In general, Photobiomodulation (PBM) and photodynamic Therapy (PDT) are two primary methods, which use light in medicine and dentistry.
Photobiomodulation uses low-level laser or LED light to induce healthy cellular activity including proliferation and repair.
Photodynamic Therapy uses low level laser or LED light combined with a photosensitizing compound (PS) to cause cell death.
Due to the fact that we do not yet fully understand the precise nature of light, as well as the physiological response to light, we consistently observe unexpected, inexplicable, and complex outcomes to the clinical use of PBM.
Thus, though light can be generated with exacting consistency, the physiological response to light can vary tremendously from patient to patient.
Thus, step-by-step protocols have yet to be developed that produce thorough, reliable, and reproducible results for most conditions.
What we do know is:
Using a specific wavelength of light that is absorbed by certain internal components of healthy cells, vital metabolic activity, healthy and balanced cellular turnover, and internal cellular functions can be stimulated and enhanced.
In cases such as COVID with severe mitochondrial disruption the photons of the correct light will stimulate ATP production, providing the damaged cell with sufficient energy to repair itself.
Given the ubiquitous cellular damage caused by the COVID spike protein’s disruption of the Electron Transport Chain in mitochondria of otherwise healthy cells, and because of ischemic tissue damage caused by systemic inflammation, stimulating healthy cellular activity as well as proliferation might prove to enhance and accelerate a COVID patient’s recovery.
Photodynamic Therapy (PDT) is a form of light therapy involving specific light, and a photosensitizing chemical substance that preferentially absorbs that light, that then interacts with molecular oxygen (O2) to generate high-energy oxygenated and toxic molecules, the cause the death of unwanted cells, such as microbial pathogens or malignant cells.
The most popular use of Photodynamic Therapy is treating acne. PDT is also used clinically to treat a wide range of medical conditions, including psoriasis, wet age-related macular degeneration, atherosclerosis, anti-viral treatments, including herpes. It also treats various cancers, including head and neck, lung, bladder, prostate, and particular skin cancers.
Basically, Photodynamic Therapy requires three elements.
The wavelength of the light source being used must be “matched” to the photosensitizer, which excites the electrons in the photosensitizer, which then transfers those electrons to oxygen which become high-energy, highly reactive, and highly cytotoxic (toxic to cells) “singlet oxygen”, which then produce high-energy free-radicals and/or “reactive oxygen species”.
First, a photosensitizer, that is not toxic until it is stimulated by its “matched” light, is administered to the patient. Administration can take three different forms:
Second, for reasons we don’t fully understand, a photosensitizer compound is characterized by its preferential attraction to damaged, diseased or malignant tissue, ignoring healthy normal tissue. During a specific period of time (“incubation”) a sufficient amount of photosensitizer will have been absorbed into the targeted tissue, while the body washes out the presence of the photosensitizer from normal healthy tissue. At the end of the incubation period, the targeted tissue is ready for treatment and is activated by exposure to the “matched” light for a specified period of time.
Third, the light dose supplies sufficient energy to stimulate the photosensitizer, without affecting the neighboring healthy tissue. The resultant cytotoxic “reactive and oxygen species” (ROS) kills the targeted cells.
For reasons that remain obscure, certain Photosensitizing compounds possess a powerful affinity for unhealthy cells, pathogenic microbes or specific components therein, especially but not limited to malignancy. For example: Methylene Blue is powerfully attracted to Malaria and is considered by many to be the perfect therapy to completely rid the patient from the infection.
Once administered to the body (IV) and given sufficient time to saturate the targeted cells (incubation time) the targeted malignant/pathogenic cells will retain the Photosensitizing compound, while healthy cells are able to clear themselves of the Photosensitizing compound during the “incubation” time.
The Photosensitizing compound must also contain the needed molecular components that when stimulated by a specific wavelength of light, are able to release the needed ROS, that will kill the malignant or pathogenic cells.
Many photo-sensitizers for Photodynamic Therapy exist. They divide into 3 groups.
Examples include aminolevulinic acid (ALA), Silicon Phthalocyanine Pc 4, methylene blue, Indocyanine green (ICG), m-tetrahydroxyphenylchlorin (mTHPC) and mono-L-aspartyl chlorin e6 (NPe6).
The major difference between photo-sensitizers is the parts of the cell that they target. Unlike in radiation therapy, where damage is done by targeting cell DNA, most photosensitizers target other cell structures.
For example, mTHPC localizes in the nuclear envelope. In contrast, ALA and Methylene Blue localize in the mitochondria. Methylene Blue also targets oxidized ferric iron (Fe+++) found in Heme molecules such as hemoglobin, which is unable to carry oxygen, typically because of CO exposure or cyanide poisoning. The donated electron reduces the iron to Fe++, allowing hemoglobin to carry oxygen normally. Methylene Blue has too many more positive physiological effects to be addressed in this writing.
The key characteristic of a photosensitizer is the ability to preferentially accumulate in diseased tissue while sparing normal tissues. Thereafter, when exposed to and absorbs its “matched” light, it interacts with oxygen inducing the formation of cytotoxic oxygen species that kills the targeted pathogenic microbes or malignant cells, without effecting the normal healthy neighboring tissues. Specific criteria include:
Photodynamic therapy (PDT) may also damage blood vessels in a tumor, effectively starving it of blood and oxygen. PDT may stimulate the immune system to attack tumor cells in a targeted lesion, as well as unknown malignant cells elsewhere in the body.
Regarding COVID, both of these modalities should theoretically be useful, perhaps even critically important if they can be combined.
1. We need to kill the virus as soon and as quickly as possible post infection. For this Photodynamic Therapy with a Photosensitizing agent that can target the virus, followed by its “matched” frequency (wavelength) of light that is absorbed by the Photosensitizing agent would destroy the virus.
Note: Ideally, in the case of an early onset of the infection, a properly constructed protocol that takes advantage of these properties will clear a patient of an entire viral load quickly, and before systemic damage is created.
Note: On the other hand, if the infection has been lingering for a sufficiently long period of time wherein systemic inflammation has caused ischemic organ damage, symptoms subsequent to the organ damage may persist long after the pathogen has been eliminated. See below.
Furthermore, because of ischemic tissue damage caused by systemic inflammation and the abnormal toxic clotting (also caused by the spike protein), restoring healthy cellular activity via the effect of PBM, that stimulates proliferation might enhance and accelerate a COVID patient’s recovery.
2. Ideally, a magical combination of the “right” Photodynamic protocol that successfully kills the COVID virus, followed by the ”right” Photobiomodulation protocol to heal and rebuild damaged tissue, would be the most effective way to heal COVID patients, especially those who postponed early treatment allowing the virus to proliferate unchecked causing extensive damage.
ALA (5-aminolaevulinic acid) is spread on the effected skin and allowed to “incubate” for 45 min to 3 hours depending on the severity of the lesions. Skin cancers require longer incubation periods.
During the incubation, the ALA saturates the cysts, who because of their hyperactive cystic activity are also saturated with naturally produced porphyrins.
Thereafter, when the correctly “matched” blue light is shined on the treated skin, through a variety of reactions between the ALA the Porphyrins and the blue light, powerfully toxic ROS such as a singlet oxygen is created that will kill the cystic cells.
As the list of drug resistant microbes continues to grow, their virulence also grows, as does the list of obsolete antibiotics.
In contrast, Photodynamic Therapy does not engage pathogens at the genetic level where resistance can be developed. Consequently, there is an increasing focus on developing new Photodynamic Protocols, including laser devices and novel photosensitizing compounds to which resistance cannot be developed.
A perfect example is the use of Methylene Blue as the photosensitizing agent of Photodynamic Therapy.
Among the many pathogens that can be targeted by PDT, viruses are perhaps the most vulnerable, as they depend on entering a host cell for survival and replication and can be inactivated by damaging the capsid or envelope molecules (lipids, carbohydrates, proteins) or internal molecules (nucleic acids).
Thus, many viruses can be treated via PDT, including papillomavirus (HPV), hepatitis A virus (HAV), and herpes simplex virus (HSV).
In general, it is believed that light energy excitation of endogenous microbial intracellular light receptors (chromophores), such as porphyrins and flavins is the mechanism of action that eliminates pathogenic microbes. Once excited, these receptors undergo energy transfer processes that lead to the generation of cytotoxic ROS which react with intracellular components resulting in photodamage and cell death by oxidative stress.
Additionally, the laboratory disinfection of biological fluids (plasma and blood products) by photo antimicrobials has been performed for decades and is a well-regarded technological application of these compounds.
For instance, extracorporeal photoinactivation of coronaviruses and other clinically relevant pathogens using methylene blue (MB)-mediated PDT has been reported.
Photobiomodulation has been used in the treatment of acute lung injury, pulmonary inflammation, and acute respiratory distress syndrome (ARDS), due to its ability to substantially reduce systemic inflammation while preserving lung function.
Though the mechanism is of yet unknown, Photobiomodulation is also effective in treating disseminated intravascular coagulation.
According to current research, Photobiomodulation and Photodynamic Therapy employing lasers and LEDs are here to stay. The existing information appears to support the hypothesis that Phototherapy does not rely solely on coherence and high energy production to produce favorable physiological effects, but also on selective wavelength application, optimal absorption, and photo-activation.
The significant combination of Photodynamic and Photobiomodulation therapies listed above are evidence of light energy’s untapped promise in the realm of regenerative medicine. Further development of Phototherapy will provide widespread clinical application and acceptance of Photomedicine and have a direct, beneficial impact on mankind by radically changing the ways we manage cancer, acute and chronic wounds, inflammation, and antimicrobial resistance.
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