
Inflammation - The Secret Killer
"Chronic, invisible inflammation sustained over a lifetime is the underlying cause of aging."
- Peter T. Pugliese MD (1989)
In February 2004, Time magazine released an issue with a shocking cover design touting inflammation as the common culprit behind all of humankind's top killers. One of the most powerful revelations of 21st century medicine is the connection experts have made between inflammation and the leading killers like heart attacks, stroke, cancer, Alzheimer’s disease, autoimmune disorders, diabetes, COPD and more! This chronic, pathological inflammation is an ongoing and destructive force with the potential to threaten all of our lives.
"-itis" = Inflammation
Inflammation is hiding in plain sight in the realm of medical terminology, which is filled with “-itises” like arthritis, colitis, hepatitis, myocarditis. “-itis” is a suffix that means inflammation, and these four examples refer to the specific part of our body that is affected – our joints, colon, liver and heart, respectively. There are well over 100 diagnosed inflammatory diseases ending with “itis.” Here are a few more familiar inflammatory diseases covering our whole body from our head to our feet: encephalitis (head), conjunctivitis, sinusitis, gingivitis, tonsillitis, appendicitis, bursitis, dermatitis, diverticulitis, gastritis, meningitis, nephritis, pancreatitis, tendonitis, plantar fasciitis (feet). More and more of us are being diagnosed with an "-itis" than ever before – almost like an “itis” epidemic!
To be fair, not all inflammation is bad. Acute inflammation is an ancestral or evolutionary trait that has a benevolent intent, which is to protect the human body from ancient killers like pathogens, poisons or any kind of trauma. In this way, it is actually a beneficial thing for our bodies to provide inflammation when we need it. We need this “good inflammation” to help our bodies heal. This kind of inflammation can even be seen with the naked eye. If we stub our toe hard on concrete, for example, swelling, heat, redness, pain - the four horsemen of inflammation - inevitably follow. We’ll refer to this short-term "good inflammation” as acute inflammation, which is both constructive and necessary.
"Chronic, invisible inflammation sustained over a lifetime is the underlying cause of aging."
- Peter T. Pugliese MD (1989)
In February 2004, Time magazine released an issue with a shocking cover design touting inflammation as the common culprit behind all of humankind's top killers. One of the most powerful revelations of 21st century medicine is the connection experts have made between inflammation and the leading killers like heart attacks, stroke, cancer, Alzheimer’s disease, autoimmune disorders, diabetes, COPD and more! This chronic, pathological inflammation is an ongoing and destructive force with the potential to threaten all of our lives.
"-itis" = Inflammation
Inflammation is hiding in plain sight in the realm of medical terminology, which is filled with “-itises” like arthritis, colitis, hepatitis, myocarditis. “-itis” is a suffix that means inflammation, and these four examples refer to the specific part of our body that is affected – our joints, colon, liver and heart, respectively. There are well over 100 diagnosed inflammatory diseases ending with “itis.” Here are a few more familiar inflammatory diseases covering our whole body from our head to our feet: encephalitis (head), conjunctivitis, sinusitis, gingivitis, tonsillitis, appendicitis, bursitis, dermatitis, diverticulitis, gastritis, meningitis, nephritis, pancreatitis, tendonitis, plantar fasciitis (feet). More and more of us are being diagnosed with an "-itis" than ever before – almost like an “itis” epidemic!
To be fair, not all inflammation is bad. Acute inflammation is an ancestral or evolutionary trait that has a benevolent intent, which is to protect the human body from ancient killers like pathogens, poisons or any kind of trauma. In this way, it is actually a beneficial thing for our bodies to provide inflammation when we need it. We need this “good inflammation” to help our bodies heal. This kind of inflammation can even be seen with the naked eye. If we stub our toe hard on concrete, for example, swelling, heat, redness, pain - the four horsemen of inflammation - inevitably follow. We’ll refer to this short-term "good inflammation” as acute inflammation, which is both constructive and necessary.

The problem is, because we have evolved, we also tend to pay what we may call the "biological price" for having such a robust immune system - the rise of all these chronic inflammatory conditions! One of the strongest theories explaining this rise in inflammation is that since ancient times, we have radically transformed our lifestyles and environments. Examples of chronic inflammatory causes include the food we eat to the air we breathe, the water we drink, electrosmog, lack of exercise, smoking, alcohol abuse, lack of sleep, injuries, too much stress, viruses/bacteria - and even how we interact with others. These factors (and more) ensure that our immune systems are constantly triggered at a low level, which leads to a silent but chronic inflammation in our body.
We know today that this type of inflammation can be an independent cause of disease! Worse, as we mentioned, chronic inflammation is directly tied to our top killers, including heart disease, cancer, stroke, COPD, diabetes and Alzheimer's disease, along with numerous psychiatric disorders, autoimmune conditions and even obesity. So most of us in the modern world are silently on fire with inflammation, something most poignantly seen in the dramatic rise in autoimmune diseases. This long-term chronic inflammation is destructive and at the root of just about every disease. Many aging scientists even now speak of “inflamm-aging” - the concept that our genes and pathways that control inflammation may very well be the key drivers of not only disease but our whole aging process [1]!
Chronic inflammation does not create disease and death overnight. It is a usually low level, invisible and can be simmering quietly in the blood of people who appear to be healthy. When this low-grade chronic inflammation from certain lifestyle factors and health conditions lasts for months or even years, it can start to cause serious health issues and even lead to death. As with acute inflammation, these triggers set off the immune system's alarm. The difference is, in this case the problem doesn't resolve itself simply as it would in the healing of a wound, for example. Chronic inflammatory conditions like heart disease, cancer, autoimmune, etc. behave like a wound that does not heal or an alarm that never turns off. Instead, they can evolve like a slow simmering fire that gradually burns down the house.
We know today that this type of inflammation can be an independent cause of disease! Worse, as we mentioned, chronic inflammation is directly tied to our top killers, including heart disease, cancer, stroke, COPD, diabetes and Alzheimer's disease, along with numerous psychiatric disorders, autoimmune conditions and even obesity. So most of us in the modern world are silently on fire with inflammation, something most poignantly seen in the dramatic rise in autoimmune diseases. This long-term chronic inflammation is destructive and at the root of just about every disease. Many aging scientists even now speak of “inflamm-aging” - the concept that our genes and pathways that control inflammation may very well be the key drivers of not only disease but our whole aging process [1]!
Chronic inflammation does not create disease and death overnight. It is a usually low level, invisible and can be simmering quietly in the blood of people who appear to be healthy. When this low-grade chronic inflammation from certain lifestyle factors and health conditions lasts for months or even years, it can start to cause serious health issues and even lead to death. As with acute inflammation, these triggers set off the immune system's alarm. The difference is, in this case the problem doesn't resolve itself simply as it would in the healing of a wound, for example. Chronic inflammatory conditions like heart disease, cancer, autoimmune, etc. behave like a wound that does not heal or an alarm that never turns off. Instead, they can evolve like a slow simmering fire that gradually burns down the house.

We are going to see how red light therapy "puts the fire out" and stops chronic inflammation, BUT it is still important for us to identify its causes. You can put a fire out, but if you keep lighting matches, the fire will return and rage anew. So clearly, the best holistic solution is to remove the sources of inflammation AND use holistically orientated anti-inflammatory solutions like red light therapy.
By the end of this chapter, we will conclude our trilogy on the fundamental mechanisms behind red light therapy. Hopefully we will answer to the raging question: "How can a single medicine treat so many different conditions?" Chapter 6 showed us the first part of this process, which was how red light therapy increases cellular energy in the form of ATP, the primary way our body stores and uses energy to perform just about every biological function. In chapter 7, we saw how red light therapy increases beneficial nitric oxide, which improves our body-wide energy and information flows (blood, lymph, air, nerve and meridian) through our five primary fractal branching trees. These networks are the primary way in which oxygen, nutrients, energy and information are delivered to all our cells, tissues and organs - and how waste products, infections and toxins are removed from our bodies. In this chapter, we will take a deep dive into how red light therapy puts a stop to chronic inflammation (and oxidative stress), and by doing so helps to prevent and reverse many of the leading causes of death and disease. This trifecta of umbrella benefits to red light therapy helps our bodies heal and stay healthy from head to toe, inside and out and from organelle to organism. We can confidently say, when the light turns red, inflammation "stops" in its tracks!
By the end of this chapter, we will conclude our trilogy on the fundamental mechanisms behind red light therapy. Hopefully we will answer to the raging question: "How can a single medicine treat so many different conditions?" Chapter 6 showed us the first part of this process, which was how red light therapy increases cellular energy in the form of ATP, the primary way our body stores and uses energy to perform just about every biological function. In chapter 7, we saw how red light therapy increases beneficial nitric oxide, which improves our body-wide energy and information flows (blood, lymph, air, nerve and meridian) through our five primary fractal branching trees. These networks are the primary way in which oxygen, nutrients, energy and information are delivered to all our cells, tissues and organs - and how waste products, infections and toxins are removed from our bodies. In this chapter, we will take a deep dive into how red light therapy puts a stop to chronic inflammation (and oxidative stress), and by doing so helps to prevent and reverse many of the leading causes of death and disease. This trifecta of umbrella benefits to red light therapy helps our bodies heal and stay healthy from head to toe, inside and out and from organelle to organism. We can confidently say, when the light turns red, inflammation "stops" in its tracks!
Even though there is a diverse source of inflammatory triggers in our modern world, all of these have a common molecular source. They create free radicals, which cause great damage to our cells, mitochondria and DNA. Oxidative stress occurs when our cells experience a high level of free radical damage. This oxidative stress leads to transcription factors that create signaling molecules called cytokines that in turn trigger an inflammatory immune response, much like an alarm going off at the fire station. Again, when inflammation is acute, the alarm goes off for a short time and when our bodies are healed, it turns off. Chronic inflammation usually results from poor diet and lifestyle choices that are ongoing. For example, eating inflammatory foods is a stressor that could potentially occur many times a day, every day if we don't change our habits!
Free Radicals, Oxidative Stress and ROS!
As we mentioned, oxidative stress comes from significant free radical damage to the cells, so let's briefly explain what a free radical is. Free radicals are produced not only from those aforementioned sources, but also from normal cell metabolism. When they’re in balance, free radicals do have useful functions in the body, but with overload comes imbalance, like chronic inflammation and damage to cells. Free radicals are atoms, molecules or ions with unpaired electrons - and electrons like to exist in pairs. Unpaired, they scavenge the body to find free electrons. This process steals electrons from other atoms or molecules, creating even more free radicals and setting off a chain reaction that contributes to chronic inflammation, which ultimately causes damage to cells. Because antioxidants have extra electrons, they can donate to a free radical to make it neutral or happy again.
As we mentioned, oxidative stress comes from significant free radical damage to the cells, so let's briefly explain what a free radical is. Free radicals are produced not only from those aforementioned sources, but also from normal cell metabolism. When they’re in balance, free radicals do have useful functions in the body, but with overload comes imbalance, like chronic inflammation and damage to cells. Free radicals are atoms, molecules or ions with unpaired electrons - and electrons like to exist in pairs. Unpaired, they scavenge the body to find free electrons. This process steals electrons from other atoms or molecules, creating even more free radicals and setting off a chain reaction that contributes to chronic inflammation, which ultimately causes damage to cells. Because antioxidants have extra electrons, they can donate to a free radical to make it neutral or happy again.
When we are dealing with too many free radicals and don't get enough antioxidants in our diet to neutralize them, we create physiological stress on the body known as oxidative stress. It turns out that oxygen and various oxygen species are by far the most common free radical in our bodies. This is because oxygen has unpaired electrons in its outer orbit and naturally seeks electrons to become neutral and “content.” This turns out to be a good thing in creating ATP, because molecular oxygen "pulls" electrons in the electron transport chain to itself, which creates protons that generate the voltage differential that drives ATP, the currency of life energy.

Rusting and Rotting - Two Examples of Free Radical Damage
Here is a concrete example of oxidation. When an apple is cut, oxygen reacts in the plant tissue that creates oxidation. Apples contain an enzyme called polyphenol oxidase and when it comes in contact with oxygen, it turns the apple brown via a pigment called melanin. Essentially, oxygen is stealing electrons, a process which damages the apple. But if you rub lemon on the apple, it doesn't turn brown because lemons have vitamin C and other antioxidants that donate electrons and "quench" or "mop up" the oxygen free radical. Similarly, when metal rusts, it is undergoing oxidative damage, and when we galvanize the metal with zinc (an antioxidant metal), we basically rust-proof the metal. The free radical theory of aging is very similar. If we have too much oxidative stress, our bodies "brown" or "rust" due to free radical damage. We can see this in the wrinkles and age spots on our skin! It’s another reason why eating a diet rich in antioxidants and using energy devices like red light therapy is important.
All the aforementioned sources of inflammation - diet, stress, smoking, UV, toxins, etc. - create inflammation and inflamm-aging because they cause free radical damage and oxidative stress! So the true root cause of inflammation is free radicals, which cause oxidative stress to the cells. This free radical damage, aka oxidative stress, can damage cell structure, cell proteins, cell enzymes like cytochrome c oxidase, cell and mitochondrial membranes, lipids, and even DNA, which in turn can cause very unfavorable mutations that impair mitochondrial and cell function if not corrected.
There are many species of free radicals coming from all these dietary and environmental sources, but THE most fundamental free radical behind all inflammation is reactive oxygen species (ROS). ROS are free radicals resulting from cell metabolism containing molecular oxygen - and the ROS levels go way up when we are stressed.
Here is a concrete example of oxidation. When an apple is cut, oxygen reacts in the plant tissue that creates oxidation. Apples contain an enzyme called polyphenol oxidase and when it comes in contact with oxygen, it turns the apple brown via a pigment called melanin. Essentially, oxygen is stealing electrons, a process which damages the apple. But if you rub lemon on the apple, it doesn't turn brown because lemons have vitamin C and other antioxidants that donate electrons and "quench" or "mop up" the oxygen free radical. Similarly, when metal rusts, it is undergoing oxidative damage, and when we galvanize the metal with zinc (an antioxidant metal), we basically rust-proof the metal. The free radical theory of aging is very similar. If we have too much oxidative stress, our bodies "brown" or "rust" due to free radical damage. We can see this in the wrinkles and age spots on our skin! It’s another reason why eating a diet rich in antioxidants and using energy devices like red light therapy is important.
All the aforementioned sources of inflammation - diet, stress, smoking, UV, toxins, etc. - create inflammation and inflamm-aging because they cause free radical damage and oxidative stress! So the true root cause of inflammation is free radicals, which cause oxidative stress to the cells. This free radical damage, aka oxidative stress, can damage cell structure, cell proteins, cell enzymes like cytochrome c oxidase, cell and mitochondrial membranes, lipids, and even DNA, which in turn can cause very unfavorable mutations that impair mitochondrial and cell function if not corrected.
There are many species of free radicals coming from all these dietary and environmental sources, but THE most fundamental free radical behind all inflammation is reactive oxygen species (ROS). ROS are free radicals resulting from cell metabolism containing molecular oxygen - and the ROS levels go way up when we are stressed.

Reactive Oxygen Species (ROS)
The "Most Wanted" Free Radical in Inflammation and Disease
As we examined in detail in Chapter 6, the main function of the mitochondria is to create ATP. Glucose and oxygen go in ATP energy comes out. But we overlooked something – that along with ATP, ROS comes out ALSO! ROS, or reactive oxygen species, are free radicals that are always present in ATP production, even in healthy people (about 1% of all oxygen is converted to ROS molecules) [2]. Just like the engine of your car has heat as a byproduct, the mitochondria have ROS molecules. If you have too much ROS, your mitochondria and cells experience oxidative stress, inflammation and free radical damage. Just as overheating a car can damage an engine, oxidative stress can damage your cells, leading to inflammation, low energy, sickness and disease. This is what most diseases have in common - oxidative stress! The main goal of this chapter will be to show how red light therapy can dramatically lower oxidative stress and inflammation, serving as an "energetic antioxidant,” but even more powerful!
The "Most Wanted" Free Radical in Inflammation and Disease
As we examined in detail in Chapter 6, the main function of the mitochondria is to create ATP. Glucose and oxygen go in ATP energy comes out. But we overlooked something – that along with ATP, ROS comes out ALSO! ROS, or reactive oxygen species, are free radicals that are always present in ATP production, even in healthy people (about 1% of all oxygen is converted to ROS molecules) [2]. Just like the engine of your car has heat as a byproduct, the mitochondria have ROS molecules. If you have too much ROS, your mitochondria and cells experience oxidative stress, inflammation and free radical damage. Just as overheating a car can damage an engine, oxidative stress can damage your cells, leading to inflammation, low energy, sickness and disease. This is what most diseases have in common - oxidative stress! The main goal of this chapter will be to show how red light therapy can dramatically lower oxidative stress and inflammation, serving as an "energetic antioxidant,” but even more powerful!
A deeper dive into ROS Reactive oxygen species
Reactive oxygen species are molecules containing oxygen that have unpaired electrons, called free radicals, such as superoxide anion (O2−), hydroxyl radical (OH·), and hydrogen peroxide (H2O2). They are created normally around 1% of the time from electrons leaking from the electron transport chain and reacting with oxygen to create the superoxide anion. These nasty little free radicals can damage the mitochondria structure and even the essential mitochondrial enzymes, which impairs ATP production through oxidative damage to different essential components of the mitochondria [3,4].
Reactive oxygen species are molecules containing oxygen that have unpaired electrons, called free radicals, such as superoxide anion (O2−), hydroxyl radical (OH·), and hydrogen peroxide (H2O2). They are created normally around 1% of the time from electrons leaking from the electron transport chain and reacting with oxygen to create the superoxide anion. These nasty little free radicals can damage the mitochondria structure and even the essential mitochondrial enzymes, which impairs ATP production through oxidative damage to different essential components of the mitochondria [3,4].
Fortunately, we have a whole host of cellular antioxidant enzymes to "quench," or neutralize, these free radicals, as shown here. Superoxide dimustase (SOD) first converts this superoxide anion to hydrogen peroxide, and glutathione peroxidase and catalase ultimately convert it into healthy water. Big problems occur when our diet and lifestyle create a high level of free radicals and our defense system cannot keep up with the resulting damage and oxidative stress, inflammation and chronic diseases. This is why most diseases can be linked to oxidative stress. Our cells and mitochondria are the building blocks of our entire body and its energy and life-force.
As we'll see, red and near infrared light therapy not only lowers ROS (hence, oxidative stress) but it also stimulates the cells to produce more naturally occurring antioxidant enzymes like superoxide dismutase (the body's most powerful antioxidant), thereby helping to "rust-proof" our cells against the scourges of aging and disease!
As we'll see, red and near infrared light therapy not only lowers ROS (hence, oxidative stress) but it also stimulates the cells to produce more naturally occurring antioxidant enzymes like superoxide dismutase (the body's most powerful antioxidant), thereby helping to "rust-proof" our cells against the scourges of aging and disease!

NF-kB - The Master Switch of Inflammation
When we are sick, injured and stressed, and later when we get old, our cells tend to be low on energy ATP and high on oxidative stress. That is, the ROS rises to unhealthy levels, causing free radical damage and inflammation while ATP go down. This leaves us with less energy and vitality.
Research has shown that if there is too much ROS for an extended length of time, a transcription factor called NF-kB is switched on. NF-kB is the master switch for inflammation, which causes the cells to make a whole host of inflammatory cytokines that can lead to inflammatory diseases. Nf-kb is short for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)! Importantly, it’s the master "switch" that can turn inflammation on or off. It is turned on by increases in ROS, free radicals and any stress on the cells. Because it is a transcription factor, it stimulates DNA to transcribe a whole host of inflammatory cytokines. While oxidative stress and free radical damage are the root cause of inflammation, we might muse that Nf-kb is the alarm switch that goes off in our body, alerting us to potential harm.
When we are sick, injured and stressed, and later when we get old, our cells tend to be low on energy ATP and high on oxidative stress. That is, the ROS rises to unhealthy levels, causing free radical damage and inflammation while ATP go down. This leaves us with less energy and vitality.
Research has shown that if there is too much ROS for an extended length of time, a transcription factor called NF-kB is switched on. NF-kB is the master switch for inflammation, which causes the cells to make a whole host of inflammatory cytokines that can lead to inflammatory diseases. Nf-kb is short for nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)! Importantly, it’s the master "switch" that can turn inflammation on or off. It is turned on by increases in ROS, free radicals and any stress on the cells. Because it is a transcription factor, it stimulates DNA to transcribe a whole host of inflammatory cytokines. While oxidative stress and free radical damage are the root cause of inflammation, we might muse that Nf-kb is the alarm switch that goes off in our body, alerting us to potential harm.
What are cytokines?
Cytokines are tiny signaling proteins secreted by both immune and non-immune cells to communicate with one another. Cytokines bind to receptors, triggering a response in the receiving cell.
Inflammatory cytokines like like TNF-α, IL-6, CRP, COX2, PGE2 are a class of cytokines that trigger certain immune cells (like macrophages) to create an inflammatory response. There are two main classes: inflammatory cytokines that trigger the immune response as we mentioned, and anti-inflammatory cytokines that turn off inflammation and trigger the healing response. Inflammatory cytokines triggered by nf-kb allow our immune system to mount a defense preventing germs or other substances that can make us sick from entering our bodies. Too many inflammatory cytokines for too long can lead to all the chronic inflammatory diseases and even causes of death we have mentioned. Oxidative stress and free radical damage to the cells is the "alarm" that triggers this inflammatory signaling cascade.
You may be familiar with these inflammatory cytokines from COVID. A lot of people died from ARDS (acute respiratory distress syndrome), which was a result of a "cytokine storm.” A cytokine storm is like a raging inferno of inflammation that snowballs out of control, causing life threatening levels of inflammation. ARDS was considered by many a leading cause of COVID deaths.
Cytokines are tiny signaling proteins secreted by both immune and non-immune cells to communicate with one another. Cytokines bind to receptors, triggering a response in the receiving cell.
Inflammatory cytokines like like TNF-α, IL-6, CRP, COX2, PGE2 are a class of cytokines that trigger certain immune cells (like macrophages) to create an inflammatory response. There are two main classes: inflammatory cytokines that trigger the immune response as we mentioned, and anti-inflammatory cytokines that turn off inflammation and trigger the healing response. Inflammatory cytokines triggered by nf-kb allow our immune system to mount a defense preventing germs or other substances that can make us sick from entering our bodies. Too many inflammatory cytokines for too long can lead to all the chronic inflammatory diseases and even causes of death we have mentioned. Oxidative stress and free radical damage to the cells is the "alarm" that triggers this inflammatory signaling cascade.
You may be familiar with these inflammatory cytokines from COVID. A lot of people died from ARDS (acute respiratory distress syndrome), which was a result of a "cytokine storm.” A cytokine storm is like a raging inferno of inflammation that snowballs out of control, causing life threatening levels of inflammation. ARDS was considered by many a leading cause of COVID deaths.
The ATP - ROS teeter totter
ROS is turned off by healthy levels of ATP in the cells. ATP and ROS are like the opposites sides of a teeter totter. When one goes up, the other goes down. This is because when oxygen docks on cytochrome c oxidase, it creates ATP while preventing the generation of ROS molecules. O2 is the final electron helping electrons to fly through the electron transport chain, making protons that drive ATP synthase to create ATP. It is only when oxygen docking is inhibited by iNOS (the bad nitric oxide) or other forms of cellular stress that it becomes the superoxide radical. Let's now take a closer look at the research on how RLT not only lowers inflammation (and pain), but also increases both tissue healing/regeneration and cell survival/longevity.
ROS is turned off by healthy levels of ATP in the cells. ATP and ROS are like the opposites sides of a teeter totter. When one goes up, the other goes down. This is because when oxygen docks on cytochrome c oxidase, it creates ATP while preventing the generation of ROS molecules. O2 is the final electron helping electrons to fly through the electron transport chain, making protons that drive ATP synthase to create ATP. It is only when oxygen docking is inhibited by iNOS (the bad nitric oxide) or other forms of cellular stress that it becomes the superoxide radical. Let's now take a closer look at the research on how RLT not only lowers inflammation (and pain), but also increases both tissue healing/regeneration and cell survival/longevity.
Signaling for "Health"!
Red light therapy isn’t a one stop shop cure-all, but to use a hip vernacular term, it “crushes” the few major things it does very well. We have seen how it increases ATP and NO for more energy and better circulation in our body. Its third key mechanism is helping modulate the production of ROS in the mitochondria - and in doing so, "switches on" or "signals" the production of many anti-inflammatory cytokines and proteins/enzymes that turn off inflammation! It also switches on or signals the production of several pro-survival/longevity proteins and enzymes along with a whole host of growth factors for tissue healing and regeneration! All this happens from the mitochondria simply absorbing red and NIR light energy!!
While stimulating more ATP in body is the core and most fundamental benefit of red light therapy, absorbing light and making ATP doesn't last long. We are constantly burning it up, so we have to keep manufacturing it. While absorbing the red and near infrared light from a good red light device produces more life-essential ATP in our cells, the energy derived from ATP is not long term. Which brings us to this additional core mechanism of red light therapy - signaling!
The broad definition of signaling molecules (like cytokines) is that they are molecules responsible for transmitting information between the cells in your body, AND between organelles like the mitochondrial and DNA. These cells signaling pathways that activate these transcription factors go into the nucleus, binding to various elements which "signal" or trigger the expression of a wide variety of genes. These genes are transcribed to produce a whole lot of beneficial new proteins or enzymes that help to switch off inflammation and switch on healing, along with many other exciting functions.
Red light therapy isn’t a one stop shop cure-all, but to use a hip vernacular term, it “crushes” the few major things it does very well. We have seen how it increases ATP and NO for more energy and better circulation in our body. Its third key mechanism is helping modulate the production of ROS in the mitochondria - and in doing so, "switches on" or "signals" the production of many anti-inflammatory cytokines and proteins/enzymes that turn off inflammation! It also switches on or signals the production of several pro-survival/longevity proteins and enzymes along with a whole host of growth factors for tissue healing and regeneration! All this happens from the mitochondria simply absorbing red and NIR light energy!!
While stimulating more ATP in body is the core and most fundamental benefit of red light therapy, absorbing light and making ATP doesn't last long. We are constantly burning it up, so we have to keep manufacturing it. While absorbing the red and near infrared light from a good red light device produces more life-essential ATP in our cells, the energy derived from ATP is not long term. Which brings us to this additional core mechanism of red light therapy - signaling!
The broad definition of signaling molecules (like cytokines) is that they are molecules responsible for transmitting information between the cells in your body, AND between organelles like the mitochondrial and DNA. These cells signaling pathways that activate these transcription factors go into the nucleus, binding to various elements which "signal" or trigger the expression of a wide variety of genes. These genes are transcribed to produce a whole lot of beneficial new proteins or enzymes that help to switch off inflammation and switch on healing, along with many other exciting functions.
In total, research by Michael Hamblin and others has identified at least 14 different signaling pathways activated in red light therapy that can up or down regulate over 100 different genes [5]! This whole beneficial process of the activation of transcription factors can last days, weeks or even a month according to one study by T. Ando and others in 2011. Think about that for a minute! A single 20-minute session with red light therapy can lead to benefits to our bodies that last up to a MONTH [6]!
Signaling Part 1: Switching Off Inflammation, ROS and oxidative Stress
Now that we know that inflammation and oxidative stress are at the root of just about every disease, what we need to prevent and reverse this epidemic of inflammation is avoid lifestyles and habits that foster inflammation and add food, supplements, healthy habits and healing tools that turn off inflammation and oxidative stress. While there is much we can do to improve our diet, lifestyle and environment, one of the most powerful tools to prevent and reverse inflammation is red and near infrared light therapy. Red and near infrared light stops inflammation by turning on anti-inflammatory cytokines and turning off inflammatory ones. In the process, swelling is reduced via increased NO, and pain is relieved by neuromodulation, leading to increased pain relief hormones like endorphins (both of which red light therapy helps). After the inflammation, swelling and pain is reduced, red light therapy begins jump starting the healing and regeneration process in many dynamic ways that we'll explore. For currently healthy people, we'll show how red light therapy makes our body stronger and more resilient to injury and disease!
Now that we know that inflammation and oxidative stress are at the root of just about every disease, what we need to prevent and reverse this epidemic of inflammation is avoid lifestyles and habits that foster inflammation and add food, supplements, healthy habits and healing tools that turn off inflammation and oxidative stress. While there is much we can do to improve our diet, lifestyle and environment, one of the most powerful tools to prevent and reverse inflammation is red and near infrared light therapy. Red and near infrared light stops inflammation by turning on anti-inflammatory cytokines and turning off inflammatory ones. In the process, swelling is reduced via increased NO, and pain is relieved by neuromodulation, leading to increased pain relief hormones like endorphins (both of which red light therapy helps). After the inflammation, swelling and pain is reduced, red light therapy begins jump starting the healing and regeneration process in many dynamic ways that we'll explore. For currently healthy people, we'll show how red light therapy makes our body stronger and more resilient to injury and disease!

How Red light therapy STOPS Inflammation!
In a nutshell, red light therapy tips the balance of the production of ATP from being too low to normal again. The process of increasing cellular ATP energy reduces ROS and oxidative stress. Red light therapy pushes the teeter totter in the right direction, as this illustration indicates! With this reduction of ROS, we get a reduction of all the inflammatory cytokines. These troublesome inflammatory cytokines are at the root of inflammation and they come from the mitochondria when it is not working properly. This is where red light therapy works its magic. It has a particularly positive effect on oxidative stressed mitochondria that are releasing too much ROS that cause the gene transcription factor nf-kb to produce cytokines that causes the inflammation. Just as nf-kb (the inflammation switch) can be turned on with too much ROS, it can also be turned off with cAMP. With increased ATP production comes more cAMP (cyclic adenosine monophosphate). Bottom line, ATP itself turns out to be one of our most important signaling molecules!
cAMP - The Anti-inflammatory Switch
It has been known for a couple decades that cyclic AMP (cAMP), a signaling molecule, has anti-inflammatory actions. These have been attributed in part to the ability of cAMP to block or "switch off" the pro-inflammatory transcription factor Nuclear Factor-kappaB (NF-κB). As we mentioned, NF-κB plays a crucial role in switching on the gene expression of a plethora of inflammatory molecules and cytokines. This is why NF-Kb is a key target for anti-inflammatory drug design.
In fact red/NIR light therapy is so effective at switching off the unhealthy functioning of nk-kb, studies have even shown that it can have anti- inflammatory effects on par with non-steroidal anti-inflammatory drugs) [7-9]. These are the anti-inflammatories routinely prescribed and typically, the over-the-counter drugs we buy when we’re in pain. It’s important to mention that chronic use of these drugs comes with a big risk of potential side effects, where red light therapy has NONE!
In a nutshell, red light therapy tips the balance of the production of ATP from being too low to normal again. The process of increasing cellular ATP energy reduces ROS and oxidative stress. Red light therapy pushes the teeter totter in the right direction, as this illustration indicates! With this reduction of ROS, we get a reduction of all the inflammatory cytokines. These troublesome inflammatory cytokines are at the root of inflammation and they come from the mitochondria when it is not working properly. This is where red light therapy works its magic. It has a particularly positive effect on oxidative stressed mitochondria that are releasing too much ROS that cause the gene transcription factor nf-kb to produce cytokines that causes the inflammation. Just as nf-kb (the inflammation switch) can be turned on with too much ROS, it can also be turned off with cAMP. With increased ATP production comes more cAMP (cyclic adenosine monophosphate). Bottom line, ATP itself turns out to be one of our most important signaling molecules!
cAMP - The Anti-inflammatory Switch
It has been known for a couple decades that cyclic AMP (cAMP), a signaling molecule, has anti-inflammatory actions. These have been attributed in part to the ability of cAMP to block or "switch off" the pro-inflammatory transcription factor Nuclear Factor-kappaB (NF-κB). As we mentioned, NF-κB plays a crucial role in switching on the gene expression of a plethora of inflammatory molecules and cytokines. This is why NF-Kb is a key target for anti-inflammatory drug design.
In fact red/NIR light therapy is so effective at switching off the unhealthy functioning of nk-kb, studies have even shown that it can have anti- inflammatory effects on par with non-steroidal anti-inflammatory drugs) [7-9]. These are the anti-inflammatories routinely prescribed and typically, the over-the-counter drugs we buy when we’re in pain. It’s important to mention that chronic use of these drugs comes with a big risk of potential side effects, where red light therapy has NONE!

Many studies show that red/NIR light therapy Increases energy and Lowers Oxidative Stress in both in vitro [10,11] and in vivo [12-14]!
Note: In vivo is Latin for “within the living.” It refers to studies that are done within living organisms, on cattle for instance. In vitro is Latin for “within the glass.” A study performed in vitro is done outside a living organism = for example, in a test tube or lab.
Note: In vivo is Latin for “within the living.” It refers to studies that are done within living organisms, on cattle for instance. In vitro is Latin for “within the glass.” A study performed in vitro is done outside a living organism = for example, in a test tube or lab.

Signaling Part 2: Turns ON Tissue Repair and Regeneration
Photobiomodulation not only lowers oxidative stress and reduces all the inflammatory cytokines, but it seems to switch on many regenerative effects as well. Shining red light on stressed cells increases ATP and lowers ROS, which in turns reduces inflammation. Yet lowering ROS or inflammation seems to concurrently turn on many tissue repair mechanisms (signaling pathways) for injuries and damaged and/or stressed tissue.
One of the ways it does this is by restoring the normal functioning of nf-kb, which like NO, is Janus faced. Through stimulating cAMP production, red light therapy turns off the inflammatory effects of the "bad" form of nf-kb. When nf-kb is restored to its proper and healthy form through RLT, it is one of the main switches for signaling tissue regenerative effects [15-17], quite literally bringing us – or at least our cells – back to life! How amazing is that?
Photobiomodulation not only lowers oxidative stress and reduces all the inflammatory cytokines, but it seems to switch on many regenerative effects as well. Shining red light on stressed cells increases ATP and lowers ROS, which in turns reduces inflammation. Yet lowering ROS or inflammation seems to concurrently turn on many tissue repair mechanisms (signaling pathways) for injuries and damaged and/or stressed tissue.
One of the ways it does this is by restoring the normal functioning of nf-kb, which like NO, is Janus faced. Through stimulating cAMP production, red light therapy turns off the inflammatory effects of the "bad" form of nf-kb. When nf-kb is restored to its proper and healthy form through RLT, it is one of the main switches for signaling tissue regenerative effects [15-17], quite literally bringing us – or at least our cells – back to life! How amazing is that?

RLT Therapy helps with all three phases of wound healing!
Research shows us that using red light therapy on injured tissues increases the immune and repair processes, like bringing in more immune cells like neutrophils and macrophages to fight infection (anti-microbial, anti-viral, etc.). Once it accomplishes that, the healing of tissue and regeneration begins. Perhaps the key immune cell in regeneration after an injury or wound is the macrophages, which etymologically means "big eater.” Like crabs and lobsters on the ocean floor, they are scavengers that constantly move around to remove dead and injured cells, along with foreign bodies such as pathogenic microbes.
Along with cleaning up our body and killing infections alongside other immune cells, the macrophages have other amazing functions because they have two phenotypes or forms. When they first arrive at the location of an injury, they are called M1 macrophages, serving the purpose of phase one of wound healing, which is fighting infection and inflammation. The problem is that in chronic inflammation, this normal functioning of macrophages becomes impaired and they stay locked in the M1 phenotype, which produces the whole spectrum of inflammatory cytokines we previously looked at.
One of the key mechanisms of the healing effects of red light therapy is its ability to turn M1 macrophages more quickly to M2, where they start releasing anti-inflammatory cytokines to reduce inflammation and also contribute key growth factors that signal for clean-up, tissue repair and regeneration! Because M1 inflammatory markers and M2 anti-inflammatory markers are well known and easy to test for, research with RLT reveals an increase in all the M2 markers and a decrease in M1. One of the markers of M2 macrophages that signals for healing and regeneration is TGF-B1, one of the most important growth factors [18-20].
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Like cytokines, growth factors typically act as signaling molecules between cells, but unlike cytokines, they are always positive in their ability to stimulate tissue healing and cellular differentiation. Red light therapy's ability to heal includes stimulating M2 macrophages (and other cells) to produce regenerative growth factors!
Here’s the main takeaway: Red and near infrared light lowers ROS and turns off inflammation - AND in so doing, turns on tissue healing and repair.
Research shows us that using red light therapy on injured tissues increases the immune and repair processes, like bringing in more immune cells like neutrophils and macrophages to fight infection (anti-microbial, anti-viral, etc.). Once it accomplishes that, the healing of tissue and regeneration begins. Perhaps the key immune cell in regeneration after an injury or wound is the macrophages, which etymologically means "big eater.” Like crabs and lobsters on the ocean floor, they are scavengers that constantly move around to remove dead and injured cells, along with foreign bodies such as pathogenic microbes.
Along with cleaning up our body and killing infections alongside other immune cells, the macrophages have other amazing functions because they have two phenotypes or forms. When they first arrive at the location of an injury, they are called M1 macrophages, serving the purpose of phase one of wound healing, which is fighting infection and inflammation. The problem is that in chronic inflammation, this normal functioning of macrophages becomes impaired and they stay locked in the M1 phenotype, which produces the whole spectrum of inflammatory cytokines we previously looked at.
One of the key mechanisms of the healing effects of red light therapy is its ability to turn M1 macrophages more quickly to M2, where they start releasing anti-inflammatory cytokines to reduce inflammation and also contribute key growth factors that signal for clean-up, tissue repair and regeneration! Because M1 inflammatory markers and M2 anti-inflammatory markers are well known and easy to test for, research with RLT reveals an increase in all the M2 markers and a decrease in M1. One of the markers of M2 macrophages that signals for healing and regeneration is TGF-B1, one of the most important growth factors [18-20].
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Like cytokines, growth factors typically act as signaling molecules between cells, but unlike cytokines, they are always positive in their ability to stimulate tissue healing and cellular differentiation. Red light therapy's ability to heal includes stimulating M2 macrophages (and other cells) to produce regenerative growth factors!
Here’s the main takeaway: Red and near infrared light lowers ROS and turns off inflammation - AND in so doing, turns on tissue healing and repair.
Growth Factors: The Signaling Molecules of Healing and Regeneration
TGF-B1 (TGF = transforming growth factor) is an important growth factor that in effect tells stem cells what to do. We end up with more cell differentiation, more cell proliferation, better cell motility and less apoptosis, all of which leads to greater healing and optimal tissue repair. Essentially, red light therapy activates stem cells to make new tissue to heal our body. TGF-B1 is also a stimulator of collagen production, the most abundant protein in the body and an integral building block for all healing and repair mechanisms! Along with TGF-B1, red light therapy also helps to stimulate other growth factors like:
By stimulating all these wonderful growth factors, red and near infrared light therapy will help to greatly accelerate the healing time after an injury – OR, in cases that never really healed, it will give our body a boost to repair old wounds as well. Let's look at a few examples. With TGF-B1, you get more fibroblasts arriving at the wound to make more collagen to repair tissue. These fibroblasts will then contract to bring the edges of a wound together to heal it up. This growth factor is at the center stage of healing and repair.
With another growth factor, vascular endothelial growth, we start to see endothelial cells making more capillaries to supply more blood to the bed of a wound. This is critical, as the improved blood supply will bring in more oxygen and nutrients, aka the building blocks for healing and repair. Nerve growth factor will help with nerve regeneration, where we can experience increased axon sprouting and axon survival. People who need bone healing or greater bone density will start to see osteoblastic and osteoclastic activity. Dentists can observe more dentin made from odontoblasts, the stem cells that reside in tooth pulp. This also applies to brain repair as well as brain derived neurotropic factor for neurogenesis and synaptogenesis. Red light therapy also activates bone marrow to release more stem cells AND tissue resident stems. They are set in motion downstream by light being absorbed in the mitochondria cascading down, leading to more robust tissue repair!
Here is a summary of the benefits of increasing various body-wide growth factors associated with all the different bodily tissue. Regardless of the tissue, whether we’re talking about muscle, nerve, bone, connective, organ, etc., red light therapy stimulates all the corresponding growth factors to develop new tissue via these fundamental mechanisms.
TGF-B1 (TGF = transforming growth factor) is an important growth factor that in effect tells stem cells what to do. We end up with more cell differentiation, more cell proliferation, better cell motility and less apoptosis, all of which leads to greater healing and optimal tissue repair. Essentially, red light therapy activates stem cells to make new tissue to heal our body. TGF-B1 is also a stimulator of collagen production, the most abundant protein in the body and an integral building block for all healing and repair mechanisms! Along with TGF-B1, red light therapy also helps to stimulate other growth factors like:
- Vascular endothelial growth factor, which is involved in angiogenesis, the formation of new blood vessels.
- Basic fibroblast growth factor and keratinocyte growth factor, which is involved in the wound healing process.
- Nerve growth factor, which is involved in neuron and brain growth and regeneration.
By stimulating all these wonderful growth factors, red and near infrared light therapy will help to greatly accelerate the healing time after an injury – OR, in cases that never really healed, it will give our body a boost to repair old wounds as well. Let's look at a few examples. With TGF-B1, you get more fibroblasts arriving at the wound to make more collagen to repair tissue. These fibroblasts will then contract to bring the edges of a wound together to heal it up. This growth factor is at the center stage of healing and repair.
With another growth factor, vascular endothelial growth, we start to see endothelial cells making more capillaries to supply more blood to the bed of a wound. This is critical, as the improved blood supply will bring in more oxygen and nutrients, aka the building blocks for healing and repair. Nerve growth factor will help with nerve regeneration, where we can experience increased axon sprouting and axon survival. People who need bone healing or greater bone density will start to see osteoblastic and osteoclastic activity. Dentists can observe more dentin made from odontoblasts, the stem cells that reside in tooth pulp. This also applies to brain repair as well as brain derived neurotropic factor for neurogenesis and synaptogenesis. Red light therapy also activates bone marrow to release more stem cells AND tissue resident stems. They are set in motion downstream by light being absorbed in the mitochondria cascading down, leading to more robust tissue repair!
Here is a summary of the benefits of increasing various body-wide growth factors associated with all the different bodily tissue. Regardless of the tissue, whether we’re talking about muscle, nerve, bone, connective, organ, etc., red light therapy stimulates all the corresponding growth factors to develop new tissue via these fundamental mechanisms.
5 MAIN STEPS INVOLVED IN TISSUE REGENERATION [21-23]
1) Red light therapy increases proliferation factors that help with cell proliferation, the process by which a cell grows and divides to produce two daughter cells via mitosis. Stated another way, healthy cells divide into more cells, a necessary process to make new tissue after a disease or injury. There is much research showing that red and near infrared light therapy helps skin cells, bone cells, cells that line blood vessels, etc. grow and replicate faster after injury (in a healthy way), which means rapid and more complete healing!
2) Red light therapy increases differentiation factors that enhance cell differentiation, where proliferation increases the number of cells. Cell differentiation is when cells acquire a specific function and form, like becoming liver cells, bone cells, etc.
3) Red light therapy increases cell motility and migration. Some types of cells (e.g. tenocytes in tendons or melanocytes in skin) need to move to travel to the location they’re most needed. Research has shown that red/NIR light can stimulate this.
4) Red light therapy increases protein synthesis. Red/NIR light can also stimulate cells (e.g. skin cells, bone cells, etc.) to produce more proteins (e.g. collagen). These proteins are at the center stage of wound healing, with collagen being the most abundant protein in the body.
5) Red light therapy helps to activate stem cells. Stem cells are apparently even more sensitive to red/NIR light, which has been proven to positively affect growth, movement and viability of stem cells. This may be relevant to both stem cells already present in our body, as well as in the context of stem cell therapy.
This is an extremely simplified explanation, but the major takeaway is that red and near infrared light therapy not only stops inflammation, but also helps switch the M1 macrophage to M2. In turn, that produces important growth factors like TGF-b1 that naturally tell cells to divide, facilitate the mobilization and differentiation of stem cells and cause proteins to be synthesized all in concert to make ANY KIND of new and healthy tissue (if a chronic or acute injury is present)!
Important Note: Research has confirmed that the key metabolic difference between M1 and M2 macrophages is that M1 macrophages operate via aerobic glycolysis, which only yields a pittance of 4 ATP per each molecule of glucose/pyruvate. M2 macrophages utilize aerobic respiration, which yields 38 ATP as we saw in chapter 6. Because red light therapy seems to "power on," or shift ALL cells more to aerobic respiration, this is perhaps the fundamental reason why using red and near infrared turns off inflammation and turns on healing (and even helps fight cancer!). So ultimately all these red light therapy mechanisms come full circle back to their ability to help the mitochondria produce more ATP via aerobic respiration!
1) Red light therapy increases proliferation factors that help with cell proliferation, the process by which a cell grows and divides to produce two daughter cells via mitosis. Stated another way, healthy cells divide into more cells, a necessary process to make new tissue after a disease or injury. There is much research showing that red and near infrared light therapy helps skin cells, bone cells, cells that line blood vessels, etc. grow and replicate faster after injury (in a healthy way), which means rapid and more complete healing!
2) Red light therapy increases differentiation factors that enhance cell differentiation, where proliferation increases the number of cells. Cell differentiation is when cells acquire a specific function and form, like becoming liver cells, bone cells, etc.
3) Red light therapy increases cell motility and migration. Some types of cells (e.g. tenocytes in tendons or melanocytes in skin) need to move to travel to the location they’re most needed. Research has shown that red/NIR light can stimulate this.
4) Red light therapy increases protein synthesis. Red/NIR light can also stimulate cells (e.g. skin cells, bone cells, etc.) to produce more proteins (e.g. collagen). These proteins are at the center stage of wound healing, with collagen being the most abundant protein in the body.
5) Red light therapy helps to activate stem cells. Stem cells are apparently even more sensitive to red/NIR light, which has been proven to positively affect growth, movement and viability of stem cells. This may be relevant to both stem cells already present in our body, as well as in the context of stem cell therapy.
This is an extremely simplified explanation, but the major takeaway is that red and near infrared light therapy not only stops inflammation, but also helps switch the M1 macrophage to M2. In turn, that produces important growth factors like TGF-b1 that naturally tell cells to divide, facilitate the mobilization and differentiation of stem cells and cause proteins to be synthesized all in concert to make ANY KIND of new and healthy tissue (if a chronic or acute injury is present)!
Important Note: Research has confirmed that the key metabolic difference between M1 and M2 macrophages is that M1 macrophages operate via aerobic glycolysis, which only yields a pittance of 4 ATP per each molecule of glucose/pyruvate. M2 macrophages utilize aerobic respiration, which yields 38 ATP as we saw in chapter 6. Because red light therapy seems to "power on," or shift ALL cells more to aerobic respiration, this is perhaps the fundamental reason why using red and near infrared turns off inflammation and turns on healing (and even helps fight cancer!). So ultimately all these red light therapy mechanisms come full circle back to their ability to help the mitochondria produce more ATP via aerobic respiration!

For Healthy People - Red Light Makes You Stronger!!
Pro-survival and Prophylactic effects = cells become more resilient.
The question now is, what if we are already healthy? If nothing on or in our body is injured or diseased, then tissue repair and regeneration is not really needed. So, is there something red light therapy can do for healthy people? The answer is YES! It turns out that for healthy people (and even animals!), red and near infrared light therapy increases many pro-survival transcription factors that better strengthen and protect our body from any future stress, injury or infection that may happen in the future. In the next chapter, we'll look at how it helps with athletic performance as well! Stay tuned!
Studies show that red light pre-treated animals and humans, when they are injured or stressed, are more resilient and recover much faster and more efficiently than control groups that are not pre-treated with red light therapy. And they heal faster even when NOT treated at all after the injury. Red light therapy (RLT) makes us stronger and more resilient! This preconditioning effect is incredibly well researched. Studies have shown red light therapy to be protective against muscle damage occurring after exercise in both animals [24,25] and humans [26,27]. Pre-treating with RLT has also been shown to be protective against cardiac damage occurring after heart attack [28], as well as brain damage [29]. There are also studies pre-treating with RLT showing improved wound healing and protection against scarring after surgery [30] and sunburn occurring after UV exposure [31]. It is important to note in these studies that the patients or subjects were only treated BEFORE, showing how RLT has powerful prophylactic effects that help the cells, tissues and body become more resilient to any stress injury or disease. When you pretreat cells with RLT, they are much harder to kill than untreated cells.
This "pre-conditioning" with red light therapy is much like exercise in that the effects of red light therapies at the cell level "mimic" exercise in many ways - which is why we call them an exercise mimetic. We know exercise is good for our heart, immune system and overall health and longevity. It turns out that humans need some of these low-level stressors in their life. Believe it or not, the absence of these stressors sabotages our health. Like exercise, red light serves a low-level stress to your cells to make them stronger, almost like a cellular exercise! The end result of these cellular adaptations to the temporary stress is healthier cells that produce more energy, have a stronger anti-oxidant and anti-inflammatory defense system and are more resilient to overall stress [32-35].
Pro-survival and Prophylactic effects = cells become more resilient.
The question now is, what if we are already healthy? If nothing on or in our body is injured or diseased, then tissue repair and regeneration is not really needed. So, is there something red light therapy can do for healthy people? The answer is YES! It turns out that for healthy people (and even animals!), red and near infrared light therapy increases many pro-survival transcription factors that better strengthen and protect our body from any future stress, injury or infection that may happen in the future. In the next chapter, we'll look at how it helps with athletic performance as well! Stay tuned!
Studies show that red light pre-treated animals and humans, when they are injured or stressed, are more resilient and recover much faster and more efficiently than control groups that are not pre-treated with red light therapy. And they heal faster even when NOT treated at all after the injury. Red light therapy (RLT) makes us stronger and more resilient! This preconditioning effect is incredibly well researched. Studies have shown red light therapy to be protective against muscle damage occurring after exercise in both animals [24,25] and humans [26,27]. Pre-treating with RLT has also been shown to be protective against cardiac damage occurring after heart attack [28], as well as brain damage [29]. There are also studies pre-treating with RLT showing improved wound healing and protection against scarring after surgery [30] and sunburn occurring after UV exposure [31]. It is important to note in these studies that the patients or subjects were only treated BEFORE, showing how RLT has powerful prophylactic effects that help the cells, tissues and body become more resilient to any stress injury or disease. When you pretreat cells with RLT, they are much harder to kill than untreated cells.
This "pre-conditioning" with red light therapy is much like exercise in that the effects of red light therapies at the cell level "mimic" exercise in many ways - which is why we call them an exercise mimetic. We know exercise is good for our heart, immune system and overall health and longevity. It turns out that humans need some of these low-level stressors in their life. Believe it or not, the absence of these stressors sabotages our health. Like exercise, red light serves a low-level stress to your cells to make them stronger, almost like a cellular exercise! The end result of these cellular adaptations to the temporary stress is healthier cells that produce more energy, have a stronger anti-oxidant and anti-inflammatory defense system and are more resilient to overall stress [32-35].

How it works
If we research photobiomodulation (PBM) or red light therapy on the internet, we see how PBM increases reactive oxygen species (ROS) – yet we just mentioned earlier in the chapter that PBM lowers it. This presents a conundrum, doesn’t it? How is it that PBM increases ROS, but inflammation goes down? It all depends on when you measure it. We learn that red light therapy increases ROS or oxidative stress for a short period of time. With stress or injured cells, you get a burst or blip of ROS for a short time and then it falls below baseline in stressed inflammatory cells. Even though it is temporarily raised, it very quickly lowers to BELOW baseline.
Red light therapy indeed increases ROS, but only with a brief spike. Unstressed or healthy cells also see a spike in ROS for a short time but then it drops back to its original baseline as if nothing seemingly happened. In healthy people, however, something significant does occur with this brief spike in ROS. Just like temporarily stressing our body with moderate exercise lowers our blood pressure, increases our energy and strength, etc., red light therapy strengthens the mitochondria and cells - and hence, our body. Other benefits that healthy people can experience with BOTH red light therapy and exercise include improved cardiovascular efficiency, more efficient delivery of blood to the muscles and increasing both mitochondrial function and number! Along with this, we get a down-regulating of inflammation as we have already seen and something new - an up-regulating of pro-survival genes that help to increase and improve our anti-oxidant defense system. In a way, red light therapy is like rust-proofing your body, making it more resilient and resistant to free radical damage, oxidative stress and inflammation, which as we have noted, is at the root of all disease and aging itself. NOTE: Just like overtraining creates too much oxidative stress, we want to make sure to get the dosage right with red light therapy to maximize its benefits (more on dosage in chapter 12).
Activation of Nrf2 pathway and INCREASE in anti-oxidant enzymes
This brief spike in ROS after red light therapy (and exercise) most notably activates the cells’ pro-survival anti-oxidant defenses. The transcription factor NF-kb is a switch for inflammation, but it can be modulated to create a very low-level inflammatory response via “good ROS.” This then triggers what is called the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which transcribes pro-survival genes, most notably all the wonderful anti-oxidant defenses like SOD, Catalase and Glutathione Peroxidase. One of the most up-regulated genes after NF-kB activation is the antioxidant superoxide dismutase [36].
These are our body's knights in shining armor that protect our cells and mitochondria from free radical damage and oxidative stress. All this helps make our cells more resistant to stress, inflammation and free radicals. It ultimately makes our cells healthier, more energetic and resilient. Another highly up-regulated gene after NF-kB activation and LED/photobiomodulation (PBM) is heat shock protein 70, a molecular chaperone for protein molecules that prevents misfolding and unwanted protein aggregation, especially at the telomeres of the DNA [37]. As some of us may know, telomere shortening is one of the most fundamental causes of aging! So here is yet another way red and near infrared light therapy is one of the best anti-aging tools available.
If we research photobiomodulation (PBM) or red light therapy on the internet, we see how PBM increases reactive oxygen species (ROS) – yet we just mentioned earlier in the chapter that PBM lowers it. This presents a conundrum, doesn’t it? How is it that PBM increases ROS, but inflammation goes down? It all depends on when you measure it. We learn that red light therapy increases ROS or oxidative stress for a short period of time. With stress or injured cells, you get a burst or blip of ROS for a short time and then it falls below baseline in stressed inflammatory cells. Even though it is temporarily raised, it very quickly lowers to BELOW baseline.
Red light therapy indeed increases ROS, but only with a brief spike. Unstressed or healthy cells also see a spike in ROS for a short time but then it drops back to its original baseline as if nothing seemingly happened. In healthy people, however, something significant does occur with this brief spike in ROS. Just like temporarily stressing our body with moderate exercise lowers our blood pressure, increases our energy and strength, etc., red light therapy strengthens the mitochondria and cells - and hence, our body. Other benefits that healthy people can experience with BOTH red light therapy and exercise include improved cardiovascular efficiency, more efficient delivery of blood to the muscles and increasing both mitochondrial function and number! Along with this, we get a down-regulating of inflammation as we have already seen and something new - an up-regulating of pro-survival genes that help to increase and improve our anti-oxidant defense system. In a way, red light therapy is like rust-proofing your body, making it more resilient and resistant to free radical damage, oxidative stress and inflammation, which as we have noted, is at the root of all disease and aging itself. NOTE: Just like overtraining creates too much oxidative stress, we want to make sure to get the dosage right with red light therapy to maximize its benefits (more on dosage in chapter 12).
Activation of Nrf2 pathway and INCREASE in anti-oxidant enzymes
This brief spike in ROS after red light therapy (and exercise) most notably activates the cells’ pro-survival anti-oxidant defenses. The transcription factor NF-kb is a switch for inflammation, but it can be modulated to create a very low-level inflammatory response via “good ROS.” This then triggers what is called the Nrf2 (Nuclear factor erythroid 2-related factor 2) pathway, which transcribes pro-survival genes, most notably all the wonderful anti-oxidant defenses like SOD, Catalase and Glutathione Peroxidase. One of the most up-regulated genes after NF-kB activation is the antioxidant superoxide dismutase [36].
These are our body's knights in shining armor that protect our cells and mitochondria from free radical damage and oxidative stress. All this helps make our cells more resistant to stress, inflammation and free radicals. It ultimately makes our cells healthier, more energetic and resilient. Another highly up-regulated gene after NF-kB activation and LED/photobiomodulation (PBM) is heat shock protein 70, a molecular chaperone for protein molecules that prevents misfolding and unwanted protein aggregation, especially at the telomeres of the DNA [37]. As some of us may know, telomere shortening is one of the most fundamental causes of aging! So here is yet another way red and near infrared light therapy is one of the best anti-aging tools available.
Putting it all together in The Physical Body - The Master Blueprint of Red Light Therapy Mechanisms.
[Conclusion to Chapters 5-8]
[Conclusion to Chapters 5-8]

The Domino Effect and Red Light Therapy
The Domino Effect is a fascinating phenomenon that demonstrates the subtle and marvelous interconnectedness of all matter. This is a sublime metaphor for how red light therapy, with just one photon of light stimulating the mitochondria, has such widespread and profound effects on the entire body.
As we’re aware, a domino is small in size, but we should never underestimate its power. Experimental evidence shows that a small domino can knock over a domino about 1.5 times larger than itself. Starting with a normal size domino which is 2 inches, if we created 24 dominos each being 1.5 times larger than the first, the 24th domino would be a little taller than the Empire State Building! That’s one gargantuan domino! We could in theory topple an Empire State Building-sized domino with a single small regular size domino if we had 24 lined up with each one being 1.5 times larger than the previous. This is an amazing amplification of energy!
Similarly, the human body being highly quantum, non-linear and interconnected, stores energy across its 37 trillion cells - and because of this is exquisitely sensitive to specific weak signals and can amplify them many orders of magnitude. Even one photon of red light can set off a chain reaction, beginning with ATP production in the tiny mitochondria and leading up to healing our entire body. This scale is even greater than a domino to the Empire State Building due to the minute size of our mitochondria.
The Domino Effect is a fascinating phenomenon that demonstrates the subtle and marvelous interconnectedness of all matter. This is a sublime metaphor for how red light therapy, with just one photon of light stimulating the mitochondria, has such widespread and profound effects on the entire body.
As we’re aware, a domino is small in size, but we should never underestimate its power. Experimental evidence shows that a small domino can knock over a domino about 1.5 times larger than itself. Starting with a normal size domino which is 2 inches, if we created 24 dominos each being 1.5 times larger than the first, the 24th domino would be a little taller than the Empire State Building! That’s one gargantuan domino! We could in theory topple an Empire State Building-sized domino with a single small regular size domino if we had 24 lined up with each one being 1.5 times larger than the previous. This is an amazing amplification of energy!
Similarly, the human body being highly quantum, non-linear and interconnected, stores energy across its 37 trillion cells - and because of this is exquisitely sensitive to specific weak signals and can amplify them many orders of magnitude. Even one photon of red light can set off a chain reaction, beginning with ATP production in the tiny mitochondria and leading up to healing our entire body. This scale is even greater than a domino to the Empire State Building due to the minute size of our mitochondria.
We are now in a position to put all these mechanisms we have looked at in chapters 5-8 together into a unified map of mechanisms. While it is beyond the scope of this book to immerse in all the signaling pathways and mechanisms, we have been very thorough covering most of the top researched reasons that underlie why red light therapy is an effective resource for just about every condition.
From this Russian doll diagram chart, we can see the main levels of action of red light therapy in improving the health and function of our body, starting with the very small molecular porphyrin based chromophore - cytochrome C oxidase (CCO) all the way to whole body systemic effects. Much like the toppling dominos of increasing size, the benefits of every photon of red light therapy absorbed by CCO get amplified many orders of magnitude. To simplify this amazing domino effect of the healing power of red light therapy, we'll break things down by using only five levels of "dominos," from photon to molecule to cell to tissue to entire body.
From this Russian doll diagram chart, we can see the main levels of action of red light therapy in improving the health and function of our body, starting with the very small molecular porphyrin based chromophore - cytochrome C oxidase (CCO) all the way to whole body systemic effects. Much like the toppling dominos of increasing size, the benefits of every photon of red light therapy absorbed by CCO get amplified many orders of magnitude. To simplify this amazing domino effect of the healing power of red light therapy, we'll break things down by using only five levels of "dominos," from photon to molecule to cell to tissue to entire body.
The 1st Domino: Light Absorbed by Chromophore (Chapter 5)
The first domino is the direct stimulation of red and near infrared light hitting a chromophore "flush," because nothing happens without light being absorbed by a chromophore. The main chromophore for red and near infrared light is cytochrome c oxidase (CCO), the fourth and most important enzyme complex in the electron transport chain. Because cytochrome c oxidase has 16 different configurations or energy states, there are at least 16 different wavelengths that it can absorb, which are between 600-880 nm excluding 700-760 (which don't seem to work). The most popular ranges used on most red light therapy products are 600-670 and 800-860. This main chromophore of red and near infrared light therapy has the ability to fortuitously absorb light in the red and near infrared spectrum, which just happen to be the deepest penetrating wavelength of the entire electromagnetic spectrum. Life is very wise indeed to utilize such a molecule because it allows light to be captured as deep as possible into our body. Our body is like a 3D solar panel, not only absorbing light at the skin, but also up to 5 cm or more deep! There are other chromophores that absorb red and near infrared (like water), but cytochrome c oxidase is by far the most important and most researched.
2nd Domino - Core Mechanisms (Chapter 6,7)
Once light is absorbed, the second domino to create a powerful healing "chain reaction" in the body is the transduction of light into energy via cytochrome c oxidase (CCO) into ATP. We are now going from the level of a photon (pure energy) to a molecule like ATP, which stores and then releases energy to power all the functions of our cells, tissues, organs and body. Just like solar panels capture and transduce light into powering our homes, so too does CCO capture light, which is then transduced to "electrifying" the electron transport chain to create more ATP energy, which powers up our cells and body. Additionally, as we mentioned in Chapter 7, red and near infrared (especially red) catalyze reactions that liberate healthy nitric oxide, which opens up all the energy flows across the entire body in the circulation, lymph, airways, nerves and meridians. Even though nitric oxide is a small "domino," it has a massive impact on the entire health of our body (as does ATP, of course). Reactive oxygen species (ROS) is the stepping-stone to our next domino. Recall that it’s created as a waste byproduct of healthy metabolism, just as heat and exhaust from your car is a product of the combustion of any solid engine. ROS created in unhealthy amounts results in oxidative stress and inflammation in your cells and tissues. But in this chapter, we also saw how just the right amount of ROS created from exercise or red light therapy (as two examples) signals for many healthy pro-survival genes and proteins.
3rd Domino - Cells and Signaling Molecules (Chapter 6,7,8)
We recently discovered that when red light is captured and transduced into ATP energy (or Nitric oxide), a great deal signaling occurs that leads to the longer term benefits of red and near infrared light therapy. This 3rd domino is in essence an extended string of dominos that connects the entire cell. ATP and ROS are at the center stage of this signaling, so we'll focus on that as we have in this chapter. It is worth noting that nitric oxide (NO) and reactive nitrogen species (RNS) have a similar role (which we hinted at in Chapter 6) on how red light therapy lowers the bad iNOS and increases the good eNOS. All those signaling pathways are beyond the scope of this book. We focused on ATP and ROS because they are by far the two most important signaling molecules that launch the whole chain reaction of either regeneration and healing OR inflammation and disease.
The key point is that red and near infrared light therapy acts like a switch that turns on ATP and turns off ROS/inflammation. Only after this inflammation is "turned off" can healing begin. Elevated levels of ATP increase cAMP, which shuts off inflammation via NF-KB, the master switch for inflammation. We can see the power of using red light to heal. Not only does RLT increase cellular energy, but at the same time it also suppresses the negative form of NF-KB and in so doing “turns off” inflammation! The process is a bit different (and less urgent!) in healthy people because they’re not dealing with injury or disease and there’s no chronic inflammation to “turn off.” In these healthy people (like athletes), RLT increases ATP and ROS is temporarily increased, just like in exercise. This brief spike of ROS triggers signaling for many pro-survival transcription factors that create antioxidant enzymes like SOD and DNA telomere, protecting proteins like heat shock protein. All these anti-inflammatory and pre-conditioning signals create a dynamic chain of dominos in the cell that enters the nucleus to trigger DNA transcription of many healthy proteins and enzymes that ultimately heal and strengthen the cell. This 3rd domino connects molecules in the mitochondria to myriad signaling pathways throughout the entire cell!
The first domino is the direct stimulation of red and near infrared light hitting a chromophore "flush," because nothing happens without light being absorbed by a chromophore. The main chromophore for red and near infrared light is cytochrome c oxidase (CCO), the fourth and most important enzyme complex in the electron transport chain. Because cytochrome c oxidase has 16 different configurations or energy states, there are at least 16 different wavelengths that it can absorb, which are between 600-880 nm excluding 700-760 (which don't seem to work). The most popular ranges used on most red light therapy products are 600-670 and 800-860. This main chromophore of red and near infrared light therapy has the ability to fortuitously absorb light in the red and near infrared spectrum, which just happen to be the deepest penetrating wavelength of the entire electromagnetic spectrum. Life is very wise indeed to utilize such a molecule because it allows light to be captured as deep as possible into our body. Our body is like a 3D solar panel, not only absorbing light at the skin, but also up to 5 cm or more deep! There are other chromophores that absorb red and near infrared (like water), but cytochrome c oxidase is by far the most important and most researched.
2nd Domino - Core Mechanisms (Chapter 6,7)
Once light is absorbed, the second domino to create a powerful healing "chain reaction" in the body is the transduction of light into energy via cytochrome c oxidase (CCO) into ATP. We are now going from the level of a photon (pure energy) to a molecule like ATP, which stores and then releases energy to power all the functions of our cells, tissues, organs and body. Just like solar panels capture and transduce light into powering our homes, so too does CCO capture light, which is then transduced to "electrifying" the electron transport chain to create more ATP energy, which powers up our cells and body. Additionally, as we mentioned in Chapter 7, red and near infrared (especially red) catalyze reactions that liberate healthy nitric oxide, which opens up all the energy flows across the entire body in the circulation, lymph, airways, nerves and meridians. Even though nitric oxide is a small "domino," it has a massive impact on the entire health of our body (as does ATP, of course). Reactive oxygen species (ROS) is the stepping-stone to our next domino. Recall that it’s created as a waste byproduct of healthy metabolism, just as heat and exhaust from your car is a product of the combustion of any solid engine. ROS created in unhealthy amounts results in oxidative stress and inflammation in your cells and tissues. But in this chapter, we also saw how just the right amount of ROS created from exercise or red light therapy (as two examples) signals for many healthy pro-survival genes and proteins.
3rd Domino - Cells and Signaling Molecules (Chapter 6,7,8)
We recently discovered that when red light is captured and transduced into ATP energy (or Nitric oxide), a great deal signaling occurs that leads to the longer term benefits of red and near infrared light therapy. This 3rd domino is in essence an extended string of dominos that connects the entire cell. ATP and ROS are at the center stage of this signaling, so we'll focus on that as we have in this chapter. It is worth noting that nitric oxide (NO) and reactive nitrogen species (RNS) have a similar role (which we hinted at in Chapter 6) on how red light therapy lowers the bad iNOS and increases the good eNOS. All those signaling pathways are beyond the scope of this book. We focused on ATP and ROS because they are by far the two most important signaling molecules that launch the whole chain reaction of either regeneration and healing OR inflammation and disease.
The key point is that red and near infrared light therapy acts like a switch that turns on ATP and turns off ROS/inflammation. Only after this inflammation is "turned off" can healing begin. Elevated levels of ATP increase cAMP, which shuts off inflammation via NF-KB, the master switch for inflammation. We can see the power of using red light to heal. Not only does RLT increase cellular energy, but at the same time it also suppresses the negative form of NF-KB and in so doing “turns off” inflammation! The process is a bit different (and less urgent!) in healthy people because they’re not dealing with injury or disease and there’s no chronic inflammation to “turn off.” In these healthy people (like athletes), RLT increases ATP and ROS is temporarily increased, just like in exercise. This brief spike of ROS triggers signaling for many pro-survival transcription factors that create antioxidant enzymes like SOD and DNA telomere, protecting proteins like heat shock protein. All these anti-inflammatory and pre-conditioning signals create a dynamic chain of dominos in the cell that enters the nucleus to trigger DNA transcription of many healthy proteins and enzymes that ultimately heal and strengthen the cell. This 3rd domino connects molecules in the mitochondria to myriad signaling pathways throughout the entire cell!
4th Domino - Macrophages, Growth Factors and Tissue Regenerative Effects (Chapter 8)
In this 4th domino, the benefits amplify from cells to tissues as cells communicate with each other via signaling molecules and growth factors that stimulate healthy stem cells, cell motility, cell proliferation, cell differentiation, protein synthesis and other processes that lead to tissue regeneration. At this step, the key is that there are various growth factors guiding the healing and regeneration of all the various tissues in the body.
Transitioning to the next domino are the whole-body effects mediated mainly through our five fractal branching networks (cardiovascular, lymphatic, nervous, pulmonary and meridian systems) that connect our entire being from head to toe and from skin to bone marrow. Also important is the improved circulation and lymphatic flow and drainage, so that nutrients, oxygen and immunity can feed the mitochondria and start this whole process. Everything comes full circle as these body-wide branching networks supply glucose/fats/proteins and oxygen (and micronutrients) as the necessary fuel needed by the mitochondria to capture light and create ATP.
In this 4th domino, the benefits amplify from cells to tissues as cells communicate with each other via signaling molecules and growth factors that stimulate healthy stem cells, cell motility, cell proliferation, cell differentiation, protein synthesis and other processes that lead to tissue regeneration. At this step, the key is that there are various growth factors guiding the healing and regeneration of all the various tissues in the body.
Transitioning to the next domino are the whole-body effects mediated mainly through our five fractal branching networks (cardiovascular, lymphatic, nervous, pulmonary and meridian systems) that connect our entire being from head to toe and from skin to bone marrow. Also important is the improved circulation and lymphatic flow and drainage, so that nutrients, oxygen and immunity can feed the mitochondria and start this whole process. Everything comes full circle as these body-wide branching networks supply glucose/fats/proteins and oxygen (and micronutrients) as the necessary fuel needed by the mitochondria to capture light and create ATP.
5th Domino - Whole Body Effects (Chapter 8 and next chapter 9)
From tissue healing and regeneration, the next domino is our whole body, which we can emphatically summarize as improved health, wellness and longevity. In the next chapter, we'll take a look at some of the most researched applications of red light therapy where all these fundamental mechanisms come together to help the body heal itself of just about every malady known to humankind!
From tissue healing and regeneration, the next domino is our whole body, which we can emphatically summarize as improved health, wellness and longevity. In the next chapter, we'll take a look at some of the most researched applications of red light therapy where all these fundamental mechanisms come together to help the body heal itself of just about every malady known to humankind!

New Discovery - Free Mitochondria
Exciting 2020 research shows that blood contains circulating cell free respiratory competent mitochondria, creating benefits for our entire body [38,39]. People have been studying blood for hundreds of years, so this is further proof that science is continuously discovering new mysteries of the human body. This explains why red and near infrared light can have significant powerful systemic effects even with penetrating only 5 cm (about 2 inches). If we shine light on one part of our body, it can have distant effects on other parts of the body that did not receive any light. This means ATP is available everywhere there is circulating blood in your body (not just limited to inside the cell). Circulating mitochondria are another discovery reminding us how everything in our body is amazingly interconnected with its energy production, energy storage and energy flows!
Exciting 2020 research shows that blood contains circulating cell free respiratory competent mitochondria, creating benefits for our entire body [38,39]. People have been studying blood for hundreds of years, so this is further proof that science is continuously discovering new mysteries of the human body. This explains why red and near infrared light can have significant powerful systemic effects even with penetrating only 5 cm (about 2 inches). If we shine light on one part of our body, it can have distant effects on other parts of the body that did not receive any light. This means ATP is available everywhere there is circulating blood in your body (not just limited to inside the cell). Circulating mitochondria are another discovery reminding us how everything in our body is amazingly interconnected with its energy production, energy storage and energy flows!
Master Blueprint of Red and Near Infrared Light Mechanisms
Let's now take a step back and end this chapter with a bird’s eye view of these fundamental mechanisms, keeping in mind that this incredibly intricate domino effect of whole-body benefits starts with the absorption of a single photon of light by a chromophore. How amazing is that!!
Let's now take a step back and end this chapter with a bird’s eye view of these fundamental mechanisms, keeping in mind that this incredibly intricate domino effect of whole-body benefits starts with the absorption of a single photon of light by a chromophore. How amazing is that!!
References Chapter 8
[1] Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
[2] Kann, O., 2016. The interneuron energy hypothesis: implications for brain disease. Neurobiol. Dis. 90, 7585.
[3] Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009; 417: 1 –13
[4] Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552: 335 –44
[5] Chung et al., 2012; Huang et al., 2009; Morries et al., 2015; Henderson and Morries, 2015a.
[6] Ando T, Xuan W, Xu T, Dai T, Sharma SK, et al. (2011) Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice. PLOS ONE 6(10): e26212.
[7] Cotler HB, Chow RT, Hamblin MR, Carroll J. The Use of Low Level Laser Therapy (LLLT) For Musculoskeletal Pain. MOJ Orthop Rheumatol. 2015;2(5):00068
[8] Lim, W., Kim, J., Kim, S., Karna, S., Won, J., Jeon, S.M., et al., 2013. Modulation of lipopolysaccharide-induced NF-kappaB signaling pathway by 635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem. Photobiol. 89 (1), 199207.
[9] Yang, Y., Gao, L., 2017. Celecoxib alleviates memory deficits by downregulation of COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a diabetic rat model. J. Mol. Neurosci. 62 (2), 188198.
[10] Huang, Y.Y., Nagata, K., Tedford, C.E., McCarthy, T., Hamblin, M.R., 2013. Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro. J. Biophotonics 6 (10), 829838.
[11] Wu, J., Xia, S., Kalionis, B., Wan, W., Sun, T., 2014. The role of oxidative stress and inflammation in cardiovascular aging. Biomed. Res. Int. 2014, 615312.
[12] Silveira, P.C., Silva, L.A., Freitas, T.P., Latini, A., Pinho, R.A., 2011. Effects of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. Lasers Med. Sci. 26 (1), 125131.
[13] Lim, J., Ali, Z.M., Sanders, R.A., Snyder, A.C., Eells, J.T., Henshel, D.S., et al., 2009. Effects of low-level light therapy on hepatic antioxidant defense in acute and chronic diabetic rats. J. Biochem. Mol. Toxicol. 23 (1), 18.
[14] Rubio, C.R., Simes, J.C., Moya, M., Soriano, F., Palma, J.A., Campana, V., 2009. Inflammatory and oxidative stress markers in experimental crystalopathy: their modification by photostimulation. Photomed. Laser Surg. 27 (1), 7984.
[15] Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6, e22453.
[16] Chung, H., Dai, T., Sharma, S.K., Huang, Y.Y., Carroll, J.D., Hamblin, M.R., 2012. The nuts and bolts of low-level laser (light) therapy. Ann. Biomed. Eng. 40, 516533.
[17] Farivar, S., Malekshahabi, T., Shiari, R., 2014. Biological effects of low level laser therapy. J. Lasers Med. Sci. 5, 5862.
[18] Fernandes, K.P., Souza, N.H., Mesquita-Ferrari, R.A., Silva, D.F., Rocha, L.A., Alves, A.N., et al., 2015. Photobiomodulation with 660-nm and 780-nm laser on activated J774 macrophage-like cells: effect on M1 inflammatory markers. J. Photochem. Photobiol. B 153, 344351.
[19] Haschemi, A., Kosma, P., Gille, L., Evans, C.R., Burant, C.F., Starkl, P., et al., 2012. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15 (6), 813826.
[20] Orihuela, R., McPherson, C.A., Harry, G.J., 2016. Microglial M1/M2 polarization and metabolic states. Br. J. Pharmacol. 173 (4), 649665.
[21] Henderson, T.A., Morries, L.D., 2015a. Near-infrared photonic energy penetration: can infrared phototherapy effectively reach the human brain? Neuropsychiatr. Dis. Treat. 11, 21912208.
[22] Huang, Y.Y., Chen, A.C., Carroll, J.D., Hamblin, M.R., 2009. Biphasic dose response in low level light therapy. Dose Response 7 (4), 358383.
[23] Morries, L.D., Cassano, P., Henderson, T.A., 2015. Treatments for traumatic brain injury with emphasis on transcranial near infrared laser phototherapy. Neuropsychiatr. Dis. Treat. 11, 21592175.
[24] Ferraresi C, de Sousa MV, Huang YY, Bagnato VS, Parizotto NA, Hamblin MR. Time response of increases in ATP and muscle resistance to fatigue after low-level laser (light) therapy (LLLT) in mice. Lasers Med Sci 2015
[25] Ferraresi C, Parizotto NA, Pires de Sousa MV, Kaippert B, Huang YY, Koiso T, Bagnato VS, Hamblin MR. Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation. J Biophotonics. 2014:9999.
[26] Ferraresi C, Beltrame T, Fabrizzi F, Nascimento ES, Karsten M, Francisco CO, Borghi-Silva A, Catai AM, Cardoso DR, Ferreira AG, Hamblin MR, Bagnato VS, Parizotto NA. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner. Physiother Theory Pract. 2015:1–8.
[27] Ferraresi C, Dos Santos RV, Marques G, Zangrande M, Leonaldo R, Hamblin MR, Bagnato VS, Parizotto NA. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players. Lasers Med Sci 2015
[28] Tuby H, Maltz L, Oron U. Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis. Lasers Surg Med. 2006;38:682–688.
[29] Uozumi Y, Nawashiro H, Sato S, Kawauchi S, Shima K, Kikuchi M. Targeted increase in cerebral blood flow by transcranial near-infrared laser irradiation. Lasers Surg Med. 2010;42:566–576.
[30] Barolet D, Boucher A. Prophylactic low-level light therapy for the treatment of hypertrophic scars and keloids: a case series. Lasers Surg Med. 2010;42:597–601.
[31] Barolet D, Boucher A. LED photoprevention: reduced MED response following multiple LED exposures. Lasers Surg Med. 2008;40:106–112.
[32] Persson, T., Popescu, B.O., Cedazo-Minguez, A., 2014. Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid. Med. Cell Longev. 2014, 427318.
[33] Steinhubl, S.R., 2008. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101 (10A), 14D19DD.
[34] Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., et al., 2014. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed. Res. Int. 2014, 761264.
[35] Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Birringer, M., Kiehntopf, M., et al., 2009. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. U.S.A. 106 (21), 86658670.
[36] Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via
generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6, e22453.
[37] Zhang, Y.H., Takahashi, K., Jiang, G.Z., Zhang, X.M., Kawai, M., Fukada, M., et al., 1994. In vivo production of heat shock protein in mouse perito- neal macrophages by administration of lipopolysaccharide. Infect Immun. 62 (10), 41404144.
[38] Song X, Hu W, Yu H, Wang H, Zhao Y, Korngold R, Zhao Y. Existence of Circulating Mitochondria in Human and Animal Peripheral Blood. Int J Mol Sci. 2020 Mar 19;21(6):2122.
[39] Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C, Arena G, Lasorsa L, Bennett A, Grange T, El Messaoudi S, Mazard T, Prevostel C, Thierry AR. Blood contains circulating cell-free respiratory competent mitochondria. FASEB J. 2020 Mar;34(3):3616-3630.
[1] Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014 Jun;69 Suppl 1:S4-9.
[2] Kann, O., 2016. The interneuron energy hypothesis: implications for brain disease. Neurobiol. Dis. 90, 7585.
[3] Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009; 417: 1 –13
[4] Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol 2003; 552: 335 –44
[5] Chung et al., 2012; Huang et al., 2009; Morries et al., 2015; Henderson and Morries, 2015a.
[6] Ando T, Xuan W, Xu T, Dai T, Sharma SK, et al. (2011) Comparison of Therapeutic Effects between Pulsed and Continuous Wave 810-nm Wavelength Laser Irradiation for Traumatic Brain Injury in Mice. PLOS ONE 6(10): e26212.
[7] Cotler HB, Chow RT, Hamblin MR, Carroll J. The Use of Low Level Laser Therapy (LLLT) For Musculoskeletal Pain. MOJ Orthop Rheumatol. 2015;2(5):00068
[8] Lim, W., Kim, J., Kim, S., Karna, S., Won, J., Jeon, S.M., et al., 2013. Modulation of lipopolysaccharide-induced NF-kappaB signaling pathway by 635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem. Photobiol. 89 (1), 199207.
[9] Yang, Y., Gao, L., 2017. Celecoxib alleviates memory deficits by downregulation of COX-2 expression and upregulation of the BDNF-TrkB signaling pathway in a diabetic rat model. J. Mol. Neurosci. 62 (2), 188198.
[10] Huang, Y.Y., Nagata, K., Tedford, C.E., McCarthy, T., Hamblin, M.R., 2013. Low-level laser therapy (LLLT) reduces oxidative stress in primary cortical neurons in vitro. J. Biophotonics 6 (10), 829838.
[11] Wu, J., Xia, S., Kalionis, B., Wan, W., Sun, T., 2014. The role of oxidative stress and inflammation in cardiovascular aging. Biomed. Res. Int. 2014, 615312.
[12] Silveira, P.C., Silva, L.A., Freitas, T.P., Latini, A., Pinho, R.A., 2011. Effects of low-power laser irradiation (LPLI) at different wavelengths and doses on oxidative stress and fibrogenesis parameters in an animal model of wound healing. Lasers Med. Sci. 26 (1), 125131.
[13] Lim, J., Ali, Z.M., Sanders, R.A., Snyder, A.C., Eells, J.T., Henshel, D.S., et al., 2009. Effects of low-level light therapy on hepatic antioxidant defense in acute and chronic diabetic rats. J. Biochem. Mol. Toxicol. 23 (1), 18.
[14] Rubio, C.R., Simes, J.C., Moya, M., Soriano, F., Palma, J.A., Campana, V., 2009. Inflammatory and oxidative stress markers in experimental crystalopathy: their modification by photostimulation. Photomed. Laser Surg. 27 (1), 7984.
[15] Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6, e22453.
[16] Chung, H., Dai, T., Sharma, S.K., Huang, Y.Y., Carroll, J.D., Hamblin, M.R., 2012. The nuts and bolts of low-level laser (light) therapy. Ann. Biomed. Eng. 40, 516533.
[17] Farivar, S., Malekshahabi, T., Shiari, R., 2014. Biological effects of low level laser therapy. J. Lasers Med. Sci. 5, 5862.
[18] Fernandes, K.P., Souza, N.H., Mesquita-Ferrari, R.A., Silva, D.F., Rocha, L.A., Alves, A.N., et al., 2015. Photobiomodulation with 660-nm and 780-nm laser on activated J774 macrophage-like cells: effect on M1 inflammatory markers. J. Photochem. Photobiol. B 153, 344351.
[19] Haschemi, A., Kosma, P., Gille, L., Evans, C.R., Burant, C.F., Starkl, P., et al., 2012. The sedoheptulose kinase CARKL directs macrophage polarization through control of glucose metabolism. Cell Metab. 15 (6), 813826.
[20] Orihuela, R., McPherson, C.A., Harry, G.J., 2016. Microglial M1/M2 polarization and metabolic states. Br. J. Pharmacol. 173 (4), 649665.
[21] Henderson, T.A., Morries, L.D., 2015a. Near-infrared photonic energy penetration: can infrared phototherapy effectively reach the human brain? Neuropsychiatr. Dis. Treat. 11, 21912208.
[22] Huang, Y.Y., Chen, A.C., Carroll, J.D., Hamblin, M.R., 2009. Biphasic dose response in low level light therapy. Dose Response 7 (4), 358383.
[23] Morries, L.D., Cassano, P., Henderson, T.A., 2015. Treatments for traumatic brain injury with emphasis on transcranial near infrared laser phototherapy. Neuropsychiatr. Dis. Treat. 11, 21592175.
[24] Ferraresi C, de Sousa MV, Huang YY, Bagnato VS, Parizotto NA, Hamblin MR. Time response of increases in ATP and muscle resistance to fatigue after low-level laser (light) therapy (LLLT) in mice. Lasers Med Sci 2015
[25] Ferraresi C, Parizotto NA, Pires de Sousa MV, Kaippert B, Huang YY, Koiso T, Bagnato VS, Hamblin MR. Light-emitting diode therapy in exercise-trained mice increases muscle performance, cytochrome c oxidase activity, ATP and cell proliferation. J Biophotonics. 2014:9999.
[26] Ferraresi C, Beltrame T, Fabrizzi F, Nascimento ES, Karsten M, Francisco CO, Borghi-Silva A, Catai AM, Cardoso DR, Ferreira AG, Hamblin MR, Bagnato VS, Parizotto NA. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner. Physiother Theory Pract. 2015:1–8.
[27] Ferraresi C, Dos Santos RV, Marques G, Zangrande M, Leonaldo R, Hamblin MR, Bagnato VS, Parizotto NA. Light-emitting diode therapy (LEDT) before matches prevents increase in creatine kinase with a light dose response in volleyball players. Lasers Med Sci 2015
[28] Tuby H, Maltz L, Oron U. Modulations of VEGF and iNOS in the rat heart by low level laser therapy are associated with cardioprotection and enhanced angiogenesis. Lasers Surg Med. 2006;38:682–688.
[29] Uozumi Y, Nawashiro H, Sato S, Kawauchi S, Shima K, Kikuchi M. Targeted increase in cerebral blood flow by transcranial near-infrared laser irradiation. Lasers Surg Med. 2010;42:566–576.
[30] Barolet D, Boucher A. Prophylactic low-level light therapy for the treatment of hypertrophic scars and keloids: a case series. Lasers Surg Med. 2010;42:597–601.
[31] Barolet D, Boucher A. LED photoprevention: reduced MED response following multiple LED exposures. Lasers Surg Med. 2008;40:106–112.
[32] Persson, T., Popescu, B.O., Cedazo-Minguez, A., 2014. Oxidative stress in Alzheimer’s disease: why did antioxidant therapy fail? Oxid. Med. Cell Longev. 2014, 427318.
[33] Steinhubl, S.R., 2008. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 101 (10A), 14D19DD.
[34] Rahal, A., Kumar, A., Singh, V., Yadav, B., Tiwari, R., Chakraborty, S., et al., 2014. Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed. Res. Int. 2014, 761264.
[35] Ristow, M., Zarse, K., Oberbach, A., Kloting, N., Birringer, M., Kiehntopf, M., et al., 2009. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. U.S.A. 106 (21), 86658670.
[36] Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via
generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6, e22453.
[37] Zhang, Y.H., Takahashi, K., Jiang, G.Z., Zhang, X.M., Kawai, M., Fukada, M., et al., 1994. In vivo production of heat shock protein in mouse perito- neal macrophages by administration of lipopolysaccharide. Infect Immun. 62 (10), 41404144.
[38] Song X, Hu W, Yu H, Wang H, Zhao Y, Korngold R, Zhao Y. Existence of Circulating Mitochondria in Human and Animal Peripheral Blood. Int J Mol Sci. 2020 Mar 19;21(6):2122.
[39] Al Amir Dache Z, Otandault A, Tanos R, Pastor B, Meddeb R, Sanchez C, Arena G, Lasorsa L, Bennett A, Grange T, El Messaoudi S, Mazard T, Prevostel C, Thierry AR. Blood contains circulating cell-free respiratory competent mitochondria. FASEB J. 2020 Mar;34(3):3616-3630.
******END OF CHAPTER*****
NO MORE EDITING OR ILLUSTRATIONS PAST THIS POINT
NO MORE EDITING OR ILLUSTRATIONS PAST THIS POINT
Some common causes of chronic inflammation?
The most obvious causes of chronic inflammation are our bad lifestyle habits and vices related to poor diet, drinking too much alcohol, smoking, not exercising, not sleeping enough, along with the multitude of things we do to create stress in our lives, whether real or imagined. A poor diet is certainly one of the biggest contributors to inflammation. Main culprits of inflammation from our diet are sugar (candy, soft drinks, etc.); refined carbohydrates like white pasta and bread; trans-fats like friend foods; hydrogenated oils; polyunsaturated fatty acids (PUFAs) like any vegetable oils; pasteurized and processed dairy products; processed meats; and of course, fast food and processed food in general, which usually contain all of the above!
Along with diet, lifestyle and bad habits, there are other contributors to inflammation that tend to be out of our control. These include our genetic history, air and water pollution, viruses and bacteria, accidents and injury, electrosmog from cell phone towers and general stress from our increasingly busy and chaotic daily lives.
Aside: Brief overview of lifestyle habits to lower inflammation
Working on our diets alone can radically lower one of the central causes of chronic inflammation. Along with cutting out inflammatory foods, we should eat more whole foods that have anti-inflammatory effects, which are foods high in fiber and antioxidants. A few examples of these are green vegetables, berries, nuts, seeds and healthy fats, whole grains, beans and legumes and fermented foods. These dietary changes go a long way to help put out the fire of chronic inflammation. Refer to the excellent book "A Silent Fire" by Shilpa Ravella to learn more about the diet - inflammation connection. She also talks about how exercise in the right balance decreases inflammation, as does intermittent fasting, stress management, better sleep and making an overall effort to remove toxic food, habits and chemicals from our day to day lives. By the end of this chapter, we'll see that full body red light therapy is also a powerful tool capable of turning off inflammation!

Action at a distance: Mitochondria in blood and also platlets in the blood are rich in mitochondria.
It was recently discovered in 2020 that blood contains circulating cell free respiratory competent mitochondria. People have studied blood for hundreds of years so it just shows you there are many mysteries of the human body that science is continuously discovering.
This can explain why PBM can have significant systemic effects. If you shine light on one part of the body it can have distant effects on other parts of the body that did not receive any light.
pg 105 brain PBM book
case for full body light bed
It was recently discovered in 2020 that blood contains circulating cell free respiratory competent mitochondria. People have studied blood for hundreds of years so it just shows you there are many mysteries of the human body that science is continuously discovering.
This can explain why PBM can have significant systemic effects. If you shine light on one part of the body it can have distant effects on other parts of the body that did not receive any light.
pg 105 brain PBM book
case for full body light bed

The Janus Brothers
RLT regulates and modulates favorably
So here are the four main mediators of mitochondrial signaling that we will look at in this chapter (and how red light therapy activates them in beneficial ways).
1. ATP-ROS (Janus Mediator)
Energy/Regeneration vs Oxidative stress/Inflammation
2. NO-RNS (Janus Mediator) -
eNOS/iNOS (NO/RNS)
Vasodilation/Regeneration vs Vasoconstriction/Inflammation
RLT regulates and modulates favorably
So here are the four main mediators of mitochondrial signaling that we will look at in this chapter (and how red light therapy activates them in beneficial ways).
1. ATP-ROS (Janus Mediator)
Energy/Regeneration vs Oxidative stress/Inflammation
2. NO-RNS (Janus Mediator) -
eNOS/iNOS (NO/RNS)
Vasodilation/Regeneration vs Vasoconstriction/Inflammation
Study Showing Mitochondrial Dysfunction and Oxidative Stress are at the Root of All Disease
Using phosphorus magnetic resonance spectroscopy, significant increases in total nucleotide triphosphates, a marker of cellular energy availability, have been observed following PBM to healthy adult beagle dogs (Mintzopoulos et al., 2017). This strongly suggested that an increase in cellular ATP production has occurred as a result of PBM. It is a general finding that mitochondrial dysfunction, inadequate supplies of ATP, and oxidative stress are contributory factors in almost all forms of disease (Kann, 2016).
Mintzopoulos, D., Gillis, T.E., Tedford, C.E., Kaufman, M.J., 2017. Effects of near-infrared light on cerebral bioenergetics measured with phosphorus magnetic resonance spectroscopy. Photomed. Laser Surg. 35 (8), 395400.
Using phosphorus magnetic resonance spectroscopy, significant increases in total nucleotide triphosphates, a marker of cellular energy availability, have been observed following PBM to healthy adult beagle dogs (Mintzopoulos et al., 2017). This strongly suggested that an increase in cellular ATP production has occurred as a result of PBM. It is a general finding that mitochondrial dysfunction, inadequate supplies of ATP, and oxidative stress are contributory factors in almost all forms of disease (Kann, 2016).
Mintzopoulos, D., Gillis, T.E., Tedford, C.E., Kaufman, M.J., 2017. Effects of near-infrared light on cerebral bioenergetics measured with phosphorus magnetic resonance spectroscopy. Photomed. Laser Surg. 35 (8), 395400.

TURNING OFF INFLAMMATION TURNS ON HEALING!!!
We have said the RLT lowers inflammation and in doing so triggers many healing and rebuilding pathways. But I want to share the core
The Master Switch
Turn On OXPHOS
Turn Off Glycolysis
Lowers Inflammation
Three very important things happen when you switch the cells from glycolysis to OXPHOS.
Glycolysis >>>> OXPHOS
1) Activation of Stem Cells
Stem cells in hypoxic niche carry out glycolysis. When mitochondria are activated, they leave their niche in search of oxygen and activate proliferation and differentiation programs. This explains why the stem cells are mobilized from their niche (which is often the bone marrow), and get out in the circulation and go where they are needed.
It should not be forgotten that when any kind of PBM light is shone onto a living animal, it is inevitable that some stem cells will be exposed to light. It is known that stem cells respond well to PBM in terms of proliferation and differentiation (Arany, 2016; Abrahamse and Hamblin, 2017). The stem cells may be located in the bone marrow underlying the tissue, and in the bones that are in the illuminated area. Farfara et al. (2015) showed that applying PBM to the bone marrow in the legs had a therapeutic effect in a mouse model of Alzheimer’s disease. The same procedure had major therapeutic benefits for reducing the infarct area in heart attack models (Blatt et al., 2016; Tuby et al., 2011), and in ameliorating ischemic kidney injury (Oron et al., 2014).
Arany, P.R., 2016. Photobiomodulation therapy: communicating with stem cells for regeneration? Photomed. Laser Surg. 34 (11), 497-499.
Abrahamse, H., Hamblin, M.R., 2017. Photomedicine and Stem Cells. IOP Science Ebooks (Morgan and Claypool Publishing), San Rafael, CA.
Farfara, D., Tuby, H., Trudler, D., Doron-Mandel, E., Maltz, L., Vassar, R.J., et al., 2015. Low-level laser therapy ameliorates disease progression in a mouse model of Alzheimer’s disease. J. Mol. Neurosci. 55 (2), 430436.
Blatt, A., Elbaz-Greener, G.A., Tuby, H., Maltz, L., Siman-Tov, Y., Ben-Aharon, G., et al., 2016. Low-level laser therapy to the bone marrow reduces scarring and improves heart function post-acute myocardial infarction in the pig. Photomed. Laser Surg. 34 (11), 516524
Tuby, H., Maltz, L., Oron, U., 2011. Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart. Lasers Surg. Med. 43 (5), 401409.
Oron, U., Tuby, H., Maltz, L., Sagi-Assif, O., Abu-Hamed, R., Yaakobi, T., et al., 2014. Autologous bone-marrow stem cells stimulation reverses post-ischemic-reperfusion kidney injury in rats. Am. J. Nephrol. 40 (5), 425433.
We have said the RLT lowers inflammation and in doing so triggers many healing and rebuilding pathways. But I want to share the core
The Master Switch
Turn On OXPHOS
Turn Off Glycolysis
Lowers Inflammation
Three very important things happen when you switch the cells from glycolysis to OXPHOS.
Glycolysis >>>> OXPHOS
1) Activation of Stem Cells
Stem cells in hypoxic niche carry out glycolysis. When mitochondria are activated, they leave their niche in search of oxygen and activate proliferation and differentiation programs. This explains why the stem cells are mobilized from their niche (which is often the bone marrow), and get out in the circulation and go where they are needed.
It should not be forgotten that when any kind of PBM light is shone onto a living animal, it is inevitable that some stem cells will be exposed to light. It is known that stem cells respond well to PBM in terms of proliferation and differentiation (Arany, 2016; Abrahamse and Hamblin, 2017). The stem cells may be located in the bone marrow underlying the tissue, and in the bones that are in the illuminated area. Farfara et al. (2015) showed that applying PBM to the bone marrow in the legs had a therapeutic effect in a mouse model of Alzheimer’s disease. The same procedure had major therapeutic benefits for reducing the infarct area in heart attack models (Blatt et al., 2016; Tuby et al., 2011), and in ameliorating ischemic kidney injury (Oron et al., 2014).
Arany, P.R., 2016. Photobiomodulation therapy: communicating with stem cells for regeneration? Photomed. Laser Surg. 34 (11), 497-499.
Abrahamse, H., Hamblin, M.R., 2017. Photomedicine and Stem Cells. IOP Science Ebooks (Morgan and Claypool Publishing), San Rafael, CA.
Farfara, D., Tuby, H., Trudler, D., Doron-Mandel, E., Maltz, L., Vassar, R.J., et al., 2015. Low-level laser therapy ameliorates disease progression in a mouse model of Alzheimer’s disease. J. Mol. Neurosci. 55 (2), 430436.
Blatt, A., Elbaz-Greener, G.A., Tuby, H., Maltz, L., Siman-Tov, Y., Ben-Aharon, G., et al., 2016. Low-level laser therapy to the bone marrow reduces scarring and improves heart function post-acute myocardial infarction in the pig. Photomed. Laser Surg. 34 (11), 516524
Tuby, H., Maltz, L., Oron, U., 2011. Induction of autologous mesenchymal stem cells in the bone marrow by low-level laser therapy has profound beneficial effects on the infarcted rat heart. Lasers Surg. Med. 43 (5), 401409.
Oron, U., Tuby, H., Maltz, L., Sagi-Assif, O., Abu-Hamed, R., Yaakobi, T., et al., 2014. Autologous bone-marrow stem cells stimulation reverses post-ischemic-reperfusion kidney injury in rats. Am. J. Nephrol. 40 (5), 425433.

PBM has been shown to be effective in regulating the amount of cytokine-inducible nitric oxide synthase (iNOS) produced by the cell. This is important because excessive amounts of iNOS can lead to the excessive production of NO, which would then signal increased production of the ROS/reactive nitrogen species (RNS) called peroxynitrite, leading to an increase in oxidative stress. Specifically, PBM could reduce peroxynitrite (Bartos et al., 2016), while still preserving the positive effects of other isoforms of NO synthase, such as endothelial nitric oxygen synthase (eNOS), which is the species primarily responsible for the vasodilating effects of PBM (Mungrue et al., 2002; Ahmed et al., 2011; Assis et al., 2013)
**Excessive amounts of NO produced by inducible nitric oxide synthase (iNOS) during inflammation can overwhelm the NO gradients produced by eNOS. The suppression of eNOS by iNOS disrupts the contraction/relaxation cycle in favor of excessive contraction and subsequent reduced flow.
Mungrue, I.N., Husain, M., Stewart, D.J., 2002. The role of NOS in heart failure: lessons from murine genetic models. Heart Fail. Rev. 7 (4), 407422.
Ahmed, I., Bose, S.K., Pavese, N., Ramlackhansingh, A., Turkheimer, F., Hotton, G., et al., 2011. Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain 134 (Pt 4), 979-986.
Assis, L., Moretti, A.I., Abrahao, T.B., de Souza, H.P., Hamblin, M.R., Parizotto, N.A., 2013. Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion. Lasers Med. Sci. 28 (3), 947-955.
**Increased oxidative/nitrosative stress usually describes a condition in which antioxidant defenses are inadequate to completely inactivate ROS/RNS produced because of excessive production of ROS/RNS, loss of antioxidant defenses, or both. RNS = reactive nitrogen species.
Nitric Oxide (like ROS) is sometimes called a Janus molecules, a little bit does you good but an awful lot of it can be harmful and damaging. RLT can work in both directions by increasing eNOS and nitric oxide in the blood vessels and lymphatics, especially the lymphatics. Research has shown the lymphatics** are VERY responsive to Nitric Oxide. PBM increases lymphatic drainage and reduces swelling.
But in acute inflammation where you have high amounts of NO, PBM can reduce it by switching the macrophage phenotype to M2 and activating OXPHOS.
**Deng J, Lukens JN, Swisher-McClure S, Cohn JC, Spinelli BA, Quinn RJ, Chittams J, McMenamin E, Lin A. Photobiomodulation Therapy in Head and Neck Cancer-Related Lymphedema: A Pilot Feasibility Study. Integr Cancer Ther. 2021 Jan-Dec
Oxidative and Nitrosative Stress (ROS + NO) a bad marriage
In studies of the effect of PBM on traumatized muscle, PBM has been shown to be effective in regulating the amount of cytokine-inducible nitric oxide synthase (iNOS) produced by the cell. This is important because excessive amounts of iNOS can lead to the excessive production of NO, which would then signal increased production of the ROS/reactive nitrogen species (RNS) called peroxynitrite, leading to an increase in oxidative stress. Specifically, PBM could reduce peroxynitrite (Bartos et al., 2016), while still preserving the positive effects of other isoforms of NO synthase, such as endothelial nitric oxygen synthase (eNOS), which is the species primarily responsible for the vasodilating effects of PBM (Mungrue et al., 2002; Ahmed et al., 2011; Assis et al., 2013).
Ahmed, I., Bose, S.K., Pavese, N., Ramlackhansingh, A., Turkheimer, F., Hotton, G., et al., 2011. Glutamate NMDA receptor dysregulation in
Parkinson’s disease with dyskinesias. Brain 134 (Pt 4), 979986.
Assis, L., Moretti, A.I., Abrahao, T.B., de Souza, H.P., Hamblin, M.R., Parizotto, N.A., 2013. Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion. Lasers Med. Sci. 28 (3), 947955.
Bartos, A., Grondin, Y., Bortoni, M.E., Ghelfi, E., Sepulveda, R., Carroll, J., et al., 2016. Pre-conditioning with near infrared photobiomodulation reduces inflammatory cytokines and markers of oxidative stress in cochlear hair cells. J. Biophotonics 9 (1112), 11251135.
Mungrue, I.N., Husain, M., Stewart, D.J., 2002. The role of NOS in heart failure: lessons from murine genetic models. Heart Fail. Rev. 7 (4),
407422.
**Excessive amounts of NO produced by inducible nitric oxide synthase (iNOS) during inflammation can overwhelm the NO gradients produced by eNOS. The suppression of eNOS by iNOS disrupts the contraction/relaxation cycle in favor of excessive contraction and subsequent reduced flow.
Mungrue, I.N., Husain, M., Stewart, D.J., 2002. The role of NOS in heart failure: lessons from murine genetic models. Heart Fail. Rev. 7 (4), 407422.
Ahmed, I., Bose, S.K., Pavese, N., Ramlackhansingh, A., Turkheimer, F., Hotton, G., et al., 2011. Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain 134 (Pt 4), 979-986.
Assis, L., Moretti, A.I., Abrahao, T.B., de Souza, H.P., Hamblin, M.R., Parizotto, N.A., 2013. Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion. Lasers Med. Sci. 28 (3), 947-955.
**Increased oxidative/nitrosative stress usually describes a condition in which antioxidant defenses are inadequate to completely inactivate ROS/RNS produced because of excessive production of ROS/RNS, loss of antioxidant defenses, or both. RNS = reactive nitrogen species.
Nitric Oxide (like ROS) is sometimes called a Janus molecules, a little bit does you good but an awful lot of it can be harmful and damaging. RLT can work in both directions by increasing eNOS and nitric oxide in the blood vessels and lymphatics, especially the lymphatics. Research has shown the lymphatics** are VERY responsive to Nitric Oxide. PBM increases lymphatic drainage and reduces swelling.
But in acute inflammation where you have high amounts of NO, PBM can reduce it by switching the macrophage phenotype to M2 and activating OXPHOS.
**Deng J, Lukens JN, Swisher-McClure S, Cohn JC, Spinelli BA, Quinn RJ, Chittams J, McMenamin E, Lin A. Photobiomodulation Therapy in Head and Neck Cancer-Related Lymphedema: A Pilot Feasibility Study. Integr Cancer Ther. 2021 Jan-Dec
Oxidative and Nitrosative Stress (ROS + NO) a bad marriage
In studies of the effect of PBM on traumatized muscle, PBM has been shown to be effective in regulating the amount of cytokine-inducible nitric oxide synthase (iNOS) produced by the cell. This is important because excessive amounts of iNOS can lead to the excessive production of NO, which would then signal increased production of the ROS/reactive nitrogen species (RNS) called peroxynitrite, leading to an increase in oxidative stress. Specifically, PBM could reduce peroxynitrite (Bartos et al., 2016), while still preserving the positive effects of other isoforms of NO synthase, such as endothelial nitric oxygen synthase (eNOS), which is the species primarily responsible for the vasodilating effects of PBM (Mungrue et al., 2002; Ahmed et al., 2011; Assis et al., 2013).
Ahmed, I., Bose, S.K., Pavese, N., Ramlackhansingh, A., Turkheimer, F., Hotton, G., et al., 2011. Glutamate NMDA receptor dysregulation in
Parkinson’s disease with dyskinesias. Brain 134 (Pt 4), 979986.
Assis, L., Moretti, A.I., Abrahao, T.B., de Souza, H.P., Hamblin, M.R., Parizotto, N.A., 2013. Low-level laser therapy (808 nm) contributes to muscle regeneration and prevents fibrosis in rat tibialis anterior muscle after cryolesion. Lasers Med. Sci. 28 (3), 947955.
Bartos, A., Grondin, Y., Bortoni, M.E., Ghelfi, E., Sepulveda, R., Carroll, J., et al., 2016. Pre-conditioning with near infrared photobiomodulation reduces inflammatory cytokines and markers of oxidative stress in cochlear hair cells. J. Biophotonics 9 (1112), 11251135.
Mungrue, I.N., Husain, M., Stewart, D.J., 2002. The role of NOS in heart failure: lessons from murine genetic models. Heart Fail. Rev. 7 (4),
407422.

3 - Solution --> Subcellular Melatonin - The Master Antioxidant and the solution to Pathological ROS
That Mops up the free radicals.
How light interacts with mitochondria and body. You probably have not heard this before.
How does the body deal with this?
At Night, Melatonin is secreted from the Pineal Gland normally if the person is not being exposed to light and this melatonin is actively secreted and actively taken up into the cell and then it goes into the mitochondria where it is the major antioxidant and it is actually the one that controls glutathione, and it is twice as potent as vitamin E, but the question is while this is happening, that's great, but what happens during the day when more energy is needed and essentially these mitochondria are revving up at higher rpms?
Well, scientists are now discovering that infrared radiation from the sun actually directly stimulates the mitochondria to produce melatonin on site where the oxidative stress is occurring. You cannot get this effect from eating Melatonin or taking a supplement, this is actually FROM THE SUN ITSELF penetrating down into the tissue stimulating the mitochondria to produce melatonin!
That Mops up the free radicals.
How light interacts with mitochondria and body. You probably have not heard this before.
How does the body deal with this?
At Night, Melatonin is secreted from the Pineal Gland normally if the person is not being exposed to light and this melatonin is actively secreted and actively taken up into the cell and then it goes into the mitochondria where it is the major antioxidant and it is actually the one that controls glutathione, and it is twice as potent as vitamin E, but the question is while this is happening, that's great, but what happens during the day when more energy is needed and essentially these mitochondria are revving up at higher rpms?
Well, scientists are now discovering that infrared radiation from the sun actually directly stimulates the mitochondria to produce melatonin on site where the oxidative stress is occurring. You cannot get this effect from eating Melatonin or taking a supplement, this is actually FROM THE SUN ITSELF penetrating down into the tissue stimulating the mitochondria to produce melatonin!
***Work in***
There is melatonin outside the cell that can come in very quickly and mop these things up because melatonin is a very powerful antioxidant. But NOW we are finding out thatspecifically this last enzyme, CCO which takes this oxygen molecule and makes it into water and makes this process go well, when this enzyme CCO is excited with a certain wavelength of light, specifically near infrared light, it actually increases melatonin production inside of the mitochondria. That's right, melatonin is produced INSIDE the mitochondria as a result of the activation of this electron transport chain, which can then neutralize the product of this electron transport chain which is not only water,
There is melatonin outside the cell that can come in very quickly and mop these things up because melatonin is a very powerful antioxidant. But NOW we are finding out thatspecifically this last enzyme, CCO which takes this oxygen molecule and makes it into water and makes this process go well, when this enzyme CCO is excited with a certain wavelength of light, specifically near infrared light, it actually increases melatonin production inside of the mitochondria. That's right, melatonin is produced INSIDE the mitochondria as a result of the activation of this electron transport chain, which can then neutralize the product of this electron transport chain which is not only water,

Acute Inflammation - Necessary and Beneficial.
As we mentioned,
- Sudden or immediate threat to the body: viruses, bacteria, injury
- Immune cells mobilized move in to eliminate threat (neutrophils, macrophages) and remove damaged tissue.
- Chemicals released during this process (cytokines - interleukins, TNF) cause inflammation
- Inflammation retreats when the threat is removed
Example - Cut on the skin.
Defend from infection
Clear the wreckage (remove damaged / necrotic tissue
Mobilize Stem cells and Release proteins and growth factors to rebuild and heal
Inflammation is one of the innate immune system’s defenses against foreign bodies such as bacteria and viruses. On a cellular level, it occurs when the transcription factor NFκB is activated. While acute inflammation is positive, chronic inflammation can have very negative effects. Many diseases can be traced at least in part to chronic inflammation.
As we mentioned,
- Sudden or immediate threat to the body: viruses, bacteria, injury
- Immune cells mobilized move in to eliminate threat (neutrophils, macrophages) and remove damaged tissue.
- Chemicals released during this process (cytokines - interleukins, TNF) cause inflammation
- Inflammation retreats when the threat is removed
Example - Cut on the skin.
Defend from infection
Clear the wreckage (remove damaged / necrotic tissue
Mobilize Stem cells and Release proteins and growth factors to rebuild and heal
Inflammation is one of the innate immune system’s defenses against foreign bodies such as bacteria and viruses. On a cellular level, it occurs when the transcription factor NFκB is activated. While acute inflammation is positive, chronic inflammation can have very negative effects. Many diseases can be traced at least in part to chronic inflammation.

There is this very interesting paper published by Scott Zimmerman and Russell Reiter, one of them a professor and one of them a light engineer that described this and I would highly recommend looking at this article. Here are the highlights
Melatonin: Potent antioxidant activity
-Melatonin is produced within the mitochondria in response to sunlight and provides targeted protection of mitochondria from reactive oxygen species.
- Accordingly Melatonin is protective against the aforementioned diseases.
- May have a role in prevention and/or treatment of Alzheimers and Parkinson's [Oxidative stress as a proposed mechanism of beta amyloid accumulation and dopaminergic neuron death, respectively].
Zimmerman, S. and Reiter, R. 2019. Melatonin and the Optics of the Human Body. Melatonin Research. 2, 1 (Feb. 2019), 138-160. DOI:https://doi.org/https://doi.org/10.32794/mr11250016.
https://www.melatonin-research.net/index.php/MR/article/view/19/213
Melatonin: Potent antioxidant activity
-Melatonin is produced within the mitochondria in response to sunlight and provides targeted protection of mitochondria from reactive oxygen species.
- Accordingly Melatonin is protective against the aforementioned diseases.
- May have a role in prevention and/or treatment of Alzheimers and Parkinson's [Oxidative stress as a proposed mechanism of beta amyloid accumulation and dopaminergic neuron death, respectively].
Zimmerman, S. and Reiter, R. 2019. Melatonin and the Optics of the Human Body. Melatonin Research. 2, 1 (Feb. 2019), 138-160. DOI:https://doi.org/https://doi.org/10.32794/mr11250016.
https://www.melatonin-research.net/index.php/MR/article/view/19/213

Considering the presence and regulation of melatonin during chick development, the responses of glutathione, cytochrome c oxidase, and ATP in liver and brain to daily LED treatment after TCDD exposure suggest that melatonin, in conjunction with cytochrome c oxidase, is a principle component of the cellular response to LED red light therapy. Melatonin is linked to mitochondrial health via interaction with complexes I and IV [1,26], whereby oxidative phosphorylation and electron transport efficiency are enhanced and cytochrome c oxidase activity (complex IV) and ATP production(complex V) are both increased.
Reiter RJ, Pablos MI, Agapito TT, Guerrero JM. Melatonin inthe context of the free radical theory of aging. Ann NY AcadSci 1996;786:362–78.
Acuna-Castroviejo D, Martin M, Macias M, Escames G, LeonJ, Khaldy H, et al. Melatonin, mitochondria, and cellularbioenergetics. J Pineal Res 2001;30:65–74
Melatonin also acts by upregulating superoxide dismutase (SOD) [30] and increasing glutathione peroxidase (GPx) and glutathione reductase (GRx) activities [31]. We have observed increased enzyme activities of all three enzymes,SOD, GPx, and GRx, in the developing liver upon daily LED treatment [18]. The coordinated efforts of all three enzymes, in addition to catalase, are responsible for the detoxification of reactive oxygen and nitrogen species. That is to say, Melatonin is one of the best antioxidants that protects the body from free radical damage. In fact, it is a "Master Antioxidant" as it controls the upregulation of known cellular antioxidants like OH-, catalase and SOD.
Antolin I, Rodriguez C, Sainz RM, Mayo JC, Uria H, KotlerML, et al. Neurohormone melatonin prevents cell damage:effect on gene expression for antioxidant enzymes. FASEB J1996;10:882–90.
Pablos MI, Reiter RJ, Ortiz GG, Guerrero JM, Agapito MT,Chuang JI, et al. Rhythms of glutathione peroxidase andglutathione reductase in brain of chick and their inhibitionby light. Neurochem Int 1998;32:69–75.
Yeager RL, Lim J, Millsap DS, Jasevicius AV, Sanders RA,Whelan HT, et al. 670 nm light treatment attenuates dioxintoxicity in the developing chick embryo. J Biochem MolecToxicol 2006;20:271–8
Various analyses [35–37] of the effects of lightand LEDs on melatonin levels and rhythms in humans have shown that while shorter wavelengths of blue (430 nm) and green (540 nm) light suppress salivary melatonin and shift the melatonin rhythm,red light (610 and 660 nm) has no effect on melatonin suppression and slightly shortens the time be-fore dim light onset of melatonin secretion.
Wright HR, Lack LC. Effect of light wavelength on suppres-sion and phase delay of the melatonin rhythm. ChronobiolInt 2001;18:801–8.[36]
Wright HR, Lack LC, Partridge KJ. Light emitting diodes canbe used to phase delay the melatonin rhythm. J Pineal Res2001;31:350–5.[37]
Zeitzer JM, Kronauer RE, Czeisler CA. Photopic transduc-tion implicated in human circadian entrainment. NeurosciLett 1997;232:135–8
Reiter RJ, Pablos MI, Agapito TT, Guerrero JM. Melatonin inthe context of the free radical theory of aging. Ann NY AcadSci 1996;786:362–78.
Acuna-Castroviejo D, Martin M, Macias M, Escames G, LeonJ, Khaldy H, et al. Melatonin, mitochondria, and cellularbioenergetics. J Pineal Res 2001;30:65–74
Melatonin also acts by upregulating superoxide dismutase (SOD) [30] and increasing glutathione peroxidase (GPx) and glutathione reductase (GRx) activities [31]. We have observed increased enzyme activities of all three enzymes,SOD, GPx, and GRx, in the developing liver upon daily LED treatment [18]. The coordinated efforts of all three enzymes, in addition to catalase, are responsible for the detoxification of reactive oxygen and nitrogen species. That is to say, Melatonin is one of the best antioxidants that protects the body from free radical damage. In fact, it is a "Master Antioxidant" as it controls the upregulation of known cellular antioxidants like OH-, catalase and SOD.
Antolin I, Rodriguez C, Sainz RM, Mayo JC, Uria H, KotlerML, et al. Neurohormone melatonin prevents cell damage:effect on gene expression for antioxidant enzymes. FASEB J1996;10:882–90.
Pablos MI, Reiter RJ, Ortiz GG, Guerrero JM, Agapito MT,Chuang JI, et al. Rhythms of glutathione peroxidase andglutathione reductase in brain of chick and their inhibitionby light. Neurochem Int 1998;32:69–75.
Yeager RL, Lim J, Millsap DS, Jasevicius AV, Sanders RA,Whelan HT, et al. 670 nm light treatment attenuates dioxintoxicity in the developing chick embryo. J Biochem MolecToxicol 2006;20:271–8
Various analyses [35–37] of the effects of lightand LEDs on melatonin levels and rhythms in humans have shown that while shorter wavelengths of blue (430 nm) and green (540 nm) light suppress salivary melatonin and shift the melatonin rhythm,red light (610 and 660 nm) has no effect on melatonin suppression and slightly shortens the time be-fore dim light onset of melatonin secretion.
Wright HR, Lack LC. Effect of light wavelength on suppres-sion and phase delay of the melatonin rhythm. ChronobiolInt 2001;18:801–8.[36]
Wright HR, Lack LC, Partridge KJ. Light emitting diodes canbe used to phase delay the melatonin rhythm. J Pineal Res2001;31:350–5.[37]
Zeitzer JM, Kronauer RE, Czeisler CA. Photopic transduc-tion implicated in human circadian entrainment. NeurosciLett 1997;232:135–8
Top Ten Reason RLT helps the body to heal itself of just about everything!
It all starts with ATP production/Metabolism & Secondarily Nitrogen Generation
1*) ATP - Energy Production
2) NO - Blood Flow/Increased Circulation/Angiogenesis
3) Melatonin - Antioxidant Effect
3) Glycosis to Oxphos M1-> M2 - Anti-inflammatory & Pain Relief
4) Oxygen Consumption - ROS - Exercise Mimetic - Preconditioning
5) Signalling ROS - Antioxidant Effect - SOD
6) Glycosis to Oxphos Increases Stem Cells [Healing and Regeneration]
7) NO creation- Lymphatic Drainage / Detox
8) Increases Immunity
1*) ATP
2) Nitric Oxide
3) M1-> M2 - Anti-inflammatory & Pain Relief
4) ROS - Exercise Hermetic - Preconditioning
5) Antioxidant Effect - SOD
6) Increases Stem Cells [Healing and Regeneration]
7) Lymphatic Drainage / Detox
8) Increases Immunity
9) Improves Sleep
10) Reduces Stress and Improves Mood (Sympathetic to Parasympathetic)
It all starts with ATP production/Metabolism & Secondarily Nitrogen Generation
1*) ATP - Energy Production
2) NO - Blood Flow/Increased Circulation/Angiogenesis
3) Melatonin - Antioxidant Effect
3) Glycosis to Oxphos M1-> M2 - Anti-inflammatory & Pain Relief
4) Oxygen Consumption - ROS - Exercise Mimetic - Preconditioning
5) Signalling ROS - Antioxidant Effect - SOD
6) Glycosis to Oxphos Increases Stem Cells [Healing and Regeneration]
7) NO creation- Lymphatic Drainage / Detox
8) Increases Immunity
1*) ATP
2) Nitric Oxide
3) M1-> M2 - Anti-inflammatory & Pain Relief
4) ROS - Exercise Hermetic - Preconditioning
5) Antioxidant Effect - SOD
6) Increases Stem Cells [Healing and Regeneration]
7) Lymphatic Drainage / Detox
8) Increases Immunity
9) Improves Sleep
10) Reduces Stress and Improves Mood (Sympathetic to Parasympathetic)
*Healthy* Angiogenesis
PBM has also been shown to stimulate increases in angiogenesis, leading to further improvements in blood flow. As demonstrated by Cury et al. (2013), PBM at 780 nm and 40 J/cm2 triggered an increase in the expression of the protein HIF1α and of vascular endothelial growth factor, and a decrease in matrix metalloproteinase two activity, all of which were found to induce angiogenesis.
Cury, V., Moretti, A.I., Assis, L., Bossini, P., Crusca Jde, S., Neto, C.B., et al., 2013. Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1alpha and MMP-2. J. Photochem. Photobiol. B 125, 164-170
PBM has also been shown to stimulate increases in angiogenesis, leading to further improvements in blood flow. As demonstrated by Cury et al. (2013), PBM at 780 nm and 40 J/cm2 triggered an increase in the expression of the protein HIF1α and of vascular endothelial growth factor, and a decrease in matrix metalloproteinase two activity, all of which were found to induce angiogenesis.
Cury, V., Moretti, A.I., Assis, L., Bossini, P., Crusca Jde, S., Neto, C.B., et al., 2013. Low level laser therapy increases angiogenesis in a model of ischemic skin flap in rats mediated by VEGF, HIF-1alpha and MMP-2. J. Photochem. Photobiol. B 125, 164-170
Ca2+ Signalling - TRP Channels
As we saw in the last chapter, TRP channels are affected by NIR light likely due to the absorption by structured water discussed earlier. PBM creates conformational change which creates nanostructered water in the channel lowering surface tension and allowing for changes in Ca2+ to more easily flow in and out in a way that modulates (in or out). That is, water is the chromophore and by far the most abundant in the body!
Ca2+ regulates almost every process in the human body (muscle contraction, blood coagulation, signal transfer in nerves, gene expression, etc.). From the change of Ca2+ you get a lot of signaling inside the cells because the calcium channels are open (just like we get a lot of signaling with the photodisassociation of NO).
Some evidence for this hypothesis comes from the research that has been done on stimulation of neurons by pulsed IR lasers. This was proposed to involve the induction of “thermally-evoked capacitive currents” that affected heat-sensitive TRP channels, specifically TRPV4. [8]
8. Albert ES, Bec JM, Desmadryl G, et al. TRPV4 channels mediate the infrared laser-evoked response in sensory neurons. J Neurophysiol 2012;107:3227–3234.
As we saw in the last chapter, TRP channels are affected by NIR light likely due to the absorption by structured water discussed earlier. PBM creates conformational change which creates nanostructered water in the channel lowering surface tension and allowing for changes in Ca2+ to more easily flow in and out in a way that modulates (in or out). That is, water is the chromophore and by far the most abundant in the body!
Ca2+ regulates almost every process in the human body (muscle contraction, blood coagulation, signal transfer in nerves, gene expression, etc.). From the change of Ca2+ you get a lot of signaling inside the cells because the calcium channels are open (just like we get a lot of signaling with the photodisassociation of NO).
Some evidence for this hypothesis comes from the research that has been done on stimulation of neurons by pulsed IR lasers. This was proposed to involve the induction of “thermally-evoked capacitive currents” that affected heat-sensitive TRP channels, specifically TRPV4. [8]
8. Albert ES, Bec JM, Desmadryl G, et al. TRPV4 channels mediate the infrared laser-evoked response in sensory neurons. J Neurophysiol 2012;107:3227–3234.
Research showing how RLT specifically can have an opposite effect on NF-KB - the master inflammatory switch
There is evidence that PBM can have opposite effects on NFκB depending on the type of cells and their activation state that is studied. Chen et al. (2011a)
nf-kb and AP-1 - NIR light also has been shown to activate nuclear factor kappa B, which is a redox-sensitive transcription factor (Chen et al., 2011). This pro-survival transcription factor modulates the expression of numerous genes, including ones involved in inflammation, early response, and cell survival.
Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via
generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6 (7), e22453.
--
Changes in intracellular signaling molecules such as calcium ions, reactive oxygen species (ROS), and redox- sensitive transcription factors like NF-kB are also thought to mediate the effects of light. Previous studies from our laboratory in mouse embryonic fibroblast cells (Chen et al., 2009) have shown that 810 nm laser induced ROS-mediated NF-kB activation.
Chen, A.C.-H., Arany, P.R., Huang, Y.-Y., Tomkinson, E.M., Saleem, T., Yull, F.E., et al., 2009. Low level laser therapy activates NF-kB via genera-
tion of reactive oxygen species in mouse embryonic fibroblasts. Proc. SPIE 7165.
(Chen et al., 2011b). Likewise Yamaura et al. (2009) found that the level of NFκB was reduced in activated rheumatoid arthritis derived synoviocytes that received PBM.
Chen, A.C., Huang, Y.Y., Sharma, S.K., Hamblin, M.R., 2011b. Effects of 810-nm laser on murine bone-marrow-derived dendritic cells. Photomed.
Laser Surg. 29 (6), 383389.
Lim, W., Kim, J., Kim, S., Karna, S., Won, J., Jeon, S.M., et al., 2013. Modulation of lipopolysaccharide-induced NF-kappaB signaling pathway by
635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem. Photobiol. 89 (1), 199207.
Yamaura, M., Yao, M., Yaroslavsky, I., Cohen, R., Smotrich, M., Kochevar, I.E., 2009. Low level light effects on inflammatory cytokine production
by rheumatoid arthritis synoviocytes. Lasers Surg. Med. 41 (4), 282290.
There is evidence that PBM can have opposite effects on NFκB depending on the type of cells and their activation state that is studied. Chen et al. (2011a)
nf-kb and AP-1 - NIR light also has been shown to activate nuclear factor kappa B, which is a redox-sensitive transcription factor (Chen et al., 2011). This pro-survival transcription factor modulates the expression of numerous genes, including ones involved in inflammation, early response, and cell survival.
Chen, A.C., Arany, P.R., Huang, Y.Y., Tomkinson, E.M., Sharma, S.K., Kharkwal, G.B., et al., 2011. Low-level laser therapy activates NF-kB via
generation of reactive oxygen species in mouse embryonic fibroblasts. PLoS One 6 (7), e22453.
--
Changes in intracellular signaling molecules such as calcium ions, reactive oxygen species (ROS), and redox- sensitive transcription factors like NF-kB are also thought to mediate the effects of light. Previous studies from our laboratory in mouse embryonic fibroblast cells (Chen et al., 2009) have shown that 810 nm laser induced ROS-mediated NF-kB activation.
Chen, A.C.-H., Arany, P.R., Huang, Y.-Y., Tomkinson, E.M., Saleem, T., Yull, F.E., et al., 2009. Low level laser therapy activates NF-kB via genera-
tion of reactive oxygen species in mouse embryonic fibroblasts. Proc. SPIE 7165.
(Chen et al., 2011b). Likewise Yamaura et al. (2009) found that the level of NFκB was reduced in activated rheumatoid arthritis derived synoviocytes that received PBM.
Chen, A.C., Huang, Y.Y., Sharma, S.K., Hamblin, M.R., 2011b. Effects of 810-nm laser on murine bone-marrow-derived dendritic cells. Photomed.
Laser Surg. 29 (6), 383389.
Lim, W., Kim, J., Kim, S., Karna, S., Won, J., Jeon, S.M., et al., 2013. Modulation of lipopolysaccharide-induced NF-kappaB signaling pathway by
635 nm irradiation via heat shock protein 27 in human gingival fibroblast cells. Photochem. Photobiol. 89 (1), 199207.
Yamaura, M., Yao, M., Yaroslavsky, I., Cohen, R., Smotrich, M., Kochevar, I.E., 2009. Low level light effects on inflammatory cytokine production
by rheumatoid arthritis synoviocytes. Lasers Surg. Med. 41 (4), 282290.
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