Chaparral

• How It Works

  Chaparral cannot treat or cure cancer or any other medical condition.

  Chaparral is a plant that grows in the desert regions of Mexico and the southwest United States with a long medicinal history. It has been used by Native Americans to treat skin sores, inflammatory disorders, rheumatism, diabetes, tuberculosis, colds, venereal disease and cancer. Chaparral tea has been employed for the treatment of kidney and gallbladder stones.

  A clinical trial found chaparral to be ineffective as an anticancer agent.
  The active compound of chaparral, known as Nordihydroguaiaretic acid (NDGA), has been shown to have antiviral, anticancer, antiparasitic effects in laboratory experiments and animal models.

  Because several patients who regularly drank chaparral tea developed kidney cysts, kidney cancer, and liver damage, chaparral products are not recommended. The FDA removed NDGA, formerly employed as a food additive in low concentrations, from its “Generally Recognized as Safe” (GRAS) substances list. Also, Masoprocol, a topical cream containing NDGA, was developed for the treatment of actinic keratoses, but it was withdrawn from the U.S. market in June 1996.

  Chaparral is an ingredient in black salve, which is promoted as an alternative cancer treatment.

• Purported Uses

  No scientific evidence supports the use of chaparral for any of the following uses:

  • To treat arthritis
  • To treat bronchitis and the common cold
  • To prevent and treat cancer
  • To reduce inflammation
  • To alleviate menstrual cramps
  • To promote urination
  • To stop muscle spasms
• Patient Warnings

  Chaparral and products containing chaparral have been associated with severe liver damage, in some cases requiring liver transplantation.

• Side Effects
  • Fatigue
  • Contact dermatitis
  • Stomach upset
  • Jaundice (yellowing of the skin)
  • Liver damage
  • Cirrhosis of the liver
  • Acute hepatitis
  • Kidney failure
• Scientific Name

  Larrea tridentate, Larrea divaricata

• Clinical Summary

  Chaparral is a plant prevalent in the desert regions of Mexico and the southwest United States with a long medicinal history. Native Americans used extracts and preparations from this plant to treat skin sores, diabetes, cancer, venereal disease, tuberculosis, colds, and rheumatism. The aqueous extract, known as chaparral tea, has been employed for the treatment of kidney and gallbladder stones.

  A phase II clinical trial found chaparral to be ineffective as an anticancer agent ⁽⁹⁾. In another small retrospective study, low intake of chaparral tincture (<10%) did not cause adverse effects ⁽³⁾, but the association between length of exposure and risk is not known;

  Nordihydroguaiaretic acid (NDGA), the active compound isolated from chaparral, has been investigated for its biological effects. In preclinical studies, it demonstrated antioxidant ⁽¹²⁾, anticancer ^{(2) (13) (19) (20)}, antiviral ⁽²¹⁾, anti-parastitic ⁽²²⁾, neuroprotective ⁽¹⁴⁾ and renoprotective ⁽¹⁵⁾ properties; and had a protective effect against diet-induced metabolic function ⁽²³⁾. A pilot study in patients with relapsed prostate cancer reported NDGA to be reasonably well tolerated and to affect increases in PSA doubling time, but was found to be associated with transaminitis in some patients ⁽¹⁶⁾.

  Several cases of reversible and irreversible liver damage ^{(4) (7) (8) (17)} have been associated with chaparral and products containing chaparral. NDGA, formerly employed as a food additive in low concentrations, has been removed by the FDA from its “Generally Recognized as Safe” (GRAS) substances list ⁽¹⁾. Also, Masoprocol, a topical cream containing NDGA, was developed for the treatment of actinic keratoses, but withdrawn from the U.S. market in June 1996 ⁽¹⁸⁾.

  Chaparral is an ingredient in black salve, which is promoted as an alternative cancer treatment.

• Purported Uses
  • Arthritis
  • Bronchitis
  • Cancer prevention
  • Cancer treatment
  • Common cold
  • Inflammation
  • Menstrual cramps
  • Promote urination
  • Spasms
• Mechanism of Action

  Nordihydroguaiaretic acid (NDGA), a lipoxygenase inhibitor, may be responsible for the biological activity of chaparral. It is believed that NDGA may have anticancer activity by blocking cellular respiration in vitro ⁽²⁾. Additional studies have shown that NDGA inhibits the growth of estrogen receptor (ER) positive MCF-7 cells that overexpress HER 2 (MCF-7/HER2-18), and had additive effects when combined with tamoxifen ⁽¹³⁾.

  In murine models, NDGA exerted neuroprotective effect against ischemic/reperfusion injury mediated via suppression of c-Jun N-terminal protein kinase (JNK) pathway ⁽¹⁴⁾; and ameliorates potassium dichromate-induced oxidative stress and nephrotoxicity ⁽¹⁵⁾.

• Warnings

  Chaparral and products containing chaparral have been associated with severe hepatotoxicity, with some cases requiring liver transplantation ^{(4) (7) (8)}.

• Adverse Reactions

  Reported: Fatigue, jaundice, cirrhosis, hepatotoxicity ^{(4) (5) (7) (8) (11)}.

• References

  1. USFDA. CFR – Code of Federal Regulations Title 21. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?…. Accessed March 6, 2019.

  2. Cunningham DC, et al. Proliferative responses of normal human mammary and MCF-7 breast cancer cells to linoleic, CLA and eicosanoid synthesis inhibitors in culture. Anticancer Res 1997;17:197-203.

  3. Pavani M, et al. Inhibition of tumoral cell respiration and growth by norhidydroguaiaretic acid. Biochem Pharmacol 1994;48:1935-42.

  4. Sheikh NM, et al. Chaparral-associated hepatotoxicity. Arch Intern Med 1997;157:913-9.

  5. Tyler V, et al. The Honest Herbal. New York: Pharmaceutical Press; 1993.

  6. Heron S, Yarnell E. The safety of low-dose Larrea tridentata (DC) Coville (creosote bush or chaparral): a retrospective clinical study. J Altern Complement Med 2001;7:175-85.

  7. Batchelor WB, et al. Chaparral-induced hepatic injury. Am J Gastroenterol 1995;90:831-3.

  8. Gordon DW, et al. Chaparral ingestion. The broadening spectrum of liver injury caused by herbal medications. JAMA 1995;273:489-90.

  9. Smart CR, et al. Clinical experience with nordihydroguaiaretic acid — “Chaparrel tea” in the treatment of cancer. Rocky Mt Med J. 1970 Nov;67(11):39-43.

  10. Gordon DW, et al. Chaparral ingestion. The broadening spectrum of liver injury caused by herbal medications. JAMA 1995;273:489-90.

  11. Kauma H, Koskela R, Mäkisalo H, et al. Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets. Scand J Gastroenterol. 2004 Nov;39(11):1168-71.

  12. Kumar S, Wedgwood S, Black SM. Nordihydroguaiaretic acid increases endothelial nitric oxide synthase expression via the transcription factor AP-1. DNA Cell Biol. 2007 Dec;26(12):853-62.

  13. Zavodovskaya M, Campbell MJ, Maddux BA, et al. Nordihydroguaiaretic acid (NDGA), an inhibitor of the HER2 and IGF-1 receptor tyrosine kinases, blocks the growth of HER2-overexpressing human breast cancer cells. J Cell Biochem. 2008 Feb 1;103(2):624-35.

  14. Liu Y, Wang H, Zhu Y, Chen L, Qu Y, Zhu Y. The protective effect of nordihydroguaiaretic acid on cerebral ischemia/reperfusion injury is mediated by the JNK pathway. Brain Res. 2012 Mar 22;1445:73-81.

  15. Yam-Canul P, Chirino YI, Sánchez-González DJ, et al. Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem Toxicol. 2008 Mar;46(3):1089-96.

  16. Ryan CJ, Harzstark AH, Rosenberg J, et al. A pilot dose-escalation study of the effects of nordihydroguareacetic acid on hormone and prostate specific antigen levels in patients with relapsed prostate cancer.  BJU Int. 2008 Feb;101(4):436-9.

  17. USFDA. https://www.accessdata.fda.gov/scripts/plantox/textResults.cfm?q=Larrea…. Accessed March 6, 2019.

  18. Drugs@FDA: FDA Approved Drug Products. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overvie…. Accessed March 6, 2019.

  19. Li X, Fan S, Pan X, et al. Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1. Oncotarget. 2016 Dec 27;7(52):86225-86238.

  20. Leon D, Parada D, Vargas-Uribe M, et al. Effect of nordihydroguaiaretic acid on cell viability and glucose transport in human leukemic cell lines. FEBS Open Bio. 2016 Aug 23;6(10):1000-1007.

  21. Merino-Ramos T, Jiménez de Oya N, Saiz JC, Martín-Acebes MA. Antiviral Activity of Nordihydroguaiaretic Acid and Its Derivative Tetra-O-Methyl Nordihydroguaiaretic Acid against West Nile Virus and Zika Virus. Antimicrob Agents Chemother. 2017 Jul 25;61(8). pii: e00376-17.

  22. Bashyal B, Li L, Bains T, Debnath A, LaBarbera DV. Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri. PLoS Negl Trop Dis. 2017 Aug 9;11(8):e0005832.

  23. Chan JKW, Bittner S, Bittner A, et al. Nordihydroguaiaretic Acid, a Lignan from Larrea tridentata (Creosote Bush), Protects Against American Lifestyle-Induced Obesity Syndrome Diet-Induced Metabolic Dysfunction in Mice. J Pharmacol Exp Ther. 2018 May;365(2):281-290.