Nordihydroguaiaretic acid/NDGA

Chaparral/Drug Interactions:

  • AbortifacientsAbortifacients: Based on animal and toxicology evidence, chaparral and NDGA may induce uterine contractions, cause reproductive toxic effects, possess anti-implantation activity, inhibit ovulation (26), or decrease the number of fetuses (in animals) (27; 28). NDGA was shown to inhibit the prolactin effects on RNA, lipid, and casein biosynthesis in cultured mouse mammary gland explants (25), although the clinical significance of this finding is unclear.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In theory, there may be an increased risk of bleeding with concurrent use of chaparral and anticoagulants or antiplatelets. The chaparral component nordihydroguaiaretic acid (NDGA) diminishes platelet aggregation evoked by collagen or adenosinediphosphate, and delays its onset (18). Pretreatment of rats with NDGA (50mg/kg body weight, by gavage) significantly aggravated indomethacin-induced gastric ulcers (19).
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Chaparral has been reported anecdotally to pose a risk of reacting with monoamine oxidase inhibitors, such as isocarboxazid (Marplan?), phenelzine (Nardil?), or tranylcypromine (Parnate?). There are limited data in this area.
  • Antidiabetic agentsAntidiabetic agents: In theory, chaparral may have additive effects when taken concurrently with hypoglycemic agents. In mouse models of type 2 diabetes, the chaparral component nordihydroguaiaretic acid (NDGA) was shown to decrease plasma glucose concentrations, without any change in insulin concentration (20). NDGA improved glucose tolerance and the ability of insulin to decrease glucose concentrations.
  • Antineoplastic agentsAntineoplastic agents: Based on in vitro and animal studies, lignans from Larrea tridentata, including NDGA, may have antineoplastic effects (56; 57; 58; 59; 60; 61; 62).
  • AntiviralsAntivirals: Based on an in vitro study, NDGA may have antiviral activity, especially against the influenza virus (13).
  • BarbituratesBarbiturates: It has been hypothesized that NDGA may inhibit barbiturate metabolism and interact with drugs, such as phenobarbital (8).
  • Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: NDGA inhibits cytochrome P450-mediated monooxygenase activity in rat hepatic microsomes and laboratory study (63; 64). A plausible mechanism in both hepatotoxicity and nephrotoxicity is the cytochrome P450-dependent metabolism of NDGA to a toxic quinone with failure to remove this reactive metabolite by conjugation if glutathione is limiting (65). NDGA can be expected to be a substrate for cytochrome P450-dependent quinone formation based on its chemical structure, as well as evidence discussed by Obermeyer et al. (14).
  • Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: In many American Indian cultures, chaparral tea has been used to treat numerous intestinal problems. In addition, in a case series of patients with advanced malignancies (types not documented), adverse reactions to chaparral tea or nordihydroguaiaretic acid (NDGA) included nausea, vomiting, diarrhea, abdominal cramps, stomatitis, and fever (29). Therefore, chaparral may theoretically interact with gastrointestinal agents.
  • Hepatotoxic agentsHepatotoxic agents: Chaparral has been reported to induce liver injury (2; 1; 3; 4; 5). Hepatotoxicity has often been reported following ingestion of chaparral over weeks to months, and case reports have noted elevated liver enzymes (11).
  • ImmunosuppressantsImmunosuppressants: It has been suggested that chaparral contains immune-stimulating polysaccharides.
  • Nephrotoxic agentsNephrotoxic agents: Theoretically, use of chaparral with other agents known to induce renal toxicity (e.g., gentamicin or vancomycin) should be avoided. Chaparral has been reported to induce kidney failure (5), and renal cell carcinoma and renal cystic disease have also been reported with chaparral (7).
  • Nonsteroidal anti inflammatory agents (NSAIDs)Nonsteroidal anti inflammatory agents (NSAIDs): In theory, there may be an increased risk of bleeding with concurrent use of chaparral and nonsteroidal anti inflammatory drugs (NSAIDS). The chaparral component nordihydroguaiaretic acid (NDGA) diminishes platelet aggregation evoked by collagen or adenosinediphosphate, and delays its onset (18).
  • Renally eliminated drugsRenally eliminated drugs: Chaparral has been reported to induce kidney failure (5), and renal cell carcinoma and renal cystic disease have also been reported with chaparral (7).
  • Thyroid agentsThyroid agents: Effects of thyroid medications may be altered, although this is unproven.

    • Chaparral/Herb/Supplement Interactions:

  • AbortifacientsAbortifacients: Based on animal and toxicology evidence, chaparral and NDGA may induce uterine contractions, cause reproductive toxic effects, possess anti-implantation activity, inhibit ovulation (26), or decrease the number of fetuses (in animals) (27; 28). NDGA was shown to inhibit the prolactin effects on RNA, lipid, and casein biosynthesis in cultured mouse mammary gland explants (25), although the clinical significance of this finding is unclear.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In theory, there may be an increased risk of bleeding with concurrent use of chaparral and anticoagulants or antiplatelets, such as garlic. The chaparral component nordihydroguaiaretic acid (NDGA) diminishes platelet aggregation evoked by collagen or adenosinediphosphate, and delays its onset (18). Another potential toxicity of chaparral due to the presence of a quinone is vitamin K antagonism since this vitamin is a quinone.
  • Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): Chaparral has been reported anecdotally to pose a risk of reacting with monoamine oxidase inhibitors, such as 5-HTP (5-Hydroxytryptophan) or DHEA (Dehydroepiandrosterone). There are limited data in this area.
  • AntineoplasticsAntineoplastics: Based on in vitro and animal studies, lignans from Larrea tridentata, including NDGA, may have antineoplastic effects (56; 57; 58; 59; 60; 61; 62).
  • AntioxidantsAntioxidants: Based on an in vitro study, lignans from Larrea tridentata, including NDGA, may have antioxidant activities (66; 67).
  • AntiviralsAntivirals: Based on an in vitro study, NDGA may have antiviral activity, especially against the influenza virus (13).
  • Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: NDGA inhibits cytochrome P450-mediated monooxygenase activity in rat hepatic microsomes and laboratory study (63; 64). A plausible mechanism in both hepatotoxicity and nephrotoxicity is the cytochrome P450-dependent metabolism of NDGA to a toxic quinone with failure to remove this reactive metabolite by conjugation if glutathione is limiting (65). NDGA can be expected to be a substrate for cytochrome P450-dependent quinone formation based on its chemical structure, as well as evidence discussed by Obermeyer et al. (14).
  • Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: In many American Indian cultures, chaparral tea has been used to treat numerous intestinal problems. In addition, in a case series of patients with advanced malignancies (types not documented), adverse reactions to chaparral tea or nordihydroguaiaretic acid (NDGA) included nausea, vomiting, diarrhea, abdominal cramps, stomatitis, and fever (29). Therefore, chaparral may theoretically interact with gastrointestinal agents.
  • Hepatotoxic herbsHepatotoxic herbs: Chaparral has been reported to induce liver injury (2; 1; 3; 4; 5). Theoretically, use of chaparral with other agents known to induce liver toxicity should be avoided. Hepatotoxicity has often been reported following ingestion of chaparral over weeks to months, and case reports have noted elevated liver enzymes (11).
  • HypoglycemicsHypoglycemics: In theory, chaparral may have additive effects when taken concurrently with hypoglycemic agents. In mouse models of type 2 diabetes, the chaparral component nordihydroguaiaretic acid (NDGA) was shown to decrease plasma glucose concentrations, without any change in insulin concentration. NDGA improved glucose tolerance and ability of insulin to decrease glucose concentrations (20).
  • ImmunostimulantsImmunostimulants: It has been suggested that chaparral contains immune-stimulating polysaccharides.
  • ImmunosuppressantsImmunosuppressants: It has been suggested that chaparral contains immune-stimulating polysaccharides.
  • Nephrotoxic agentsNephrotoxic agents: Theoretically, use of chaparral with other agents known to induce renal toxicity should be avoided. Chaparral has been reported to induce kidney failure (5), and renal cell carcinoma and renal cystic disease have also been reported with chaparral (7).
  • Renally eliminated herbs and supplementsRenally eliminated herbs and supplements: Chaparral has been reported to induce kidney failure (5), and renal cell carcinoma and renal cystic disease have also been reported with chaparral (7).
  • Thyroid agentsThyroid agents: Effects of thyroid medications may be altered, although this is unproven.
  • Vitamin KVitamin K: Due to the presence of a quinone, there is a potential risk of vitamin K antagonism when taken concomitantly with vitamin K because this vitamin is a quinone.

    • Chaparral/Lab Interactions:

  • Blood glucoseBlood glucose: Chaparral may lower serum glucose levels. In mouse models of type 2 diabetes, the chaparral component nordihydroguaiaretic acid (NDGA) was shown to decrease plasma glucose concentrations, without any change in insulin concentration. NDGA improved glucose tolerance and ability of insulin to decrease glucose concentrations (20).
  • Liver enzymesLiver enzymes: Hepatotoxicity has often been reported following ingestion of chaparral over weeks to months, and case reports have noted elevated liver enzymes (11; 22; 11; 23; 5).
  • Serum creatinineSerum creatinine: Chaparral has been reported to induce kidney failure (5), and has been associated with elevations of creatinine to 1.5mg/dL (without subsequent improvement of renal function despite cessation of chaparral therapy) (7).