Tongkat Ali Extract

Tongkat Ali is a well-known herb native to Southeast Asia, known for its therapeutic effects on sexual and hormonal health. Tongkat Ali contains a variety of bioactive compounds, including eurycomanones, glycosaponins, and polysaccharides, which have been shown to support increased sex drive, testosterone production, and improve sperm parameters in men  [3].

A meta analysis done in 2021 by Lazarus et al evaluating 7 human trials found a positive net change in total testosterone levels with Tongkat Ali supplementation compared to placebo, in both hypo & eugonadal men.

Lazarev, A., & Bezuglov, E. (2021). Testosterone Boosters Intake in Athletes: Current Evidence and Further Directions. Endocrines, 2(2), 109-120. https://doi.org/10.3390/endocrines2020011

Testosterone Boosters Intake in Athletes: Current Evidence and Further Directions

Endocrines | Free Full-Text | Testosterone Boosters Intake in Athletes: Current Evidence and Further Directions. (n.d.). Retrieved March 18, 2022, from https://www.mdpi.com/2673-396X/2/2/11

How Does Tongkat Ali Work?

Tongkat Ali extract works through a variety of mechanisms to support sexual and hormonal function. It is hypothesized that Tongkat’s active ingredients work as a 17α-hydroxylase activator, an aromatase inhibitor and demonstrates PDE5 inhibition to a notable degree  [4,3].

By possible upregulation of 17α-hydroxylase, Tongkat Ali can increase the production of the sex hormones: pregnenolone, 17-OH-pregnenolone, DHEA, progesterone, 17-OH-progesterone, and 4-androstenedione [4]. This results in increased total testosterone & neurosteroid levels; on the other hand, by inhibiting the aromatase enzyme & enzymatic production of cortisol, Tongkat Ali can promote increases in total/free testosterone [1,2,3].

Ashwagandha Extract (Sensoril)

Ashwagandha is an Ayurvedic herb historically used as an adaptogen. It can significantly increase testosterone levels in males and is thought to do so by downregulation of cortisol. The systematic review below provides an overview of the effects of this herb on male sex hormones and its safety profile.

Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review: Ashwagandha

Smith, S., Lopresti, A., Teo, S., & Fairchild, T. (2020). Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review. Advances in Nutrition, 12. https://doi.org/10.1093/advances/nmaa134

D-Chiro Inositol

D-Chiro Inositol is a cyclic sugar alcohol with biological activity as a second-messenger in the insulin signalling cascade, possessing anti-hyperglycemic and aromatase inhibiting properties, it has been shown to positively affect testosterone levels in males [6,7]. In a pilot trial on 10 healthy males, oral administration of D-chiro-inositol administration at 1g/day was associated with reduced serum levels of estrone (- 85.0%) and estradiol (- 14.4%), and increased serum levels of testosterone (+ 23.4%) and dehydroepiandrosterone (DHEA) (+ 13.8%) [7]. Additionally, epiandrosterone levels were higher (+39%) after treatment [7].

 Fig. 1 Effect of D-chiro-inositol (DCI) treatment on total testosterone (T) levels. Total serum T levels from 10 male volunteers at baseline (t0) and after 30 days of treatment (t1) with 1 g DCI per day are presented as: a median values of total T (box plots). The boxes denote the interquartile range between the first and third quartiles (25th and 75th percentiles, respectively), the whiskers represent the minimum and maximum values, and the line inside the boxes represents the median value (p = 0.0020; Wilcoxon signed rank sum test);[7]

Fig. 4 Effect of D-chiro-inositol (DCI) treatment on estrone (E1) levels. E1 levels from 10 male volunteers at baseline (t0) and after 30 days of treatment (t1) with 1 g DCI per day are presented as: a median values of E1 (box plots) (p = 0.0020; Wilcoxon signed rank sum test) [7]

Fenugreek Extract

Fenugreek is a spice which has an extensive use in food preparation and more recently sports supplementation, a recent meta analysis by Isenmann et al conducted a quantitative analysis on 6 human trials evaluating the effects of fenugreek preparations on sex hormones and athletic markers in healthy individuals; a statistically significant improvement was noted in total testosterone levels, free testosterone levels, and reductions of estradiol, stating that “chronic application of fenugreek has performance-enhancing and anabolic effects in male athletes” [19].

NAC (N-Acetyl-Cysteine) & Selenium

In a randomized double blind placebo controlled trial published in The Journal of Urology by Safarinejad et al, it was found that administration of NAC (600mg/daily) and Selenium (200mcg/daily) in combination led to a significant increase in serum testosterone levels and improvement of sperm parameters in infertile men [20].

The exact mechanism is unknown, the authors state: “A prominent hypothesis is that decreased antioxidant function may be a contributing factor (of hypogonadism).”, indicating that the improvements in testicular function may be attributed to a reduction of oxidative stress affecting the leydig and sertoli cells of the testes [20].

Boron

Boron is a trace mineral found in coffee, dairy, fruits and vegetables. Supplementation with boron has been shown to increase free testosterone levels in males, primarily through its effects on the metabolism of sex hormones and SHBG [8,9].

Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines

Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M.-S. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology: Organ of the Society for Minerals and Trace Elements (GMS), 25(1), 54–58. https://doi.org/10.1016/j.jtemb.2010.10.001

Shilajit Extract (std. 50% Fulvic Acid, generic)

Shilajit is an ingredient derived from decomposed organic plant material and minerals, characterized by its richness in fulvic acid amongst other organic compounds [23].

It has a long history of use in South and East Asia for increasing vitality [23].

Trials evaluating Shilajit’s effects on males’ testosterone levels are promising, in which the greatest response was seen in hypogonadal men, seeing a +23.5% improvement in total testosterone levels [21].

In another human trial, Shilajit administration was also shown to significantly increase total testosterone, free testosterone and DHEA-S levels in healthy volunteers compared to placebo [22].

Wild Yam Extract (std. for Diosgenin)

Wild yam extract contains a significant amount of Diosgenin, a steroidal saponin which has been studied in humans as being a beneficial natural compound for improving athletic performance and increasing sex hormone levels in healthy males [18]. In a randomized placebo controlled trial, Diosgenin supplementation combined with resistance training increased serum DHEA, serum DHT, serum free testosterone, increased 1-rep max on the deadlift and increased arm fat-free mass compared to placebo [18].

Horii, N., Hasegawa, N., Fujie, S., Iemitsu, K., Uchida, M., Hamaoka, T., & Iemitsu, M. (2020). Effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in sprint athletes. Journal of Clinical Biochemistry and Nutrition, 67(3), 338–343. https://doi.org/10.3164/jcbn.19-124

Zinc Citrate

Zinc deficiency can be a cause of low testosterone levels in men, zinc supplementation has been shown to reliably increase testosterone production in zinc-deficient men and is a first line intervention when trying to naturally increase testosterone levels in the context of nutrient deficiency [10,11]. 

Zinc status and serum testosterone levels of healthy adults

As, P., Cs, M., Fw, B., Jw, H., & Gj, B. (1996). Zinc status and serum testosterone levels of healthy adults. Nutrition (Burbank, Los Angeles County, Calif.), 12(5). https://doi.org/10.1016/s0899-9007(96)80058-x

P5P (Pyridoxal phosphate, active form of vitamin B6)

The active form of vitamin B6, P5P, has been shown to improve outcomes in the context of hyperprolactinemia, a possible endocrine cause of hormonal suppression (excess prolactin secretion results in secondary hypogonadism) [12,13,14]. Although the trials evaluating Vitamin B6/P5P’s effects on hyperprolactinemia used a very high dosage (300mg q12h PO), we felt a lower dose was warranted as the degree of hyperprolactinemia experienced by the participants in this trial was pharmacologically induced (secondary to antipsychotic use), above and excess of what might exist in individuals who do not have prolactinomas or concurrent use of antipsychotics. The dosage we used was less than the studied dosage with intent to target a favorable safety profile (some individuals can experience peripheral neuropathy with very high doses of vitamin B6).

Vitamian B6 (P5P): Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia

Zhuo, C., Xu, Y., Wang, H., Fang, T., Chen, J., Zhou, C., Li, Q., Liu, J., Xu, S., Yao, C., Yang, W., Yang, A., Li, B., Chen, Y., Tian, H., & Lin, C. (2021). Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia. Frontiers in Psychiatry, 12. 

Vitamin D3

Vitamin D3 deficiency is a common global health issue which exists primarily in higher latitudes where individuals may not get adequate sunlight exposure throughout the year, some forms of secondary hypogonadism have a strong association with vitamin D deficiency [16]. Correcting deficient vitamin D levels is a safe and effective way to promote optimal health outcomes, especially in the context of deficiency. G Test+ implements a dosage in line with the RDA for vitamin D3 as a conservative approach, to reduce the risk of hypervitaminosis D for those who already consume a daily vitamin D supplement or plan to take this perpetually (fat-soluble vitamins can accumulate in tissues if taken in excess for long durations and can lead to toxicity if levels become too high).

Effect of vitamin D supplementation on testosterone levels in men

Pilz, S., Frisch, S., Koertke, H., Kuhn, J., Dreier, J., Obermayer-Pietsch, B., Wehr, E., & Zittermann, A. (2011). Effect of Vitamin D Supplementation on Testosterone Levels in Men. Hormone and Metabolic Research, 43(3), 223–225. https://doi.org/10.1055/s-0030-1269854

1. Chan, K. Q., Stewart, C., Chester, N., Hamzah, S. H., & Yusof, A. (2021). The effect of Eurycoma Longifolia on the regulation of reproductive hormones in young males. Andrologia, 53(4). https://doi.org/10.1111/and.14001

2. Leisegang, K., Finelli, R., Sikka, S. C., & Selvam, M. K. P. (2022). Eurycoma longifolia (Jack) Improves Serum Total Testosterone in Men: A Systematic Review and Meta-Analysis of Clinical Trials. Medicina, 58(8). https://doi.org/10.3390/medicina58081047 

3. Rehman, S. U., Choe, K., & Yoo, H. H. (2016). Review on a Traditional Herbal Medicine, Eurycoma longifolia Jack (Tongkat Ali): Its Traditional Uses, Chemistry, Evidence-Based Pharmacology and Toxicology. Molecules, 21(3), Article 3. https://doi.org/10.3390/molecules21030331

4. Eng, A. (2007). Correcting systemic androgen levels using Eurycoma longifolia (United States Patent No. US20070009621A1). https://patents.google.com/patent/US20070009621A1/en

5. Chinnappan, S. M., George, A., Pandey, P., Narke, G., & Choudhary, Y. K. (2021). Effect of Eurycoma longifolia standardised aqueous root extract-Physta® on testosterone levels and quality of life in ageing male subjects: a randomised, double-blind, placebo-controlled multicentre study. Food & nutrition research, 65, 10.29219/fnr.v65.5647. https://doi.org/10.29219/fnr.v65.5647

6. Montt-Guevara, M. M., Finiguerra, M., Marzi, I., Fidecicchi, T., Ferrari, A., Genazzani, A. D., & Simoncini, T. (2021). D-Chiro-Inositol regulates insulin signaling in human adipocytes. Frontiers in Endocrinology, 12, Article 660815. https://doi.org/10.3389/fendo.2021.660815

7. Monastra, G., Vazquez-Levin, M., Bezerra Espinola, M.S. et al. D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: a pilot study. Basic Clin. Androl. 31, 13 (2021). https://doi.org/10.1186/s12610-021-00131-x

8. Naghii, M. R., Mofid, M., Asgari, A. R., Hedayati, M., & Daneshpour, M.-S. (2011). Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. Journal of Trace Elements in Medicine and Biology: Organ of the Society for Minerals and Trace Elements (GMS), 25(1), 54–58. https://doi.org/10.1016/j.jtemb.2010.10.001

9. Pizzorno L. Nothing Boring About Boron. Integr Med (Encinitas). 2015 Aug;14(4):35-48. PMID: 26770156; PMCID: PMC4712861.

10. Khan, S. S., Carter, R. E., & Greenland, P. (2023). Association of anemia with cardiovascular disease: A cohort study. The American Journal of Medicine. Advance online publication. https://doi.org/10.1016/j.amjmed.2023.01.045

11. As, P., Cs, M., Fw, B., Jw, H., & Gj, B. (1996). Zinc status and serum testosterone levels of healthy adults. Nutrition (Burbank, Los Angeles County, Calif.), 12(5). https://doi.org/10.1016/s0899-9007(96)80058-x

12. Zhuo, C., Xu, Y., Wang, H., Fang, T., Chen, J., Zhou, C., Li, Q., Liu, J., Xu, S., Yao, C., Yang, W., Yang, A., Li, B., Chen, Y., Tian, H., & Lin, C. (2021). Safety and Efficacy of High-Dose Vitamin B6 as an Adjunctive Treatment for Antipsychotic-Induced Hyperprolactinemia in Male Patients With Treatment-Resistant Schizophrenia. Frontiers in Psychiatry, 12.

13. Witwit, Suha. (2018). The Role of Vitamin B6 in Reducing Serum Prolactin in Comparison to Cabergoline. International Journal of Pharmaceutical Quality Assurance. 10. 10.25258/ijpqa.10.1.17.

14. Araújo, A. N., Wessling, A., & Bugalho, M. J. (2018). Male hypogonadism – when two endocrine causes merge in the same patient. Endocrine Abstracts, 56, P810. https://doi.org/10.1530/endoabs.56.P810

15. Janz, T., & Pearson, C. (2013). Vitamin D blood levels of Canadians. Health at a Glance. Statistics Canada Catalogue no. 82-624-X. https://www150.statcan.gc.ca/n1/pub/82-624-x/2013001/article/11727-eng.htm

16. Lee, D. M., Tajar, A., Pye, S. R., Boonen, S., Vanderschueren, D., Bouillon, R., O'Neill, T. W., Bartfai, G., Casanueva, F. F., Finn, J. D., Forti, G., Giwercman, A., Han, T. S., Huhtaniemi, I. T., Kula, K., Lean, M. E., Pendleton, N., Punab, M., Wu, F. C., & EMAS study group (2012). Association of hypogonadism with vitamin D status: the European Male Ageing Study. European journal of endocrinology, 166(1), 77–85. https://doi.org/10.1530/EJE-11-0743

17. Pilz, S., Frisch, S., Koertke, H., Kuhn, J., Dreier, J., Obermayer-Pietsch, B., Wehr, E., & Zittermann, A. (2011). Effect of Vitamin D Supplementation on Testosterone Levels in Men. Hormone and Metabolic Research, 43(3), 223–225. https://doi.org/10.1055/s-0030-1269854

18. Horii, N., Hasegawa, N., Fujie, S., Iemitsu, K., Uchida, M., Hamaoka, T., & Iemitsu, M. (2020). Effects of Dioscorea esculenta intake with resistance training on muscle hypertrophy and strength in sprint athletes. Journal of Clinical Biochemistry and Nutrition, 67(3), 338–343. https://doi.org/10.3164/jcbn.19-124

19. Isenmann, E., Alisauskas, P., Flenker, U., Schalla, J., & Diel, P. (2023). The Anabolic Effect of Fenugreek: A Systematic Review with Meta-analysis. International journal of sports medicine, 44(10), 692–703. https://doi.org/10.1055/a-2048-5925

20. Safarinejad, M. R., & Safarinejad, S. (2009). Efficacy of selenium and/or N-acetyl-cysteine for improving semen parameters in infertile men: a double-blind, placebo controlled, randomized study. The Journal of urology, 181(2), 741–751. https://doi.org/10.1016/j.juro.2008.10.015

21. Biswas, T. K., Pandit, S., Mondal, S., Biswas, S. K., Jana, U., Ghosh, T., Tripathi, P. C., Debnath, P. K., Auddy, R. G., & Auddy, B. (2010). Clinical evaluation of spermatogenic activity of processed Shilajit in oligospermia. Andrologia, 42(1), 48–56. https://doi.org/10.1111/j.1439-0272.2009.00956.x

22. Pandit, S., Biswas, S., Jana, U., De, R. K., Mukhopadhyay, S. C., & Biswas, T. K. (2016). Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers. Andrologia, 48(5), 570–575. https://doi.org/10.1111/and.12482

23. Carrasco-Gallardo, C., Guzmán, L., & Maccioni, R. B. (2012). Shilajit: a natural phytocomplex with potential procognitive activity. International journal of Alzheimer's disease, 2012, 674142. https://doi.org/10.1155/2012/674142