Long-term high-dose l-arginine supplementation in patients with vasculogenic erectile dysfunction: a multicentre, double-blind, randomized, placebo-controlled clinical trial
Open accessAbstract
Purpose: The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of l-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild–moderate and severe vasculogenic ED. Methods: The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU). Results: l-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p < 0.0001) and in subgroups of patients with mild–moderate (p < 0.0001) and severe (p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p < 0.0001) and in patients with mild–moderate (p < 0.0001), but not severe vasculogenic ED. At study completion, 74% of patients improved ED degree category, although only 24% of patients, mainly belonging to the baseline category of mild ED, reached IIEF-6 scores compatible with absence of ED; moreover, 20% of patients, exclusively belonging to the baseline category of mild–moderate vasculogenic ED, reached PSV values compatible with absence of ED. Conclusion: The results of the current study demonstrated that supplementation with relatively high doses of l-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild–moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that l-ARG might be an alternative treatment in mild–moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds.
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Previous studies showed using L-arginine has no significant patient side effects.
“As previous studies showed, using L-arginine has no significant patient side effects.”
From Effect of l-arginine compared to placebo on sexual function in women with major depressive disorder: a randomized controlled trial (2024) · cites this paper as [46]
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“The results of the study showed no serious complications reported in patients who received L-arginine [46].”
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- Authors
- Menafra, D., de Angelis, C., Garifalos, F., Mazzella, M., Galdiero, G., Piscopo, M., Castoro, M., Verde, N., Pivonello, C., Simeoli, C., Auriemma, R. S., Colao, A., & Pivonello, R.
- Affiliations
- University of Naples Federico II (IT)
- Corresponding author
- Pivonello, R.
- ORCID
- Venue
- Journal of Endocrinological Investigation
- Published
- 2022-01-01
- Volume
- 45
- Issue
- 5
- Pages
- 941-961
- ISSN
- 0391-4097 (ISSN-L)
- 1720-8386
- PMC
- PMC8995264
- OpenAlex
- W4205467611
- Cited by
- 15
- References
- 62
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 2
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Endocrinological Investigation (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Università degli Studi di Roma Tor Vergata
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
- Health Sciences › Medicine › Urology › Urological Disorders and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- L-arginine, vasculogenic erectile dysfunction, erectile function, ED severity
- MeSH terms
- Arginine, Double-Blind Method, Humans, Erectile Dysfunction, Male, Penile Erection, Penis, Treatment Outcome, Dietary Supplements
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