Augmented Glutathione Absorption from Oral Mucosa and its Effect on Skin Pigmentation: A Clinical Review

Treatment of dark skin with glutathione has become popular due to its depigmenting properties and low toxicity. Glutathione has been used topically, orally and parenterally in the management of dark skin. There are no clear published guidelines for management of skin pigmentation despite some clinical trials of shorter duration and small sample sizes. We examined published scientific and patient data to generate guidance for the clinician for managing hyperpigmentation using glutathione by orobuccal route. Various aspects of glutathione bioavailability were examined when administered by oral routes. Absorption of glutathione from the gastrointestinal tract is poor. Some trials have favored administering high oral doses to achieve therapeutic effect. General consensus remains against treatment of hyperpigmentation with glutathione by the oral route. Clinical and experimental evidence supporting significant glutathione absorption from orobuccal mucosa was examined. The latter is superior to the oral route since glutathione passes directly into systemic circulation resulting in a much higher rate of absorption compared to that achieved by oral intake. High blood levels thus achieved have therapeutic value. Treatment of hyperpigmentation with glutathione by the orobuccal route using hydroxypropyl cellulose (HPC) film was reviewed to formulate clinical guidance from published data. A future randomized, double-blind, placebo-controlled trial should study treatment of hyperpigmentation with glutathione using oral dispersible HPC film, with longer-term follow-up and larger sample size. This paper will hopefully offer broad guidance for the clinician on use of glutathione for hyperpigmentation management, until outcomes of larger, longer duration trials become available.