Pilot Study Tests Oral NAC as Adjunct in Vitiligo Therapy

A recent small, single-blind phase 1 clinical trial suggests that oral N-acetylcysteine (NAC) used in combination with narrow-band ultraviolet B (NB-UVB) phototherapy may enhance patient satisfaction and clinical improvement in vitiligo compared to NB-UVB alone.¹ Although statistical significance was not achieved, the study highlights a potential new avenue for addressing oxidative stress—a key element in the disease’s pathogenesis.

Background

“Oxidative stress not only initiates melanocyte injury but may also sustain autoimmune activity by exposing hidden epitopes,” the study authors noted.

Given this, antioxidant supplementation has emerged as a logical therapeutic adjunct. NAC, a precursor of cysteine and glutathione, enhances the body’s endogenous antioxidant defense mechanisms and is thought to mitigate oxidative injury. Narrow-band UVB phototherapy, one of the most effective treatments for vitiligo, has also been shown to improve oxidative balance by reducing lipid peroxidation and increasing glutathione levels.²

The current study sought to assess whether combining oral NAC with NB-UVB phototherapy could provide additive clinical benefit compared with NB-UVB alone.¹

Study Design and Methods

This single-blind, randomized phase 1 trial was conducted at the dermatology clinic of Rasool Akram Hospital, Iran University of Medical Sciences, between February and August 2022.

Sixteen adults with generalized vitiligo (vulgaris, acrofacial, or universal types) were enrolled. Participants were randomly assigned to one of two groups:

• Group A (intervention): Oral NAC 600 mg twice daily, starting 2 weeks before and continuing throughout NB-UVB therapy.
• Group B (control): NB-UVB phototherapy alone.

NB-UVB treatments (311 nm) were administered 3 times weekly using a Dermalight 3000 device. The initial dose was 65 mJ/cm², increased incrementally by 65 mJ/cm² per session to a maximum of 1000 mJ/cm².

The primary endpoint was improvement in the Vitiligo Extent Tensity Index (VETI) score, which accounts for both disease area and pigmentation severity. Secondary endpoints included patient satisfaction (5-point Likert scale) and treatment tolerability.

Results

Both groups demonstrated significant improvement over the 4-month treatment period, though intergroup differences did not reach statistical significance.

Baseline VETI scores were 3.11 ± 3.31 in the NAC + NB-UVB group and 3.32 ± 3.58 in the NB-UVB-only group (p = 0.90). After 2 months, these decreased to 1.79 ± 1.96 and 2.13 ± 2.39, respectively (p = 0.71). At 4 months, scores further declined to 1.28 ± 1.34 and 1.89 ± 2.15 (p = 0.57).

Patient satisfaction was notably higher in the combination group. At the 2 month evaluation, 62.5% of patients in the NAC group rated their response as “excellent,” compared to none in the NB-UVB group (p = 0.01). This difference, however, was no longer statistically significant at the 4-month follow-up.

Adverse events were minimal. Only 1 patient (12.5%) in the NAC + NB-UVB arm experienced dizziness, which resolved after dose adjustment. No serious adverse effects were reported.

Given the small cohort (eight participants per arm), post-hoc power analysis revealed a statistical power of 32%, underscoring the preliminary nature of the findings.

Discussion

While both treatment groups achieved significant improvement, the trend toward enhanced efficacy and satisfaction in the NAC + NB-UVB group is biologically plausible. NAC replenishes intracellular glutathione, counteracts lipid peroxidation, and may suppress pro-inflammatory cytokines—all mechanisms relevant to vitiligo pathogenesis.

“Combining NAC with NB-UVB may act synergistically to restore oxidative balance and promote repigmentation,” the authors explained.

Similar synergistic effects have been reported with other antioxidants, such as vitamin E and alpha-lipoic acid, when combined with phototherapy. However, this is the first clinical trial to investigate oral NAC as an adjunct to NB-UVB for vitiligo.

The authors caution that conclusions are limited by the small sample size and short follow-up. “Although the improvements were not statistically significant, the observed trends suggest a potential therapeutic role for NAC,” they stated. Larger, randomized controlled trials are needed to confirm efficacy, optimize dosing, and explore biomarkers such as serum glutathione or malondialdehyde (MDA) to verify oxidative stress modulation.

Clinical Implications

For clinicians, NB-UVB phototherapy remains the cornerstone of vitiligo management. Nonetheless, adjunctive antioxidant therapy represents a growing area of interest, particularly for patients with active or extensive disease. NAC’s favorable safety profile and oral administration make it an attractive potential complement to established regimens.

As the authors conclude, “Oral NAC was well tolerated and may offer potential benefits when combined with NB-UVB phototherapy in patients with generalized vitiligo. Further randomized controlled trials with larger sample sizes and longer follow-up are warranted.”

References

1. Sadeghzadeh-Bazargan A, Farahani S, Goodarzi A, et al. The effectiveness and safety of oral N-acetylcysteine in combination with narrow-band ultraviolet B (NB-UVB) phototherapy compared with NB-UVB phototherapy alone in the treatment of vitiligo: a pilot study. Health Sci Rep. 2025. doi:10.1002/hsr2.71467
2. Karsli N, Akcali C, Ozgoztasi O, Kirtak N, Inaloz S. Role of oxidative stress in the pathogenesis of vitiligo with special emphasis on the antioxidant action of narrowband ultraviolet B phototherapy. J Int Med Res. 2014;42(3):799-805. doi:10.1177/0300060513516294