TAXONOMY

Kingdom: Plantae (Plants)

Phylum: Tracheophyta

Clade: Angiosperms (Flowering plants), Eudicots (True dicots), Rosids

Order: Sapindales

Family: Simaroubaceae (Quassia family)

Genus: Eurycoma

Species: Eurycoma longifolia

Alchemical Signature

Primary: MARS

Secondary: Sun

Traditional use and prep

“Tonic” anti aging and aphrodisiac

When used in modern dietary supplements, tongkat ali is intended to improve libido and energy, improve stress resilience, restore hormonal balance (cortisol/testosterone levels), and enhance both sports performance and weight loss.

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. 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 plant parts have been traditionally used for its antimalarial, aphrodisiac, anti-diabetic, antimicrobial and anti-pyretic activities, which have also been proved scientifically.

SCIENTIFIC LITERATURE

Principle Specialized Metabolite

The plant parts are rich in various bioactive compounds (like eurycomaoside, eurycolactone, eurycomalactone, eurycomanone, and pasakbumin-B) among which the alkaloids and quassinoids form a major portion.

Eurycomanone

A Quassinoid (actually a degraded triterpenoid) that is taxonomically restricted to the Simaroubaceae family. Which contain over 200 known quassinoids. Eurycomanone is distributed throughout the plant, with the highest concentration in leaves. Researchers measured 6.0568 μg/mL in leaves, and only 0.3533 μg/mL in roots. A highly bioactuve compound. Note ether linkage /epoxide bridge and lactone structure contribute to its diverse bioactivity.

https://pubmed.ncbi.nlm.nih.gov/23810842/

Quassin  is the mother of quassinoids,  its skeleton possesses 20 carbon atoms, quassin despite containing 20 carbon atoms is not a diterpene but rather a triterpene lactone, which derives from euphol by loss of 10 carbon atoms including c4. it is One of the most bitter substances in nature 50x more bitter than quinine (bitter threshold of 0.08ppm). Medicinal properties possessing antimalarial,[15][22]antifeedant,[23] insecticidal,[24] anti-inflammatory,[25] and anticancer (or anti-leukemic)[11][26][27] properties. The quassinoid bruceantin reached two separate phase II clinical trials in 1982[28] and 1983.[29]

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Pharmacology

CHIEFLY AFFECTING THE improved rat spermatogenesis by affecting the hypothalamic-pituitary-gonadal axis. ONLY PHARMACOLOGICAL STUDIES HAVE BEEN DONE IN RATS. TO DATE THERE ARE NO HUMAN CLINICAL TRIALS.

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The follwoing information was summarized from the linked study above, Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology.

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Key Pharmacological Actions

1. Regulation of the HPG Axis:
   • Hypothalamus: Stimulates the hypothalamus to increase secretion of Gonadotropin-Releasing Hormone (GnRH), which promotes downstream hormonal activity.
   • Pituitary Gland: Enhances the release of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH), which are critical for testicular function.
   • Testes: Directly supports testosterone production in Leydig cells and spermatogenesis in Sertoli cells.
2. Inhibition of Aromatase Activity:
   • Eurycomanone inhibits the aromatase enzyme, reducing the conversion of testosterone into estrogen, thereby maintaining higher circulating testosterone levels. This mechanism is critical for addressing testosterone-deficient infertility and age-related declines in testosterone.
3. Enhanced Steroidogenesis:
   • E. longifolia promotes steroidogenesis in Leydig cells, demonstrated by dose-dependent increases in testosterone production at concentrations as low as 0.1 μM.
   • Likely mechanisms include upregulation of StAR protein (Steroidogenic Acute Regulatory Protein), facilitating cholesterol transport into mitochondria—the rate-limiting step in testosterone synthesis.
4. Reduction of Stress-Induced Hormonal Dysregulation:
   • By modulating cortisol levels, E. longifolia indirectly supports the HPA (Hypothalamic-Pituitary-Adrenal) axis, preventing cortisol-induced suppression of testosterone synthesis. This stress-adaptive effect aligns with its traditional use as an adaptogen.
5. Proandrogenic Effects:
   • Enhances the testosterone-to-epitestosterone (T/E) ratio, a marker of anabolic activity, as observed in human and animal studies. This action improves not only reproductive parameters but also muscle strength and vitality.

Quassinoid Effects on Fertility

The quassinoids in E. longifolia, including eurycomanone, contribute to its biological activity by targeting:

• Testicular Leydig Cells: Stimulation of testosterone synthesis.
• α-2-HS Glycoprotein Suppression: Reduces glycoprotein that negatively regulates testosterone and insulin sensitivity, thus improving endocrine balance.
• Phosphodiesterase Inhibition: At higher concentrations, this may enhance cyclic AMP (cAMP) pathways, further supporting testosterone biosynthesis.

Animal Studies Highlighting HPG Modulation

• Rat Studies: Oral administration of E. longifolia extracts significantly increased sperm count and motility by enhancing hypothalamic stimulation of the gonadotropic axis and supporting Sertoli cell function.
• Hormonal Effects: Rats treated with eurycomanone demonstrated increased LH, FSH, and testosterone levels, validating the herb’s role in activating the HPG axis.

Human Studies on Testosterone Regulation

1. Clinical Trials:
   • Randomized trials (300–400 mg/day) showed significant increases in testosterone levels and improvements in fertility markers (e.g., sperm motility, semen volume).
2. Aging Male Symptoms (AMS):
   • In men with late-onset hypogonadism, E. longifolia improved testosterone levels and reduced symptoms such as fatigue and low libido, demonstrating its efficacy in HPG axis rejuvenation.

Interaction with the HPA Axis

• While primarily targeting the HPG axis, E. longifolia also supports the HPA axis by:
  • Reducing cortisol levels, which can otherwise suppress GnRH and downstream testosterone production.
  • Enhancing stress resilience, further improving hormonal balance and fertility outcomes.

Conclusion

The pharmacological effects of Eurycoma longifolia on male fertility are rooted in its ability to modulate the HPG axis, enhance steroidogenesis, and reduce aromatase activity, thereby increasing testosterone levels. Additionally, its adaptogenic impact on the HPA axis helps mitigate stress-related suppression of reproductive hormones, making it a multifaceted therapeutic option for testosterone-deficient infertility and hypogonadism.

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Summary: Male Fertility Enhancement Effects of Eurycoma longifolia (Tongkat Ali)

Overview

Eurycoma longifolia (Tongkat Ali) is a plant with potential applications for addressing male infertility, characterized by low sperm count, reduced motility, or hormonal imbalances. Several studies demonstrate its efficacy in improving male reproductive health by enhancing testosterone levels, sperm parameters, and sexual function.

Key Findings

1. Improved Testosterone Production:
   • Eurycomanone, a major compound in E. longifolia, increases testosterone production by inhibiting aromatase (which converts testosterone to estrogen) and possibly through phosphodiesterase inhibition. Dose-dependent effects have been observed in both animals and humans.
2. Enhanced Sperm Parameters:
   • Studies in rats and humans show increased sperm count, motility, and viability after treatment with E. longifolia extracts.
   • Human trials revealed improvements in semen volume (+18.2%), motility (+44.4%), and morphology.
3. Hypothalamic-Pituitary-Gonadal Axis Modulation:
   • Animal studies indicate that E. longifolia positively affects the hypothalamic-pituitary-gonadal axis, boosting spermatogenesis and overall fertility.
4. Aphrodisiac and Sexual Function Benefits:
   • In both animal and human trials, supplementation with E. longifolia extracts improved erectile function, libido, and sexual performance.
   • Clinical trials reported significant improvement in erection quality, libido, and sexual health inventory scores in middle-aged and elderly men.
5. Safety and Tolerability:
   • Randomized, double-blind, placebo-controlled trials confirm that E. longifolia is safe for prolonged use at standard doses, with no adverse effects on liver or kidney function.
   • It has potential as a natural alternative to testosterone replacement therapy (TRT), avoiding TRT's side effects like prostate cancer risk.

Specific Studies

• Human Trials:
  • A 12-week trial with 300 mg/day water extract showed significant improvements in erectile function, libido, and semen quality.
  • A 9-month study in 350 infertile men (200 mg/day) improved semen parameters and resulted in spontaneous pregnancies in 14.7% of participants.
• Animal Studies:
  • Rats treated with E. longifolia showed increased testosterone (+30.2%), sperm motility, and enhanced sexual behaviors.
  • Repeated dosing enhanced copulatory activity and reduced ejaculation latency in sexually sluggish rats.
• Elderly Populations:
  • In aged participants (57–72 years), 400 mg/day for 5 weeks increased testosterone levels, improved muscle strength, and overall well-being.

Potential as a Testosterone Alternative

• E. longifolia serves as a safe and effective herbal alternative to TRT. It helps manage testosterone deficiency symptoms such as low libido, fatigue, and erectile dysfunction while improving physical and sexual health in aging males.

Conclusion

E. longifolia shows consistent evidence of efficacy in enhancing male fertility, testosterone levels, and sexual health in both animal and human studies. While it holds promise as a phytomedicine for idiopathic male infertility and hypogonadism, further robust clinical trials are needed to strengthen its therapeutic credentials.

5.1. Male Fertility Enhancement Effect

Infertility is a major clinical problem, which affects the people medically, economically and psychosocially. Almost, 15% of all couples in the U.S. are infertile, and it is predicted that the male factor is responsible in many of such cases [104]. Male infertility refers to a male’s inability to achieve a pregnancy in a fertile female. In humans, this accounts for 40%–50% of infertility cases [105,106]. Infertility in males is a multifactorial disease, based on numerous factors including reduced spermatogenesis and also production of dysfunctional sperm, which are the major prevalent underlying characteristic in idiopathic male infertility cases [107,108]. One meta-analysis of sixty-one studies worldwide reported s downward trend in the sperm count and semen volume over the past fifty years [109,110].

Mostly, the water-soluble E. longifolia extracts were reported to be able to enhance male fertility (with regards to higher semen volumes, spermatozoa count, and motility) in rodents [111,112] and in human trials [86,113,114].

Secondary Specialized Metabolites

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 and biphenyl neolignan, eurycolactone, laurycolactone, and eurycomalactone, and bioactive steroids. Among these phytoconstituents, quassinoids account for a major portion of the E. longifolia root phytochemicals.

 chemistry/biosynthesis

The squalene derivatives include teurilene, eurylene; 14-deacetyleurylene; and longilene peroxide [53,54].

The biphenyl neolignans class includes; 2-hydroxy-3,2,6-trimethoxy-4-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)-biphenyl; two isomeric 2,2-dimethoxy-4-(3-hydroxy-1-propenyl)-4-(1,2,3-trihydroxypropyl) diphenyl ethers; and 2-hydroxy-3,2-dimethoxy-4-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl [55].

Alkaloids included 5,9-dimethoxycanthin-6-one; 9,10-dimethoxycanthin-6-one, 11-hydroxy-10-methoxycanthin-6-one; 10-hydroxy-9-methoxycanthin-6-one; and 9-methoxy-3-methylcanthin-5,6-dione [45,56,57].

Major isolated chemical constituents with metabolites from E. longifolia Jack and their pharmacological effects, are listed in Table 1, while their chemical structures are presented in Figure 1.

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Extraction Optimization

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15th ed. MERCK MONOGRAPH OF QUASSIN

c22h28o6; MOL WT 388.46. One of the bitter conffstituents fo Quassia amara L., Simaroubaceae kow icommerce as Surinam quassia. Obtained by the resolution of the mixture of bitter constituents of quassia wood. Very bitter rectangular plates from dilute methanol, mp 222*C. UV Max 255nm. Soluble in Benzene, alc, acetone, chloroform, pyridine, acetic acid, ht ethyl acetate. Sparingly sol in ether, petr ethr. Bitterness threshold 1:60,000. Antehelmintic.

DISCLAIMER

An acute toxicity study has 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. Liver and renal function tests showed no adverse changes at normal daily dose and chronic use of E. longifolia.