Photomedicine relies on the use of either LEDs or lasers as light sources which interact with the human body in fundamentally distinct ways.

Keywords:

photomedicine, UVA, UVB

Lasers produce heat effects and may cause burns because they produce a specific type of light, namely the coherent light. In technical terms, coherent light consists of photons of the same frequency and whose wavelengths are in phase with one another. Incoherent light, like the one generated by LEDs, generates photons whose frequencies are not the same and their wavelengths are not in phase with one another. Coherent light is very efficient in transferring and focusing energy on the target, however it also generates a large amount of heat which may be counterproductive for the therapeutic purposes.

LEDs, on the other hand, generate incoherent light, which may penetrate as deeply into the human body as the laser light, but without adverse effects such as burning. Lasers can have a very narrow bandwidth; for instance in gas lasers it can be a fraction of a nanometer, while in diode lasers the bandwidth is typically 1-2 nm. Laser-based devices can deliver substantially greater energy of light than LEDs, up to 1,600 J/cm2, however energies in excess of 750 J/cm2 can be detrimental, with negative outcomes attributed mainly to thermal effects. Here J denotes Joule, the unit of energy which is equal to Watt per second). Also, the focal nature of laser light delivery narrows the irradiation areas. LED devices energy delivery is limited to approximately 30 J/cm2. The light produced by LEDs can be either continuous or photomodulated. Photomodulation means that the light is generated in the pulse mode with specific pulse sequences and specific durations. Pulsed light affects cells and tissues in a different way as compared to the continuous one.

Commercially available LEDs for therapeutic purposes have wavelengths in the yellow, blue, red and near infrared parts of the spectrum. Red light, also used in the Lucha t8 device, penetrates deeper into the tissue than yellow or blue light. Illustration of penetration depth for each type of light is presented in Fig. 1. Yellow, blue and green light (wavelengths less than 630 nm) are considerably blocked by the hemoglobin in the blood, so they do not penetrate deeply. As a matter of fact, this could be checked by covering LED with the finger resulting in only the red light being transmitted through the finger tissue and appearing visible on the other side of the finger. Wavelengths greater than 900 nm are blocked by liquid from the skin and connective tissues. Many wavelengths in this range emit a large amount of energy that cannot be seen by the human eye, producing a certain amount of heat when interacting with the human skin.

Fig. 1 Tissue penetration depths of light of various wavelengths (https://www.beautyandlongevity.com/photonic-light/)

Red light penetrates the body beyond blood vessels and capillaries and it also reaches the periphery nerve endings as well. Note that near infrared light can penetrate deeper in the body than the UVA light rays. UVA has wavelengths in the range 315 – 400 nm (nanometers), while UVB range is 280 – 315 nm. Illustration of UV penetration into the tissue is presented in Fig.2.

Fig. 2 Penetration effects of UVA and UVB light

There are also short-wavelength UVC rays in the range 100 – 280 nm, however they are completely filtered by the atmosphere and they do not reach the surface of the earth. UVB cannot penetrate beyond the superficial skin layers and causes short term effects such as delayed tanning. It enhances skin aging and may cause the development of skin cancer. UVA accounts to approximately 95% of all UV rays that reach the Earth. It causes immediate tanning effects (compare the UVB delayed tanning effect) and also contributes to the skin aging. It may also be responsible for the development of melanoma.

The absorption of UV light within the skin and peripheral tissue causes a complex cascade of processes that involve damage and repair of the cells, pigmentation changes, immunosuppression effects and vascular changes. On the molecular level UV wavelengths are absorbed by the nucleic acid bases that tend to have broad peaks around the 260 nm – 340 nm range. The chemical processes caused by the UV interaction with the tissue results in the formation of several types of DNA lesions which may lead to melanoma and non-melanoma skin cancer. However, there is a counterbalancing beneficial effect of the exposure to UV radiation. This is the vitamin D biosynthesis due to the conversion of provitamin D3 to previtamin D3. The previtamin D3 is then thermally converted to vitamin D3 which is then transported to the liver by the D-binding protein.

Since red light has the most important and beneficial therapeutic effects further exposition is focused exclusively on the LED generated red light in the near infrared and infrared part of the spectrum. The reason why red light penetrates deeper than other colors is that skin consists of a range of chromophores (light absorbing molecules) which have highly wavelength dependent scattering and absorption coefficients. The scattering property (graphically represented in Fig. 1) refers to the light dispersion in the tissue and reduction of energy with increasing penetration depth. Thus, the chromophores of the skin and the tissue immediately beneath the skin have high absorption coefficients and low scattering coefficients for the wavelengths in the red part of the spectrum. The therapeutic benefits are achieved via various pathways, but most research indicates that red light appears to affect cellular metabolism by initiating photobiochemical reactions.

Observed effects include increased energy cellular levels by increased ATP (adenosine triphosphate), induction of transcription factors, modulation of oxygen species, stimulation of angiogenesis and increased blood flow. Red lights generated by LEDs have been studied for a wide variety of uses, including wound healing, the treatment of certain types of nonmelanoma skin cancers, tumors, warts and the prevention of mucositis in cancer patients. A study of red light of 633 nm wavelength on patients who have undergone blepharoplasty (a type of surgery that repairs droopy eyelids and may involve removing excess skin, muscle and fat), showed statistical significant improvement of erythema, bruising, edema and pain reduction on the side of the face treated by this red LED light. This list of beneficial effects of red LED treatment is not exhaustive as research activities in this area are very active.

Although the mechanism which causes cellular photobiostimulation by red light is not yet completely understood, it is clear that the effects are evident on the molecular, cellular and tissue levels. The fundamental biological mechanism behind the effects of red light is through the absorption of light by mitochondrial chromophores which are located in the mitochondria of the respiratory system, in particular cytochrome c oxidase (CCO), which releases bound nitric oxide NO. This enables oxygen to re-bind CCO and resume respiratory activity, leading to the synthesis of the ATP and calcium signaling. The absorption also takes place within the photo-sensitive molecules in the plasma membrane of cells. During inflammation and cell stress, high levels of NO block CCO functioning and consequently limit repair functions.

It has been proposed that the extracellular release of NO, ATP, or growth factors may activate autocrine signaling which results in beneficial effects of phototherapy. Autocrine signaling refers to the processes in which a cell secretes a hormone that binds to the appropriate receptors on that same cell, causing changes in the cell. In less technical terms, a cascade process is initiated in the mitochondria which leads to biostimulation of various processes through enhancement of enzyme activity, electron transport and ATP production. With more energy, cells can function more efficiently, rejuvenate themselves, and repair damage. By changing the cellular oxidation state a number of intracellular signaling pathways are activated and the affinity of transcription factors concerned with cell proliferation, tissue repair and regeneration is also altered.

The efficacy of the Red LED light used for therapeutic purposes, depends mainly upon these factors:

  • irradiance,
  • wavelength,
  • type of light (continuous or pulsating) and
  • usage pattern.

Irradiance refers to the energy generated by the red LED per unit of area and is given in Watts/cm2 or J/cm2. In general, the higher the irradiance the better the results from therapy may be expected. Since Lucha t8 is not conceived as a therapeutic device targeting a specific health problem, this energy is low as only one LED is used. The choice of wavelength is also important since different wavelengths are administered for different types of health problems. Longer wavelengths penetrate deeper in the tissue and experimental and practical studies indicate that red light in the range of 630-660 nm and near-infrared light in the range 800-830 nm provide the best results for most ailments and health issues. Usage pattern should be individually determined depending on the health condition which is treated and expected results, however it seems that consistency in daily or weekly treatments yields the best results.

The aim of many research projects was to discern the benefits of different wavelengths for the treatment of certain health conditions. Based on the experimental evidence so far, a general consensus is that wavelengths between 625 nm and 900 nm are the most effective for healing wounds, tissue repair and other skin conditions. At the lower end, 630 nm and 660 nm appear to show the best effects, while at the high end 850 nm and 880 nm are the most effective. However, there are many ongoing research projects that may contribute to the better understanding of the effects of these and other wavelengths.

Several studies have discovered that the average wavelength of cell tissue in the human body ranges between 600nm and 720nm, with 660nm being the median. A wavelength of 660nm seems to be the most efficient because the corresponding frequency, inversely proportional to the wavelength, is closer to the resonant frequency of cell tissue, allowing it to absorb better in hemoglobin. Hemoglobin is a red protein responsible for transporting oxygen in the blood. The mitochondria can absorb red light easily at the 630nm and 660nm wavelengths, which roughly coincide with the absorption peaks of cytochrome c oxidase (the target of light therapy).