Eurycoma longifolia is an herbal medicinal plant found in South East Asia (Malaysia, Vietnam, Java, Sumatra, Thailand). In Malaysia, it is commonly called tongkat ali and has a range of medicinal properties as a general health tonic, including improvement in physical and mental energy levels and overall quality of life [1, 2]. The roots of tongkat ali, often called “Malaysian ginseng”, are used as an adaptogen and as a traditional “anti-aging” remedy to help older individuals adapt to the reduced energy, mood, and libido that often comes with age [3–7]. In modern dietary supplements, tongkat ali can be found in a variety of products intended to improve libido and energy, restore hormonal balance (cortisol/testosterone levels) and enhance both sports performance and weight loss. The objective of this study was to evaluate the effects of tongkat ali extract on stress hormone balance (cortisol/testosterone) and psychological mood state in moderately stressed subjects.
In both men and women, testosterone levels peak between 25 to 30 years of age - and thereafter drop approximately 1-2% annually [8, 9]. At the age of 60, testosterone levels are typically only 40-50% of youthful levels and may be lower due to stress and related lifestyle issues such as diet, exercise, and sleep patterns [10, 11]. The benefits of maintaining a youthful testosterone levels are many, including increased muscle mass and reduced body fat, high psychological vigor (mental/physical energy), and improved general well-being [12, 13].
Eurycoma 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 [14–16]. The effects of tongkat ali in restoring normal testosterone levels appears to be less due to actually “stimulating” testosterone synthesis, but rather by increasing the release rate of “free” testosterone from its binding hormone, sex-hormone-binding-globulin (SHBG) [17, 18]. In this way, eurycoma may be considered not so much a testosterone “booster” (such as an anabolic steroid), but rather a “maintainer” of normal testosterone levels and a “restorer” of normal testosterone levels (from “low” back “up” to normal ranges) . This would make eurycoma particularly beneficial for individuals with sub-normal testosterone levels, including those who are dieting for weight loss, middle-aged individuals suffering with fatigue or depression, and intensely training athletes who may be at risk for overtraining [20, 21].
Decoctions of tongkat ali roots have been used for centuries in Malaysia and Southeast Asia as an aphrodisiac for loss of sexual desire and impotence, as well as to treat a range of ailments including post-partum depression, malaria, high blood pressure, and fatigue .
Tongkat ali has been referred to as Malaysia’s “home-grown Viagra”  with the Malaysian government investing considerable effort to license, develop, and sustain research into the potential health benefits of Eurycoma longifolia through a variety of governmental organizations, including the Forest Research Institute of Malaysia (FIRM) .
Numerous commercial tongkat ali supplements claim “extract ratios” from 1:20 to 1:200 without any information about bioactive constituents, extraction methodology (e.g. ethanol versus water), or extract purity. Alcohol extracts of eurycoma have been studied in mice for antimalarial effects of concentrated eurycomalactone  but also exhibit toxic effects at high doses (LD50 at 2.6 g/kg), which would preclude safe use in humans as a long-term dietary supplement [24, 25]. In contrast, hot-water root extracts standardized for known bioactive components (1% eurycomanone, 22% protein, 30% polysaccharides, 35% glycosaponin) have been demonstrated to be extremely safe at high doses and for long-term consumption [26–28].
Properly standardized hot-water extracts [2, 26, 29] have a distinctly bitter taste due to the presence of quassinoids, which are recognized as some of the bitterest compounds in nature [30, 31]. Tongkat ali extracts that do not taste bitter are either not true Eurycoma longifolia root (there are many commercial examples of “fake” tongkat ali extracts) or are sub-potent in terms of bioactive constituents, and thus would also be expected to have low efficacy. Because of tongkat ali’s reputation for libido benefits, there are several examples of dietary supplements labeled as Eurycoma longifolia, but containing none of the actual root, and instead being “spiked” with prescription erectile dysfunction drugs including tadalafil/Cialis, sildenafil/Viagra, and vardenafil/Levitra [4, personal communication].
Laboratory and animal research
Bhat and Karim  conducted an ethnobotanical and pharmacological review on tongkat ali, noting that laboratory research such as cell assay studies offer possible mechanistic support for the myriad traditional uses of tongkat ali, including aphrodisiac , antimalarial , antimicrobial , anti-cancer , and anti-diabetic effects .
Numerous rodent studies exist demonstrating reduced anxiety and improved sexual performance following tongkat ali feeding [37–40], with such effects thought to be due to a restoration of normal testosterone levels. Eurycoma’s anxiolytic effects have been demonstrated in a variety of behavioral tests, including elevated plus-maze, open field, and anti-fighting, suggesting an equivalent anti-anxiety effect to diazepam as a positive control .
Animal studies have shown that many of the effects of the extract are mediated by its glycoprotein components . 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 . This glycoprotein water-soluble extract of Eurycoma longifolia has been shown to deliver anti-aging and anti-stress benefits subsequent to its testosterone-balancing effects [41, 42].
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 and Labeling of Chemicals (GHS).
In addition to the very high safety profile demonstrated in the rodent toxicity studies, there are no reported adverse side effects in human studies of tali supplementation. For example, one 2-month human supplementation trial  of twenty healthy males (age range 38–58), found high doses of Eurycoma longifolia extract (600 mg/day) to have no influence on blood profiles (hemoglobin, RBC, WBC, etc.) or any deleterious effects on measures of liver or renal function. Typical dosage recommendations, based on traditional use and on the available scientific evidence in humans, including dieters and athletes, call for 50-200 mg/day of a water-extracted tongkat ali root standardized to 22% eurypeptides.
Human supplementation trials
Based on a long history of traditional use and confirmation of biological activity via cell culture and animal feeding studies, several human supplementation studies have been conducted to evaluate the potential benefits of tongkat ali for sexual function, exercise performance, weight loss, and vigor (mental/physical energy).
Importantly, all of the 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) . The 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 4300 dalton glycopeptide with 36 amino acids) that is responsible for its effects in maintaining testosterone levels. The bioactive fraction of Eurycoma longifolia root delivers a demonstrated ability to improve testosterone levels , increase muscle size and strength [43, 44], improve overall well-being [45, 46], accelerate recovery from exercise  enhance weight loss [48, 49], reduce stress , and reduce symptoms of fatigue [51–53].
Based on it’s long history of traditional medicinal use as an “anti-aging” remedy and the series of animal and human supplementation studies investigating it’s use as a physical and mental performance aid, we undertook a study of the effects of tongkat ali root extract supplementation in moderately stressed subjects. Our hypothesis was that tongkat ali supplementation may influence anabolic/catabolic stress hormone balance and mood state parameters in a group of volunteers with moderate stress levels.