BACKGROUND: Reactive oxygen species have a major role in the UV-induced short and long term damage, thus the exogenous supplementation of antioxidant molecules may allow better skin protection. Despite glutathione has pivotal properties in the complex cytoplasmic antioxidant system, its supplementation is hampered by limited transmembrane absorption. Modification of glutathione pharmacokinetic properties via acetylation with long chain polyunsaturated fatty acid may improve its passage through phospholipidic membranes. METHODS: This was a single center randomized double-blinded clinical trial, versus placebo, cross sectional pairwise at time 0. The partecipants were 10 healthy volunteers with skin phototypes II or III and age >/=18 years interested in performing MED evaluation performed by photoallergology unit of Dermatology division, P. Palagi hospital, Florence. Each volunteer underwent UVB phototesting, treating 4 distinct areas with increasing UVB doses in 4 distinct conditions. One arm was treated as standard procedure ("Naive" arm), one applying linolenic-glutathione conjugate (Lin-GSH) cream 2% before irradiation ("Pre Lin-GSH" arm), one with placebo ("placebo" arm) and one applying Lin-GSH cream 2% after irradiation ("post Lin-GSH" arm). The aim was to evaluate efficacy of Lin-GSH cream 2% before UVB irradiation compared with placebo. Secondary objective is the evaluation of the same cream applied after irradiation compared to no treatment. Other Secondary objective is the evaluation of safety in both conditions. Mean MED was evaluated at distinct conditions. Safety was evaluated reporting all grade 3-4 adverse events up to 30 days after treatment. All volunteers were treated in all 4 experimental conditions. "Pre Lin-GSH" and "Placebo" arms were applied in a double blind condition in each volunteer. Neither the volunteer nor the investigator executing MED evaluation knew which arm contained Lin-GSH and which one contained placebo. RESULTS: Ten volunteers among 12 recruited for the study were correctly randomized and completed all study evaluations. Recruitment went from 01 April 2016 to 01 May 2016, up to adequate population number. Mean MED in "Pre Lin-GSH" arm was superior to mean MED in "placebo" arm (135 mJ/cm2 +/- 5.53 vs 105 mJ/cm2 +/- 7.64, p=0.0003. No difference was observed among mean MED in "Post Lin-GSH" and "Naive" arms. No grade 3-4 Adverse Events were reported. CONCLUSIONS: Lin-GSH 2% cream seems a safe and effective molecule able to exert significant increase in MED compared with placebo thanks to its antioxidant properties.