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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 23, 2017.



Cascara is a popular herbal medication and over-the-counter therapy of constipation. Cascara is generally safe and well tolerated, but can cause adverse events including clinically apparent liver injury when used in high doses for longer than recommended periods.


Cascara sagrada is an herbal medication used for centuries as a laxative which is now available in the United States without prescription for short term treatment of constipation. Cascara is typically an extract from the dried, aged bark of Rhamnus purshiana, a species of buckthorn tree or shrub native to North America. Cascara sagrada is Spanish for “sacred bark” and was used for centuries by Native Americans as a laxative. Cascara became accepted in western medical practice in the 19th century and is still used in over-the-counter laxative preparations, often in combination with other herbals such as aloe vera. The active laxative components in cascara are anthraquinone derivatives and their glucosides, referred to as cascarosides. They appear to act locally as an irritant to the colon promoting peristalsis and stool evacuation. Anthraquinones also inhibit reabsorption of electrolytes and water from the colon. Cascara is minimally absorbed. The typical dose is 300 mg once daily, but it is recommended for short term use only (less than one week). Side effects include abdominal cramps and electrolyte imbalance. Long term use or abuse can lead to “cathartic” colon with diarrhea, cramps, weight loss and darkened pigmentation of the colonic mucosa.


Use of cascara in the recommended doses for a limited period of time has been associated with few side effects, most of which are mild and transient. With longer term use of high doses of cascara, however, adverse events have been described including several cases of clinically apparent liver injury. The time to onset of liver injury has varied from a few days to 2 months of use, and the pattern of serum enzyme elevations varied from hepatocellular to cholestatic. The liver injury ranged from mild to severe, but usually resolved rapidly with discontinuation. Immunoallergic features and autoimmune markers were not prominent or consistently present in the published cases.

Mechanism of Injury

The liver injury due to cascara has been attributed to the direct toxicity of anthraquinone derivatives in the herbal extract; however, the clinical characteristics of the published cases suggest an idiosyncratic rather than direct hepatotoxic etiology. Other anthraquinones used to treat constipation have been implicated in causing liver injury with long term use, including sennosides and hydroxyanthraquinone. As with other herbal toxicities, the hepatic injury attributed to cascara may actually have been due to a undisclosed contaminant.

Outcome and Management

Liver injury from long term cascara use is rare and most cases have been self-limited and rapidly reversible upon stopping the laxative. However, severe cases with acute liver failure and development of ascites and portal hypertension have been described. There is no evidence of cross sensitivity to hepatic damage with other laxatives. Restarting cascara has been associated with recurrence of liver injury and should be avoided.

Drug Class: Herbal and Dietary Supplements

Other drugs in the Anthraquinone Subclass: Senna



Cascara – Generic


Herbal and Dietary Supplements


Fact Sheet at MedlinePlus, NLM


Cascara 8047-27-6 Herbal mixtureNot applicable


References updated: 23 January 2017

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    (Expert review of hepatotoxicity published in 1999; cascara is not discussed).
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    (Review of hepatotoxicity of herbal and dietary supplements [HDS]; cascara is listed as having been linked to cases of cholestatic hepatitis).
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    (52 year old woman developed jaundice, acute liver failure, lactic acidosis, and phosphate wasting nephropathy after ingesting herbal tea made from senna fruits for 3 years [bilirubin 6.2 mg/dL, ALT 9160 U/L, INR 5.3], requiring ventilator support, ultimately resolving).
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    (77 year old male developed jaundice after taking a senna preparation for constipation for 3 months [bilirubin 4.9 rising to 16.9 mg/dL, ALT 657 U/L, Alk P 160 U/L], resolving within 1 month of stopping the herbal).
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    (Five cases of hepatotoxicity of Copalchi in 4 men and 1 woman ages 59 to 77 years, taking herb for 2 to 13 months [bilirubin 0.7-13 mg/dL, ALT 403-865 U/L, GGT 54-116 U/L], resolving in all).
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    (Among 521 cases of drug induced liver injury submitted to Spanish registry, 13 [2%] were due to herbals, including one due to Rhamnus purshianus [cascara], with onset after 2 months [bilirubin 7.1 mg/dL, ALT 56 times ULN, Alk P normal], resolving in 3 months).
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    (Among 519 adverse events attributed to herbals reported to an Italian registry between 2002 and 2011, 26 were related to herbal laxatives, including 3 cases of liver injury, 1 due to cascara and 2 to senna).
  • Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int. 2012;32:1543–56. [PubMed: 22928722]
    (A systematic compilation of all publications on the hepatotoxicity of specific herbals identified 185 publications on 60 different herbs, herbal drugs and supplements, including 1 implicating cascara [Nadir 2000] and 3 senna [Beuers 1991, Seybold 2004, Vanderperren 2005]).
  • Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. Aliment Pharmacol Ther. 2013;37:3–17. [PubMed: 23121117]
    (Systematic review of the literature on HDS associated hepatotoxicity mentions that cascara has been implicated in causing clinically apparent acute liver injury).
  • Teschke R, Schulze J, Schwarzenboeck A, Eickhoff A, Frenzel C. Herbal hepatotoxicity: suspected cases assessed for alternative causes. Eur J Gastroenterol Hepatol. 2013;25:1093–8. [PubMed: 23510966]
    (Review of the literature of case series of suspected HDS related liver injury found evidence of other explanations for the liver injury in 19 of 23 publications involving 278 of 573 patients [49%], and that these other diagnoses weakened the causality assessment in most instances; cascara associated cases not mentioned).
  • Björnsson ES, Bergmann OM, Björnsson HK, Kvaran RB, Olafsson S. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144:1419–25. [PubMed: 23419359]
    (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, including 15 [16%] due to herbal and dietary supplements, but none were attributed to cascara containing products).
  • Licata A, Macaluso FS, Craxì A. Herbal hepatotoxicity: a hidden epidemic. Intern Emerg Med. 2013;8:13–22. [PubMed: 22477279]
    (Review and commentary on herb rekated hepatotoxicity discusses pyrrolizidine alkaloids, green tea, Echinacea, kava, usnic acid, ephedra and products made by Herbalife, Hydroxycut and LipoKinetix; no mention of cascara containing products).
  • Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. Clin Liver Dis. 2013;17:715–35. [PubMed: 24099027]
    (Review of HDS induced liver injury including regulatory problems, difficulties in diagnosis and causality assessment; no mention of cascara contianing products).
  • Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, Reddy KR, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60:1399–408. [PMC free article: PMC4293199] [PubMed: 25043597]
    (Among 85 cases of HDS associated liver injury [not due to anabolic steroids] enrolled in a US prospective study between 2004 and 2013, none were attributed specifically to cascara).
  • Navarro VJ, Lucena MI. Hepatotoxicity induced by herbal and dietary supplements. Semin Liver Dis. 2014;34:172–93. [PubMed: 24879982]
    (Review of HDS induced liver injury including regulatory problems, difficulties in diagnosis and causality assessment; lists cascara as possibly causing cholestatic hepatitis).
  • Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology. 2015;148:517–532.e3. [PubMed: 25500423]
    (Extensive review of possible beneficial as well as harmful effects of herbal products on the liver mentions that multi-ingredient supplements have been implicated in many cases of liver injury; cascara is not discussed).
  • Nakasone ES, Tokeshi J. A serendipitous find: A case of cholangiocarcinoma identified incidentally after acute liver injury due to cascara sagrada ingestion. Hawaii J Med Public Health. 2015;74:200–2. [PMC free article: PMC4477433] [PubMed: 26114074]
    (77 year old woman developed jaundice shortly after a 3 day course of an over-the-counter cascara product [bilirubin 18.5 mg/dL, ALT 465 U/L, Alk P not given], while imaging showed cholangiocarcinoma; no follow up or justification of diagnosis of cascara induced liver injury given).
  • Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. Arch Toxicol. 2015;89:851–65. [PubMed: 25680499]
    (Extensive review of liver injury due to HDS lists cascara as possibly causing cholestatic hepatitis).
  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]
    (Among 899 cases of drug induced liver injury enrolled in a prospective database between 2004 and 2012, HDS were implicated in 145 [16%], but none specifically implicated cascara: see Navarro [2014]).


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