Sassafras

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Sassafras

Common Names

  • Ague tree
  • Saxifrax
  • Cinnamonwood
  • Saloop
  • Smelling-stick

For Patients & Caregivers

Tell your healthcare providers about any dietary supplements you’re taking, such as herbs, vitamins, minerals, and natural or home remedies. This will help them manage your care and keep you safe.


How It Works

Safrole and oil of sassafras has been banned as a food additive by the FDA due to carcinogenic concerns, and should not be used to treat medical conditions.

Sassafras is a perennial tree native to Eastern United States. Native Americans used infusions made from the root bark as a remedy to treat fevers, diarrhea, and rheumatism. Sassafras was even used as a flavoring for root beer decades ago. However, sassafras contains safrole, a volatile oil, which has been classified as a likely carcinogen to humans, and banned as a food additive by the FDA. 

Purported Uses

There is no scientific evidence to support the claims below:

  • To detoxify
  • For general health maintenance
  • To reduce inflammation, including mucositis (sores in the mouth and throat)
  • To treat 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
  • Safrole and oil of sassafras has been banned as a food additive by the FDA due to carcinogenic concerns, and should not be used to treat any medical conditions.
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.
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For Healthcare Professionals

Scientific Name
Sassafras albidum
Clinical Summary

Sassafras is a perennial 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. It was also used to scent perfume and even as a flavoring for root beer decades ago.

Studies of sassafras are quite limited and have only been conducted in vitro or in animals. A few experiments suggested antidiabetic (12) and anticancer effects (7) (8) (9) (10) (11). However, safrole was shown to be a carcinogen (5) (13), causing it to be banned as a food additive since the 1960s  (5). Based on these data, the FDA continues to classify safrole as a Substance Generally Prohibited From Direct Addition or Use as Human Food (14).

Purported Uses
  • Detoxification
  • Inflammation
  • Arthritis
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).

However, despite potential apoptotic and cytotoxic effects, data indicates that safrole is “Reasonably anticipated to be a human carcinogen” (5).

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

Case Report

Hot flashes and diaphoresis: due to the ingestion of sassafras tea. (4)

Herb-Drug Interactions

Cytochrome P450 substrates: In vitro, safrole inhibited human CYP1A2, CYP2A6, and CYP2E1 (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, 2nd ed. Sandy (OR): Eclectic Medical Publications; 1998.
  4. Haines JD. Sassafras tea and diaphoresis. Postgrad Med 1991;90;75-6.
  5. National Toxicology Program, Department of Health and Human Services. Safrole. Report on Carcinogens, Fourteenth Edition. Accessed May 13, 2020.
  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 May 13, 2020.
  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.
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