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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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Turmeric

Last Update: May 11, 2021.

OVERVIEW

Introduction

Turmeric is a popular herb derived from the roots of the plant Curcuma longa found mostly in India and Southern Asia. Turmeric has an intense yellow color and distinct taste and is used as a dye as well as a spice in the preparation of curry. Turmeric and its purified extract curcumin are also used medically for their purported antiinflammatory and antioxidant effects to treat digestive complaints including ingestion, diarrhea and liver diseases. Turmeric and curcumin have been associated with a low rate of transient serum enzyme elevations during therapy and while having a long history of safety, turmeric products have recently been implicated in over a dozen instances of clinically apparent acute liver injury.

Background

Turmeric (tur mer' ik) is a widely used herbal product derived from the roots of Curcuma longa, a perennial plant belonging to the ginger family (Zingiberaceae) that is native to India but grown throughout Southern Asia and in central America. Extracts of the rhizomes of turmeric contain volatile oils and curcuminoids (such as curcumin, demethoxycurcumin and others) which are believed to be the active antiinflammatory components of the herb and are often collectively referred to as curcumin. The antiinflammatory effects of turmeric and curcumin are thought to be mediated by inhibition of leukotriene synthesis. Curcumin has also been reported to have antineoplastic effects, mediated perhaps by inhibition of intracellular kinases. Turmeric has been used in traditional Indian (Ayurvedic) medicine to treat many conditions including indigestion, upper respiratory infections and liver diseases. Turmeric and curcumin are under active evaluation as antiinflammatory and antineoplastic agents, for treatment of diabetes and hyperlipidemia and as therapy of liver diseases including nonalcoholic steatohepatitis (NASH). The scientific bases for the purported effects of turmeric are not well established and rigorous proof of its efficacy in any medical condition is lacking. Commercial preparations of turmeric and curcumin vary widely in curcuminoid content. The recommended daily dose varies widely (100 to >1,000 mg daily), depending on the preparation used (curcuminoids vs turmeric extract), formulation (tablets, liquid, root extract, tea) and indications. Side effects are uncommon and mild but may include dermatitis and gastrointestinal upset.

Hepatotoxicity

Both turmeric and curcumin were considered to be generally safe and for many years had not been linked to instances of liver injury in any consistent way. Studies of its use in various diseases showed low rates of transient and asymptomatic serum enzyme elevations during therapy, but without instances of clinically apparent acute liver injury. Indeed, turmeric was evaluated as a potential therapy of acute and chronic liver injury and although its efficacy and safety were not clearly shown, therapy with turmeric and curcumin did not seem to worsen the preexisting liver conditions. Recently, isolated case reports of liver injury arising during use of turmeric dietary supplements have been published. Initially, these episodes were attributed to other exposures that might have accounted for the injury or possible contaminants in the commercial turmeric products. One reason given for the safety and lack of hepatotoxicity of curcumin was that it is poorly absorbed by the oral route, and it was unclear whether there was adequate systemic exposure to achieve any of the purported beneficial or adverse effects of turmeric or curcumin.

Importantly, means of increasing the bioavailability of curcumin were developed using piperine (black pepper) or nanoparticle delivery methods to increase absorption. These high bioavailability forms of turmeric were subsequently linked to several cases of liver injury and mentioned as a possible cause of outbreaks of acute hepatitis with jaundice in Italy. The clinical features of the liver injury attributed to high bioavailable forms of turmeric have recently become better defined. The latency to onset of liver injury has varied from a few weeks to as long as eight months but is typically 1 to 3 months. The onset is insidious with fatigue, nausea and poor appetite followed by dark urine and jaundice. Rash and fever are absent or mild. Laboratory tests at onset typically show marked elevations in serum aminotransferase levels (often above 1000 U/L) with only mild increases in alkaline phosphatase. Jaundice occurs if the agent is continued. While signs of hypersensitivity are not prominent, many patients develop autoantibodies and the clinical syndrome and histological features can resemble autoimmune hepatitis. Prednisone has been used to treat severe cases of turmeric hepatotoxicity, but is probably not needed as recovery is rapid once the herbal product is discontinued. Neither acute liver failure nor chronic hepatitis or vanishing bile duct syndrome have been described in cases of turmeric associated liver injury, but the hepatocellular pattern of injury and frequency of jaundice suggest that fatal instances might occur, particularly if the product is not discontinued promptly.

Likelihood score: B (likely rare cause of clinically apparent liver injury).

Drug Class: Herbal and Dietary Supplements

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Turmeric – Generic

DRUG CLASS

Herbal and Dietary Supplements

COMPLETE LABELING

Fact Sheet at National Center for Complementary and Integrative Health

CHEMICAL FORMULA AND STRUCTURE

DRUGCAS REGISTRY NUMBERMOLECULAR FORMULASTRUCTURE
Turmeric458-37-7C21-H20-O6image 134973130 in the ncbi pubchem database

ANNOTATED BIBLIOGRAPHY

References updated: 11 May 2021

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    (Expert review of hepatotoxicity published in 1999; turmeric and curcumin are not discussed).
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    (Review of hepatotoxicity of herbal and dietary supplements [HDS]; turmeric and curcumin are not discussed).
  • Turmeric. In, PDR for herbal medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 864-7.
    (Compilation of short monographs on herbal medications and dietary supplements).
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    (Review and description of patterns of liver injury, including discussion of potential risk factors, and herb-drug interactions; no mention of curcumin).
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    (Among 60 patients with major depression treated with fluoxetine or curcumin or both for 6 weeks, improvements in depression rating scales were similar in all 3 groups and “there was no significant difference in … laboratory tests … from baseline”).
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  • Lukefahr AL, McEvoy S, Alfafara C, Funk JL. Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use. BMJ Case Rep. 2018;2018:bcr2018224611. [PMC free article: PMC6144106] [PubMed: 30206065]
    (71 year old woman developed serum ALT elevations without jaundice 8-10 months after starting turmeric [ALT ~325 U/L, Alk P and bilirubin normal; ANA 1:320], which gradually fell into the normal range after stopping).
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    (A 52 year old woman and 55 year old man developed evidence of liver injury 1 and 5 months after starting a turmeric supplement [bilirubin 9.5 and 1.3 mg/dL, ALT 2591 and 1149 U/L, Alk P 263 and 145 U/L], which resolved on stopping and recurred in the first patient on restarting the supplement [bilirubin 3.5 mg/dL, ALT 2093 U/L], which was tested and found free of adulterants).
  • Suhail FK, Masood U, Sharma A, John S, Dhamoon A. Turmeric supplement induced hepatotoxicity: a rare complication of a poorly regulated substance. Clin Toxicol (Phila). 2020;58:216–7. [PubMed: 31271321]
    (61 year old woman with polycystic liver disease developed fatigue and dark urine 6 weeks after starting turmeric supplements [bilirubin total 1.6, direct 1.0, ALT 2607 U/L, Alk P 246 U/L, ANA 1:250 normal IgG levels], responding rapidly to a course of prednisone and tests remaining normal after stopping).
  • Donelli D, Antonelli M, Firenzuoli F. Considerations about turmeric-associated hepatotoxicity following a series of cases occurred in Italy: is turmeric really a new hepatotoxic substance? Intern Emerg Med. 2020;15:725–6. [PubMed: 31278559]
    (Letter mentioning an outbreak of acute cholestatic hepatitis in Italy related to use of a turmeric based dietary supplement with high bioavailability, perhaps due to its combination with piperine [black pepper] which increases curcumin absorption).
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    (62 year old white woman developed fatigue, rash and jaundice 10 months after starting turmeric [bilirubin >17 mg/dL, ALT 2308 U/L, Alk P not provided, ANA negative, IgG 1670 mg/dL], improving rapidly upon stopping the herbal supplement).
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    (55 year old woman developed jaundice 3 months after starting Quinol Liquid Turmeric [15 mL daily] [bilirubin 11.8 mg/dL, ALT 2743 U/L, Alk P 204 U/L, INR 1.0, ANA 1:80 rising to 1:320], biopsy showing interface hepatitis and plasma cells, and she rapidly improved once turmeric was stopped).
  • Lombardi N, Crescioli G, Maggini V, Ippoliti I, Menniti-Ippolito F, Gallo E, Brilli V, et al. Acute liver injury following turmeric use in Tuscany: An analysis of the Italian Phytovigilance database and systematic review of case reports. Br J Clin Pharmacol. 2021;87:741–53. [PubMed: 32656820]
    (Analysis of the Italian Phytovigilance system identified 37 cases of liver injury attributed to high bioavailability curcumin; 7 cases reported from Tuscany included 6 women and 1 man, ages 45 to 68 years, taking turmeric for 2 weeks to 8 months [bilirubin 6 to 25 mg/dL, ALT 257 to 3303 U/L, GGT 124 to 504 U/L]; follow up after discontinuation was not always available).
  • Abdallah MA, Abdalla A, Ellithi M, Abdalla AO, Cunningham AG, Yeddi A, Rajendiran G. Turmeric-associated liver injury. Am J Ther. 2020;27(6):e642–e645. [PubMed: 31283536]
    (51 year old white woman developed jaundice 2 months after starting a turmeric supplement [500 mg daily] [bilirubin total 2.4, direct 0.9 mg/dL, ALT 2484 U/L, Alk P 226 U/L], biopsy showing portal infiltrates including eosinophils, with rapid improvement upon stopping and normal liver tests 8 weeks later).
  • Koenig G, Callipari C, Smereck JA. Acute liver injury after long-term herbal "liver cleansing" and "sleep aid" supplement use. J Emerg Med 2021: S0736-4679(21)00004-4. [PubMed: 33579656]
    (53 year old woman developed jaundice 3-4 weeks after starting 2 herbal supplements, “Liver Detoxifier” which has 16 ingredients including turmeric and “Restful Sleep” with 5 components including valerian and melatonin [bilirubin 25.4 mg/dL, ALT 89 U/L, Alk P 174 U/L, albumin 2.0, INR 1.4], with rapid improvement on stopping).

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