Sassafras

• How It Works

  Because there is no evidence of effectiveness, sassafras should not be used to treat rheumatoid arthritis, infections, or any other medical condition.

  Sassafras is a pernnial tree native to Eastern United States. The Native Americans used infusions made from the root bark as a remedy to treat fevers, diarrhea and rheumatism. Sassafras contains safrole, a volatile oil, which showed anticancer effects in lab and animal studies, but it is also a carcinogen. Human studies have not yet been conducted.

• Purported Uses

  There is no scientific evidence to support the claims below:

  • To detoxify
  • For general health maintenance
  • To reduce inflammation
  • To treat mucositis (inflammation of the mucous membranes of the mouth and throat)
  • To treat rheumatoid arthritis
  • To treat sprains
  • To treat syphilis
  • To treat urinary tract disorders
• Patient Warnings
  • Sassafras is classified as a carcinogenic substance. It caused liver cancer in laboratory animals; the risk of developing cancer increases with the amount consumed and duration of consumption.
• Do Not Take If
  • You are taking drugs that are substrates of Cytochrome P450 1A2, 2A6, and 2E1: Safrole may increase the risk of side effects of these drugs.
• Side Effects
  • Hot flashes
  • Profuse perspiration
• Special Point
  • Sassafras was once used as flavoring agent in root beer and candies, but the Food and Drug Administration has prohibited the use of sassafras as a food additive due to its carcinogenic effects.
• Scientific Name

  Sassafras albidum

• Clinical Summary

  Sassafras is a pernnial tree native to Eastern United States. The Native Americans used infusions made from the root bark as a remedy to treat fevers, diarrhea and rheumatism. Sassafras oil, extracted from the root bark, is used to perfume soaps and to flavor tea and rootbeer.

  Oral administration of safrole significantly improved the diabetic condition in Streptozotocin-induced diabetic rats ⁽¹²⁾, but human studies are lacking.

  Pharmacological studies revealed that sassafras oil contains safrole, a volatile oil, that exerts anticancer effects in vitro and in animal models ^{(7) (8) (9) (10) (11)}. However, safrole has also been shown to be a potent carcinogen ^(5) (13). Based on these data, the FDA classified safrole as a Substance Generally Prohibited From Direct Addition or Use as Human Food ⁽¹⁴⁾.

• Purported Uses
  • Detoxification
  • Health maintenance
  • Inflammation
  • Mucositis
  • Rheumatoid arthritis
  • Sprains
  • Syphilis
  • Urinary tract disorders
• Mechanism of Action

  Safrole, the main active constituent, shows cytotoxic effects in human tongue squamous carcinoma SCC-4 cells by apoptosis via the mitochondria- and caspase-dependent signal pathways ⁽⁷⁾; and through the endoplasmic reticulum stress and intrinsic signaling pathways in human leukemia HL-60 cells ⁽⁹⁾. It also suppressed myelomonocytic leukemia WEHI-3 cells in vivo, and stimulated macrophage phagocytosis and natural killer cell cytotoxicity in leukemic mice ⁽⁸⁾.

  Toxic effects of safrole in Madin-Darby canine kidney (MDCK) cells were shown to be via induction of an increase in cytosolic free Ca2+ by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion, and by inducing Ca2+ influx ⁽¹⁶⁾.

• Warnings

  Sassafras contains safrole, which causes liver cancer in animal models and is classified as a carcinogenic substance. Risk increases with length of exposure and amount consumed. ⁽⁵⁾

• Adverse Reactions

  Common: Hot flashes and diaphoresis. ⁽⁴⁾

• Herb-Drug Interactions

  Cytochrome P450 substrates: Safrole inhibits human CYP1A2, CYP2A6, and CYP2E1 and can affect the intracellular concentration of drugs metabolized by these enzymes ⁽¹⁷⁾.

• References

  1. Newall C, et al. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996.

  2. De Smet PA, et al. Adverse Effects of Herbal Drugs, Vol 3. New York: Springer; 1997.

  3. Brinker F, Herb Contraindications and Drug Interactions, 2^nd ed. Sandy (OR): Eclectic Medical Publications; 1998.

  4. Haines JD. Sassafras tea and diaphoresis. Postgrad Med 1991;90;75-6.

  5. Safrole. Report on Carcinogens. https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html#toc1. Accessed June 30, 2017.

  6. Foster S, et al. Tyler’s Honest Herbal: A Sensible Guide to the Use of Herbs and Related Remedies. New York: Haworth Herbal Press; 1999.

  7. Yu FS, Huang AC, Yang JS, et al. Safrole induces cell death in human tongue squamous cancer SCC-4 cells through mitochondria-dependent caspase activation cascade apoptotic signaling pathways. Environ Toxicol. 2012 Jul;27(7):433-44.

  8. Yu FS, Yang JS, Yu CS, et al. Safrole suppresses murine myelomonocytic leukemia WEHI-3 cells in vivo, and stimulates macrophage phagocytosis and natural killer cell cytotoxicity in leukemic mice. Environ Toxicol. 2013 Nov;28(11):601-8.

  9. Yu CS, Huang AC, Yang JS, et al. Safrole induces G0/G1 phase arrest via inhibition of cyclin E and provokes apoptosis through endoplasmic reticulum stress and mitochondrion-dependent pathways in human leukemia HL-60 cells. Anticancer Res. 2012 May;32(5):1671-9.

  10. Yu FS, Yang JS, Yu CS, et al. Safrole induces apoptosis in human oral cancer HSC-3 cells. J Dent Res. 2011 Feb;90(2):168-74.

  11. Chang HC, Cheng HH, Huang CJ, Chet al. Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells. J Recept Signal Transduct Res. 2006;26(3):199-212.

  12. Rani S, Sharma S, Kumar S. To Investigate Antihyperglycemic and Antihyperlipidemic Potential of Safrole in Rodents by in-vivo and in-vitro Study. Drug Res (Stuttg). 2013 Oct 16. [Epub ahead of print]

  13. Vesselinovitch SD. Perinatal hepatocarcinogenesis. Biol Res Pregnancy Perinatol. 1983;4(1):22-5.

  14. CFR – Code of Federal Regulations Title 21. Safrole. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=189.180. Accesssed December 16, 2013.

  15. Kamdem DP, Gage DA. Chemical composition of essential oil from the root bark of Sassafras albidum. Planta Med. 1995 Dec;61(6):574-5.

  16. Chen WC, Cheng HH, Huang CJ, et al. The carcinogen safrole increases intracellular free Ca2+ levels and causes death in MDCK cells. Chin J Physiol. 2007 Feb 28;50(1):34-40.

  17. Ueng YF, Hsieh CH, Don MJ. Inhibition of human cytochrome P450 enzymes by the natural hepatotoxin safrole. Food Chem Toxicol. 2005 May;43(5):707-12.