Eurypeptides

Other Names

Akar Jangat SemangAkar Pasak BumiAntong SarAntoung SarBabi KurusBatang Pasak BumiBedara MerahBedara PutihBidara Lautbioactive complex polypeptidesbioactive glycoproteinCanne d'AliCây Bá BệnhEurycoma longifoliaEurycoma longifolia JackGinseng de Malaisieglycopeptide fraction of Eurycoma longifoliaHae Phan ChanHempedu PahitKayu DaliLan-donLangir SiamLempedu PahitLong JackLongjackMalaysian GinsengMuntah BumiPasak BumiPayong AliPayung AliPenawar BiasPenawar PahitPetala BumiPhiakPlaa Lai PhuenkSengkayapSetunjang BumiTho NanTongkat AliTongkat BagindaTongkat RasulTung SawTungke AliUmpudumaiduWonod Mondou

Synopsis

Eurypeptides: A Comprehensive Encyclopedic Reference

1. Identity and Natural Source

1.1 Terminology and Botanical Classification

Eurypeptides is the collective term for a class of bioactive glycopeptides isolated from the roots of Eurycoma longifolia Jack — the plant more commonly known as Tongkat Ali, Malaysian Ginseng, or Longjack. The term "eurypeptides" is derived from the genus name Eurycoma and is used specifically in the dietary supplement and research literature to describe the peptide fraction of the root extract considered responsible for several of the plant's hormonal and adaptogenic effects.

Eurycoma longifolia Jack (known as tongkat ali) is a popular traditional herbal medicine and a flowering plant of the family Simaroubaceae, native to Indonesia, Malaysia, Vietnam, and also Cambodia, Myanmar, Laos, and Thailand — where it is one of the well-known folk medicines for aphrodisiac effects as well as intermittent fever (malaria) in Asia.

The plant is a medium-sized slender shrub that can reach 10 m (33 ft) in height, and is often unbranched. It grows relatively slowly, sometimes requiring two decades or more to reach full maturity, and prefers the sandy soils of lowland forests.

1.2 Common Names by Region

The plant is known by many regional names: 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 Laos.

1.3 Chemical Identity of Eurypeptides

A patent discloses a process whereby Eurycoma longifolia roots undergo an aqueous extraction combined with HPLC and size-exclusion chromatography to yield a bioactive peptide fraction — a 4,300-dalton glycopeptide with 36 amino acids — that is responsible for its effects in maintaining testosterone levels.

A 36-amino acid, 4.3 kDa peptide was also found to be the active component of the Physta® extract responsible for modulating healthy testosterone levels. This 4.3 kDa peptide from E. longifolia was found to be responsible for its sexual-enhancing effects, and may also mediate other effects of E. longifolia.

Eurypeptides are therefore characterized as water-soluble glycoproteins — specifically, low-molecular-weight polypeptides that are part of a broader spectrum of phytochemicals present in the root. The Physta™ freeze-dried standardized extract of the root of Eurycoma longifolia contains numerous active compounds including phenolic components, tannins, high molecular weight polysaccharides, glycoproteins, and mucopolysaccharides — with eurypeptides representing the glycoprotein fraction specifically linked to androgenic and stress-hormonal activity.

1.4 Broader Phytochemical Context

Eurypeptides exist within a richly diverse phytochemical matrix. The plant 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, biphenyl neolignan, eurycolactone, laurycolactone, eurycomalactone, and bioactive steroids. Beside quassinoids (a group of nortriterpenoids), which account for a major portion of the E. longifolia root phytochemicals, the plant is reported to contain also 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). The eurypeptide fraction is distinguished from these small-molecule compounds by its protein/glycoprotein nature and is recovered specifically through aqueous (hot-water) extraction protocols.

1.5 Common Forms and Preparations

In the supplement market, eurypeptides are not typically sold as an isolated compound. Rather, they are present — along with other phytoconstituents — in standardized root extracts. Physta® is a freeze-dried proprietary water extract of the roots of E. longifolia, manufactured using a patented extraction technology developed by the Massachusetts Institute of Technology (MIT) and Malaysia's Ministry of Science, Technology and Innovation (MOSTI). Physta® contains 0.8–1.5% eurycomanone, >22% total protein, >30% total polysaccharide, and >40% glycosaponin.

All of the major human trials have used the same water-extracted and standardized eurycoma root for which a patent has been issued jointly to the Government of Malaysia and the Massachusetts Institute of Technology (United States Patent #7,132,117).

Products in the broader market take several forms. The herb can be consumed in various forms, including boiling the root to make tea, mixing it into other beverages as a powder, or soaking it in alcohol to create tinctures. Modern dietary supplement presentations include capsules, tablets, and sachet powders. Products stating various E. longifolia extract ratios of 1:50, 1:100, and 1:200 are common on the market; however, extracts based on this ratio system are often misleading and hard to verify.

2. Traditional and Historical Use

2.1 Geographic and Cultural Origins

Tongkat Ali (or Akar Ali) has been used as a traditional herbal medicine for centuries by the indigenous Orang Asli peoples of Malaysia. The traditional approach of drinking boiled freshly-cut roots is widely practiced and used as an aphrodisiac, antibiotic, appetite stimulant, and to promote general well-being.

The leaves, roots, and bark of Eurycoma longifolia have been used extensively in traditional medicine for many conditions including diabetes, arthritis, liver diseases, malaria, dysentery, and erectile dysfunction.

2.2 Parts Used and Preparations

Different parts of the plant were employed for different therapeutic purposes within folk traditions. 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.

2.3 Therapeutic Applications in Traditional Medicine

Mostly, the roots extract 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.

The roots are also used as an aphrodisiac, antibiotic, appetite stimulant, and health supplement. The species was reportedly so highly regarded that it became known locally as "the tree that cures a hundred diseases" due to the wide range of conditions it was believed to address.

2.4 Botanical Documentation

The original description of the Eurycoma longifolia species was published in the Malayan Miscellanies, Volume 2, in 1822. The original publication was reprinted in the book titled Description of Malayan Plants, I–III, Bencoolen 1820–1822, by Boerhaave Press, Leiden, in 1977.

2.5 Regulatory and Pharmacopeial Status

While E. longifolia is recognized in traditional medicine across Southeast Asia and regulated in markets like the EU, the official pharmacopeial status appears to be limited to three countries: Malaysia, Indonesia, and Vietnam. E. longifolia is not considered to be generally recognized as safe (GRAS) by the US Food and Drug Administration.

3. Key Constituents and Active Compounds

3.1 The Eurypeptide Fraction

Within the total phytochemical profile of Eurycoma longifolia, the eurypeptide fraction occupies a specific and intensively studied role. The root extract contains bioactive peptides called "eurypeptides" that play a crucial role in enhancing testosterone biosynthesis.

Animal studies have shown that many of the effects of the extract are mediated by its glycoprotein components. The identification of the specific eurypeptide fraction traces to academic and patent work. The currently touted mechanism of Eurycoma longifolia for increasing testosterone levels is traced to the eurypeptide content, which is claimed to increase the activity of the CYP17 enzyme in the testes. These claims are traced back to a university dissertation by Ali and Saad (1993) from the University of Malaya, which is not available online.

3.2 Quassinoids

Eurycomanone is the primary bioactive compound (a quassinoid) found in the root of Eurycoma longifolia. Eurycomanone (CAS number 84633-29-4) has been proposed as the major marker compound for the specification of standardized extracts.

The major compounds found in the roots belonging to quassinoids (degraded triterpenes) are among the compounds known to contribute to various medicinal effects based on in vitro or in vivo studies including anticancer properties. Other quassinoids identified include eurycomalactone, 13α(21)-epoxyeurycomanone, 13α,21-dihydroeurycomanone, and eurycomanol.

3.3 Canthin-6-one Alkaloids

9-Hydroxycanthin-6-one, isolated from Eurycoma longifolia, appears to be a candidate for the bioactive compound relevant to erectile function. In vitro, 9-hydroxycanthin-6-one was able to induce relaxation of epinephrine-contracted cavernosal strips with an EC50 of 6.7 ± 0.9 μM.

3.4 β-Carboline Alkaloids and Anti-inflammatory Compounds

The β-carboline alkaloid 7-MCPA (7-methoxy-(9H-β-carbolin-1-yl)-(E)-1-propenoic acid) isolated from E. longifolia hairy-root cultures activated Nrf2 via a ROS-dependent p38 MAPK pathway, and its anti-inflammatory effects were associated with activation of the Nrf2/HO-1 pathway. This study clarified the molecular mechanisms underlying the anti-inflammatory activities of β-carboline alkaloids of E. longifolia.

Eurycomalactone, 14,15β-dihydroklaieanone, and 13,21-dehydroeurycomanone were identified as potent NF-κB inhibitors with IC50 values of <1 μM.

3.5 Tirucallane Triterpenes and Steroids

Piscidinol A, 24-epi-piscidinol A, bourjotinolone A, and scopoletin were found to play an important role in suppressing nitric oxide levels without cytotoxicity. The Western blot method was used to investigate the mechanism of these compounds by analyzing the level of inflammation-related proteins, such as iNOS, IL-6, and NF-κB in LPS-stimulated RAW264.7 cells. Consequently, these compounds were found to significantly inhibit LPS-induced protein expression of IL-6, NF-κB, and iNOS in the NF-κB signaling pathway.

4. Mechanisms of Action

4.1 CYP17 Enzyme Activation (Steroidogenic Pathway)

The primary and most extensively cited mechanism attributed to eurypeptides is their activation of the steroidogenic enzyme CYP17. The mechanism of action of the bioactive complex polypeptides ("eurypeptides" with 36 amino acids) has been shown to activate the CYP17 enzyme (17 alpha-hydroxylase and 17,20-lyase) to enhance the metabolism of pregnenolone and progesterone to yield more DHEA (dehydroepiandrosterone) and androstenedione, respectively.

These compounds activate the CYP17 enzyme (17α-hydroxylase/17,20-lyase), which enhances the metabolism of pregnenolone and 17-OH-pregnenolone to yield more DHEA. This cascade continues as progesterone and 17-OH-progesterone are further metabolized to 4-androstenedione and ultimately to testosterone.

4.2 SHBG Modulation and Free Testosterone Liberation

Eurypeptides increase the release rate of free testosterone from its binding proteins, specifically sex hormone-binding globulin (SHBG). This mechanism is particularly significant because of the physiological constraints on testosterone bioavailability. In the human body, approximately 98% of testosterone is bound to proteins — primarily SHBG and albumin — rendering it biologically inactive. Only the remaining 2% is "free" and capable of binding to androgen receptors in muscle and nervous tissue.

This mechanism explains why some clinical trials observe improvements in libido, energy, and muscle power output even when total testosterone levels do not show massive, supraphysiological spikes.

4.3 Aromatase and Phosphodiesterase Inhibition

Eurycomanone, the major quassinoid in Tongkat Ali, has been shown to increase testosterone production through two primary mechanisms: aromatase inhibition — eurycomanone inhibits the aromatase enzyme that converts testosterone to estrogen, thereby preserving testosterone levels — and phosphodiesterase inhibition: at higher concentrations, eurycomanone may also inhibit phosphodiesterase, thereby increasing cyclic AMP levels in Leydig cells, stimulating testosterone production.

4.4 Anti-inflammatory Mechanisms

The mechanism of anti-inflammatory activity of certain E. longifolia constituents may be related to the inhibition of iNOS expressions through suppressing the IL-6-induced NF-κB pathway.

4.5 Eurypeptides and Glucose Metabolism

The effects of E. longifolia water extract (Physta®) and its 4.3 kDa peptide (EP) were evaluated on insulin secretion and glucose uptake in vitro. Cultured cells (3T3-L1, L6, BRIN-BD-11, and Caco-2 cells) were incubated with concentrations of the extract or peptide, and non-toxic doses were used to determine glucose uptake and insulin secretion. This represents an emerging mechanistic area and does not yet have confirmation in human trials.

4.6 Important Caveats on Mechanistic Claims

The currently touted mechanism of eurypeptides for increasing testosterone levels is traced to the eurypeptide content, which is claimed to increase the activity of the CYP17 enzyme in the testes. These claims are traced back to a 1993 university dissertation that is not available online. Accordingly, while the CYP17 mechanism is frequently cited in both academic reviews and supplement literature, independent experimental confirmation in peer-reviewed human studies remains limited.

5. Scientific Evidence by Area of Use

5.1 Testosterone Levels and Male Hypogonadism

The most extensively studied application of eurypeptide-containing extracts is support of testosterone levels in men. After literature screening, a total of nine studies was included in a systematic review. 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 the total testosterone levels in men receiving E. longifolia supplementation, which was confirmed in the hypogonadism subgroup.

Despite this positive meta-analytic result, the overall evidence base has limitations: the total number of included RCTs was small (five), the studies used varying extract types and dosages, and the clinical significance of the testosterone changes observed relative to established thresholds for hypogonadism treatment remains a subject of ongoing debate. Tongkat ali is known for its aphrodisiac and profertility effects. It is also promoted as a "testosterone booster," and while some evidence exists for this effect in men with low testosterone and the mechanisms are plausible, the data aren't convincing.

A notable placebo-controlled multicentre study examined the Physta® extract specifically. Physta® supplementation at 100 mg and 200 mg was able to improve total testosterone levels, reduce ageing symptoms, and reduce fatigue as early as 4 and 2 weeks of supplementation, respectively. DHEA levels significantly increased (P < 0.05) within-group in both Physta® groups from week 2 onwards. 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.

A further consideration regarding the nature of testosterone support is provided by research indicating that it can be suggested that E. longifolia supplementation does not indiscriminately increase testosterone levels as do exogenous testosterone supplementation, but modulates to optimal levels according to one's current hormonal levels.

Evidence strength: Moderate (several small-to-medium RCTs, one positive systematic review and meta-analysis, but methodological heterogeneity and small total sample sizes limit conclusions).

5.2 Sexual Health, Libido, and Erectile Function

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 in 109 men between 30 and 55 years of age consisted of either treatment of 300 mg of water extract of E. longifolia (Physta) or placebo. Primary endpoints were Quality of Life (SF-36 questionnaire), Sexual Well-Being (IIEF and SHQ), Seminal Fluid Analysis, fat mass, and safety profiles.

The E. longifolia group significantly improved in the domain Physical Functioning of SF-36 from baseline to week 12 compared to placebo (P = 0.006) and in between-group comparison at week 12 (P = 0.028). The EL group showed higher scores in the overall Erectile Function domain in IIEF (P < 0.001), sexual libido (14% by week 12), sperm motility at 44.4%, and semen volume at 18.2% at end of treatment.

A systematic review of clinical studies on EL and male sexual health found that out of 150 articles, 11 met the inclusion criteria, the majority of which were randomized placebo-controlled trials, multiple cohort studies, or pilot trials. All demonstrated considerable effects of EL on male sexual health disorders. Among them, 7 studies revealed a remarkable association between EL use and efficacy in the treatment of male sexual disorders, and the remaining 4 studies failed to demonstrate sufficient effects.

Regarding erectile function specifically, 9-hydroxycanthin-6-one does not appear to be mediated by nitric oxide or alpha-adrenoreceptors like yohimbine, but appears to inhibit Ca2+ release. In vivo testing in rabbits noted that direct injections of up to 0.2 mg of this compound increased intracavernosal pressure.

Evidence strength: Moderate for libido and self-reported sexual well-being; preliminary for erectile function specifically (requires more robust RCTs).

5.3 Male Fertility and Semen Parameters

One study investigated the effect of treatment with a proprietary standardized, water-soluble extract of the root of Eurycoma longifolia Jack on semen volumes, sperm concentrations, the percentage of normal sperm morphology, and sperm motility in male partners of sub-fertile couples with idiopathic infertility. A total of 350 patients were given 200 mg of the extract daily, and follow-up semen analyses were performed every 3 months for 9 months. Of these 350 patients, 75 patients completed one full cycle of 3 months. Follow-up semen analyses showed significant improvement in all semen parameters. The proprietary extract significantly improved sperm quality, allowing for 11 (14.7%) spontaneous pregnancies.

In the 12-week RCT in 109 men: sperm motility improved from a mean of 33.8% at baseline to 48.8% at end of treatment. Comparing these data to an earlier study (Bin and Imran), the effect was more prominent, leading to the assumption that the higher dose of 300 mg per day of E. longifolia root extract is more effective on semen parameters.

Animal data are also supportive: eurycomanone alone was detected in rat testis homogenates by HPLC-UV and confirmed by LC/MS, and may have contributed toward the improvement of sperm quality.

Evidence strength: Preliminary-to-moderate. Human data exist but the primary infertility study lacked a control arm; the RCT data on sperm motility are promising but from a single trial.

5.4 Stress Hormones and Mood

Stress hormones and mood state were assessed in 63 subjects (32 men and 31 women) screened for moderate stress and supplemented with a standardized hot-water extract of TA root or placebo for 4 weeks. Significant improvements were found in the TA group for Tension (−11%), Anger (−12%), and Confusion (−15%). Stress hormone profile (salivary cortisol and testosterone) was significantly improved by TA supplementation, with reduced cortisol exposure (−16%) and increased testosterone levels.

A longer-duration study also assessed this outcome: a randomised, double-blind, placebo-controlled 24-week study enrolled 93 participants aged 25–65 years with a BMI of 18–30 kg/m², scoring ≤18 in tension and ≤14 in fatigue subscale of the Profiles of Mood Scores (POMS) questionnaire, and supplemented with EL plus multivitamins or placebo.

The roots of EL are largely responsible for its biological activity due to the presence of alkaloids, quassinoids, quassinoid diterpenoids, eurycomacoside, eurycolactone, and peptides. It has been demonstrated to reduce stress through the reduction of cortisol with a concurrent increase in lymphocytes and natural killer cells.

Evidence strength: Preliminary. The main human stress study (Talbott et al.) is small (63 subjects), short (4 weeks), and used a multi-ingredient product in some formulations. Results are consistent and encouraging but not yet confirmed by large-scale RCTs.

5.5 Athletic Performance and Body Composition

Laboratory evidence shows that eurycoma peptides stimulate release of free testosterone from binding proteins and improve overall hormone profiles. More than a dozen rodent-feeding studies have demonstrated improved sex drive, balanced hormonal profiles, and enhanced physical function. Human supplementation trials show clear indications of reduced fatigue, heightened energy and mood, and a greater sense of wellbeing in subjects consuming properly-standardized tongkat ali root extracts.

However, not all human performance data are uniformly positive. Counter-movement jump peak power, height, and reactive strength index decreased at 24 h after eccentric exercise without significant differences between ELJ and placebo groups, and muscle soreness and plasma creatine kinase activity increased similarly in both groups. These results showed that 7-day ELJ supplementation prior to eccentric exercise had no significant effects on hormones, performance, and muscle damage markers for elite athletes.

A study in endurance athletes noted that Physta® supplementation at 400 mg/day was associated with significant reduction of muscle soreness and creatinine kinase up to 48 hours post-leg press exercise.

Evidence strength: Mixed and preliminary. Results across different athlete populations and study designs are inconsistent. Short supplementation periods (7 days) in elite athletes may be insufficient to capture effects.

5.6 Anticancer Properties (Preclinical Only)

Eurycoma longifolia has gained recognition due to its versatile pharmacological activities including anticancer, antimalarial, antimicrobial, antioxidant, aphrodisiac, anti-inflammatory, anxiolytic, anti-diabetic, antirheumatism, and anti-ulcer properties. A plethora of in vitro and in vivo studies have evidenced excellent antiproliferative and anticancer efficacy against various types of human cancers.

Eurycomanone and eurycomalactone exhibited in vitro anticancer effects with IC50 values of 4.58 ± 0.090 μM and 1.60 ± 0.12 μM (HeLa), 1.22 ± 0.11 μM and 2.21 ± 0.049 μM (HT-29), and 1.37 ± 0.13 μM and 2.46 ± 0.081 μM (A2780), respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners.

Out of 65 medicinally active compounds isolated from various parts of Eurycoma longifolia, 16 compounds have shown promising anti-proliferative and anticancer efficacies. Intraperitoneal administration of TAF273 (an E. longifolia fraction, 50 mg/kg) resulted in significant growth inhibition of subcutaneous tumor in animal models.

Evidence strength: Preclinical only (in vitro and animal models). No human clinical trials on cancer have been conducted. These findings do not constitute evidence for therapeutic use in humans.

5.7 Antimalarial Activity (Preclinical)

The roots of E. longifolia have been reported to have various medicinal properties including antibacterial, cytotoxic/anticancer, antimalarial, antiulcer, antiparasitic, and antipyretic activity. Antimalarial applications were among the most important traditional uses, and phytochemical research has identified quassinoids as likely contributors to this activity. However, as with anticancer research, no human clinical trials have been conducted specifically for malaria treatment using standardized eurypeptide extracts.

Evidence strength: Traditional use corroborated by preclinical data; no human trial evidence.

6. Body Systems and Health Areas

Endocrine system: Steroidogenic support via CYP17 activation; modulation of testosterone and DHEA biosynthesis; reduction of cortisol.
Male reproductive system: Aphrodisiac and libido effects; improvements in sperm motility, concentration, and morphology; erectile function support.
Musculoskeletal system: Proposed support for muscle strength (via testosterone modulation); some evidence for post-exercise recovery.
Immune and stress response: Cortisol reduction; increase in natural killer cells and lymphocytes observed in some studies.
Inflammatory pathways: NF-κB inhibition by quassinoids; iNOS suppression; Nrf2/HO-1 pathway activation by β-carboline alkaloids.
Oncological (preclinical only): Apoptotic activity against several cancer cell lines via p53-mediated and TNF-α/DHFR inhibitory pathways.
Metabolic/glycemic (preclinical/in vitro only): Potential for enhanced glucose uptake and insulin secretion observed in cell culture studies.
Antiparasitic/antimalarial (preclinical): Quassinoids exhibit antiplasmodial activity in preclinical models, consistent with traditional use.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are reported directly from the cited research literature and do not represent clinical recommendations.

A study in 64 subjects (32 men and 32 women) used 200 mg/day of Physta™ or placebo for 4 weeks.
A 12-week RCT in 109 men between 30 and 55 years of age used 300 mg of water extract of E. longifolia (Physta) or placebo.
A study in men with idiopathic infertility administered 200 mg of the extract daily with follow-up semen analyses every 3 months for 9 months.
Physta® supplementation at 100 mg and 200 mg improved total testosterone levels and reduced ageing symptoms and fatigue.
One endurance exercise study used Physta® supplementation at 400 mg/day.

Physta® contains 0.8–1.5% eurycomanone, >22% total protein, >30% total polysaccharide, and >40% glycosaponin. Standardization to eurycomanone content is used as the primary chemical marker for extract quality in several formulations.

8. Safety Considerations and Interactions

8.1 General Acute Toxicology

Oral toxicity studies (Wistar rats) have determined the LD50 of tongkat ali root extract as 2,000 mg/kg body weight (acute) and the NOAEL (no observed adverse effect level) as greater than 1,000 mg/kg body weight (28-day sub-acute feeding), resulting in a classification as Category 5 (extremely safe) according to the United Nations Globally Harmonized System of Classification.

Safety information for the aqueous extract form has been previously reported with a NOAEL of more than 3 g/kg in mice and more than 1 g/kg and 5 g/kg in rats in two separate studies.

8.2 Hepatotoxicity Signals

Tongkat ali has recently become a popular herbal supplement in the United States, as extracts of its roots have been promoted as increasing testosterone levels and improving athletic performance. Reports of clinically apparent liver injury attributed to tongkat ali in bodybuilders have recently appeared.

These reports have largely been in young male bodybuilders, 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). Tongkat ali has multiple constituents and the chemical compounds that are possibly responsible for liver injury are not known.

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.

8.3 EFSA Novel Food Assessment and Genotoxicity Concern

A significant regulatory safety signal arose in the European Union context. In a requested follow-up in vivo mammalian alkaline comet assay, the novel food extract 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. The Panel concluded that the novel food extract has the potential to induce DNA damage, 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.

8.4 Heavy Metal Contamination

Contamination or adulteration of herbal medicinal products with heavy metals such as lead, arsenic, mercury, cadmium, and copper are always of great concern. Some E. longifolia herbal medicinal products sold in the market have been reported to contain some of these common heavy metals. A 2004 quality assessment study determined that a substantial proportion of commercially available products contained mercury beyond legally permitted limits, as noted in the Wikipedia article on Eurycoma longifolia.

8.5 Common Adverse Effects Reported

Side effects of using supplements may include nausea, abdominal discomfort, diarrhea, or headaches. Rare cases of liver injury have occurred from its use, mostly in bodybuilders.

8.6 Drug Interactions

Eurycoma longifolia may decrease the serum concentration of propranolol, according to a 2010 study. Extracts of E. longifolia should not be used in prostate cancer due to observed increased levels of testosterone in rodent studies.

8.7 Pregnancy

E. longifolia supplements should not be used during pregnancy.

8.8 Long-Term Safety Data Gap

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. Information for TA extract long-term consumption is limited and its use as a herbal additive in food products warrants further investigation.

8.9 Regulatory Status (USA)

E. longifolia is not considered to be generally recognized as safe (GRAS) by the US Food and Drug Administration. It is, however, sold as a dietary supplement in the United States under the Dietary Supplement Health and Education Act (DSHEA) framework.

References

Health Conditions

Health conditions that Eurypeptides may help support.

Andropause (Male Hormonal Aging)Scientific
Eurypeptides are bioactive peptide fractions from Eurycoma longifolia (Tongkat Ali) root that directly enhance testosterone biosynthesis in Leydig cells by stimulating CYP450c17 and 17β-HSD enzyme activities. They are cited in RCT publications as a key mechanism by which Tongkat Ali extracts increase testosterone in men with androgen deficiency of aging males (ADAM).
Libido & Sexual Vitality (Men's)Scientific
Eurypeptides are low-molecular-weight peptides isolated from Eurycoma longifolia (Tongkat Ali) root that stimulate release of free testosterone by displacing it from sex hormone-binding globulin (SHBG). They are a key bioactive fraction alongside eurycomanone for testosterone support and male sexual vitality.

Body Systems

Body systems that Eurypeptides may help support.

No body systems available.