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Eurycoma Longifolia

Scientific Name(s): Eurycoma longifolia Jack
Common Name(s): Cay Ba Binh, Eurycoma, Malaysian ginseng, Pasak bumi, Tongkat Ali

Clinical Overview

Use

Animal and in vitro trials have evaluated E. longifolia for its antimalarial, anxiolytic, and antihyperglycemic activity; however, clinical evidence is lacking to support these uses. Limited clinical trial data suggest potential benefit for erectile dysfunction, but trials were of poor quality.

Dosing

Dosing recommendations are largely based on historical practice or manufacturer recommendations, as clinical studies are lacking.

Doses ranging from 100 to 800 mg daily have been reported.

Contraindications

Contraindications have not been clearly defined. Extracts of E. longifolia should not be used in patients with prostate cancer.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Limited information is available.

Toxicology

No data.

Botany

The Simaroubaceae family consists of 30 genera and 200 species. E. longifolia is a tall, slender, shrubby tree that grows in sandy soil. The plant is indigenous to Southeast Asia countries, including Myanmar, Thailand, Laos, Cambodia, and Malaysia.1, 2, 3

History

A decoction of the roots, root bark, or bark of E. longifolia has been consumed orally to treat many conditions, including diarrhea, fever, glandular swelling, bleeding, edema, persistent cough, hypertension, bone pain, and tertian malaria. The bark has also been used topically to treat wounds, ulcers, syphilitic sores, and headache. The plant has traditionally been used as an aphrodisiac, with recent increases in demand for E. longifolia products due to its aphrodisiac properties.1, 2, 3

Chemistry

Numerous reviews and studies of the phytochemical components of E. longifolia have been conducted.1, 2, 3 The plant's pharmacological activity is attributed to various quassinoids and quassinoid diterpenoids, squalene derivatives, biphenylneolignans, tirucallane-type triterpenes, canthine-6-1, and beta-carboline alkaloids.4, 5 Other identified constituents include eurycomaoside,eurycolactone, laurycolactone, and eurycomalactone.

Quassinoids, including eurycomanol, eurycomanol-2-O-beta-D-glycopyranoside, 13beta,18-dihydroeurycomanol, 14,15p-dihydroxyklaineanone, and 6-alpha-hydroxyeurycomalactone, have been isolated from the roots. Pasakbumins A-D (also known as eurycomanones) have also been isolated.4, 6, 7, 8, 9

Squalene derivatives include eurylene, 14-deacetyl eurylene, longilene peroxide, and teurilene.10, 11

Biphenylneolignans include the following: 2 isomeric 2,2-dimethoxy-4-(3-hydroxy-1-propenyl)-4-(1,2,3-trihydroxypropyl) diphenyl ethers and 2 biphenyls, 2-hydroxy-3,2,6-trimethoxy-4-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)-biphenyl, and 2-hydroxy-3,2-dimethoxy-4-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)-biphenyl.12

Alkaloids include 9,10-dimethoxycanthin-6-one, 10-hydroxy-9-methoxycanthin-6-one, 11-hydroxy-10-methoxycanthin-6-one, 5,9-dimethoxycanthin-6-one, and 9-methoxy-3-methylcanthin-5,6-dione.13, 14

Uses and Pharmacology

Antihyperglycemic activity

Animal data

Blood glucose levels decreased in streptozotocin-induced hyperglycemic adult rats after treatment with aqueous extracts of E. longifolia 150 mg/kg body weight. Blood glucose levels decreased 38% (P<0.05) and 47% (P<0.001) with 2 different extracts.15

Antimalarial activity

Animal and in vitro data

In one study, eurycomalactone, at a concentration of 2.5 mg/kg, exhibited antimalarial activity and prolonged survival time in mice infected with Plasmodium berghei. However, this concentration also caused early death in some of the infected mice. Additional experiments using a 34% alcoholic extract, water extract, n-hexane fraction, chloroform fraction, and 95% ethanolic fraction were also toxic to the test animals.16 In vitro, antimalarial activity against P. berghei was observed at an inhibitory concentration of 4.5 × 107 g/mL.1, 2, 3, 16

Antiulcer activity

In vitro data

In a bioassay study, 2 quassinoids, pasakbumin A (also known as eurycomanone) and pasakbumin B, exhibited antiulcer activity.9

Anxiolytic activity

Animal data

The anti-anxiety effects of various fractions of E. longifolia were investigated in mice using various behavioral tests, including the open-field (emotional state), elevated plus-maze (anxiolytic and anxiogenic drug effects), and fighting tests. The plant's anxiolytic effect was similar to the diazepam positive control.17, 18

Clinical data

A study in adults (N=63) with moderate stress reported improvements in stress hormone profiles and some mood indices with administration of an E. longifolia hot water extract over 4 weeks.2

Epstein-Barr virus

In vitro data

The quassinoid 14,15beta-dihydroxyklaineanone inhibited tumor promoter–induced Epstein-Barr virus activation at an in vitro 50% inhibitory concentration (IC50) of 5 mcM.19

Immunomodulatory effects

Clinical data

In a clinical study of middle-aged Japanese subjects (N=84), an immunomodulating effect was reported (ie, increased total T cells, CD4+ T cells, and naive T cell numbers) following administration of an E. longifolia 200 mg preparation taken daily for 4 weeks.20

Testosterone deficiency/Androgen-deficient osteoporosis

Reviews have reported improvements in androgen-related osteoporosis and ergogenic/muscle mass with E. longifolia, possibly related to increased testosterone levels and antioxidant effects associated with its use.2, 3, 21

In vitro data

In osteoblast cell lines, treatment with E. longifolia aqueous root extracts demonstrated greater cell proliferation and calcium deposition than testosterone-treated cells.22

Testosterone deficiency/Sexual performance

Animal data

In a study evaluating the effects of E. longifolia extract on the initiation of sexual performance in rats, doses of 200, 400, and 800 mg/kg body weight were administered orally twice daily for 10 days and continued throughout the 1-month testing period. Testosterone 15 mg/kg was used as a positive control. E. longifolia promoted the growth of both ventral prostate and seminal vesicles compared with control, but was associated with lower sexual performance than the testosterone-treated group.23 Other studies have demonstrated similar results.24, 25

Clinical data

A systematic review of randomized controlled trials (published through October 2014) investigating the use of E. longifolia extract (tongkat ali) compared with placebo for improvement in erectile dysfunction identified 2 trials (N=139) that met inclusion criteria. One trial used a combination product of E. longifolia 200 mg plus Polygonium minus 100 mg, whereas the second trial used E. longifolia as a single constituent at 300 mg/day (two 75 mg capsules twice daily); both were 12-week trials. The trials were prone to a high risk of bias, did not specify that a diagnosis of erectile dysfunction was needed, and had differences in baseline erectile dysfunction index scores. At week 12, pooled weighted mean difference in change of erectile function index score was 0.91 (95% confidence interval [CI], –1.5 to 3.33; P=0.002), with high heterogeneity (I2=89.5%); subgroup analysis revealed the improvement was specific to subjects with a lower baseline index score (ie, at or below 15.77 in the study using the combination product) and did not apply to those with a higher baseline index score (ie, 21.3 or above in the E. longifolia monotherapy study). No significant differences were observed between treatment and placebo groups.21, 26, 27

Dosing

Dosing recommendations are largely based on historical practice or manufacturer recommendations, as clinical studies are lacking.

Doses ranging from 100 to 800 mg daily have been reported.3

Male infertility

200 mg of a water-soluble extract of E. longifolia root taken twice daily for up to 3 months has been suggested.2

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Antiestrogenic effects have been demonstrated in rodents.2

Interactions

Case reports are lacking; however, in a study of healthy volunteers, the bioavailability of a single dose of propranolol was decreased when coadministered with an E. longifolia aqueous extract.28

Adverse Reactions

Limited information is available. Extracts of E. longifolia should not be used in prostate cancer due to observed increased levels of testosterone in rodent studies.2

Data collected from the Drug-Induced Liver Injury Network between 2004 and 2013 among 8 US centers revealed 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements. Of the 217 supplement products implicated in liver injury, E. longifolia was among the 22% (116) labeled as single-ingredient products.29

Toxicology

Limited clinical information is available regarding toxicity of E. longifolia. E. longifolia is not considered to be generally recognized as safe (GRAS) by the US Food and Drug Administration.3

In one study, the median lethal dose for an oral E. longifolia alcoholic extract in mice was determined to be 2.6 g/kg; symptoms of acute toxicity included depression, shallow respiration, and convulsion. In this study, 95% of mice died at a dose of 0.43 g/kg, and increased weight of the liver, kidneys, spleen, and testes was observed.16

One product, M-Tongkat Ali, harvested and prepared in Malaysia, was found to have higher than normal traces of lead (10.64 ± 0.37 ppm).30

References

1. Bhat R, Karim AA. Tongkat Ali (Eurycoma longifolia Jack): a review on its ethnobotany and pharmacological importance. Fitoterapia. 2010;81(7):669-679.20434529
2. 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(3):331.26978330
3. 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(1):54-83.23419023
4. Chan KL, Iitaka Y, Noguchi H, Sugiyama H, Saito I, Sankawa U. 6 alpha-Hydroxyeurycomalactone, a quassinoid from Eurycoma longifolia. Phytochemistry. 1992;3:4295-4298.
5. Le-Van-Thoi, Nguyen-Ngoc-Suong. Constituents of Eurycoma longifolia Jack. J Org Chem. 1970;35(4):1104-1109.5436496
6. Chan KL, Lee SP, Sam TW, Han BH. A quassinoid glycoside from the roots of Eurycoma longifolia. Phytochemistry. 1989;28:2857-2859.
7. Chan KL, Lee SP, Sam TW, Tan SC, Noguchi H, Sankawa U. 13 beta, 18-dihydroeurycomanol, a quassinoid from Eurycoma longifolia. Phytochemistry. 1991;30:3138-3141.
8. Darise M, Kohda H, Mizutani K, Tanaka O. Eurycomanone and eurycomanol, quassinoids from the roots of Eurycoma longifolia. Phytochemistry. 1982;21:2091-2093.
9. Tada H, Yasuda F, Otani K, Doteuchi M, Ishihara Y, Shiro M. New antiulcer quassinoids from Eurycoma longifolia. Eur J Med Chem. 1991;26:345-349.
10. Itokawa H, Kishi E, Morita H, Takeya K, Iitaka Y. Eurylene, a new squalene-type triterpene from Eurycoma longifolia. Tetrahedron Lett. 1991;15:1803-1804.
11. Morita H, Kishi E, Takeya K, Itokawa H, Iitaka Y. Squalene derivatives from Eurycoma longifolia. Phytochemistry. 1993;34:765-771.
12. Morita H, Kishi E, Takeya K, Itokawa H. Biphenylneolignans from wood of Eurycoma longifolia. Phytochemistry. 1992;31:3993-3995.
13. Mitsunaga K, Koike K, Tanaka T, et al. Canthin-6-one alkaloids from Eurycoma longifolia. Phytochemistry. 1994;35:799-802.
14. Choo CY, Chan KL. High performance liquid chromatography analysis of canthinone alkaloids from Eurycoma longifolia. Planta Med. 2002;68(4):382-384.11988873
15. Husen R, Pihie AH, Nallappan M. Screening for antihyperglycaemic activity in several local herbs of Malaysia. J Ethnopharmacol. 2004;95(2-3):205-208.15507337
16. Satayavivad J, Soonthornehareonnon N, Somanabandhu A, Thebtaranonth Y. Toxicological and antimalerial activity of eurycomalactone and Eurycoma longifolia Jack extracts in mice. Thai J Phytopharmacy. 1998;5:14-27.
17. Ang HH, Cheang HS. Studies on the anxiolytic activity of Eurycoma longifolia Jack roots in mice. Jpn J Pharmacol. 1999;79(4):497-500.10361892
18. Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, Part 1: a review of preclinical studies. CNS Drugs. 2013;27(3):207-219.23436255
19. Jiwajinda S, Santisopasri V, Murakami A, et al. In vitro anti-tumor promoting and anti-parasitic activities of the quassinoids from Eurycoma longifolia, a medicinal plant in Southeast Asia. J Ethnopharmacol. 2002;82:55-58.
20. George A, Suzuki N, Abas AB, et al. Immunomodulation in middle-aged humans via the ingestion of Physta® standardized root water extract of Eurycoma longifolia Jack--a randomized, double-blind, placebo-controlled, parallel study. Phytother Res. 2016;30(4):627-635.26816234
21. George A, Henkel R. Phytoandrogenic properties of Eurycoma longifolia as natural alternative to testosterone replacement therapy. Andrologia. 2014;46(7):708-721.24386995
22. Thu HE, Mohamed IN, Hussain A, Shuid AN. Eurycoma longifolia as a potential alternative to testosterone for the treatment of osteoporosis: exploring time-mannered proliferative, differentiative and morphogenic modulation in osteoblasts. J Ethnopharmacol. 2017;195:143-158.27818256
23. Ang HH, Cheang HS, Yusof AP. Effects of Eurycoma longifolia Jack (Tongkat Ali) on the initiation of sexual performance of inexperienced castrated male rats. Exp Anim. 2000;49(1):35-38.10803359
24. Ang HH, Cheang HS. Effects of Eurycoma longifolia jack on laevator ani muscle in both uncastrated and testosterone-stimulated castrated intact male rats. Arch Pharm Res. 2001;24(5):437-440.11693547
25. Ang HH, Ngai TH, Tan TH. Effects of Eurycoma longifolia Jack on sexual qualities in middle aged male rats. Phytomedicine. 2003;10(6-7):590-593.13678248
26. Kotirum S, Ismail SB, Chaiyakunapruk N. Efficacy of Tongkat Ali (Eurycoma longifolia) on erectile function improvement: systematic review and meta-analysis of randomized controlled trials. Complement Ther Med. 2015;23(5):693-698.26365449
27. Malviya N, Jain S, Gupta VB, Vyas S. Recent studies on aphrodisiac herbs for the management of male sexual dysfunction--a review. Acta Pol Pharm. 2011;68(1):3-8.21485695
28. Salman SA, Amrah S, Wahab MS, et al. Modification of propranolol's bioavailability by Eurycoma longifolia water-based extract. J Clin Pharm Ther. 2010;35(6):691-696.
29. Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. Drug-Induced Liver Injury Network. Hepatology. 2014;60(4):1399-1408.25043597
30. Ang HH, Lee EL, Matsumoto K. Analysis of lead content in herbal preparations in Malaysia. Hum Exp Toxicol. 2003;22(8):445-451.12948085

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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