Red Light Therapy(RLT) and Photobiomodulation(PBM): Mechanisms, Efficacy, and Protocols

The following is an excerpt from an objective evidence summary, written to inform product development.

Mechanisms

Chromophore vs Photoacceptor

The first law of photobiology says that photons must be absorbed by a molecule in the cell to have any biological effect.  This molecule can be a chromophore or a photoacceptor. Melanin, hemoglobin and water are the main chromophores in skin.  They absorb light and convert it into heat. 

PBM involves photoacceptors, which are molecules that absorb light, causing a chemical reaction. 

COX

 The main photoacceptor targeted in PBM is cytochrome c oxidase (CCO or COX).  COX is a component of the electron transport chain in mitochondria. Photon absorption by COX increases cellular respiration, and therefore increases ATP, and the cell’s ability to do work. 

The leading hypothesis to explain exactly how light increases CCO enzyme activity, is that nitric oxide, which is known to bind to CCO and inhibit respiration, can be displaced by a photon of red or NIR light.

COX has two absorption bands, in the RL (665 nm) and in the NIR (810 nm) regions.  

The skin has an optical wavelength window (600–1300 nm) in which melanin, hemoglobin, and water absorption coefficients are the smallest. Within this optical window, RL and IRA light is absorbed by COX to trigger non-thermal photobiomodulatory effects.

Wavelengths

PBM efficacy depends on the parameters of the treating light, including 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 pulse mode.

The optical properties of the skin or tissue being treated will affect the outcome.  Light is scattered by keratin and melanosomes in the epidermis, and collagen in the dermis, reducing the amount that is absorbed.  Short wavelengths scatter more than longer wavelengths. 

Estimated penetration depth:

633 nm RL: 1 to 3 mm 

810 nm NIR: 2 to 10 mm

890 nm NIR: 5 to 15 mm

1072 nm NIR: 5-10 mm

The deepest penetration is achieved by NIR at around 810 nm.  Depth of penetration is directly proportional to wavelength, but also wavelength is inversely proportional to power.  Longer wavelengths start to become absorbed by water, abundant in superficial layers of skin.

There is often an underlying assumption that a more focused higher power incident beam results in better delivery of light at depth. It was demonstrated >30 years ago that a specific wavelength of light delivered to tissue at a uniform and constant power density resulted in substantially greater depths of penetration when the light was delivered over a larger area. Two other features of note in their study were the fact that the irradiance required to achieve the same power density over the larger area was significantly greater than that for the small spot, and they also found that laser light focused on tissue behaved in the same manner as the same wavelength delivered through a fiber. Therefore, it would make sense to use light arrays or larger diameter beams with sufficiently high irradiances for PBMT regimes rather than treating using multiple treatments at individual points, at least for some PBM applications.

ROS 

The secondary effects of photon absorption include increases in ATP, an increase in nitric oxide, change in calcium levels, and a brief burst in ROS as a byproduct of cellular respiration.  These then lead to the activation transcription factors of many genes that lead to increased proliferation and migration, and new protein synthesis, and increased survival.

ROS are by-products of aerobic metabolism. Low levels of ROS (0.001-0.7 μM) promote cell metabolism whereas high levels (20-200 μM) result in destruction due to oxidative stress and damage.  At low levels, ROS may act as a messenger leading to the activation of many cytokines and messengers involved in inflammation and repair.

Biphasic Dose Response 

PBM shows a biphasic dose response, meaning a very low dose of light has no effect, a somewhat bigger dose has a positive effect, until a plateau is reached. If the dose is increased beyond that point, the benefit decreases, until the baseline (no effect) is reached, and then any further increases will start to have damaging effects on the tissue. This curve is known as hormesis. 

 TPRV1 Channel

Exposure to NIR can also promote ATP production through a temperature-dependent increase in activity of transient receptor potential vanilloid 1 (TRVP1, temperature range: 40-45 °C). The increase in TRVP1 activity modulates calcium levels resulting in cell proliferation and differentiation.  This was much later discovered, and still not as accepted as an established mechanism compared to COX. 

TRPs are non-specific cation channels that respond to heat, and a variety of noxious stimuli.  They are important in the endings of pain neurons.  Activation allows an influx of Ca++, which leads to increased metabolism and excitability of cells, such as mast cells and fibroblasts.

A study in 2017 corroborated the involvement of TRPV with experiments on wavelengths 810nm and 980 nm.  Both these wavelengths are effective in PBM, and both produce increased ATP and mitochondrial activity, but it was not known what was absorbing the 980nm.  In this experiment, their peak activity was 10-100 times different, 810 peaking at 3 J/cm2, and 980 at 0.3-0.03 J/cm2.  The effects of 980nm could be blocked by calcium channel blockers which had no effect on 810nm. The researchers theorized that the photons could be heating the water around the TRPV channels, activating the channels.  This was supported when the cells were chilled, and the effects of 980, but not 810, were blocked.

Effects 

Reduction of Lines and Wrinkles 

Most studies focus on RL, NIR, and amber light (AL), a light of 590 nm close to red light. RL has shown improvement in wrinkles and signs of photodamage when applied alone in repeated sessions. Histologically, a decrease in aging damage, such as an increase in type I collagen and a slight decrease in metalloproteinases, was observed.

The combination of RL and NIR was evaluated, and a significant improvement in wrinkles, smoothness, and skin firmness was observed. RL, NIR, and their combination were compared, and RL was found to be more effective in reducing blemishes and dark stains since NIR showed higher effectiveness in improving skin elasticity and wrinkles. These authors recommended using the combination of both RL and NIR when treating photoaging.

The combination of RL with white light was evaluated in two studies, and it was found that both produced significant improvement in wrinkles without finding differences between the application of both types of wavelengths

RL was compared with amber light (AL) of 590 nm for the treatment of periorbital wrinkles, and both lights achieved a decrease in wrinkles around the eyes, with slightly better results with RL…..