Biphasic Dose Response in Low Level Light Therapy – an Update

TLDR

Low‑level laser therapy, known since 1967, remains controversial because of incomplete mechanistic understanding and inappropriate dosimetry, yet biphasic dose–response relationships have been demonstrated in vitro and in animal studies, with mediators such as ATP and mitochondrial potential showing biphasic patterns and reactive oxygen species exhibiting a triphasic response whose Janus nature may explain in‑vivo effects. This review updates previous coverage of LLLT biphasic dose responses and aims to clarify their extent to optimize clinical treatment protocols. The authors synthesize recent evidence on cellular mediators and ROS dynamics underlying the biphasic response in LLLT, highlighting how dose and treatment frequency influence therapeutic outcomes. In mice, transcranial LLLT for traumatic brain injury produced a distinct biphasic pattern, with peak neurological benefits occurring at specific numbers of treatments and energy densities.

Abstract

Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous ( Huang et al. 2009 ) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.