ALA-PDT with high-fluence red light has shown impressive results in reducing acne lesions. Unfortunately, the pain and swelling associated with the treatment make it a poor choice for acne patients, particularly those with facial acne. In an effort to maintain results but reduce pain, Fernanda Sakamoto, MD, and her colleagues performed a randomized, double-blinded control study to compare conventional ALA-PDT to a new inhibitory PDT method (iPDT) that involves irradiating the aminolevulinic acid (ALA) with low-levels of blue light during the incubation period. The researchers found that low-level light exposure during ALA metabolism prevented the accumulation of epidermal porphyrins, while allowing for accumulation in deeper tissues, including the sebaceous glands. Blinded evaluation of histopathology samples showed a reduction of sebaceous glands and inflammatory acne in areas treated with ALA-PDT and those treated with iPDT. Both methods demonstrated significant improvement in the 18 subjects that finished the study (out of 29 original participants), but the intense pain and immediate inflammatory side effects were reduced in iPDT-treated sites. Delayed side effects were not reduced with the new protocol.