Table 2.
Alternative medicines and herbal remedies investigated in ED
| Study design | Intervention dosage and duration | Patient cohort description (n) | Control group (n) | IIEF outcomes | Other outcomes | Adverse effects | Reference | |
|---|---|---|---|---|---|---|---|---|
| Single herbal extractions | ||||||||
| Double-blind, randomised, placebo-controlled crossover trial | Korean ginseng (2700 mg/day for 4 weeks) | Patients with ED (45) | Placebo (45) | Significant increase in IIEF and the Erectile Function, Intercourse Satisfaction and Sexual Desire domains compared to control | Significant increase in percentage of rigidity of the tip of the penis compared to control; no significant difference in end-diastolic velocity, post-systolic velocity, and percentage of rigidity for the base of the penis compared to control |
No adverse events reported by participants | 23 | |
| Multicentre, double-blind, randomised, placebo-controlled trial | Korean ginseng berry extract (1400 mg/day for 8 weeks) | Mild-to-moderate ED (59) | Placebo (59) | Significant increase in IIEF-15 compared to control after 4 weeks; No significant increase in IIEF-15 compared to control after 8 weeks; Significant intragroup improvement for IIEF-15 after 4 and 8 weeks |
No significant changes for total testosterone, HDL, LDL, and prolactin compared to control | No adverse events reported by participants | 26 | |
| Double-blind, randomised, placebo-controlled trial | Korean ginseng (tissue-cultured mountain ginseng extract 2000 mg/day for 8 weeks) | Patients with ED (65) | Placebo (21) | Significant increase in IIEF and the Erectile Function, Intercourse Satisfaction and Overall Satisfaction domains compared to control | No significant changes for testosterone, LH, FSH, prolactin and oestradiol compared to control | Not reported by the authors | 24 | |
| Double-blind, randomised, placebo-controlled trial | Korean ginseng (3000 mg/day for 12 weeks) | Patients with ED (30) | Placebo (30) | Significant increase in the IIEF-5 compared to control | No significant changes for testosterone, prolactin and cholesterol compared to control | Not reported by the authors | 25 | |
| Double-blind, randomised, placebo-controlled trial | Panax notoginseng extract (1 capsule/day for 12 weeks) | Japanese adult men with low libido and IIEF scores (22) | Placebo (22) | Significant increase in the Intercourse Satisfaction of the IIEF compared to control | Significant increase in Androgen Deficiency in the Aging Male questionnaire, pre- and post-sleep penile circumference compared to control; No increase on serum PSA compared to control |
No adverse events reported by participants | 30 | |
| Double-blind, randomised, placebo-controlled trial | Pycnogenol (Pinus pinaster subsp. Atlantica 120 mg/day for 3 months |
Patients with ED (21) | Placebo (21) | Significant increase in IIEF-5 compared to control | Significant increase of plasma antioxidant activity and significant decrease in total cholesterol and LDL compared to control | Not reported by the authors | 31 | |
| Double-blind, randomised, placebo-controlled trial | Pycnogenol (Pinus pinaster subsp. Atlantica 120 mg/day for 4 months) | Patients with ED (32) | Placebo (21) | Significant increase in the Erectile Function domain of the IIEF compared to control | Significant reduction in total cholesterol and LDL compared to control; No significant change in HDL, triglycerides or glucose compared to control |
No adverse events reported by participants | 32 | |
| Double-blind, randomised, placebo-controlled trial | Tribestan (Tribulus terrestris herba extractum siccum (35–45:1) 1560 mg standardised to 675 mg furostanol saponins/day for 12 weeks) | Mild-to-moderate ED >6 months (86) | Placebo (86) | Significant increase in IIEF and the Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control |
Significant increase in Global Efficacy Question compared to control; No significant difference in total cholesterol, LDL, HDL, triglycerides, blood pressure, total and free testosterone, DHEA-S, and SHBG compared to control. |
Reported as well tolerated with no significant difference between groups. | 38 | |
| Double-blind, randomised, placebo-controlled trial | Trib Gold (Tribulus terrestris, standardised to contain 45% steroidal saponins, 750 mg/day for 3 months) |
Ageing patients with ED and LUTS (35) | Placebo (35) | Significant increase in IIEF-5 compared to control | Significantly increased aspartate transaminase and PSA compared to control; No significant change in IPSS compared to control |
Not reported by the authors | 37 | |
| Double-blind, randomised, placebo-controlled trial | Lepidium meyenii (2400 mg/day for 12 weeks) | Mild ED (25) | Placebo (25) | Significant increase in IIEF-5 compared to control | Significant improvement in the Satisfaction Profile compared to control; No significant difference testosterone, FSH, LH and prolactin compared to control |
No adverse events reported by participants | 41 | |
| Double-blind, randomised, placebo-controlled crossover trial | Pomegranate juice (237 mL [8 fl oz] beverage/day for 4 weeks) | Mild-to-moderate ED (53) | Placebo (53) | No significant increase in IIEF-5 compared to control | Significant improvements in Global Assessment Questionnaires compared to control | Upper respiratory infections (8%), diarrhoea (2%), flatulence (2%), hyperlipidaemia (2%), nasal congestion (2%) and hypertension (2%) | 56 | |
| Randomised, placebo-controlled trial | Ashvattha Kshirpaka (20 g powder of root, stem with bark, and budding leaves with 1 glass of milk/day for 45 days) | Diabetic and non-diabetic patients with ED (22) | Placebo (22) | Significant increase in IIEF and the Erectile Function, Intercourse Satisfaction and Orgasmic Function domains compared to control | No significant changes in total cholesterol, HDL, LDL, triglycerides, glucose, urea, creatinine, testosterone and DHEA-S compared to control | Not reported by the authors | 57 | |
| Double-blind, randomised, placebo-controlled trial | Butea superba tubers (500 mg/day for 4 days followed by 1000 mg/day for a total of 3 months) | Patients with ED (17) | Placebo (14) | Significant intragroup increase in 4 of the 5 questions of the IIEF-5 | No intragroup changes in haematology and blood chemistry analysis | Not reported by the authors | 58 | |
| Double-blind, randomised, placebo-controlled trial | Withania somnifera (6000 g/day for 60 days) | Psychogenic ED (41) | Placebo (45) | No significant effect on IIEF-5 and IIEF-15 compared to control | None | Not reported by the authors | 59 | |
| Combination herbal formula | ||||||||
| Multicentre single-blind, randomised, placebo-controlled trial | Tradamix TX1000 (Ecklonia bicyclis 600 mg), Tribulus terrestris 900 mg, and glucosamine oligosaccharide 500 mg daily for 3 months) | Mild-to-moderate ED (87) | Placebo (90) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase in the Male Sexual Health Questionnaire (Ejaculation Disorder), the Sexual Quality of Life scores and post-systolic velocity compared to control; No change in end-diastolic velocity or serum testosterone compared to control |
No adverse events reported by participants | 39 | |
| Multicentre Double-blind, randomised, placebo-controlled trial | VXP (Panax ginseng root 200 mg, Serenoa repens berry 200 mg, Crategus rivularis berry 200 mg, Ginkgo biloba leaf, Turnera diffusa leaf 200 mg, Tribulus terrestris vine 150 mg, Erythroxylum catuaba bark 100 mg, Ptychopetalum olacoides bark 100 mg, Cuscuta chinensis seed 50 mg, Epimedium sagittatum leaf 30 mg and Bioperine extract from Piper nigrum fruit 10 mg daily for 12 weeks) | Mild-to-moderate ED (39) | Placebo (36) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase in EDITS score compared to control; No significant change in testosterone, sperm count, semen volume, sperm motility, and investigator’s global assessment and subjects’ opinion compared to control |
Well tolerated with minor adverse events not statistically different from placebo | 29 | |
| Double-blind, randomised, placebo-controlled trial | Cappra® (Cervus Nippon Temminck 150 g, Epimedium Drevicornum Maxim 120 g, Cynomorium Songaricum Rupr 844 g, Carthamus Tinctorius 138 g, and Cistanche Deserticola 150 g daily for 2 weeks) | Mild-to-moderate ED (63) | Placebo (63) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | No changes in haemoglobin, haematocrit, platelet count, alanine transaminase, aspartate transaminase, alkaline phosphatase, blood urea nitrogen, serum creatinine and glucose | Reported as well tolerated; minor reports included dizziness (13.3%), face numbness (1.6%), and tachycardia (1.6%) | 60 | |
| Double-blind, randomised, placebo-controlled trial | NRL/MW/201,901 (L-citrulline and extracts of Withania somnifera, Mucuna Pruriens, Anacyclus pyrethrum, Abutilon indicum, Trigonella foenum-qraecum, Ginkqo biloba, Myristica fragrans, Pansx ginseog, Tribulus terrestris and Svzygium aromaticum daily for 60 days) | Mild-to-moderate ED (50) | Placebo (36) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase in Quality of Erection questionnaire, number of sexual encounters, intra-vaginal ejaculation latency time and serum testosterone compared to control | No adverse effects reported by participants | 40 | |
| Preliminary randomised, placebo-controlled trial | KBMSI-2 (Ginseng Radix Rubra, Dioscorea tenui-pes, Cornus officinalis Sieb. et Zucc., Lycium chinense Mill, and Curcuma longa Linn – 12 g/day for 6 weeks) | Patients with ED (19) | Placebo (20) | Significant increase in IIEF, Erectile Function and Intercourse Satisfaction domains compared to control | No significant changes in Aging Males’ Symptoms Scale and serum total testosterone compared to control | One mild adverse event reported | 28 | |
| Combination herbal formula and non-herbal nutraceuticals | ||||||||
| Double-blind, randomised, placebo-controlled crossover trial | Prelox (L-arginine aspartate 3 g and Pycnogenol 80 mg daily for 1 month) | Mild-to-moderate ED (50) | Placebo (50) | Significant increase in IIEF-15 compared to control | Significant increase in sperm intracellular e-NOS and serum testosterone compared to control | No adverse events reported by participants | 33 | |
| Double-blind, randomised, placebo-controlled trial | Prelox (L-arginine aspartate 2.8 g and Pycnogenol 80 mg daily for 6 months) | Mild-to-moderate ED (54) | Placebo (57) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase serum testosterone compared to control; No significant effects on blood pressure, cholesterol or glucose compared to control |
Excellent risk profile with few adverse effects reported by participants | 34 | |
| Double-blind, randomised, placebo-controlled trial | L- arginine (690 mg), aspartic acid (552 mg) and Pycnogenol (Prelox) (60 mg) daily for 2 months | Mild-to-moderate ED (11) | Placebo (12) | Significant increase in IIEF and the Intercourse Satisfaction domain compared to control | Significant decrease in blood pressure, aspartate transaminase and γ‐glutamyl transpeptidase, and increase in salivary testosterone compared to control | No adverse events reported by participants | 36 | |
| Double-blind, randomised, placebo-controlled crossover trial | Pycnogenol® (80 mg), roburins, L-arginine, L-citrulline (1 month) | Moderate ED (25) | Placebo (25) | Significant increase in IIEF and Erectile Function domain compared to control | None | Without unwanted side-effects | 35 | |
| Double-blind, randomised, placebo-controlled trial | SX (L-arginine glutamate and yohimbine (daily for 4 weeks) | Mild-to-moderate ED (20) | Placebo (20) | Significant improvement in Erectile Function domain compared to control | None | Adverse events not statistically different from placebo | 44 | |
| Double-blind, randomised, placebo-controlled three-way crossover trial | L-arginine glutamate (6 g) and yohimbine hydrochloride (6 mg) daily for 2 weeks | Mild-to-moderate ED >3 months (48) | Placebo (48) | Significant increase in IIEF and Erectile Function, Intercourse Satisfaction and Overall Satisfaction domains compared to control | None | Well tolerate and few adverse events. Minor adverse events included headache and insomnia | 43 | |
| Yohimbine hydrochloride (6 mg) daily for 2 weeks | No significant increase in IIEF compared to control; Significant intragroup improvement for IIEF |
|||||||
| Double-blind, randomised, placebo-controlled trial | Vitamin E (100 IU), Korean ginseng (67 mg) and Eleutherococcus senticosus (40 mg) daily for 6 weeks | Patients with ED (26) | Placebo (26) | Significant increase in Erectile Function domain of IIEF compared to control | None | No clinically important adverse effects reported | 27 | |
| Non-herbal nutraceuticals | ||||||||
| Double-blind, randomised, placebo-controlled trial | L-arginine (5 g) daily for 4 weeks | Type 2 diabetics with mild-to-moderate ED (40) | Placebo (26) | Significant increase IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase in testosterone compared to control | Not reported by the authors | 42 | |
| Double-blind, randomised, placebo-controlled crossover trial | L-arginine aspartate (8 g) and adenosine monophosphate (200 mg) taken 1–2 h before intercourse | Mild-to-moderate ED (26) | Placebo (26) | Significant increase in overall IIEF, the Erectile Function and Intercourse Satisfaction domains compared to control | Significant increase in Erection Hardness Score and EDITS score compared to control | Reported as well tolerated; minor GIT complaints reported in 2 patients | 44 | |
| Double-blind, randomised, placebo-controlled trial | Myoinositol (4 mg) and folic acid (400 µg) daily for 12 weeks | Type 2 diabetes with ED >6 months (88) | Placebo (88) | Significant intragroup increase in IIEF-5 | Significant intragroup increase in end-diastolic velocity and post-systolic velocity compared to control | Not reported by the authors | 61 | |
| Double-blind, randomised, placebo-controlled trial | Niacin 1500 mg/day for 12 weeks | ED with hyperlipidaemia (61) | Placebo (65) | Significant intragroup increase in the IIEF and Erectile Function domain compared to control | Significant intragroup increase in the Sexual Health Inventory for Men | Patients reported flushing (36.3%), itchiness (32.5%), headache (5%), gastric discomfort (3.8%), palpitations (3.8%), presyncope (2.5%), chest pain (1.3%) and others (10%). Flushing and itchiness were reported significantly more compared to control | 62 | |
| Double-blind, randomised, placebo-controlled trial | DHEA 50 mg/day for 24 weeks | Patients with ED (17) | Placebo (13) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | Significant increase in DHEA and testosterone compared to control; No significant change in prolactin, PSA, prostate volume and post-void residual volumes compared to control |
No adverse effects reported by participants | 63 | |
| Acupuncture and moxibustion | ||||||||
| Randomised, placebo-controlled trial | Acupuncture specific against ED (unreported duration) | Psychogenic ED (19) | Acupuncture specific against headache (1) | Significant intragroup increase in overall IIEF, Erectile Function and Intercourse Satisfaction domains | None | Not reported by the authors | 46 | |
| Randomised, placebo-controlled trial | Acupuncture with warm needling moxibustion (4 sessions) | Patients with ED (24) | Conventional acupuncture without warm needling moxibustion (22) | Significant increase in IIEF-5 compared to control | None | Not reported by the authors | 47 | |
| Lifestyle (diet and nutrition) | ||||||||
| Single-blind, randomised, controlled trial | Tailed caloric intake reduction and physical activity increase advice to achieve a loss of ≥10% in their total body weight for 2 years | Obese males with ED without diabetes, hypertension, or hyperlipidaemia (55) | General information about healthy food choices and exercise (55) | Significant increase in IIEF-5 compared to control | Significant decrease in BMI, cholesterol, triglycerides, glucose, insulin, IL6, IL8 and CRP compared to control | Not reported by the authors | 48 | |
| Single-blind, randomised controlled trial | Detailed advice about how to reduce body weight, improve quality of diet, and increase physical activity for 2 years | Male patients with ED (104) | General information about healthy food choices and exercise (105) | Significant increase in IIEF-5 compared to control | Significant decrease in BMI, waist circumference, blood pressure, glucose and insulin, and increase in HDL, compared to control; no significant change in total cholesterol and insulin |
Not reported by the authors | 49 | |
| Parallel feeding, randomised, controlled trial | 60 g/day of a mixture of raw walnuts, almonds, and hazelnuts for 14 weeks | Males with ED (43) | Usual Western-style diet avoiding nuts (40) | Significant increase in the Orgasmic Function and Sexual Desire domains of the IIEF compared to control | No difference in serum NO and E-selectin compared to control | No adverse events reported by participants | 50 | |
| Lifestyle (exercise) | ||||||||
| Randomised controlled trial | Interval exercise training programme (8 weeks of 60–79% heart rate max reserve for 45–60 min/day) | Hypertensive patients with ED (21) | Age-matched sedentary hypertensive control group (21) | Significant increase in IIEF compared to control | Significant decrease in serum CRP compared to control | Not reported by the authors | 52 | |
| Randomised controlled trial | Aerobic physical activity (150 min of moderate intensity aerobic activity/week for 3 months) | Vascular ED (50) | Age-matched patients with vascular ED who did not accept the physical activity (50) | Significant increase in IIEF-5 compared to control | Significant increase in peak systolic velocity and significant decrease in acceleration time compared to control; significantly lower serum concentrations of original immunophenotype endothelial progenitor cells and endothelial microparticles compared to control | Not reported by the authors | 51 | |
| Randomised controlled crossover trial | Pelvic floor muscle exercises enhanced by manometric biofeedback and lifestyle changes (reducing alcohol consumption, stopping smoking, reducing weight, getting fit and avoiding bicycle saddle pressure) daily for 3 months | ED >6 months (28) | Lifestyle changes (27) | Significant intragroup increase in IIEF-5 | Significant intragroup improvement in men with post-micturition dribble | Not reported by the authors | 54 | |
| Randomised controlled crossover trial | Pelvic floor muscle exercises enhanced by manometric biofeedback and lifestyle changes | ED >6 months (28) | Lifestyle changes (27) | Significant increase in the Erectile Function domain of IIEF compared to control | Significant improvement in anal pressure and digital anal grades compared to control | Not reported by the authors | 53 | |
| Randomised controlled trial | Sexual rehabilitation (physical exercise training, pelvic floor exercise and psychoeducation for 4 months) | ED with ischaemic heart disease or implantable cardioverter defibrillator (77) | Usual care (77) | Significant increase in IIEF-5 compared to control | Significant increase exercise capacity and pelvic floor strength compared to control; no significant difference in the Psychosocial Adjustment to Illness Scale compared to control | Not reported by the authors | 55 | |
| Topical treatments | ||||||||
| Double-blind, randomised, placebo-controlled trial | Crocus sativus gel (pea-sized amount on half the penis 30 min before intercourse for 1 month) | Diabetic men with ED (25) | Placebo (25) | Significant increase in IIEF and the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse Satisfaction and Overall Satisfaction domains compared to control | None | Not reported by the authors | 64 | |
BMI: body mass index; CRP: C-reactive protein; EDITS: Erectile Dysfunction Inventory of Treatment Satisfaction; GIT: gastrointestinal tract; HDL: high-density lipoprotein; IL: interleukin; LDL: low-density lipoprotein; SHBG: sex hormone-binding globulin.