Friday, May 26, 2017

The Therapeutic Effects of Red and Near-Infrared Light (2017)

1. Introduction

I have previously written about the vast research showing that irradiation by red light or near-infrared appears to have health benefits. Thousands of research articles showing these benefits have been published.

In the scientific literature, this treatment with red light or near-infrared is called either photobiomodulation (PBM) or low-level laser (light) therapy (LLLT). I will be using the term photobiomodulation.

In photobiomodulation, the affected tissue is irradiated by light, usually from a laser or LED source. This irradiation appears to improve the function of the malfunctioning tissue.







2. Mechanisms of photobiomodulation

Most wavelengths of light (ultraviolet, blue, green, infrared) do not penetrate the skin at all. Instead, they are absorbed in the outer layers of skin.

On the other hand, red light and near-infrared belong to the so-called optical window. These wavelengths are able to significantly penetrate through the skin:

The mobile phone flashlight emits blue, green and red light.
Only the red light penetrates through the finger.

Red light and near-infrared are able to induce significant physiological changes inside the tissue. According to modern knowledge, the red light inside the cells activates the mitochondrial enzyme cytochrome c oxidase, improving the mitochondrial respiration and oxygen consumption (de Freitas&Hamblin 2016, Wang et al. 2017).

This shift in cellular metabolism leads to other changes in cell function, eg. gene expression and growth factor production (Prindeze et al. 2012).



In the scientific literature, there are numerous examples of the significant cellular effects of red light and near-infrared. Some of these discoveries were briefly presented in this dissertation from the University of Gothenburg.



Red light has been repeatedly shown to have positive effects on the markers of energy metabolism and inflammation in animal studies. The following table shows some of these results:

Photobiomodulation results (animal studies)
Indication
Animal
Findings
Mouse
↑ATP, ↑cytochrome oxidase expression
Rat
↑IFN-γ, ↓IgE, ↓IL-4, ↓Th1/Th2 ratio
Rat
↑ATP, ↑mitochondrial membrane potential, ↑cytochrome oxidase, ↑memory function, ↓reactive gliosis, ↓inflammation, ↓tau hyperphosphorylation
Rat
↑ATP, ↑cytochrome oxidase, ↑G6PD, ↑NADPH, ↑pAMPKα, ↓NADP, ↓LDH
Mouse
↑ATP, ↑exercise performance, ↑cytochrome oxidase
Rat
↓TNF-α, ↓IL-1β, ↓macrophage and CD8 lymphocyte infiltration
Fruit fly
↑ATP, ↑lifespan, ↑mobility, ↓complement C3
Rat
↓AST, ↓ALT, ↓LDH, ↓cirrhotic areas, ↓collagen deposition
Mouse
↑IL-10, ↑IL-4, ↓TNF-α, ↓IFN-γ, ↓disease symptoms
Rat
↓CK, ↓O2, ↓SOD, ↓TBARS
Dog, rat
↑ATP, ↓mortality, ↓infarct size, ↓troponin T
Rat
↓IL-1β, ↓CX3CL1, ↓dorsal gliosis, ↓hyperalgesia
Rat
↓TNF-α, ↓IL-1β, ↓IL-6, ↓neutrophils, ↓macrophages
Rat
↑bone formation, ↑granulation tissue, ↑collagen fibers
Rabbit
↑lumen area, ↓myointimal hyperplasia, ↓intima:media ratio
Rat
↓TNF-α, ↓IL-1β, ↓hyperalgesia
Mouse
ATP, ↓ROS, ↓injured area


Since the disturbances of energy metabolism have been associated to all kinds of chronic diseases, the suggested disease-relieving mechanism of red light by improving mitochondrial function is very plausible.

Photobiomodulation requires red or near-infrared light. While there is a plenty of talk about the beneficial effects of far-infrared radiation, it probably doesn’t have the same mechanisms and benefits as photobiomodulation. (The majority of infrared saunas don’t emit any near-infrared, though some companies have started selling saunas with near-infrared-emitting heat lamps.)






3. Human research on photobiomodulation

In humans, photobiomodulation has been studied for a few dozen different ailments. The list below shows some of these possible indications. New clinical trials are also constantly in progress.


Photobiomodulation studies (humans)
Erythema (UV-induced)



Regarding some of these indications, systematic reviews have also been published. The table below presents some of those, featuring over 6500 patients from over 140 randomized and controlled trials (RCTs).

Photobiomodulation: systematic reviews
Indication
Author
Review
Year
N
n
Quality
Results
Ren
M
2017
7
180
C
➕/➖ Photobiomodulation decreased pocket depth only in short term (1-2 months).
Tchanque...
S
2016
4
131
C
➕ Photobiomodulation hastened the healing of foot ulcers.
Zarei
S
2016
5
394
B / C
➕ Photobiomodulation was beneficial for androgenetic alopecia in men and women.
Ribeiro
S
2016
11
555
C
➕ Photobiomodulation decreased pain.
Delayed-onset muscle soreness
(DOMS)
Nampo
M
2016
15
317
C
➖ Photobiomodulation wasn’t associated with significant benefits. The meta-analysis was critisized for it’s methodological shortcomings, which might partially explain the negative result (Baroni&Leal-Junior 2016).
Huang
M
2015
7   
211
B / C
➕/➖Photobiomodulation decreased pain, but didn’t improve function.
Chen
M
2015
14
454
C
➕/➖ Photobiomodulation didn’t decrease pain, but brought functional improvements.
Leal-Junior
M
2015
13
134+
C
➕ Photobiomodulation improved exercise performance and postexercise recovery.
Huang
M
2015
9
518
B
➖ Photobiomodulation didn’t ameliorate pain. However, another research group re-analyzed the same material, and got a positive result (Stausholm et al. 2016).
Orthodontic tooth movement
Ge
M
2015
9
211
C
➕ Photobiomodulation increased orthodontic tooth movement.
Smoot
M
2015
7
262
C
➕ Photobiomodulation decreased pain and upper limb volume.
SBU
S
2014
18
1007
C
➕ Photobiomodulation decreased pain after the intervention and in the follow-up.
Oberoi
M
2014
18
1144
B
➕ Photobiomodulation decreased pain and the risk of severe mucositis.
Borsa
S
2013
10
147
B
➕ Photobiomodulation improved exercise performance and postexercise recovery.
Gross
M
2013
2
109
C
➕ Photobiomodulation improved the markers (pain/disability/QoL/GPE).
Brignard...
S
2012
9
599
C
➖ Photobiomodulation didn’t decrease pain of edema significantly.
Tumilty
M
2010
25
963
B
➕/➖  Photobiomodulation was effective in 12 studies, and ineffective in 13 studies. The conflicting results might be related to treatment parameters.
Chow
M
2009
16
820
B
➕ Photobiomodulation decreased pain acutely and in the long-term.
Bjordal
M
2008
13
730
B / C
➕ Photobiomodulation decreased pain.
Bjordal
S
2006
9
609
B / C
➕ Photobiomodulation decreased pain.
Chow
S
2005
5
273
C
➕ Photobiomodulation decreased pain.
Bjordal
S
2003
11
565
C
➕ Photobiomodulation decreased pain.
M = meta-analysis; S = systematic review; N = amount of controlled studies; n = amount of subjects


The table includes my estimation of the quality of the evidence. B stands for “moderate evidence” and C for “weak evidence”. My estimates are not based on as strict criteria as GRADE scoring used by Cochrane Library.

It can be seen that many of these systematic reviews were published between 2014 and 2016. Photobiomodulation research is currently accumulating with a very fast pace, approximately 400 research articles per year. There will probably be dozens of new systematic reviews before the year 2020.

My overall conclusion of these systematic reviews is that photobiomodulation appears to be beneficial for a large variety of different indications. The evidence is mainly of moderate/weak quality, which implicates a need for additional randomized trials of high methodological quality.








4. Animal research on photobiomodulation

Photobiomodulation has not been studied solely in humans. If you look at the literature, you can find studies conducted also in rats, mice, rabbits, dogs, pigs, minipigs, monkeys, sheep, horses, bovines, cats, sand rats, gerbils, guinea pigs, frogs, bumblebees, fruit flies, sea urchin larvae, snails, roundworms, earthworms and flat worms.

In animal studies, photobiomodulation has been studied with good results for nearly a hundred different indications. Impressive results have been reported for autoimmune diseases, brain diseases, osteoporosis, joint inflammation and dozens of other diseases:


Photobiomodulation indications (animal studies)


As the list shows, there is a vast literature on photobiomodulation. The total amount of these animal studies indexed in PubMed is more than 700.




5. The comprehensive research database

In order to learn as much as possible about red light and near-infrared, I spent a couple of months compiling photobiomodulation research into a spreadsheet. My spreadsheet includes currently more than 2250 scientific articles on the subject:











6. Photobiomodulation research examples: Eyes

6.1. Human studies

In 2008, two German physicians published a retrospective report of 203 patients with the age-related macular degeneration. According to the paper, treatment with near-infrared light (780 nm) improved visual acuity in 95 percent of the patients, and the treatment was also associated with reduced edema, bleeding, metamorphopsia, scotopia and dyschromatopsia.

The beneficial results lasted for 3-36 months after the treatment. The report was generally very promising. However, these kinds of retrospective reports are considered to have a high risk of bias, and should be confirmed by high-quality controlled studies (Ivandic&Ivandic 2008).

In 2016, Canadian researchers published very similar results from an observational study, where they used mainly a red LED light (660 nm). The therapy was associated with improved visual acuity and contrast sensitivty, and reduced drusen (Merry et al. 2016). This research group is currently working on a randomized trial (LIGHTSITE1) in order to repeat these findings with a proper methodology.


6.2. Animal studies


Research groups from a wide range of countries (UK, Australia, Spain, Iran, Italy, India, USA) have studied the effects of photobiomodulation on retinal diseases.

According to the study results, red light appears protective against various sources of retinal degeneration, eg. age-related macular degeneration, diabetic retinopathy, light-induced retinal damage, oxygen-induced retinopathy and methanol toxicity (Eells et al. 2016, Geneva 2016).

Photobiomodulation: effects on eyes
Reference
Country
Animal
Model
💡
λ (nm)
Results
Iran
Rat
Methanol toxicity (retinal injury)
LED
670
↓RGC death, ↓injury of visual cortex
Canada
Human
Age-related macular degeneration
LED
670
↑visual acuity, ↑contrast sensitivity, ↓drusen
UK
Rat
Age-related macular degeneration
LED
670
↑oxidation of cytochrome oxidase
Iran
Rabbit
Corneal alkali burn
Laser
810
↓injury area, ↓inflammation
Australia
Rat
Light-induced retinal damage
LED
670
↓photoreceptor cell death, ↑ONL thickness
Spain
Rat
Retinal ischemia
LED
630
↓RGC death, ↓GFAP
USA (OH)
Mouse
Diabetic retinopathy
LED
670
↓retinal O2, ↓leukostasis, ↓ICAM-1 expression,
↓iNOS expression, ↓Ca2+ channel dysfunction
UK
Mouse
Age-related macular degen. CFH(-/-)
LED
670
↑ATP
UK
Mouse
Age-related macular degeneration
LED
670
↑ATP, ↑cytochrome oxidase expression
Australia
Rat
Light-induced retinal damage
LED
670
↓photoreceptor cell death, ↓8OHDG
Italy
Rat
Light-induced retinal damage
LED
670
↑b-wave amplitude, ↓photoreceptor cell death, ↓GFAP
India
Rat
Light-induced retinal damage
LED
670
↑ONL cells, ↑ONL thickness
Italy
Rat
Light-induced retinal damage
LED
670
↓photoreceptor cell death, ↓GFAP
USA (OH)
Rat
Diabetic retinopathy
LED
670
↓RGC death, ↓retinal O2, ↓leukostasis, ↓ICAM-1 expression
Australia
M&R
Oxygen-induced retinopathy
LED
670
↓photoreceptor cell death, ↓retinal neovascularisation
UK
Mouse
Age-related macular degen. CFH(-/-)
LED
670
↓TNF-α expression, ↓TLR2/4 expression, ↓macrophage activation, ↓MIF and calcitonin expression
UK
Mouse
Age-related macular degeneration
LED
670
↑mitochondrial membrane potential, ↓TNF-α, ↓C3d, ↓macrophages
UK
Mouse
Age-related macular degen. CFH(-/-)
LED
670
↑cytochrome oxidase, ↓C3, ↓GFAP,
Australia
Mouse
Oxygen-induced retinopathy
LED
670
↓oxidative stress, ↓C3
Australia
Rat
Light-induced retinal damage
LED
670
↓C1s, ↓C2, ↓C3, ↓C4b, ↓C3aR1, ↓C5r1
Australia
Rat
Light-induced retinal damage
LED
670
↓photoreceptor cell death,↓LIF-, Edn2 and TNF-α gene expression, ↓Müller cell proliferation, etc.
Australia
Rat
Light-induced retinal damage
LED
670
↑b-wave amplitude, ↓photoreceptor cell death
Australia
Rat
Light-induced retinal damage
LED
670
↑a-wave amplitude, ↑b-wave amplitude, ↓photoreceptor cell death, ↓macrophages, ↓microglial activation
China
Rat
Light-induced retinal damage
LED
670
↑b-wave amplitude, ↓ONL damage
Australia
Rat
Light-induced retinal damage
LED
670
↓expression of genes/ncRNA related to light-induced retinal damage
USA (TX)
Rat
Mitochondrial optic neuropathy
LED
633
↑retinal structure, ↑cytochrome oxidase expression
USA (WI)
Rat
Methanol toxicity (retinal injury)
LED
670
↑rod and cone function (ERG amplitude), ↓retinal histopathology








7. Photobiomodulation research examples: Bone

7.1. Human studies

In a randomized trial of 50 patients with hand/wrist fractures, photobiomodulation with near-infrared laser (830 nm) reduced the pain and greatly improved functional parameters compared to the placebo group. Each subject had ten treatment sessions, each of which lasted 10 minutes per each fractured site (Chang et al. 2014).



7.2. Animal studies

Nearly one hundred scientific articles reporting the effects of photobiomodulation on bone repair have been published. The results have been mostly positive, and numerous research groups have reported similar changes, e.g. improved bone formation (Pinheiro et al. 2015).


Photobiomodulation effects on bone tissue (animal studies)
Reference
Country
Animal
Indication/model
💡
λ (nm)
Results
Brazil
Rat
Osteoporosis (ovx)
Laser
780
↑trabecular bone formation, ↑collagen fiber area
Turkey
Rat
Midpalatal suture expansion
Laser
820
↑bone formation
Brazil
Rat
Bone defect
Laser
670
↑bone stiffness, ↑serum ALP
Turkey
Rat
Suture expansion
LED
618
↑bone formation, ↑osteoblasts, ↑osteoclasts
Egypt
Rat
Gamma radiation of mandible
Laser
904
↑trabecular area
Japan
Rat
Orthodontic mini-implant (tibia)
Laser
830
↑bone formation, ↑BMP-2 expression
Brazil
Rat
Osteoporosis (ovx)
Laser
830
↑bone and collagen formation, ↔biomechanical properties
Brazil
Rat
Osteoporosis (ovx)
Laser
904
↑bone formation
Brazil
Rabbit
Orthodontic implant (tibia)
Laser
830
↑bone formation (CHA concentration)
Israel
Rat
Mandibular trauma
Laser
633
↑bone mineralization
Israel
Rat
Tibial injury
Laser
333
↑bone formation, ↑ALP activity





8. Photobiomodulation research examples: Hypothyroidism

In a Brazilian randomized trial with 43 hypothyroid patients, ten sessions of photobiomodulation with a near-infrared laser (830 nm) resulted in a decreased levothyroxine requirement in the patients at the 9-month follow up.

Remarkably, forty-eight percent of the patients were able to keep their thyroid hormone levels within the reference ranges completely without a medication (Höfling et al. 2013, Höfling et al. 2010).


Similar positive results have also been reported in several Russian and Ukrainian studies that I’ve covered in another blog article.




9. Photobiomodulation research examples: Parkinson’s disease

In 2008, researchers from Wisconsin found that photobiomodulation was beneficial for an in vitro model of Parkinson’s disease (Liang et al. 2008). After that, researchers from Australia, France and Switzerland have published a large amount of research showing that photobiomodulation protects the brain and reduces the motor symptoms in various animal models of Parkinson’s disease, including MPTP- or 6OHDA-injected and α-synuclein overexpressing animals (Johnstone et al. 2016).

In 2016, a paper titled Near-infrared light is neuroprotective in a monkey model of Parkinson disease was published in the high-impact journal Annals of Neurology. In this study, red light was administered into MPTP-poisoned macaque monkey brain via an optical fiber. This treatment reversed most of the clinical symptoms in the majority of the monkeys (Darlot et al. 2016).

Most of the studies have used red light (670 nm), but in some of the papers, near-infrared (810 nm) has also been used. Usually the light has been administered transcranially or straight to the head via an optic fiber, but in one study, body irradiation also had remote neuroprotective effects on the brain, suggesting that photobiomodulation might have systemic effects (Johnstone et al. 2014, Kim et al. 2017).

(Johnstone et al. 2016)




10. Photobiomodulation research examples: Heart and circulation

Research groups from Israel, USA, China and Brazil have investigated the effects of photobiomodulation on the recovery from myocardial infarct. Data from numerous trials conducted in mice, rats, dogs and pigs indicate that illuminating the heart with red light after an infarct could significantly decrease the injured area and therefore improve the heart function (Carlos et al. 2016, Blatt et al. 2016).



As an example, in this experimental study with dogs, photobiomodulation with near-infrared light appeared to decrease the injured area by approximately 50%. The treatment also reduced mortality in the dogs (Oron et al. 2001):


Brazilian researchers have also noted that photobiomodulation could alleviate pain, bleeding and other complications related to sternotomy (Fernandes et al. 2016, Lima et al. 2016a, Lima et al. 2016b, de Oliveira et al. 2014).

In the end of 1990s, researchers from the USA studied the effects of red light on restenosis and neointimal hyperplasia after balloon angioplasty in rabbits. The highly promising results were published in high-impact journals JACC and Circulation. Some additional studies have also been conducted in pigs and humans (Kipshidze et al. 1998, Kipshidze et al. 2001, Derkacz et al. 2010, De Scheerder et al. 1998, De Scheerder 2000, De Scheerder 2001a, De Scheerder et al. 2001b).

In 2012, a group of Austrian researchers discovered that red light induces the vasodilation of coronary arteries. The researchers concluded: “As LED sources are of small size, simple, and inexpensive build-up, they may be used during routine coronary artery bypass surgery to ease suturing of anastomosis by target vessel vasodilation” (Plass et al. 2012)

Korean researchers have also shown that illuminating rabbits with polarized light from a regular tungsten lamp could protect the animals from experimental atherosclerosis (Park et al. 2012).






11. Photobiomodulation research examples: Other indications

Alzheimer’s disease:

Exercise performance:

Hearing loss:

Oral mucositis:


Thrombocytopenia:

  • Quite recently a research group from Harvard Medical School published two papers, in which they demonstrated that photobiomodulation with visible red light can protect mice from multiple different models of this dangerous bleeding disorder. The first article was published in the high-impact journal Science Translational Medicine (Zhang et al. 2016, Yang et al. 2016).

Wound healing:




12. Photobiomodulation treatment 101

12.1. Introduction

In photobiomodulation, the body is locally irradiated by visible red light or invisible near-infrared.

It might look like this, though the beam size (1mm2 - 32cm2) and other parameters
(wavelength, intensity, energy, number of sessions) vary a lot.
(Image source: SpinalStenosis)

The light is usually produced by a laser or LED device. Unlike common lamp light, in photobiomodulation light is monochromatic, consisting of one wavelength. Some of the most common wavelengths are presented below.

Common wavelengths in photobiomodulation
Visible red
630, 633, 655, 660, 670 nm
Near-infrared (NIR)
780, 808, 810, 830, 850, 890, 904, 940, 1064, 1072 nm


Usually a wavelength ranging from 600 to 1100 nanometers is used. Within this range, some wavelengths have a stronger cellular effect than others, and some wavelengths (eg. 730 nm) might be utterly ineffective. These differences appear to be explained by absorption spectra of cytochrome c oxidase (Karu 2010, Wong-Riley et al. 2005, Gupta et al. 2014, Wu et al. 2012).

There is also some evidence suggesting that longer wavelengths (eg. 980 or 10600 nm) might have an unique mechanism of action that isn't based on absorption by cytochrome c oxidase. Some hypotheses have been published, describing intracellular water as the primary photoacceptor mediating the photomodulatory effects observed with longer wavelengths (Wang et al. 2017, Hamblin 2017).

Near-infrared penetrates the tissue better than red light, so it’s more commonly used for treating body parts that are under the skin (brain, glands, joints, muscles). Visible red light is more commonly used in the treatment of wounds or skin diseases.



12.2. Treatment parameters

The following table provides the basic information about the most relevant treatment parameters (Hadis et al. 2016, Jenkins&Carroll 2011).


Photobiomodulation parameters
Parameter
Alternative terms
Symbol
Unit
Usual range
Wavelength
-
λ
nm
630 - 1072 nm
Power (output)
Radiant flux
Φ
mW
50 - 1000 mW
Irradiance
Intensity, power density
E
W/cm2, mW/cm2
3 mW/cm2 - 70 W/cm2
Radiant energy
Energy, dose
Q
J
0.1 - 3000 J
Radiant exposure
Energy density, fluence, dose
H
J/cm2
1 - 400 J/cm2
Beam area
Spot size
A
cm2, mm2
1 mm2 - 32cm2

Here are some examples from various human trials. It can be noted that there are huge differences between the experiments (note: the energy density isn't reported - I will add it later).


Photobiomodulation parameters: examples
Indication
Wavelength
Power
Spot size
Energy
Irradiance
Treatment duration
Sessions
690 nm
80 mW
1 cm2
48 J
80 mW/cm2
10 minutes
10 sessions in 14d
670 nm
40 mW
0.79 cm2
1.6 J
51 mW/cm2
40 seconds
1 session
830 nm
50 mW
0.28 mm2
40 J
17 680 mW/cm2
13,3 minutes
10 sessions in 8wk
850 nm
100 mW
0.79 mm2
48 J
13 000 mW/cm2
8 minutes
8 sessions in 4wk
830 nm
800 mW
25 cm2
1250 J
32 mW/cm2    
32 minutes
12 sessions in  6wk
780 nm
7.5 mW
0.071 cm2
0.3 J
106 mW/cm2
40 seconds
4 sessions in 2wk



12.3. Dose response

The therapeutic window of photobiomodulation is somewhat narrow and looks like this:


Underdosing has been suggested to explain many of the negative results in clinical photobiomodulation trials (Tunér&Hode 1998). The ineffectiveness of overdosing has also been demonstrated, especially in dozens of experimental studies (Huang et al. 2011). Thus, biphasic dose-response appears to be a very significant issue in photobiomodulation. 

Low-to-moderate doses of light are often described as stimulating and high doses as inhibitory, because some markers that can be increased by low doses of light, have been shown to decrease with excessive light doses.

The exact mechanism of biphasic dose-response is not known, but it might be related to excessive formation of reactive oxygen species (ROS): “The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo” (Huang et al. 2011)

In some reviews articles, photobiomodulation is said to have a hormesis-like effect: “The hormetic response of both LLLT and MB consists of an increase in the effect at a low dose, followed by a decrease in the same effect with an intermediate dose, until the effect is equal to a control-type effect. With doses increasing beyond the hormetic zone, the effect decreases even further, until it is below the control effect.” (Rojas&Gonzalez-Lima 2013)




12.4. Treatment devices

In the past, the photobiomodulation light sources were mostly laser-based, expensive and only available to clinicians. Nowadays, the situation has improved and many companies are selling much cheaper LED devices directly to patients.

In the table below, I list some of the photobiomodulation devices that I’m aware of.

Photobiomodulation devices (for consumers)
Device
💡
λ
nm
Φ
mW
E
mW/cm2
A
cm2
Comments
Price
B-Cure
Laser
808

67.5
15
4.5
+ Decent parameters
+ Device is small and battery-powered
~$700
LightWorks LW2
LED
660
850
718
455
25
16
29
+ Decent parameters
+ Large spot size
± Device emits both red light and NIR simultaneously
~$400
Handy Cure
LED
635
875
905
60-90
15-23
4
+ Decent parameters
+ Device is small and battery-powered
± Device emits both red light and NIR simultaneously
~$400

LED
830
?
200 (10cm)
20 (70cm)
?
+ Decent parameters
~$400
LED
670
?
200 (0cm)
20 (60cm)
?
+ Decent parameters
~$90
LED
850
?
200 (0cm)
10 (6cm)
?
+ Cheap and small (see my YouTube video)
- Very small spot size
~$20
Halogen lamps
-
Broad
spectrum
?
?
?
+ Halogen and incandescent lamps emit red light and NIR, so they could theoretically be suitable for photobiomodulation
- Broad spectrum light hasn’t been studied significantly. Research has been done with monochromatic light (eg. 670 or 830 nanometers).
- It might be very difficult to find the right dose
$5
Sunlight
-
Broad
spectrum
?
?
?
+ In some studies, sunlight has been associated with better health outcomes, which could be related to the red light/NIR exposure.
-  Broad spectrum light hasn’t been studied significantly. Research has been done with monochromatic light (eg. 670 or 830 nanometers).
Free


There are some arguments about the efficacy of laser vs. LED lights in photobiomodulation. In the past, photobiomodulation was called low-level laser therapy (LLLT) and basically all of the research was conducted with low-level lasers.

Nowadays there is an overwhelming evidence showing that photobiomodulation doesn’t require coherent light and light-emitting diodes (LEDs) are suitable for photobiomodulation, though laser light might have a better penetration depth into the tissue, because it produces so-called laser speckles.

“Most of the early work in this field was carried out with various kinds of lasers, and it was thought that laser light had some special characteristics not possessed by light from other light sources such as sunlight, fluorescent or incandescent lamps and now LEDs. However all the studies that have been done comparing lasers to equivalent light sources with similar wavelength and power density of their emission, have found essentially no difference between them.” (Hamblin 2017)

Since the light intensity decreases when the device is used from longer distance, it might sometimes be useful to have a measurement device to examine the light intensity from various distances. I’m using Tenmars TM-206 device, which costed approximately $50 in eBay.


Tenmars TM-206




12.5. Sunlight

“Wherever primitive races abandon nakedness for clothing, at once the tendency to disease, mortality, and degeneracy notably increases, though it must be remembered that the use of clothing is commonly accompanied by the introduction of other bad habits.” - Havelock Ellis (1909)

In many epidemiological studies, sunlight exposure and low latitude have been correlated with improved health, eg. decreased mortality, lower cholesterol levels and lower cancer incidence. The effects of sunlight have usually been attributed to increased synthesis of Vitamin D, but since sunlight also contains high amounts of red and near-infrared light, the beneficial effects could also be due to photobiomodulation (Lindqvist et al. 2014, Lindqvist et al. 2010, Grant&Mohr 2009, Grimes et al. 1996, Wong 2008).

In a way, photobiomodulation could possibly be described as a way to substitute for the lack of daylight. If modern humans would start spending their days mostly in outdoors without shirts, our direct exposure to light would probably increase up to 100,000-fold and would be comparable to the doses used in photobiomodulation therapies.

Light intensity in different contexts
Place or context
Irradiance (mW/cm2)
Bedroom
0.01
Sunlight
5 - 20
Photobiomodulation
20 - 5000



12.6. Incandescent/halogen/heat lamps

In the beginning of 20th century, some physicians used incandescent lamps in the treatment of various ailments such as diabetes, obesity, chronic fatigue, insomnia, baldness and cachexia (Kellogg 1910, Cleaves 1904). Since incandescent lamps produce large amounts of red and near-infrared light, spectrum being comparable to sunlight, it is likely that their possible beneficial effects could be due to photobiomodulation.

However, since the amount of therapeutic wavelengths is difficult to measure with broad-spectrum lamps, it might be very difficult to find the optimal dosage. Therefore, I would not recommend incandescent, halogen or heat lamps for photobiomodulation purposes until there will be more scientific research about their usage.

Margaret Cleaves' 1904 book Light energy, its physics, physiological action
and therapeutic applications
 has some interesting chapters about

incandescent lamp therapy.







13. Photobiomodulation science: 7 facts

Fact 1: The amount of photobiomodulation research has been growing exponentially. At the moment, approximately 400 new scientific articles are being published annually.



Fact 2: Photobiomodulation has dozens of different names. In the past, there was no consensus of the name of this treatment, so many different ones were used:

660nm LED light source
Laser light irradiation
Low-level light
Photobioactivation
670nm light
Laser phototherapy
Low-level light therapy
Photobiomodulation
λ780 nm laser light
Laser therapy
Low-power laser therapy
Photobiostimulation (PBM therapy)
830nm laser
Laser treatment
Low-power laser irradiation (LPLI)
Photo-enhancement
810-nm diode laser
LED-based red light photo-stimulation
Low-power laser stimulation
Photoradiation
CLASS IV laser therapy
LED-light
Low-power laser treatment
Photostimulation
Cold laser
LED phototherapy
Low power red laser light (LPRLL)
Physiotherapy laser
Far-red light
Light-emitting diode irradiation
Low-level phototherapy
Singlet oxygen energy (SOE light)
Far red/near infrared light
Light-Emitting Diode Phototherapy
Low reactive-level laser therapy
Short pulsed nonablative infrared laser irradiation
Helium-neon laser
Low dose laser irradiation
MID-laser therapy
Soft laser
He-Ne laser
Low-energy Helium-Neon laser irradiation
Monochromatic phototherapy
Therapeutic photobiomodulation
High fluence low-power laser irradiation
Low-energy laser irradiation
Nanoparticle-emitted light
Transcranial infrared laser therapy
Intravascular red laser therapy
Low energy light irradiation
Narrow-band light
Transcranial Laser Stimulation
Intravascular Low-Power Laser Illumination
Low-intensity laser irradiation (LILI)
Narrow-band red light phototherapy
Transcranial laser therapy
Intravascular low-power red laser light
Low-intensity laser therapy
Near infra-red
Transcranial low level laser (light) therapy
Irradiation
Low-level laser
Near-infrared light
Visible light
Laser 904 nm
Low-level laser energy
Near-infrared light treatment
Water-filtered infrared-A
Laser acupuncture
Low-level laser therapy
Polarized light therapy



Fact 3: Over 120 decent scientific journals (impact factor at least 3.0), and nearly 500 journals in total, have published at least one paper on photobiomodulation!

Some top journals are included, eg. The Lancet, PNAS, Circulation, Blood, Annals of Neurology and Science Translational Medicine. Click HERE for a detailed list about the articles published in these high-impact journals.



Fact 4: Photobiomodulation has also been mentioned in news feature articles published in the top journals Nature and Science.
“Eells and her colleagues found that NIR phototherapy counters methanol poisoning, which injures the retina and optic nerve, often causing blindness. The toxic metabolite is formic acid, which inhibits cytochrome oxidase. ‘In a rat model, NIR phototherapy is able to restore virtually normal retinal function, at least as judged by the electroretinogram,’ says Eells.
And neurobiologist Margaret Wong-Riley and her colleagues at the Medical College of Wisconsin in Milwaukee have shown that NIR phototherapy can also oppose the effects of cyanide on cell cultures. Cyanide poisons by binding to cytochrome oxidase. Wong-Riley’s team showed that phototherapy could halve the rate of apoptosis in cultured neurones, even when given before cyanide treatment. 
But can NIR phototherapy relieve not just acute toxicity, but more chronic inflammatory conditions? The signs augur well. Eells and her colleagues have shown that NIR phototherapy could cut the rate of apoptosis by 50% in a rat model of retinitis pigmentosa, in which photoreceptors die by apoptosis during postnatal development causing retinal degeneration and blindness” (Nature 2006
“Previous studies have shown that exposing cells to a particular wavelength of light, 670 nanometers, toward the red end of the visible spectrum, causes their energy-producing mitochondria to boost production of adenosine triphosphate, which powers the cells.” (Science 2017)


Fact 5: There are five scientific journals that have published a very large amount of photobiomodulation research. These journals are also feature many other light-related subjects in addition to photobiomodulation.

Photobiomodulation: important scientific journals
Publisher
Journal Title
Impact Factor
Wiley
Journal of Biophotonics
3.8
Elsevier
Journal of Photochemistry and Photobiology B: Biology
3.0
Springer
Lasers in Medical Science
2.5
Wiley
Lasers in Surgery and Medicine
2.1
Mary Ann Liebert
Photomedicine and Laser Surgery
1.6



Fact 6: Photobiomodulation research has been published in approximately 40 different countries.


Photobiomodulation research countries
Amount of articles
Country
Hundreds (> 400)
Brazil
Hundreds (> 200)
United States (~20 different states)
Dozens (> 50)
Australia, China, Iran, Israel, Italy, Korea, Turkey
Dozens
Canada, India, Japan, Russia, Spain, Taiwan, United Kingdom
Dozen (~10)
Croatia, Czech Republic, Egypt, France, Hungary, Norway, Sweden, Switzerland, New Zealand, South Africa, Ukraine
A few
Argentina, Austria, Belgium, Germany, Greece, Malaysia, Netherlands, Portugal, Poland, Saudi Arabia, Serbia, Slovakia, Slovenia, Sudan




Fact 7: Hall of Fame of the photobiomodulation research is presented below:

Photobiomodulation: notable researchers
Name
Position
University
Speciality
Research focus
Professor
University of Wisconsin-Milwaukee
Biosciences
Photobiomodulation and retinal degeneration.
Assistant professor
University at Buffalo
Oral biology
TGFß1 in photobiomodulation mechanisms.
Assistant professor
Harvard Medical School
Dermatology
Photobiomodulation and the brain. Has written dozens of articles and edited photobiomodulation-related books.
Professor
Russian Academy of Sciences
Biophysics
Photobiomodulation and cell function.
Professor
The University of Sydney
Neurobiology
Photobiomodulation and Parkinson’s disease.
Professor
The University of Sydney
Anatomy
Photobiomodulation and Parkinson’s disease.
Assistant professor
Australian National University
Anatomy
Photobiomodulation and retinal degeneration.
Professor
University of Johannesburg
Photobiology
Photobiomodulation and stem cells.
Professor
University College London (UCL)
Neurosciences
Photobiomodulation, mitochondria and retina.
Professor
University of Bergen
Physiatry
Photobiomodulation, muscle and exercise.
Professor
The University of Texas
Neurosciences
Photobiomodulation, brain and cognition.
Professor
University of Birmingham
Oral biology
Photobiomodulation and oral physiology.
Professor
Tel Aviv University

Photobiomodulation and heart.
Professor

Photobiomodulation, nerves and pain.
Dean
University of Otago
Physiotherapy
Photobiomodulation, wound healing and Achilles tendon.
Provost
San Diego State University

Photobiomodulation, wounds and injuries.
Professor
Federal University of Bahia

Photobiomodulation and bone tissue.
Research professor
Boston University
Neurology
Photobiomodulation and traumatic brain injury.
Professor
Medical College of Wisconsin
Neurology
Photobiomodulation and wound healing.
Professor
Medical College of Wisconsin
Oral biology
Photobiomodulation and nerves.
Dentist
-
Dentistry
Photobiomodulation treatment parameters. Has written many reviews and books on the subject.





14. The ongoing clinical trials

I checked the ClinicalTrials.gov database to see whether there are any ongoing clinical trials examining the health effects of photobiomodulation. The amount of active trials was not high, but there were dozens of studies that are still recruiting participants:

Ongoing PBM/LLLT clinical trials
Treatment indication
Country
Responsible party
Status
Identifier
Canada
LumiThera, Inc.
Active
NCT02725762
USA
Theradome, Inc.
Active
NCT02528552
Brazil
Federal University of Health Science of Porto Alegre
Recruiting
NCT02688426
USA
University of Minnesota
Active
NCT02000908
USA
University of Texas at Austin
Recruiting
NCT02851173
USA
University of Florida
Recruiting
NCT02582593
Norway
University of Bergen
Recruiting
NCT02749929
Norway
University of Bergen
Recruiting
NCT03014024
USA
University of California
Recruiting
NCT03160027
Iran
Shahid Beheshti University
Recruiting
NCT03023761
Brazil
University of Nove de Julho
Active
NCT02529657
USA
University of Texas Southwestern Medical Center
Recruiting
NCT02948634
Brazil
Uni. Estadual Paulista Júlio de Mesquita Filho
Recruiting
NCT02995070
USA
VA Office of Research and Development
Recruiting
NCT01782378
USA
University of North Carolina
Recruiting
NCT03044106
Brazil
University of Nove de Julho
Active
NCT02636764
Brazil
Federal University of Uberlandia
Recruiting
NCT03072004
Brazil
University of Nove de Julho
Recruiting
NCT02529670
USA
University of Texas at Austin
Recruiting
NCT02898233
USA
Massachusetts General Hospital
Recruiting
NCT02959307
Migraine
USA
The San Francisco Clinical Research Center
Recruiting
NCT02969642
USA
Erchonia Corporation
Recruiting
NCT03163810
USA
Erchonia Corporation
Recruiting
NCT03066336
USA
University of Pittsburgh
Recruiting
NCT02682992
USA
Barbara Ann Karmanos Cancer Institute
Recruiting
NCT02723604
France
Institut de Cancérologie de la Loire
Recruiting
NCT02696408
France
Institut Cancerologie de l'Ouest
Recruiting
NCT01772706
France
Nantes University Hospital
Recruiting
NCT02181439
USA
Biolux Research Ltd.
Recruiting
NCT03202355
USA
Biolux Research Ltd.
Recruiting
NCT02954133
Brazil
Universidade Cidade de Sao Paulo
Recruiting
NCT02898025
Brazil
Uni. Estadual Paulista Júlio de Mesquita Filho
Recruiting
NCT03000426
Sweden
Uppsala University
Recruiting
NCT02789735
Hong Kong
The University of Hong Kong
Recruiting
NCT02352038
USA
University of Texas at Austin
Recruiting
NCT02926352
Germany
Landstuhl Regional Medical Center
Recruiting
NCT03015116
Brazil
Hospital de Clinicas de Porto Alegre
Recruiting
NCT02296697
Belgium
Hasselt University
Recruiting
NCT02738268
USA
University of Pittsburgh
Recruiting
NCT02384434
USA
Cutera Inc.
Recruiting
NCT02910492
Brazil
University of Nove de Julho
Recruiting
NCT03031223
Spain
University of Castilla-La Mancha
Active
NCT02971215
Brazil
University of Nove de Julho
Recruiting
NCT02839967
Brazil
University of Nove de Julho
Recruiting
NCT03257748
Brazil
University of Nove de Julho
Recruiting
NCT02928809
Brazil
University of Sao Paulo
Recruiting
NCT02602431
USA
Massachusetts General Hospital
Recruiting
NCT02233413
USA
VA Office of Research and Development
Recruiting
NCT02356861
Brazil
Hospital de Clinicas de Porto Alegre
Recruiting
NCT03229330
Brazil
University of Nove de Julho
Active
NCT02416531
USA
Mayo Clinic
Recruiting
NCT02877004

This seems like a decent amount of effort from the scientific community, to investigate the effects of photobiomodulation in humans.




15. Summary

  1. Red light and near-infrared irradiation produce measurable changes locally in cells/tissues/organs. This form of light therapy is called photobiomodulation (PBM).
  2. Animal studies show that photobiomodulation therapy could be beneficial for over 90 different diseases. Evidence from human studies is also emerging in a fast pace.
  3. Over 2000 photobiomodulation papers have been published in PubMed-indexed journals, over 120 of which have a good impact factor (> 3.0). Research has been conducted in 40 different countries.

Thanks for reading. If this article got you interested in photobiomodulation, please consider joining our discussion group in Facebook.


Best,
Vladimir Heiskanen
Dental student (University of Helsinki)
Finland




Appendix 1: Recommended reading


Scientific review articles
Journal
Article title
AIMS Biophysics
Mechanisms and applications of the anti-inflammatory effects of photobiomodulation
Frontiers in Neuroscience
BBA Clinical
Biochemical Pharmacology
Annals of Biomedical Engineering



Appendix 2: Photobiomodulation on social media

Photobiomodulation on social media
Site
Category
Title
Facebook
Group
Facebook
Page
Facebook
Page
Facebook
Page
Facebook
Page