What is Red Light Therapy?
A general overview of Red Light Therapy concepts and research
Written for CytoLED.com by Vladimir Heiskanen
Takeaways/highlights:
● Red light therapy, or photobiomodulation, is an increasingly popular treatment based on irradiating the body with various light sources, most often LEDs and lasers.
● Red and near-infrared light produces measurable biological effects, including anti-inflammatory signaling and improved mitochondrial function.
● Over seven thousand studies on red light therapy have been published in scientific journals, also including high-impact journals such as The Lancet, Circulation, PNAS and Science Translational Medicine.
● Evidence from systematic reviews suggest that red light therapy could be useful in the treatment of various ailments including knee pain, diabetic foot ulcers, hair loss and burning mouth syndrome.
● Red light has recently become popular as a means to improve general well-being, and it can be used as an additional method along with improving nutrition, sleep and other lifestyle factors.
Introduction
Red light therapy (RLT) is a form of treatment in which body parts are locally irradiated with visible red light or invisible near-infrared light to treat various indications including pain, wounds and chronic diseases.
The treatment has been around for approximately 50 years, but it has become more popular during the 21st century. In the scientific community, red light therapy is nowadays most usually called photobiomodulation therapy (PBMT) or low-level laser (light) therapy (LLLT).
While previously the common knowledge in human biology has been that visible light can affect human bodily processes predominantly via the eyes, red light therapy is based on a large body of scientific findings demonstrating that light can have effects in the irradiated tissues via a multitude of mechanisms.
More than seven thousand research articles on red light therapy have been published. The tentative findings suggest that red light therapy could be potentially helpful for the ailments of brain, eyes, heart, lungs, joints, muscles, nerves and other body parts (1-7).
How does Red Light Therapy work?
Primary mechanisms
The basic principle in red light therapy is that irradiating a body part with red or near-infrared can induce biological mechanisms that can locally improve cell and tissue function.
There are a plenty of articles that have aimed to summarize the mechanisms of red light therapy. The most extensive review is the Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy (2016) written by Lucas de Freitas and Michael Hamblin (8).
The primary mechanism of photobiomodulation refers to the effects that occur immediately when the cell is irradiated with light. There is still uncertainty about the main primary mechanism in red light therapy. The most common theory posits that red light is absorbed by a mitochondrial structure called cytochrome c oxidase (CCO) (9). However, this theory might not explain the effects completely, since it has been reported that even cell lines that do not express cytochrome c oxidase seem to respond to red light irradiation (10).
In addition to this popular CCO theory, there are some alternative explanations to explain intracellular photobiomodulation effects. Some evidence suggests that the effect might be related to production and release of nitric oxide (NO) from CCO or photolabile molecules such as nitrosyl hemoglobin and S-nitrosothiols (11,12). Longer wavelengths of near-infrared light (eg. 980 nm) might also affect heat-gated TRP calcium ion channels within the cells (13). It has also been tentatively suggested that red light might decrease water viscosity within mitochondrial proteins, thus improving ATP production within the cells (14).
Secondary mechanisms
The secondary mechanisms are the actual changes than happen as a result of red light irradiation. It has been reported that red light therapy induces numerous measurable changes in the cellular gene expression, signalling pathways, inflammatory processes and mitochondrial function (15-17).
It has been widely acknowledged that systemic chronic inflammation and mitochondrial dysfunction are likely to be major mechanisms in a most age-related chronic diseases. During the last years, there has been an increasing number of review articles suggesting the involvement of these mechanisms in the common chronic diseases such as cancer, heart disease and diabetes.
“[R]ecent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders.” (19)
“Mitochondrial dysfunction is a key pathophysiological component of many acute and chronic diseases.” (20)
“Mitochondrial dysfunction and oxidative stress are largely involved in aging, cancer, age-related neurodegenerative and metabolic syndrome.” (21)
The red light therapy research community appears to strongly believe that effects of red light therapy could be related to healing systemic chronic inflammation and mitochondrial dysfunction. The view is largely supported by animal research findings, in which it is common to measure markers of inflammatory and mitochondrial function.
For example, the decrease of inflammatory markers is one of the most common findings in the preclinical research on red light therapy. As summarised in one of the recent review articles: “One of the most reproducible effects of [red light therapy] is an overall reduction in inflammation, which is particularly important for disorders of the joints, traumatic injuries, lung disorders, and in the brain (...) [red light therapy] can reduce inflammation in the brain, abdominal fat, wounds, lungs, spinal cord”. (17)
There is also experimental basis to support the idea of improving mitochondrial dysfunction with red light therapy. Irradiation of cell cultures or animals with red or near-infrared light appears to beneficially affect the mitochondrial function (18). For example, studies have shown increased ATP levels, increased mitochondrial membrane potential (ΔΨm), increased cytochrome oxidase expression, increased oxygen consumption and upregulation of SIRT1/PGC1α pathway (22). It has also been shown that red light can also protect cells against mitochondrial toxins such as potassium cyanide and tetrodotoxin (23). Thus it seems plausible that red light could have positive effects on cellular energy metabolism.
The History of Red Light Therapy
It is fair to say the majority of the relevant red light therapy research has been published during the past 15 years. However, we can go more than 100 years back in history to find traces of early reports of red light therapy. For example, physicians John Harvey Kellogg and Margaret Abigail Cleaves had written their books in 1904-1910 describing the treatment of chronic fatigue, baldness and diabetes using incandescent lamps. At the same time, therapeutic practices utilizing sunlight (heliotherapy) were also relatively popular.
The history of modern red light therapy research goes back into late 1960s, when a Hungarian researcher Endre Mester showed that red laser light may increase hair growth in mice, and later published many reports of also treating human ulcers successfully (24). After Mester’s initial reports, it took several years until researchers in other countries such as USSR, Germany, USA, Italy, Japan and Israel started also reporting beneficial effects from laser light (25-30).
While the rate of publication was relatively slow up until the 90s, the pace has been steadily increasing. In the year 2000, the total number of red light therapy articles in scientific journals was approximately 500. Now in the year 2021, we have already exceeded the total number of 7,000 articles.
We can also see that by now, red light therapy research has spread to approximately 70 different countries around the world. The most important countries to publish red light therapy research have been Brazil and the USA.
1000+
Brazil
400+
United States (in 33 different States)
100+
China, Iran, Israel, Italy, Japan, Korea, Russia, Turkey
50-99
Australia, Canada, Germany, India, Spain, Taiwan, UK
10-49
Argentina, Austria, Belgium, Czech Republic, Denmark, Egypt, France, Greece, Hungary, Netherlands, New Zealand, Norway, Poland, Romania, Saudi Arabia, Serbia, Slovakia, South Africa, Sweden, Switzerland
<10
Bosnia-Herzegovina, Bulgaria, Chile, Colombia, Costa Rica, Croatia, Cuba, Cyprus, Finland, Indonesia, Iraq, Ireland, Jordan, Kazahkstan, Kuwait, Macedonia, Malaysia, Mexico, Monaco, Nepal, Pakistan, Portugal, Puerto Rico, Qatar, Singapore, Slovenia, Sudan, Syria, Thailand, Ukraine, United Arab Emirates, Venezuela, Yemen, Yugoslavia
In tandem with increased scientific publication rates, many books on red light therapy are also being written nowadays both for academic and non-academic audiences.
Red light therapy books for academics
Red light therapy books for laypeople
During the past few years, red light therapy has been also covered in various magazines. The news features in science-oriented magazines have usually focused on the promise of treating specific diseases with light, while the everyday magazines usually focus on supporting skin health or general well-being.
Red Light Therapy Research Overview
General Overview
The available red light therapy research can be readily accessed via scientific databases such as PubMed.gov or the PBM Database Project spreadsheet.
To this date, approximately 5,000 research articles related to red light therapy have been published. The box below shortly summarizes the study types that are included in this number.
Animal Research
In medical research, the evaluated treatments are usually tested in laboratory animals before proceeding to clinical studies with humans. The most common laboratory research animals are rats, mice and rabbits.
Red light therapy has been evaluated for approximately 140 different ailments in animals. For most of those ailments, the study results have been relatively positive.
However, it should be acknowledged that the findings of animal studies do not always translate to benefit in humans. It has been reported that less than 8% of cancer treatments successful in animals pass the phase I trials in humans (31).
Human Research
Red light therapy has been also tested in a range of human studies. The effects on more than 120 different ailments have been evaluated so far. There has been variability between the study results, some showing benefits (eg. knee osteoarthritis) and some showing no effect (eg. pain after wisdom tooth extraction) (4,32).
Note: Asterisks (*) denote the indications that have not been evaluated in randomized controlled trials (RCT)
The effect of red light therapy on some of these ailments has been tested in multiple human studies. In research literature, systematic reviews compile and describe findings from multiple studies examining the same study question that is usually “does a treatment A have an effect on a disease B”.
Numerous systematic reviews have been published on red light therapy, a major portion of them suggesting positive treatment outcomes. In some of those, the included studies have recruited more than a thousand patients in total.
Burning mouth syndrome
Zhang 2020
12 (574)
+ PBM decreased pain and improved quality of life
Delayed-onset muscle soreness (DOMS)
Nampo 2016
15 (317)
- PBM did not significantly improve delayed-onset muscle soreness
Diabetic foot ulcer
Dos Santos 2020
13 (361)
+ PBM decreased the ulcer size
Exercise performance
Leal-Junior 2015
13 (134+)
+ PBM improved performance and recovery from exercise
Hair loss
Gupta 2019
15 (895)
+ PBM increased hair count (in men and women)
Knee osteoarthritis
Stausholm 2019
22 (1063)
+ PBM decreased pain after the treatment and in the 2-12 week follow-up
Low back pain
Tomazoni 2020
14 (1045)
- PBM did not alleviate pain or disability compared to sham
Lymphedema
Chen 2019
9 (316)
- PBM did not affect arm circumference, grip strength or pain
Neck pain
SBU 2014
18 (1007)
+ PBM alleviated pain immediately after the treatment and during the follow-up
Oral mucositis
Peng 2020
30 (1168)
+ PBM decreased the risk of severe oral mucositis
Periodontitis
Ren 2017
7 (180)
+/- PBM decreased periodontal probing depth only in the short-term
Plantar fascitis
Dos Santos 2019
4 (223)
+ PBM decreased pain and improved the Foot Function Index
Shoulder pain
Awotidebe 2019
11 (585)
+/- PBM decreased overall pain but did not improve shoulder function or range of motions
Temporomandibular disorders (TMD)
Xu 2018
17 (643)
+ PBM alleviated pain and improved functional outcomes of temporomandibular joint function
Tennis elbow
Bjordal 2008
13 (730)
+ PBM alleviated pain in tennis elbow
Wisdom tooth extraction (lower jaw)
Domah 2020
17 (1064)
+/- PBM reduced edema but not pain or trismus
From lasers to LEDs and sunlight
One of the most important events in the history of red light therapy has been the introduction of light-emitting diodes (LEDs).
Before the year 2000, researchers had conducted their red light therapy research mainly with lasers as their light sources, and some researchers even claimed that ordinary sources of red light might not have similar effects as lasers (33).
However, US physician Harry Whelan and his group from Wisconsin published multiple reports in the early 2000s claiming improved wound healing and other benefits from LEDs (34). Since then, a large body of evidence has been published confirming that LEDs are as suitable as lasers for red light therapy, and hundreds of reports utilizing LEDs have been already published in scientific journals (35).
It is nowadays considered likely that any light source that emits red and near-infrared light may have red light therapy-like effects. Beneficial effects have been reported even with incandescent lamps, heat lamps and halogen lamps (36-38).
Sunlight may also have health-improving effects due to the fact that a major portion of sunlight’s spectrum actually consists of red and near-infrared light. Sunlight exposure has been associated with decreased mortality and other health benefits, but it is not yet clear whether these associations are truly causal or confounded by other relevant factors (39,40).
Pursuing Systemic Health Effects
Recently there have been reports and scientific reviews suggesting that application of red light to one body part might also have favorable effects on other body parts. For example, irradiating the bodies of mice appears to protect their brain from a neurotoxin (MPTP), and irradiating tibia and iliac bones of pigs appears to protect their hearts from a myocardial infarct.
These are called “remote”, “abscocal” or “systemic” effects of red light therapy and have been reviewed in the scientific literature. The majority of these findings have been reported in animal studies (41-43).
There is some preliminary evidence that red light therapy may have positive effects on metabolic health. Pilot trials in humans have shown that exercise-related metabolic benefits such as fat loss, muscle mass maintenance and insulin sensitivity might be greater in the subjects receiving red light therapy. Results from animal studies also suggest that red light therapy may improve diet-related insulin resistance, fatty liver and adipose tissue inflammation in mice (44-47).
The idea that red light may be beneficial for metabolic health has presumably contributed to the current popularity of whole-body red light therapy with large LED panels. Despite the fact that majority of red light therapy research to this date has been conducted with small devices, it is likely more and more research into large panels will come in the next years.
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