Red Light Therapy (Photobiomodulation)

This sample contains selected excerpts from an approximately 30-page evidence synthesis I prepared on red light therapy and photobiomodulation. Although I was already familiar with photobiology through the company’s far-infrared product lines, red and near-infrared photobiomodulation involve different wavelengths, biological targets, and proposed mechanisms of action, many of which were new to me.

The assignment was to evaluate the scientific literature on red light therapy and summarize the most relevant findings in a technical report for the CEO and product-development team. The goal was to provide enough scientific and clinical context to support early planning for a potential new product line.

Photobiomodulation (PBM) was discovered in 1967 by Hungarian physician Endre Mester, who was studying lasers and tumor ablation. He noticed that in areas where the power of the laser was insufficient to ablate the tumor, there was an increase in hair growth. The initial term “Low Level Laser Therapy" was replaced by “photobiomodulation” or PBM, in the late 2010s.  "Low level" was rather subjective and non-scientific, and lasers were rapidly being replaced by LEDs in delivery devices.[1]

Mechanisms  

Cytocrome C Oxidase

The first law of photobiology says that to have a biological effect, a photon must be absorbed by a molecule in the cell.  This can be a chromophore or a photoacceptor. The important chromophores in the skin are melanin, hemoglobin and water.  The distinction is that the chromophores absorb light and convert the energy into heat. A photoacceptor absorbs photons and uses the energy to catalyze a chemical reaction. PBM primary involves using photoacceptors to cataylze reactions.

The photoacceptor thought to be central to the effects of PBM cytochrome c oxidase (CCO or COX).  CCO is a component of the electron transport chain in the mitochondrial membrane. Photon absorption by CCO increases cellular respiration, thus increasing ATP, and the cell’s ability to do work. The leading hypothesis to explain exactly how light increases CCO activity is that nitric oxide, which is known to bind to CCO and inhibit respiration, is displaced by a photon of red or NIR light. So, it disables an inhibitor. [2] 

Secondary Mechanisms

Reactive Oxygen Species

The secondary effects of photon absorption include increases in ATP, an increase in nitric oxide, change in calcium levels, and a brief burst of reactive oxygen species (ROS). Reactive oxygen species are by-products of aerobic (using oxygen) metabolism. They are unstable molecules that want to “steal” electrons from other molecules to become more stable.  In doing so, they disrupt other molecules, potentially causing damage to proteins, cells, and DNA.

Low levels of ROS are normal and may even be necessary in our cells. They are thought to stimulate metabolism by activating transcription factors genes that can increase proliferation and protein synthesis, and to be important in cell signaling and immune system activation [3].

Our cells have natural defenses to combat incidental damage that occurs at normal physiologic levels. It is when we are exposed to unusually high levels that our defenses can become overwhelmed, fail to keep up with the damage, and result in lasting damage and cell death. This concept of very different effects at different doses is an example of hormesis, which is also observed in PBM.

TRPV1 Channel

While a much less well established pathway than that of the photoacceptor CCO, An interesting in-vitro study done in 2017 suggests a mechanism involving Transient Receptor Potential Vanilloid 1 channels (TRPV-1). TRPV channels are non-specific cation channels that respond to heat and other noxious stimuli.  They are abundant in the endings of pain neurons.  Activation allows an influx of Ca++, which leads to increased metabolism and excitability of cells.

The study used wavelengths 810 nm and 980 nm.  Both these wavelengths produced increased ATP and mitochondrial activity, but it was not known what the 980 was being absorbed by.  Also, in this experiment, the peak activity was 10-100 times different, 810 nm peaking at 3 J/cm2, and 980 at 0.3-0.03 J/cm2.  When they found that effects of the 980 nm wavelengths, but not the 810 nm, could be blocked by calcium channel blockers, the researchers theorized that the photons could be activating the TRPV channels by heating the water around them.  This was further supported when the effects of the 910 nm wavelengths were also locked when the cells were chilled. [4]

Mechanics/ Optics

The mechanics of light in the skin, how and where the interaction occurs, is dependent on the parameters of the photon, and the properties of the skin.  What happens when a photon enters the skin?  The photons can either scatter, which can be thought of as bouncing around or back out, they can pass through (although this is minimal in most normal-thickness skin), or they can be absorbed. As stated above, to have a biological effect, they must be absorbed. The variables of the light that affect the mechanics and the results are wavelength, fluence (J/cm2), power density (W/cm2, or J/s/cm2), treatment area, treatment duration, the distance of the light source from the treatment area, and the use of pulse mode or continuous.

 The wavelength of a photon determines what molecules will absorb it.  The shorter wavelengths of the visible spectrum, the blue and ultraviolet wavelengths, are best absorbed by melanin and hemoglobin.  Melanin serves as a natural UV protectant, preventing UV rays from damaging deeper structures.  This is why light-skinned people are more vulnerable to damage from UV light.

On the other side of the PBM wavelengths are the longer wavelengths of far infrared, which are readily absorbed by water molecules.   

The chromophores in the skin have the lowest absorption between wavelengths 600 to 1300 nm, or the red and NIR wavelengths. Within that range, the photo acceptor CCo appears to have two absorption bands, 665 nm in the red region, and 810 nm, in the near infrared (NIR or IR-A) region.[3]

Depth of penetration

Depth of penetration receives considerable attention in consumer marketing, often accompanied by the assumption that “deeper is better.” Frequently repeated claims that red or near-infrared light penetrates two to four inches into tissue are difficult to reconcile with optical-tissue research.

Penetration varies with wavelength, tissue, pigmentation, irradiance, and the threshold used to define meaningful penetration. In a separate analysis of the optical literature, I found support for measurable penetration on the order of millimeters to approximately 1.5 cm under some conditions—not for the several inches commonly claimed in consumer marketing. [5]

Also important to note and correct is that greater penetration is not inherently more effective. A therapeutic effect requires sufficient light to be absorbed by a relevant biological target. Depth is not a meaningful measure of treatment quality. In fact, it could be the opposite, if the light is passing right through the tissue you are intending to treat!

In the epidermis, light is scattered by keratin and melanosomes, and by collagen in the dermis.  Shorter wavelengths are scattered more than longer wavelengths. However, longer wavelengths also carry less energy and are rapidly absorbed by water in the superficial layers of skin. Evidence has supported a maximum depth achieved by wavelengths around 890 nm, with both shorter and longer wavelengths scattered or absorbed more superficially. [6]

Effects

Reduction of Fine Lines and Wrinkles

Most studies focus on RL, NIR, and amber light (AL), a light of 590 nm adjacent to red light. Red light therapy has been shown to improve the appearance of wrinkles and signs of photodamage when applied alone in repeated sessions. Histologically, a decrease is seen in typical signs of aging damage, such as an increase in type I collagen and a slight decrease in metalloproteinases…….

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References

1.         Glass GE. Photobiomodulation: The Clinical Applications of Low-Level Light Therapy. Aesthet Surg J. 2021;41(6):723-738. doi:10.1093/asj/sjab025

2.         Austin E, Geisler AN, Nguyen J, et al. Visible light. Part I: Properties and cutaneous effects of visible light. J Am Acad Dermatol. 2021;84(5):1219-1231. doi:10.1016/j.jaad.2021.02.048

3.         Maghfour J, Ozog DM, Mineroff J, Jagdeo J, Kohli I, Lim HW. Photobiomodulation CME part I: Overview and mechanism of action. J Am Acad Dermatol. 2024;91(5):793-802. doi:10.1016/j.jaad.2023.10.073

4.         Wang Y, Huang YY, Wang Y, Lyu P, Hamblin MR. Photobiomodulation of human adipose-derived stem cells using 810nm and 980nm lasers operates via different mechanisms of action. Biochim Biophys Acta. 2017;1861(2):441-449. doi:10.1016/j.bbagen.2016.10.008

5.         Lanzafame R. Light Dosing and Tissue Penetration: It Is Complicated. Photobiomodulation Photomed Laser Surg. 2020;38(7):393-394. doi:10.1089/photob.2020.4843

6.         Lister T, Wright PA, Chappell PH. Optical properties of human skin. J Biomed Opt. 2012;17(9):90901-90901. doi:10.1117/1.JBO.17.9.090901