Abbreviations: DSHEA, Dietary Supplement Health and Education Act; HDS, herbal and dietary supplements.
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; several herbal medications linked to liver injury are discussed, but ginger is not mentioned).
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 herbals does not mention ginger).
Ginger. PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007; pp. 365-70.
(Compilation of short monographs on herbal medications and dietary supplements).
PhillipsS, RuggierR, HutchinsonSE. Zingiber officinale (ginger)—an antiemetic for day case surgery.Anaesthesia.1993;48:715-7. [PubMed: 8214465]
(Among 120 patients undergoing outpatient laparoscopic gynecological surgery treated postoperatively with ginger [1 g], metoclopramide [10 mg], or placebo twice daily for 4 days, nausea and vomiting were similar between the two treatment arms and slightly lower than with placebo, while “side effects were very low and not different between groups”).
SchmidR, SchickT, SteffenR, TschoppA, WilkT. Comparison of seven commonly used agents for prophylaxis of seasickness.J Travel Med.1994;1:203-206. [PubMed: 9815340]
(Among 1489 participants in a whale watch boat trip treated with one of 7 drugs to prevent seasickness, 203 were given ginger [250 mg], slight sickness occurred in 19-27% [ginger 22%] with vomiting in 4-10% [ginger 8%]; no mention adverse events).
ErnstE, PittlerMH. Efficacy of ginger for nausea and vomiting: a systematic review of randomized clinical trials.Br J Anaesth.2000;84:367-71. [PubMed: 10793599]
(A systematic review of studies of prophylaxis with ginger against nausea and vomiting, found that ginger had a beneficial effect in most studies, but did not prevent all symptoms and some trials demonstrated no effect; no mention or discussion of adverse events).
AltmanRD, MarcussenKC. Effects of a ginger extract on knee pain in patients with osteoarthritis.Arthritis Rheum.2001;44:2531-8. [PubMed: 11710709]
(Among 247 adults with painful knee osteoarthritis treated with an herbal preparation with ginger [Zingiber officinalis] and a related ginger [Alpinia galanga] or placebo twice daily for 6 weeks, reduction in knee pain upon standing and after walking was greater with the ginger product as were adverse event rates [59% vs 37%], discontinuations for adverse events [13% vs 6%], and gastrointestinal side effects [45% vs 16%]; ALT levels were not monitored and there were no hepatic serious adverse events).
VutyavanichT, KraisarinT, RuangsriR. Ginger for nausea and vomiting in pregnancy: randomized, double-masked, placebo-controlled trial.Obstet Gynecol.2001;97:577-82. [PubMed: 11275030]
(Among 70 women with nausea and vomiting of pregnancy treated with ginger [1 g] or placebo once daily for 4 days, both nausea and vomiting episodes improved more with ginger, and side effects included only mild heartburn, abdominal discomfort and headache in one patient each; no serious adverse events or mention of hepatotoxicity).
WillettsKE, EkangakiA, EdenJA. Effect of a ginger extract on pregnancy-induced nausea: a randomised controlled trial.Aust N Z J Obstet Gynaecol.2003;43:139-44. [PubMed: 14712970]
(Among 120 pregnant women with daily morning sickness treated with either ginger [1.5 g] or placebo 4 times daily for 4 days, nausea symptom scores decreased in both groups, but more with ginger while vomiting scores did not differ, and adverse events of ginger leading to discontinuation included heartburn in 4, spontaneous abortion in 3, and an allergic reaction in one; ALT levels were not done).
ManusirivithayaS, SripramoteM, TangjitgamolS, SheanakulC, LeelahakornS, ThavaramaraT, TangcharoenpanichK. Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin.Int J Gynecol Cancer.2004;14:1063-9. [PubMed: 15571611]
(Among 48 women with gynecologic cancer receiving cisplatin based chemotherapy treated with either ginger root powder or metoclopramide for 5 days and crossed over during the next cycle, control of nausea and vomiting was no different with the two drug regimens, although side effects were less with ginger [19% vs 28%], restlessness in 5% vs 19%, constipation in 7% vs 14%, and diarrhea in 14% vs 5%; no mention of ALT elevations or 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 were specifically attributed to a product containing ginger).
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 Spanish registry, 13 [2%] were due to herbals, but none were attributed to ginger).
NavarroVJ. Herbal and dietary supplement hepatotoxicity.Semin Liver Dis2009; 29: 373-82. [PubMed: 19826971]
(Review of the problems of causality assessment in herbal and dietary supplement [HDS] associated liver disease, including the variable clinical presentations, the complexity and lack of information on their components, absence of controlled trials demonstrating safety and efficacy, the possibility of contamination or incorrect labeling, and the frequent underreporting of herbal use by patients. Regulation of HDS is under DSHEA, which requires manufacturers to determine safety and prohibits claims of efficacy in treating specific diseases. The US Pharmacopeia sets standards for food and drugs and includes HDS; HDS induced liver injury is a growing problem and currently accounts for at least 10% of cases of acute liver injury due to medications).
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; no mention of ginger).
ReubenA, KochDG, LeeWM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study.Hepatology2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]
(Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 [11%] were attributed to drug induced liver injury of which 12 [9%] were due to herbals, but none were attributed to ginger).
TeschkeR, WolffA, FrenzelC, SchulzeJ, EickhoffA.Herbal hepatotoxicity: a tabular compilation of reported cases.Liver Int2012; 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, but ginger was not listed or mentioned).
NavarroVJ, BarnhartH, BonkovskyHL, DavernT, FontanaRJ, GrantL, ReddyKR, et al.Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network.Hepatology2014; 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 to a product containing ginger).
ChalasaniN, BonkovskyHL, FontanaR, LeeW, StolzA, TalwalkarJ, ReddyKR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study.Gastroenterology2015; 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%], the single major herbal cause being green tea and none were attributed to ginger [see also Navarro et al Hepatology 2014]).
SuzukiY, YamazakiY, HashizumeH, OyamaT, HoriguchiN, SatoK, KakizakiS, et al.[Drug-induced liver injury caused by a dietary supplement (Kin-toki Shoga(®)) made from ginger]. Nihon Shokakibyo Gakkai Zasshi.2015;112:108-14. Japanese. [PubMed: 25744927]
(70 year old woman developed abdominal pain and dark urine followed by jaundice two months after starting a supplement called Kin-toki Shoga ginger [bilirubin 10.8 mg/dL, ALT 2052 U/L, Alk P 784 U/L], liver biopsy showing an acute hepatitis and resolving over the 4 to 6 weeks after stopping).
McParlinC, O'DonnellA, RobsonSC, BeyerF, MoloneyE, BryantA, BradleyJ, et al.Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review.JAMA. 2016;316:1392-1401. [PubMed: 27701665]
(Systematic review including 17 randomized controlled trials of ginger for nausea and vomiting of pregnancy concluded that ginger had greater benefit than placebo and that side effects are generally mild, most frequently acid reflux).
García-CortésM, Robles-DíazM, Ortega-AlonsoA, Medina-CalizI, AndradeRJ. Hepatotoxicity by dietary supplements: A tabular listing and clinical characteristics.Int J Mol Sci2016; 17: 537. [PMC free article: PMC4848993] [PubMed: 27070596]
(Listing of published cases of liver injury from HDS products, but does not mention or list ginger).
BrownAC. An overview of herb and dietary supplement efficacy, safety and government regulations in the United States with suggested improvements. Part 1 of 5 series.Food Chem Toxicol2017; 107: 449-71. [PubMed: 27818322]
(Summary of the US regulations on safety and efficacy of herbal and dietary supplements).
BrownAC. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series.Food Chem Toxicol2017; 107: 472-501. [PubMed: 27402097]
(Description of an online compendium of cases of liver toxicity attributed to HDS products, does not mention or list ginger).
NavarroVJ, KhanI, BjörnssonE, SeeffLB, SerranoJ, HoofnagleJH. Liver injury from herbal and dietary supplements.Hepatology2017; 65: 363-73. [PMC free article: PMC5502701] [PubMed: 27677775]
(Review of the problems of liver injury and HDS products, mentions that multiingredient dietary supplements account for the major of cases but does not mention a product with ginger as a component).
BossiP, CortinovisD, FatigoniS, Cossu RoccaM, FabiA, SeminaraP, RipamontiC, et al.A randomized, double-blind, placebo-controlled, multicenter study of a ginger extract in the management of chemotherapy-induced nausea and vomiting (CINV) in patients receiving high-dose cisplatin.Ann Oncol.2017;28:2547-2551. [PubMed: 28666335]
(Among 251 adults undergoing chemotherapy for cancer with a cisplatin-based regimen treated with a purified extract of ginger [40 mg] or placebo twice daily for 4 days, nausea and vomiting symptom scores did not differ in the two groups and adverse event rates were similar and largely unrelated to therapy).
AnhNH, KimSJ, LongNP, MinJE, YoonYC, LeeEG, KimM, KimTJ, et al.Ginger on human health: a comprehensive systematic review of 109 randomized controlled trials.Nutrients.2020;12:157. [PMC free article: PMC7019938] [PubMed: 31935866]
(An extensive systematic review of clinical trials of ginger for various conditions identified 109 qualifying trials including 43 considered to be of high quality, providing convincing data of the benefit of ginger for nausea and vomiting of pregnancy, inflammation [including osteoarthritis], metabolic function [hyperlipidemia, glucose control], digestive function, and colorectal cancer markers, whereas the beneficial effects of ginger in other conditions studied were “relatively controversial”, but adverse events are mostly mild gastrointestinal complaints; no mention of serious adverse events or hepatoxicity).
MartinsLB, RodriguesAMDS, MontezeNM, TibaesJRB, AmaralMHA, GomezRS, TeixeiraAL, et al.A double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine.Cephalalgia.2020;40:88-95. [PubMed: 31398997]
(Among 107 adults with episodic migraine treated with ginger [200 mg] or placebo 3 times daily for 3 months, there was no difference in rate of migraine episodes in the two groups, but adverse events were more frequent with ginger including heartburn in 12 [23%] that led to early discontinuation in 4 [7.5%], no mention of ALT elevations or hepatoxicity).
NocerinoR, CecereG, MicilloM, De MarcoG, FerriP, RussoM, BedogniG, et al.Efficacy of ginger as antiemetic in children with acute gastroenteritis: a randomised controlled trial.Aliment Pharmacol Ther.2021;54:24-31. [PMC free article: PMC8252074] [PubMed: 34018223]
(Among 150 children with acute gastroenteritis treated with ginger extract [10 mg in 20 liquid drops, repeated every 8 hours until vomiting stops] vs placebo, episodes of vomiting occurred in 67% vs 87% in the subsequent two days and there were no adverse events reported from either group).
BallotinVR, BigarellaLG, BrandãoABM, BalbinotRA, BalbinotSS, SolderaJ. Herb-induced liver injury: Systematic review and meta-analysis.World J Clin Cases.2021;9:5490-5513. [PMC free article: PMC8281430] [PubMed: 34307603]
(Systematic review of the literature on herb induced liver injury identified 446 references describing 936 cases due to 79 different herbal products, the most common being He Shou Wu [91], green tea [90] Herbalife products [64], kava kava [62] and greater celandine [48]; ginger was not among the 79 implicated products).
BessoneF, García-CortésM, Medina-CalizI, HernandezN, ParanaR, MendizabalM, SchinoniMI, et al.Herbal and dietary supplements-induced liver injury in Latin America: experience from the LATINDILI Network.Clin Gastroenterol Hepatol.2022;20:e548-e563. [PubMed: 33434654]
(Among 367 cases of hepatotoxicity enrolled in the Latin American DILI Network between 2011 and 2019, 29 [8%] were attributed to herbal products, the most frequent being green tea [n=7], Herbalife products [n=5] and garcinia [n=3], while ginger is not mentioned).
SamadiM, MoradinazarM, KhosravyT, SoleimaniD, JahangiriP, KamariN.A systematic review and meta-analysis of preclinical and clinical studies on the efficacy of ginger for the treatment of fatty liver disease.Phytother Res.2022;36:1182-1193. [PubMed: 35106852]
(Review of the literature on efficacy of ginger in nonalcoholic fatty liver disease in animal models and in 3 human studies suggested that therapy with ginger reduced serum ALT by 3 U/L, AST by 1 U/L, cholesterol by 3.5 mg/dL, triglycerides by 5 mg/dl and fasting blood sugar by 2.5 mg/dL; no mention of adverse events).
ChoiJ, LeeJ, KimK, ChoiHK, LeeSA, LeeHJ. Effects of ginger intake on chemotherapy-induced nausea and vomiting: a systematic review of randomized clinical Trials.Nutrients.2022;14:4982. [PMC free article: PMC9739555] [PubMed: 36501010]
(Systematic review of 23 randomized controlled trials found no evidence for a benefit effects of therapy with ginger in preventing early or delayed nausea or vomiting and while 9 studies reported no adverse events, 7 studies reported adverse event rates that were similar to those in placebo recipients, the most common being gastrointestinal symptoms; no mention of ALT elevation or hepatotoxicity).
Sarecka-HujarB, Szulc-MusiołB. Herbal medicines-are they effective and safe during pregnancy?Pharmaceutics.2022;14:171. [PMC free article: PMC8802657] [PubMed: 35057067]
(Literature review of the safety and efficacy of selected herbal therapies [cranberry, chamomile, Echinacea, garlic, ginkgo, peppermint, and ginger] concludes that data on safety are somewhat sparse for most agents, but data fairly strongly indicate that doses of ginger 1000 mg/kg or less in animals and 1000 mg or less in humans have no adverse effects on pregnancy or fetal health and development).
AfsharF, AbdolahiN, AminG, EsmailyH, ZiayieS, AzimiS, DarvishiB, et al.A randomized, double-blind placebo-controlled phase I clinical study on safety and efficacy of the G-Rup® syrup (a mixture of ginger extract and honey) in symptomatic treatment of knee osteoarthritis.J Clin Pharm Ther.2022;47:2295-2301. [PubMed: 36453014]
(Among 44 adults with osteoarthritis of the knee treated with a commercial syrup containing ginger and honey or placebo twice daily for 12 weeks, symptom scores for pain, stiffness, and function improved more with the ginger syrup than placebo and adverse event rates were similar in the two groups; no mention of hepatotoxicity).
MahawerSK, KumarR, PrakashO, AryaS, SinghS, de OliveiraMS, RawatDS. A comprehensive review on phytochemistry, ethnopharmacology, and pharmacological properties of Zingiber roseum (Roxb.) Roscoe.Curr Top Med Chem.2023;23:931-942. [PubMed: 36703584]
(Review of the phytochemistry, traditional uses, pharmacology, and biologic activities of ginger).
