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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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Tongkat Ali

Last Update: October 18, 2024.

OVERVIEW

Introduction

Tongkat ali (Eurycoma longifolia Jack), also known as “Long Jack”, is a flowering, shrubby, slow growing tree native to Southeast Asia, the leaves, roots, and bark of which have been used extensively in traditional medicine for many conditions including diabetes, arthritis, liver diseases, malaria, dysentery, and erectile dysfunction. It has recently become a popular herbal supplement in the United States, as extracts of tongkat ali roots have been promoted as increasing testosterone levels and improving athletic performance. Reports of clinically apparent liver injury attributed to tongkat ali in body builders have recently appeared.

Background

Tongkat ali (Eurycoma longifolia), also known as “Long Jack”, is a flowering, shrubby, slender, slow growing evergreen tree native to Southeast Asia, the leaves, roots, and bark of which have been used extensively in traditional medicine for a variety of conditions including diabetes, rheumatism, jaundice, malaria, asthma, depression, fever, fungal infections, and as an aphrodisiac. Components of Eurycoma longifolia have been found to have possibly beneficial biologic activities in animal models including hypoglycemic, diuretic, antioxidant, antiinflammatory, analgesic, antimalarial, antiviral, anticoagulant, hepatoprotective, immunomodulatory, antineoplastic, and aphrodisiac activities. Chemical analyses have demonstrated more than 65 compounds in extracts from Eurycoma longifolia including glycosaponins, quassinoids (eurycomanone, eurycomanols, eurycomalactones), canthine-6-one alkaloids, phenolic derivatives, coumarin, tannins, and triterpenes. It is not clear which of the identified compounds have the claimed biologic or clinical activities of tongkat ali either in animals or humans. Several studies in humans have shown mild increases in serum total testosterone levels in patients treated with tongkat ali, usually requiring several weeks for a full response and with no increase in free testosterone levels or in sex hormone binding globulin. The increases in testosterone levels have been generally associated with improved symptoms and mild increases in muscle strength in response to resistance training but have not been linked to improved athletic performance. Tongkat ali is available over the counter in various forms including raw powders, blends with tea or coffee, and capsules alone or in combination with other herbal products or dietary supplements. The typical dose in traditional medicine is 100 to 400 mg daily, but higher amounts (1,000 to 1,600 mg) are available in capsules sold online in products advertised as increasing testosterone levels, alleviating erectile dysfunction and “low T” syndrome as well as aiding body building and improving muscle strength. Side effects of tongkat ali in conventional doses are uncommon but may include nausea, abdominal discomfort, diarrhea, headaches, and rash. Its long term safety has not been well documented in humans.

Hepatotoxicity

In small rather short term clinical studies of different preparations and concentrations of tongkat ali, adverse side effects were usually described as uncommon, unrelated to therapy, and minimal with no changes in serum ALT, AST, GGT or bilirubin levels. The effects of long term use and of higher doses, however, have not been assessed in humans. Furthermore, there is no standardization of purity and concentration of the extracts used. Recently, there have been isolated reports of clinically apparent liver injury in patients taking tongkat ali (Case 1). These reports have largely been in young male body builders and the possibility of unacknowledged anabolic steroid use weakens the evidence that the injury was due to Eurycoma longifolia.

Likelihood score: D (possible rare cause of clinically apparent liver injury).

Mechanism of Injury

Tongkat ali has multiple constituents and the chemical compounds that are possibly responsible for liver injury are not known. The clinical features of tongkat ali liver injury suggest that it is immunologically mediated. Cases may be more frequent and more severe in patients with preexisting liver disease and most clinical studies of tongkat ali have excluded patients with preexisting liver disease.

Outcome and Management

Liver injury reported from tongkat ali has been self-limited in course and chronic injury has not been clearly described. At issue with most cases has been the possible role of unacknowledged anabolic steroid use or preexisting liver disease.

Drug Class: Herbal and Dietary Supplements

Other names: Eurycoma longifolia, Ali’s walking stick, Long Jack, Cay Ba Binh (Vietnam), Piak Saw (Thailand), Natural Viagra, Malaysian Ginseng

CASE REPORT

Case 1. Acute liver injury with jaundice attributed to a tongkat ali for body building.(1)

A 47 year old man developed upper abdominal discomfort, nausea and vomiting followed by dark urine and jaundice a week after starting a new herbal supplement for body building that contained tongkat ali. He was otherwise healthy except for hypertension. He was taking no other medications and denied a history of liver disease or risk factors for viral hepatitis. He drank alcohol socially and smoked cigarettes but denied drug abuse or use of other herbal medications. On examination he had normal vital signs except for hypertension and jaundice. Laboratory testing demonstrated a total bilirubin of 7.5 mg/dL, ALT 470 U/L, AST 234 U/L, Alk P 192 U/L, and INR 1.0 (R=7.5). Tests for hepatitis A, B and C were negative as were ANA and SMA. Abdominal ultrasound and computerized tomography (CT) were normal without evidence of gallstones or biliary dilatation. He was admitted to the hospital and the herbal supplement was withdrawn. Liver tests worsened for a few days and then began to improve (Table). He did not undergo liver biopsy and was not treated with corticosteroids.

Key Points

Medication:Tongkat ali (Eurycoma longifolia) for 2 weeks, unknown dose
Pattern:R=7.5 (hepatocellular)
Severity:3+ (jaundiced and hospitalized)
Latency:1 week
Recovery:1-2 months suspected
Other medications:None reported

Laboratory Values

Time After
Starting		Time After
Stopping		ALT
(U/L)		Alk P
(U/L)		Bilirubin
(mg/dL)		Comments
0PreStarted tongkat ali for bodybuilding
7 daysPreDeveloped nausea and abdominal pain
10 daysPre4701927.5Emergency room
14 days087523814.3Admitted, supplement stopped
16 days2 days74422013.2
17 days3 days64723512.9Discharged
34 days20 days1931575.3Symptoms improved
Upper Limit of Normal 40* 125* 1.2

* Standard values

Comment

A 47 year old male body builder developed nausea, abdominal pain, and jaundice within a week or two of starting an herbal product containing tongkat ali. The injury was mildly hepatocellular and associated with moderate jaundice. The report lacked information on dose and had only partial follow up, not documenting whether full recovery occurred. This was the first published case of possible drug induced liver injury due to Eurycoma longifolia. While the clinical, laboratory, and radiologic evaluation was thorough in ruling out other causes of liver injury, an important cause to consider in body builders is the unacknowledged use of anabolic steroids. These products are illegal, of unknown purity and potency, and taken without medical supervision, often in excessive doses. The onset of liver injury and jaundice is usually after 1 to 3 months of taking anabolic steroids. Patients frequently do not admit to taking anabolic steroids and may specifically deny it. Itching is a frequent but not invariable symptom.

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Tongkat ali – Generic

DRUG CLASS

Herbal and Dietary Supplements

DRUGCAS REGISTRY NUMBERMOLECULAR FORMULASTRUCTURE
Eurycomanone 84633-29-4 C20-H24-O9SID: 135254161

CITED REFERENCE

1.
Kaliounji A, Shadid G, Saba H, Ahlawat S. A rare case of Tongkat ali-induced liver injury: a case report. Cureus. 2024; 16: e56639. [PMC free article: PMC11032125] [PubMed: 38646387]

ANNOTATED BIBLIOGRAPHY

References updated: 24 October 2024

Abbreviations: 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 are discussed, but not tongkat ali).
  • Liu LU, Schiano TD. Hepatotoxicity of herbal medicines, vitamins and natural hepatotoxins. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 2nd ed. New York: Informa Healthcare USA, 2007, pp. 733-54.
    (Review of hepatotoxicity of herbal and dietary supplements [HDS] published in 2007; no mention of tongkat ali).
  • 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: 19650152]
    (Review of 778 spontaneous reports of adverse reactions to herbals in a Swedish Registry does not list tongkat ali among products associated with 5 or more reports).
  • Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia. 2010;81:669-79. [PubMed: 20434529]
    (Review of the taxonomy, traditional uses, chemical composition, biologic activities, and safety of tongkat ali mentions that extracts of roots of the Eurycoma longifolia tree are used for increasing testosterone levels, but that there are no standards for purity of the plant extract or specific chemical component responsible for its activity and no available reports on the side effects of long term use).
  • Chen CK, Muhamad AS, Ooi FK. Herbs in exercise and sports. J Physiol Anthropol. 2012;31:4. [PMC free article: PMC3375032] [PubMed: 22738233]
    (Review of the efficacy and safety of various herbal products in sports with mention of tongkat ali which has been shown to raise testosterone levels and increase sexual activity in rodents, but its effects in humans are less well established; no mention of ALT elevations during therapy or hepatotoxicity).
  • Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2012;44 Suppl 1:226-30. [PubMed: 21671978]
    (Description of controlled trials of Eurycoma longifolia extracts versus placebo in increasing athletic performance of professional cyclists, mentions two studies that showed no evidence of an effect on performance but also no evidence of toxicity).
  • Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int 2012; 32: 1543-56. [PubMed: 22928722]
    (A systematic compilation of all publications on the hepatotoxicity of specific herbals identified 185 publications on 60 different herbs and herbal supplements but does not mention or list tongkat ali).
  • Li CH, Liao JW, Liao PL, Huang WK, Tse LS, Lin CH, Kang JJ, et al. Evaluation of acute 13-week subchronic toxicity and genotoxicity of the powdered root of Tongkat ali (Eurycoma longifolia Jack). Evid Based Complement Alternat Med. 2013;2013:102987. [PMC free article: PMC3767077] [PubMed: 24062779]
    (Studies in rodents found no evidence of hepatic toxicity or elevations in serum ALT or AST from single doses or from 4- and 13-week daily therapy with Eurycoma longifolia root extracts in daily amounts of up to 2 gm/kg body weight).
  • Ulbricht C, Conquer J, Flanagan K, Isaac R, Rusie E, Windsor RC. An evidence-based systematic review of tongkat ali (Eurycoma longifolia) by the Natural Standard Research Collaboration. J Diet Suppl. 2013;10:54-83. [PubMed: 23419023]
    (Extensive systematic review of the biologic activities, clinical efficacy, and safety of tongkat ali concludes that there is little information available on the adverse effects associated with Eurycoma longifolia; no discussion of hepatotoxicity or effects on ALT or AST levels).
  • Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. Clin Liver Dis 2013; 17: 715-35. [PubMed: 24099027]
    (Review of the epidemiology, regulatory status, diagnosis, pathogenesis and causes of liver injury from herbal products with specific discussion of conjugated linoleic acid, ephedra, germander, green tea, usnic acid, flavocoxid, aloe vera, chaparral, greater celandine, black cohosh, comfrey, kava, skullcap, valerian, noni juice, pennyroyal, and traditional herbal remedies, but does not mention tongkat ali).
  • 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. Hepatology 2014; 60: 1399-408. [PMC free article: PMC4293199] [PubMed: 25043597]
    (Among 839 cases of liver injury from drugs collected in the US between 2004 and 2013, 130 were due to HDS products, including 45 from body building agents [probably anabolic steroids] and 85 from diverse HDS products, but no case was attributed specifically to tongkat ali).
  • Henkel RR, Wang R, Bassett SH, Chen T, Liu N, Zhu Y, Tambi MI. Tongkat Ali as a potential herbal supplement for physically active male and female seniors—a pilot study. Phytother Res. 2014;28:544-50. [PubMed: 23754792]
    (Among 97 overweight or obese adults treated with an herbal product containing a blend of Citrus bergamia and Eurycoma longifolia [200 or 400 mg] or placebo once daily for 112 days, body mass index decreased with the herbal supplement by 1.0 kg/m2 vs an increase of 0.5 kg/m2 with placebo but without a change in lean body weight or fat mass and with no differences in changes in ALT, AST and GGT levels).
  • Chen CK, Mohamad WM, Ooi FK, Ismail SB, Abdullah MR, George A. Supplementation of Eurycoma longifolia Jack extract for 6 weeks does not affect urinary testosterone: epitestosterone ratio, liver and renal functions in male recreational athletes. Int J Prev Med. 2014;5:728-33. [PMC free article: PMC4085925] [PubMed: 25013692]
    (Among 13 healthy male recreational athletes treated with Eurycoma longifolia extract [400 mg] or placebo once daily for 6 weeks with subsequent cross-over, there was no change in the testosterone: epitestosterone ratio and no changes in renal or liver tests).
  • Kreipke VC, Allman BR, Kinsey AW, Moffatt RJ, Hickner RC, Ormsbee MJ. Impact of four weeks of a multi-ingredient performance supplement on muscular strength, body composition, and anabolic hormones in resistance-trained young men. J Strength Cond Res. 2015;29:3453-65. [PubMed: 26595135]
    (Among 27 young resistance trained men treated with a multi-ingredient product containing tongkat ali, beta alanine, branched chain amino acids, and a ”proprietary blend” versus placebo daily during a 4 week high intensity resistance training program, herbal treated patients showed greater increases in press weight [6 vs 5 kgs] and total weight lifted [34 vs 24 kgs] but no change in psychological or blood test results; no mention of testosterone, ALT or AST results).
  • Rehman SU, Choe K, Yoo HH. Review on a traditional herbal medicine, Eurycoma longifolia Jack (Tongkat ali): its traditional uses, chemistry, evidence-based pharmacology and toxicology. Molecules. 2016;21:331. [PMC free article: PMC6274257] [PubMed: 26978330]
    (Review of the traditional use, chemistry, pharmacology, and toxicology of tongkat ali, mentions that it has been used as an aphrodisiac as well as treatment for malaria, fever, dysentery, and high blood pressure, and concludes that it has been shown to be safe when given in standard doses but that more information is needed on its safety).
  • Brown AC. Liver toxicity related to herbs and dietary supplements: online table of case reports. Part 2 of 5 series. Food Chem Toxicol 2017; 107: 472-501. [PubMed: 27402097]
    (Description of an online compendium of cases of liver toxicity attributed to HDS products does not list or discuss tongkat ali).
  • Medina-Caliz I, Garcia-Cortes M, Gonzalez-Jimenez A, Cabello MR, Robles-Diaz M, Sanabria-Cabrera J, Sanjuan-Jimenez R, et al.; Spanish DILI Registry. Herbal and dietary supplement-induced liver injuries in the Spanish DILI Registry. Clin Gastroenterol Hepatol. 2018;16:1495-1502. [PubMed: 29307848]
    (Among 856 cases of hepatotoxicity enrolled in the Spanish DILI Registry between 1994 and 2016, 32 were attributed to herbal products, the most frequent cause being green tea [n=8] and Herbalife products [n=6], no mention of tongkat ali or Eurycoma longifolia).
  • Balasubramanian A, Thirumavalavan N, Srivatsav A, Yu J, Hotaling JM, Lipshultz LI, Pastuszak AW. An Analysis of popular online erectile dysfunction supplements. J Sex Med. 2019;16:843-852. [PMC free article: PMC9555224] [PubMed: 31036522]
    (Among the 6 most frequently ordered herbal products advertised for erectile dysfunction on Amazon, 5 had multiple ingredients, 3 of which contained tongkat ali).
  • Chen CK, Ooi FK, Abu Kasim NA, Asari MA. Effects of Eurycoma Longifolia Jack supplementation combined with resistance training on isokinetic muscular strength and power, anaerobic power, and urinary testosterone: epitestosterone ratio in young males. Int J Prev Med. 2019;10:118. [PMC free article: PMC6639844] [PubMed: 31367282]
    (Among 40 healthy males ages 19 to 25 years treated with Eurycoma longifolia [200 mg] or placebo once daily with or without resistance training for 8 weeks, increase in muscle strength was found with resistance training but not with Eurycoma longifolia alone; no mention of adverse events).
  • Chinnappan SM, George A, Evans M, Anthony J. Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled study. Food Nutr Res. 2020;64:3665. [PMC free article: PMC7534949] [PubMed: 33061884]
    (Among 119 healthy women with menopausal symptoms treated with an herbal supplement with Labisia pumila and Eurycoma longifolia or with placebo, symptoms improved in both groups while ALT, AST and GGT levels remained within normal limits).
  • Brunetti P, Lo Faro AF, Tini A, Busardò FP, Carlier J. Pharmacology of herbal sexual enhancers: a review of psychiatric and neurological adverse effects. Pharmaceuticals (Basel). 2020;13: 309. [PMC free article: PMC7602496] [PubMed: 33066617]
    (Review of literature on central nervous system adverse events of herbal sexual enhancers mentions that there were no reports on the psychiatric or neurological side effects of Eurycoma longifolia).
  • Ballotin VR, Bigarella LG, Brandão ABM, Balbinot RA, Balbinot SS, Soldera J. 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]; no mention of Eurycoma longifolia or tongkat ali).
  • Leitão AE, Vieira MCS, Gomes DA, Boing L, Pelegrini A, Luiz E, Guimarães ACA. Exercise associated or not to the intake of Eurycoma longifolia improves strength and cardiorespiratory fitness in men with androgen deficiency. Complement Ther Clin Pract. 2021;42:101301. [PubMed: 33445146]
    (Among 37 men, ages 40 to 59 years, with androgen deficiency of aging who were randomized to receive Eurycoma longifolia [200 mg] or placebo daily combined with or without concurrent exercise training, muscular strength increased, and symptomatology improved in both groups with concurrent exercise training but there were no consistent differences with addition of Euryocoma longifolia).
  • Leitão AE, Vieira MCS, Pelegrini A, da Silva EL, Guimarães ACA. A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM). Maturitas. 2021;145:78-85. [PubMed: 33541567]
    (Among 105 adult men with low testosterone levels treated with an extract of roots of Eurycoma longifolia [100 or 200 mg] or placebo once daily for 12 weeks, total testosterone levels rose with herbal therapy compared to placebo as did improvements in symptoms and fatigue).
  • Chinnappan SM, George A, Pandey P, Narke G, Choudhary YK. Effect of Eurycoma longifolia standardised aqueous root extract-Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study. Food Nutr Res. 2021;65:5647. [PMC free article: PMC8254464] [PubMed: 34262417]
    (Among 105 men, ages 50 to 70 years, with low testosterone levels [<300 ng/dL] treated with an aqueous extract of Eurycoma longifolia roots [100 or 200 mg] vs placebo once daily for 12 weeks, symptom of fatigue improved and total testosterone levels increased in a dose dependent manner on the herbal extract [by 16 ng/dL and 25 ng/dL: +9% and +12.5% vs -3%], while free testosterone and sex hormone binding globulin levels were similar in all groups and serum ALT, AST, and bilirubin levels did not change).
  • Hancke J, Srivastava S, Caceres DD, Burgos RA, Alarcon P. An exploratory double-blind, randomized, placebo-controlled study to assess the efficacy of CitruSlim on body composition and lipid parameters in obese individuals. Phytother Res. 2021;35:7039-7049. [PubMed: 34794202]
    (Among 97 overweight or obese adults treated with two doses of an herbal supplement containing Citrus begamia and Eurycoma longifolia vs placebo 3 times daily for 112 days, change in mean BMIs were -1.0 on the supplement vs +0.5 on placebo without differences in lean body mass or percent body fat, while therapy was well tolerated and serum levels of ALT, AST and Alk P did not change).
  • EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA); Turck D, Bohn T, Castenmiller J, De Henauw S, Hirsch-Ernst KI, Maciuk A, Mangelsdorf I, et al. Safety of Eurycoma longifolia (Tongkat Ali) root extract as a novel food pursuant to Regulation (EU) 2015/2283. EFSA J. 2021;19:e06937. [PMC free article: PMC8693240] [PubMed: 34987621]
    (Analysis of the safety of Eurycoma longifolia root extract as a food supplement by the European Food Safety Commission [EFSA] expressed concern that the herbal supplement induced evidence of DNA damage and concluded that its “safety has not been established under any condition of use”).
  • Bessone F, García-Cortés M, Medina-Caliz I, Hernandez N, Parana R, Mendizabal M, Schinoni MI, 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 tongkat ali was not mentioned).
  • Zakaria AZ, Washif JA, Lim BH, Nosaka K. Effects of Eurycoma longifolia Jack supplementation on eccentric leg press exercise-induced muscle damage in rugby players. Biol Sport. 2023;40:691-697. [PMC free article: PMC10286614] [PubMed: 37398958]
    (Among 18 young male Rugby players treated with Eurycoma longifolia [400 mg] or placebo daily for 7 days before performing repeated leg press exercises to failure, there were no differences between the two groups in peak force, strength, muscle soreness, and CPK elevations, and salivary testosterone levels did not change; no mention of adverse events or serum ALT or AST elevations).
  • Kaliounji A, Shadid G, Saba H, Ahlawat S. A rare case of tongkat ali-induced liver injury: a case report. Cureus. 2024;16:e56639. [PMC free article: PMC11032125] [PubMed: 38646387]
    (47 year old man developed abdominal pain and jaundice one week after starting a new herbal supplement containing tongkat ali [bilirubin 7.5 rising to 14.1 mg/dL, ALT 470 U/L, Alk P 192 U/L], resolving after stopping: Case 1).

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