The Role of Nutraceuticals and Phytotherapy in Andrological Diseases: Tips and Tricks for Everyday Clinical Practice

Abstract

Background/Objectives: Interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased markedly in recent years. In particular, growing attention has been directed toward the treatment of patients affected by erectile dysfunction (ED), male infertility, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and induratio penis plastica (IPP). However, several areas of uncertainty remain. This narrative review aims to examine the role of nutraceuticals and phytotherapeutic agents in the management of andrological disorders. Methods: A narrative review was conducted using PubMed, Scopus, Cochrane CENTRAL, and EMBASE to identify relevant studies published over the past 25 years. Only articles published in English and involving adult populations were included in the analysis. Results: Nutraceuticals and phytotherapeutic compounds have been extensively investigated in the current literature, and certain formulations—particularly specific combinations—have been evaluated in high-quality studies. Conversely, other compounds lack sufficient scientific evidence and therefore should not be recommended in routine clinical practice. In the management of ED, the following compounds, administered either alone or in combination, have demonstrated clinically significant effects: Panax ginseng, Tribulus terrestris, L-arginine, and Withania somnifera. L-carnitine, combined with micronutrients, antioxidants, and various traditional herbal supplements, appears to be an effective therapeutic option for male infertility and subfertility. Pollen extracts play an important role in the management of CP/CPPS, while carnitine, coenzyme Q10, silymarin, bromelain, and curcumin show promising potential in the treatment of IPP. Conclusions: Nutraceuticals and phytotherapeutic agents may provide favorable outcomes in the management of andrological diseases. Although current evidence is encouraging, larger prospective studies employing standardized protocols and treatment schedules are required to confirm long-term efficacy and to optimize therapeutic strategies.

1. Introduction

Andrological diseases affect at least 15% of couples worldwide and are associated with substantial healthcare costs and a significant negative impact on the quality of life of both patients and their partners [1,2]. Although international guidelines have been recently updated and now reflect a higher level of evidence, several aspects of andrological disease management remain controversial or insufficiently defined [3]. Many patients express dissatisfaction with currently available therapies due to their high cost, potential adverse effects, and perceived limited efficacy [4,5].

Against this background, interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased considerably in recent years. Nutraceuticals lie at the interface between nutrition and pharmacology and involve the use of bioactive compounds derived from food sources with the aim of preventing or treating diseases. Numerous studies have investigated the clinical efficacy of nutraceuticals and phytotherapeutic agents in the management of andrological disorders. However, establishing their true effectiveness—and determining whether specific formulations are superior to others—remains challenging for at least two main reasons. First, for most treatment regimens, evidence of efficacy is derived from a single study or a limited number of studies; consequently, meta-analyses often report a class effect rather than effects attributable to individual compounds. Second, direct head-to-head comparisons between different nutraceutical or phytotherapeutic interventions are rarely available [6,7].

Furthermore, existing studies must be critically interpreted considering compound selection and manufacturing processes. Several pharmacological factors should be considered when choosing an appropriate product, as commercially available supplements frequently differ in terms of composition, dosage, and formulation [8]. This variability complicates the identification of an optimal dietary supplement and may significantly influence clinical outcomes. Based on these considerations, the present narrative review aims to examine the role of nutraceuticals and phytotherapy in the management of andrological diseases, with the goal of providing practical guidance for everyday clinical practice grounded in the most recent evidence and recommendations. This narrative review focuses on erectile dysfunction (ED), induratio penis plastica (IPP), chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and male infertility. These conditions share several common pathophysiological mechanisms, including oxidative stress, chronic inflammation, and endothelial dysfunction. Owing to their antioxidant, anti-inflammatory, and vasoprotective properties, nutraceuticals may represent a valuable adjunct to conventional therapeutic approaches. Nevertheless, their use should be guided by the highest possible level of scientific evidence, with careful consideration of formulation quality, bioavailability, dosage, and treatment duration [9]. Finally, this narrative review aims to provide clinicians with a practical guide for the use of nutraceuticals in the management of andrological diseases in routine clinical practice, based on a consensus discussion among experienced andrologists affiliated with the Italian Society of Andrology.

2. Materials and Methods

2.1. Research Strategy

To identify relevant sources for this review, a comprehensive literature search was performed in major databases, including PubMed, Cochrane CENTRAL, Scopus, and EMBASE databases, until October 2025. The search strategy combined keywords such as “nutraceuticals,” “phytotherapy,” “food supplements,” “food supplementation,” “erectile dysfunction,” and “Induratio Penis Plastica” OR “Peyronie’s disease.”

2.2. Inclusion and Exclusion Criteria

Cross-sectional, case–control, prospective and retrospective studies, randomized controlled trials (RCTs), reviews, and meta-analyses were considered eligible for inclusion. Any disagreement among the three reviewers was resolved through consultation with the supervising authors (T. Cai and N.M.). The following filters were applied during the search process: clinical trials, human studies, English language, and adult populations. Initial study selection was based on title and abstract screening. When abstract evaluation was insufficient to determine eligibility, a full-text review was performed. Given the extensive body of literature available on nutraceuticals in general and on individual active compounds, the authors deemed a narrative review format to be the most appropriate approach for synthesizing and presenting the evidence.

2.3. Selected and Analyzed Paper

A total of 267 records were initially identified through database searching. After screening, 218 articles were assessed for eligibility, and 49 studies were ultimately included in this narrative review.

3. Research Evidence

3.1. Erectile Dysfunction

Erectile dysfunction (ED) is defined by the International Society of Sexual Medicine as the persistent inability to attain or maintain an erection sufficient for satisfactory sexual performance [10]. It is a highly prevalent condition, with incidence increasing with age, although it may also affect younger individuals, particularly in the presence of metabolic, cardiovascular, or psychological comorbidities. The European Association of Urology (EAU) reports prevalence rates exceeding 50% among elderly men [11].

The physiology of penile erection is governed by a complex interplay of neurological, vascular, hormonal, and psychological pathways [12]. During sexual stimulation, nitric oxide (NO) is released from parasympathetic nerve endings and endothelial cells within the corpora cavernosa, promoting smooth muscle relaxation and increasing blood inflow into erectile tissues [13,14]. Endothelial dysfunction, oxidative stress, and chronic inflammation are central pathophysiological contributors to ED, as they impair NO production and bioavailability, disrupting the erectile cascade [14].

In this context, nutraceuticals have garnered increasing attention for their potential to enhance erectile function through mechanisms such as vasodilation, antioxidant activity, and hormonal modulation.

L-arginine, a precursor of NO, has been extensively studied. Daily supplementation at doses ranging from 1500 to 5000 mg has demonstrated significant efficacy in improving erectile function compared to placebo, as reported in a meta-analysis of ten randomized controlled trials (RCTs) [15]. L-citrulline, an endogenous precursor of L-arginine, has been investigated for its potential to sustain NO production more effectively over time [16].

A recent RCT evaluated a nutraceutical formulation containing L-citrulline, L-carnitine, botanical extracts, and micronutrients, administered with or without concomitant tadalafil. The study found that combined treatment with both the nutraceutical formulation and tadalafil resulted in significantly greater improvements in International Index of Erectile Function (IIEF-5) scores than either tadalafil or the supplement alone, suggesting a synergistic interaction between nutraceuticals and pharmacotherapy [7].

Ginseng, a phytotherapeutic agent with longstanding traditional use for it tonifying properties, has been investigated for ED. Its active constituents, ginsenosides, may promote NO release and enhance penile vascular responsiveness. Preliminary evidence indicates potential benefits for erectile function, although data remain limited and methodologically heterogeneous, necessitating further robust clinical trials [17].

Yohimbine, an alkaloid derived from Pausinystalia yohimbe, exerts its effects via a neuroadrenergic mechanism by antagonizing alpha-2 adrenergic receptors, thereby increasing sympathetic tone and noradrenaline release. While clinical trials have shown superiority over placebo, its use has declined due to safety concerns and limited contemporary evidence [18].

Micronutrient supplementation with zinc and selenium has been associated with support of testicular function and hormonal regulation. Zinc deficiency impairs testosterone biosynthesis, reducing libido and erectile quality. Observational studies suggest that higher dietary intake of zinc and selenium correlates with a lower prevalence of ED, highlighting a potential preventive role [19].

Tribulus terrestris, traditionally employed to enhance libido, has been proposed to exert androgenic effects. Some studies report that increased endogenous testosterone levels and improved erectile function. However, a recent systematic review concluded that evidence supporting its efficacy is weak and inconsistent, particularly in patients with organic causes of ED [7].

Withania somnifera (Ashwagandha) has demonstrated promising effects in sexual health. Preclinical studies in male rats suggested improvements in sexual competence [20], while a recent RCT reported enhancements in orgasmic function, sexual desire, and overall sexual satisfaction after eight weeks of oral administration, without significant direct effects on erectile function [21].

Given the multifactorial nature of ED, an integrated therapeutic approach incorporating nutraceuticals may be particularly beneficial in the early stages of the condition. Although these agents cannot replace first-line pharmacologic therapies, such as phosphodiesterase type-5 inhibitors (PDE5-Is), they may provide a valuable adjunct for patients with mild ED, contraindications to pharmacotherapy, or a preference for non-pharmacologic interventions. A multimodal strategy allows tailoring interventions to individual clinical profiles, preferences, and therapeutic responses, integrating conventional pharmacology, dietary supplementation, and lifestyle modifications.

International Guidelines

The EAU guidelines on Sexual and Reproductive Health address herbal medicine and food supplements in ED management. Based on a Cochrane review, ginseng may have only minimal effects on erectile function or sexual satisfaction compared to placebo [17,22]. The guidelines emphasize the lack of well-designed clinical trials demonstrating the efficacy of nutraceuticals or food supplements as monotherapy for ED. They note that these products may have a supportive role when used in combination with PDE5-Is, but they are not recommended as standalone treatments.

In everyday clinical practice, consistent with EAU guidance on male sexual dysfunction [23], the following approach is suggested:

• Conduct a comprehensive assessment of all risk factors and, where possible, implement targeted interventions through patient counseling.
• Evaluate the severity of ED.
• Consider on-demand PDE5-Is in combination with an evidence-based nutraceutical formulation.
• Select nutraceuticals that target both sexual desire (e.g., via modulation of testosterone production) and erectile function (e.g., enhancing NO-mediated vasodilation and endothelial function), with compounds such as Tribulus terrestris and ginseng.
• Schedule follow-up at three months to evaluate treatment efficacy and monitor potential adverse effects. Consider the possibility of reducing PDE5-I dosage while continuing nutraceutical therapy.

Selection of nutraceuticals should be guided by current evidence regarding efficacy, mechanism of action, and product quality.

3.2. Induratio Penis Plastica

Induratio Penis Plastica (IPP), also referred to as Peyronie’s disease, is an uncommon andrological disorder characterized by progressive penile curvature and shortening. It is a fibro-sclerotic condition affecting the tunica albuginea of the corpora cavernosa, marked by the formation of fibrous plaques that can result in penile curvature during erection, pain, and, in advanced cases, erectile dysfunction [24]. Reported prevalence varies widely, ranging from 0.4% to 20.3%, with peak incidence observed between the fifth and sixth decades of life [25]. Although more common in men over 50, cases in younger individuals, with onset as early as 18 years, have been documented [26]. IPP significantly impacts quality of life, affecting sexual function, self-esteem, intimate relationships, and overall psychological well-being. From a pathophysiological perspective, IPP is considered a chronic condition with multifactorial etiology [27,28]. Repeated microtrauma to the erect penis, most frequently during sexual activity, is hypothesized to trigger an inflammatory response in the tunica albuginea. In genetically or biologically predisposed individuals, this response may fail to resolve, evolving into chronic inflammation characterized by pro-inflammatory cytokine release, oxidative stress, and dysregulated collagen deposition by fibroblasts [28]. These processes lead to the formation of inelastic fibrotic tissue, which may calcify or stiffen, thereby reducing tunical elasticity and resulting in penile curvature, shortening, pain, impaired penetrative function, and, in some cases, ED [29].

The early, active phase of IPP represents an optimal therapeutic window for nutraceutical intervention, as inflammatory and fibrotic processes remain potentially modifiable. Several naturally derived compounds have demonstrated, in vitro or clinically, the capacity to modulate IPP pathophysiology [30,31].

Vitamin E, a lipophilic antioxidant, may limit lipid peroxidation in fibroblast membranes and attenuate pro-fibrotic signaling pathways such as TGF-β1. Clinical evidence, however, remains inconclusive, and major urological guidelines do not recommend Vitamin E as monotherapy. Its benefit appears most relevant during the early, active phase when combined with other interventions [30,32].

Carnitine esters, key regulators of mitochondrial energy metabolism, exhibit anti-inflammatory and anti-fibrotic properties, including downregulation of pro-inflammatory interleukins (e.g., IL-6) and inhibition of fibroblast activation. Comparative studies suggest L-carnitine may be superior to Vitamin E in reducing pain and improving curvature; nevertheless, robust RCT evidence is lacking, and guidelines do not currently endorse their routine use [30,33].

Coenzyme Q10, a mitochondrial cofactor with antioxidant properties, contributes to energy metabolism and oxidative stress mitigation. In IPP patients, supplementation has been associated with reduced progression of penile curvature and potential plaque size reduction, particularly during the active disease phase [34]. Mechanistically, CoQ10 may inhibit lipid peroxidation and modulate intracellular inflammatory signaling. Although evidence derives from a single RCT, some guidelines consider its use as part of a multimodal therapeutic approach [30]. Other compounds, including Vitamin B10 and omega-3 fatty acids, have not demonstrated clinically meaningful efficacy in reducing plaque size or curvature [30]. Additional naturally occurring agents with anti-inflammatory and antifibrotic potential have been explored. Propolis, a resinous bee product rich in flavonoids and polyphenols, inhibits pro-inflammatory cytokines such as TNF-α and suppresses fibroblast activation in vitro [35]. Preclinical studies suggest early administration may attenuate collagen deposition during active inflammatory phases [36]. Other phytochemicals, including silymarin (from milk thistle), bromelain (from pineapple), and curcumin (from turmeric), have shown preliminary anti-inflammatory and antifibrotic effects [37]. However, high-quality clinical evidence remains lacking.

International Guidelines

The EAU guidelines on Sexual and Reproductive Health report that no nutraceutical compounds can be recommended for IPP management based on well-conducted clinical trials. Specifically, oral treatments with Vitamin E, potassium para-aminobenzoate (Potaba), and acetyl esters of carnitine are not recommended for Peyronie’s disease [23].

In everyday clinical practice, we suggest:

Counseling patients regarding the natural history of IPP and clearly explaining the limited evidence for nutraceutical interventions. Using antioxidants only as part of a multimodal approach, with transparent discussion of the paucity of supportive data.

Recognizing that the role of dietary supplements in IPP management is limited.

In conclusion, while nutraceuticals have a plausible pathophysiological rationale—targeting oxidative stress, inflammation, and aberrant collagen deposition—their clinical efficacy remains unproven. Existing studies are limited by high variability in compound selection, dosage, administration schedule, and treatment duration. Their therapeutic benefit appears most pronounced during the early, inflammatory phase of IPP, with minimal expected efficacy in stabilized or calcified disease. Therefore, nutraceuticals should be considered adjunctive to comprehensive treatment strategies, which may include pharmacologic therapy, extracorporeal shockwave therapy (ESWT), and surgical intervention when indicated. The absence of large, well-designed RCTs with standardized diagnostic criteria and long-term follow-up precludes definitive recommendations regarding the role of nutraceuticals in IPP management.

3.3. Male Infertility

Male infertility affects approximately 15% of couples worldwide and accounts for 40–50% of infertility cases [38]. The World Health Organization defines infertility as the inability to achieve conception after at least 12 months of regular, unprotected sexual intercourse [39]. Its etiology is multifactorial, encompassing anatomical, endocrinological, genetic, infectious, and immunological abnormalities, as well as environmental and behavioral factors. Nonetheless, in approximately 30–40% of cases, no definitive cause can be identified, a condition classified as idiopathic infertility [40].

Among the most recognized pathophysiological mechanisms is oxidative stress, reflecting an imbalance between reactive oxygen species (ROS) production and the antioxidant defense system. Excessive ROS damages sperm membranes, impairs mitochondrial function, and contributes to sperm DNA fragmentation [23]. Consistent with other andrological conditions, nutraceuticals have emerged as promising adjuncts, particularly in idiopathic infertility, due to their potential to mitigate oxidative stress, enhance mitochondrial function, and preserve sperm genetic integrity [41,42].

A recent systematic review demonstrated improvements in semen parameters among infertile men receiving dietary supplements, particularly combinations of antioxidants such as coenzyme Q10, vitamin C, and vitamin E, highlighting the role of nutraceuticals in male infertility management [43].

3.3.1. Evidence for Specific Compounds

Zinc and selenium are among the most frequently used trace elements. Zinc is critical for spermatogenesis and membrane stability, and supplementation has been shown to improve sperm motility and morphology, particularly in oligozoospermic or asthenozoospermic men [44]. Selenium, a cofactor for glutathione peroxidase, protects against oxidative damage. Combined supplementation with selenium and N-acetylcysteine has been associated with improved seminal fluid quality [45].

Vitamins C and E contribute to antioxidant defense in semen. Vitamin C primarily acts in the seminal plasma, while vitamin E stabilizes sperm membranes by reducing lipid peroxidation. Their combined use has been shown to significantly decrease sperm DNA fragmentation [46].

Coenzyme Q10, a mitochondrial cofactor with antioxidant properties, improves sperm motility and concentration in patients with asthenozoospermia, likely by reducing intracellular oxidative stress [47].

Folic acid, a B-group vitamin involved in DNA synthesis and methylation, is essential for sperm genomic integrity. Deficiency is associated with increased DNA fragmentation, whereas supplementation may enhance sperm maturation and genetic stability [48].

The potential role of probiotic supplementation in male infertility has gained attention, as probiotics may influence hormone secretion, scavenge free radicals, and improve the reproductive tract microenvironment, thereby indirectly enhancing sperm function [23]. Studies indicate that prebiotic/probiotic compounds can improve sperm parameters and DNA integrity compared with placebo [49,50]. However, these studies are limited by small sample sizes, heterogeneous formulations, and methodological biases.

3.3.2. International Guidelines

The EAU guidelines on Sexual and Reproductive Health indicate that there is currently insufficient evidence from well-conducted clinical trials to recommend nutraceutical compounds for male infertility [23]. Specifically, while antioxidants or prebiotic/probiotic supplementation may improve semen parameters, no conclusive data support their effect on pregnancy rates.

3.3.3. Practical Recommendations

In clinical practice, we suggest:

• Counseling patients regarding modifiable risk factors and potential lifestyle interventions.
• Recognizing that dietary supplements are widely used but have not demonstrated efficacy in improving pregnancy rates.
• Considering nutraceuticals as adjuncts to other treatments to optimize semen parameters, while clearly communicating limitations regarding reproductive outcomes.
• Discussing treatment costs relative to the demonstrated clinical benefits.

Overall, nutraceuticals appear to be a safe and potentially effective adjunct in male infertility management, particularly in idiopathic cases. Their use should occur within a clearly defined clinical framework under medical supervision, taking into account individual patient needs, product quality, potential interactions, and existing clinical evidence. Patient education is essential to ensure realistic expectations and adherence. A comprehensive, integrated strategy combining nutraceuticals, lifestyle modifications, and, when indicated, pharmacological or assisted reproductive interventions represents the most effective approach to address the multifactorial challenge of male infertility. Nutraceuticals have been shown to improve semen parameters, however there is conflicting evidence on their impact on pregnancy rates. This should be taken into consideration by all doctors treating male infertility.

3.4. Chronic Prostatitis/Chronic Pelvic Pain Syndrome

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex urological condition associated with significant impairment in quality of life and substantial healthcare costs. According to the National Institutes of Health (NIH) classification, CP/CPPS is the most frequent form of prostatitis, with high prevalence in men under 50 years of age [51,52]. Current management strategies include antibiotics, anti-inflammatory agents, and alpha-blockers, though findings regarding their efficacy are often inconsistent [53,54].

In recent years, several nutraceuticals and phytotherapeutic compounds have been proposed as adjunctive treatments. Among these, herbal-based therapies have been most frequently studied, with some evidence suggesting efficacy superior to certain conventional interventions [55]. However, high-quality evidence remains limited and heterogeneous. Consequently, the American Urological Association (AUA) guidelines do not recommend any single supplement as standard therapy but support a multimodal strategy that may include food supplements [56].

Among the most studied nutraceuticals for CP/CPPS are quercetin, pollen extract, saw palmetto, and astaxanthin.

Quercetin, a bioflavonoid with antioxidant and anti-inflammatory properties, has been evaluated in several clinical trials. In RCTs, quercetin 500 mg twice daily demonstrated a response rate of 67% (≥25% improvement in NIH-CPSI score) compared to 20% for placebo (p = 0.001) [57]. A systematic review and meta-analysis confirmed that quercetin significantly improves NIH-CPSI scores compared with placebo, with a mean difference of approximately 7 points (95% CI: −8.32 to −5.60; p < 0.00001), while maintaining a favorable safety profile [58].

Pollen extract is one of the most extensively studied compounds in CP/CPPS management [59]. Multiple clinical trials have demonstrated that patients with inflammatory CP/CPPS experience meaningful improvements in symptoms, pain, and quality of life without serious adverse effects [60,61,62,63,64,65,66]. Notably, Wagenlehner et al., in a multicenter, double-blind, placebo-controlled phase 3 trial, reported a response rate (≥25% or ≥6-point reduction in NIH-CPSI) of 70.6% for pollen extract versus 50% for placebo (p = 0.0141) after 12 weeks of treatment, with only minor side effects [60]. Matsukawa et al. also found that pollen extract provided greater pain relief than tadalafil when combined with alpha-blocker therapy [65].

Saw palmetto (Serenoa repens) has been evaluated in several trials, but evidence does not support its efficacy in CP/CPPS. Standard doses (320–325 mg daily) have not demonstrated significant or sustained improvement in NIH-CPSI scores compared to placebo [66,67,68].

Astaxanthin, a potent anti-inflammatory compound in preclinical models, has not yet been evaluated in RCTs for CP/CPPS. While its antioxidant and anti-inflammatory properties suggest potential utility, further clinical studies are required before any recommendations can be made [69,70].

3.4.1. International Guidelines

The EAU guidelines on chronic pelvic pain note that phytotherapy may reduce pain scores in CP/CPPS compared with placebo, highlighting its potential adjunctive role in clinical practice [54,71]. Specifically, RCTs and systematic reviews support the use of pollen extract (oral or suppository) due to demonstrated efficacy. Quercetin has demonstrated clinical benefit only in small-scale RCTs, limiting the strength of recommendations. Saw palmetto has not consistently improved NIH-CPSI scores and is therefore not recommended as a primary therapy [54,57,72,73].

3.4.2. Practical Recommendations

In everyday clinical practice, we suggest:

• Counseling patients about the multifactorial etiology of CP/CPPS and the need for multimodal therapy targeting multiple pathways.
• Considering pollen extract (oral or suppository) as adjunctive option for selected patients.
• Recognizing that other supplements, such as quercetin, may provide benefit but should be considered adjunctive and individualized.

While nutraceuticals, particularly pollen extract, may provide symptomatic relief for select CP/CPPS patients, their use should complement, not replace, guideline-directed multimodal therapy [54]. Clinicians should consider limitations such as publication bias, heterogeneous study populations, and lack of direct head-to-head trials comparing phytotherapy to established treatments. Patient selection remains crucial, and non-pharmacological approaches, including physical therapy, may be particularly effective for specific clinical phenotypes. Treatment should be individualized according to symptom profile and patient preference.

Table 1. The table summarizes all clinical intervention studies on the role of food supplements in the management of andrological diseases.

Study	Substance	Dose	Treatment Duration	Indication	Clinical Outcome
Novak et al. [32]	Interferon α-2B ± Vitamin E	4 × 106 IU weekly (INF-alfa); Vitamin E 400 IU BID	10 weeks	Peyronie’s disease	IIEF-5 > in the two groups Penile curvature < in the two groups Plaque size < in the two groups Note: vitamin E did not confer additional clinical benefit.
Safarinejad [34]	Coenzyme Q10	300 mg/day	24 weeks	Early Peyronie’s disease	IIEF-5 > in the treatment group Penile curvature < in the treatment group Plaque size < in the treatment group
Paulis et al. [35]	Verapamil + antioxidants	Verapamil 10 mg intralesional q2w; antioxidants 600–1000 mg/day	6 months	Peyronie’s disease	IIEF-5 > in all groups Penile curvature < in all groups Plaque size < in all groups Note: greater benefit has been observed with combined therapy
Paulis et al. [37]	Multimodal antioxidant therapy	Multiple agents	18–36 months	Active Peyronie’s disease	IIEF-5 > in all treated patients Penile curvature < in all treated patients Plaque size < in all treated patients
Alahmar et al. [47]	Coenzyme Q10	200 mg/day	3 months	Idiopathic male infertility	Semen parameters > in all treated patients DNA fragmentation < in all treated patients Oxidative stress markers < in all treated patients
Abbasi et al. [49]	Synbiotic	500 mg/day	80 days	Idiopathic male infertility	Semen parameters > in all treated patients DNA fragmentation < in all treated patients Oxidative stress markers < in all treated patients
Asadi et al. [50]	Probiotic	1 capsule BID (109 CFU)	3 months	Post-varicocelectomy infertility	Semen parameters > in the treatment group
Wagenlehner et al. [60]	Pollen extract (60 mg Cernitin T60 and 3 mg Cernitin GBX)	Standard formulation	12 weeks	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in the treatment group Quality of life > in the treatment group
Cai et al. [61]	Flower pollen extract (Graminex® 500 mg per tablet) + vitamins	1 g/day	3 months	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in the treatment group Quality of life > in the treatment group Seminal interleukin-8 levels < in the treatment group
Cai et al. [62]	Flower pollen extract (Graminex® 500 mg per tablet) + vitamins	Standardized dosing	8 weeks–6 months	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in the treatment group Quality of life > in the treatment group
Elist [63]	Pollen extract (74 mg highly defined extract of pollen from Graminae species)	Standard formulation	12 weeks	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in the treatment group Quality of life > in the treatment group
Iwamura et al. [64]	Herbal extract vs. pollen extract	Standard dosing	8 weeks	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in both groups Quality of life > in both groups
Matsukawa et al. [65]	Cernitin pollen extract vs. tadalafil	63 mg/day vs. 5 mg/day	12 weeks	Refractory CP/CPPS	NIH-CPSI score (total and pain sub-score) > in the pollen extract group IPSS > in the tadalafil group
Zhang et al. [72]	Serenoa repens extract	320 mg/day	12 weeks	CP/CPPS	NIH-CPSI score (total and pain sub-score) > in both groups Quality of life > in both groups

shows all included clinical intervention studies, while

Table 2. The table summarizes all pre-clinical intervention studies on the role of food supplements in the management of andrological diseases.

Study	Model	Substance	Dose/Range	Duration	Indication	Outcome
Ilayperuma et al. [20]	Adult male rats	Withania somnifera root extract	3000 mg/kg/day (oral)	7 days (+follow-up)	Experimental sexual dysfunction	IIEF-5 > in all treated patients Note: no changes in testosterone levels
Wang et al. [48]	Mice; germ cells	Folate deficiency	0.3 vs. 20 mg/kg diet; 0–200 ng/mL (cells)	Chronic; 6 days (cells)	Male infertility	DNA fragmentation > in all treated patients Note: the treatment resulted in increasing of chromatin instability, and impaired DNA repair mechanisms
Liu et al. [69]	Mouse and cell models	Astaxanthin	25 mg/kg/day; 1–10 µM	14–28 days	CP/CPPS	Oxidative stress markers < in all treated patients Pro-inflammatory cytokines < in all treated patients Note: treatment modulated of gut microbiota composition

shows all included pre-clinical studies.

4. Conclusions and Future Perspective

Although andrological diseases are generally benign, their management often requires a complex, multidisciplinary therapeutic approach. Clinical outcomes may be unsatisfactory due to treatment-related adverse effects or limited efficacy. In this context, nutraceuticals and food supplements may provide additional benefits. The EAU guidelines offer physicians evidence-based recommendations for managing these conditions, while highlighting that several areas remain under debate. Even though the study methodology has certain drawbacks, several substances have shown intriguing clinical significance, as supported by several trials. Future investigations of nutraceuticals in andrology should adhere to rigorous methodologies, analogous to those used in drug development, to provide clinicians with reliable tools for everyday practice.