Eurycoma Longifolia

Eurycoma Longifolia (Tongkat Ali)

1. Identity and Botanical Characterization

Accepted scientific name: Eurycoma longifolia Jack. Eurycoma longifolia Jack is a popular traditional herbal medicine, a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam, and also Cambodia, Myanmar, Laos, and Thailand. It is native to Indochina — including Cambodia, Laos, Malaysia, Myanmar, Thailand, and Vietnam — and to Indonesia, specifically the islands of Borneo and Sumatra, but has also been found in the Philippines.

The plant is a medium-sized slender shrub that can reach 10 m (33 ft) in height and is often unbranched. Tongkat ali is an evergreen slow-growing herbal plant that completely matures after 25 years and can be harvested only after 5 years of cultivation.

Common names by region: The plant is known as Tongkat Ali, Ali's Umbrella, or Malaysian ginseng in Malaysia; Pasak Bumi or Bedara Pahit in Indonesia; Ian-don in Thailand; Cay ba benh in Vietnam; and tho nan in Laotian. In English-language commerce it is also referred to as "longjack" and "long jack."

Plant part used: The root is the most valuable part, often used in traditional remedies and supplements. Among a range of medicinally active compounds isolated from various parts — roots, stem, bark, and leaves — of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies.

Common Commercial Preparations and Forms

• The root of Tongkat Ali is typically boiled and consumed as a decoction or incorporated into traditional herbal formulas.
• Today, Eurycoma longifolia preparations are commercially available and advertised to enhance athletic performance and muscle strength.
• These health effects led to the inclusion of E. longifolia in dietary supplements, particularly for bodybuilding purposes.
• The EFSA Panel on Nutrition, Novel Foods, and Food Allergens evaluated a standardized water extract prepared from the dried ground root chips of Tongkat Ali, proposed for use as a food supplement in amounts up to 200 mg/day.

2. Traditional and Historical Use

The root has been used in traditional medicine in Southeast Asia over centuries. E. longifolia is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia.

Different plant parts were assigned distinct therapeutic roles in traditional systems. Decoctions of E. longifolia leaves are used for washing itches, while its fruits are used in curing dysentery. Its bark is mostly used as a vermifuge, while the taproots are used to treat high blood pressure, and the root bark is used for the treatment of diarrhea and fever.

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.

Mostly, root extracts of E. longifolia are used as folk medicine for sexual dysfunction, aging, malaria, cancer, diabetes, anxiety, aches, constipation, exercise recovery, fever, increased energy, increased strength, leukemia, osteoporosis, stress, syphilis, and glandular swelling.

Eurycoma longifolia Jack is popularly used as a sexual tonic in traditional medicine for aphrodisiac activity and improvement of fertility and male libido.

The Malay common name "Tongkat Ali" literally means "Ali's walking stick," which refers to its aphrodisiac property.

For centuries, different parts of the plant have been used as a natural remedy to treat fever, hypertension, or sexual insufficiency.

3. Phytochemistry: Key Constituents and Active Compounds

E. longifolia Jack is reported to be rich in various classes of bioactive compounds such as quassinoids, canthin-6-one alkaloids, β-carboline alkaloids, triterpene tirucallane type, squalene derivatives and biphenyl neolignans, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids.

These effects are mediated by a myriad of bioactive compounds belonging to quassinoids, canthin-6-one alkaloids, tirucallane triterpenes, squalene derivatives, and bioactive steroids. Among these phytoconstituents, quassinoids account for a large portion of E. longifolia root phytochemicals.

Beside quassinoids (a group of nortriterpenoids), which account for a major portion of the E. longifolia root phytochemicals, the plant is also reported to contain canthin-6-one alkaloids, β-carboline alkaloids, coumarins, squalenes, triterpenes, and biphenylneolignans. More than 85 compounds have been reported from aqueous extracts of E. longifolia and characterized by liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Marker Compounds

• Eurycomanone: Eurycomanone (a quassinoid, CAS number 84633-29-4) was proposed as the major marker compound for the specification of standardized novel food applications. Eurycomanone was reported to be the dominant contributor of pharmacological properties, particularly anticancer, antimalarial, and anti-inflammation of E. longifolia.
• Glycosaponins: The characteristic components of a standardized novel food water extract are glycosaponins (40–65%) and eurycomanone (0.8–1.5%). It can also contain canthin-6-one alkaloids and isoscopoletin (coumarin).
• Eurypeptides: Previous studies have determined that Eurycoma longifolia contains a group of small peptides referred to as "eurypeptides" that are known to have effects in improving energy status and sex drive in studies of rodents.
• Additional quassinoid and lactone compounds identified from root extracts include: eurycomalide C, eurycomalactone, 5,6-dehydro-eurycomalactone, longilactone, 14,15β-dihydroklaieanone, 11-dehydroklaieanone, 9-hydroxycanthin-6-one, and 9-methoxycanthin-6-one.

Established Mechanisms of Action

Eurycoma longifolia is famously known for its aphrodisiac effect, which is due to its ability to stimulate the production or action of androgen hormones, especially testosterone.

Several studies have demonstrated a testosterone-boosting effect that might be caused by the release of free testosterone from the sex-hormone-binding globulin.

The prime mode of cytotoxicity of Eurycoma longifolia and its medicinal compounds is the induction of apoptosis (programmed cell death) via the up-regulation of the expression of p53 (tumor suppressor protein) and pro-apoptotic protein (Bax) and downregulation of the expression of anti-apoptotic protein (Bcl-2).

Eurycoma longifolia has been well documented to exert antioxidative properties due to its high concentrations of superoxide dismutase (SOD).

The significance of the biological activities is strongly dependent upon types of quassinoids and their derivatives with different functional groups, as well as the synergistic effects in the plant extracts or fractions.

4. Scientific Evidence by Area of Use

4.1 Testosterone and Male Androgen Status

This is the most extensively investigated clinical area. A systematic review and meta-analysis of randomized clinical trials (RCTs) was conducted according to PRISMA guidelines, with relevant articles retrieved from PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar. A total of nine studies were included in the systematic review, of which five RCTs were included in the meta-analysis. A significant improvement in total testosterone levels after E. longifolia treatment was mostly reported in both healthy volunteers and hypogonadal men.

The random model effect revealed a significant increase (SMD = 1.352, 95% CI 0.565 to 2.138, p = 0.001) in total testosterone levels in men receiving E. longifolia supplementation, which was confirmed in the hypogonadism subgroup.

One specific RCT frequently cited in the literature examined the Physta® formulation (a freeze-dried standardized aqueous root extract). A randomized, double-blind, placebo-controlled, parallel-group study was carried out to investigate the clinical evidence of E. longifolia in men. The 12-week study enrolled 109 men between 30 and 55 years of age, who received either 300 mg of water extract of E. longifolia (Physta) or placebo. Primary endpoints were Quality of Life (SF-36), Sexual Well-Being (IIEF and Sexual Health Questionnaires), Seminal Fluid Analysis, fat mass, and safety profiles.

A multicentre study with the same standardized extract further explored dosing. Cortisol levels significantly (p < 0.01) decreased in the Physta® 200 mg group, while muscle strength significantly (p < 0.001) increased in both Physta® groups at week 12 in the within-group comparison. There were no significant changes in SHBG. No safety-related clinically relevant changes were observed. Supplementation of Physta® at 200 mg was able to increase serum total testosterone, reduce fatigue, and improve quality of life in ageing men within 2 weeks.

A separate double-blind, placebo-controlled, crossover study in athletic subjects examined the effects of Physta® (a standardized water extract of E. longifolia) at 400 mg/day for 6 weeks on testosterone:epitestosterone (T:E) ratio, liver, and renal functions in male recreational athletes. A total of 13 healthy male recreational athletes were recruited in this double-blind, placebo-controlled, cross-over study.

Limitations: Many included trials are small, of short duration, and several were funded by or conducted in collaboration with commercial producers of proprietary extracts (notably Physta®/Biotropics Malaysia Berhad). The total number of participants across all RCTs in the meta-analysis remains modest, and further large independent trials are needed.

4.2 Erectile Function and Male Sexual Health

Eurycoma longifolia has been well recognized as a booster of male sexual health. Over the past few decades, numerous in vivo animal studies and human clinical trials have been conducted across the globe to explore the promising role of EL in managing various male sexual disorders, which include erectile dysfunction, male infertility, low libido, and downregulated testosterone levels.

The findings of human clinical studies revealed a promising efficacy of EL to treat erectile dysfunction in sexually sluggish males by improving penile erection, erectile hardness, and sexual performance. The clinical significance of EL in male infertility was also evidenced by significantly improving semen volume, concentration of sperms, proportion of sperms having normal morphology, sperm motility, sexual libido, and overall sexual satisfaction.

From the 12-week Physta® RCT (109 men): The EL group showed higher scores in the overall Erectile Function domain in IIEF (p < 0.001), sexual libido (14% by week 12), and seminal fluid analysis showed sperm motility at 44.4% and semen volume at 18.2% at the end of treatment.

In one systematic review, out of 150 articles screened, 11 met inclusion criteria. The majority of articles included were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All these studies demonstrated considerable effects of EL on male sexual health disorders.

Limitations: While E. longifolia is very promising as a natural therapeutic agent for altered sexual function, it is important to note that its effectiveness may vary between individuals and that further research is certainly needed to determine its long-term benefits and the optimal dose for therapy.

4.3 Stress, Mood, and Cortisol Modulation

Eurycoma longifolia is a medicinal plant commonly called tongkat ali and "Malaysian ginseng." TA roots are a traditional "anti-aging" remedy and modern supplements are intended to improve libido, energy, sports performance, and weight loss.

A key human study assessed stress hormones and mood: 63 subjects (32 men and 31 women) screened for moderate stress were supplemented with a standardized hot-water extract of TA root or placebo for 4 weeks. It has been demonstrated to reduce stress through the reduction of cortisol, with a concurrent increase in lymphocytes and natural killer cells.

A 24-week randomized study further evaluated the combination with multivitamins: This study investigated the safety and efficacy of Eurycoma longifolia in combination with multivitamins (EL+MV) versus placebo on improving quality of life (QoL), mood, and stress in moderately stressed healthy participants. This randomized, double-blind, placebo-controlled 24-week study enrolled 93 participants aged 25–65 years, supplemented with EL+MV or placebo. The primary endpoints were QoL measured by SF-12 questionnaire and mood measured by POMS. The secondary endpoint was stress measured by Multi-Modal Stress Questionnaire (MMSQ).

These findings are in agreement with several recent supplementation trials in humans, suggesting that tongkat ali may be an effective approach to shielding the body from the detrimental effects of chronic stress from daily stressors, dieting for weight loss, sleep deprivation, and intense exercise training.

The precise mechanism by which eurypeptides or tongkat ali root extract restores normal testosterone levels is unknown, but has been suggested as influencing the release rate of "free" testosterone from its binding hormone, sex-hormone-binding globulin.

Limitations: The combination-with-multivitamin design in some trials makes it difficult to isolate the contribution of E. longifolia alone. The stress-reduction effects appear more pronounced in populations with documented elevated baseline cortisol.

4.4 Athletic Performance and Muscle Strength

Eurycoma longifolia Jack has been shown to elevate serum testosterone and increase muscle strength in humans. Derivatives of this plant have been used to restore and enhance energy levels, to improve physical and mental performance, endurance and stamina, and quality of life, as evidenced by a decrease in aging males symptoms score and an increase in serum testosterone levels.

However, results are not uniformly positive. A study in elite rugby players found that 7-day ELJ supplementation prior to leg press eccentric exercise had no significant effects on hormones, performance, and muscle damage markers for the athletes. ELJ supplementation (400 mg daily for seven days) had no effects on muscle functions, hormones, and muscle damage markers among elite rugby players.

The null result in the rugby player study may be attributable to duration: a longitudinal study to observe ergogenic effects of ELJ supplementation is warranted.

Overall evidence strength for athletic performance: Preliminary and mixed. Positive findings tend to come from longer supplementation periods (weeks to months) in recreational athletes or middle-aged men, rather than in elite athletes over short durations.

4.5 Bone Health and Osteoporosis

Eurycoma longifolia has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Though numerous animal studies have explored the bone-forming capacity of EL, the exact mechanism was yet to be explored.

In vitro mechanistic studies have investigated both sides of the bone remodeling equation: E. longifolia exerts proandrogenic effects that enhance the testosterone level, as well as stimulate osteoblast proliferation and osteoclast apoptosis. This will maintain bone remodeling activity and reduce bone loss. Phytochemical components of E. longifolia may also prevent osteoporosis via its antioxidative property. Hence, E. longifolia has the potential as a complementary treatment for male osteoporosis.

A further in vitro mechanistic study found: The inhibitory effects of E. longifolia on the differentiation and functioning of osteoclasts are regulated through mechanisms involving down-regulation of RANKL-induced TRAP activity and expression of various bone-resorption related protein biomarkers including MMP-9, cathepsin-K, TRAP, and NFATc1.

Evidence strength for bone health: Preclinical only (in vitro and animal models). No published human clinical trials specifically investigating bone density outcomes in human subjects have been identified in the reviewed sources. This area requires human clinical investigation before efficacy conclusions can be drawn.

4.6 Antimalarial Activity

Eurycomanone and eurycomanol were likely to be compounds of quassinoids in promoting the other frequently reported activities such as antimalarial and anti-hyperglycaemic potentials. The plant parts have been traditionally used for their antimalarial, aphrodisiac, anti-diabetic, antimicrobial, and anti-pyretic activities, which have also been proved scientifically.

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.

Evidence strength for antimalarial use: Preclinical (in vitro and animal) only. There is a strong ethnobotanical and mechanistic rationale, but human clinical data is absent from the published literature reviewed.

4.7 Anticancer Activity

A plethora of in vitro and in vivo studies evidenced excellent antiproliferative and anticancer efficacy against various types of human cancers. Eurycomanone, one of the most active medicinal compounds of Eurycoma longifolia, displayed a strong dose-dependent anticancer efficacy against lung carcinoma (A-549 cells) and breast cancer (MCF-7 cells); however, showed moderate efficacy against gastric (MGC-803 cells) and intestinal carcinomas (HT-29 cells).

The major quassinoid from the plant is eurycomanone, which exhibits many prominent effects on various cancer cell lines. Numerous studies have shown that eurycomanone inhibits cancerous cell growth and encourages cell death both in vitro and in vivo. Even though analyses of safety and toxicity have been conducted, there is still a substantial knowledge barrier when it comes to providing a scientific foundation for the molecular mechanism as well as intervention strategy in living people.

Among a range of medicinally active compounds isolated from various parts of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Eurycoma longifolia and its medicinal constituents exhibit promising anticancer efficacy and thus can be considered as potential complementary therapy for the treatment of various types of human cancers.

Evidence strength for anticancer use: Preclinical only. All human cancer-related evidence is derived from in vitro and animal studies. No human clinical trials on cancer endpoints have been reported in the reviewed sources.

4.8 Anti-inflammatory and Analgesic Activity

E. longifolia is reported to have anti-inflammatory and immune-regulating properties, such as improving osteoporosis, diabetes, and metabolic complications, as well as having anti-malarial, anti-anxiolytic, cytotoxic, and anti-proliferative functions in malignancy.

A β-carboline alkaloid from Eurycoma longifolia, 7-methoxy-(9H-β-carbolin-1-il)-(E)-1-propenoic acid, exhibits anti-inflammatory effects by activating the Nrf2/heme oxygenase-1 pathway.

Evidence strength for anti-inflammatory use: Preliminary; primarily in vitro and animal evidence. Mechanistic pathways have been identified, but this has not translated to confirmed human clinical outcomes.

5. Body Systems and Health Areas Associated with E. longifolia

• Endocrine / Reproductive (male): Testosterone modulation, support for hypogonadism, erectile function, male fertility and sperm parameters
• Neuroendocrine / Stress-Adrenal: Cortisol reduction in moderately stressed subjects; mood improvement
• Musculoskeletal: Muscle strength; preclinical bone formation and anti-resorptive activity
• Immune: Increased lymphocytes and natural killer cell activity reported in one human study
• Oncology (preclinical): Antiproliferative and pro-apoptotic activity in multiple cancer cell lines
• Infectious Disease (preclinical): Antimalarial (quassinoid-mediated) and antimicrobial activity in vitro
• Metabolic / Endocrine (preclinical): Antidiabetic and anti-hyperglycemic activity in animal models

6. Dosage Forms and Doses Reported in Clinical Studies

The following doses are drawn exclusively from clinical research sources; they are not recommendations.

• The 12-week RCT in 109 men used 300 mg of water extract of E. longifolia (Physta) or placebo.
• Physta® standardized water extract at 400 mg/day for 6 weeks was investigated for testosterone:epitestosterone ratio, liver, and renal function in male recreational athletes.
• In a multicentre RCT in ageing men, Physta® at 200 mg/day significantly decreased cortisol levels and increased serum total testosterone within 2 weeks.
• The EFSA novel food application proposed the standardized water extract for use as a food supplement in amounts up to 200 mg/day.
• A study in elite rugby players used 400 mg daily for seven days.
• A 4-week stress study supplemented 63 subjects with a standardized hot-water extract of TA root or placebo.

Taken together, most human clinical trials have used standardized water (aqueous) root extracts in a range of 200–400 mg per day, for durations spanning 4 to 12 weeks. The Physta® branded extract is the most frequently studied formulation in published clinical trials.

7. Safety Considerations

7.1 Acute and Subchronic Toxicology

An acute toxicity study found that the oral Lethal Dose 50 (LD50) of the alcoholic extract of E. longifolia in mice is between 1500–2000 mg/kg, while the oral LD50 of the aqueous extract form is more than 3000 mg/kg.

The no observed adverse effect level (NOAEL) for E. longifolia in its aqueous extract form has been previously reported to be more than 3 g/kg in mice and more than 1 g/kg and 5 g/kg in rats in two separate studies, while the powdered form of the root was reported to have an acute limit dose of more than 6 g/kg.

Although these studies reported a high tolerance of the highest dose used, they also reported hydropic liver histology indicating hepatotoxicity and minor yet significant hematology and clinical biochemistry changes.

Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia.

7.2 Genotoxicity: The EFSA 2021 Opinion

The most significant regulatory safety signal comes from the European Food Safety Authority. The EFSA Panel noted positive results from the submitted in vitro chromosome aberration test, which indicates clastogenic properties of the novel food.

In the requested follow-up in vivo mammalian alkaline comet assay, the novel food induced positive results at the highest dose tested (2,000 mg/kg body weight) at the tissues of the first site of contact (stomach and duodenum). Histopathological evaluation of the tested tissues indicated that the positive results of the comet assay were rather due to genotoxicity than cytotoxicity. Taken together, the Panel concluded that the NF has the potential to induce DNA damage, which is of concern, particularly locally for tissues that represent first sites of contact. The Panel concluded that the safety of the novel food has not been established under any condition of use.

This 2021 EFSA opinion is a critical regulatory landmark: it represents an official European Union finding that the standardized water extract of E. longifolia (as submitted by the applicant) could not be approved as a novel food under EU regulations on the basis of genotoxicity signals, though this assessment applied specifically to the extract evaluated at the doses and conditions described in the application.

7.3 Heavy Metal Contamination

The contamination or adulteration of herbal medicinal products with heavy metals such as lead, arsenic, mercury, cadmium, and copper are always of great concern. Some of the E. longifolia herbal medicinal products sold in the market have been reported to contain some of these common heavy metals.

Among 100 herbal medicinal products analyzed, 8% of samples contained lead between 12.24–20.72 ppm, which does not comply with quality requirements for traditional medicine in Malaysia (not to exceed 5 ppm as stipulated by the Drug Control Agency). Further, none of these herbal medicinal products was registered with the Drug Control Agency.

The rigorous implementation of Good Agricultural and Collection Practices (GACP) and Good Manufacturing Practices (GMP) would undoubtedly reduce the risk of external issues. Through the use of modern analytical methods and pharmaceutical techniques, previously unsolved internal issues have become solvable.

7.4 Allergenic Potential

EFSA reported that within the same family Simaroubaceae, eventual allergenic potential is seen in two out of 19 plant genera only (Ailanthus and Alvaradoa), whereas no data are available on the genus Eurycoma and on the species E. longifolia. The Panel considers that the likelihood of allergenic reactions to the novel food is low.

7.5 Pregnancy, Lactation, and Special Populations

The standardized water extract novel food was proposed for use in amounts up to 200 mg/day. The target population is the adult population, except pregnant and lactating women. No human clinical safety data for pregnant or lactating women exists in the reviewed sources.

7.6 Drug Interactions and Doping Considerations

Several studies have demonstrated a testosterone-boosting effect that might be caused by the release of free testosterone from the sex-hormone-binding globulin. This mechanism has implications for interactions with sex hormone-based therapies.

In the context of anti-doping, a crossover study specifically investigated: the effects of Physta® (400 mg/day for 6 weeks) on testosterone:epitestosterone (T:E) ratio, liver, and renal functions in male recreational athletes, as the T:E ratio is a recognized marker used in sports doping control.

7.7 Product Adulteration and Misidentification

External issues including contamination (toxic metals, pesticide residues, and microbes), adulteration, and misidentification are documented quality concerns. Complexity and non-uniformity of the ingredients in herbal medicines are internal issues affecting the quality of herbal medicines.

Tongkat ali (Eurycoma longifolia), also known as long jack, is an herbal plant that grows in Malaysia and other parts of Southeast Asia. It has been used traditionally for centuries as an energy enhancer and aphrodisiac, and to reduce fevers, blood pressure, and fatigue. As an ingredient in dietary supplements, tongkat ali is often marketed to boost testosterone levels, reduce stress, improve mood, and enhance athletic and sexual performance. More evidence is needed to confirm any marketed benefits of tongkat ali.

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