The present clinical trial evaluated the efficacy and safety of an investigational product containing a combination of herbal extracts and vitamins/minerals for the management of Erectile Dysfunction (ED) in adult males. The rationale for the chosen ingredients was based on their potential mechanisms of action and previous scientific evidence supporting their roles in improving various aspects of male sexual health.

The study demonstrated notable improvements in various parameters related to male sexual function and associated factors in the test group compared to the placebo group. Significant enhancements were observed in the test group for erectile function, sexual desire, orgasmic function, intercourse satisfaction, overall satisfaction, and quality of erection scores at both Day 30 and Day 90 assessments. Furthermore, the test group exhibited a substantial 41.90% increase in serum total testosterone levels by Day 90, while the placebo group showed only a modest 5.23% increase. Notably, the test group also demonstrated a 47.39% increase in the number of sexual encounters and a prolonged intra-vaginal ejaculatory latency time by Day 90, suggesting improved sexual stamina and satisfaction. The study also revealed higher treatment satisfaction scores, as assessed by EDITS, for both patients and their partners in the test group compared to the placebo group.

The study findings demonstrate excellent drug compliance rates in both the test and placebo groups. Notably, there were no adverse events observed throughout the study duration. Comprehensive laboratory investigations, including hematological, lipid profile, liver function, renal function, and urine analysis, revealed no significant changes from baseline in either group after treatment at Day 90. Additionally, all patients consistently reported excellent tolerability levels in response to the investigational product. Furthermore, vital signs remained within normal ranges throughout the study period, with no clinically significant differences observed between the test and placebo groups. These findings collectively suggest that the intervention administered to the test group had a comprehensive and favorable impact on various aspects of male sexual health and performance.

One of the key components, Ashwagandha (Withania somnifera), is an ancient Ayurvedic herb known for its adaptogenic and rejuvenating properties. Several studies have demonstrated the potential benefits of Ashwagandha in improving sexual function, particularly in cases of ED. The proposed mechanisms involve modulating stress-related hormones, enhancing nitric oxide bioavailability, and exhibiting antioxidant and anti-inflammatory effects, all of which can contribute to improved vascular function and sexual performance. In a randomized, double-blind, placebo-controlled study, after 90 days of treatment, the Ashwagandha group showed significant improvements in sexual function, as evidenced by increased serum testosterone levels, sperm counts, and seminal motility compared to the placebo group [15].

Our study results align with previous findings by Dongre et al. investigated the effects of Ashwagandha root extract in 50 men aged 22-40 years with ED. The results showed significant improvements in the IIEF scores, indicating enhanced erectile function, sexual desire, and overall satisfaction in the Ashwagandha group compared to the placebo group [16]. The potential mechanism of action for Ashwagandha in improving erectile function is thought to be multifaceted. It may involve modulating stress-related hormones, enhancing nitric oxide bioavailability, and exhibiting antioxidant and anti-inflammatory effects, all of which can contribute to improved vascular function and sexual performance [17].

Another key ingredient, Mucuna pruriens, is renowned for its aphrodisiac properties and potential to increase testosterone levels and sperm count [18,19]. The proposed mechanisms involve stimulating the secretion of L-Dopa, which converts to dopamine, subsequently enhancing the release of FSH and LH from the pituitary gland. Increased LH levels can then facilitate testosterone production, leading to improved spermatogenesis and sexual performance. Additionally, Mucuna pruriens has been found to inhibit prolactin secretion, which can contribute to improving sexual drive and erectile function [20,21].

The stigmas of Saffron (Crocus sativus) flower have various photochemically active components such as crocin, crocetin, picrocrocin, and safranal [22]. In a randomized double-blind placebo-controlled study, 30 men with erectile dysfunction were recruited in two groups of intervention (received saffron) and control (received placebo) for 4 weeks. The findings indicated that saffron had a statistically significant effect on erectile function improvement and intercourse satisfaction among men [23]. In a clinical trial, 20 men with erectile dysfunction were studied before and after the intervention. The status of erectile dysfunction before intervention was evaluated by a questionnaire of international indicators of erectile function before the study and then after 10-day treatment with saffron tablets. The results showed that the use of saffron tablet resulted in an improvement of erectile function and all subscales including dyspepsia, sexual desire, sexual satisfaction, and general satisfaction [24].

The investigational product also contained vitamins C, D3, and B12, as well as the mineral magnesium, which have been explored for their potential roles in supporting male sexual health. Vitamin C, a potent antioxidant, has been shown to improve endothelial function and enhance nitric oxide bioavailability, contributing to improved vascular function and erectile function [25]. Vitamin B12 plays a role in cell metabolism, nerve function, and red blood cell production, which can indirectly influence erectile function [26]. Magnesium, an essential mineral, has been shown to promote vasodilation and improve endothelial function, thereby potentially enhancing erectile function [27]. Similarly, Vitamin D3 has been associated with vascular function, androgen production, and inflammatory processes, all of which can impact erectile function. A randomized, double-blind, placebo-controlled trial investigated the effects of vitamin D3 supplementation in 86 men with ED. In this study, a 3-month supplementation with 4000 IU/ day VD3 significantly increased serum 25(OH) VD3, PTH, phosphorus, and seminal and serum calcium; and total and progressive sperm motilities in infertile men [28].

The absence of adverse events related to the investigational product, alongside stable vital signs throughout the study, further underscores favorable safety profile of PR/HC/1718/002 capsules. Collectively, these findings indicate that the investigational product exhibited a high level of safety and tolerability, making it a promising therapeutic option for further exploration and potential clinical application. Further research, including long-term follow-up and comparisons with other interventions, as well as clinical trials elucidating the mechanism of action, could provide additional insights into the optimal management of erectile dysfunction using the PR/HC/1718/002 capsule.