Herbal and nutritional medicine are commonly used to support health and wellbeing however what often lets consumers down is the use of proven extracts and medicinal synergies between bioactive compounds. Herbs and nutrients noteworthy of use in men’s health is tribulus, horny goat weed, saw palmetto, zinc, magnesium and B6 which in part are often misunderstood due to conflicting results within the scientific community. Here the aim is to explore the roles of high quality raw materials in herbal and nutritional medicine with a focus on clinical trials which provide reliable evidence based information to provide complimentary avenues to consumers and patients of health care practitioners.
Tribulus Terrestris (TT) is a chemically complex herb which has been traditionally used to improve libido, endocrine support, manage stress (adaptogen) and improve cardiovascular health. Its use in modern medical science has largely been focused on its immunomodulatory, hepatoprotective, hypolipidemic, anti-carcinogenic and aphrodisiac effects in experimental trials (1-3). Due to the phytochemical complexity of TT, there are various types of TT on the market which quite often contain very different plant bioactive compounds and qualities of these compounds. One of these phytochemicals examined in research are steroidal saponins, of which the two furostanol glycosides, protodioscin and protribestin exert powerful pharmacological activity. However, analytic studies of TT in the US alone reveals most TT contain insufficient levels of these furostanol glycosides except tribulus products derived from Bulgaria (Eastern Europe) due to soil and growing conditions (4-7). Therefore, TT products on the market don’t often contain the bioactive compounds needed to elicit potential pharmacological activity which contributes to mixed results in the literature due to widespread inconsistency in TT extracts. Many pharmaceutical and food science manufactures who know this information often mix a very low percentage of Bulgarian TT with predominantly cheaper TT herbs sourced outside of eastern Europe in order to still falsely and misleadingly make claims of potency.
The most supported effects of TT in humans is its effect on sexual function with results from a recent large randomised, double blind, placebo controlled trial published examining erectile dysfunction in those without hypoactive sexual desire disorder, found a statistically significant improvement in sexual function with no difference in adverse events (side effects) compared to placebo. Thus, supporting its efficacy and safety for sexual function (8). Furthermore, the use of TT has also been supported for its use in women for increasing sexual desire (libido) and hormone support through the hypothalamic pituitary and adrenal axis (Testosterone & DHEA) (9-13). The mechanism behind TT aphrodisiac effects are not clear however it is theorised that it may be due to an increase in androgen receptor density and/or elevations in testosterone. To date the effects on testosterone are controversial in human trials primarily due to unstandardized TT extracts being used and not tested for furostanol glycosides content, however, based on the available research it does appear to have an effect on androgen receptor content and function within the brain which is hypothesised to be responsible for the aphrodisiac properties (14-16).
Saw Palmetto (SP) is an herb containing many complex fatty acids and phytosterols. It is commonly used to treat urogenital and male reproductive conditions of which its use for benign prostatic hyperplasia (BPH) has been most documented in the literature to date. While results in human trials can appear mixed, there are significant high quality trials which supports its use for improving symptoms associated with BPH, particularly urinary flow reported within a Cochrane systematic review (17). Furthermore, based on experimental research, there is evidence to suggest SP reduces receptor binding of DHT and testosterone to the prostate and inhibits 5-alpha reductase activity, therefore somewhat exerting androgen modulating effects which is an area of future research to explore (18-21).
Epimedium sagittatum (Horny Goat Weed) is a medicinal herb which containsphytochemical properties which has been traditionally used as an aphrodisiac. However, in modern medical sciences, the compound Icariin within Epimedium species has been demonstrated to exert significant cardiovascular protective properties including ant-atherosclerotic effects, which for males, especially those who have or are taking anabolic steroids, minimising the risk of gradual cardiovascular decline should be a priority (22-24). Furthermore, bioactive compounds within Epimedium sagittatum also appear to exert smooth cell phosphodiesterase inhibitory activity similar to that of Viagra in treating erectile dysfunction. This is also the case for bioactive compounds in Tribulus Terrestris and Epimedium sagittatum which work by improving haemodynamic (blood flow dynamics) function fostering improved sexual function (24-27). Furthermore, this medicinal herb also exerts significant benefits for women
Nutritional Medicine (Minerals and Vitamins)
Of all minerals affected by exercise, zinc and magnesium would be the most disrupted minerals in those who train. Zinc specifically has been well established to support energy, metabolism, hormones, fertility and protein synthesis, of which, in those who exercise, suboptimal levels are more prevalent than people realise. Numerous very high quality trials (systematic reviews and meta-analyses) support this and the potential need for greater zinc intakes to support the needs of those who exercise, specifically in maintaining endocrine function and recovery (28-31). In addition, zinc plays a critical role in fertility, especially sperm motility, with its role in reported function being supported in the literature at the highest levels (32, 33). Furthermore, the risk of digestive cancers in men is significant but also somewhat overlooked. Suboptimal levels of magnesium and zinc is associated with higher rates of digestive cancers (colorectal), therefore those who have higher zinc intakes also appear to have lower rates of digestive cancers. While association doesn’t infer causation, the association at a meta-analyses level provides insight into the potential protective effect these minerals can have on digestive cancers (34, 35). In addition, animal studies indicate that zinc deficient states resulted in significantly lower serum concentrations of luteinizing hormone, estradiol, testosterone and greater aromatisation particularly in males suffering from hypogonadism (31, 36, 37).
Moreover, pyridoxine (B6) is a key essential vitamin that becomes depleted in those who exercise and who are under stress. Its use for the symptomatic treatment of stress has been explored and proposed to assist in the biosynthesis of neurotransmitters such as GABBA and serotonin which are adversely impacted in pyridoxine deficient states resulting in mood disturbances (38).
While research examining the efficacy of herbs such as the aforementioned at times can be mixed, it Is clear that there is limited high quality research examining the correct herbal extract types and bioactive compounds in clinical trials. Due to the chemical complexities of herbal medicines it provides promising avenues in health and wellbeing such as the diverse role of steroidal saponins and other phytochemicals in health. In the meantime, there is sufficient good quality trials which support a beneficial complimentary supplementation with products containing proven herbal and nutrient mixtures to support vitality and wellbeing.
Summary of and Key Practice Points for Male Fuel (Gen-Tec Nutrition)
Are there any side effects?
1. Wei S, Fukuhara H, Chen G, Kawada C, Kurabayashi A, Furihata M, et al. Terrestrosin D, a steroidal saponin from Tribulus terrestris L., inhibits growth and angiogenesis of human prostate cancer in vitro and in vivo. Pathobiology : journal of immunopathology, molecular and cellular biology. 2014;81(3):123-32.
2. James JT, Dubery IA. Pentacyclic triterpenoids from the medicinal herb, Centella asiatica (L.) Urban. Molecules (Basel, Switzerland). 2009;14(10):3922-41.
3. Shahid M, Riaz M, Talpur MM, Pirzada T. Phytopharmacology of Tribulus terrestris. Journal of biological regulators and homeostatic agents. 2016;30(3):785-8.
4. Rawat AKS, Srivastava A, Tiwari SS, Srivastava S. QUANTIFICATION OF PROTODIOSCIN AND PROTOTRIBESTIN IN FRUITS OF TRIBULUS TERRESTRIS L. COLLECTED FROM DIFFERENT PHYTO-GEOGRAPHICAL ZONES OF INDIA. Journal of Liquid Chromatography & Related Technologies. 2013;36(13):1810-21.
5. Man S, Gao W, Zhang Y, Wang J, Zhao W, Huang L, et al. Qualitative and quantitative determination of major saponins in Paris and Trillium by HPLC-ELSD and HPLC-MS/MS. Journal of chromatography B, Analytical technologies in the biomedical and life sciences. 2010;878(29):2943-8.
6. Dinchev D, Janda B, Evstatieva L, Oleszek W, Aslani MR, Kostova I. Distribution of steroidal saponins in Tribulus terrestris from different geographical regions. Phytochemistry. 2008;69(1):176-86.
7. Ganzera M, Bedir E, Khan IA. Determination of steroidal saponins in Tribulus terrestris by reversed-phase high-performance liquid chromatography and evaporative light scattering detection. Journal of pharmaceutical sciences. 2001;90(11):1752-8.
8. Kamenov Z, Fileva S, Kalinov K, Jannini EA. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction-A prospective, randomized, double-blind, placebo-controlled clinical trial. Maturitas. 2017;99:20-6.
9. Vale FBC, Zanolla Dias de Souza K, Rezende CR, Geber S. Efficacy of Tribulus Terrestris for the treatment of premenopausal women with hypoactive sexual desire disorder: a randomized double-blinded, placebo-controlled trial. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2017:1-4.
10. Gama CR, Lasmar R, Gama GF, Abreu CS, Nunes CP, Geller M, et al. Clinical Assessment of Tribulus terrestris Extract in the Treatment of Female Sexual Dysfunction. Clinical medicine insights Women's health. 2014;7:45-50.
11. de Souza KZ, Vale FB, Geber S. Efficacy of Tribulus terrestris for the treatment of hypoactive sexual desire disorder in postmenopausal women: a randomized, double-blinded, placebo-controlled trial. Menopause (New York, NY). 2016;23(11):1252-6.
12. Bone K. Principles and Practice of Phytotherapy (Second Edition) - Monograph In: Mills S, editor. Principles and Practice of Phytotherapy (Second Edition). Saint Louis: Churchill Livingstone; 2013. p. 353-961.
13. Romm A, Clare B, Stansbury JE, Ryan L, Trickey R, Lee L, et al. CHAPTER 5 - Menstrual Wellness and Menstrual Problems. Botanical Medicine for Women's Health. Saint Louis: Churchill Livingstone; 2010. p. 97-185.
14. Gauthaman K, Adaikan PG. Effect of Tribulus terrestris on nicotinamide adenine dinucleotide phosphate-diaphorase activity and androgen receptors in rat brain. Journal of ethnopharmacology. 2005;96(1-2):127-32.
15. Wu Y, Yang H, Wang X. The function of androgen/androgen receptor and insulin growth factor1/insulin growth factor1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise. Mol Med Rep. 2017;16(3):2931-8.
16. Kovac JR, Pan M, Arent S, Lipshultz LI. Dietary Adjuncts for Improving Testosterone Levels in Hypogonadal Males. American journal of men's health. 2016;10(6):Np109-np17.
17. Tacklind J, MacDonald R, Rutks I, Wilt TJ. Serenoa repens for benign prostatic hyperplasia. The Cochrane database of systematic reviews. 2009(2):Cd001423.
18. el-Sheikh MM, Dakkak MR, Saddique A. The effect of Permixon on androgen receptors. Acta obstetricia et gynecologica Scandinavica. 1988;67(5):397-9.
19. Di Silverio F, Monti S, Sciarra A, Varasano PA, Martini C, Lanzara S, et al. Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia. The Prostate. 1998;37(2):77-83.
20. Habib FK, Ross M, Ho CK, Lyons V, Chapman K. Serenoa repens (Permixon) inhibits the 5alpha-reductase activity of human prostate cancer cell lines without interfering with PSA expression. International journal of cancer. 2005;114(2):190-4.
21. Novara G, Giannarini G, Alcaraz A, Cozar-Olmo JM, Descazeaud A, Montorsi F, et al. Efficacy and Safety of Hexanic Lipidosterolic Extract of Serenoa repens (Permixon) in the Treatment of Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia: Systematic Review and Meta-analysis of Randomized Controlled Trials. European urology focus. 2016;2(5):553-61.
22. Fang J, Zhang Y. Icariin, an Anti-atherosclerotic Drug from Chinese Medicinal Herb Horny Goat Weed. Frontiers in pharmacology. 2017;8:734.
23. Li C, Li Q, Mei Q, Lu T. Pharmacological effects and pharmacokinetic properties of icariin, the major bioactive component in Herba Epimedii. Life sciences. 2015;126:57-68.
24. Shindel AW, Xin ZC, Lin G, Fandel TM, Huang YC, Banie L, et al. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. The journal of sexual medicine. 2010;7(4 Pt 1):1518-28.
25. Ning H, Xin ZC, Lin G, Banie L, Lue TF, Lin CS. Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells. Urology. 2006;68(6):1350-4.
26. Dell'Agli M, Galli GV, Dal Cero E, Belluti F, Matera R, Zironi E, et al. Potent inhibition of human phosphodiesterase-5 by icariin derivatives. Journal of natural products. 2008;71(9):1513-7.
27. Xin ZC, Kim EK, Lin CS, Liu WJ, Tian L, Yuan YM, et al. Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities. Asian journal of andrology. 2003;5(1):15-8.
28. Chu A, Holdaway C, Varma T, Petocz P, Samman S. Lower Serum Zinc Concentration Despite Higher Dietary Zinc Intake in Athletes: A Systematic Review and Meta-analysis. Sports Med. 2018;48(2):327-36.
29. Chu A, Petocz P, Samman S. Plasma/Serum Zinc Status During Aerobic Exercise Recovery: A Systematic Review and Meta-Analysis. Sports Med. 2017;47(1):127-34.
30. Chu A, Petocz P, Samman S. Immediate Effects of Aerobic Exercise on Plasma/Serum Zinc Levels: A Meta-analysis. Med Sci Sports Exerc. 2016;48(4):726-33.
31. Kilic M, Baltaci AK, Gunay M, Gokbel H, Okudan N, Cicioglu I. The effect of exhaustion exercise on thyroid hormones and testosterone levels of elite athletes receiving oral zinc. Neuro endocrinology letters. 2006;27(1-2):247-52.
32. Sun J, Yu G, Zhang Y, Liu X, Du C, Wang L, et al. Heavy Metal Level in Human Semen with Different Fertility: a Meta-Analysis. Biological trace element research. 2017;176(1):27-36.
33. Irani M, Amirian M, Sadeghi R, Lez JL, Latifnejad Roudsari R. The Effect of Folate and Folate Plus Zinc Supplementation on Endocrine Parameters and Sperm Characteristics in Sub-Fertile Men: A Systematic Review and Meta-Analysis. Urology journal. 2017;14(5):4069-78.
34. Chen GC, Pang Z, Liu QF. Magnesium intake and risk of colorectal cancer: a meta-analysis of prospective studies. Eur J Clin Nutr. 2012;66(11):1182-6.
35. Li P, Xu J, Shi Y, Ye Y, Chen K, Yang J, et al. Association between zinc intake and risk of digestive tract cancers: A systematic review and meta-analysis. Clinical Nutrition. 2014;33(3):415-20.
36. Om AS, Chung KW. Dietary zinc deficiency alters 5 alpha-reduction and aromatization of testosterone and androgen and estrogen receptors in rat liver. The Journal of nutrition. 1996;126(4):842-8.
37. Netter A, Hartoma R, Nahoul K. Effect of zinc administration on plasma testosterone, dihydrotestosterone, and sperm count. Archives of andrology. 1981;7(1):69-73.
38. McCarty MF. High-dose pyridoxine as an 'anti-stress' strategy. Medical hypotheses. 2000;54(5):803-7.