Oral Antioxidant Therapy With L-Glutathione and Vitamin C for Persistent Post-Hepatitis B Vaccine Nodules: A Pilot Prospective Interventional Study

Background: Persistent subcutaneous nodules following Hepatitis B vaccination are uncommon but distressing adverse events, often associated with aluminum-based adjuvants. These lesions may persist for months to years, causing discomfort, itching, and cosmetic concerns. Current treatment options such as intralesional corticosteroids or surgical excision are invasive and carry risks of scarring and recurrence. Given the central role of oxidative stress and chronic inflammation in granuloma formation, antioxidant therapy presents a potential non-invasive therapeutic alternative. Objective: This pilot study aimed to evaluate the effectiveness and safety of oral L-glutathione and vitamin C in the treatment of chronic subcutaneous nodules induced by Hepatitis B vaccination. Methods: Five adults (aged 24–31 years) with persistent nodules lasting more than 12 months post-Hepatitis B vaccination were enrolled in a prospective interventional study. Participants received oral reduced L-glutathione (750 mg twice daily) and vitamin C (1000 mg daily) for four months. Outcomes included ultrasound-based nodule volume measurements, clinical assessments of size and firmness, and patient-reported itching severity on a 5-point Likert scale, measured at baseline, two months, and four months. Compliance was monitored through pill counts and adherence diaries. Results: All participants completed the study. Mean baseline nodule duration was 42.6 months. At two months, all cases demonstrated partial regression in size and firmness, with ultrasound showing a mean reduction in nodule volume from 0.52 cm³ to 0.28 cm³. By four months, four of five participants exhibited complete clinical and ultrasound resolution, while one showed a 70% reduction in volume (final volume: 0.15 cm³). Moderate localized itching was reported by three participants, with no adverse events recorded. Conclusion: Oral antioxidant therapy with L-glutathione and vitamin C demonstrated promising effectiveness in reducing or resolving persistent post-vaccine nodules without adverse effects. This safe, accessible, and non-invasive intervention may represent a viable alternative to surgical or corticosteroid-based treatments. Larger randomized controlled trials are warranted to validate these findings and establish standardized treatment protocols.