Herbal dietary supplements for erectile dysfunction: A systematic review and meta-analysis of randomized-controlled trials

Abstract

Background and aim

Interest of herbal supplements as alternatives to conventional treatments for erectile dysfunction (ED) has increased markedly. This systematic review and meta-analysis aimed to evaluate the effectiveness of herbal supplements in treating ED.

Experimental procedure

Pubmed, Embase, and Cochrane CENTRAL databases were searched for relevant studies published until June 1, 2023. Randomized controlled trials (RCTs) evaluating herbal supplements for ED compared to a placebo or no intervention were eligible for inclusion. The outcomes of interest included erectile function, orgasmic function, sexual desire, subjective satisfaction, and serum testosterone levels.

Results and conclusion

Fourteen RCTs with a total of 1227 males with ED were included. Mean age of study participants ranged from 35 to 65 years; and follow-up ranged from 1 month to 6 months. Herbal dietary supplements had a significant, positive effect on erectile function (standard mean difference (SMD) = 1.20, 95 % confidence interval (CI): 0.64–1.76), orgasmic function (SMD = 1.09, 95 % CI: 0.34–1.83), sexual desire (SMD = 1.02, 95 % CI: 0.45–1.60), intercourse satisfaction (SMD = 1.48, 95 % CI: 0.83–2.13), overall satisfaction (SMD = 0.93, 95 % CI: 0.45–1.40), and serum testosterone level (SMD = 0.54, 95 % CI: 0.04–1.05) compared to effects in the control groups. Saffron was effective in improving erectile function, orgasmic function, and intercourse satisfaction, while ginseng benefited erectile function, orgasmic function, sexual desire, overall satisfaction, and serum testosterone levels. In contrast, evidence for other agents such as Tribulus terrestris and Maca remains insufficient, underscoring the need for larger, high-quality trials with longer follow-up.

Graphical abstract

Highlights

• •The meta-analysis demonstrates the efficacy of herbal supplements in improving various aspects of male sexual health.
• •Saffron and ginseng significantly enhance erectile function and satisfaction, with ginseng also improving testosterone level.
• •These findings provide a systematic evidence base for herbal supplements as distinct alternatives to conventional therapy.

List of abbreviations

CI

Confidence interval

ED

Erectile dysfunction

FSH

Follicle-stimulating hormone

IIEF

International Index of Erectile Function

MeSH

Medical Subject Headings

PDE5

Phosphodiesterase type 5

PICOS

Participants, intervention, comparison, outcomes, study design

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

RCT

Randomized controlled trial

SD

Standard deviation

SMD

Standard mean difference

1. Introduction

Erectile dysfunction (ED) is the inability to achieve or maintain a firm penile erection for satisfactory sexual intercourse. It commonly affects men older than age 40 years. Incidence of ED is reported to increase with increasing age.¹ An estimated 8.3 % of insured men in the United States have been diagnosed with ED, translating to approximately 10.3 million men seeking care for this condition as of 2022. ED is shown to markedly reduce patients’ quality of life and self-esteem.^{2, 3, 4} Estimating ED prevalence is challenging due to substantial variations worldwide, and interfering factors such as the ED definition used, population selection criteria, and survey methods/tools. Nonetheless, study reports have estimated that ED rates range from 1 % to 10 % among men younger than age 40 years, increasing to 50 %–100 % for men older than age 70 years.^{2,5, 6, 7}

Current strategies for managing ED revolve primarily around pharmacotherapy, with the primary drug being phosphodiesterase type 5 (PDE5) inhibitors.⁸ However, dietary habits may influence the effectiveness of PDE5 inhibitors, and they are administered with caution if combined with nitrates or alpha-blockers due to the potential risk of life-threatening hypotension.⁹

Recent studies have explored the role of herbal dietary supplements in the prevention and management of certain chronic diseases, with several studies reporting promising outcomes.^{4,10, 11, 12} Interest in herbal dietary supplements as potential safe and effective alternatives to conventional drugs for treating ED has been growing.^13,14 Herbal supplements are often perceived by non-medical professionals in the public as having a potentially lower risk of adverse reactions than drugs that may also confer additional positive health benefits.^15,16

However, in the US and some European countries, herbal supplements do not undergo the rigorous and robust testing for safety and effectiveness as do pharmaceutical medications that undergo FDA testing for use for specific indications as claimed by the manufacturer, and claims regarding the effectiveness of herbal supplements may be exaggerated or false. As such, it is essential to investigate the safety and efficacy of herbal supplements given the abundance of herbal dietary supplements on the market. To date, the results of systematic reviews and meta-analyses investigating the effectiveness of herbal supplements for treating ED have been somewhat inconsistent.^{14,17, 18, 19, 20} Although many clinical trials have been conducted an updated meta-analysis is warranted to examine the effectiveness of herbal supplements for treating ED.

Therefore, this study aimed to determine the effectiveness of herbal dietary supplements for treating ED by conducting a systematic review of the literature and meta-analysis of the selected studies.

2. Methods

2.1. Search strategy

This systematic review and meta-analysis was conducted in accord with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).²¹ PubMed, Embase, and Cochrane CENTRAL databases were searched using combinations of keywords, including“erectile dysfunction” and “herbal supplement,” combined with Boolean operators and Medical Subject-Headings (MeSH) terms where appropriate, for studies published up to June 1, 2023. The detailed search strategies and filters used for each database are summarized in Supplementary Table S1. In addition, the reference lists of included studies were hand-searched to identify other potentially relevant studies.

2.2. Selection criteria

The PICOS criteria (population, intervention, comparison, outcomes, study design) were used to identify studies to be included in the analysis. Eligible studies were those investigating patients with ED (P) using herbal/plant dietary supplements including: Tribulus terrestris, ginseng, saffron, Pinus pinaster (a complex extract of French maritime pine bark and other plant extracts marketed as Prelox®, Pycnogenol, and other names), Lepidium meyenii, Tongkat ali, and any other single or multi-herb product as treatment (I). The comparison group (control) was one in which a placebo was given, or there was no active intervention (C). The outcomes of interest were quantitative outcomes of erectile function, orgasmic function, sexual desire, and subjective satisfaction (O). Only published RCTs were considered for inclusion (S).

Studies without quantitative outcomes of interest and those that were not RCTs, (including reviews, letters, comments, editorials, case reports, proceedings, personal communications, conference abstracts, and non-human studies) were excluded. The eligibility of studies was confirmed by two independent reviewers, and a third reviewer was consulted when uncertainty arose regarding eligibility.

2.3. Main outcome measures and data extraction

The outcomes of interest were erectile function, orgasmic function, sexual desire, intercourse satisfaction, and overall satisfaction assessed by the International Index of Erectile Function (IIEF) scale, and serum testosterone levels of all subjects. These results were assessed by measuring the standardized mean difference (SMD) from baseline. In cases where the standard deviation (SD) was not reported and only the mean and range were provided, the SD was calculated using the equation: $\text{SD}\approx \frac{Range}{4}$.

2.4. Ethics statement

This systematic review and meta-analysis of published studies neither required nor used raw patient data and private information, therefore approval of the protocol by the study hospital Institutional Review Board (IRB) and informed consent from study subjects were waived by the ethics committee.

2.5. Risk of bias assessment

The quality of the included studies was assessed using the Cochrane Collaboration tool for literature review and meta-analyses, RevMan®.²² RevMan assesses risk of bias via the 7 criteria: selection bias (random sequence generation and allocation concealment), performance bias (blinding of participants and personnel), detection bias (blinding of outcome assessment), attrition bias (incomplete outcome), reporting bias (selective outcome reporting), and inclusion of intention-to-treat analysis. Quality assessment was performed by two independent reviewers, and a third reviewer was consulted if any discrepancies arose.

2.6. Statistical analysis

Heterogeneity across the included studies was evaluated using the I² statistic, with criteria as follows: 0 %–24 %, no heterogeneity; 25 %–49 %, moderate heterogeneity; 50 %–74 %, high heterogeneity; and 75 %–100 %, extreme heterogeneity. Random effects models were used to estimate the pooled effect for all outcomes. Subgroup analysis was performed on the basis of types of herbal supplements. Meta-analysis was performed using R-studio software with R packages “meta,”, “dmetar,” “metafor,” “esc” and “tidyverse.” Publication bias was assessed using Egger's test when >10 studies were analyzed. All analyses were 2-sided, and p values < 0.05 were established as statistical significance.

3. Results

3.1. Search results

A flow diagram of the study selection process is shown in Fig. 1. Searching the PubMed, CENTRAL, and Embase databases and manual searches identified 361 eligible studies. After removing duplicates and irrelevant studies by screening the titles and abstracts, the remaining 250 studies underwent full-text review based on the inclusion and exclusion criteria. Subsequently, 14 studies remained for inclusion in the meta-analysis.^{23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36} All of the included studies were RCTs, which together included 1227 males with ED (Fig. 1).

Fig. 1.

PRISMA flow diagram of study selection.

3.2. Study characteristics

Table 1 summarizes the characteristics of 14 RCTs conducted across Europe, America, and Asia between 2002 and 2021, with three studies conducted in Korea, two in Italy, two in Brazil, two in Iran, and one each in Serbia, Egypt, Bulgaria, and India, and a joint study between Italy and the UK. Tribulus terrestris and ginseng were the most investigated supplements. Specifically, of the 14 studies, four studies^25,27,33,35 (35.7 %) investigated Tribulus terrestris as the intervention, four studies^23,24,26,28 investigated ginseng and its extracts, two studies^31,32 investigated saffron, one study investigated Maca,³⁶ one study investigated Tongkat ali,³⁰ one investigated VigRX Plus®,³⁴ and one study investigated Prelox®.²⁹ The age range of study subjects across the studies was 35–65 years, and follow-up duration ranged from one month to six months (Table 1). All studies included a placebo-controlled group, with treatment and control group sizes generally well-balanced, ensuring the robustness of comparative analyses.

Table 1.

Characteristics of included studies.

First author (publication year)	Country	Study design	Type of herbal dietary supplement	Number of patients (total/treatment/control [placebo])	Mean age (years)	Evaluation time points (months)
Leitao AE (2021)	Brazil	RCT	Tongkat ali	23/11/12	47	4 mo
Stanojevic N (2020)	Serbia	RCT	Tribulus terrestris	92/56/36	56	2 mo
Gamal El Din SF (2019)	Egypt	RCT	Tribulus terrestris	70/35/35	57	3 mo
Kamenov Z (2017)	Bulgaria	RCT	Tribulus terrestris	180/90/90	43	3 mo
Mohammadzadeh-Moghadam H (2015)	Iran	RCT	saffron	50/25/25	59	1 mo
Sansalone S (2014)	Italy	RCT	Tribulus terrestris	177/87/90	65	3 mo
Choi YD (2013)	Korea	RCT	ginsenga	118/59/59	57	2 mo
Modabbernia A (2012)	Iran	RCT	saffron	30/15/15	39	1 mo
Shah GR (2012)	India	RCT	VigRX Plus ®	78/39/39	35	3 mo
Ledda A (2010)	Italy and UK	RCT	Prelox ®	111/54/57	44	6 mo
Zenico T (2009)	Italy	RCT	Maca	50/25/25	36	3 mo
Kim TH (2009)	Korea	RCT	ginsengb	143/75/68	59	2 mo
de Andrade E (2007)	Brazil	RCT	ginsengc	60/30/30	53	3 mo
Hong B (2002)	Korea	RCT	ginsengc	45/22/23	54	4.5 mo

RCT, randomized controlled trial. Months, mo.

^aStandardized Korean ginseng berry (SKGB).

^bTissue-cultured mountain ginseng extract (TMGE).

^cKorean Red Ginseng.

3.3. Risk of bias

Results of the quality assessment for the included studies are shown in Fig. 2A and B. All studies claimed randomization; however, most of the studies did not report details of allocation concealment. Double-blinding was applied in the majority of studies except for three, although most studies had no blinding of outcome assessors. In general, risk of bias in selective reporting and incomplete data were low, and bias regarding inclusion of intention-to-treat analysis was low to moderate. Overall, the assessment indicated that most of the included studies were of moderate-to-high quality.

Fig. 2.

Risk of bias assessment (A) Risk of bias summary. (B) Risk of bias graph.

3.4. Outcomes of interest

3.4.1. Erectile function

Twelve studies^{23,24,26,28, 29, 30, 31, 32, 33, 34, 35, 36} evaluated changes in erectile function, and the results of the meta-analysis are summarized in Fig. 3A. Due to the high heterogeneity (I² = 93 %), a random-effects model was used to estimate the pooled effect. The analysis revealed a pooled SMD (pSMD) = 1.20 (95 % confidence interval [CI]: 0.64 to 1.76), indicating that taking herbal dietary supplements was associated with a greater improvement in erectile function as compared to controls. In subgroup analysis by type of herbal supplement, no heterogeneity was detected among the saffron and ginseng subgroups. Saffron (pSMD = 2.23, 95 % CI: 1.66 to 2.80) and ginseng (pSMD = 0.41, 95 % CI: 0.20 to 0.62) were each significantly associated with greater improvement in ED compared to that of controls, whereas Tribulus terrestris was shown to have positive effects on ED compared to controls, but the difference was not statistically significant (pSMD = 0.74, 95 % CI: −0.24 to 1.72). In the one study investigating Prelox®, Ledda et al. (2010),²⁹ participants with moderate ED (ages 30–50) took Prelox® for 6 months, and ED improved significantly, particularly in those receiving longer treatment; in the present meta-analysis, Prelox® had a significantly positive effect on ED compared to controls.

Fig. 3.

Meta-analysis of changes in (A) erectile function; (B) orgasmic function; (C) sexual desire; (D) intercourse satisfaction; (E) overall satisfaction; and (F) serum testosterone level associated with herbal supplements.

3.4.2. Orgasmic function

Nine studies^{23,26,28, 29, 30, 31, 32, 33, 34} reported data of orgasmic function, and results of the meta-analysis are shown in Fig. 3B. A random-effects model was used (I² = 87 %), and the analysis revealed that the herbal supplements had a significantly positive effect on orgasmic function compared to controls (pSMD = 1.09, 95 % CI: 0.34–1.83). Subgroup analysis indicated that saffron (pSMD = 1.01, 95 % CI: 0.32–1.70, I² = 52 %) and ginseng (pSMD = 0.24, 95 % CI: 0.02–0.47, I² = 0 %) had significantly greater positive effects compared to controls.

3.4.3. Sexual desire

Nine studies^{23,26,28, 29, 30, 31, 32, 33, 34} reported sexual desire results, and a random-effects model (I² = 85 %) was used (Fig. 3C). The present meta-analysis showed a significant positive effect on sexual desire for herbal dietary supplements as compared to controls (pSMD = 1.02, 95 % CI: 0.45–1.60). In subgroup analysis, ginseng had a significant positive effect compared to controls (pSMD = 0.45, 95 % CI: 0.22–0.67, I² = 0 %); however, no differences were found between saffron and controls.

3.4.4. Satisfaction with intercourse

Nine studies^{23,26,28, 29, 30, 31, 32, 33, 34} reported data of intercourse satisfaction, and a random-effects model was used for analysis (I² = 93 %) (Fig. 3D). The present meta-analysis found a significant positive effect of herbal dietary supplements on subjective intercourse satisfaction compared to that of controls receiving placebo (pSMD = 1.48, 95 % CI: 0.83–2.13). Subgroup analysis indicated that saffron had a significant positive effect compared to controls (pSMD = 1.81, 1.15–2.47, I² = 36 %), whereas no differences were found between ginseng and controls.

3.4.5. Overall satisfaction

Nine studies^{23,26,28,29,31, 32, 33, 34,36} reported data of overall satisfaction, and a random-effects model was used for analysis (I² = 90 %) (Fig. 3E). The present meta-analysis found a significantly positive effect for intercourse satisfaction after treatment with herbal dietary supplements compared to that in controls (pSMD = 0.93, 95 % CI: 0.45–1.40). In subgroup analysis, ginseng had a significantly positive effect compared to that of controls receiving placebo or no treatment (pSMD = 0.32, 95 % CI: 0.09–0.55, I² = 0 %), whereas no differences were found between saffron and controls.

3.4.6. Serum testosterone level

Eight studies^{23, 24, 25,27,28,30,34,36} reported data of serum testosterone levels, and a random-effects model of analysis was used (I² = 74 %) (Fig. 3F). Meta-analysis indicated a significantly positive effect on serum testosterone levels after treatment with herbal dietary supplements than that of controls (pSMD = 0.54, 95 % CI: 0.04–1.05). Subgroup analysis indicated that ginseng had a significantly positive effect compared to controls (pSMD = 0.23, 95 % CI: 0.01–0.45, I² = 0 %), whereas no difference was noted between Tribulus terrestris and controls.

3.5. Publication bias analysis

Funnel plots were not constructed for most outcomes because the number of studies was insufficient (<10 studies). However, Fig. 4 shows a funnel plot for publication bias for erectile function. The data points in the funnel plot seem to be symmetric; however, evidence of publication bias was identified by Egger's test (p = 0.024).

Fig. 4.

Funnel plot for erectile function.

4. Discussion

This systematic review and meta-analysis of RCTs evaluated the effectiveness of herbal dietary supplements for ED by measuring changes from before to after treatment with the specific supplements compared to placebo. The results of studies of the individual supplements revealed that overall, herbal dietary supplements have a significant positive effect on erectile function, orgasmic function, sexual desire improvement, intercourse satisfaction, overall satisfaction, and serum testosterone levels as compared to placebo. Subgroup analyses of all included herbal supplements indicate that saffron is particularly beneficial for erectile function, orgasmic function, and intercourse satisfaction, and ginseng for erectile function, orgasmic function, sexual desire, subjective satisfaction, and serum testosterone levels. These findings suggest that herbal dietary supplements, particularly saffron and ginseng, effectively improve various aspects of erectile function and sexual satisfaction in individuals with ED, and may offer a viable treatment option for ED patients looking for alternatives to conventional therapies.

The evaluation of over-the-counter supplements for improving ED revealed a significant disconnect between marketing claims and scientific evidence. Balasubramanian et al.¹⁷ analyzed top-rated Amazon products and found only 17 % of human studies assessed single ingredients, with a sharp drop (up to 90 %) in reported benefits after filtering unreliable reviews, raising concerns about false advertising. Similarly, Kuchakulla et al.¹⁹ reported that 68 % of ingredients in popular supplements marketed for ED and testosterone lacked solid RCT evidence (grade C or D), and no complete product had been clinically tested. Petre et al.²⁰ documented that, in Italy, 80 % of ED supplements sold contained ingredients below the minimal effective dose, and only 8 % had a formulation suggesting potential efficacy based on RCT-supported scoring. Collectively, these observations emphasize the need for further scientific evidence, informed clinical guidance, and regulatory oversight, because most supplements marketed for ED lack robust evidence-based support.

Previous meta-analysis, Borrelli et al. (2018)¹⁸ included 24 RCTs and 2080 men with ED, synthesized evidence on several herbal agents for erectile dysfunction but provided quantitative analyses primarily for ginseng, leaving other supplements like saffron, Tribulus terrestris, Pinus pinaster, and Lepidium meyenii either narratively described or insufficiently assessed. The results showed that only ginseng may be an effective treatment for ED, and only 7 studies had a low risk of bias.¹⁸ In contrast, evidence for saffron and Tribulus terrestris was mixed, and studies of other agents such as Pinus pinaster and Lepidium meyenii were too limited to make firm conclusions.¹⁸ Authors of that study concluded that though adverse events were infrequent and comparable to placebo, the overall evidence base remains insufficient to support the routine use of herbal dietary supplements for ED.¹⁸ A subsequent systematic review published in 2021 examined 42 articles and concluded that the evidence supporting the use of ginseng, Tribulus terrestris, and L-arginine for treating ED was promising.¹⁴ Notably, the authors of that review postulated that the mechanism of action may be in part to increase nitric oxide synthesis (discussed below). While adverse events were rare, the inconsistent methodological quality and short trial durations limit generalizability. Authors of that review emphasized the value of lifestyle interventions (e.g., diet and exercise) as adjunct strategies, especially in patients with metabolic comorbidities.¹⁴

Similarly, the Cochrane review by Lee et al. (2022)³⁷ offered the most rigorous evaluation of ginseng to date but was restricted to a single herb, with clinical benefits deemed only trivial in magnitude and largely derived from Korean populations. These studies highlight an undressed gap: the lack of a comprehensive quantitative synthesis comparing diverse herbal dietary supplements across multiple populations. However, our study addresses this undressed gap by integrating randomized controlled trials on a wide range of herbal interventions—including ginseng, saffron, Tribulus terrestris, Maca, Tongkat ali, Prelox®, and others—allowing for both pooled and subgroup analyses of efficacy outcomes. This broader synthesis provides a more complete and generalizable evidence base for evaluating herbal supplements as potential alternatives or adjuncts in the management of erectile dysfunction. Importantly, our results show that saffron and ginseng are consistently associated with improvements in multiple sexual function domains, while other supplements demonstrate variable or population-specific effects.

The Cochrane systematic review by Lee et al. (2022) provides the most rigorous evaluation to date on the efficacy of ginseng for ED, synthesizing data from nine randomized controlled trials with 587 participants.³⁷ However, while ginseng demonstrated a statistically significant improvement in the Erectile Function Domain of the International Index of Erectile Function-15 (IIEF)-15 (MD 3.52, 95 % CI 1.79–5.25) and IIEF-5 scores (MD 2.39, 95 % CI 0.89–3.88), these changes were below the predefined minimum clinically important difference (MCID),which represents the smallest change in a patient-reported outcome measure (PROM) that is considered meaningful by patients and clinicians, suggesting, in this instance, that clinical benefits were only trivial. Additionally, although ginseng may improve self-reported ability to have intercourse (RR 2.55, 95 % CI 1.76–3.69), its effect on subjective satisfaction with intercourse was marginal (MD 1.19, 95 % CI 0.41–1.97). Adverse events did not differ significantly from those of placebo.

To explore the broader effects of herbal supplements, Lu et al. (2021)³⁸ collected the data of 19 systematic reviews and meta-analyses that examined the effects of saffron on health outcomes, finding that saffron improved sexual dysfunction and also reduced fasting blood glucose, waist circumference, diastolic blood pressure, total cholesterol and low-density lipoprotein cholesterol, and improved symptoms of depression and cognitive function compared with effects of saffron on these factors in controls (who received mainly placebos). However, 17 out of 19 reviews were rated as "critically low" quality on AMSTAR-2, with common deficits including lack of protocol registration, inadequate search strategies, and failure to report funding sources. The authors qualified the results by suggesting that the quality of future studies needs to be improved. Further, although saffron appeared to be generally safe, with only mild adverse effects reported, the studies were predominantly conducted in Iran, limiting generalizability to other populations.

Although not specifically included in the present analysis, a number of studies have examined the effect of arginine supplements in treating ED. In particular, a systematic review and meta-analysis (10 RCTs and 540 patients) by Rhim et al. (2020)³⁹ examined the effect of arginine in treating ED. The results showed that arginine supplements administered as dosages ranging from 1500 to 5000 mg significantly improved ED compared to placebo or no treatment (OR = 3.37, p = 0.01), and also significantly improved overall satisfaction, intercourse satisfaction, and orgasmic function. The effect of arginine supplementation for treating ED is proposed to be the result of increased nitric oxide synthesis.¹⁴ By increasing nitric oxide synthesis, arginine acts as an anti-oxidant. Nitric oxide supplementation is reported to improve cardiac health and reduce ED, and L-arginine and L-citrulline are common supplements that increase nitric oxide levels.⁴⁰ A recent systematic review and meta-analysis (18 studies, 1331 patients with ED) by Su et al.⁴¹ examined the effect of antioxidant supplements on ED. While antioxidants alone yielded only modest improvements in IIEF scores compared with placebo (SMD = 1.93; 95 % CI: 0.15–3.72), the efficacy of antioxidants was more pronounced with antioxidant compounds (SMD = 2.74; 95 % CI: 1.67–3.81), suggesting possible synergistic effects when multiple antioxidant agents are used. This possibility is further supported by the fact that the combination of antioxidants and PDE5 inhibitors produced even greater improvements in erectile function and sexual satisfaction, surpassing the effects of PDE5 inhibitors alone (SMD for IIEF = 1.10; 95 % CI: 0.51–1.68). These findings support the hypothesis that oxidative stress contributes to ED pathophysiology and that targeting this pathway may enhance standard pharmacotherapy outcomes.

Other studies have shown good results for combined treatments for ED. Wang et al.⁴² offered compelling evidence that combining Chinese herbal medicine with tadalafil provided superior therapeutic benefit for ED compared to that achieved with tadalafil alone. The combination therapy significantly improved IIEF-5 scores (WMD = 2.67; 95 % CI: 2.19–3.15), sexual function measures (SEP-Q2 and SEP-Q3), and overall treatment efficacy (RR = 1.15; 95 % CI: 1.06–1.25), without increasing the incidence of adverse effects. Subgroup and sensitivity analyses further demonstrated that these benefits were particularly consistent in patients receiving low-dose tadalafil (5 mg daily), highlighting a dose-sparing synergy. The concept of de-escalation therapy—where tadalafil is gradually reduced and withdrawn while maintaining Chinese herbal medicine—emerged as a promising long-term strategy, with studies showing sustained or even improved erectile function after discontinuing tadalafil.⁴² These findings not only support the integration of Chinese herbal medicine into standard ED management but also raise the possibility of reducing drug dependency and cost through strategic combination and tapering protocols. However, future large-scale, multicenter RCTs are still needed to confirm these results and optimize treatment algorithms.

Additionally, previous studies have proposed detailed mechanistic pathways of dietary herbal supplements discussed herein, including ginseng, saffron, tribulus terrestris, Ginkgo biloba, and Maca, for improving libido and ED. These include contributions of the herbs to enhancing testosterone levels, boosting nitric oxide production, supporting vascular health, and reducing oxidative stress. Table 2 summarizes these mechanisms.

Table 2.

Mechanisms underlying the beneficial effects of herbal dietary supplements for ED.

Type of herbal dietary supplement	Mechanisms underlying the beneficial effects of herbal supplements used for erectile dysfunction
ginseng37,46	Ginsenosides in ginseng promote nitric oxide release, relaxing corpus cavernosum smooth muscle and enhancing blood flow during arousal. Ginseng may normalize testosterone levels, improving libido and erectile function, while its antioxidant properties protect endothelial cells from oxidative stress, supporting vascular health.
saffron47	Saffron exhibits antioxidant properties, which reduce oxidative stress, improving vascular health and erectile function. It may enhance nitric oxide production, promoting vasodilation and increased penile blood flow. Saffron influences testosterone levels, boosting libido and sexual function, while its mood-enhancing effects may indirectly improve sexual performance by reducing anxiety and depression.
Tribulus terrestris48, 49, 50	Tribulus terrestris may enhance testosterone production by stimulating luteinizing hormone, which has been shown to improve libido and erectile function. It boosts nitric oxide synthesis, promoting vasodilation and increasing penile blood flow. Its antioxidant properties, driven by saponins and flavonoids, support vascular health by reducing oxidative stress, essential for sustaining erections.
Ginko biloba51,52	Ginkgo biloba may enhance nitric oxide production, which promotes vasodilation and improves penile blood flow during sexual stimulation. Its flavonoid antioxidants reduce oxidative stress, protecting endothelial function, while its neuroprotective effects may benefit erectile dysfunction caused by neurologic issues.
Lepidium meyenii (Maca)14,51,52	Maca may boost testosterone levels, supporting libido and erectile function. It enhances energy and reduces fatigue, improving physical stamina for better sexual performance. Additionally, Maca's flavonoid antioxidants reduce oxidative stress, promoting vascular health and improving penile blood flow essential for erections.

Beyond oral herbal supplements, other traditional Chinese medicine (TCM) modalities such as acupuncture have also been explored for their therapeutic potential in managing ED. Acupuncture, a cornerstone of TCM, has gained attention as a complementary therapy for ED.^{43, 44, 45} Conventional therapies for ED such as PDE5 inhibitors offer short-term efficacy but are often associated with adverse effects such as headaches, myalgia, and potential cardiovascular risk.⁴³ Amid these limitations, acupuncture has emerged as a non-pharmacologic alternative rooted in TCM philosophy of restoring qi flow and organ harmony. Electroacupuncture at points like Zusanli (ST36) and Guanyuan (RN4) reportedly increases cavernous blood flow and modulates neurotransmitters such as 5-HT and nitric oxide.⁴³ Also, since psychological factors contribute significantly to ED, the anxiolytic effects of acupuncture may improve erection indirectly via stress response attenuation and sympathetic modulation.⁴⁴ Authors of one study proposed that acupuncture may regulate testosterone and activity of the hypothalamic-pituitary-gonadal axis, although direct evidence remains limited and inconclusive.⁴⁴ These mechanisms align with both TCM theory (e.g., kidney-yang deficiency) and biomedical concepts (e.g., endothelial dysfunction), indicating the potential bidirectional regulation of physiological and psychological domains. All three reviews reported that acupuncture is well-tolerated,^{43, 44, 45} with only minimal adverse events such as transient needling pain or subcutaneous bruising. Compared to pharmacologic therapies, the absence of systemic side effects (e.g., hypotension, hearing loss) enhances the safety profile of acupuncture. Lack of placebo-controlled, double-blind, multicenter RCTs limits causal inferences. Potential publication bias in Chinese-language journals also warrants caution.

4.1. Strengths and limitations

A major strength of this meta-analysis is that only high quality RCTs were included. The combined effect sizes consistently exhibited narrow confidence intervals, indicating robust accuracy and reliability of the research outcomes. Furthermore, subgroup analyses were performed to address heterogeneity among the studies. The present study has several limitations. First, the number of studies was limited and, because adverse events were not adequately described in the studies, we were unable to evaluate them. Future research may focus on cost-effectiveness and the use of herbal supplements in combination with other therapeutic modalities.

4.2. Clinical implications

Within an evidence-informed, shared decision-making framework, both saffron and ginseng may be considered as adjunctive supplements for patients with ED—particularly in cases where PDE5 inhibitors yield suboptimal efficacy, are poorly tolerated, or when patients express a preference for integrative or complementary approaches. For individuals with metabolic comorbidities, lifestyle modifications—including dietary optimization, regular physical activity, and weight management—should remain central to management alongside any nutraceutical supplementation. Clinicians are advised to monitor blood pressure, lipid profiles, hepatic and renal function, and to remain vigilant for potential drug–herb interactions. Furthermore, patients should be counseled regarding the variability in quality, purity, and potency among over-the-counter herbal products.

4.3. Research and regulatory recommendations

4.3.1. Trial quality and relevance

Future RCTs should adhere strictly to CONSORT guidelines, including pre-registration of study protocols and statistical analysis plans. Methodological rigor must be ensured through appropriate randomization procedures, allocation concealment, and blinding of participants and investigators. Trials should incorporate extended follow-up durations to assess durability of effect and explicitly define and evaluate minimal clinically important differences to contextualize clinical significance beyond statistical outcomes.

4.3.2. Populations and settings

Subsequent research should prioritize multicenter and multi-ethnic cohorts to enhance external validity and generalizability beyond single-country or homogeneous populations. Inclusion of diverse geographic, cultural, and healthcare settings will allow more representative assessment of efficacy and safety across global populations.

4.3.3. Products and dosing

Investigational products should utilize standardized extracts with clearly defined marker compounds, validated quality control procedures, and batch-to-batch consistency specifications. Transparent reporting of composition and dosage is essential. Future studies should explore dose–response relationships and combination regimens—for example, antioxidants co-administered with PDE5 inhibitors, or herbal formulations combined with low-dose PDE5 inhibitors—to evaluate potential synergistic effects and optimize therapeutic efficacy.

4.3.4. Safety and economic evaluation

Adverse events should be systematically collected and reported with standardized definitions, clear denominators, and temporal associations. In parallel, cost-effectiveness analyses and treatment de-escalation strategies (such as dose-sparing or step-down algorithms) should be incorporated to inform rational, sustainable clinical implementation.

4.3.5. Mechanistic linkage

To substantiate biological plausibility, future trials should integrate biomarker-based endpoints—including nitric oxide bioavailability, redox balance, endothelial function, and relevant hormonal parameters. Where feasible, omics-level profiling (e.g., metabolomics, proteomics, transcriptomics) should be employed to elucidate mechanistic pathways and identify potential predictors of response.

5. Conclusions

Herbal dietary supplements demonstrate generally favorable effects across multiple outcomes related to ED, with the most robust and consistent evidence observed for saffron and ginseng. Mechanistically, nitric oxide–mediated and antioxidant pathways, as well as combination strategies incorporating PDE5 inhibitors, appear particularly promising and biologically plausible. Nonetheless, for botanicals other than saffron and ginseng, the supporting evidence remains limited by the small number, short duration, and variable quality of existing clinical trials. Therefore, routine clinical use of these agents cannot yet be endorsed until larger, longer-term, and better-standardized RCTs are available. With the advancement of methodologically rigorous research, standardized product formulations, and comprehensive evaluations of safety and cost-effectiveness, herbal interventions could be more confidently incorporated into evidence-based management frameworks for ED.

Authorship contribution statement

Chao-Yen Ho: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Supervision, Writing - original draft, Writing - review & editing.

Chung-Hua Hsu: Conceptualization, Data curation, Formal analysis, Writing - original draft, Writing - review & editing.

Tsai-Ju Chien: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing.

All authors read and approved the final manuscript.

Funding source

This study received no funding.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary data

The following is the Supplementary data to this article: