Jackson
Male sexual dysfunction encompasses various conditions, including erectile dysfunction (ED) and abnormal ejaculation, that can impair the ability to have a satisfying sexual relationship. ED, in particular, is the most prevalent form of sexual dysfunction and is characterized by the persistent or recurrent inability to achieve or maintain an erection sufficient for satisfactory sexual performance.
The prevalence of ED is significant, with approximately 52% of non-institutionalized men aged 40-70 reporting some degree of ED in the Massachusetts Male Aging Study conducted between 1987 and 1989. Although ED is not life-threatening, it has a profound impact on the physical and mental well-being of individuals and their partners, as well as their overall quality of life.
Current medical interventions for ED primarily involve drug therapy, vacuum constriction devices, intracavernous injections, and surgical options. Oral phosphodiesterase type 5 (PDE5) inhibitors are the most commonly prescribed drugs and are recommended as first-line treatment. Examples of PDE5 inhibitors approved by the US Food and Drug Administration include sildenafil, tadalafil, vardenafil, and avanafil. However, despite their effectiveness, up to 35% of patients may not respond satisfactorily to PDE5 inhibitors, and adverse effects such as headache, flushing, and visual impairment can limit their tolerability.
Moreover, treatment discontinuation rates can be high, with up to 50% of patients discontinuing therapy due to various reasons such as cost, lack of efficacy, and adverse events. Consequently, there is a need to explore alternative compounds that are potentially effective, well-tolerated, and cost-effective compared to PDE5 inhibitors.
Natural products have long served as a valuable source for the development of novel therapeutic agents in medicine. Traditional medicinal plants, in particular, have provided inspiration for the discovery of new drugs. According to the World Health Organization, approximately 25% of modern medicine is either directly derived from or inspired by traditional plant-based remedies. Additionally, between 1981 and 2014, around 26% of newly approved medicines were natural products or their derivatives, with an additional 21% being natural product mimics.
Considering the potential of natural products, there is growing interest in investigating medicinal plants traditionally used as aphrodisiacs for the development of more effective treatments for ED. To contribute to this quest, We selected several commonly studied components of these plants and gained insight into their potential use in treating ED.
Ginseng
Ginseng is a herb derived from the plant Panax genus. Ginseng plants are colloquially named according to their geographical origin, with Asian ginseng and American ginseng being the two most commonly studied varieties.
Ginseng less than 4 years old is classified as fresh ginseng, while white ginseng (4-6 years old) and red ginseng (dried ginseng over 6 years old) are characterized based on their longer processing times. Ginseng extracts and powders have historically been used in Asian cultures as an aphrodisiac and herbal remedy to enhance sexual function and satisfaction. Ginseng continues to be used to improve sexual performance and is the most commonly used ingredient in male health supplements for ED.
Ginseng consists of biologically active compounds ginsenosides and ginsenosides. Both compounds increase NO synthase activity and promote blood flow to the corpus cavernosum. Studies evaluating the mechanism of action of ginseng berry extract in a rat model showed that the herb increased intracavernous pressure in a dose-dependent manner.
Nitric oxide production: Ginseng is thought to enhance the production of nitric oxide (NO), a molecule that plays a crucial role in enabling erections. NO helps to relax and dilate blood vessels, allowing increased blood flow to the penis. This improved blood flow can enhance erectile function.
Improved blood flow: Ginseng may enhance blood circulation, which is essential for achieving and maintaining an erection. By improving blood flow to the genital region, ginseng may aid in facilitating erectile function.
Hormonal effects: Ginseng has been shown to influence hormone levels, particularly testosterone. Testosterone is vital for sexual health, including libido and erectile function. Some studies suggest that ginseng can increase testosterone levels, which may contribute to its positive effects on ED.
Anti-inflammatory and antioxidant effects: Chronic inflammation and oxidative stress can negatively impact erectile function. Ginseng possesses anti-inflammatory and antioxidant properties, which may help protect against damage to blood vessels and erectile tissues, potentially improving ED symptoms.
Psychological benefits: ED can often have a psychological component, with stress, anxiety, and depression contributing to its development or exacerbation. Ginseng has been found to have adaptogenic properties, meaning it may help the body better cope with stress and improve overall well-being. These psychological benefits could indirectly enhance sexual function.
It is important to note that more research is needed to further substantiate the effects of ginseng on ED. The specific dosage, duration of treatment, and optimal form (Asian ginseng or American ginseng) of ginseng for ED management also remain areas of investigation. Furthermore, individual responses to ginseng can vary, and it may not be effective or suitable for everyone.
L-arginine
L-arginine is a semi-essential amino acid that plays a crucial role in the synthesis of proteins in the body. It is also a precursor to nitric oxide (NO), a molecule that helps relax blood vessels and regulate blood flow. L-arginine is often used as a dietary supplement for various health purposes, including its potential effects on erectile dysfunction.
Nitric oxide production: L-arginine is converted into nitric oxide by the enzyme nitric oxide synthase (NOS). Nitric oxide acts as a signaling molecule in the body, helping to relax and dilate blood vessels, thus improving blood flow. This enhanced blood flow is beneficial for erectile functioning, as it enables a sufficient supply of blood to the penis, facilitating erections.
Improved endothelial function: The endothelium is the inner lining of blood vessels. L-arginine has been shown to improve endothelial function, promoting better blood vessel health. This can positively impact erectile function as healthy blood vessels are essential for achieving and maintaining erections.
Support for penile tissue: L-arginine is involved in the production of collagen, an essential component of connective tissues. It can also support the production of elastin, which helps maintain the elasticity of tissues. These properties may be beneficial for maintaining penile tissue integrity, which is crucial for erectile function.
L-arginine is often combined with other supplements, such as pycnogenol or yohimbine, in formulations marketed for improving erectile function. Some studies suggest that these combinations may have synergistic effects, potentially enhancing their effectiveness in managing erectile dysfunction.
Tongkat Ali
Tongkat Ali is an herbal supplement derived from a long-leaved true-leaf plant native to Southeast Asia.
It has traditionally been used as an aphrodisiac due to its ability to increase testosterone levels. A number of active compounds can be isolated from Tongkat Ali, including cansi-6-one alkaloids, jossanes, squalene derivatives, and euclidean. Specific studies on the enhancing properties of these chemicals, and their effects on The mechanism are poorly understood.
Tongkat Ali has been studied in animal models, and studies have reported rats showing increases in mating behavior and sexual activity in middle-aged and elderly subjects. However, subsequent research on the effects of tongkat ali on erectile function in men is limited. In a 2015 meta-analysis, Kotirum et al reported that two RCTs on the effects of Tongkat Ali on men with ED indicated that herbal supplementation may have a positive effect on erectile function. Although both studies noted improvements in erectile function, the study by Ismail et al., which included patients who reported higher baseline levels of erectile function, improved the IIEF total score from 25.37 +/− 0.48 to 26.79 +/− 0.44 ( p < 0.001) [31]. Udani et al. showed a significant increase (p < 0.05) in 11 of 7 categories of assessment (SIA); however, this may be attributable to overall lower baseline erectile function.
Horny Goat Weed
Horny Goat Weed is a herbal supplement that has been used in traditional Chinese medicine for centuries. It is believed to have potential benefits for various health conditions, including erectile dysfunction (ED).
Horny Goat Weed contains several bioactive compounds, including icariin, which is considered the main active ingredient responsible for its potential effects on ED. Icariin is a flavonoid that has been shown to have anti-inflammatory, antioxidant, and pro-erectile properties.
Some studies suggest that Icariin has PDE5 inhibitor activity in vitro and may mimic some properties of testosterone. Studies have shown that icariin also enhances smooth muscle proliferation and has neurotrophic effects, which may be beneficial in refractory ED in the setting of hypertension or diabetes-induced endothelial cell damage.
Shindel et al. examined the effect of different doses of icariin (5 mg/kg, 10 mg/kg, and 4 mg/kg) on intracavernous pressure (ICP) in rats with surgically injured cavernous nerves over 1 week. Icariin increased intracavernosal pressure, and the ICP/MAP ratio of rats in the 1 mg/kg and 10 mg/kg groups was significantly increased (p < 0.05). Rats treated with 5 mg/kg icariin had higher mean ICP/MAP ratios, but the difference was not statistically significant (confidence interval: -0.8187–0.0313). Icariin also increased the expression of neuronal NO synthase on western blots in all treatment groups compared to rats that did not receive icariin.
Although these initial studies are promising, further research on the use of icariin in animal and human models is scarce. Furthermore, there are no definitive studies characterizing the efficacy or toxicity of icariin in humans. Due to the lack of evidence-based efficacy and understanding of its side effects, icariin should be further studied to evaluate its use in the treatment of ED.
Tribulus Terrestris
Tribulus Terrestris is an herbal supplement derived from a plant that grows in various parts of the world, including Asia, Europe, and Africa. It has a long history of use in traditional medicine systems, particularly in Ayurveda and Traditional Chinese Medicine. Tribulus Terrestris has been traditionally used as an aphrodisiac and to promote sexual health in both men and women. It is believed to enhance libido, increase sexual desire, and improve overall sexual function.
Tribulus Terrestris contains various bioactive compounds, including steroidal saponins, flavonoids, alkaloids, and glycosides.
Tribulus has also been reported to increase serum testosterone in a rat model of sexual dysfunction. Although these animal studies are promising, Qureshi et al. reported in a systematic review of the performance-enhancing effects of Tribulus that no increase in testosterone was observed in men, despite increased serum testosterone in animal models.
Less research has been done on the effects of Tribulus terrestris on erectile function in humans. In an RCT, Santos et al found no improvement in ED symptoms or IIEF scores in men treated with Tribulus compared with placebo. However, a recent double-blind RCT by Kamenov et al. reported that although treatment with 12 mg of Tribulus did not increase serum testosterone levels over 1500 weeks, men treated with Tribulus had a 2.7 higher IIEF score compared to the placebo point.
Maca
Maca is a vegetable derived from plants in the order Lepidoptera that has been used historically as a nutritional supplement and fertility enhancer. There is limited research on the use of maca for sexual enhancement, and there is no clearly understood mechanism of action to date. When studied in an animal model, a lipid extract from the Lepidium meyenii plant increased sexual performance in male mice and rats as measured by the number of complete introductions over a 3-hour period. There are no specific research reports on the effects of Maca on ED in animals in the literature.
Only one study reported that maca improved erectile function in men with ED, and limited other literature suggests that maca is an effective supplement for ED treatment. Additionally, maca has not been studied for its adverse effects, and its side effects remain unknown; therefore, further research is needed to determine its role in ED management.
Saw palmetto
Saw palmetto is an herbal supplement popular in the southern regions of North America. Extracted from the American palm tree, it is well-documented for treating lower urinary tract symptoms. Saw palmetto contains several bioactive compounds, including fatty acids and phytosterols, that possess anti-inflammatory properties. This may contribute to its potential benefits for urinary tract health and reducing inflammation associated with prostate conditions.
However, the effects of saw palmetto on sexual function are understudied. Yang et al. reported that saw palmetto has PDE5 inhibitor properties and noted increased expression of NO synthase mRNA induced on Western blot in rat and rabbit cavernosal muscle tissue. These studies have not been replicated in human trials. The paucity of data examining the effects of saw palmetto on erectile function underscores the importance of further research to assess whether it should be included in ED-directed nutraceuticals.
Fenugreek
Fenugreek is a plant-derived herb that has a long history of use in traditional medicine, particularly in Ayurvedic, Chinese, and Unani medicine. It contains various compounds, including enzymes, amino acids (such as arginine), vitamins, and lipids. A fenugreek seed extract has been studied for its potential effects on blood sugar control, cholesterol levels, and circadian rhythm.
There have been previous research studies examining the relationship between fenugreek and sexual health. One study conducted on sexually immature rats found that fenugreek extract increased anabolic activity and muscle mass but did not affect testosterone levels or testicular structure at the histological level. Only two randomized controlled trials have investigated fenugreek for sexual dysfunction in humans. One trial reported that oral fenugreek treatment increased sexual function in men, but serum testosterone levels were unaffected. Another study reported that fenugreek supplementation for 8 weeks significantly improved symptoms of low testosterone and sexual function in hypogonadal men, as measured by the IIEF (International Index of Erectile Function) scores.
It is worth noting that consuming fenugreek can have toxic effects. Studies have reported teratogenic (causing birth defects), antifertility, and neuropathological effects associated with fenugreek consumption in animal models. Researchers have observed spermatozoic effects and decreased testicular weight in various animal models. However, data on fenugreek’s effectiveness in improving sexual function are limited, sometimes conflicting, and no studies have specifically examined its use in treating erectile dysfunction (ED). Therefore, further research is needed to assess the safety and efficacy of fenugreek therapy.
Yohimbine
Yohimbine is derived from the bark of the Pausinystalia yohimbe tree and is commonly used as a dietary supplement to potentially improve sexual dysfunction, particularly erectile dysfunction (ED). It acts as an alpha-2 adrenergic receptor antagonist, which means it blocks the receptors that inhibit the release of nitric oxide, a compound that plays a crucial role in the relaxation of blood vessels in the penis, leading to increased blood flow and improved erectile function.
Numerous studies have investigated the effectiveness of yohimbine in treating ED. The aforementioned 1998 meta-analysis, which included 18 randomized controlled trials, found that yohimbine was more effective than placebo in improving erectile function in men with ED. However, it is important to note that the quality of evidence from these studies was generally low, and there is a lack of recent comprehensive reviews on the topic.
When it comes to safety, yohimbine is generally considered safe when used appropriately. However, some individuals may experience side effects such as increased heart rate, elevated blood pressure, anxiety, irritability, and gastrointestinal distress. It should be used with caution, especially in individuals with underlying cardiovascular conditions, as it can potentially worsen these conditions.
Sources：
[1]Kim TH, Jeon SH, Hahn EJ, et al. Effects of tissue-cultured mountain ginseng (Panax ginseng CA Meyer) extract on male patients with erectile dysfunction. Asian J Androl. 2009;11(3):356-361.
[2]Neychev VK, Mitev VI. The aphrodisiac herb Tribulus terrestris does not influence androgen production in young men. J Ethnopharmacol. 2005;101(1-3):319-323.
[3]Shindel AW, Xin ZC, Lin G, et al. Erectogenic and neurotrophic effects of icariin, a purified extract of horny goat weed (Epimedium spp.) in vitro and in vivo. J Sex Med. 2010;7(4 Pt 1):1518-1528.
[4]Srivatsav A, Balasubramanian A, Pathak UI, Rivera-Mirabal J, Thirumavalavan N, Hotaling JM, Lipshultz LI, Pastuszak AW. Efficacy and Safety of Common Ingredients in Aphrodisiacs Used for Erectile Dysfunction: A Review. Sex Med Rev. 2020 Jul;8(3):431-442. doi 10.1016/j.sxmr.2020.01.001. Epub 2020 Mar 2. PMID: 32139335; PMCID: PMC7340557.
