Beta-Alanine and Aquagenic Pruritus: Proposed Neuroimmune Mechanism.

Unlabelled: Aquagenic pruritus (AP) is a rare itch disorder with limited effective treatments, and emerging clinical observations suggest that oral β-alanine may reduce symptoms. The purpose of this viewpoint is to propose a biologically plausible mechanism through which β-alanine may alleviate primary AP. We reviewed published case reports and patient-reported survey data describing β-alanine use in AP and integrated these clinical observations with experimental data on MAS-related G protein-coupled receptor D (MrgprD)-expressing sensory neurons and their role in mast-cell regulation. Published case reports describe marked improvement in water-induced pruritus following prophylactic oral β-alanine administration, and a recent survey of patients with idiopathic AP reported substantial symptom relief among β-alanine users. Preclinical data indicate that MrgprD-neuronal glutamate release suppresses mast cell hyperresponsiveness, suggesting a potential pathway for the observed antipruritic effect. Additional mechanisms, including β-alanine metabolism to carnosine and its potential mast cell-stabilizing effects, may also contribute. β-alanine may act through modulation of a nonhistaminergic neuroimmune circuit and represents a promising therapeutic candidate for further investigation in AP.