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

Abstract

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm² ). 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 3 weeks at fluences of 160-640 J/cm² for all skin types (STARS 1, n = 60) and at 480-640 J/cm² 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. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm² in STARS 1 (n = 1) and 640 J/cm² in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm² for skin of color and 480 J/cm² 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.

Keywords: low-level light therapy; phototherapy; randomized controlled trial; skin pigmentation.

Figure 1.

Study design schematic and dose escalation algorithm for STARS 1.

Figure 2.

Study design schematic and dose escalation algorithm for STARS 2.

Figure 3.

CONSORT flow diagram for STARS 1.

Figure 4.

CONSORT flow diagram for STARS 2.

Figure 5.

(A) Development of a 5 mm blister on the volar forearm of an African American subject after receiving the first HF-LED-RL treatment session (480 J/cm²). (B) Biopsy of the blister edge shows a subepidermal split with partial re-epithelialization and no significant underlying inflammatory infiltrate (hematoxylin & eosin, 100x). (C) On higher magnification, necrotic keratinocytes within the blister roof are evident, along with clumping of melanin pigment (hematoxylin & eosin, 200x).