Link Between Melatonin and Vitiligo
Current Understanding of Melatonin's Role in Vitiligo
The evidence suggests melatonin plays a complex role in vitiligo pathophysiology, but its use as a treatment remains experimental with limited clinical evidence. While melatonin metabolism is disrupted in vitiligo patients, the therapeutic application of melatonin supplementation has not been established as an effective treatment in clinical guidelines 1.
Pathophysiological Connection
Disrupted Melatonin Metabolism in Vitiligo
Epidermal melatonin production is significantly impaired in vitiligo patients due to H₂O₂/ONOO⁻-mediated oxidative stress that damages tryptophan hydroxylase (TPH) and dopa decarboxylase (DDC) enzymes, leading to decreased serotonin and melatonin synthesis 2.
Patients with non-segmental vitiligo and stress history show below-normal plasma melatonin levels (as low as 4.05 pg/ml compared to normal range of 20.2-31.1 pg/ml), with direct correlation between low melatonin levels and disease duration 3.
The depletion of L-tryptophan metabolism affects immune response mechanisms and eliminates melatonin as a relevant contributor to epidermal redox balance in vitiligo 2.
Theoretical Mechanisms
One historical hypothesis proposed that abnormalities in putative melatonin receptors on melanocytes might contribute to vitiligo pathogenesis, though this has not been definitively demonstrated 4.
Melanocytes possess melatonin receptors, and UV exposure through phototherapy might theoretically synchronize circadian melatonin regulation, potentially improving sleep quality and enhancing anti-inflammatory properties 5.
Clinical Evidence for Melatonin Treatment
Limited Therapeutic Data
Only one small prospective comparative study (n=13) examined melatonin treatment in chronic vitiligo, showing larger BCVA improvement compared to controls with no reported side effects in 3 patients 1.
This single study is insufficient to establish melatonin as a recommended treatment, and melatonin is not mentioned in the British Association of Dermatologists' comprehensive vitiligo treatment guidelines 1.
Phototherapy as Indirect Melatonin Modulator
Narrow-band UVB phototherapy remains the gold standard treatment for vitiligo primarily through immunomodulatory effects, not melatonin modulation 5.
The potential benefits of phototherapy on circadian melatonin regulation and subsequent sleep improvement require further investigation, as current evidence is conflicting and insufficient 5.
Clinical Implications and Recommendations
Current Treatment Approach
Melatonin supplementation cannot be recommended as a treatment for vitiligo based on the available evidence, which consists of only one small uncontrolled study 1.
The British Association of Dermatologists guidelines do not include melatonin in their treatment algorithms for vitiligo, focusing instead on topical corticosteroids, phototherapy, and surgical interventions 1.
If Considering Melatonin Use
If melatonin is considered for sleep disturbances in vitiligo patients (not for treating vitiligo itself), start with 3mg immediate-release formulation 1.5-2 hours before bedtime 6.
Choose United States Pharmacopeial Convention Verified formulations due to concerns about purity and reliability of stated doses in dietary supplements 1, 6.
Monitor for potential side effects including headaches, gastrointestinal upset, and changes in blood pressure (both hypotension and hypertension have been reported) 1, 6.
Be aware that melatonin has been associated with impaired glucose tolerance in healthy women after acute administration 1, 6.
Important Caveats
The systemic and physiological properties of melatonin regulated by phototherapy may theoretically be more relevant than topical or oral melatonin supplementation, but this remains speculative 5.
The evidence suggests that melatonin depletion is a consequence of vitiligo's oxidative stress rather than a primary cause, making supplementation unlikely to address the underlying pathophysiology 2.
Any consideration of melatonin should be as an adjunct for sleep regulation or general well-being, not as a primary vitiligo treatment, and only after established therapies have been appropriately utilized 1, 5.