Is L-Arginine Ready for Clinical Use in Chronic Anal Fissure?A Critical Appraisal of the Current Evidence

Document Type : Letter to the Editor

Authors

1 Acibadem Kent Hospital, Department of General Surgery, Izmir, Turkey

2 KRC Clinic for Colorectal Surgery and Peritoneal Surface Malignancies, Izmir, Turkey

10.30476/acrr.2026.110366.1281

Abstract

Chronic anal fissure (CAF) is a common benign anorectal condition driven by internal anal sphincter hypertonicity and impaired anodermal perfusion, often resulting in persistent symptoms and high recurrence rates after medical therapy. L-arginine has recently been proposed as a conservative treatment option based on its role as a nitric oxide precursor and its potential to induce sphincter relaxation and improve local blood flow. This article provides a critical appraisal of the biological rationale and available clinical evidence supporting L-arginine in CAF management. Although early physiological studies and limited clinical trials suggest possible reductions in resting anal pressure and symptom improvement, the overall evidence remains limited and heterogeneous. Existing studies are constrained by small sample sizes, short follow-up, variable routes of administration, and non-standardized outcome measures, with a lack of direct comparisons to established first-line therapies such as topical nitrates or calcium channel blockers. Moreover, conflicting experimental data raise unresolved mechanistic questions regarding dosing, administration route, and patient selection. At present, L-arginine should be regarded as an investigational or adjunctive therapy rather than a validated alternative in routine CAF treatment. Well-designed randomized controlled trials with standardized endpoints and long-term follow-up are required to define its clinical role

Highlights

Semra Demirli Atici (Googlescholar)

Keywords

References

1. Shojaei-Zarghani S, Hosseini SV.
Could L-Arginine Be a Feasible
Treatment for Chronic Anal Fissure?
Iran J Colorectal Res. 2025;13:30-1.
2. Lu Y KM, Lin AY. Diagnosis and
Treatment of Anal Fissures in 2021.
JAMA 2021;7(325):688-9.
3. Nelson RL TK, Morgan J, Jones
A. Non surgical therapy for anal
fissure. Cochrane Database Syst Rev
2012;2012(2).
4. Griffin N ZD, Briel JW, Gruss HJ,
et al. Topical L-arginine gel lowers
resting anal pressure: possible
treatment for anal fissure. Dis Colon
Rectum. 2002;45(10):1332-6.
5. Gosselink MP DM, Zimmerman
DD, Gruss HJ, et al. Treatment of
chronic anal fissure by application
of L-arginine gel: a phase II study
in 15 patients. Dis Colon Rectum.
2005;48(4):832-7.
6. Khalighi Sikaroudi M SM, Shidfar
F, Talebi S, Hosseini-Baharanchi
FS, et al. L-Arginine is a feasible
supplement to heal chronic anal
fissure via reducing internal anal
sphincter pressure: a randomized
clinical trial study. Amino Acids.
2023;55(2):193-202.
7. Prins HA GM, Mitales LE, Buise MP,
et al. The effect of oral administration
of L-arginine on anal resting pressure
and anodermal blood flow in healthy
volunteers. Tech Coloproctol.
2005;9(3):229-32;discussion 32-3.
8. Acheson AG GN, Scholefield JH,
Wilson VG. L-arginine-induced
relaxation of the internal anal
sphincter is not mediated by nitric
oxide. Br J Surg. 2003;90(9):1155-62.
9. Sierra-Arango F dlH-VJ, Espinosa
JP, Moreno-Montoya J, et al. Clinical
Outcomes of Medical Management
Options for Chronic Anal Fissures in
a Long-Term Follow-up: Systematic
Review and Meta-Analysis. Dig Dis.
2023;41(5):822-32.
10. Arslan C KE, Altintas T, Pekuz C,
et al. Retrospective analysis on the
efficacy of botulinum toxin alone
versus combined botulinum toxin and
topical diltiazem. Int J Colorectal Dis.
2025;40(1)(54).
11. Realis Luc A DVA, Salvatore
A, Gravante G, et al. Long-term
incontinence rates after traditional
lateral internal sphincterotomy: a
5-year retrospective analysis from a
high-volume tertiary referral center
for proctologic disorders. . Tech
Coloproctol. 2025;29(1)(149).
12. Motamed-Gorji N MM, Sikaroudi
MK, Agah S, Masoodi N. Exploring
the therapeutic potential of L-arginine
in chronic anal fissure management: a
comprehensive review. Amino Acids.
2025;57(1).
Iranian Journal of Colorectal Research
Volume 13, Issue 3
September 2025
Pages 109-110

Files

Share

How to cite

Statistics