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yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK548113_"><span class="title" itemprop="name">Cascara</span></h1><p class="fm-aai"><a href="#_NBK548113_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><div id="Cascara.OVERVIEW"><h2 id="_Cascara_OVERVIEW_">OVERVIEW</h2><div id="Cascara.Introduction"><h3>Introduction</h3><p>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.</p></div><div id="Cascara.Background"><h3>Background</h3><p>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.</p></div><div id="Cascara.Hepatotoxicity"><h3>Hepatotoxicity</h3><p>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.</p></div><div id="Cascara.Mechanism_of_Injury"><h3>Mechanism of Injury</h3><p>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.</p></div><div id="Cascara.Outcome_and_Management"><h3>Outcome and Management</h3><p>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.</p><p>Drug Class: <a href="/books/n/livertox/HerbalDietarySuppl/?report=reader">Herbal and Dietary Supplements</a></p><p>Other drugs in the Anthraquinone Subclass: <a href="/books/n/livertox/Senna/?report=reader">Senna</a></p></div></div><div id="Cascara.PRODUCT_INFORMATION"><h2 id="_Cascara_PRODUCT_INFORMATION_">PRODUCT INFORMATION</h2><p>
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<b>REPRESENTATIVE TRADE NAMES</b>
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</p><p>Cascara – Generic</p><p>
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<b>DRUG CLASS</b>
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</p><p>Herbal and Dietary Supplements</p><p>SUMMARY INFORMATION</p><p>
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<a href="https://www.nlm.nih.gov/medlineplus/druginfo/natural/773.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Fact Sheet at MedlinePlus, NLM</a>
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</p></div><div id="Cascara.CHEMICAL_FORMULA_AND_STRUCTURE"><h2 id="_Cascara_CHEMICAL_FORMULA_AND_STRUCTURE_">CHEMICAL FORMULA AND STRUCTURE</h2><div class="iconblock whole_rhythm clearfix ten_col table-wrap" id="figCascaraTc"><a href="/books/NBK548113/table/Cascara.Tc/?report=objectonly" target="object" title="Table" class="img_link icnblk_img figpopup" rid-figpopup="figCascaraTc" rid-ob="figobCascaraTc"><img class="small-thumb" src="/books/NBK548113/table/Cascara.Tc/?report=thumb" src-large="/books/NBK548113/table/Cascara.Tc/?report=previmg" alt="Image " /></a><div class="icnblk_cntnt"><h4 id="Cascara.Tc"><a href="/books/NBK548113/table/Cascara.Tc/?report=objectonly" target="object" rid-ob="figobCascaraTc">Table</a></h4></div></div></div><div id="Cascara.ANNOTATED_BIBLIOGRAPHY"><h2 id="_Cascara_ANNOTATED_BIBLIOGRAPHY_">ANNOTATED BIBLIOGRAPHY</h2><p>References updated: 23 January 2017</p><ul class="first-line-outdent"><li><div class="bk_ref" id="Cascara.REF.zimmerman.1999">Zimmerman HJ. Unconventional drugs. Miscellaneous drugs and diagnostic chemicals. In, Zimmerman, HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott,1999: pp. 731-4.<div><i>(Expert review of hepatotoxicity published in 1999; cascara is not discussed).</i></div></div></li><li><div class="bk_ref" id="Cascara.REF.seeff.2013">Seeff L, Stickel F, Navarro VJ. Hepatotoxicity of herbals and dietary supplements. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 631-58.<div><i>(Review of hepatotoxicity of herbal and dietary supplements [HDS]; cascara is listed as having been linked to cases of cholestatic hepatitis).</i></div></div></li><li><div class="bk_ref" id="Cascara.REF3">Cascara sagrada. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 161-4.<div><i>(Compilation of short monographs on herbal medications and dietary supplements).</i></div></div></li><li><div class="bk_ref" id="Cascara.REF.tolman.1976.290">Tolman KG, Hammar S, Sannella JJ. Possible hepatotoxicity of Doxidan. <span><span class="ref-journal">Ann Intern Med. </span>1976;<span class="ref-vol">84</span>:290–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1259264" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1259264</span></a>]<div>
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<i>(24 year old man developed fatigue 6 months after starting Doxidan [containing hydroxyanthraquinone] for chronic constipation and at 12 months developed nausea and syncope [bilirubin 0.8 mg/dL, AST 560 U/L, Alk P 339 U/L, ANA negative, slight neutropenia], liver biopsy showing chronic hepatitis, resolving within 1 month of stopping, recurring upon rechallenge).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.beuers.1991.372">Beuers U, Spengler U, Pape GR. Hepatitis after chronic abuse of senna. <span><span class="ref-journal">Lancet. </span>1991;<span class="ref-vol">337</span>:372–3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/1671276" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 1671276</span></a>]<div>
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<i>(26 year old nurse taking high doses of senna alkaloids developed jaundice and pruritus [bilirubin not given, ALT 303 U/L, Alk P 227 U/L], resolving within a few weeks of stopping and recurring upon restarting [ALT >280 U/L]).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.franz.1993.2">Franz G. The senna drug and its chemistry. <span><span class="ref-journal">Pharmacology. </span>1993;<span class="ref-vol">47</span> Suppl 1:2–6.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/8234429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8234429</span></a>]<div>
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<i>(Senna is dried leaflets or fruits of Cassia senna, either acutifolia [Alexandrian] or angustifolia [Indian senna], native to Northern Africa, middle East and India, similar constituents including anthraquinone glycosides, called sennosides).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.woolf.1999.1560">Woolf GM. Senna-induced hepatotoxicity. <span><span class="ref-journal">Hepatology. </span>1999;<span class="ref-vol">550A</span>:1560.</span><div>
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<i>(81 year old woman developed recurrent jaundice after taking senna for one month [bilirubin 3.2 rising to 29.6 mg/dL, peak ALT 1455 U/L, Alk P 168 U/L], recurring more rapidly and recovering more slowly after each of 3 episodes after reexposure).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.nadir.2000.3634">Nadir A, Reddy D, Van Thiel DH. Cascara sagrada-induced intrahepatic cholestasis causing portal hypertension: case report and review of herbal hepatotoxicity. <span><span class="ref-journal">Am J Gastroenterol. </span>2000;<span class="ref-vol">95</span>:3634–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/11151906" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11151906</span></a>]<div>
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<i>(48 year old man developed jaundice 3 days after starting cascara sagrada [bilirubin 11.8 mg/dL, ALT 999 U/L, Alk P 309 U/L, ANA 1: 640], developing ascites, but recovering within 3 months of stopping).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.wurtz.2002.941">Wurtz AS, Vial T, Isoard B, Saillard E. Possible hepatotoxicity from Copaltra, an herbal medicine. <span><span class="ref-journal">Ann Pharmacother. </span>2002;<span class="ref-vol">36</span>:941–2.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12014355" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12014355</span></a>]<div>
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<i>(49 year old woman developed jaundice 3 months after starting Copaltra tea [Coutarea latiflora and Centaurium erythreae] for diabetes [bilirubin 20.8 mg/dL, ALT 3010 U/L, Alk P 132 U/L], with recovery in 3 months).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.de_smet.2002.2046">De Smet PAGM. Herbal remedies. <span><span class="ref-journal">N Engl J Med. </span>2002;<span class="ref-vol">347</span>:2046–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12490687" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12490687</span></a>]<div>
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<i>(Review of status and difficulties of herbal medications including lack of standardization, federal regulation, contamination, safety, hepatotoxicity and drug-herb interactions; specific discussion of 4 herbs with therapeutic promise: ginkgo, hawthorn, saw palmetto and St. John’s wort).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.stedman.2002.195">Stedman C. Herbal hepatotoxicity. <span><span class="ref-journal">Semin Liver Dis. </span>2002;<span class="ref-vol">22</span>:195–206.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12016550" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12016550</span></a>]<div>
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<i>(Review and description of patterns of liver injury, including discussion of potential risk factors, and herb-drug interactions; cascara is listed as causing liver injury).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.schiano.2003.453">Schiano TD. Hepatotoxicity and complementary and alternative medicines. <span><span class="ref-journal">Clin Liver Dis. </span>2003;<span class="ref-vol">7</span>:453–73.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/12879994" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 12879994</span></a>]<div>
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<i>(Comprehensive review of herbal associated hepatotoxicity; cascara is listed as a potential hepatotoxin).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.ernst.2004.767">Ernst E. Risks of herbal medicinal products. <span><span class="ref-journal">Pharmacoepidemiol Drug Saf. </span>2004;<span class="ref-vol">13</span>:767–71.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15386721" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15386721</span></a>]<div>
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<i>(Review of the adverse effects of over-the-counter herbal medications, focusing on the hepatotoxicity of kava, drug interactions with St. John’s wort, and contamination of traditional Chinese medications with heavy metals [arsenic, lead, mercury, thallium] and conventional western medications).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.russo.2004.1018">Russo MW, Galanko JA, Shrestha R, Fried MW, Watkins P. Liver transplantation for acute liver failure from drug-induced liver injury in the United States. <span><span class="ref-journal">Liver Transpl. </span>2004;<span class="ref-vol">10</span>:1018–23.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15390328" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15390328</span></a>]<div>
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<i>(Among ~50,000 liver transplants reported to UNOS between 1990 and 2002, 270 [0.5%] were done for drug induced acute liver failure, including 7 [5%] for herbal medications, none attributed to cascara).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.seybold.2004.650">Seybold U, Landauer N, Hillebrand S, Goebel FD. Senna-induced hepatitis in a poor metabolizer. <span><span class="ref-journal">Ann Intern Med. </span>2004;<span class="ref-vol">141</span>:650–1.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15492352" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15492352</span></a>]<div>
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<i>(28 year old woman developed jaundice after drinking herbal tea containing senna leaves with positive rechallenge [ALT ~1390 U/L, GGT ~190 U/L], with Rhein anthrone detectable in serum).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.vanderperren.2005.1353">Vanderperren B, Rizzo M, Angenot L, Haufroid V, Jadoul M, Hantson P. Acute liver failure with renal impairment related to the abuse of senna anthraquinone glycosides. <span><span class="ref-journal">Ann Pharmacother. </span>2005;<span class="ref-vol">39</span>:1353–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15956233" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15956233</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.sonmez.2005.385">Sonmez A, Yilmaz MI, Mas R, Ozcan A, Celasun B, Dogru T, Taslipinar A, Kocar IH. Subacute cholestatic hepatitis likely related to the use of senna for chronic constipation. <span><span class="ref-journal">Acta Gastroenterol Belg. </span>2005;<span class="ref-vol">68</span>:385–7.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/16268429" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 16268429</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.bruguera.2007.66">Bruguera M, Herrera S, Lazaro E, Madurga M, Navarro M, De Abajo FJ. <span><span class="ref-journal">Gastroenterol Hepatol. </span>2007;<span class="ref-vol">30</span>:66–8.</span> [Acute hepatitis associated with consumption of Copalchi: a summary of 5 cases] [<a href="https://pubmed.ncbi.nlm.nih.gov/17335712" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 17335712</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.garc_acort_s.2008.688">García-Cortés M, Borraz Y, Lucena MI, Peláez G, Salmerón J, Diago M, Martínez-Sierra MC, et al. Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry. <span><span class="ref-journal">Rev Esp Enferm Dig. </span>2008;<span class="ref-vol">100</span>:688–95.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19159172" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19159172</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.chalasani.2008.1924">Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J., Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. <span><span class="ref-journal">Gastroenterology. </span>2008;<span class="ref-vol">135</span>:1924–34.</span> [<a href="/pmc/articles/PMC3654244/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3654244</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18955056" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18955056</span></a>]<div>
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<i>(Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 9% of cases were attributed to herbal medications, but none were specifically linked to cascara).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.freeman.2008.4296">Freeman HJ. "Melanosis" in the small and large intestine. <span><span class="ref-journal">World J Gastroenterol. </span>2008;<span class="ref-vol">14</span>:4296–9.</span> [<a href="/pmc/articles/PMC2731179/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC2731179</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/18666316" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 18666316</span></a>]<div>
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<i>(Pigment found in small and large intestine with long term anthracene laxative [cascara, senna, aloes and rhubarb], use is usually lipofuscin rather than hemosiderin or melanin and is present in macrophages in the lamina propria).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.jacobsen.2009.3367">Jacobsen C, Semb S, Kromann-Andersen H. <span><span class="ref-journal">Ugeskr Laeger. </span>2009;<span class="ref-vol">171</span>:3367–9.</span> [Toxic hepatitis following consumption of the herbal medicinal product Cascara Sagrada] Danish. [<a href="https://pubmed.ncbi.nlm.nih.gov/19925744" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19925744</span></a>]<div>
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<i>(49 year old woman developed jaundice 4 weeks after starting daily cascara sagrada for constipation [bilirubin 8.4 rising to 24.6 mg/dL, ALT 944 U/L, ascites], resolving within 4 months of stopping).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.jacobsson.2009.1039">Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden. <span><span class="ref-journal">Pharmacoepidemiol Drug Saf. </span>2009;<span class="ref-vol">18</span>:1039–47.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/19650152" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 19650152</span></a>]<div>
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<i>(Review of 778 spontaneous reports of adverse reactions to herbals to Swedish Registry does not list or mention senna or cascara).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.muellerlissner.2010">Mueller-Lissner SA, Wald A. Constipation in adults. Clin Evid (Online) 2010 Jul 5; 2010. pii: 0413. [<a href="/pmc/articles/PMC3217654/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC3217654</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/21418672" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21418672</span></a>]<div><i>(Review of evidence of efficacy of conventional therapies of constipation; states that there is no published evidence from randomized controlled trials for benefit of cascara for idiopathic chronic constipation).</i></div></div></li><li><div class="bk_ref" id="Cascara.REF.vitalone.2012.231">Vitalone A, Menniti-Ippolito F, Raschetti R, Renda F, Tartaglia L, Mazzanti G. Surveillance of suspected adverse reactions to herbal products used as laxatives. <span><span class="ref-journal">Eur J Clin Pharmacol. </span>2012;<span class="ref-vol">68</span>:231–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/21964980" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 21964980</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.teschke.2012.1543">Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. <span><span class="ref-journal">Liver Int. </span>2012;<span class="ref-vol">32</span>:1543–56.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22928722" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22928722</span></a>]<div>
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<i>(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]).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.bunchorntavakul.2013.3">Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement hepatotoxicity. <span><span class="ref-journal">Aliment Pharmacol Ther. </span>2013;<span class="ref-vol">37</span>:3–17.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23121117" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23121117</span></a>]<div>
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<i>(Systematic review of the literature on HDS associated hepatotoxicity mentions that cascara has been implicated in causing clinically apparent acute liver injury).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.teschke.2013.1093">Teschke R, Schulze J, Schwarzenboeck A, Eickhoff A, Frenzel C. Herbal hepatotoxicity: suspected cases assessed for alternative causes. <span><span class="ref-journal">Eur J Gastroenterol Hepatol. </span>2013;<span class="ref-vol">25</span>:1093–8.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23510966" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23510966</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.bj_rnsson.2013.1419">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. <span><span class="ref-journal">Gastroenterology. </span>2013;<span class="ref-vol">144</span>:1419–25.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/23419359" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 23419359</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.licata.2013.13">Licata A, Macaluso FS, Craxì A. Herbal hepatotoxicity: a hidden epidemic. <span><span class="ref-journal">Intern Emerg Med. </span>2013;<span class="ref-vol">8</span>:13–22.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/22477279" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 22477279</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.navarro.2013.715">Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. <span><span class="ref-journal">Clin Liver Dis. </span>2013;<span class="ref-vol">17</span>:715–35.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24099027" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24099027</span></a>]<div>
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<i>(Review of HDS induced liver injury including regulatory problems, difficulties in diagnosis and causality assessment; no mention of cascara contianing products).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.navarro.2014.1399">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. <span><span class="ref-journal">Hepatology. </span>2014;<span class="ref-vol">60</span>:1399–408.</span> [<a href="/pmc/articles/PMC4293199/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4293199</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25043597" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25043597</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.navarro.2014.172">Navarro VJ, Lucena MI. Hepatotoxicity induced by herbal and dietary supplements. <span><span class="ref-journal">Semin Liver Dis. </span>2014;<span class="ref-vol">34</span>:172–93.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/24879982" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 24879982</span></a>]<div>
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<i>(Review of HDS induced liver injury including regulatory problems, difficulties in diagnosis and causality assessment; lists cascara as possibly causing cholestatic hepatitis).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.seeff.2015.517">Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. Herbal products and the liver: a review of adverse effects and mechanisms. <span><span class="ref-journal">Gastroenterology. </span>2015;<span class="ref-vol">148</span>:517–532.e3.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25500423" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25500423</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.nakasone.2015.200">Nakasone ES, Tokeshi J. A serendipitous find: A case of cholangiocarcinoma identified incidentally after acute liver injury due to cascara sagrada ingestion. <span><span class="ref-journal">Hawaii J Med Public Health. </span>2015;<span class="ref-vol">74</span>:200–2.</span> [<a href="/pmc/articles/PMC4477433/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4477433</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/26114074" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 26114074</span></a>]<div>
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<i>(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).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.stickel.2015.851">Stickel F, Shouval D. Hepatotoxicity of herbal and dietary supplements: an update. <span><span class="ref-journal">Arch Toxicol. </span>2015;<span class="ref-vol">89</span>:851–65.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/25680499" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25680499</span></a>]<div>
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<i>(Extensive review of liver injury due to HDS lists cascara as possibly causing cholestatic hepatitis).</i>
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</div></div></li><li><div class="bk_ref" id="Cascara.REF.chalasani.2015.1340">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. <span><span class="ref-journal">Gastroenterology. </span>2015;<span class="ref-vol">148</span>:1340–52.e7.</span> [<a href="/pmc/articles/PMC4446235/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC4446235</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/25754159" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 25754159</span></a>]<div>
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<i>(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]).</i>
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</div></div></li></ul></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK548113_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Last Update: <span itemprop="dateModified">January 23, 2017</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="https://www.niddk.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Institute of Diabetes and Digestive and Kidney Diseases</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Cascara. [Updated 2017 Jan 23].<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/livertox/Carvedilol/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/livertox/Casimersen/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="table-wrap" id="figobCascaraTc"><div id="Cascara.Tc" class="table"><p class="large-table-link" style="display:none"><span class="right"><a href="/books/NBK548113/table/Cascara.Tc/?report=objectonly" target="object">View in own window</a></span></p><div class="large_tbl" id="__Cascara.Tc_lrgtbl__"><table><tbody><tr><th id="hd_b_Cascara.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">DRUG</th><th id="hd_b_Cascara.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">CAS REGISTRY NUMBER</th><th id="hd_b_Cascara.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">MOLECULAR FORMULA</th><th id="hd_b_Cascara.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">STRUCTURE</th></tr><tr><td headers="hd_b_Cascara.Tc_1_1_1_1" scope="row" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Cascara</td><td headers="hd_b_Cascara.Tc_1_1_1_2" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">
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<a href="https://pubchem.ncbi.nlm.nih.gov/substance/135325291" ref="pagearea=body&targetsite=entrez&targetcat=link&targettype=pubchem">8047-27-6</a>
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</td><td headers="hd_b_Cascara.Tc_1_1_1_3" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Herbal mixture</td><td headers="hd_b_Cascara.Tc_1_1_1_4" rowspan="1" colspan="1" style="text-align:left;vertical-align:top;">Not applicable</td></tr></tbody></table></div></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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