When it comes to "natural boosters", the question "how does it work" usually remains unanswered. For fadogia, agrestis and tongkat ali suggest different mechanisms of influence on testosterone, and their level of validity is not the same. The editors compared what is known about the mechanisms of action and unwanted effects of both plants, and separated experimental hypotheses from clinical facts.
How testosterone is regulated
To appreciate the mechanisms of any plant, you need to remember how the body controls testosterone levels. The hypothalamus secretes gonadoliberin, which stimulates the pituitary gland to produce luteinizing hormone (LH). LH acts on the Leydig cells in the testes and triggers the synthesis of testosterone from cholesterol through a chain of enzymatic reactions.
The system works on the principle of negative feedback: when testosterone and oestradiol are sufficient, the hypothalamus and pituitary gland reduce stimulation. Therefore, a healthy body actively resists attempts to "raise" the hormone above the individual norm, and a stable supraphysiological increase without pharmacological means is unlikely.
In the blood, most of the testosterone is bound to sex hormone-binding globulin (SHBG) and albumin. Free and albumin-bound fractions are considered biologically available. Some additives can theoretically affect the distribution between fractions without changing the overall level.
So, the potential points of influence of herbal remedies are LH stimulation, direct action on steroidogenesis enzymes in the testicles, reduction of the conversion of testosterone to oestradiol, influence on SHBG or on cortisol, which suppresses the gonadal axis. Next, we will consider which of these points are attributed to each plant.
The mechanism of action of fadogia: what animals have shown
In a rat study by Yakubu et al., an aqueous extract of the stem of fadogia increased serum testosterone levels and, according to the authors, LH levels. The authors attributed this to the presence of alkaloids, saponins, and flavonoids in the extract, but the specific active compound responsible for the effect was not identified.
They also described an increase in the cholesterol content in the testicles and changes in the activity of enzymes, which the authors interpreted as an increase in steroidogenesis. However, these results were obtained in small groups of animals, with doses calculated on the weight of the rat, and without independent reproduction by other laboratories.
It is important that the following work of the same group (2008) described changes in testicular function indicators, which the authors regarded as signs of a possible toxic effect. That is, even within the limits of the animal model, the stimulating effect did not look "pure" and was accompanied by alarming signals.
For humans, the mechanism of action of fadogia is actually unknown. There are no data on the bioavailability of its components, pharmacokinetics or effective and safe doses. The claim that phadogia "mimics LH" or "directly stimulates Leydig cells in humans" is currently an extrapolation.
Mechanism of action of tongkat ali
Tongkat ali root contains quassinoids (especially eurycomanone), alkaloids and other compounds. In experimental works, the effect on steroidogenesis in Leydig cells and, according to some data, the reduction of aromatization of testosterone was described for them. These mechanisms have mostly been studied in vitro and in animals.
Clinical studies hint at another possible pathway—through stress. Talbott et al (2013) reported decreased cortisol and increased testosterone in individuals with moderate chronic stress. Because cortisol suppresses the gonadal axis, reducing the stress response could theoretically support testosterone production indirectly.
Some authors also suggest that tongkat ali may affect SHBG and thus increase the proportion of free testosterone. However, data on this are inconsistent, and methods for measuring free testosterone in small studies are not always reliable.
In general, in men with reduced testosterone (Tambi et al., 2012; Leitão et al., 2021), an increase in the hormone was observed against the background of standardised extracts, while the effect was less convincing in healthy young men. This is consistent with the idea that the plant "maintains" the suppressed axis rather than raising the level above normal.
Adverse effects and toxicity
The safety profiles of the two plants differ primarily in the amount of information. For tongkat ali, there are at least a few clinical studies where adverse events were recorded; there is no such data on humans for fadogia.
| Aspect | Fadogia agrestis | Tongkat Ali |
|---|---|---|
| Safety data in humans | Missing | Limited, short-term RCTs |
| Signals from animal studies | Changes in indicators of testicular function | Toxicity mainly at very high doses |
| Reported adverse events | Anecdotal: testicular pain, insomnia | Insomnia, irritability, restlessness |
| Risk of impurities | High due to non-standardised raw materials | Present, particularly heavy metals |
| Interactions with drugs | Not studied | Not studied enough |
For fadogia in Internet communities there are reports of discomfort or pain in the testicles during use. Such evidence is not scientific data, but when combined with the results in rats, it is a reason for caution. Any pain in the testicles is a reason to stop taking and consult a urologist.
For tongkat ali, sleep disturbance, feeling agitated, and irritability are most commonly mentioned. In theory, people with hormone-dependent diseases, cardiovascular problems, or those who take anticoagulants, antihypertensive drugs, or hormonal drugs should be especially careful, because the interactions are practically unknown.
The common risk of both categories is the quality of raw materials. Herbal supplements may contain heavy metals, and "testosterone boosters" as a category are known for cases of undeclared pharmacological substances. For athletes, this is also the risk of a positive doping test.
Comparative assessment of risk and benefit
Taken together, tongkat ali has plausible mechanisms, partially supported by human data, and a relatively favourable, albeit understudied, safety profile. The expected effect is small and most likely in people with low testosterone or chronic stress.
Fadogia has only animal data on the mechanism and at the same time animal signals of possible harm. According to the editors, the ratio of the expected benefit to the unknown risk for a person is unfavourable.
- Phadogy: mechanism — hypothesis from studies on rats; safety for humans has not been established.
- Tongkat ali: mechanism — several hypotheses, partially confirmed indirectly; safety has been studied in short-term studies.
- Both: do not replace diagnosis and treatment of hypogonadism.
We advise people with symptoms of androgen deficiency to undergo an examination first. True hypogonadism has causes that require medical evaluation, and no single plant is an adequate treatment for it.
Editorial conclusions
The mechanism of action of fadogia is known only from studies on rats: it is possible to increase LH and stimulate steroidogenesis, but nearby - signs of possible damage to the testicles.
Several mechanisms are considered for tongkat ali: a direct effect on steroidogenesis, an effect on SHBG, and a reduction in the stress response. Clinical data are limited but exist, and few serious side effects have been reported in short-term studies.
The main practical risks of both plants are unknown long-term effects, drug interactions, and supplement quality.
We also recommend reading our articles on the hypothalamic-pituitary-testicular axis, SHBG and free testosterone, and how to test supplements for undeclared substances.
List of used literature
- Yakubu MT, Akanji MA, Oladiji AT. Aphrodisiac potentials of the aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem in male albino rats. Asian J Androl. 2005;7(4):399â404.
- Yakubu MT, Akanji MA, Oladiji AT. Effects of oral administration of aqueous extract of Fadogia agrestis (Schweinf. Ex Hiern) stem on some testicular function indices of male rats. J Ethnopharmacol. 2008;115(2):288â292.
- Talbott SM, Talbott JA, George A, Pugh M. Effect of Tongkat Ali on stress hormones and psychological mood state in moderately stressed subjects. J Int Soc Sports Nutr. 2013;10(1):28.
- Tambi MI, Imran MK, Henkel RR. Standardised water-soluble extract of Eurycoma longifolia, Tongkat ali, as testosterone booster for managing men with late-onset hypogonadism? Andrologia. 2012;44(Suppl 1):226â230.
- Henkel RR, Wang R, Bassett SH, et al. Tongkat Ali as a potential herbal supplement for physically active male and female seniors â a pilot study. Phytother Res. 2014;28(4):544â550.
- Leitão AE, Vieira MCS, Pelegrini A, et al. A 6-month, double-blind, placebo-controlled, randomized trial to evaluate the effect of Eurycoma longifolia (Tongkat Ali) and concurrent training on erectile function and testosterone levels in androgen deficiency of aging males (ADAM). Maturitas. 2021;145:78â85.
- Clemesha CG, Thaker H, Samplaski MK. 'Testosterone boosting' supplements composition and claims are not supported by the academic literature. World J Mens Health. 2020;38(1):115â122.
