The light dose
It is well known that photobiomodulation (PBM) has biostimulatory action. However, these beneficial properties can only be achieved when using and applying PBM in a clever way. PBM converts light energy into metabolic and thus triggers multiple factors that contribute to several processes, such as the increase of ATP.1,2 It is important to note that the effects are only possible within an ideal therapeutic window characterized by a specific response of each tissue and/or cell type3.
All about the correct dose
Currently, there is already pre-established knowledge that PBM therapy may present stimulatory and inhibitory results, as well as no effects at all, depending on the dose used, resulting in the so-called biphasic dose/response.4 This curve was first identified and named in the late 19th century,5 but it certainly offered another proof of the Arndt-Schultz Law. This rule, named after Hugo Schulz and Rudolf Arndt in 1888, basically states that, for every substance, small doses stimulate, moderate doses inhibit, and large doses kill. For an even older source, Paracelsus stands out with one of his famous phrases: “The dose makes the poison,” claiming that poison is in everything, and nothing is without poison: the dosage makes it either a poison or a remedy. The principles of biphasic response state that a very low dose of light has no effect, and a lightly higher dose generates a positive effect until a threshold is reached.3 If the dose of light is increased beyond that point, the benefit progressively decreases until the baseline (no effect) is reached, and further increases will have detrimental effects on the tissue.3-6 Variables can be analyzed in isolation, but the proper understanding of PBM parameters, as well as its application time, is more an integration exercise than a memorization one: this understanding is mandatory to achieve clinical results and biological benefits.
Some authors like to consider irradiation parameters as the “medicine” and irradiation time as the “dose”.7 This is not the only approach. Besides, since it has been demonstrated that these are not necessarily reciprocal (e.g., if the power is doubled and the time is halved, then the same energy is delivered, but a different biological response is often observed6), it is probably an oversimplification of the matter. Still, it is useful to properly understand PBM parametrization.
The dose/response curve
The evaluation and knowledge of the dose/response curve can be of great value in the choice of protocols to be proposed and can be used in the scientific and clinical settings in different types of pathologies.3 The “medicine” parameters—wavelength, irradiance, pulse structure, coherence, and polarization—are summarized in Table 1. The “dose” parameters—energy, energy density, irradiation time, and treatment interval—are summarized in Table 2.
As with any other forms of technology-based treatment, there is a lot of physics behind PBM. Wavelength, for example, shows an effective optical window that runs from about 600 nm to 1200 nm, where tissue penetration of light is maximized. This is the reason why the use of PBM in animals and human beings involves red and infra-red lights almost exclusively.8
As regards the energy involved in PBM treatments, published articles applied diverse energy densities on cells, typically ranging from 0.1 J/cm2 to 7.5 J∕cm2, with 1 J/cm2 and 5 J/cm2 sweet spots.9 Power densities at the site normally range from 0, 1.67 mW∕cm2 to 12.5 mW∕cm2, since the energy is usually delivered in 10 minutes. In spite of these, some studies have examined power up to 1000 mW.9 Results show that diverse cell types may respond differently to light and that their responses were dose dependent.10Again, the following must be taken under consideration: i) if doses are too low, they will not trigger the metabolic paths that will ultimately lead to PBM biological benefits,11 and ii) very high doses will be harmful. Therefore, 5 J/cm2 as a sweet spot was applied to different cell types.12,13
Dosimetry in PBM, laser and LLLT is highly complicated. Due to the large number of interrelated parameters, there are no comprehensive studies analyzing the change of effects when individual parameters are varied one by one, and it must be pointed out that it is unlikely that such a study will ever be carried out.14 This considerable level of complexity means that the choice of parameters often depends on the experimenter’s or the practitioner’s personal preference or experience rather than on a consensus by an authoritative body.
1- Hamblin MR. Mechanisms and mitochondrial redox signaling in photobiomodulation. Photochem Photobiol 2018;94:199–212.
2- Karu T. Mitochondrial mechanisms of photobiomodulation in context of new data about multiple roles of ATP. Photomed Laser Surg 2010;28:159–60.
3- Flores Luna GL, de Andrade ALM, Brassolatti P, Bossini PS, Anibal FF, Parizotto NA, Leal ÂMO. Biphasic Dose/Response of Photobiomodulation Therapy on Culture of Human Fibroblasts. Photobiomodul Photomed Laser Surg. 2020 Jul;38(7):413-18.
4- Hawkins D, Houreld N, Abrahamse H. Low level laser therapy (LLLT) as an effective therapeutic modality for delayed wound healing. Ann N Y Acad Sci 2005;1056: 486–93.
5- Mester E, Nagylucskay S, Waidelich W, TiszaS, Greguss P, Haina D, et al. Effect of direct laser radiation on human lymphocytes. Arch Dermatol Res 1978;263:241-5.
6- Mignon C, Uzunbajakava NE, Castellano-Pellicena I, Botchkareva NV, Tobin DJ. Differential response of human dermal fibroblast subpopulations to visible and near-infrared light: potential of photobiomodulation for addressing cutaneous conditions. Lasers Surg Med 2018; 50:859–82.
7- Huang YY, Chen AC, Carroll JD, Hamblin MR. Biphasic dose response in low level light therapy. Dose Response 2009;7(4):358-83.
8- Karu TI, Afana ́aseva NI. Citochrome C oxidase as the primary photoacceptor upon laser exposure of cultured cells to visible and near IR-range light. Dokl Akad nauk 1995;342:693-5.
9- Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012Feb;40(2):516-33.
10-Sungsoo N, ThucNhi Truong V, Feifei J, Joll JE, Yunxia G, Achint U, et al. Dose analysis of photobiomodulation therapy on osteoblast, osteoclast, and osteocyte. J Biomed Opt 2018;23(7): 0750081-8.
11-Barolet D. Light-emitting diodes (LEDs) in dermatology. Semin Cutan Med Surg. 2008Dec;27(4):227- 38.
12- Han B, Fan J, Liu L, Tian J, Gan C, Yang Z, et al. Adipose-derived mesenchymal stem cells treatments for fibroblasts of fibrotic scar via downregulating TGF-β1 and Notch-1 expression enhanced by photobiomodulation therapy. Lasers Med Sci. 2019Feb;34(1):1-10.
13-Ahrabi B, Rezaei Tavirani M, Khoramgah MS, Noroozian M, Darabi S, Khoshsirat S, et al. The Effect of Photobiomodulation Therapy on the Differentiation, Proliferation, and Migration of the Mesenchymal Stem Cell: A Review. J Lasers Med Sci. 2019Fall;10(Suppl 1):S96-S103.
14-Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. The nuts and bolts of low-level laser (light) therapy. Ann Biomed Eng. 2012Feb;40(2):516-33.