Leisegang K, Finelli R, Sikka SC, S Panner Selvam MK. Eurycoma longifolia (Jack) improves serum total testosterone in men: A systematic review and meta-analysis of clinical trials. Medicina (Kaunas). August 4, 2022;58(8):1047. doi: 10.3390/medicina58081047.

Hypogonadism in males is a condition characterized by reduced libido, erectile dysfunction, infertility, obesity, reduced lean body mass, fatigue, and depression. The biochemical definition remains unclear; however, a 300 ng/dL testosterone (T) threshold is generally considered the lowest normal limit. Treatment for hypogonadism focuses on T replacement therapy (TRT); however, the condition tends to go undiagnosed and only a small proportion of those affected receive therapy. In patients whom T is contraindicated, the benefits of TRT compared to its long-term risks remain widely unknown, deterring some providers from prescribing it. Alternatively, tongkat ali (Eurycoma longifolia, Simaroubaceae) is reported to improve libido, and recent systematic reviews have reported its benefits for men’s reproductive health. Even so, its effects on serum T remains unclear. This study aimed to investigate the efficacy of tongkat ali for increasing T in men by systematic review and meta-analysis.

PubMed, Scopus, Web of Science, Cochrane, Ovid/Embase, and Google Scholar were searched from inception to July 10, 2021, using relevant keywords. Studies that investigated the use of tongkat ali as a sole intervention in adult males and reported changes in serum T were eligible for inclusion. Both observational and randomized controlled trials (RCTs) were included in the systematic review, whereas the meta-analysis contained RCTs only. The RCT quality and risk of bias were assessed using the Cochrane risk-of-bias tool. Publication bias was assessed by the Begg and Egger tests. A subgroup analysis was performed for patients with low T (< 300 ng/dL) prior to tongkat ali treatment.

Of the 387 original articles, nine were included in the systematic review and five in the meta-analysis. The articles included in the systematic review were published between 2012 and 2021. Of these, two were comparative prospective studies, five were double-blind controlled trials (of which, four were randomized), and two RCTs were published as Doctor of Philosophy degree (PhD) dissertations. Three studies investigated hypogonadal males and six included males with normal T levels. Tongkat ali was investigated primarily as a commercial water-extract product (Physta^®; Biotropics; Berhad, Kuala Lampur, Malaysia) in seven of the nine studies in dosages ranging from 100 to 600 mg daily for as few as three days and up to six months. Most studies (n = 7) reported a significant improvement in total T after tongkat ali treatment, with the remaining two studies reporting no improvement when used for three to eight weeks.

Free T, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) levels were reported in some studies as secondary outcomes. Three of the six studies that analyzed free T reported significant increases with tongkat ali supplementation. Six of the nine studies reporting on SHBG found no significant changes after treatment. Two studies reported on DHEA and reported no significant changes. One study reported gastrointestinal symptoms and itching associated with tongkat ali treatment, while a different study observed adverse events in both the treatment and placebo groups.

Five eligible RCTs measuring T levels in men (n = 232) were included in the meta-analysis. Of these, some showed low (n = 2) or high (n = 1) risk of bias, while others showed concern (n = 2) for performance biases. Significant heterogeneity was observed across the five studies (P < 0.0001) with 87.27% inconsistency. Furthermore, publication biases were apparent (P = 0.0243) based on the Begg’s test. Using a random effects model, a significant increase in total T was observed with tongkat ali supplementation (P = 0.001). Results from the subgroup analysis demonstrated increases in total T levels in men with and without total T, with the effect being in the hypogonadism group only. Heterogeneity was noticed among the studies in both groups, and the Begg and Egger tests revealed significant levels of publication bias among studies included in the hypogonadism group.

The present data highlight the potential use of tongkat ali supplementation for enhancing T, particularly in hypogonadal males. Most of the studies used the same commercial extract (Physta), which is standardized to 0.8–1.5% eurycomanone, not < 22% of total protein, not < 30.0% of total polysaccharide, and not < 40.0% of glycosaponin. Animal studies have demonstrated increases in T levels and anti-estrogenic activity with eurycomanone derivatives. In humans, tongkat ali has a possible use for treating male infertility. The authors recognized the low number of studies available for analysis as a limitation, which were heterogeneous in terms of the study design, included population, dosage, length of treatment, and sample sizes. Additionally, most of the included studies utilized the same commercial product for tongkat ali supplementation, limiting the extrapolation of these data to include other supplemental forms of tongkat ali that contain low or no levels of eurycomanone. The authors call for more research before its use in clinical practice but suggest it may represent a safe and promising therapeutic option.

The authors report no conflicts of interests.

—Gavin Van De Walle, MS, RDN