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.
(Expert review of hepatotoxicity published in 1999; turmeric and curcumin are not discussed).
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.
(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).
StedmanC.Herbal hepatotoxicity.Semin Liver Dis2002; 22: 195-206. [PubMed: 12016550]
(Review and description of patterns of liver injury, including discussion of potential risk factors, and herb-drug interactions; no mention of curcumin).
De SmetPAGM. Herbal remedies.N Engl J Med2002; 347: 2046-56. [PubMed: 12490687]
(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, but not curcumin).
SchianoTD. Hepatotoxicity and complementary and alternative medicines.Clin Liver Dis2003; 7: 453-73. [PubMed: 12879994]
(Comprehensive review of herbal associated hepatotoxicity; curcumin is not listed as causing hepatotoxicity).
RussoMW, GalankoJA, ShresthaR, FriedMW, WatkinsP. Liver transplantation for acute liver failure from drug-induced liver injury in the United States.Liver Transpl2004; 10: 1018-23. [PubMed: 15390328]
(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 curcumin or turmeric use).
García-CortésM, BorrazY, LucenaMI, PeláezG, SalmerónJ, DiagoM, Martínez-SierraMC, et al.[Liver injury induced by “natural remedies”: an analysis of cases submitted to the Spanish Liver Toxicity Registry]. Rev Esp Enferm Dig2008; 100: 688-95. Spanish. [PubMed: 19159172]
(Among 521 cases of drug induced liver injury submitted to a Spanish registry, 13 [2%] were due to herbals, but none were attributed to turmeric or curcumin).
ChalasaniN, FontanaRJ, BonkovskyHL, WatkinsPB, DavernT, SerranoJ, YangH, RochonJ; Drug Induced Liver Injury Network (DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States.Gastroenterology2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]
(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 linked to turmeric or curcumin use).
JacobssonI, JönssonAK, GerdénB, HäggS. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances in Sweden.Pharmacoepidemiol Drug Saf2009; 18: 1039-47. [PubMed: 19650152]
(Review of 778 spontaneous reports of adverse reactions to herbals to Swedish Registry, none of which were attributed to turmeric or curcumin).
NavarroVJ. Herbal and dietary supplement hepatotoxicity.Semin Liver Dis2009; 29: 373-82. [PubMed: 19826971]
(Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; curcumin is not listed as a potentially hepatotoxic botanical).
WongcharoenW, Jai-AueS, PhrommintikulA, NawarawongW, WoragidpoonpolS, TepsuwanT, SukonthasarnA, et al.Effects of curcuminoids on frequency of acute myocardial infarction after coronary artery bypass grafting.Am J Cardiol2012; 110: 40-4. [PubMed: 22481014]
(Among 121 Thai patients who were undergoing coronary artery bypass surgery treated with “curcuminoids” or placebo for 8 days perioperatively, rates of postoperative myocardial infarction were less with curcuminoids [13% vs 30%] as were ALT elevations above 3 times ULN [0% vs 3%]).
DulbeccoP, SavarinoV. Therapeutic potential of curcumin in digestive diseases.World J Gastroenterol2013; 19: 9256-70. [PMC free article: PMC3882399] [PubMed: 24409053]
(Review of pharmaco*kinetics, physical and molecular properties and potential uses of curcumin in digestive diseases; mentions that “as curcumin is particularly concentrated in the human liver, the risk of hepatotoxicity has been closely evaluated, but liver function tests have been shown to be unaffected with doses as high as 2 to 4 g/d”).
MengB, LiJ, CaoH. Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications.Curr Pharm Des2013; 19: 2101-13. [PubMed: 23116316]
(Review of the in vivo and in vitro evidence of antioxidant and antiinflammatory activity of curcumin and the rationale for its use in diabetes; “and it has no known side effects”).
BunchorntavakulC, ReddyKR. Review article: herbal and dietary supplement hepatotoxicity.Aliment Pharmacol Ther2013; 37: 3-17. [PubMed: 23121117]
(Systematic review of literature on HDS associated liver injury; does not discuss curcumin or turmeric).
SanmukhaniJ, SatodiaV, TrivediJ, PatelT, TiwariD, PanchalB, GoelA, et al.Efficacy and safety of curcumin in major depressive disorder: a randomized controlled trial.Phytother Res2014; 28: 579-85. [PubMed: 23832433]
(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”).
KuptniratsaikulV, DajprathamP, Taechaarp*rnkulW, BuntragulpoontaweeM, LukkanapichonchutP, ChootipC, SaengsuwanJ, et al.Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study.Clin Interv Aging2014; 9: 451-8. [PMC free article: PMC3964021] [PubMed: 24672232]
(Among 367 adults with knee osteoarthritis treated with ibuprofen [1.2 g daily] or curcumin extracts [1.5 g daily] for 4 weeks, pain, stiffness and function scores improved equally in both groups and adverse event rates were similar [36% vs 30%]; no mention of ALT elevations or hepatotoxicity).
RahmaniS, AsgaryS, AskariG, KeshvariM, HatamipourM, FeiziA, SahebkarA. Treatment of non-alcoholic fatty liver disease with curcumin: a randomized placebo-controlled trial.Phytother Res2016; 30: 1540-8. [PubMed: 27270872]
(Among 80 Iranian patients with nonalcoholic fatty liver disease treated with curcumin [500 mg once daily] or placebo for 8 weeks, improvements, as assessed by ultrasonography, were more frequent with curcumin [79% vs 28%], and it was well tolerated with no serious adverse events and mean ALT levels decreased more with curcumin [from 39 to 36 U/L] than placebo [30 to 29 U/L]).
PanahiY, KianpourP, MohtashamiR, JafariR, Simental-MendíaLE, SahebkarA. Efficacy and safety of phytosomal curcumin in non-alcoholic fatty liver disease: a randomized controlled trial.Drug Res (Stuttg)2017; 67(4): 244-51. [PubMed: 28158893]
(Among 102 patients with nonalcoholic fatty liver disease treated with curcumin [500 mg twice daily] or placebo for 8 weeks, improvements as assessed by hepatic ultrasound were more frequent with curcumin [75% vs 5%] and mean ALT levels fell from 35 to 25 U/L; there were no serious adverse events).
MirzaeiH, ShakeriA, RashidiB, JaliliA, BanikazemiZ, SahebkarA.Phytosomal curcumin: A review of pharmaco*kinetic, experimental and clinical studies.Biomed Pharmacother2017; 85: 102-12. [PubMed: 27930973]
(Review of the chemical characteristics, in vitro antioxidant activity and clinical effects of phytosomal curcumin; mentions that “curcumin is safe and could be tolerated even at very high doses”).
NelsonKM, DahlinJL, BissonJ, GrahamJ, PauliGF, WaltersMA. The essential medicinal chemistry of curcumin.J Med Chem2017; 60: 1620-37. [PMC free article: PMC5346970] [PubMed: 28074653]
(Review of the pharmacology and clinical evidence for efficacy of curcumin concludes that the multiple in vitro effects represent assay interference, that it is poorly absorbed and that there is no evidence that it has any effect in humans despite claims for benefit in many conditions including erectile dysfunction, hirsutism, baldness, cancer, and Alzheimer disease).
FarzaeiMH, ZobeiriM, ParviziF, El-SendunyFF, MarmouziI, Coy-BarreraE, NaseriR, et al.Curcumin in liver diseases: a systematic review of the cellular mechanisms of oxidative stress and clinical perspective.Nutrients2018; 10: 855. [PMC free article: PMC6073929] [PubMed: 29966389]
(Review of the in vitro and in vivo results showing activity of curcumin in decreasing oxidative stress and summary of clinical studies demonstrating efficacy in liver disease).
SaadatiS, HatamiB, YariZ, ShahrbafMA, EghtesadS, MansourA, PoustchiH, et al.The effects of curcumin supplementation on liver enzymes, lipid profile, glucose homeostasis, and hepatic steatosis and fibrosis in patients with non-alcoholic fatty liver disease.Eur J Clin Nutr2019; 73: 441-9. [PubMed: 30610213]
(Among 50 patients with nonalcoholic liver disease given lifestyle advice and either curcumin [1500 mg] or placebo daily for 12 weeks, there were no differences between the two groups in weight loss [-2.4 vs -3.9 kg], changes in ALT [-6 vs -7 U/L] or in controlled attenuation parameter score for hepatic steatosis [-16 vs -32 dB/m]).
LukefahrAL, McEvoyS, AlfafaraC, FunkJL. Drug-induced autoimmune hepatitis associated with turmeric dietary supplement use.BMJ Case Rep2018; 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).
LuberRP, RentschC, LontosS, PopeJD, AungAK, SchneiderHG, KempW, et al.Turmeric induced liver injury: a report of two cases.Case Reports Hepatol2019; 2019: 6741213. [PMC free article: PMC6535872] [PubMed: 31214366]
(A 52year 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).
ImamZ, KhasawnehM, JomaaD, IftikharH, SayedahmadZ. Drug induced liver injury attributed to a curcumin supplement.Case Rep Gastrointest Med.2019;2019:6029403. [PMC free article: PMC6855017] [PubMed: 31781418]
(A 78 year old woman with diabetes developed jaundice one month after starting curcumin for hypercholesterolemia [bilirubin 12.8 mg/dL, ALT 609 U/L, Alk P 171 U/L, INR 1.1, ANA 1:320, IgG 951], which resolved on stopping and all liver tests were normal 2 months later).
SuhailFK, MasoodU, SharmaA, JohnS, DhamoonA. 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).
DonelliD, AntonelliM, FirenzuoliF. Considerations about turmeric-associated hepatotoxicity following a series of cases occurred in Italy: is turmeric really a new hepatotoxic substance?Intern Emerg Med2020; 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).
ChandS, HairC, BeswickL.A rare case of turmeric-induced hepatotoxicity.Intern Med J2020; 50: 258-9. [PubMed: 32037709]
(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).
Nouri-VaskehM, Malek MahdaviA, AfshanH, AlizadehL, ZareiM.Effect of curcumin supplementation on disease severity in patients with liver cirrhosis: a randomized controlled trial.Phytother Res2020; 34: 1446-54. [PubMed: 32017253]
(Among 70 patients with cirrhosis treated with curcumin [1000 mg daily] or placebo for 3 months, those on curcumin had improvements in MELD scores [INR decreasing from 1.57 to 1.49 and bilirubin from 2.5 to 2.1], while those on placebo worsened).
LeeBS, BhatiaT, ChayaCT, WenR, TairaMT, LimBS. Autoimmune hepatitis associated with turmeric consumption.ACG Case Rep J2020; 7: e00320. [PMC free article: PMC7162126] [PubMed: 32337301]
(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).
LombardiN, CrescioliG, MagginiV, IppolitiI, Menniti-IppolitoF, GalloE, BrilliV, 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 Pharmacol2021; 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).
AbdallahMA, AbdallaA, EllithiM, AbdallaAO, CunninghamAG, YeddiA, RajendiranG. Turmeric-associated liver injury.Am J Ther2020; 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).
KoenigG, CallipariC, SmereckJA. Acute liver injury after long-term herbal "liver cleansing" and "sleep aid" supplement use.J Emerg Med.2021;60(5):610-614. [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).
KnoxC, BertouchJ, AlmeidaJ. Turmeric hepatotoxicity, cause or coincidence?Intern Med J.2021;51:153. [PubMed: 33572032]
(Letter in response to Chand [2020] requesting more information about the dose and other ingredients in the turmeric supplement).
SohalA, AlhankawiD, SandhuS, ChintanaboinaJ.Turmeric-induced hepatotoxicity: report of 2 cases.Int Med Case Rep J.2021;14:849-852. [PMC free article: PMC8711139] [PubMed: 34992472]
(Two cases, 57- and 53-year old women developed symptoms of liver injury 3 and ~2 months after starting turmeric [bilirubin 8.6 and 1.8 mg/dL, ALT 1414 and 733 U/L, Alk P not given, INRs normal], resolving within 2 and 1 months of stopping the supplement).
SunagawaSW, HoulihanC, ReynoldsB, KjerengtroenS, MurryDJ, KhouryN. Turmeric-associated drug-induced liver injury.ACG Case Rep J.2022;9:e00941. [PMC free article: PMC9794274] [PubMed: 36600786]
(49 year old woman developed jaundice 6 weeks after starting turmeric with black pepper [bilirubin 7.1 mg/dL, ALT 3289 U/L, Alk P 138 U/L, INR normal], resolving within 71 days of stopping the supplement).
EghbaliA, NourigheimasiS, GhasemiA, AfzalRR, AshayeriN, EghbaliA, KhanzadehSet al.The effects of curcumin on hepatic T2*MRI and liver enzymes in patients with β-thalassemia major: a double-blind randomized controlled clinical trial.Front Pharmacol.2023;14:1284326. [PMC free article: PMC10757948] [PubMed: 38164474]
(Among 158 patients [above the age of 5] with beta-thalassemia treated with curcumin [500 mg] or placebo twice daily for 6 months, serum ALT levels decreased in those on curcumin [~152 to 105 U/L vs ~152 to 156 U/L], while Alk P levels rose and direct bilirubin levels decreased slightly in both groups; no patient reported any specific side effects from curcumin consumption and “all patients tolerated the capsules well in general.”).
Halegoua-DeMarzioD, NavarroV, AhmadJ, AvulaB, BarnhartH, BarrittAS, BonkovskyHL, et al.Liver injury associated with turmeric-a growing problem: ten cases from the Drug-Induced Liver Injury Network[DILIN]. Am J Med.2023;136:200-206. [PMC free article: PMC9892270] [PubMed: 36252717]
(Ten cases of turmeric-associated liver injury presenting between 2011 and 2022 in the US, all adults [ages 35-71 years], mostly women [80%] and white [90%], with hepatocellular injury [90%], jaundice [50%], and 1 fatality; median ALT 1140 U/L, Alk P 164 U/L, bilirubin 2.5 mg/dL, and a strong association with HLA-B*35:01 [70% vs 12% in controls]).
SmithDN, PungweP, ComerLL, AjayiTA, SuarezMG. Turmeric-associated liver Injury: a rare case of drug-induced liver injury.Cureus.2023;15:e36978. [PMC free article: PMC10149439] [PubMed: 37139288]
(62 year old woman developed jaundice 3 weeks after starting turmeric tea [bilirubin 13.9 mg/dL, ALT 1889 U/L, Alk P 134 U/L, INR normal], with resolution within a month of stopping).
AjitkumarA, MohanG, GhoseM, YarrarapuS, AfiniwalaS. Drug-Induced liver injury secondary to turmeric use.Eur J Case Rep Intern Med.2023;10:003845. [PMC free article: PMC10187097] [PubMed: 37205206]
(55 year old woman developed jaundice 1 month after starting 1500 mg of a turmeric supplement daily [bilirubin 8.1 mg/dL, ALT 2143 U/L, Alk P 590 U/L, INR 1.2] who was treated with intravenous N-acetyl cysteine and resolved the injury within 2 months of stopping the supplement).
ArzallusT, IzagirreA, CastiellaA, TorrenteS, GarmendiaM, ZapataEM. Drug induced autoimmune hepatitis after turmeric intake.Gastroenterol Hepatol.2023;46:805-806. [PubMed: 36634868]
(28 year old man developed jaundice 5 months after starting turmeric [bilirubin 7.3 mg/dL, ALT 3770 U/L, Alk P 200 U/L, ANA 1:160, IgG 823 mg/dL, HLA-B*35:01 positive], and treated with prednisone and azathioprine and eventually had normal liver tests apparently off of immunosuppression).
FoxonF.How prevalent is liver injury attributed to turmeric?Am J Med.2024;137:e18. [PubMed: 38061832]
(Letter in response to Halegoua-DeMarzio [2023] suggesting that turmeric-associated liver injury is very rare and not likely to be increasing in frequency, because turmeric has been used for centuries, although not as purified curcumin extracts).
HaloubK, McNamaraE, YahyaRH. An unusual case of dietary-induced liver Injury during pregnancy: a case report of probable liver injury due to high-dose turmeric intake and literature review.Case Reports Hepatol.2024;2024:6677960. [PMC free article: PMC10864038] [PubMed: 38352658]
(A pregnant woman developed pruritus during the 23rd week of pregnancy and while taking turmeric [bilirubin 0.2 mg/dL, ALT 734 U/L, Alk P 175 U/L] and improved with stopping turmeric and starting ursodiol, but presented again at 35 weeks with pruritus [bilirubin 0.2 mg/dL, ALT 51 U/L, Alk P 256 U/L, and elevated bile acids], which was interpreted as idiopathic cholestasis of pregnancy and resolved after delivery).
AlghzawiF, JonesR, HaasC.Turmeric-induced liver injury.J Commun Hosp Intern Med Perspectives.2024;14:55-59. Not in PubMed.
(66 year old African American woman with a recent episode of hepatitis attributed to turmeric, redeveloped jaundice a month after restarting turmeric [bilirubin 29 mg/dL, ALT 738 U/L, Alk P 397 U/L, INR 1.8] with rapid worsening of liver function, hepatorenal syndrome, and death from acute liver failure).
CartyJ, NavarroVJ. Dietary supplement-induced hepatotoxicity: A clinical perspective.J Diet Suppl.2024:1-20. Epub ahead of print. [PubMed: 38528750]
(Review of the challenges, diagnosis, and clinical management of liver injury due to HDS including anabolic steroids, aegeline, ashwagandha, ephedra, garcinia, green tea, kratom, and turmeric, mentions that turmeric typically causes hepatocellular injury arising after 1-4 months of therapy).
