Stesura Seveso 373Archivio Italiano di Urologia e Andrologia 2022; 94, 3 LETTER TO EDITOR No conflict of interest declared. Submitted 3 July 2022; Accepted 9 July 2022 To the Editor, Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfacto- ry sexual performance (1). ED represents one of the most important male sexual dysfunctions with a prevalence of 52% and affecting more than 150 million men worldwide (estimated to be 322 million worldwide for 2025) (2-4). In the last years, several dietary supplements and herbal remedies have been introduced alone or in combinations with other treat- ments. These products have been used in traditional medicine for their aphrodisiac proprieties or as compounds that increase sexual arousal, libido, potency (erection) and/or sexual pleasure. Panax ginseng (Korean ginseng), Tribulus terrestris (Tribulus), Epimedium gradiflorum (Horny goat weed), Lepidium meyenii (Maca), Ginkgo biloba (Ginkgo), Eurycoma longifo- lia Jack (Tongkat ali), and Pausinystalia johimbe (yohimbine), B complex vitamins, zinc, trace minerals, L-arginine, aspar- tate and dehydroepiandrosterone (DHEA) have been reported as the most used products on the market (5-6). Despite the increasing use, very low scientific evidence has been described, particularly regarding efficacy, safety, extractions, and dosage. Mobile phone applications (MHAs) are mobile software programs, providing information and support to patients in many fields including health. Nowadays, more than 325,000 MHAs are available and widely used in the healthcare set- ting, to provide information about several medical conditions including sexual dysfunction, but the scientific evidence is very poor (7). In our previous study we analyzed MHAs for ED using the Mobile Application Rating Scale (MARS scale) and reported their adherence to European urology Guidelines. MARS is a multidimensional instrument evaluating engagement (items assessing the extent to which the app engages target users), functionality (items assessing how easy the app is to navigate and the overall app performance), esthetics (items assessing visual appearance and style), information (items assessing accuracy, quality, and quantity of the app), app subjective quality, and app-specific, showing a very acceptable reliability and validity) (8). We found an overall low quality of MHAs and poor adherence to EAU guidelines. Among treatments they suggested there were both herbal interventions and non-herbal nutraceuticals, alone or in com- binations. Over the time several studies suggested herbal interventions in ED management with a high scientific support. Balasubramanian et al. in a recent meta-analysis reported the most popular erectile dysfunction supplements available on online marketplaces: Ginseng is the most popular followed by L-arginine, and Tongkat ali (9). Interestingly, none of the analyzed apps reported any of the supplements in this list or the most popular used ones. Furthermore, ginseng and L- arginine as shown by Borrelli et al. are the only two supplements that showed an effective efficacy in ED treatment (10). MHAs suggested using (Table 1): garlic, bryonia laciniosa, butea superba, ginger, ginkgo Biloba, carrots, pomegranate juice, onion, almonds and clove. Garlic (Allium sativum) represents one of the oldest plants, recognized for its health benefits in cardiovascular diseases (11). The most important bioactive component is S-allyl cysteine (SAC) which possesses antioxi- dant property (12). Bryonia laciniosa is characterized by antimicrobial, larvicidal, anti-inflammatory, cytotoxic, analgesic, and antipyretic activities and it is very used in India as a tonic and enhancer of sexual behaviors. Butea superba increased intracavernous pressure and cavernous smooth muscle relaxation (13). One MHA suggested using ginger, the only nutraceutical that showed to enhance iNOS activity in vitro. Other MHA sug- gested products were carrots that improve sexual function and desire through testosterone enhancing; pomegranate juice which is characterized by antioxidant activity (anthocyanins) and involved in endothelial nitric oxide (NO) levels regula- tion; in the end, onion which is a source of hydrogen sulfide and quercetin, involved in erection and antioxidant path- way respectively (14, 15). Almond is characterized by antistress, antidiabetic, antihypertensive and antioxidant propri- eties (16, 17). Many of these home remedies have not reported a great scientific support and few studies have been con- ducted on human, with several drawbacks: regarding garlic, Nishimatsu et al. reported his experience in 24 men using a preparation containing garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb, with improvement of ED (18). Despite all this, the negative role of oxidative stress and of endothelial dysfunction in ED patho- physiology is well established, and all dietary supplements suggested reported antioxidant effects. According to the cur- rent data no strong scientific evidence supports nutraceutical products suggested by MHAs. Therefore, further work, and more involvement of healthcare are necessary to improve the quality of scientific evidences reported by MHAs. Natural treatments for erectile dysfunction: A focus on mobile health applications Luigi Napolitano, Luigi Cirillo, Giovanni Maria Fusco, Marco Abate, Vincenzo Morgera, Gianluigi Cacace, Giuseppe Celentano, Biagio Barone, Lorenzo Spirito, Vincenzo Mirone, Roberto La Rocca Department of Neurosciences, Reproductive Sciences and Odontostomatology, School of Medicine, University of Naples "Federico II", Naples, Italy. DOI: 10.4081/aiua.2022.3.373 Archivio Italiano di Urologia e Andrologia 2022; 94, 3 L. Napolitano, L. Cirillo, G.M. Fusco, M. Abate, et al. 374 REFERENCES 1. Pastuszak AW. Current diagnosis and management of erectile dysfunction. Curr Sex Health Rep. 2014; 6:164-76. 2. Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. J Urol. 1994; 151:54-61. 3. Romano L, Granata L, Fusco F,, et al. Sexual dysfunction in patients with chronic gastrointestinal and liver diseases: a neglected issue. Sex Med Rev. 2021; S2050-0521(21)00039-1. 4. Mirone V, Napolitano L, D’Emmanuele di Villa Bianca R, et al. A new original nutraceutical formulation ameliorates the effect of Tadalafil on clinical score and cGMP accumulation. Arch Ital Urol Androl. 2021; 93:221-6. 5. Kuchakulla M, Narasimman M, Soni Y, et al. A systematic review and evidence-based analysis of ingredients in popular male testosterone and erectile dysfunction supplements. Int J Impot Res. 2021; 33:311-7. 6. Corazza O, Martinotti G, Santacroce R, et al. Sexual enhancement products for sale online: raising awareness of the psychoactive effects of yohimbine, maca, horny goat weed, and Ginkgo biloba. Biomed Res Int. 2014; 2014:841798. 7. Napolitano L, Fusco GM, Cirillo L, et al. Erectile dysfunction and mobile phone applications: Quality, content and adherence to European Association guidelines on male sexual dysfunction. Arch Ital Urol Androl. 2022; 94:211-6. 8. Stoyanov SR, Hides L, Kavanagh DJ, et al. Mobile app rating scale: a new tool for assessing the quality of health mobile apps. JMIR MHealth UHealth. 2015; 3:e27. 9. Balasubramanian A, Thirumavalavan N, Srivatsav A, et al. An analysis of popular online erectile dysfunction supplements. J Sex Med. 2019; 16:843-52. 10. Borrelli F, Colalto C, Delfino DV, et al. Herbal dietary supplements for erectile dysfunction: a systematic review and meta-analysis. Drugs. 2018; 78:643-73. 11. Brace LD. Cardiovascular benefits of garlic (Allium sativum L). J Cardiovasc Nurs. 2002; 16:33-49. 12. Colín-González AL, Santana RA, Silva-Islas CA, et al. The antioxidant mechanisms underlying the aged garlic extract- and S-allylcysteine- induced protection. Oxid Med Cell Longev. 2012; 2012:907162. 13. Tocharus C, Smitasiri Y, Jeenapongsa R. Butea superba Roxb. enhances penile erection in rats. Phytother Res. 2006; 20:484-9. 14. Gur S, Kadowitz PJ, Sikka SC, et al. Overview of potential molecular targets for hydrogen sulfide: A new strategy for treating erectile dys- function. Nitric Oxide Biol Chem. 2015; 50:65-78. 15. Zhang W, Wang Y, Yang Z, et al. Antioxidant treatment with quercetin ameliorates erectile dysfunction in streptozotocin-induced diabetic rats. J Biosci Bioeng. 2011; 112:215-8. 16. Siriwardhana SSKW, Shahidi F. Antiradical activity of extracts of almond and its by-products. J Am Oil Chem Soc. 2002; 79:903-8. 17. Adefegha SA, Oboh G, Oyeleye SI, Ejakpovi I. Erectogenic, antihypertensive, antidiabetic, anti-oxidative properties and phenolic composi- tions of almond fruit (Terminalia catappa L.) parts (hull and drupe) - in vitro. J Food Biochem. 2017; 41:e12309. 18. Nishimatsu H, Kitamura T, Yamada D, et al. Improvement of symptoms of aging in males by a preparation LEOPIN ROYAL containing aged garlic extract and other five of natural medicines - comparison with traditional herbal medicines (Kampo). Aging Male Off J Int Soc Study Aging Male. 2014; 17:112-6. Table 1. App characteristics. Name of application Android/Apple/Both Producer Category Nutraceutical product Erectile dysfunction treatment Android Revolxa inc. Medicine Asian ginger, Ginkgo biloba Erectile dysfunction remedy 2021 Android Maftal Almafary Education Asian ginger, Ginkgo biloba Erectile dysfunction remedies Android StatesApps Health and Fitness Garlic, cloves, fruit nut mix, onion, drumstick, butea superba Home remedies Android Cutepad studio Medicine Ginger, Onion, Pomegranate juice, Almonds, Garlic, Carrots Herbal cure Android NovaRadix Medicine Bryonia 101 Natural Home Android XL Tech Apps Garlic Correspondence Luigi Napolitano, MD - luiginap89@gmail.com Luigi Cirillo, MD (Corresponding Author) - cirilloluigi22@gmail.com Giovanni Maria Fusco, MD - giom.fusco@gmail.com Marco Abate, MD - marcoabate5@gmail.com Biagio Barone,MD - biagio.barone@unina.it Vincenzo Morgera, MD - vincemorgera87@gmail.com Gianluigi Cacace, MD - cacace.gianlu@gmail.com Giuseppe Celentano, MD - dr.giuseppecelentano@gmail.com Lorenzo Spirito, MD - lorenzospirito@msn.com Vincenzo Mirone, MD - mirone@unina.it Roberto La Rocca, MD - robertolarocca87@gmail.com Department of Neurosciences, Reproductive Sciences and Odontostomatology, Urology Unit, University of Naples "Federico II", Naples, (Italy) Via Sergio Pansini n 5, Naples (NA) (Italy)