madman
Super Moderator
ABSTRACT
Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts, and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng, and forskolin root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made.
Introduction
From the age of 30 onwards, testosterone concentrations in men tend to decline at a rate of ∼1% per year (1– 6). Low testosterone, also known as androgen deficiency (AD), or late-onset hypogonadism (LOH) when it occurs in men >40 y of age, is associated with a range of morbidities including major depressive disorder (7), type 2 diabetes (8), obesity (9), and cardiovascular disease (CVD) (10). AD is also associated with a reduced quality of life (11) and an increased risk of mortality in men (12–14). For example, Laughlin et al. (12) observed over an 11.8-y period that men with the lowest total testosterone (TT) concentrations had a 40% greater likelihood of dying compared with men with higher testosterone concentrations, even after controlling for age, obesity, and lifestyle, whereas Pye et al. (13) noted a 5-fold greater risk of all-cause mortality in men with severe LOH compared with men without the condition, after controlling for age, BMI, current smoking, and poor general health. Testosterone replacement therapy (TRT), on the other hand, was found to significantly increase survival rates of hypogonadal men (15, 16).
Despite TRT being the primary treatment for men with AD, its use remains controversial due to its association with an increased risk of exacerbating pre-existing medical conditions. Accordingly, men with existing prostate disease, elevated hematocrit concentrations, high CVD risk, or obstructive sleep apnea may be contraindicated for TRT (17–20). Moreover, according to the US FDA, TRT is only recommended for cases of “classic” or irreversible AD rather than “functional”, age, or comorbidity-related AD (21). This recommendation is endorsed by the Endocrine Society of Australia (20). Therefore, strategies to increase testosterone production and testosterone concentrations in men, without the potential drawbacks associated with TRT, are highly desirable and are key clinical objectives.
Plants and plant-based products, including herbs and spices, have been used for millennia to improve the flavor of food as well as to treat disease and improve overall health and well-being (22). For example, saffron has demonstrated antidepressant and anxiolytic effects (23), curcumin appears to offer pain relief for sufferers of arthritis (24), and cinnamon may support blood-sugar regulation in type 2 diabetics (25). The popularity of herbal products in the United States continues to rise steadily, with annual sales increasing every year for over a decade, with approximately US$8.8 billion worth of products being sold in 2018 (26). The growth in popularity of herbal products is reportedly due to several factors, including perceived efficacy associated with a long history of traditional use and apparent safety due to the perceived absence of serious side effects (27). Given the increasing body of research on herbal supplementation to support natural hormone production, it presents as a potential treatment option for AD. A recent narrative review by Clemesha et al. (28) concluded that many supplements claiming “testosterone boosting” properties, including formulations using herbs, spices, plants, or their extracts, do not appear to be supported by scientific evidence. However, the review of Clemesha et al. (28) had several limitations such as using only a single search term, “testosterone booster,” using only Google to search for existing research and examining only the top 50 supplements. Therefore, the aim of this systematic review was to summarize and critically evaluate randomized controlled trials conducted to assess the efficacy of single herbal ingredients on testosterone concentrations, in addition to their fractions or binding proteins, in men. “Herbs, spices, plants, or their extracts” will henceforth be referred to as “herbs.”
Panax ginseng (Asian ginseng)
Trigonella foenum-graecum (fenugreek)
Withania somnifera (ashwagandha)
Tribulus terrestris (tribulus)
Lepidium meyenii (maca)
Rhodiola rosea (rhodiola)
Chlorophytum borivilianum (musali)
Garcinia cambogia (garcinia)
Coleus forskohlii (forskohlii)
Ganoderma lucidum (reishi)
Urtica dioca (stinging nettle)
Eurycoma longifolia (longjack)
Cordyceps sinensis (cordyceps)
Conclusions
This systematic review provides some evidence that certain herbs and herbal extracts increase testosterone concentrations in men. Currently, the strongest evidence is for fenugreek seed extracts (Trigonella foenum-graecum; details of extract preparation not provided) and ashwagandha roots and leaves (Withania somnifera; water-based or ethanol: waterbased, 70:30, extracts). However, conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Further research is required before definitive conclusions on efficacy and safety can be made. Moreover, making specific recommendations for certain herbs should be done cautiously until further robust research is conducted.
*Strengths and limitations
A strength of this systematic review is the inclusion of only randomized controlled trials investigating the effect of a single herb on testosterone concentrations in men. In addition, given the existing controversy regarding the relative importance of “bound” and “unbound” testosterone (34), data for testosterone fractions and binding proteins were extracted and presented in the current review to increase the scope of findings. A limitation of this review is the exclusion of non-English studies. In addition, many of the studies included in this review have design flaws that adversely affect the strength of conclusions derived from this systematic review. The heterogeneity of herbal extracts, various dosages used, and differences in sample types (serum, plasma, and saliva samples) make comparing studies and conducting a meta-analysis difficult. For example, the studies on ashwagandha used dosages ranging from 240 to 675 mg/d, with varying standardization and extraction processes and different sample types. Also, the studies on fenugreek used 4 different extracts, with dosages ranging from 250 mg/d up to 600 mg/d. Moreover, several studies did not provide specific details of extracts as recommended by the National Center for Complementary and Integrative Health (88), making duplication of those studies difficult.
Testosterone concentrations in males tend to decline with advancing age. Low testosterone, also known as androgen deficiency (AD), is associated with an increased risk of morbidity and mortality. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts, and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. Also, some evidence exists for another herb and herbal extract, Asian red ginseng, and forskolin root extract. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Moreover, 6 studies out of 32 were judged as having a low risk of bias. Current evidence is largely based on young, nonclinical populations, with 16 out of 32 studies using men <40 y of age. Conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Also, further research is required before definitive conclusions on efficacy and safety can be made.
Introduction
From the age of 30 onwards, testosterone concentrations in men tend to decline at a rate of ∼1% per year (1– 6). Low testosterone, also known as androgen deficiency (AD), or late-onset hypogonadism (LOH) when it occurs in men >40 y of age, is associated with a range of morbidities including major depressive disorder (7), type 2 diabetes (8), obesity (9), and cardiovascular disease (CVD) (10). AD is also associated with a reduced quality of life (11) and an increased risk of mortality in men (12–14). For example, Laughlin et al. (12) observed over an 11.8-y period that men with the lowest total testosterone (TT) concentrations had a 40% greater likelihood of dying compared with men with higher testosterone concentrations, even after controlling for age, obesity, and lifestyle, whereas Pye et al. (13) noted a 5-fold greater risk of all-cause mortality in men with severe LOH compared with men without the condition, after controlling for age, BMI, current smoking, and poor general health. Testosterone replacement therapy (TRT), on the other hand, was found to significantly increase survival rates of hypogonadal men (15, 16).
Despite TRT being the primary treatment for men with AD, its use remains controversial due to its association with an increased risk of exacerbating pre-existing medical conditions. Accordingly, men with existing prostate disease, elevated hematocrit concentrations, high CVD risk, or obstructive sleep apnea may be contraindicated for TRT (17–20). Moreover, according to the US FDA, TRT is only recommended for cases of “classic” or irreversible AD rather than “functional”, age, or comorbidity-related AD (21). This recommendation is endorsed by the Endocrine Society of Australia (20). Therefore, strategies to increase testosterone production and testosterone concentrations in men, without the potential drawbacks associated with TRT, are highly desirable and are key clinical objectives.
Plants and plant-based products, including herbs and spices, have been used for millennia to improve the flavor of food as well as to treat disease and improve overall health and well-being (22). For example, saffron has demonstrated antidepressant and anxiolytic effects (23), curcumin appears to offer pain relief for sufferers of arthritis (24), and cinnamon may support blood-sugar regulation in type 2 diabetics (25). The popularity of herbal products in the United States continues to rise steadily, with annual sales increasing every year for over a decade, with approximately US$8.8 billion worth of products being sold in 2018 (26). The growth in popularity of herbal products is reportedly due to several factors, including perceived efficacy associated with a long history of traditional use and apparent safety due to the perceived absence of serious side effects (27). Given the increasing body of research on herbal supplementation to support natural hormone production, it presents as a potential treatment option for AD. A recent narrative review by Clemesha et al. (28) concluded that many supplements claiming “testosterone boosting” properties, including formulations using herbs, spices, plants, or their extracts, do not appear to be supported by scientific evidence. However, the review of Clemesha et al. (28) had several limitations such as using only a single search term, “testosterone booster,” using only Google to search for existing research and examining only the top 50 supplements. Therefore, the aim of this systematic review was to summarize and critically evaluate randomized controlled trials conducted to assess the efficacy of single herbal ingredients on testosterone concentrations, in addition to their fractions or binding proteins, in men. “Herbs, spices, plants, or their extracts” will henceforth be referred to as “herbs.”
Panax ginseng (Asian ginseng)
Trigonella foenum-graecum (fenugreek)
Withania somnifera (ashwagandha)
Tribulus terrestris (tribulus)
Lepidium meyenii (maca)
Rhodiola rosea (rhodiola)
Chlorophytum borivilianum (musali)
Garcinia cambogia (garcinia)
Coleus forskohlii (forskohlii)
Ganoderma lucidum (reishi)
Urtica dioca (stinging nettle)
Eurycoma longifolia (longjack)
Cordyceps sinensis (cordyceps)
Conclusions
This systematic review provides some evidence that certain herbs and herbal extracts increase testosterone concentrations in men. Currently, the strongest evidence is for fenugreek seed extracts (Trigonella foenum-graecum; details of extract preparation not provided) and ashwagandha roots and leaves (Withania somnifera; water-based or ethanol: waterbased, 70:30, extracts). However, conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Further research is required before definitive conclusions on efficacy and safety can be made. Moreover, making specific recommendations for certain herbs should be done cautiously until further robust research is conducted.
*Strengths and limitations
A strength of this systematic review is the inclusion of only randomized controlled trials investigating the effect of a single herb on testosterone concentrations in men. In addition, given the existing controversy regarding the relative importance of “bound” and “unbound” testosterone (34), data for testosterone fractions and binding proteins were extracted and presented in the current review to increase the scope of findings. A limitation of this review is the exclusion of non-English studies. In addition, many of the studies included in this review have design flaws that adversely affect the strength of conclusions derived from this systematic review. The heterogeneity of herbal extracts, various dosages used, and differences in sample types (serum, plasma, and saliva samples) make comparing studies and conducting a meta-analysis difficult. For example, the studies on ashwagandha used dosages ranging from 240 to 675 mg/d, with varying standardization and extraction processes and different sample types. Also, the studies on fenugreek used 4 different extracts, with dosages ranging from 250 mg/d up to 600 mg/d. Moreover, several studies did not provide specific details of extracts as recommended by the National Center for Complementary and Integrative Health (88), making duplication of those studies difficult.
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