Man Pulse
SCIENTIFIC RESEARCH ON THE FOLLOWING INGREDIENTS:
Tribulus terrestris
Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction-A prospective, randomized, double-blind, placebo-controlled clinical trial
Abstract
Objective: The primary objectives were to compare the efficacy of extracts of the plant Tribulus terrestris (TT; marketed as Tribestan), in comparison with placebo, for the treatment of men with erectile dysfunction (ED) and with or without hypoactive sexual desire disorder (HSDD), as well as to monitor the safety profile of the drug. The secondary objective was to evaluate the level of lipids in blood during treatment.
Participants and design: Phase IV, prospective, randomized, double-blind, placebo-controlled clinical trial in parallel groups. This study included 180 males aged between 18 and 65 years with mild or moderate ED and with or without HSDD: 90 were randomized to TT and 90 to placebo. Patients with ED and hypertension, diabetes mellitus, and metabolic syndrome were included in the study. In the trial, an herbal medicine intervention of Bulgarian origin was used (Tribestan®, Sopharma AD). Each Tribestan® film-coated tablet contains the active substance Tribulus terrestris, herba extractum siccum (35-45:1) 250mg which is standardized to furostanol saponins (not less than 112.5mg). Each patient received orally 3×2 film-coated tablets daily after meals, during the 12-week treatment period. At the end of each month, participants' sexual function, including ED, was assessed by International Index of Erectile Function (IIEF) Questionnaire and Global Efficacy Question (GEQ). Several biochemical parameters were also determined. The primary outcome measure was the change in IIEF score after 12 weeks of treatment. Complete randomization (random sorting using maximum allowable% deviation) with an equal number of patients in each sequence was used. This randomization algorithm has the restriction that unequal treatment allocation is not allowed; that is, all groups must have the same target sample size. Patients, investigational staff, and data collectors were blinded to treatment. All outcome assessors were also blinded to group allocation.
Results: 86 patients in each group completed the study. The IIEF score improved significantly in the TT group compared with the placebo group (P<0.0001). For intention-to-treat (ITT) there was a statistically significant difference in change from baseline of IIEF scores. The difference between TT and placebo was 2.70 (95% CI 1.40, 4.01) for the ITT population. A statistically significant difference between TT and placebo was found for Intercourse Satisfaction (p=0.0005), Orgasmic Function (p=0.0325), Sexual Desire (p=0.0038), Overall Satisfaction (p=0.0028) as well as in GEQ responses (p<0.0001), in favour of TT. There were no differences in the incidence of adverse events (AEs) between the two groups and the therapy was well tolerated. There were no drug-related serious AEs. Following the 12-week treatment period, significant improvement in sexual function was observed with TT compared with placebo in men with mild to moderate ED. TT was generally well tolerated for the treatment of ED.
Source: 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 May;99:20-26. doi: 10.1016/j.maturitas.2017.01.011. Epub 2017 Feb 12. PMID: 28364864.
Tongkat Ali (Eurycoma longifolia)
Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men
Abstract
A randomized, double-blind, placebo-controlled, parallel group study was carried out to investigate the clinical evidence of E. longifolia in men. Primary endpoints were the Quality of Life investigated by SF-36 questionnaire and Sexual Well-Being investigated by International Index of Erectile Function (IIEF) and Sexual Health Questionnaires (SHQ); Seminal Fluid Analysis (SFA), fat mass and safety profiles. The E. longifolia (EL) group significantly improved in the domain Physical Functioning of SF-36, from baseline to week 12 compared to placebo (P = 0.006) and in between group at week 12 (P = 0.028). All safety parameters were comparable to placebo.
Source: Ismail SB, Wan Mohammad WM, George A, Nik Hussain NH, Musthapa Kamal ZM, Liske E. Randomized Clinical Trial on the Use of PHYSTA Freeze-Dried Water Extract of Eurycoma longifolia for the Improvement of Quality of Life and Sexual Well-Being in Men. Evid Based Complement Alternat Med. 2012;2012:429268. doi: 10.1155/2012/429268. Epub 2012 Nov 1. PMID: 23243445; PMCID: PMC3518798.
Ashwagandha
A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha (Withania somnifera) in Aging, Overweight Males
Abstract
Ashwagandha (Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. In this 16-week, randomized, double-blind, placebo-controlled, crossover study, its effects on fatigue, vigor, and steroid hormones in aging men were investigated. Overweight men aged 40–70 years, with mild fatigue, were given a placebo or an ashwagandha extract (Shoden beads, delivering 21 mg of withanolide glycosides a day) for 8 weeks. Outcome measures included the Profile of Mood States, Short Form (POMS-SF), Aging Males’ Symptoms (AMS) questionnaire, and salivary levels of DHEA-S, testosterone, cortisol, and estradiol. Fifty-seven participants were enrolled, with 50 people completing the first 8-week period of the trial and 43 completing all 16 weeks. Improvements in fatigue, vigor, and sexual and psychological well-being were reported over time, with no statistically significant between-group differences. Ashwagandha intake was associated with an 18% greater increase in DHEA-S (p = .005) and 14.7% greater increase in testosterone (p = .010) compared to the placebo. There were no significant between-group differences in cortisol and estradiol. In conclusion, the intake of a standardized ashwagandha extract (Shoden beads) for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being. Further studies with larger sample sizes are required to substantiate the current findings.
Source: Lopresti AL, Drummond PD, Smith SJ. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha ( Withania somnifera) in Aging, Overweight Males. Am J Mens Health. 2019 Mar-Apr;13(2):1557988319835985. doi: 10.1177/1557988319835985. PMID: 30854916; PMCID: PMC6438434.
Fenugreek
Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study
Abstract
Purpose To evaluate the efficacy and safety of the glycoside fraction of fenugreek (Trigonella foenum-graecum) seeds (Fenu-FG) on physiological parameters related to muscle anabolism, androgenic hormones, and body fat in healthy male subjects during an 8-week resistance training program using a prospective, randomized, double-blind, placebo controlled design.
Methods: Sixty healthy male subjects were randomized to ingest capsules of Fenu-FG (1 capsule of 300 mg, twice per day) or the matching placebo at a 1:1 ratio. The subjects participated in a supervised 4-day per week resistance-training program for 8 weeks. The outcome measurements were recorded at recruitment (baseline) and at the end of the treatment (8 weeks). The efficacy outcome included serum testosterone (total and free) levels, muscle strength and repetitions to failure, metabolic markers for anabolic activity (serum creatinine and blood urea nitrogen), and % body fat. The standard safety measurements such as adverse events monitoring, vital signs, hematology, biochemistry, and urinalysis were performed.
Results: Fenu-FG supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo. Fenu-FG treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplementation was found to be safe and well-tolerated.
Conclusion: Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects.
Source: Wankhede S, Mohan V, Thakurdesai P. Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: A randomized controlled pilot study. J Sport Health Sci. 2016 Jun;5(2):176-182. doi: 10.1016/j.jshs.2014.09.005. Epub 2015 Mar 7. Erratum in: J Sport Health Sci. 2018 Apr;7(2):251. doi: 10.1016/j.jshs.2018.03.001. PMID: 30356905; PMCID: PMC6191980.
D-Aspartic acid
The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats
Abstract
Background: D-aspartic acid is an amino acid present in neuroendocrine tissues of invertebrates and vertebrates, including rats and humans. Here we investigated the effect of this amino acid on the release of LH and testosterone in the serum of humans and rats. Furthermore, we investigated the role of D-aspartate in the synthesis of LH and testosterone in the pituitary and testes of rats, and the molecular mechanisms by which this amino acid triggers its action.
Methods: For humans: A group of 23 men were given a daily dose of D-aspartate (DADAVIT) for 12 days, whereas another group of 20 men were given a placebo. For rats: A group of 10 rats drank a solution of either 20 mM D-aspartate or a placebo for 12 days. Then LH and testosterone accumulation was determined in the serum and D-aspartate accumulation in tissues. The effects of D-aspartate on the synthesis of LH and testosterone were gauged on isolated rat pituitary and Leydig cells. Tissues were incubated with D-aspartate, and then the concentration (synthesis) of LH and cGMP in the pituitary and of testosterone and cAMP in the Leydig cells was determined.
Results: In humans and rats, sodium D-aspartate induces an enhancement of LH and testosterone release. In the rat pituitary, sodium D-aspartate increases the release and synthesis of LH through the involvement of cGMP as a second messenger, whereas in rat testis Leydig cells, it increases the synthesis and release of testosterone and cAMP is implicated as second messenger. In the pituitary and in testes D-Asp is synthesized by a D-aspartate racemase which convert L-Asp into D-Asp. The pituitary and testes possesses a high capacity to trapping circulating D-Asp from hexogen or endogen sources.
Conclusions: D-aspartic acid is a physiological amino acid occurring principally in the pituitary gland and testes and has a role in the regulation of the release and synthesis of LH and testosterone in humans and rats.
Source: Enza Topo, Andrea Soricelli, Antimo D'Aniello, Salvatore Ronsini, and Gemma D'Aniello. “The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats” Reproductive Biology & Endocrinology (2009) 27;7:120.
Vitamin D
Effect of vitamin D supplementation on testosterone levels in men
Abstract
The male reproductive tract has been identified as a target tissue for vitamin D, and previous data suggest an association of 25-hydroxyvitamin D [25(OH)D] with testosterone levels in men. We therefore aimed to evaluate whether vitamin D supplementation influences testosterone levels in men. Healthy overweight men undergoing a weight reduction program who participated in a randomized controlled trial were analyzed for testosterone levels. The entire study included 200 nondiabetic subjects, of whom 165 participants (54 men) completed the trial. Participants received either 83 μg (3,332 IU) vitamin D daily for 1 year (n = 31) or placebo (n =2 3). Initial 25(OH)D concentrations were in the deficiency range (< 50 nmol/l) and testosterone values were at the lower end of the reference range (9.09-55.28 nmol/l for males aged 20-49 years) in both groups. Mean circulating 25(OH)D concentrations increased significantly by 53.5 nmol/l in the vitamin D group, but remained almost constant in the placebo group. Compared to baseline values, a significant increase in total testosterone levels (from 10.7 ± 3.9 nmol/l to 13.4 ± 4.7 nmol/l; p < 0.001), bioactive testosterone (from 5.21 ± 1.87 nmol/l to 6.25 ± 2.01 nmol/l; p = 0.001), and free testosterone levels (from 0.222 ± 0.080 nmol/l to 0.267 ± 0.087 nmol/l; p = 0.001) were observed in the vitamin D supplemented group. By contrast, there was no significant change in any testosterone measure in the placebo group. Our results suggest that vitamin D supplementation might increase testosterone levels. Further randomized controlled trials are warranted to confirm this hypothesis.
Source: Pilz S, Frisch S, Koertke H, Kuhn J, Dreier J, Obermayer-Pietsch B, Wehr E, Zittermann A. Effect of vitamin D supplementation on testosterone levels in men. Horm Metab Res. 2011 Mar;43(3):223-5. doi: 10.1055/s-0030-1269854. Epub 2010 Dec 10. PMID: 21154195.
Ginger Extract
Ginger and Testosterone
Abstract
Enhancing and protecting testosterone production is one target for many scientists because of its crucial role as a primary sex hormone in males. Several in vivo trials have utilized different dietary supplements and medicinal plants to enhance testosterone production in males. Since 1991, various in-vivo, as well as basic research studies, have discovered a link between ginger (Zingiber officinale) and testosterone. However, such a link has not yet been collectively reviewed. This review systematically discusses and summarizes the effect of ginger and ginger extracts on testosterone. To achieve this contribution, we searched the PubMed, Scopus, and Web of Science databases for English language articles (full texts or abstracts) from November 1991 through August 2018 using the keywords “ginger” and “Zingiber officinale” versus “testosterone”. Additionally, the references from related published articles were also reviewed, only if relevant. In conclusion, the mainstream of research that links ginger to testosterone demonstrated that ginger supplementation, particularly in oxidative stress conditions, enhances testosterone production in males. The mechanisms by which this occurs mainly by enhancing luteinizing hormone (LH) production, increasing the level of cholesterol in the testes, reducing oxidative stress and lipid peroxidation in the testes, enhancing the activity of the antioxidant enzymes, normalizing blood glucose, increasing blood flow in the testes, increasing testicular weight, and recycling testosterone receptors. However, the effect of ginger on testosterone is not yet confirmed in humans. Therefore, clinical studies in this context of research are imperative.
Effect of Ginger on Testosterone: Until now, almost all studies that have found a direct link between ginger and testosterone were in vivo studies. Table 1 summarizes the direct studies conducted on ginger and its extracts or derived compounds and their reported effects on serum testosterone. Almost all of these studies were conducted on diabetic rat models. As shown in the table, diabetic and hypertensive rat models supplemented with ginger and its extracts had a higher serum testosterone level compared to controls. While ginger-derived compounds (zingerone, geraniol, and 6-gingerol), when taken separately, did not affect serum testosterone level in diabetic rats.
Conclusions and Future Perspectives: To date, the mainstream of research linking dietary ginger to testosterone has revealed that ginger or ginger extracts have an impact on testosterone as testosterone production was enhanced upon ginger supplementation.
The mechanisms through which ginger enhances testosterone production are mainly by increasing LH production, increasing the level of cholesterol in testes, reducing oxidative stress and lipid peroxidation in the testes, enhancing the activity of certain antioxidant enzymes, normalizing blood glucose, enhancing nitric oxide production and increasing blood flow in Leydig cells, increasing testicular weight, and recycling testosterone receptors.
However, the effect of ginger or ginger extracts on testosterone is not yet confirmed in humans. Therefore, human studies in this context of research are of great importance.
Source: Banihani SA. Ginger and Testosterone. Biomolecules. 2018 Oct 22;8(4):119. doi: 10.3390/biom8040119. PMID: 30360442; PMCID: PMC6316093.
Cordyceps
Abstract
To determine the effects of a mushroom blend containing cordyceps militaris on high intensity exercise after 1- and 3-weeks of supplementation. Twenty-eight individuals (Mean ± SD; Age=22.7 ± 4.1 yrs; Height=175.4 ± 8.7 cm; Weight=71.6 ± 12.0 kg) participated in this randomized, repeated measures, double-blind, placebo-controlled design. Maximal oxygen consumption (VO2max), time to exhaustion (TTE), and ventilatory threshold (VT) were measured during a maximal graded exercise test on a cycle ergometer. Relative peak power output (RPP), average power output (AvgP), and percent drop (%drop) were recorded during a 3-minute maximal cycle test with resistance at 4.5% body weight. Subjects consumed 4 g·d−1 mushroom blend (MR) or maltodextrin (PL) for 1 week. Ten volunteers supplemented for an additional 2 weeks. Exercise tests were separated by at least 48-hours and repeated following supplementation periods. One week of supplementation elicited no significant time × treatment interaction for VO2max (p=0.364), VT (p=0.514), TTE (p=0.540), RPP (p=0.134), AvgP (p=0.398), or %drop (p=0.823). After 3-weeks, VO2max significantly improved (p=0.042) in MR (+4.8 ml·kg−1·min−1), but not PL (+0.9 ml·kg−1·min−1). Analysis of 95% confidence intervals revealed significant improvements in TTE after 1- (+28.1 s) and 3-weeks (+69.8 s) in MR, but not PL, with additional improvements in VO2max (+4.8 ml·kg−1·min−1) and VT (+0.7 l·min−1) after 3-weeks. Acute supplementation with a cordyceps militaris containing mushroom blend may improve tolerance to high intensity exercise; greater benefits may be elicited with consistent chronic supplementation.
Methods: Prior to testing, all participants signed a written informed consent approved by the University's Institutional Review Board and underwent a 12-lead electrocardiogram and physical examination. Once cleared for participation, baseline testing consisted of a maximal oxygen consumption (VO2max) test and a three-minute maximal cycle test, separated by a minimum of 48 hours and no more than one week. In a randomized, double-blind, placebo-controlled design, participants were randomly assigned, using Random Allocation Software (Version 1.0.0; Isfahan, Iran), into one of two treatment groups: mushroom (MR) or placebo (PL). Subjects ingested either 1.3 grams of a mushroom blend (PeakO2, Compound Solutions, Inc., USA; Table 3) or 1.3 grams of maltodextrin (PL) in the form to two capsules, taken orally three times per day (4 grams daily) for one week (Phase I). Capsules were identical in color and taste and packaged in white opaque bottles, randomized and coded by the manufacturer. Participants were randomized using block randomization with codes de-identified from separate white envelopes. Following the one-week supplementation period, baseline exercise tests were repeated. A sub-set of participants volunteered to complete an additional two weeks of supplementation (Phase II), for a total of three weeks of supplementation, followed by exercise testing.
In conclusion, one week of supplementation with a cordyceps militaris containing mushroom blend had minimal benefits to high intensity aerobic and anaerobic exercise. Greater benefits may be elicited with longer supplementation, with potential improvements in oxygen consumption, ventilatory threshold, time to exhaustion, and relative peak power output at a dosage of 4 g·d−1. Future studies should aim to establish dosage for maximal ergogenic benefits.
Source: Hirsch KR, Smith-Ryan AE, Roelofs EJ, Trexler ET, Mock MG. Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation. J Diet Suppl. 2017 Jan 2;14(1):42-53. doi: 10.1080/19390211.2016.1203386. Epub 2016 Jul 13. PMID: 27408987; PMCID: PMC5236007.
Zinc
Abstract
Zinc (Zn) is the second most abundant trace element in human, which can’t be stored in the body, thus regular dietary intake is required. This review explained the physiological and pathogenesis roles of zinc in men’s health and its potentials in germination, quality of sperm, and fertilization. Our investigation showed that Zn contained many unique properties in human, especially males. The antioxidant quality is one of them. Also, the increased reactive oxygen species levels in the seminal plasma of men who are both infertile and smokers influence the Zn content of seminal plasma in a way that physiology of spermatozoa can be affected as well. Moreover, Zn acts as a toxic repercussionagainst heavy metals and cigarette inflammatory agents. Zinc as a hormone balancer helps hormones such as testosterone, prostate and sexual healthand functions as an antibacterial agent in men’s urea system. It plays a role in epithelial integrity, showing that Zn is essential for maintaining the lining of the reproductive organs and may have a regulative role in the progress of capacitation and acrosome reaction. In contrast, Zn deficiency impedes spermatogenesis and is a reason for sperm abnormalities and has a negative effect on serum testosterone concentration. Based on these findings, Zn microelement is very essential for male fertility. It could be considered as a nutrient marker with many potentials in prevention, diagnosis, and treatment of male infertility.
Roles of Zn in health: The human body contains 2–3 grams (2000–3000 milligrams) of Zn and nearly 90% is found in muscles and bones. The nearby organs include prostate, liver, the gastrointestinal tract; kidney, skin, lung, adrenals, brain, heart, eyes and pancreas contain estimable concentrations of Zn. Blood tests for Zn deficiency are inaccurate because majority of Zn is cumulative inside cells and is not free in the blood. There are several reasons that Zn is important to men’s health. Assisting immune function, patronage of healthy cell growth, having a role in preserving prostate health, sexual health and testosterone hormone levels are typical examples. It has been demonstrated that Zn plays a significant role in reproductive functions (14, 17). Hosseinzadeh Colager et al. reported Zn levels in fertile groups for whom the seminal plasma was significantly higher than the level in infertile groups. The level of Zn in fertile men was 14.08± 2.01 and in the infertile group was 10.32±2.98 (mg/100 ml) (6).
There are many reports that showed reduction or increase in consumption of Zn which let to overindulge vis-a-vis deficiency damages in many of the human organs (Table 1). For example, Zn deficiency is correlated with reduction in testis volume, a decrease in testicular weight, hypogonadism, gonadal dysfunction, inadequate development of secondary sex specifications in human, shrinkage of seminiferous tubules, the failure of spermatogenesis, male gonad growth and hypogonadism (8). And so, there are many reports for Zn-physiological roles in human (Table 2), including its role in gonads- and some enzyme-functions, treatments of some diseases, and better function of apoptosis and immune systems. Some of these Zn-physiological roles are indicated below.
Conclusion: Adequate Zn content of seminal plasma is needed for men’s health, germination, normal sperm function and fertilization. In contrast, highly toxic content of Zn may have negative effect on sperm quality. Although it certainly cannot be said that seminal Zn deficiency causes infertility, many studies prove that the association of the seminal plasma Zn concentration with physiological and pathogenesis roles of sperm and its quality parameters indicates that Zn deficiency is a menace for sperm dysfunction and male fertility. On the other hand, levels of seminal plasma in Zn may contribute to the effect of cigarette smoking on sperm parameters. Smokers and infertile men with increased ROS levels are susceptible to Zn deficiency in semen, decrease in antioxidant levels and increase in oxidative stress in their seminal fluid. Smokers may not experience decreased fertility but smokers and infertile men with severe Zn deficiency, if they quit smoking or take Zn supplementation, can benefit from it. Therefore, further studies, especially in men with a history of infertility, are required to prove this claim and the assessment of seminal Zn level in IVF center will help in such cases.
Source: Fallah A, Mohammad-Hasani A, Colagar AH. Zinc is an Essential Element for Male Fertility: A Review of Zn Roles in Men's Health, Germination, Sperm Quality, and Fertilization. J Reprod Infertil. 2018 Apr-Jun;19(2):69-81. PMID: 30009140; PMCID: PMC6010824.
References:
- https://www.sciencedirect.com/science/article/pii/S2095254615001271?via%3Dihub
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6274257/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438434/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191980/
- https://pubmed.ncbi.nlm.nih.gov/19860889/
- https://pubmed.ncbi.nlm.nih.gov/21154195/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6316093/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC5236007/
- https://pmc.ncbi.nlm.nih.gov/articles/PMC6010824/