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
Atici et al. (Mon,) studied this question.