Red Light and Photobiomodulation: ATP from Photons

Key takeaways:
~ Mitochondria can directly produce (a little) ATP from certain wavelengths of red and near-infrared light.
~ Photobiomodulation is the application of red light to improve health, with studies showing many different benefits.
~ Light intensity and wavelength are important in determining whether the light therapy is beneficial. Time of day is also important.

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Energy from light: Producing ATP from Photons

In elementary school science, you likely learned about photosynthesis –  that sunlight hitting a green plant is turned into energy. The absorption of certain wavelengths of light by chlorophylls, the pigments that make leaves green, drives the plant’s energy production.

Sun + water + CO2 gets converted to energy and stored in plants.

The interaction of light (photons) within our own human cells can also produce (a little) energy.

I still find it a bit mind-boggling that under the right conditions the mitochondria in our cells can generate energy from light. However, new research clearly shows that cells can use light of certain wavelengths to produce energy (ATP).[ref] In addition, other wavelengths and intensities can cause other effects in cells.

Photobiomodulation is a light therapy used for pain, inflammation, joint health, wound healing, muscle recovery, and skin health. It sounds like something out of science fiction, but the research into how it works is fascinating.

Let’s dive into the research on how photobiomodulation works, starting with how mitochondria make energy and what spectrum of light can interact with mitochondria.

Mitochondria, Light, and Energy:

ATP is the molecule used by living organisms to store energy and rapidly release it.

Our cells can make ATP in three ways:[ref][ref]

1. in the cytosol, the conversion of glucose to pyruvate produces some ATP
2. in the mitochondria, pyruvate is used in the citric acid cycle (Krebs cycle) to produce a little more ATP
3. in the mitochondria, oxidative phosphorylation produces the majority of the ATP using the electron transport chain

We will focus on the electron transport chain here.

Within the inner membrane of the mitochondria, are “complexes” that transport electrons and eventually produce ATP — called the electron transport chain.

In the mitochondrial electron transport chain (pictured above) you’ll see Cyt C, which stands for cytochrome C oxidase. In complex II and complex III, you’ll find cytochrome b and cytochrome c which are pigments that can move electrons.[ref] Cytochromes are pigments that contain an iron atom and can rapidly accept or lose electrons. Chromophores are molecules that can absorb specific wavelengths of light. Thus, cytochrome c is a chromophore in the mitochondria. (Chlorophyll is a chromophore in the chloroplast of plants.)

Cytochrome c oxidase is the protein complex that contains cytochrome c. This is found in complex IV and is key to the production of energy from light. Additionally, the flavin proteins (FAD, FAHD) are an essential part of the electron transport chain. The flavin proteins are derived from riboflavin, a B vitamin. Flavins are also chromophores.[ref]

Different wavelengths, different effects:

Researchers have found that complex IV: “acts as a photo acceptor at 632.8 nm due to two heme A moieties and two copper centers.” The research shows that complex IV absorbs light at 620 – 680, and 760 – 895 nm (red and infrared). In addition, cytochrome b in complex III is activated at 980 nm (infrared). To add a little more complexity to this, light in the 400–500 nm wavelengths excites flavins, such as FAD from riboflavin.[ref]

Research shows that stimulation of cellular functions is seen at specific wavelengths: between 613 and 623 nm, between 750-772 nm, and between 812-846 nm. [ref]

Near-infrared to infrared light at 1200 nm and 1700 nm also interacts with water in the cell, exciting the water and affecting temperature-gated ion channels and lipids. [ref][ref]

OK, so we have studies showing that cytochrome c is activated at specific wavelengths of red and infrared light. What does this mean for mitochondrial energy? 

Creating energy (ATP) in the mitochondria directly from photons:

Measuring the increase in mitochondrial ATP from photons at specific wavelengths is difficult and, until recently, it hadn’t been measured directly.

Mitochondrial complexes work in concert, so a recent study looked at the output of total mitochondrial energy from different photobiomodulation wavelengths. The researchers explained that they viewed PBM “as a thermodynamic process of conversion of electromagnetic energy absorbed by mitochondria into excess of chemical energy produced by the same organelles,”.  The researchers found that 0.5W for 30 seconds or 1W for 60 seconds increased mitochondrial energy output for about 2 minutes. They used red light at 810 nm for the experiment.[ref]

The researchers stated in the study that the energy produced in the mitochondria was ‘not negligible’ meaning that it was a measurable increase in ATP. They calculated based on their experiments that the maximum energy production from light interacting with mitochondria should be 0.2%. Compare this to plants, which typically have a photosynthetic output of 0.5-1.5%, but with a theoretical maximum of 10%.[ref]

What does this mean? Well, animal cells with mitochondria aren’t as good at producing energy as plant cells with chloroplasts — which is why animals eat plants for food. But it is still pretty darn cool that researchers can show that mitochondria can produce some energy from red light.

Nitric oxide release:

Studies on photobiomodulation (PBM) also show that nitric oxide can be released from red light therapy. This may be beneficial for blood pressure and vascular health. The release of nitric oxide is thought to occur either through interaction with iron and copper in complex IV activation or through upregulation of cytochrome c oxidase.[ref]

More than just wavelength:

When looking at photobiomodulation studies, there is more to them than just the wavelength used.

Let’s look at three other variables that are involved:

1. The power or intensity of the light
2. Temperature of the cells
3. Circadian rhythm and time of day of light application

1) Power:

The power of the light also makes a difference in whether the mitochondria can use it to synthesize ATP. Power is measured in watts (W), which is equal to 1 J/second.  One Joule (J) is one kg*m^2/s^2.

A cell study showed that at lower power, the light at 980nm had an inhibitory effect on ATP synthesis. At an intermediate 0.3-0.7 W, the 908 nm light had no effect on mitochondrial energy, but at 0.8 – 1.1 W, the mitochondria produced ATP from the light due to an interaction at complex III and complex IV. Importantly, a very low power of 0.1 W induced oxidative stress along with inhibition of ATP synthesis.[ref]

In general, studies seem to show that lower power requires a longer duration to be effective, while higher power is effective at a shorter duration.[ref]

2) Temperature: 

A study investigating photobiomodulation at 810 nm and 980 nm (near-infrared) showed that the different wavelengths had different optimal doses on adipose-derived stem cells. The 980 nm light produced a cellular response (caused the stem cells to differentiate) that was dependent on the activation of calcium ion channels and temperature. A calcium channel blocker could block the effect of the 980nm light, and cold or heat could also block the effect.[ref]

I’m not sure how important temperature is for PBM, but I found it interesting that cold and heat altered the effect of 980 nm photobiomodulation. Also, calcium channel blockers are commonly prescribed as heart medications.

3) Time of day: 

An animal study showed that the most effective time for photobiomodulation to increase whole-body ATP was between 8 and 11 a.m [ref]

Other studies show that transcranial photobiomodulation applied during the day or night has different effects. When it is applied during sleep, PBM improves glymphatic clearance of waste from the brain at night.[ref]

How far does red light penetrate?

You may remember as a child holding a flashlight to your hand and seeing the light come through. While we don’t often think of light penetrating skin, it does – depending on the intensity and wavelength.

One study showed that very low-intensity 810 nm red light didn’t penetrate tissue or bone. However, high-intensity (10-15 W) light at 810 nm could penetrate up to 2 – 3 cm (an inch or more). [ref]

What about through the skull?
Normally, light enters the brain only through the eyes. However, depending on the wavelength and intensity, research shows that transcranial photobiomodulation is possible. The light can penetrate 10 to 15 mm beneath the skull and into the cerebral cortex. fMRI brain imaging can show the effects of photobiomodulation on certain tasks. This is all through the effect of activating cytochrome c oxidase and increasing hemoglobin oxygenation.[ref][ref]

There are some interesting studies on red light therapy for TBI (traumatic brain injury, concussion). These studies suggest that transcranial or intranasal photobiomodulation has a physiological effect. Animal studies show that photobiomodulation can increase BDNF levels, which helps the brain heal and make new connections.[ref]

In addition, there are studies looking at transcranial photobiomodulation to enhance learning tasks. One study found that infrared laser stimulation of the prefrontal cortex significantly improved rule-based learning, but didn’t improve information-integration learning.[ref] Another clinical trial compared infrared ( 1064 nm) for 8 minutes on the forehead to the memory improvements seen with exercise. The study included a control group (no exercise, no light) and a combined treatment group. Results showed that both light therapy and exercise improved cognitive performance, but that the combination of both light plus exercise didn’t show a greater improvement than either one alone.[ref]

A recent study looked at what happens when different wavelengths hit the brain. The study was done during awake brain surgery on a man with a brain tumor. Doctors removed the tumor from the temporal lobe. They then exposed the brain to different wavelengths of light while measuring brain waves. There were rapid, almost instantaneous changes in brain waves when different wavelengths of light were shone on the brain. The researchers theorize that this was due to the production of brain plasma — electrified fluid carrying charged ions, lighting is an example of plasma.[ref — open access study, fascinating]

Photobiomodulation studies:

Photobiomodulation (PBM) and low-level laser light therapy (LLLT) are two terms applied to using specific wavelengths of light at specific intensities for health benefits. Photobiomodulation seems to be the more current term used in research studies.

There are thousands of studies on PBM for many different conditions ranging from nerve pain to muscle recovery to mood disorders. This is just a sampling of recent clinical trials to show the range of effects of red light therapy (a.k.a. photobiomodulation, low-level laser therapy).

• Blood sugar: A 15-minute exposure to red light reduced blood glucose by 27% over two hours. From the study: “A 15 min exposure to 670 nm light reduced the degree of blood glucose elevation following glucose intake by 27.7%, integrated over 2 h after the glucose challenge. Maximum glucose spiking was reduced by 7.5%.” [ref]
• Pre-exercise PBM: A recent meta-analysis of 34 PBM trials examined the efficacy of pre-exercise PBM for injury prevention and endurance. The results showed that pre-exercise photobiomodulation therapy improved muscle endurance, muscle strength recovery, and injury prevention in physically inactive individuals and elite athletes. However, it was not statistically beneficial for people who are generally physically active and engaged in resistance training.[ref]
• Myopia (nearsightedness): Adding red-light therapy to corrective contact lenses (Ortho-K) improved vision slightly more after 1 year than just the Ortho-K lenses, which reshape the eye.[ref] Another study just using red light (three minutes, 650 nm, low level, twice daily) in children with myopia showed statistical improvement in three months. But it wasn’t a cure…[ref]
• Autism: A randomized, sham-controlled clinical trial involving thirty children with autism looked at pulses of near-infrared light to selected brain regions (transcranial photobiomodulation). The researchers used 850 nm at 40 Hz, twice a week for eight weeks. The difference between the sham group and the active group was statistically significant. The children receiving the active near-infrared light to the brain improved their Childhood Autism Rating Scale score by 7 points more than the sham group. There were also changes seen on the EEGs.[ref]
• Vulvar lichen sclerosus: In women with treatment-resistant lichen sclerosus, low-level laser therapy (808 nm, 500 mW) once or twice a week for 8 weeks improved their health-related quality of life.[ref]
• Hair regrowth: A clinical trial in men with male pattern baldness showed that red light therapy combined with finasteride or minoxidil worked better than medication alone.[ref]
• TMJ, orofacial pain: A meta-analysis of clinical trials of PBM for orofacial pain showed that the combination of PBM with physical therapy was better than physical therapy alone, especially for TMJ.[ref]
• Tooth root regeneration: Red light at 810nm, pulsed at 4.4.J for 22  seconds was applied 13 times over the course of a year. The tooth root had new regrowth with completed closure of the apex after a year.[ref]
• Gingivitis: A study showed that PBM at 880 nm on human gingival cells induced antimicrobial peptides, promoted ROS scavenging, and down-modulated proinflammatory activity.[ref]
• Ankle sprain: A meta-analysis shows that PBM “is quite effective for patients with an ankle sprain. PBMT showed high effect size with a moderate level of evidence on pain intensity.”[ref]

What are the drawbacks to photobiomodulation?

There are still many questions about the optimal wavelengths, power, and timing. The range of benefits for ATP production is narrow, and some studies suggest that ATP production is decreased and oxidative stress is slightly increased at the wrong intensity and duration[ref]

The studies also appear to be short-term, leaving the question of whether there are any long-term negative effects on PBM. (Of course, we’ve all been exposed to sunlight long-term… so it is unlikely that duration will make a big difference here in safety studies.)

What about melanin? 

Melanin is a pigment produced in specific skin cells called melanocytes and is what gives skin and hair their color. Melanin is also a light-absorbing pigment and is activated at specific wavelengths with multiple effects. This is a huge topic on its own, and I’m going to cover it in a separate article.

Genetic interactions:

A preprint study shows that photobiomodulation can improve color discrimination in people with certain colorblindness mutations. The study found that OPN1LW mutations, but not OPN1MW mutations, were helped by PBM. [ref]

Check your color blindness mutations here.

A study looking at gene expression in dental pulp stem cells shows that photobiomodulation specifically interacts with TNF and RANKL gene expression. Using a low-level laser light at 808 nm, researchers found that the light reduced TNF expression in stem cells exposed to lipopolysaccharide compared to a control group that was not exposed to PBM.[ref]

The TNF gene encodes TNF-alpha, an inflammatory cytokine. Blocking TNF-alpha reduces inflammation and promotes cell survival and health. The TNFSF11 gene encodes the RANKL protein. (Both are included in the Genotype Report section below)

Lifehacks:

The PBM studies all use narrow bands of light, usually from a low-level laser device or red/near-infrared LED lights. LEDs are commonly used in photobiomodulation because they typically have low power emission and therefore don’t irritate or burn the skin. They can be used for longer periods of time without causing cell damage. [ref]

Red heat lights, such as those used to keep baby chicks warm, produce wavelengths from about 650 nm to 2000 nm, according to Phillips bulb specifications.[ref]

What about sunlight?

The natural and obvious takeaway here is that intense sunlight, such as around noon, also penetrates the skin and tissues, and it includes the red and infrared wavelengths that activate cytochrome c oxidase. The question is one of intensity as to how far the sunlight is going to penetrate the skin.

The animal study that showed the greatest increase in ATP production with red light application from 8 to 11 a.m. makes a lot of biological sense. The research showed that there was little effect with red light on the animals in the evening and at night.[ref] This, combined with the idea that too much irradiation decreases ATP, makes sense for getting outside in the morning to soak up the sun. It also makes sense that many animals (and some humans) seek shade in the afternoon to rest.

Safety:

There aren’t many long-term studies on red light therapy, but short-term studies show no negative impacts from red or near-infrared light at the power used in PBM devices. Near-infrared light is non-ionizing electromagnetic radiation, and safety studies show that it doesn’t perturb cellular processes.[ref] In skin cells, PBM doesn’t induce changes that could cause cancer or the proliferation of cancer.[ref]

Of course, the power of the red light device is important — it must be enough to penetrate the skin, but not enough to cause damage (like a powerful laser). Staring at a GE red heat lamp (250 watts) for 5 to 10 minutes from a distance of 20 centimeters causes changes in the eyes that may promote cataracts (animal study).[ref]

Exposure to sunlight can, of course, give you a sunburn. Use your common sense here: Don’t stay in the sun after you’ve turned red, and don’t stare at bright lights.

Supplement to stack with red light therapy:

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