Tuesday, August 19, 2014

Eurycoma Longifolia aka "Long Jack" a Natural Alternative to Testosterone Replacement Therapy? A Review of Its Effects on Fertility, Muscle, Bone, Boners & More!

As its Western name already implies "Long Jack" has traditionally been used as libido booster. As Tongkat Ali or E. Longifolia extract it is yet also an ingredient of "Testosterone Boosters", these days - rightly so?
In spite of the fact that you'll probably agree, when I say that the risks of classic (hormonal) testosterone replacement therapy are largely overblown in the never-ending debate about the alleged negative side effect of "The Big T" (learn more about Testosterone), it would still be nice if there were natural and thus easily accessible alternatives, right? An alternative like the one A. George & R. Henkel, two scientists from Malaysia and South Africa believe to have found in Eurycoma longifolia aka "Long Jack" or "Tongkat Ali" (George. 2014).

In their latest paper in the peer-reviewed scientific journal Andrologia, George & Henkel claim that the contemporary evidence would suggest that "Tongkat Ali" (TA) would qualify as a "safe alternative to TRT" (George. 2014).
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Eurycoma longifolia is popularly known as Tongkat Ali (TA) in Malaysia, Pasak Bumi in Indonesia and Cay Ba Bihn in Vietnam (Goreja, 2004). In Europe and the US extracts are often sold as "Long Jack". They contain an extract from the roots of a medium size slender tree from the family of Simaraubaceae, which is largely found as an under-storey growth of lowland forests in Peninsula Malaysia and other Southeast Asian regions (Samy. 2005).
"The root of the plant is traditionally boiled and consumed as a tonic for aphrodisiac effects and energy in men. Eurycoma longifolia (El) is reputed to be a cure for many conditions including malaria, high blood pressure, fatigue, migraine, fever, arthritis, improvement of testosterone production and symptoms of impotence, loss of desire/ libido, improved physical and mental performance, enhanced energy levels, endurance and stamina, improved skin and muscle tone and enhancement of the immune system." (George. 2014)
In view of the plethora of alleged health benefits, it's no wonder that there are over 202 registered Tongkat Ali products registered with the National Pharmaceutical Control Bureau of Malaysia (NPCB, 2013). The products range from raw crude powders of the root, over capsules and tablets with single or multiple ingredients to "functional foods" such as TA-enhanced coffee.

Previous studies have identifies 65 different potentially bioactive compounds in TA (Kuo. 2003). Of those, the alkaloids and quassinoids eurycomaoside, eurycolactone, eurycomalactone, eurycomanone and pasakbumin-B  are thought of as the actual working ingredients. In that, the quassinoid compound eurycomanone is used as a marker in standardized water extract according to SIRIM standards (Malaysian Standards, 2011) and has been found to increase testosterone levels and increase the production of sperm in animal models (Low. 2013b).  The extract has been described as an adaptogen (Tambi. 2006) and a traditional anti-aging remedy, particularly for aging men to improve age-related reduced energy level, mood, sexual function and libido (Adimoelja, 2000; Cyranoski, 2005).

How does Tongkat Ali work?

There appears to be more than one mechanism of action in the increase of serum testosterone levels upon supplementation with Tongkat Ali:
  • enhanced metabolism of pregnenolone and 17-OH-pregnenolone due to increase CYP17 activity ⇒ increased DHEA production (Ali. 1993)
  • enhanced testosterone production by Leydig cell explants via the inhibition of phosphodiesterase and aromatase by eurycomanone, a major quassinoid compound present in E.. longifolia root extracts (Low. 2013a) 
  • reduced estrogen levels ⇒ decreased hypothalamic negative feedback ⇒ increase in LH and FSH levels (Prakash. 2007; Low. 2013b)
  • reduction of  SHGB binding (will not increase total testosterone) and thus increases in unbound testosterone (Chaing. 1994; Henkel. 2013; Talbott. 2013)
As you can see in Figure 1, these beneficial effects are highly dose dependent. While a dosage of 25 mg/kg body weight of the quassinoid-rich fractions increased the Leydig cell testosterone production in rodents, a higher dosage of 50 mg/kg resulted in significantly lower Leydig cell testosterone production (Low. 2013b).
Figure 1: Testosterone concentration in plasma and testes (left) and estrogen concentration in plasma (right) of male rats after being treated with 25mg/kg or 50mg/kg body weight TA extract (Low. 2013b)
In addition, despite the fact that this low concentration (25 mg/kg) of the extract stimulated higher LH secretion than the high dose (50 mg/kg), the serum oestrogen levels showed an inverse picture.
The human equivalent doses for the effective and ineffective (over-)dose are 4mg/kg and 8mg/kg. If we assume that the results are applicable to men, as well, this would mean that a daily dose of 320mg of Tongkat Ali root extract would increase your testosterone and decrease your estrogen levels, while a dosage of 640mg per day would not.
Now, normal testosterone levels are nice. In isolation, however, having a normal lab value is pretty useless. It is thus important to check, whether the previously reported increases in testosterone levels will also translate into measurable health benefits, such as...
  • fertility: Tambi & Imran (2010) report a significant improvement in semen profiles (increased semen volume, sperm concentration and number of sperm with normal morphology and motility) in response to the ingestion of 200mg of a standardized aqueous extract of TA called
    Physta. An improvement in volumes of seminal fluid and sperm motility was also demonstrated in a subpopulation with low baseline values in another study (Ismail. 2012).
  • sexual health: In spite of the fact that Asian men swear by Tongkat Ali (Low. 2002), there is only a single 12 week trial by Ismail et al. (2012), which resports increased sexual libido scores for subjects who received the previously mentioned patented TA extract Physta.
    Figure 2: Changes (%) in selected parameters of sexual health in healthy young men in response to 12-week supplementation with patented TA extract Physta (Ismail. 2012).
    The same trial also mentions significant improvements in sexual satisfaction after 12 weeks of treatment (P=0.001). Specifically, Ismail et al. report a 14.4% increase in interest in sex, a 17.1% increase in the frequency of sexual intercourse and a self-reported improvement of erectile functioning in the healthy men who had been randomized to the E. longifolia arm of the study.

    In another study, the same standardized aqueous extract of TA (Physta) was administered to mildly erectile dysfunctional men in a randomized, placebo-controlled trial that involved 26 subjects (Udani. 2011). After 12 weeks the researchers recorded significant improvements in several parameters of sexual health, including erection hardness scale (P=0.012), sexual health inventory for males (P=0.03) and aging male symptom score (P=0.047).
  • Figure 3: Osteoporosis, i.e. the loss of bone mass, is by no means an exclusive "female" problem. Men lose bone mass, as well - specifically if their testosterone and general androgen levels drop faster than normal (Wikipedia. 2014)
    bone health: Often mis-labeled as a "female problem", men tend to lose bone mass just as women, when they go "andropause" or suffer from reduced testosterone levels due to (other) health issues (Kaufman. 2000). Bone formation is after all the result of testosterone being converted to dihydrotestosterone (DHT), a potent AR activator which will stimulate osteoblast proliferation and differentiation (Vanderschueren. 2004). Since testosterone directly inhibits the opposite effect, i.e. the formation of bone resorption osteoclasts (Michael. 2005), the loss of testosterone will lead to similar rapid bone loss in men as the menopausal loss of estrogen in women.

    Against that background, it would be great if we had convincing evidence that Tongkat Ali could counter the low-T induced loss of bone mass. A glimpse at the literature does yet reveal inconclusive results with somewhat promising evidence from rodent models of age-related hypogonadism (Shuid. 2012) and rather disappointing results from studies with rodent eunuchs (Tajul Ariff. 2012). 
  • athletic performance: In Asia TA may in fact be used as a health supplement. Over here in the West, on the other hand, bodybuilders and fitness enthusiasts are probably the main target audience of Tongkat Ali marketing which is mainly, but not exclusively, based on the testosterone boosting effects of TA extracts. When all is said and done, the one thing people are really interested in is yet not a higher T-number on their lab reports, but rather the increase in strength and muscle gains they (falsely) associate with said number.

    Several studies have investigated the use of TA for ergogenic benefits. Hamzah & Yusof (2003) tested 14 healthy male adults who were randomly given either 100 mg of an aqueous extract of TA or placebo and study participants performed an intensive strength training program for 8 weeks.
    Figure 2: Higher lean mass, fat loss and strength gains in an 8-week resistance training study with tongkat ali vs. placebo supplement; do not overrate the results, the study is somewhat dubious and not of high quality and potential conflicts of interests are not declared (Hamzah. 2014)
    At the end of the study, the subjects  in the group that consumed TA had increased their strength by 6.78%, while those in the control group gained only 2.77%. A similar, albeit statistically less significant image emerges for the increases in lean body mass, and reductions in body fat mass.

    The title of the study, "The Ergogenic Effects Of Eurycoma Longifolia Jack: A Pilot Study", does however tell you that we are not yet at a point, where we can say that there is more than initial evidence from "pilot studies" that oral TA supplements have measurable, if not recognizable beneficial effects on training induced strength increases and changes in body composition. Studies such as the one by Henkel et al. (2013) who observed significant increases in muscle strength and testosterone levels in the male and female physically active seniors (57-72 years) who participated in their 2013 study on the effects of 400 mg/day of standardised aqueous extract of Tongkat Ali (Physta).
    Table 1: In seniors the patented TA extract had significant (all highlighted in green) effects on selected clinical and biochemical parameters in men and women (table shows data for men, only | Henkel. 2013)
    A result that stands in contrast to the findings Muhamadet et al presented in a previous studies in young men whose running performance did not benefit from the provision of 150 mg TA extract per day.

    Overall, it would seem that both study duration (7 days vs. multiple weeks), dosage and type of supplement 400mg of patented standardized extract vs. 150mg of regular TA extract and the age of the subjects would determine the study outcome. In that, your best chance to actually see results would probably be achieved at 400mg of Physta, taken for 8-12 weeks, when you're 60+ years old.
  • blood glucose management: Data on the beneficial anti-diabetic effects of TA is restricted to rodent studies. Husen et al .(2004) reported a significant antihyperglycaemic effect of TA in a rat model where diabetes was induced by streptozotocin. In this study, four Malaysian
    plant extracts were administered to the animals at different concentrations. Among these four extracts, only the extracts of E. longifolia and Andrographis paniculata revealed a significant antihyperglycaemic effect.

    The existing human studies, on the other hand, do not support the hypothesis that TA could be used as an effective andi-diabesity agent. In fact, the non-diabetic subjects in a 2010 study by Talbott et al. did not experience any effects on blood glucose levels. For the average consumer buying at TA containing test booster the potential anti-diabesity effects are thus not of interest.
Now that we've learned that the 60+ years old not exactly fit baby-boomer is the person who is most likely to benefit from a (hopefully) standardized Tongkat Ali extract, if he has the funds to buy enough to supplement at dosages of 100-400mg per day for 3 months or longer, it would appear prudent to take a parting look at the safety profile of this herbal supplement.

Is Tongkat Ali / E. longifolia / Long Jack even safe?

In animal studies, no negative effect on the offspring could be found, neither in terms of  malformations nor of any effect on body weight or the number of the offspring (Solomon et al., 2013). Yet subacute toxicity tests in rats revealed an LD50 for an ethanolic and aqueous extract of TA of 2000 and 3000 mg/kg body weight, respectively (Satyavivad, 1998; Kuo, 2003).
How much is too much? Based on rodent studies we can assume that dosages of up to 48mg/kg or 3,891mg for a man with a body weight of 80kg are safe for all sorts of supplements. For the previously mentioned patented extract Physta, rodent data suggests safety up to 25g per day... in view of the fact that you probably need max. 400mg/day to see results, it would yet be plain-out stupid to play human Guniea pig and consume more than 500mg/day on an ongoing basis.
As the authors of a recent review point out Satyavivad & Kuo further showed that dosages of 200 mg/kg body weight of the ethanolic extract and 300 mg/kg of the aqueous extract daily were not toxic. Only at dosages above 1200 mg/kg body weight, significant hepatotoxic effects were shown in the rat (Shuid. 2011a).

Recently, Choudhary et al. (2012) investigated the acute, subacute and subchronic toxicity of the standardised aqueous E. longifolia extract (Physta) in a rat model [note: Obviously this is a sponsored study!]: Male and female Wistar rats were treated for 90 days with TA concentrations from 250 mg/kg body weight to 2000 mg/kg body weight. Results clearly show no significant changes in blood chemistry and haematological parameters. There were also no histopathological changes and even in acute toxicity tests, no changes in mortality or in the behaviour of the animals could be seen.
Bottom line: I don't see Tongkat Ali (let alone any other natural T-booster) as a legit alternative to real testosterone replacement.On the other hand, I do have to admit that Long Jack, as Tongkat Ali is often called in the West is one of the most promising agents in this group of supplemental non-starters.

TA Boosts Testosterone in Late Onset Hypogonadism | learn more
Not promising enough to make it into my supplement regimen, but probably promising enough to be the #1 choice for those of you whose testosterone levels have been on the decline for 25 years or more (everyone beyond the age of 25 years) who insist on giving one of the countless testosterone boosters on the market a try - based on the previous elaborations you will probably agree that the chances that a standardized (!) E. longfolia based product does something are not high, but at least higher than they are for 99% of the other allegedly testosterone-boosting herbs on the market | Comment on Facebook!
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