Safety of light emitting diode-red light on human skin: Two randomized controlled trials

BACKGROUND: Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. OBJECTIVES: To evaluate the safety of high fluence LED-RL (≥160 J/cm(2)). METHODS: In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for three weeks at fluences of 160 to 640 J/cm(2) for all skin types (STARS 1, n=60) and at 480 to 640 J/cm(2) for non-Hispanic Caucasians (STARS 2, n=55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. RESULTS: Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm(2) in STARS 1 (n=1) and 640 J/cm(2) in STARS 2 (n=2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. CONCLUSIONS: LED-RL is safe up to 320 J/cm(2) for skin of color and 480 J/cm(2) for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02630303 and NCT03433222