What exactly is Low-Level-Light Therapy? Or should we be calling it Low-Level-Laser Therapy? Or Low-Level-Laser-(light) Therapy? Or Cold Laser Therapy? Or Photobiomodulation Therapy? What the heck is Low-Level-LED-Therapy? Who is in charge of naming these things anyways? What is the point of all these syllables?
Tongue-twisters aside, these questions are important. How are we able to have an intelligent discussion about this topic if we are not sure what exactly we are discussing? The semantics can be surprisingly difficult to sort through, in no short measure due to misinformation (perhaps purposefully) perpetuated by medical device marketers, and unqualified keyboard warriors (with hopeful exception of the present blogger). Even the scientific literature can be misleading, due to non-standard and constantly changing terminology.
The terms listed above are often used interchangeably, referring to either identical or very similar therapies. A brief history lesson can help to explain why.
In 1967, shortly after the development of the first working laser (the ruby laser), Hungarian Scientist Endre Mester, was trying to replicate an experiment in which red laser light was demonstrated to eliminate malignant tumors in rats. Mester did not cure any tumors, as his laser contained only a small fraction of the power of that used in the prior experiment. However his low power red laser did produce some interesting effects – namely accelerated wound healing, and hair growth .
Mester called this “Laser Biostimulation,” referring to the stimulatory, and regenerative effects he saw. As therapeutic applications arose for low-powered red lasers, the term Low-Level-Laser Therapy (abbreviated LLLT), was coined. “Low-level” of course described the to the power of lasers used, but more specifically the intensity of treatment, which was too low to cause excessive heating and/or damage to tissues. Although “low-level” is somewhat ambiguous, it made some sense, as it differentiated LLLT from other early applications of lasers in medicine, using much higher intensity for ablation, cutting, and thermal coagulation of tissues. Various other alternative terms reflect this dichotomy such as “cold laser therapy,” “soft laser therapy,” “low-intensity laser therapy,” “low-power laser therapy,” and so on .
Low-Level-Laser Therapy is still used very frequently today, at least recently more frequently than any alternative . However many became dissatisfied with this term when it was demonstrated similar therapeutics effects could be produced using non-laser light sources, such as light-emitting diodes (LEDs) . To account for this, some replaced Low-Level-Laser with Low-Level-Laser-(light), Low-Level-LED, or the more inclusive term, Low-Level-Light Therapy. All of these terms are commonly abbreviated LLLT.
Today the acronym LLLT is widely utilized in both academia, and industry. It may refer to any one of the above terms, but most often Low-Level-Laser, or Low-Level-Light. Regardless of the specific name, LLLT is used to described the same therapeutic – application of non-ionizing light at low power intensity for pain relief, immuno-modulation, healing, and/or tissue regeneration. Most also consider LLLT specific to a narrow range of wavelengths within the electromagnetic spectrum, usually corresponding to red or near infrared (NIR), but others expanded it to all non-ionizing wavelengths with the infrared, and visible spectrums [3,4].
So which one is the correct LLLT? According to the National Library of Medicine (NLM), this would be Low-Level-Light Therapy, which is the official term in their Medical Subject Headings (MeSH) database. For those unfamiliar with MeSH, it is basically an advanced thesaurus for biomedical literature – a database of hierarchically-organized terms used for example to catalog and index pubmed. You can also search the Mesh database (https://www.ncbi.nlm.nih.gov/mesh), for lists of “synonymous” – highly associated and/or interchangeable terms relating to a particular topic. Each list has a header term, which is the official term as recognized by the NLM. So if we search “LLLT,” or any of the various non-abbreviated versions, we find ourselves on the same page, headed by Low-Level-Light Therapy. We can also see the official NLM definition: “Treatment using irradiation with light of low power intensity so that the effects are a response to the light and not due to heat. A variety of light sources, especially low-power lasers are used.” 
But we are not done yet sorry guys – despite its official recognition, many argue that Low-Level-Light Therapy is too broad, as it can also describe clinical applications of low-intensity, non-ionizing light, such as photodynamic therapy (PDT), and optogenetics, which have with distinctly different methods of application, mechanisms of action, and biological effects .
This notion has become stronger in recent years, concurrent with an increase in understanding of how exactly these therapies work on the cellular and molecular level. We now know that when cells are exposed to low intensity light a biological effect can arise from absorption by intracellular molecules called chromophores. These molecules are uniquely able to absorb light due to their specialized, pigment-containing functional groups. When these functional groups are exposed to light of appropriate wavelength, they are able to absorb it to induce functional changes in the chromophore. With sufficient absorption in many chromophores, these functional changes can in turn cascade into larger-scale, long-lasting effects within the cell and the local tissue .
For example, in mammals, red and near infrared (NIR) light is absorbed by the enzyme cytochrome c oxidase (CCO), embedded in the inner mitochondrial membrane. As part of the electron transport chain, CCO plays an integral role in oxidative metabolism. Light absorption increases the activity of CCO, which in turn improves efficiency of cellular respiration, increasing production of ATP. A primary effect of this is that, all else equal, the cell is able to function more efficiently, allowing it to “work” harder, with less metabolic input. Additionally, downstream effects of CCO photoactivation result in production of various secondary mediators, such as reactive oxygen species and nitric oxide, which can result in dramatic, long-term effects on cell behavior through modulation of intracellular signaling, and transcriptional pathways .
Now we are able to have a more mechanistic basis for our definition of these low-intensity, non-ionizing light therapies. Due to low-intensity, they did not damage tissue, or result in other heat-related effects. Similarly, due to non-ionizing wavelengths, they did not damage to cells, tissues, or DNA, in short or long term. Instead the chromophore activation mechanism is allowed to propagate, and be primarily responsible for the biologic effects we observe. The chromophore mechanism also explains why we can see different biologic effects from different non-ionizing wavelengths, as different chromophores are sensitive only to very specific wavelengths of light .
Rooting our definition in the physiological mechanism, allows us to draw a clear line between LLLT, and other applications of low-intensity, non-ionizing light. Specifically both PDT and optogentics involve introduction of new chromophores, either exogenous (in the case of PDT), or through genetic engineering (in the case of optogenetics). By comparison, LLLT as it is normally defined relies wholly on activation of endogenous chromophores .
With mechanism in mind, “Photobiostimulation Therapy,” a variation of Endre Mesters original term “Laser Biostimulation” has been historically argued to be a more scientifically valid than “low-level” terminologies. However it soon became clear that photobiostimulation was inadequate as well, as research revealed a characteristic bi-phasic dose response, which indicated that, although low-intensity light can be stimulatory at low doses, higher does can actually be inhibitory .
Reflecting this, “Photobiomodulation Therapy” (PBMT) has been deemed superior to Photobiostimulation Therapy, as it most accurately describes the mechanistic basis on which these treatments operate. PBMT (or Photobiomodulation (PBM) if referring to the biological process), has gained widespread acceptance within the scientific community as the optimal term describing biomedical application of low-intensity, non-ionizing light, for pain relief, healing, and regeneration. This largely is a result of a recent, concerted effort within the scientific community, including a nomenclature consensus meeting, organized under a joint conference of the North American Association for Light Therapy and the World Association for Laser Therapy in September, 2014 . This meeting provided an updated, arguably more comprehensive definition for Photobiomodulation Therapy (aka Low-Level-Light Therapy), which is “A form of light therapy that utilizes non-ionizing forms of light sources, including lasers, LEDs, and broadband light, in the visible and infrared spectrum. It is a nonthermal process involving endogenous chromophores eliciting photophysical (i.e., linear and nonlinear) and photochemical events at various biological scales. This process results in beneficial therapeutic outcomes including but not limited to the alleviation of pain or inflammation, immunomodulation, and promotion of wound healing and tissue regeneration.” .
So which should we use? Photobiomodulation Therapy, or Low-Level-Light Therapy? PBMT or LLLT? If you’ve stayed with me so far hopefully you are not more confused than when we started.
Arguably either is acceptable. While PBMT benefits from greater specificity and scientific validity, LLLT benefits from greater recognition.
In this blog we will be using LLLT, which will always stand for Low-Level-Light Therapy. This is partially because LLLT is easier for me to type, but mostly because among all alternative terms, we feel it has the best combination of inclusivity and name-recognition. We will consider LLLT and PBMT equivalent, defining both as described in bold above.
- Hamblin MR. Photobiomodulation or low-level laser therapy. J Biophotonics. 2016;9(11-12):1122-1124. doi:10.1002/jbio.201670113. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215795/
- Anders JJ, Lanzafame RJ, Arany PR. Low-level light/laser therapy versus photobiomodulation therapy. Photomed Laser Surg. 2015;33(4):183-184. doi:10.1089/pho.2015.9848. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4390214/
- Hamblin MR. Mechanisms and Mitochondrial Redox Signaling in Photobiomodulation. Photochem Photobiol. 2018;94(2):199-212. doi:10.1111/php.12864. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844808/
- Tsai S-R, Hamblin MR. Biological effects and medical applications of infrared radiation. J Photochem Photobiol B. 2017;170:197-207. doi:10.1016/j.jphotobiol.2017.04.014. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505738/
- National Center for Biotechnology Information. Medical Subject Headings (MeSH) database (accessed March 2019). https://www.ncbi.nlm.nih.gov/mesh/?term=LLLT