GINSENG (PANAX GINSENG)
Ginseng is a popular herbal medication and extract derived from the roots of a perennial plant (Panax ginseng) found mostly in China, Korea and Siberia. Ginseng is used is to promote health and improve wellness, as well as to treat stress and as a mild stimulant. Ginseng has not been implicated in causing liver injury although it may have the potential of causing significant herb-drug interactions that can lead to liver injury.
Ginseng (jin' seng) is a widely used herbal derived from the roots of eleven distinct species of plants belonging to the genus Panax and family Araliaceae. Ginseng grows in the Northern Hemisphere in eastern Asia, mostly China, Korea and Siberia. The form of ginseng most commonly used is Asian (or Chinese) ginseng made from the dried roots of Panax ginseng. American ginseng (Panax quinquefolius) has similar properties. The word ginseng derives from the Chinese character “rénshen” meaning “man root”, which refers to the ginseng root’s characteristic forked shape. The botanical name Panax is derived from the Greek word meaning “all-heal” as in the term panacea. Ginseng is taken promote health and healing, as an adaptogen (to treat stress and enhance recovery from illness), aphrodisiac (to aid in sexual desire and performance) and a stimulant (wakefulness and mental acuity). Ginseng is also claimed to lower blood glucose levels and to be beneficial in diabetes. Ginseng is found in energy drinks as well as in many cosmetic preparations. The scientific bases for the purported effects of ginseng are not well established. Ginseng contains 30 different triterpene saponins, referred to as ginsenosides and panaxosides, which are considered the active compounds and which have antioxidant and stimulatory activities. Commercial preparations of ginseng vary widely in ginsenoside content (some have none at all), which may cause variation in their biologic effects. The recommended daily dose varies widely (100 to >1,000 mg daily), depending on the preparation used (capsules, tablets, liquid, root extract, tea) and indications. Side effects of ginseng are uncommon and mild, and include inability to sleep, nausea, morning diarrhea, headaches and nose bleeds.
Despite wide spread use, ginseng by itself has not been linked to liver injury, either in the form of transient serum enzyme elevations or clinically apparent acute liver injury. Indeed, ginseng is sometimes used to treat acute or chronic liver injury, although its efficacy and safety in this situation have not been proven. Nevertheless, ginseng has been reported to affect cytochrome P450 activity and cause significant herb-drug interactions that can lead to adverse events including liver injury. In vitro studies have found that different gensinosides have different effects on cytochrome P450 activity and some inhibit CYP 3A4 sufficiently to cause such interactions. Thus, different ginseng preparations may exhibit varying degrees of herb-drug interaction. Liver injury has been reported to develop 1 to 3 months after starting ginseng in patients who previously tolerated the potentially toxic agent (imatinib, raltegravir) without liver injury and who later tolerated restarting the medication without concurrent ginseng use.
REPRESENTATIVE TRADE NAMES
Ginseng – Generic
Herbals and Dietary Supplements
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References updated: 17 March 2014
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herbal and dietary supplements [HDS]; ginseng is not discussed).
Ginseng. In, PDR for Herbal Medicines. 4th ed. Montvale, New Jersey: Thomson Healthcare Inc. 2007: pp. 384-92. (Compilation of short monographs on herbal medications and dietary supplements).
Cui J, Garle M, Eneroth P, Bjorkhem I. What do commercial ginseng preparations contain? Lancet 1994; 344: 134. PubMed Citation (Analysis of 50 commercial ginseng products sold in 11 countries found concentration of ginsenosides varied from 1.9-9%, and 6 [12%] had none and were likely not made from ginseng).
Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Health Syst Pharm 1997; 54: 692-3. PubMed Citation (47 year old man on anticoagulation for a mechanical heart valve with INR maintained between 3.0 and 4.0 started ginseng capsules three times daily and, two weeks later, INR was 1.5, returning to previous level upon stopping ginseng).
Vogler BK, Pittler MH, Ernst E. The efficacy of ginseng. A systematic review of randomised clinical trials. Eur J Clin Pharmacol 1999; 55: 567-75. PubMed Citation (Systematic review of the literature found 16 trials of ginseng root extract, but found that evidence for benefit was not compelling for any indication: physical and psychomotor performance, cognitive function, diabetes and herpes simplex).
Kitts D, Hu C. Efficacy and safety of ginseng. Public Health Nutr 2000; 3: 473-85. PubMed Citation (Review of the history, composition, purported effects, clinical efficacy and safety of ginseng).
Stedman C. Herbal hepatotoxicity. Semin Liver Dis 2002; 22: 195-206. PubMed Citation (Review and description of patterns of liver injury, including discussion of potential risk factors, and herb-drug interactions; ginseng may interact with warfarin causing a decrease in anticoagulation).
De Smet PAGM. Herbal remedies. N Engl J Med 2002; 347: 2046-56. PubMed Citation (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).
Schiano TD. Hepatotoxicity and complementary and alternative medicines. Clin Liver Dis 2003; 7: 453-73. PubMed Citation (Comprehensive review of herbal associated hepatotoxicity; ginseng is not listed as causing hepatotoxicity).
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. Liver Transpl 2004; 10: 1018-23. PubMed Citation (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 ginseng use).
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]. Rev Esp Enferm Dig 2008; 100: 688-95. Spanish. PubMed Citation (Among 521 cases of drug induced liver injury submitted to a Spanish registry, 13 [2%] were due to herbals, but none were attributed to ginseng).
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. Gastroenterology 2008; 135: 1924-34. PubMed Citation (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 ginseng use).
Saxena A, Tripathi KP, Roy S, Khan F, Sharma A. Pharmacovigilance: effects of
herbal components on human drugs interactions involving cytochrome P450.
Bioinformation 2008; 3: 198-204. PubMed Citation (Review of effects of St. John's wort, piperine, ginsenosides and ginkgolic acid on cytochrome P450 activity; in vitro ginsenosides have inhibitory activity against CYP 2E1 and CYP 3A4).
Hao M, Zhao Y, Chen P, Huang H, Liu H, Jiang H, Zhang R, Wang H.
Structure-activity relationship and substrate-dependent phenomena in effects of
ginsenosides on activities of drug-metabolizing P450 enzymes. PLoS One 2008; 3: e2697. PubMed Citation (Ginsenosides with different structures have different effects on cytochrome P450 activity).
Navarro VJ. Herbal and dietary supplement hepatotoxicity. Semin Liver Dis 2009; 29: 373-82. PubMed Citation (Overview of the regulatory environment, clinical patterns, and future directions in research with HDS; ginseng is not listed as a potentially hepatotoxic botanical).
Jacobsson I, Jönsson AK, Gerdén B, Hägg S. Spontaneously reported adverse reactions in association with complementary and alternative medicine substances
in Sweden. Pharmacoepidemiol Drug Saf 2009; 18: 1039-47. PubMed Citation (Review of 778 spontaneous reports of adverse reactions to herbals to Swedish Registry found 14 [2%] attributed to ginseng, including 2 with a "mixed liver reaction" and 2 with enzyme elevations, but no details given).
Bilgi N, Bell K, Ananthakrishnan AN, Atallah E. Imatinib and Panax ginseng: a
potential interaction resulting in liver toxicity. Ann Pharmacother 2010; 44: 926-8. PubMed Citation (26 year old man with CML on imatinib for 7 years developed symptomatic liver injury 3 months after starting daily use of an energy drink with Panax ginseng [bilirubin 1.4 mg/dL, ALT 1069 U/L, Alk P 124 U/L] which resolved with stopping both medications, but he was able to restart imatinib without recurrence of liver injury after recovery and while remaining off of ginseng).
Mateo-Carrasco H, Gálvez-Contreras MC, Fernández-Ginés FD, Nguyen TV. Elevated
liver enzymes resulting from an interaction between Raltegravir and Panax
ginseng: a case report and brief review. Drug Metabol Drug Interact
2012; 27: 171-5. PubMed Citation (Abstract only: Patient with chronic hepatitis C and HIV infection on long term antiretroviral therapy with raltegravir, lopinavir and ritonavir developed jaundice 39 days after starting ginseng tablets, resolving with stopping herbal intake).
Bunchorntavakul C, Reddy KR. Review article: herbal and dietary supplement
hepatotoxicity. Aliment Pharmacol Ther 2013; 37: 3-17. PubMed Citation (Systematic review of literature on HDS associated liver injury mentions that ginseng can have significant herb-drug interactions).
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