in 1991 (Olsen et al., JAAD 1991;24:738–743), and this study is referenced repeatedly in guideline documents. Masoprocol, a topical cream containing NDGA for the treatment of actinic keratoses, was withdrawn from the US market in June 1996. The withdrawal was due to a high rate of contact dermatitis, not loss of efficacy. The evidence base for this application is, uniquely among NDGA uses, supported by controlled human clinical trial data that resulted in initial FDA approval.

5.2 Oncology — Prostate Cancer

The efficacy of NDGA, a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic hormone-sensitive prostate cancer (HSPC) in a phase II clinical trial. NDGA 2000 mg was given orally daily in 28-day cycles and treatment continued until PSA progression or toxicity. Accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled. Seven patients experienced non-sustained declines in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of 1.4 months for all evaluable patients when compared to pretreatment PSADT (range −6.1 to +19.8 months). The trial was terminated per protocol for lack of efficacy. In this study, NDGA was well tolerated. Diarrhea and elevation in hepatic transaminases were the most common side effects, however they were mild (CTC grade 2 or less) in the majority of patients. There were no grade 4 or 5 events.

A separate phase I trial (NCT00313534, University of California, San Francisco/NCI) investigated the maximum tolerated dose and PSA-modulating effects of NDGA in patients with nonmetastatic biochemically relapsed prostate cancer. This phase I trial studied the side effects and best dose of nordihydroguaiaretic acid in treating patients with nonmetastatic relapsed prostate cancer. The primary objective was to determine the maximum tolerated dose, with secondary objectives including prostate-specific antigen-modulating effects.

Evidence strength: For prostate cancer, the evidence is limited to early-phase clinical trials; the phase II study was terminated early due to failure to meet the primary endpoint. Preclinical evidence is robust, but clinical translation has not been demonstrated.

5.3 Oncology — Breast Cancer (Preclinical)

NDGA promoted cell death of trastuzumab-naive and trastuzumab-refractory HER2-overexpressing breast cancer cells. NDGA induced DNA fragmentation, cleavage of poly(ADP-ribose) polymerase and caspase-3, and inhibition of colony formation. In addition, NDGA inhibited insulin-like growth factor-I and HER2 signaling in trastuzumab-refractory cells, with reduced downstream PI3K/Akt signaling. Importantly, combination treatment with NDGA and trastuzumab suppressed proliferation and survival of trastuzumab-refractory cells to a greater degree than either agent alone, suggesting that NDGA increases the sensitivity of refractory cells to trastuzumab. These results are preclinical (cell line and animal model). No human clinical trials in breast cancer have been completed using NDGA itself.

5.4 Oncology — Pancreatic and Cervical Cancer (Preclinical)

The 5-lipoxygenase inhibitor NDGA potently inhibits anchorage-independent growth of human pancreatic and cervical cancer cells in soft agar and delays growth of pancreatic and cervical tumours established in athymic mice. Furthermore, NDGA induces apoptosis of these cancer cells in vitro and in vivo. Evidence strength: Preclinical only; no human data.

5.5 Oncology — NDGA Derivative Terameprocol in Clinical Trials

Terameprocol (a methylated analogue of NDGA) entered Phase I/II clinical trials in patients with recurrent high-grade lymphoma or advanced forms of leukemia, but proved only low anti-tumor activity. These results, while not directly about NDGA itself, provide the most advanced human clinical data on the class of compounds.

5.6 Metabolic Syndrome, Diabetes, and Dyslipidemia (Preclinical)

NDGA exerts profound effects on several components of the metabolic syndrome including lowering of blood glucose, free fatty acids (FFA), and triglyceride (TG) levels and attenuation of elevated blood pressure in several rodent models of dyslipidemia, insulin resistance, diabetes, and hypertension. Feeding ob/ob mice a chow diet supplemented with either low (0.83 g/kg diet) or high-dose (2.5 g/kg diet) NDGA for 16 weeks significantly improved plasma triglyceride (TG), inflammatory chemokine levels, hyperinsulinemia, insulin sensitivity, and glucose intolerance. NDGA treatment caused a marked reduction in liver weight and TG content, while enhancing rates of fatty acid oxidation. Evidence strength: Preclinical (rodent) only. No human clinical trials have investigated these metabolic endpoints for NDGA.

5.7 Neurological and Neurodegenerative Conditions (Preclinical)

NDGA significantly protects against post-ischemic cellular and functional damage in the brain by multiple mechanisms, including an α-tocopherol-like scavenging of lipid hydroperoxides. As neurodegenerative diseases are tightly connected to oxidative stress, NDGA's antioxidant characteristics make it a potential therapeutic tool for protection against oxidative stress in cerebellar neurons by activation of the nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis.

In a fruit fly model of Parkinson's disease, NDGA delayed the loss of climbing ability associated with onset of neurodegeneration. NDGA also decreased motor dysfunction in a mouse model of amyotrophic lateral sclerosis and extended lifespan by 10% in this context. Furthermore, NDGA restored synapse structure and extended lifespan by 19% in a mouse model of Huntington's disease and decreased amyloid-beta deposition in the brains of mouse models of Alzheimer's disease. Evidence strength: Preclinical only. All neuroprotective evidence currently comes from cell culture and animal models.

5.8 Aging and Longevity

NDGA was identified by the National Institute on Aging's Interventions Testing Program (ITP) as one of a small number of agents that reproducibly extend lifespan in heterogeneous mice. The ITP identified six drugs — including rapamycin, aspirin, acarbose, nordihydroguaiaretic acid (NDGA), protandim, and 17α-estradiol — that were associated with increased median lifespan. In particular, NDGA showed a consistent median lifespan extension by 8–10% at three different doses in mice, particularly in males. NDGA also extends median lifespan in evolutionarily distant organisms, such as fruit flies (by 12%) and mosquitoes (by 50%).

Pooling data from all three test sites, a log-rank test showed that both NDGA (p = 0.0006) and aspirin (p = 0.01) led to increased lifespan of male mice. The results for NDGA revealed that males in each dosage group had higher median plasma concentrations of NDGA than females; this difference was two-fold at the original dose used in the survival studies. It is plausible that NDGA may have extended the lifespan of male mice and not females because of differences between the sexes in peak or average NDGA serum concentrations.

Old mice (22 months old) treated with NDGA showed improved grip duration and rotarod performance, indicating better muscle function than untreated age-matched animals. Evidence strength: Animal model data only; no human longevity or aging clinical trials have been conducted.

5.9 Anti-inflammatory and Skin Effects

A mouse skin study provided direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress, corroborating its chemopreventive potential against skin cancer. Pre-treatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. Evidence strength: Predominantly animal model and in vitro data; the clinical use in actinic keratosis (see Section 5.1) is the best-supported human application for skin.

6. Body Systems and Health Areas Associated with NDGA

Based on peer-reviewed literature, NDGA has been studied across multiple biological systems:

Oncology: NDGA, the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders, and cancers.
Integumentary system (skin): Studied for actinic keratosis, atopic dermatitis, and skin tumor promotion inhibition.
Cardiovascular system: NDGA has been shown to have promising applications in the treatment of cardiovascular diseases. Animal models have demonstrated blood pressure reduction and anti-atherogenic effects through LOX inhibition.
Immune system: The antioxidant activity of NDGA strongly diminishes cytokine secretion by dendritic cells.
Nervous system: Neuroprotection through NRF2/HO-1 activation and LOX inhibition, studied in models of ischemia-reperfusion, Alzheimer's disease, Parkinson's disease, Huntington's disease, and ALS.
Metabolic/endocrine: Blood glucose lowering, insulin sensitization, and triglyceride reduction in rodent models, mediated in part via PPARα agonism.
Renal system: Studied in models of nephrotoxicity prevention, though chronic use of chaparral extracts is associated with renal toxicity in humans.
Microbiology/Infectious disease: Anti-biofilm effects against uropathogenic E. coli and broader antiviral activity studied in preclinical settings.

NDGA has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging.

7. Dosage Forms and Doses Reported in Studies

Oral Dosing (Human Clinical Trials)

In the UCSF phase II prostate cancer trial, the first six patients enrolled were treated with a single 750 mg dose of oral NDGA on day −7 with measurement of pharmacokinetic parameters over eight hours after the dose, then began treatment with 2000 mg of oral NDGA daily. Every four weeks, measurement of pharmacokinetic parameters at steady state was performed. This represents the only published dose-finding data for oral NDGA in human subjects.

Animal/Preclinical Doses

In longevity experiments, B6C3F1 mice were fed AIN-93M diet supplemented with 1.5, 2.5, 3.5, or 4.5 g NDGA/kg diet (1.59, 2.65, 3.71, and 4.77 mg/kg body weight/day) beginning at 12 months of age.

In metabolic studies, feeding ob/ob mice a chow diet supplemented with either low (0.83 g/kg diet) or high-dose (2.5 g/kg diet) NDGA for 16 weeks significantly improved plasma triglyceride levels, inflammatory chemokine levels, hyperinsulinemia, insulin sensitivity, and glucose intolerance.

In human monocyte cell culture experiments, NDGA at 20 μM attenuated cell death caused by oxidative stressors.

Topical Formulation (Historical Pharmaceutical)

The FDA-approved masoprocol product Actinex was a topical cream formulation applied to actinic keratosis lesions. The double-blind vehicle-controlled clinical trial supporting its approval was conducted with a standard topical cream formulation applied to the head and neck (Olsen et al., JAAD 1991;24:738–743), though specific concentration details from the approval dossier are not replicated in the open literature sources consulted.

Chaparral (extract of the creosote bush) has been reported to be hepatotoxic at doses of crude herb from 1.5–3.5 g/day. Chaparral tea has traditionally been prepared with 1 teaspoon of chaparral leaves or flowers steeped in 1 pint of water for 15 minutes.

8. Safety Considerations and Interactions

Hepatotoxicity

Chaparral and products containing chaparral have been associated with severe hepatotoxicity, with some cases requiring liver transplantation. Human consumption of creosote leaf and stem extracts as dietary supplements led to cases of hepatitis, cirrhosis, and fulminant liver failure. NDGA may contribute to the hepatotoxicity of L. tridentata. Glucuronidation has been identified as a potential detoxification mechanism for NDGA. Both mono- and diglucuronide conjugates of NDGA are formed after intravenous dosing. The monoglucuronide is also formed after incubation of NDGA with human hepatic microsomes, suggesting that glucuronide conjugation is important in the metabolism of NDGA by humans.

Renal Toxicity

Kidney toxicity associated with NDGA, leading to cystic nephropathy, was initially reported in rats. Later, a case report in humans further associated high consumption of chaparral tea with cystic renal disease and cystic adenocarcinoma of the kidney.

Although consumption of low doses of chaparral products appears to be harmless, high doses have been associated with dermatitis, nephrotoxicity, biliary toxicity, and hepatotoxicity in humans, which includes fulminant liver failure and renal cell carcinoma.

DNA and Protein Reactivity

The oxidation of the catechols to the corresponding quinones may elicit alterations in proteins and DNA that raise safety concerns. This quinone formation, which occurs when the catechol groups of NDGA are oxidized, represents a mechanistic basis for NDGA's potential genotoxic risk.

FDA Regulatory Actions

The FDA removed NDGA, formerly used as a food additive in low concentrations, from its "Generally Recognized as Safe" (GRAS) substances list. The withdrawal of the GRAS designation, combined with the withdrawal of the masoprocol topical product, means that NDGA has no currently approved or GRAS-recognized use in the United States, though chaparral-containing supplements remain available.

Platelet Aggregation Inhibition and Drug Interactions

Because NDGA inhibits platelet aggregation, there is a potential increased risk for bleeding in people taking anticoagulants, antiplatelet drugs, or supplements with these properties. NDGA blocks the activity of cytochrome P450 (the enzyme family that metabolizes many medications) and therefore may increase the risk for toxicity from co-administered drugs. An increased risk for toxicity is expected in people taking renal or hepatotoxic medications.

Safety in Clinical Trial Context

In the phase II prostate cancer trial, NDGA was well tolerated. Diarrhea and elevation in hepatic transaminases were the most common side effects, however they were mild (CTC grade 2 or less) in the majority of patients. Diarrhea in all cases was amenable to supportive care and in all cases but one, liver function test abnormalities resolved spontaneously without study drug discontinuation. This clinical context involved a controlled dose of 2000 mg/day with active safety monitoring and is not directly comparable to uncontrolled herbal supplement use.

Despite compelling preclinical evidence on the potential benefits of NDGA treatment in various pathologies, the major drawback for further clinical development is related to its important side-effects. Most of the available information about safety issues in humans has been obtained from consumption of the chaparral infusion, which is a non-standardized mixture of compounds.

Overall Evidence Landscape

Despite the existence of many preclinical studies that highlight the therapeutic potential of NDGA, the fact is that most of its beneficial effects are not supported by clinical studies. Several medicinal properties have been supported in cell culture and animal studies as well as historical reports. However, the safety and possible toxicity from its application must still be determined in clinical studies. Although lab studies suggest an active compound in chaparral, NDGA, has antiviral, anticancer, and antiparasitic properties, a clinical trial found chaparral was ineffective as an anticancer agent.

References

Health Conditions

Health conditions that Nordihydrocapsaicinguaiaretic acid may help support.

No conditions available.

Body Systems

Body systems that Nordihydrocapsaicinguaiaretic acid may help support.

No body systems available.