Radiation-induced hyposalivation is a common and debilitating side effect of head and neck radiotherapy, significantly impairing patients’ quality of life. Alpha-lipoic acid (ALA), a potent antioxidant, is hypothesized to enhance salivary secretion and promote the regeneration of acinar cells. Our study aimed to evaluate the effect of ALA on unstimulated salivary flow rate in patients undergoing head and neck radiotherapy.

This double-blind, randomized controlled clinical trial included 20 patients undergoing head and neck radiotherapy. Participants were randomly assigned to the intervention group (receiving 1200 mg/day ALA) or to the control group (receiving placebo) for three months. Unstimulated whole salivary flow rate (mL/min) was measured using the spitting method at baseline (pre-radiotherapy) and at weeks 2, 6, 8, and 12 post-radiotherapy. Xerostomia severity was assessed using the Numeric Rating Scale (NRS), alongside clinical signs of hyposalivation (e.g., frothy saliva, mucosal adherence). Data were analyzed using t-tests and Fisher’s exact test in SPSS version 25.00, with a significance level of 0.05.

Although both groups indicated a decline in salivary flow over time, no significant intergroup differences were observed at any follow-up point (P > 0.05). Within the ALA group, pairwise comparisons revealed a significant reduction in salivary flow from baseline to weeks 6, 8, and 12 (P = 0.02, P = 0.01, and P = 0.003, respectively). Additionally, a significant reduction was observed between weeks 2 and 6 (P = 0.011). No significant differences between groups were found in NRS scores or clinical indicators of hyposalivation during any follow-up session (P > 0.05).

Administration of 1200 mg/day ALA may temporarily delay the onset of salivary gland dysfunction in the early phases of radiotherapy. However, this effect was not statistically significant and may not have a sustained clinical benefit.

This clinical trial was approved by the Research Ethics Committee of Shahid Beheshti University of Medical Sciences (IR.SBMU.DRC.REC.1401.062) and registered in the Iranian Registry of Clinical Trials (IRCT20221219056864N1, registered on December 19, 2022).