madman
Super Moderator
ABSTRACT
Ethno-pharmacological relevance: Phytotherapeutic approaches have been widely proposed to improve male health. Despite the well-touted effects of Tribulus (Tribulus Terrestris L) on men's health, optimal phytotherapy remains an elusive challenge.
Aim of the review: We sought to critically analyze the evidence in the phytotherapeutic literature beyond the effects of Tribulus on testosterone (T) concentration and sperm analysis to also include indications for prostate health.
Materials and methods: A focused literature search was conducted to include studies published in Cochrane, Pubmed, and Web of Science databases between the years 2002 and 2018.
Results: The use of Tribulus and maca (Lepidium meyenii Walp, Brassicaceae) were not scientifically supported to improve serum T levels in men. Moderate evidence supports the use of long Jack (Eurycoma longifolia Jack, Simaroubaceae), mucuna (Mucuna pruriens (L.) DC., Fabaceae), ashwagandha (Withania somnifera (L.) Dunal, Solanaceae), fenugreek (Trigonella foenum-graceum L., Fabaceae), and black seeds (Nigella sativa L., Ranunculaceae) to increase total T and improve seminal parameters. Data suggests an increase in total T with the use of 5000 mg/d of powdered mucuna seed and ashwagandha root (151 and 143 ng/dL, respectively) over a 12- week period in patients with oligozoospermia. The use of mucuna was supported for patients with oligozoospermia to improve sperm parameters, with an increase of 83.3 million/mL observed after the use of 5000 mg/d of powdered mucuna seed over a 12-week period. Evidence supporting the use of saw palmetto (Serenoa repens, (W.Bartram) Small, Arecaceae) to improve prostate health remains equivocal; whereas, evidence supporting the use of Pygeum africanum Hook.f., Rosaceae, Urtica dioica L., Urticaceae, beta-sitosterols, pollen extract, onion, garlic, and tomato, appears favorable and promising.
Conclusion: Scientific evidence supports the use of mucuna and ashwagandha as phytotherapeutics for improving serum T concentrations and semen parameters. Despite inconclusive evidence for use of Tribulus as a T booster, it may provide advantageous effects on sperm parameters in men with idiopathic infertility. Nutraceutical strategies and some phytotherapeutics may also be effective to promote prostate health. Popular foodstuffs (onion, garlic, and tomato), nutraceutical agents (pollen extract and beta-sitosterols), and herbal medicines (Pygeum africanum and Urtica dioica) are rational approaches.
3. Tribulus Terrestris: myth or reality?
4. Total and free testosterone increase
5. LH and FSH variations
6. Sperm parameters improvement
Given the previous examination of Tribulus administration repercussions in the recent systematic review by Sanagoo et al., Table 2 summarizes phytotherapeutics with the potential to ameliorate sperm parameters beyond the use of Tribulus (Sanagoo et al., 2019). Improvements in sperm count and motility were further noted. For instance, among studies that detected increases in sperm count, the changes occurred between 5.7 and 83.3 million/mL (Table 2). Interestingly, mucuna supplementation was again noteworthy, reporting the highest increase in sperm count, after the use of 5000 mg/d of mucuna seeds, during 12-week administration in patients with oligozoospermia (Ahmad et al., 2008). Importantly, in the Tambi and Imran study, eleven spontaneous pregnancies involving female partners of male study subjects were reported over the course of nine months using 200 mg/d of a soluble extract of long Jack, with male patients presenting a mean infertility history of 5.3 years (Bin Mohd Tambi and Imran, 2010a). To date, only one study analyzed the effects of black seeds in men, with daily administration of 5 mL in oil form improving sperm parameters in infertile subjects after two months of intervention (Kolahdooz et al., 2014).
7. Testosterone and sperm pathways
8. Libido increase in men and women
9. Prostate support
9.1. Phytotherapy based on systematic reviews and meta-analyses
9.2. Promising herbal medicines for male health: in vitro and in vivo studies
9.2.1. Angelica Gigas Nakai
9.2.2. Cynanchum wilfordii Cyna
9.2.3. Moringa oleifera
10. Foodstuffs vs. phytoterapics
10.1. Prostate health and dietary strategies
10.2. Traditional food spices
10.2.1. Chili peppers/Capsaicin
10.2.2. Cinnamon
10.2.3. Ginger
10.2.4. Curcumin
10.2.5. Garlic
15. Limitations and perspectives
Overall, the effect of phytotherapeutics on low total T levels was not analyzed in human studies in this review. Only Tambi et al. analyzed the impact of phytotherapy using long Jack in individuals with extremely low T levels due to hypogonadism (Tambi et al., 2012). Albeit, being diagnosed with hypogonadism, the increase in T levels by long Jack administration was not sufficient to achieve a normal range in this study. Therefore, further investigations are warranted to analyze other phytotherapeutics under hypogonadal conditions.
In addition to hypogonadism, the treatment of hyperprolactinemia with herbal medicines also lacks proven potential. Although mucuna may decrease serum prolactin levels in men, the reported physiological values in these studies do not correspond to hyperprolactinemia, whose primary therapies consist mainly of bromocriptine (Triebel et al., 2017), cabergoline (Colao et al., 2006), and selegiline (Kodesh et al., 2003). Moreover, moringa requires paramount value given to prolactin analysis and clarification pertaining to possible mechanisms that may ameliorate male health. Further research with moringa leaf extract has shown a capacity to modulate dopamine and inhibit monoamine oxidase B (MAO-B) in stressed male rats, likely due to a high content of phenylalanine (Prabsattroo et al., 2015). Additionally, another future research direction is the use of moringa as a galactagogue agent for pregnant patients (Raguindin et al., 2014).
There are currently no upper limits for herbal medicines in humans. In this field, there is a critical need to establish the upper limits of herbal medicines for safety and efficacy reasons. First, herbal medicines are no different than traditional therapeutics in the sense that both contain biologically active substances and exert different levels of xenobiotic metabolism. Hence, herbal medicines have the potential for toxicity and harm but are amenable to toxicological analysis in the same manner as pharmaceuticals. In regards to efficacy, the use of the long Jack aqueous extract from 200 to 400 mg/d and dry fenugreek extract from 500 to 600 mg/d exhibit potential to improve T levels and sperm production (Henkel et al., 2014; Ismail et al., 2012; Maheshwari et al., 2017; Rao et al., 2016; Steels et al., 2011; Tambi et al., 2012; Udani et al., 2014). In this scenario, higher doses might promote greater increases in T levels in a research setting, but these effects, in clinical practice, could come with the price of increasing toxicity and lower safety. Hence, thorough toxicology studies are needed to establish upper limits and safety margins.
In the studies assessed in this review, the highest reported doses of phytotherapeutics occurred in studies using maca, mucuna, and ashwagandha (Ahmad et al., 2008; Ambiye et al., 2013; Gonzales et al., 2003; Shukla et al., 2009). In the studies of maca and ashwagandha, the root powder extract was used, while in the studies of mucuna, the research was conducted using the seed powder extract (Ambiye et al., 2013; Gonzales et al., 2003). Maca intake is frequent in Peru as a common food item (Zhang et al., 2015). Hence, maca administration may be further studied regarding larger doses, since it is considered a food item, and exhibits sweet taste with good general acceptability. Still, the use of maca to improve T levels lacks scientific support, which further strengthens the need for further studies to evaluate and clarify clinical potential (Beharry and Heinrich, 2018).
Black seeds positively influence sperm parameters, Leydig cells, reproductive organs, and sexual hormones. However, the current body of evidence for black seeds is based on animal studies as detailed in a 2015 systematic review (Mahdavi et al., 2015). Hence, there is insufficient evidence to make recommendations on the use of black seeds as an adjunct therapy for infertility. Given that only one study analyzed the effects of black seeds in human sperm parameters (Kolahdooz et al., 2014), further investigation is warranted to determine the magnitude of effects on T concentrations.
Finally, emerging human studies have shown the use of nuts and other foodstuffs to support healthy sperm parameters (Robbins et al., 2012; Salas-Huetos et al., 2018). Thus, more research is required to identify foodstuffs with potential effects on fertility and T levels and map the potential actions involved with supporting fertility, since nuts and other foodstuffs have already demonstrated clinical importance with other conditions such as prostate disease (Curtis Nickel et al., 2008; Galeone et al., 2007; Rowles et al., 2018).
16. Conclusion
The use of mucuna (Mucuna pruriens (L.) DC., Fabaceae), long Jack (Eurycoma longifolia Jack, Simaroubaceae), ashwagandha (Withania somnifera (L.) Dunal, Solanaceae), fenugreek (Trigonella foenum-graceum L., Fabaceae), and black seed (Nigella sativa L., Ranunculaceae) has been shown to exert promising effects on T and sperm parameters. However, the increases in serum T caused by these compounds, although useful to address fertility, are largely irrelevant towards body composition and/or enhanced sports performance. Thus far, tribulus (Tribulus terrestris L., Zygophyllaceae) and maca (Lepidium meyenii Walp, Brassicaceae) remain unsubstantiated T boosters contingent to the dose tested. Tribulus administration can provide favorable effects on sperm parameters in men with idiopathic infertility. For prostate support, the use of saw palmetto (Serenoa repens, (W.Bartram) Small, Arecaceae) is controversial, whereas, the use of Pygeum africanum Hook.f., Rosaceae, Urtica dioica L., Urticaceae, and nutraceutical agents such as beta-sitosterols, pollen extract, and some food items (e.g. onion, garlic, and tomato) confers propitious clinical value. Upper dose limits of phytotherapeutics widely used for male health are unknown and warrant further toxicology studies, as the ascertainment of higher doses is needed, especially in individuals with low T levels, to clarify findings of previous studies and inform recommended dosage guidelines.
Ethno-pharmacological relevance: Phytotherapeutic approaches have been widely proposed to improve male health. Despite the well-touted effects of Tribulus (Tribulus Terrestris L) on men's health, optimal phytotherapy remains an elusive challenge.
Aim of the review: We sought to critically analyze the evidence in the phytotherapeutic literature beyond the effects of Tribulus on testosterone (T) concentration and sperm analysis to also include indications for prostate health.
Materials and methods: A focused literature search was conducted to include studies published in Cochrane, Pubmed, and Web of Science databases between the years 2002 and 2018.
Results: The use of Tribulus and maca (Lepidium meyenii Walp, Brassicaceae) were not scientifically supported to improve serum T levels in men. Moderate evidence supports the use of long Jack (Eurycoma longifolia Jack, Simaroubaceae), mucuna (Mucuna pruriens (L.) DC., Fabaceae), ashwagandha (Withania somnifera (L.) Dunal, Solanaceae), fenugreek (Trigonella foenum-graceum L., Fabaceae), and black seeds (Nigella sativa L., Ranunculaceae) to increase total T and improve seminal parameters. Data suggests an increase in total T with the use of 5000 mg/d of powdered mucuna seed and ashwagandha root (151 and 143 ng/dL, respectively) over a 12- week period in patients with oligozoospermia. The use of mucuna was supported for patients with oligozoospermia to improve sperm parameters, with an increase of 83.3 million/mL observed after the use of 5000 mg/d of powdered mucuna seed over a 12-week period. Evidence supporting the use of saw palmetto (Serenoa repens, (W.Bartram) Small, Arecaceae) to improve prostate health remains equivocal; whereas, evidence supporting the use of Pygeum africanum Hook.f., Rosaceae, Urtica dioica L., Urticaceae, beta-sitosterols, pollen extract, onion, garlic, and tomato, appears favorable and promising.
Conclusion: Scientific evidence supports the use of mucuna and ashwagandha as phytotherapeutics for improving serum T concentrations and semen parameters. Despite inconclusive evidence for use of Tribulus as a T booster, it may provide advantageous effects on sperm parameters in men with idiopathic infertility. Nutraceutical strategies and some phytotherapeutics may also be effective to promote prostate health. Popular foodstuffs (onion, garlic, and tomato), nutraceutical agents (pollen extract and beta-sitosterols), and herbal medicines (Pygeum africanum and Urtica dioica) are rational approaches.
3. Tribulus Terrestris: myth or reality?
4. Total and free testosterone increase
5. LH and FSH variations
6. Sperm parameters improvement
Given the previous examination of Tribulus administration repercussions in the recent systematic review by Sanagoo et al., Table 2 summarizes phytotherapeutics with the potential to ameliorate sperm parameters beyond the use of Tribulus (Sanagoo et al., 2019). Improvements in sperm count and motility were further noted. For instance, among studies that detected increases in sperm count, the changes occurred between 5.7 and 83.3 million/mL (Table 2). Interestingly, mucuna supplementation was again noteworthy, reporting the highest increase in sperm count, after the use of 5000 mg/d of mucuna seeds, during 12-week administration in patients with oligozoospermia (Ahmad et al., 2008). Importantly, in the Tambi and Imran study, eleven spontaneous pregnancies involving female partners of male study subjects were reported over the course of nine months using 200 mg/d of a soluble extract of long Jack, with male patients presenting a mean infertility history of 5.3 years (Bin Mohd Tambi and Imran, 2010a). To date, only one study analyzed the effects of black seeds in men, with daily administration of 5 mL in oil form improving sperm parameters in infertile subjects after two months of intervention (Kolahdooz et al., 2014).
7. Testosterone and sperm pathways
8. Libido increase in men and women
9. Prostate support
9.1. Phytotherapy based on systematic reviews and meta-analyses
9.2. Promising herbal medicines for male health: in vitro and in vivo studies
9.2.1. Angelica Gigas Nakai
9.2.2. Cynanchum wilfordii Cyna
9.2.3. Moringa oleifera
10. Foodstuffs vs. phytoterapics
10.1. Prostate health and dietary strategies
10.2. Traditional food spices
10.2.1. Chili peppers/Capsaicin
10.2.2. Cinnamon
10.2.3. Ginger
10.2.4. Curcumin
10.2.5. Garlic
15. Limitations and perspectives
Overall, the effect of phytotherapeutics on low total T levels was not analyzed in human studies in this review. Only Tambi et al. analyzed the impact of phytotherapy using long Jack in individuals with extremely low T levels due to hypogonadism (Tambi et al., 2012). Albeit, being diagnosed with hypogonadism, the increase in T levels by long Jack administration was not sufficient to achieve a normal range in this study. Therefore, further investigations are warranted to analyze other phytotherapeutics under hypogonadal conditions.
In addition to hypogonadism, the treatment of hyperprolactinemia with herbal medicines also lacks proven potential. Although mucuna may decrease serum prolactin levels in men, the reported physiological values in these studies do not correspond to hyperprolactinemia, whose primary therapies consist mainly of bromocriptine (Triebel et al., 2017), cabergoline (Colao et al., 2006), and selegiline (Kodesh et al., 2003). Moreover, moringa requires paramount value given to prolactin analysis and clarification pertaining to possible mechanisms that may ameliorate male health. Further research with moringa leaf extract has shown a capacity to modulate dopamine and inhibit monoamine oxidase B (MAO-B) in stressed male rats, likely due to a high content of phenylalanine (Prabsattroo et al., 2015). Additionally, another future research direction is the use of moringa as a galactagogue agent for pregnant patients (Raguindin et al., 2014).
There are currently no upper limits for herbal medicines in humans. In this field, there is a critical need to establish the upper limits of herbal medicines for safety and efficacy reasons. First, herbal medicines are no different than traditional therapeutics in the sense that both contain biologically active substances and exert different levels of xenobiotic metabolism. Hence, herbal medicines have the potential for toxicity and harm but are amenable to toxicological analysis in the same manner as pharmaceuticals. In regards to efficacy, the use of the long Jack aqueous extract from 200 to 400 mg/d and dry fenugreek extract from 500 to 600 mg/d exhibit potential to improve T levels and sperm production (Henkel et al., 2014; Ismail et al., 2012; Maheshwari et al., 2017; Rao et al., 2016; Steels et al., 2011; Tambi et al., 2012; Udani et al., 2014). In this scenario, higher doses might promote greater increases in T levels in a research setting, but these effects, in clinical practice, could come with the price of increasing toxicity and lower safety. Hence, thorough toxicology studies are needed to establish upper limits and safety margins.
In the studies assessed in this review, the highest reported doses of phytotherapeutics occurred in studies using maca, mucuna, and ashwagandha (Ahmad et al., 2008; Ambiye et al., 2013; Gonzales et al., 2003; Shukla et al., 2009). In the studies of maca and ashwagandha, the root powder extract was used, while in the studies of mucuna, the research was conducted using the seed powder extract (Ambiye et al., 2013; Gonzales et al., 2003). Maca intake is frequent in Peru as a common food item (Zhang et al., 2015). Hence, maca administration may be further studied regarding larger doses, since it is considered a food item, and exhibits sweet taste with good general acceptability. Still, the use of maca to improve T levels lacks scientific support, which further strengthens the need for further studies to evaluate and clarify clinical potential (Beharry and Heinrich, 2018).
Black seeds positively influence sperm parameters, Leydig cells, reproductive organs, and sexual hormones. However, the current body of evidence for black seeds is based on animal studies as detailed in a 2015 systematic review (Mahdavi et al., 2015). Hence, there is insufficient evidence to make recommendations on the use of black seeds as an adjunct therapy for infertility. Given that only one study analyzed the effects of black seeds in human sperm parameters (Kolahdooz et al., 2014), further investigation is warranted to determine the magnitude of effects on T concentrations.
Finally, emerging human studies have shown the use of nuts and other foodstuffs to support healthy sperm parameters (Robbins et al., 2012; Salas-Huetos et al., 2018). Thus, more research is required to identify foodstuffs with potential effects on fertility and T levels and map the potential actions involved with supporting fertility, since nuts and other foodstuffs have already demonstrated clinical importance with other conditions such as prostate disease (Curtis Nickel et al., 2008; Galeone et al., 2007; Rowles et al., 2018).
16. Conclusion
The use of mucuna (Mucuna pruriens (L.) DC., Fabaceae), long Jack (Eurycoma longifolia Jack, Simaroubaceae), ashwagandha (Withania somnifera (L.) Dunal, Solanaceae), fenugreek (Trigonella foenum-graceum L., Fabaceae), and black seed (Nigella sativa L., Ranunculaceae) has been shown to exert promising effects on T and sperm parameters. However, the increases in serum T caused by these compounds, although useful to address fertility, are largely irrelevant towards body composition and/or enhanced sports performance. Thus far, tribulus (Tribulus terrestris L., Zygophyllaceae) and maca (Lepidium meyenii Walp, Brassicaceae) remain unsubstantiated T boosters contingent to the dose tested. Tribulus administration can provide favorable effects on sperm parameters in men with idiopathic infertility. For prostate support, the use of saw palmetto (Serenoa repens, (W.Bartram) Small, Arecaceae) is controversial, whereas, the use of Pygeum africanum Hook.f., Rosaceae, Urtica dioica L., Urticaceae, and nutraceutical agents such as beta-sitosterols, pollen extract, and some food items (e.g. onion, garlic, and tomato) confers propitious clinical value. Upper dose limits of phytotherapeutics widely used for male health are unknown and warrant further toxicology studies, as the ascertainment of higher doses is needed, especially in individuals with low T levels, to clarify findings of previous studies and inform recommended dosage guidelines.
