The Science and Benefits of Red Light Therapy

If you're involved in the alternative health or biohacker community you may have already heard about using red light to stimulate your mitochondria, the powerhouse of your cells. There are expensive whole-body devices offered by companies like Joovv, and there are many smaller, more targeted devices on the market.

Red light therapy, also known as low-level light therapy (LLLT), also known as photobiomodulation (the latest scientific term), is creeping into the mainstream. Your massage therapist might offer it to you soon, if they haven't already, and you may see an option for a "collagen red light facial" at your dermatologist or nearest medspa.

This is an emerging field of science that has progressed rapidly over the last few decades. Red light therapy is now commonly used to reduce pain and inflammation, speed up wound healing, regenerate tissues and nerves, and prevent skin damage.[1][2][3] It has also been demonstrated to be a promising therapeutic option for a range of cosmetic use cases.[1]

Ancient history to Nobel Prize

Light therapy may be one of the oldest therapeutic methods used by humans – historically as solar therapy by Egyptians, the Greeks (Heliopolis, the city of the sun, was famous for its healing temples), and other cultures.[4]

Modern use of light therapy started in the 19th century and reached a climax when Niels Finsen received the Nobel Prize in 1903 for using ultraviolet (UV) light to treat lupus vulgaris, the disfiguring and painful skin lesions caused by tuberculosis.[5]

Throughout his life, Niels Finsen suffered from a metabolic disease that caused weakness and fatigue, but he noticed that light made him feel more energetic. This led him to study the medical benefits of light. The Nobel Prize remarked that his work "opened a new avenue for medical science."[5]

This set the start of modern phototherapy. UV irradiation was used in thermal stations for treatment of tuberculosis, in the treatment of leg ulcers in wartime, and in the treatment of skin diseases.[6] In 1925, it was shown that food irradiated with UV light prevented rickets in rats, which paved the way for the discovery of vitamin D.[7]

This period also coincided with the development of dedicated facilities in Europe and North America which used sun therapy (heliotherapy) for the treatment of tuberculosis. All around the world there were sanatoriums where tuberculosis was treated with sunlight and dry air.

The greatest area for sanatoriums was in Tucson, Arizona. By 1920, Tucson had 7,000 people who had come for treatment of tuberculosis. So many people came west that not enough housing was available for them all and tent cities began to pop up in different areas.[8]

For a time, up until the 1940s-1950s, light therapy was widespread, but eventually it was replaced by antibiotics.[9]

The laser that grew hair

The scientific interest in red light started in 1965, only a few years after the first working laser was invented. Dr. Endre Mester wanted to test if laser radiation could destroy malignant tumors, so he implanted tumor cells under the skin of lab rats and exposed them to a low-powered ruby laser. The tumor cells were not destroyed, and to his surprise, the skin incisions appeared to heal faster in the treated animals.[10][11]

Fascinated by this development, Dr. Mester carried out other experiments that showed how skin defects, burns, ulcers, and infected wounds also healed faster in response to his laser treatment.[12][13] Following his earlier observations on skin, Dr. Mester showed how the same treatment could also accelerate hair growth in mice.[14]

This was the first demonstration of the "bio-stimulation" effect of lasers.[15]

Modern era of light therapy

The use of lasers, and now more commonly light-emitted diodes (LEDs), as light sources were the next step in the technological development of light therapy, which is now applied to many thousands of people worldwide each day.[15]

Nowadays, the question is not whether light has biological effects, but rather how energy from lasers and LEDs work at the cellular and organism levels, and what are the optimal parameters.[15]

The scientific approach

In the study of light's effect on biology (photobiology), the first law of photobiology states that:

Photons of light must be absorbed for light to have any effect on a living biological system.[16]

Light is electromagnetic energy that travels in distinct packets and also has wave-like properties. The wavelength of light is measured in nanometers (nm) and is visible in the 400–700 nm range. Different wavelengths of light are perceived as different colors by the human eye.

Each chemical compound absorbs light differently based on its unique structure. Therefore, an absorption spectrum will tell the probability that light of a given wavelength will be absorbed, and therefore the possibility of producing a photobiological effect.[15]

Below is the absorption spectrum of human tissue showing that water, hemoglobin (blood), and melanin (skin) are the primary absorbers of light energy. Melanin is the pigment that makes skin dark and is effective at defending the body against UV and other light energy.

However, there is a so-called "optical window" between 600-1200 nanometers where light is less blocked by the body's main absorbers of light energy and has a chance to reach important cellular molecules.[15]

Therefore, although blue, green, and yellow light may have significant effects on the body, the use of light therapy almost exclusively involves red, infrared, and near-infrared light.

Tissue absorption spectrum showing "optical window" due to reduced absorption at 600-1200 nm.

Once a photobiological response is observed, it's necessary to produce an action spectrum to plot the effectiveness of different wavelengths of light in causing the effect.

For example, the action spectrum for killing bacteria mimics the absorption spectrum of deoxyribonucleic acid (DNA), which is understandable because of the importance of DNA to a cell.[16]

Below is the action spectrum of cytochrome c oxidase (CCO), an important enzyme in mitochondria, the powerhouse of the human cell.[17][18] I will discuss the implications of this more below, but note the activation peaks at wavelengths in the "optical window" of red light mentioned above.

Cytochrome c oxidase action spectrum showing peaks at 620, 680, 750, and 820-830 nm.

Conservation of energy

There is another important scientific law we need to discuss: the first law of thermodynamics. Applying this law to photobiology we get:

The light energy delivered to any biological tissue must be conserved.[15]

The energy output of light depends on the number of photons and their color (wavelength). These photons will be absorbed or scattered, and scattered light will eventually be absorbed or escape.[15]

When a photon is absorbed by a molecule, the electrons of that molecule are raised to a higher energy state. This excited molecule must lose its extra energy, and it can do so in three ways: [15][16]

  1. Heat – This is the most common pathway that occurs when light is absorbed by living tissue. The excitation energy is given off as molecular vibrations or heat.
  2. Fluorescence – This is when the absorption of a photon triggers the emission of another photon with a longer wavelength. Any energy difference between the absorbed and emitted photons ends up as molecular vibrations or heat.
  3. Photobiological responses – Reactions occur that are highly important in the mitochondrial respiratory chain, where the principal molecules involved in laser therapy are thought to be situated.

What happens in the cell?

The third pathway, the path of photons being converted into biological responses, is what we are focused on with light therapy, but what exactly is happening at the cellular level?

Cell biology is quite technical so the following will largely be a summarization of Dr. Hamblin's wonderful introduction to low-level light therapy.

Mitochondria

The most prominent role of mitochondria is to produce the energy currency of the cell, ATP, and to regulate cellular metabolism.

It is believed that light therapy activates mitochondria to increase ATP production, release nitric oxide, and promote the formation of reactive oxygen species (ROS), which have important roles in cell signaling. Combined, these stimulate transcription factors, which help to turn specific genes "on" or "off", and gene expression of proteins.

Therefore, light therapy is capable of stimulating processes responsible for tissue repair, wound healing, and prevention of cell death (apoptosis).[19]

Cytochrome c oxidase (CCO)

It is believed that cytochrome c oxidase (CCO) is the most important molecule in cells that absorb red light. As was shown in the picture of the action spectrum above, CCO activates at peaks in the "optical window" of human tissue in the red, infrared, and near-infrared wavelengths.

The many different oxidation states of the enzyme have different absorption levels, which probably accounts for the slight differences in action spectra during light therapy.[15]

The absorption of photons by CCO leads to electronically excited states and consequently can lead to the increase of electron transfer reactions, leading to increased production of cellular energy, ATP.[20]

A simple way to think of this process is that photons are charging your cellular batteries.

Nitric oxide (NO)

The activity of CCO is typically inhibited by nitric oxide (NO), but it is believed that red light therapy reverses this inhibition by releasing NO from its binding sites in the respiratory chain and elsewhere.[21][22]

Some light can also be absorbed by hemoglobin in red blood cells, and that can release NO. Since red blood cells are continuously delivered to the area of treatment, there is a natural supply of NO that can be released from each new cell that passes under the light source.

Blood vessels use NO to signal muscle relaxation, causing widening of the blood vessels (vasodilation) and increasing blood flow. As an example, Viagra works on the NO pathway to make erections easier.

Light-mediated vasodilation was first described in 1968 by Dr. Robert Furchgott, which led to his receipt of the Nobel Prize thirty years later in 1998.[23][24] Later studies demonstrated the ability of light to influence the localized production or release of NO, and to therefore stimulate vasodilation.

Since the half-life of the NO released is only 2-3 seconds, NO release is very local, preventing the effect of increased NO from being manifested in other portions of the body.

Cell signaling and gene expression

It is believed that light therapy produces a shift in overall cell redox state, which is believed to regulate cell signaling pathways, activating or inhibiting signaling pathways that control gene expression.

Changes in redox state induce the activation of many intracellular signaling pathways, such as nucleic acid synthesis, protein synthesis, enzyme activation, and cell cycle progression.

Specific wavelengths of red light stimulate production of ATP, NO, and ROS, which affect cell signaling and gene expression.

Exposure of human collagen to red light has been shown to affect cell growth directly by gene expression related to cell proliferation, and indirectly through regulation of genes related to cell migration and remodeling, DNA synthesis, and cell metabolism. Red light also enhanced cell proliferation by suppression of programmed cell death (apoptosis).

More light is not always better

There is something called a biphasic dose response in light therapy, which simply means that if too little energy is applied there will be no response, and if too much energy is applied then the stimulation is replaced by inhibition.[25]

Light energy terms

Using proper dosage in light therapy is crucial. Using the analogy of plumbing: both the diameter of the pipe and the amount of water are important variables.

  • Irradiance – represented as milliwatts per centimeter squared. It's a snapshot of power per unit of area and does not indicate time or dose of treatment. Think of this as the diameter of the pipe.
  • Fluence – represented as joules per centimeter squared. A joule is a measure of energy transferred or work done, so this represents the dose of energy received. Think of this as the amount of water that has flowed through the pipe.

By knowing these two parameters you can calculate the total amount of energy transferred, at what rate, for how long.

Excess light inhibits healing

As an example of the importance of dosing light therapy correctly, a study was done of wound healing in mice. A cut was made on the back of the mice and then they were treated with 635 nm red light 30 minutes later. Different amounts of light energy were applied (1, 2, 10, and 50 J/cm2) at a constant rate of 100 mW/cm2 and taking 10, 20, 100 and 500 seconds respectively.

Researchers noted that wounds typically expand for 2-3 days after they're made, but even a brief exposure to red light soon afterward reduced or stopped the expansion of the wound.

As shown below, the difference in wound healing compared to the control group (no incision) was maximum at 2 J/cm2. However, the high dose of 50 J/cm2 actually worsened the wound healing. In other words, there was a greater expansion of the wound compared to the control group and the mouse would have been better off with no light therapy at all.[26]

Wound healing at different light therapy doses compared to control group. A clear maximum is seen at 2 J/cm2, while a high dose of 50 J/cm2 worsened the wound healing.

Proven therapeutic effects

There is evidence in animal models and extensive evidence in vitro (test tube / Petri dish) that most cell types respond to red light therapy.

The cellular responses observed after red light therapy can be broadly classed as increases in metabolism, migration, proliferation, cell synthesis, and production of various proteins.

All genes related to antioxidants, energy metabolism, and respiratory chain have been shown to become more sensitive (upregulated) under light therapy. Most genes related to cell proliferation are upregulated too.

Damage and inflammation

  • Burns / wound healing - Studies have shown that light therapy improves new blood vessel formation (angiogenesis) in vitro and in chick embryo models,[27] and reduces necrosis and improves collagen content for skin grafts in rats.[28][69]
  • Neuronal toxicity – Studies have explored the use of red light to combat damage caused by neurotoxins, showing that nerve function could be significantly recovered, and neuronal death reduced in rat models. In some cases, light therapy was able to completely reverse the effect of a neurotoxin.[29][30]
  • Nerve regrowth / regeneration – Studies have shown that light therapy can improve nerve repair in the spinal cord and facial nerves of rats.[31][32]
  • Anti-inflammatory / anti-edemaIn vitro studies exist that show light therapy reduces inflammatory responses in cells.[33][34][35][36] Studies in animals and humans show that light therapy reduce inflammation and mucus in airways, help inhibit and repair inflammatory dental root condition, and reduce the incidence and severity of mucositis in patients treated with chemotherapy.[72][73][75]
  • Muscle injury prevention / recovery – In a study on hamstring strain injuries in humans, it was shown that light therapy applied before a simulated soccer match (300J per thigh) proved to be effective in reducing the hamstrings' muscle fatigue.[74]
  • Brain disease – Red light therapy modulates various molecular pathways to the brain. In a mouse model of Parkinson's disease pre-conditioning has been shown to provide neuroprotection.[76]

Cosmetic and dermatology

In the field of cosmetics and dermatology, light therapy is becoming popular due to being non-invasive, having mild side-effects, and its convenience of use.

Much of the following will be a summarization of Dr. Hamblin and Dr. Sawhney's paper about light therapy for cosmetic medicine and dermatology.

  • Acne – Nearly 90% of adolescents get acne, which can have emotional and social impacts on their life. Infrared light has been shown to destroy oil glands in the skin (sebaceous glands), reduce acne bumps. and reduce inflammation.[37][38] Several studies have demonstrated the ability of light (630-1000 nm) for the treatment of acne.[39] One study demonstrated a significant reduction in active acne bumps after treatment (630 nm, 12 J/cm2) twice a week for 12 sessions.[40]
  • Sun damage– It is broadly accepted that UV radiation due to chronic sunlight exposure is responsible for most skin damage. Some studies suggest that red light therapy may provide protection against UV damage due to the fact that in the morning, red to near-infrared wavelengths dominate the solar spectrum, and prepare the skin for the harmful UV radiation that comes later in the day.[41] One study using light therapy (700-2000 nm) was able to generate long-lasting (>24 hour) cellular defense against UV toxicity, and it was believed to be a cumulative phenomenon.[42]
  • Herpes – Herpes simplex virus (HSV) infections are some of the most common types of infections in the present age, and persist life-long within the host’s body. Red light therapy provides accelerated healing, reduced symptoms, and management of recurrent outbreaks. One study administered red light therapy to a group of 50 patients suffering from recurrent HSV infections (690 nm, 80 mW/cm2, 48 J/cm2) and a reduction in the frequency of herpes episodes was observed.[43] In another study (647 nm, 50 mW/cm2, 4.5 J/cm2), it was reported that remission was prolonged from 30 days to 73 days in patients with recurrent HSV infections.[44]
  • Vitiligo – Vitiligo is an acquired pigmentary disorder characterized by depigmentation of the skin and hair. One study showed that after 6-8 months of red light therapy (633 nm, 25 mW/cm2) there was a noticeable degree of repigmentation in 64% of the patients.[45]
  • Pigmented scars – Several studies, especially for vitiligo, show that light therapy exhibits stimulatory effects on pigmentation. One study showed that the effects of blue light (415 nm, 40 mW/cm2, 48 J/cm2) and red light (633 nm, 80 mW/cm2, 96 J/cm2) in combination showed an overall decrease in melanin.[46]
  • Scars and keloids – Thick scars and raised scar tissue (keloids) are benign and usually develop following surgery, trauma, or acne, and are difficult to remove. In studies investigating light therapy as a way to impair the formation of scars or keloids, it was observed that the treated scars showed significant improvement over the control group.[47]
  • Burns – A study of 10 patients with sunburn who used red light therapy once or twice a day for 3 days (590 nm, 0.1 J/cm2) showed a reduction in redness, swelling, burning, and peeling. A study of 74 mice, where each mouse received third-degree burns and then treated with an infrared laser (2.3 and 11.7 J/cm2). showed a reduction in microbial infections and enhanced tissue healing. The higher fluence of 11.7 J/cm2 provided the most substantial increases.[48][49]
  • Psoriasis – Psoriasis is a chronic and recurrent inflammatory skin condition that affects about 1 to 3% of the population.[50] A study which used a combination of red (630 nm) and near-infrared (830 nm) light for two, 20-minute sessions, spaced 48 hours apart for a total of 4 or 5 weeks, resolved the patients' psoriases and did not display any adverse effects.[51]

Hair loss

  • Hair loss – Hair is amongst the fastest growing tissues of the body, undergoing repetitive and regenerative cyclical changes.[52] In 2007, the United States Food and Drug Administration (FDA) approved light therapy as a possible treatment for hair loss. It is believed that light therapy can stimulate re-entry of hair follicles, increase proliferation, and extend the duration of the growth phase.[53]
  • Alopecia areata – Alopecia areata is an autoimmune disease that causes hair loss. One study with a sample size of 15 patients using red to near-infrared light (600-1600 nm) with 3-minute laser treatment on the scalp, either once a week or once every 2 weeks, showed that 47% of the patients experienced hair growth 1.6 months earlier on treated areas compared to control.[54]
  • Androgenetic alopecia – In studies of male-pattern baldness, mice were injected with testosterone and exposed to red lasers (633 nm, 1 and 5 J/cm2) at 24-hour intervals for 5 days. Mice that received treatment at a dosage of 1 J/cm2 showed greater amounts of hair follicles in the growth phase, while mice given a dose of 5 J/cm2 showed a decrease in hair follicles, which could be due to the biphasic dose response of light therapy.[55]
  • Chemotherapy-induced alopecia – About 65% of patients that receive chemotherapy develop hair loss, which can have effects on the psychological health of the patient.[56] In a study where rats were administered chemotherapy in combination with light therapy, hair regrowth occurred at a faster rate, and the light therapy did not reduce the efficacy of the chemotherapy treatment.[57]

Fat reduction and cellulite

  • Lipoplasty / liposuction – Red light therapy has been explored as a supplement to liposuction surgery, and has been shown to reduce procedure time, allow for greater extraction of fat, and reduce the energy expenditure of the surgeon. Using a red laser (635 nm, 10mW, 1.2 to 3.6 J/cm2) it was demonstrated that fat cells (adipocytes) exhibited pore formation and this enabled the release of intracellular lipids from the adipocytes.[58]
  • Lipolysis –  As an alternative to surgery, red light therapy can help the breakdown of fats non-invasively. Several devices are on the market and the scientific literature has supported their efficacy.[59][60]
  • Cellulite – Cellulite is observed in about 85% of adult women, posing a major cosmetic concern in the area of the thighs and buttocks. In a study of 83 subjects, a dual-wavelength (650 nm and 915 nm) laser, in combination with a massage device, demonstrated an improvement in cellulite appearance and a 71% reduction in the circumference of patient thighs (compared to a 53% reduction in the control group).[61]

Discovering optimal parameters

The biological effects of certain wavelengths of light on human biology are well established, however the wide range of parameters that can be applied have sometimes led to contradictory results. The scientific community is now focused on discovering the optimal parameters and protocols for treatment.[70]

  • Wavelength – Wavelength affects tissue penetration. Shorter wavelengths in the red 600-700 nm range are considered best for treating superficial tissue, while longer infrared wavelengths between 780-950 nm are chosen for deeper-seated tissues, due to longer optical penetration distances through tissue. For example, infrared wavelengths show better effects on bone repair compared to red wavelengths.[70]
  • Laser vs LED –  One widely discussed issue is whether lasers have additional benefits compared to an LED light source. The light emitted by lasers are almost always within 1 nm or less of a specific wavelength, and all the photons are in phase (coherent), while the light from LEDs is broader, within 10-20 nm of each other, and non-coherent. Laser light is unique in that it produces a phenomenon in biological tissue known as laser speckle, which has been thought to stimulate mitochondria better than LEDs.[70] However, a recent review concluded that there were no substantial differences between lasers and LEDs given that all other parameters were the same.[71]
LEDs are non-coherent and emit a wider range of wavelengths (+/- 20 nm), while lasers are coherent and have a narrow range (within 1 nm) of wavelengths.
  • Dose – The existence of a biphasic dose response makes choosing the correct dosage of light for a specific medical condition difficult. It is believed that mitochondrial density of the tissues may be an important factor, with higher-density tissues (muscle, brain, heart, nerve) responding better to light therapy than those with less mitochondria (skin, tendon, cartilage).[70] Depth of penetration also seems to matter, with superficial diseases tending to use red light with doses of 4 J/cm2 with a range of 1-10 J/cm2, and deeper-seated issues using near-infrared wavelengths in the range of 10-50 J/cm2. Treatment is usually repeated every day or every other day.
  • Pulsed or continuous wave – Some studies show that pulsing the light energy produces better effects, but the underlying mechanism is still unclear and results have been contradictory.[70] Using near-infrared lasers (830 nm) to study the stimulation of rat bone cells, a pulse rate of 1-2 Hz  (1 hertz = 1 cycle per second) produced better effects than 8 Hz or continuous energy. The amount of time a pulse remains "on" over the duration of the cycle (duty cycle) may also be a parameter.[62][63]
  • Polarization – Polarized light (light that is vibrating in the same plane) vs non-polarized light has been studied as a parameter in light therapy. However, polarized light is rapidly scrambled in the upper layers of skin and tissue and therefore seems unlikely to play a major role.[64]
  • Treatment site – The optimal treatment site for different conditions is still being researched. In a study of skin grafts in rats, some treatment sites resulted in less necrosis and more collagen content than others.[28] In a mouse model of Parkinson's disease, remote pre-conditioning provided neuroprotection.[76]
  • Systemic effects – There are reports of systemic effects of light therapy acting at sites distant from the area treated.[65][66] Laser acupuncture is an emerging field in which effects at distant locations are observed similar to needle acupuncture.[68] Remote pre-conditioning has been shown to provide neuroprotection in one study.[76]

Try it for yourself

The therapeutic use of red to near-infrared light has been known for decades, however, light therapy still remains controversial in mainstream medicine.

I encourage you to go try it for yourself. With reasonable light intensity and dosage it's highly unlikely to cause any harmful effects, and it may in fact be helpful to you.

It's not hard to imagine a time in the future when daily at-home light therapy treatment is commonplace for pain relief, trauma, improved skin, and overall anti aging.