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
Age-related macular degeneration	Mouse	↑ATP, ↑cytochrome oxidase expression
Allergic asthma	Rat	↑IFN-γ, ↓IgE, ↓IL-4, ↓Th1/Th2 ratio
Alzheimer’s disease	Rat	↑ATP, ↑mitochondrial membrane potential, ↑cytochrome oxidase, ↑memory function, ↓reactive gliosis, ↓inflammation, ↓tau hyperphosphorylation
Burn wound	Rat	↑ATP, ↑cytochrome oxidase, ↑G6PD, ↑NADPH, ↑pAMPKα, ↓NADP, ↓LDH
Exercise performance	Mouse	↑ATP, ↑exercise performance, ↑cytochrome oxidase
Glomerulonephritis	Rat	↓TNF-α, ↓IL-1β, ↓macrophage and CD8 lymphocyte infiltration
Lifespan	Fruit fly	↑ATP, ↑lifespan, ↑mobility, ↓complement C3
Liver cirrhosis	Rat	↓AST, ↓ALT, ↓LDH, ↓cirrhotic areas, ↓collagen deposition
Multiple sclerosis (EAE)	Mouse	↑IL-10, ↑IL-4, ↓TNF-α, ↓IFN-γ, ↓disease symptoms
Muscle injury	Rat	↓CK, ↓O2−, ↓SOD, ↓TBARS
Myocardial infarct	Dog, rat	↑ATP, ↓mortality, ↓infarct size, ↓troponin T
Neuropathic pain	Rat	↓IL-1β, ↓CX3CL1, ↓dorsal gliosis, ↓hyperalgesia
Osteoarthritis	Rat	↓TNF-α, ↓IL-1β, ↓IL-6, ↓neutrophils, ↓macrophages
Osteoporosis	Rat	↑bone formation, ↑granulation tissue, ↑collagen fibers
Restenosis (abdom. aorta)	Rabbit	↑lumen area, ↓myointimal hyperplasia, ↓intima:media ratio
Spinal cord injury	Rat	↓TNF-α, ↓IL-1β, ↓hyperalgesia
Traumatic brain injury	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)
Achilles tendinitis	Low back pain
Acne	Lymphedema
Age-related macular degeneration	Meniscal pathology
Alzheimer’s disease	Muscle gain
Aphthous ulcers	Muscle pain
Bell’s palsy	Neck pain
Body contouring	Neuropathic foot ulcer
Bone fractures (hand/wrist)	Nipple pain
Burn scars	Oral mucositis
Burning mouth syndrome	Orthodontic pain
Carpal tunnel syndrome	Orthodontic tooth movement
Chronic joint disorders	Osteoarthritis
Cognitive performance	Periodontitis
COPD	Postherpetic neuralgia
Dental implant stability	Pressure ulcer
Dentin hypersensitivity	Radiation dermatitis
Depression	Raynaud’s phenomenon
Diabetic foot ulcer	Restenosis
Dry mouth (xerostomy)	Rheumatoid arthritis
Dysmenorrhea	Shoulder tendinopathy
Erythema (UV-induced)	Skin aging
Exercise performance	Sternotomy healing
Fibromyalgia	Stroke
Frozen shoulder	Temporomandibular disorders
Hair loss (alopecia)	Tennis elbow (lateral epicondylitis)
Hand-foot-and-mouth disease	Traumatic brain injury
Hypothyroidism	Venous leg ulcer
Labial herpes	Vitiligo
Lichen planus	Wound healing

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
Periodontitis	Ren	M	2017	7	180	C	➕/➖ Photobiomodulation decreased pocket depth only in short term (1-2 months).
Diabetic foot ulcer	Tchanque...	S	2016	4	131	C	➕ Photobiomodulation hastened the healing of foot ulcers.
Hair loss (alopecia)	Zarei	S	2016	5	394	B / C	➕ Photobiomodulation was beneficial for androgenetic alopecia in men and women.
Healing from tooth extraction	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).
Chronic low back pain	Huang	M	2015	7	211	B / C	➕/➖Photobiomodulation decreased pain, but didn’t improve function.
Temporomandibular disorders	Chen	M	2015	14	454	C	➕/➖ Photobiomodulation didn’t decrease pain, but brought functional improvements.
Exercise performance	Leal-Junior	M	2015	13	134+	C	➕ Photobiomodulation improved exercise performance and postexercise recovery.
Osteoarthritis (knee)	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.
Lymphedema (in breast cancer)	Smoot	M	2015	7	262	C	➕ Photobiomodulation decreased pain and upper limb volume.
Neck pain	SBU	S	2014	18	1007	C	➕ Photobiomodulation decreased pain after the intervention and in the follow-up.
Oral mucositis	Oberoi	M	2014	18	1144	B	➕ Photobiomodulation decreased pain and the risk of severe mucositis.
Exercise performance	Borsa	S	2013	10	147	B	➕ Photobiomodulation improved exercise performance and postexercise recovery.
Chronic neck pain	Gross	M	2013	2	109	C	➕ Photobiomodulation improved the markers (pain/disability/QoL/GPE).
Tooth extraction (lower 3rd molar)	Brignard...	S	2012	9	599	C	➖ Photobiomodulation didn’t decrease pain of edema significantly.
Tendinopathies	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.
Neck pain	Chow	M	2009	16	820	B	➕ Photobiomodulation decreased pain acutely and in the long-term.
Tennis elbow	Bjordal	M	2008	13	730	B / C	➕ Photobiomodulation decreased pain.
Acute pain	Bjordal	S	2006	9	609	B / C	➕ Photobiomodulation decreased pain.
Neck pain	Chow	S	2005	5	273	C	➕ Photobiomodulation decreased pain.
Chronic joint disorders	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, hamsters, gerbils, guinea pigs, frogs, toads, 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)
Acne	Lung fibrosis
Achilles tendinitis	Lung hemorrhage
Acute pain	Lung inflammation (acute)
Acute respiratory distress syndrome	Lung injury
Adipose tissue inflammation	Lymphedema
Age-related macular degeneration	Mastitis
Allergic asthma	Methanol toxicity (retinal injury)
Allergic contact dermatitis	Morphine withdrawal
Allergic rhinitis	Multiple sclerosis (EAE)
Allodynia	Muscle injury
Alzheimer’s disease	Myocardial infarct
Amyotrophic lateral sclerosis (familial)	Myonecrosis
Aneurysm (abdominal aorta)	Myopathy (mdx)
Arthritis (microcrystalline arthropathies)	Nerve injury (alveolaris inferior)
Arthritis (zymosan-induced)	Nerve injury (facialis)
Atherosclerosis	Nerve injury (ischiadus)
Atrophic gastritis	Neuropathic pain
Auditory neuropathy	Oral mucositis
Bone fracture	Oral ulcer (formocresol-induced)
Bone grafts	Osteoarthritis
Burn injury	Osteomyelitis
Cancer	Osteoporosis
Colitis	Parkinson’s disease
COPD	Paw edema (inflammatory)
Crescentic glomerulonephritis	Periodontitis
Delayed hypersensitivity	Peritonitis
Dentin regeneration	Pleurisy
Depression	Pressure ulcer
Dermal abrasions	Radiation injury
Diabetes (kidney)	Restenosis (abdominal aorta)
Diabetes (eyes)	Retinitis pigmentosa
Diaphragm muscle dysfunction	Rheumatoid arthritis
Endophthalmitis	Sarcopenia
Exercise performance	Sciatica
Haemarthrosis	Spinal cord injury
Hair loss (alopecia)	Stroke
Heart failure	Submandibular gland inflammation
Hearing loss (noise-induced)	Surgical wound infection
Hyperalgesia	Teeth re-implantation
Hypertension	Temporomandibular joint inflammation
Kidney fibrosis	Tendinopathy
Kidney injury	Thrombocytopenia
Laryngitis	Tinnitus
Ligament injury (ACL)	Tympanic membrane perforation
Ligament injury (MCL)	Tracheal incision healing
Listeria infection	Traumatic brain injury
Liver cirrhosis	Wound healing
Liver regeneration

As the list shows, there is a vast literature on photobiomodulation. The total amount of these animal studies indexed in PubMed is more than 1100.




5. The comprehensive research database

In order to learn as much as possible about red light and near-infrared, I have spent a plenty of time compiling photobiomodulation research into a spreadsheet. My spreadsheet includes currently more than 3800 scientific articles on the subject:

Low level laser therapy (LLLT) / photobiomodulation (PBM) / red/NIR phototherapy studies - a comprehensive database by Vladimir Heiskanen

Here are some statistics that I've made based on the data. The PBM literature includes...

• 500 randomized studies (incl. 220 double-blind and 80 single-blind studies)
• 1170 animal studies (800 rat studies, 220 mouse studies, 90 rabbit studies)
• 620 in vitro studies
• 340 narrative reviews & editorials
• 130 systematic reviews (incl. 54 meta-analyses)

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
Ghanbari 2017	Iran	Rat	Methanol toxicity (retinal injury)	LED	670	↓RGC death, ↓injury of visual cortex
Merry 2016	Canada	Human	Age-related macular degeneration	LED	670	↑visual acuity, ↑contrast sensitivity, ↓drusen
Kaynezhad 2016	UK	Rat	Age-related macular degeneration	LED	670	↑oxidation of cytochrome oxidase
Rezaei Kanavi 2016	Iran	Rabbit	Corneal alkali burn	Laser	810	↓injury area, ↓inflammation
Chu-Tan 2016	Australia	Rat	Light-induced retinal damage	LED	670	↓photoreceptor cell death, ↑ONL thickness
Del Olmo-Aguado 2016	Spain	Rat	Retinal ischemia	LED	630	↓RGC death, ↓GFAP
Saliba 2015	USA (OH)	Mouse	Diabetic retinopathy	LED	670	↓retinal O2−, ↓leukostasis, ↓ICAM-1 expression, ↓iNOS expression, ↓Ca2+ channel dysfunction
Calaza 2015	UK	Mouse	Age-related macular degen. CFH(-/-)	LED	670	↑ATP
Gkotsi 2014	UK	Mouse	Age-related macular degeneration	LED	670	↑ATP, ↑cytochrome oxidase expression
Giacci 2014	Australia	Rat	Light-induced retinal damage	LED	670	↓photoreceptor cell death, ↓8OHDG
Di Marco 2014	Italy	Rat	Light-induced retinal damage	LED	670	↑b-wave amplitude, ↓photoreceptor cell death, ↓GFAP
Ahamed Basha 2014	India	Rat	Light-induced retinal damage	LED	670	↑ONL cells, ↑ONL thickness
Di Marco 2013	Italy	Rat	Light-induced retinal damage	LED	670	↓photoreceptor cell death, ↓GFAP
Tang 2013	USA (OH)	Rat	Diabetic retinopathy	LED	670	↓RGC death, ↓retinal O2−, ↓leukostasis, ↓ICAM-1 expression
Natoli 2013	Australia	M&R	Oxygen-induced retinopathy	LED	670	↓photoreceptor cell death, ↓retinal neovascularisation
Kokkinopoulos 2013b	UK	Mouse	Age-related macular degen. CFH(-/-)	LED	670	↓TNF-α expression, ↓TLR2/4 expression, ↓macrophage activation, ↓MIF and calcitonin expression
Kokkinopoulos 2013a	UK	Mouse	Age-related macular degeneration	LED	670	↑mitochondrial membrane potential, ↓TNF-α, ↓C3d, ↓macrophages
Begum 2013	UK	Mouse	Age-related macular degen. CFH(-/-)	LED	670	↑cytochrome oxidase, ↓C3, ↓GFAP,
Albarracin 2013	Australia	Mouse	Oxygen-induced retinopathy	LED	670	↓oxidative stress, ↓C3
Rutar 2012	Australia	Rat	Light-induced retinal damage	LED	670	↓C1s, ↓C2, ↓C3, ↓C4b, ↓C3aR1, ↓C5r1
Albarracin&Valter 2012b	Australia	Rat	Light-induced retinal damage	LED	670	↓photoreceptor cell death,↓LIF-, Edn2 and TNF-α gene expression, ↓Müller cell proliferation, etc.
Albarracin&Valter 2012a	Australia	Rat	Light-induced retinal damage	LED	670	↑b-wave amplitude, ↓photoreceptor cell death
Albarracin 2011	Australia	Rat	Light-induced retinal damage	LED	670	↑a-wave amplitude, ↑b-wave amplitude, ↓photoreceptor cell death, ↓macrophages, ↓microglial activation
Qu 2010	China	Rat	Light-induced retinal damage	LED	670	↑b-wave amplitude, ↓ONL damage
Natoli 2010	Australia	Rat	Light-induced retinal damage	LED	670	↓expression of genes/ncRNA related to light-induced retinal damage
Rojas 2008	USA (TX)	Rat	Mitochondrial optic neuropathy	LED	633	↑retinal structure, ↑cytochrome oxidase expression
Eells 2003	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
Scalize 2015	Brazil	Rat	Osteoporosis (ovx)	Laser	780	↑trabecular bone formation, ↑collagen fiber area
Altan 2015	Turkey	Rat	Midpalatal suture expansion	Laser	820	↑bone formation
Mota 2013	Brazil	Rat	Bone defect	Laser	670	↑bone stiffness, ↑serum ALP
Ekizer 2013	Turkey	Rat	Suture expansion	LED	618	↑bone formation, ↑osteoblasts, ↑osteoclasts
El-Maghraby 2013	Egypt	Rat	Gamma radiation of mandible	Laser	904	↑trabecular area
Omasa 2012	Japan	Rat	Orthodontic mini-implant (tibia)	Laser	830	↑bone formation, ↑BMP-2 expression
Bossini 2012	Brazil	Rat	Osteoporosis (ovx)	Laser	830	↑bone and collagen formation, ↔biomechanical properties
Pires-Oliveira 2010	Brazil	Rat	Osteoporosis (ovx)	Laser	904	↑bone formation
Lopes 2007	Brazil	Rabbit	Orthodontic implant (tibia)	Laser	830	↑bone formation (CHA concentration)
Rochkind 2004	Israel	Rat	Mandibular trauma	Laser	633	↑bone mineralization
Barushka 1995	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:

• Photobiomodulation has been studied for various animal models of Alzheimer’s disease, with good results (Lu et al. 2017, Farfara et al. 2015, Purushothuman et al. 2014, Grillo et al. 2013).

Exercise performance:

• Photobiomodulation has shown some efficacy for exercise performance, muscle growth, sarcopenia, myopathies and muscle injuries in animal and human studies (Ferraresi et al. 2016, Baroni et al. 2014, Leal-Junior et al. 2014, Corazza et al. 2013).

Hearing loss:

• Photobiomodulation appears to protect rodents from noise-induced hearing loss (Tamura et al. 2015, Lee et al. 2016, Tamura et al. 2016).

Oral mucositis:

• One of the most common complications of cancer treatments is the painful inflammation of oral mucosa. Photobiomodulation has been studied for this indication in approximately twenty randomized trials, very often with great results (Oberoi et al. 2014, Silva et al. 2015, Soto et al. 2015, Ferreira et al. 2016).

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:

• Photobiomodulation has been studied in the treatment wounds and burns. More than a hundred animal studies have been published, but the human research is somewhat scarce (Gupta et al. 2015, Keshri et al. 2016, Ojea et al. 2016, Tchanque-Fossuo et al. 2016).

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 1999, Karu 2010, Wong-Riley et al. 2005, Gupta et al. 2014, Wu et al. 2012).

It has also been shown that wavelengths 750 and 950 nm can inhibit mitochondrial function at the electron transport chain (ETC) level. While this might sound like a paradoxical and undesired effect, there is some evidence suggesting that it could actually be used after ischemia to effectively reduce the ischemia-reperfusion (IR) injury, for example in stroke (Sanderson et al. 2018).

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
Labial herpes	690 nm	80 mW	1 cm2	48 J	80 mW/cm2	10 minutes	10 sessions in 14d
Labial herpes	670 nm	40 mW	0.79 cm2	1.6 J	51 mW/cm2	40 seconds	1 session
Hypothyroidism	830 nm	50 mW	0.28 mm2	40 J	17 680 mW/cm2	13,3 minutes	10 sessions in 8wk
Osteoarthritis	850 nm	100 mW	0.79 mm2	48 J	13 000 mW/cm2	8 minutes	8 sessions in 4wk
Osteoarthritis	830 nm	800 mW	25 cm2	1250 J	32 mW/cm2	32 minutes	12 sessions in  6wk
Age-related macular degeneration	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. (A note: As of 2019, this table is not really up-to-date anymore.)

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
Infrared Mini 830	LED	830	?	200 (10cm) 20 (70cm)	?	+ Decent parameters	~$400
Red Mini 670	LED	670	?	200 (0cm) 20 (60cm)	?	+ Decent parameters	~$90
NIR torch	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. However, it should noted that the device might overestimate the irradiance of near-infrared wavelengths up to 2-fold.

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 (Barolet et al. 2016, Karu 2010).

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 approximately 700 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 the 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 71 different countries.

Photobiomodulation research countries
Amount of articles	Country
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
Less than 10	Bosnia-Herzegovina, Bulgaria, Chile, Colombia, Costa Rica, Croatia, Cuba, Cyprus, Finland, Indonesia, Iraq, Ireland, Jordan, Kazakhstan, Kuwait, Macedonia, Malaysia, Mexico, Monaco, Nepal, Pakistan, Portugal, Puerto Rico, Qatar, Singapore, Slovenia, Sudan, Syria, Thailand, Ukraine, United Arab Emirates, Venezuela, Yemen, Yugoslavia

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

Photobiomodulation: notable researchers
Name	Position	University	Speciality	Research focus
Janis Eells	Professor	University of Wisconsin-Milwaukee	Biosciences	Photobiomodulation and retinal degeneration.
Praveen Arany	Assistant professor	University at Buffalo	Oral biology	TGFß1 in photobiomodulation mechanisms.
Michael Hamblin	Assistant professor	Harvard Medical School	Dermatology	Photobiomodulation and the brain. Has written dozens of articles and edited photobiomodulation-related books.
Tiina Karu	Professor	Russian Academy of Sciences	Biophysics	Photobiomodulation and cell function.
Jonathan Stone	Professor	The University of Sydney	Neurobiology	Photobiomodulation and Parkinson’s disease.
John Mitrofanis	Professor	The University of Sydney	Anatomy	Photobiomodulation and Parkinson’s disease.
Krisztina Valter-Kocsi	Assistant professor	Australian National University	Anatomy	Photobiomodulation and retinal degeneration.
Heidi Abrahamse	Professor	University of Johannesburg	Photobiology	Photobiomodulation and stem cells.
Glen Jeffery	Professor	University College London (UCL)	Neurosciences	Photobiomodulation, mitochondria and retina.
Jan Bjordal	Professor	University of Bergen	Physiatry	Photobiomodulation, muscle and exercise.
Francisco Gonzalez-Lima	Professor	The University of Texas	Neurosciences	Photobiomodulation, brain and cognition.
Paul Cooper	Professor	University of Birmingham	Oral biology	Photobiomodulation and oral physiology.
Uri Oron	Professor	Tel Aviv University		Photobiomodulation and heart.
Juanita Anders	Professor	USUHS		Photobiomodulation, nerves and pain.
David Baxter	Dean	University of Otago	Physiotherapy	Photobiomodulation, wound healing and Achilles tendon.
Chukuka Enwemeka	Provost	San Diego State University		Photobiomodulation, wounds and injuries.
Antonio Pinheiro	Professor	Federal University of Bahia		Photobiomodulation and bone tissue.
Margaret Naeser	Research professor	Boston University	Neurology	Photobiomodulation and traumatic brain injury.
Harry Whelan	Professor	Medical College of Wisconsin	Neurology	Photobiomodulation and wound healing.
Margaret Wong-Riley	Professor	Medical College of Wisconsin	Oral biology	Photobiomodulation and nerves.
Jan Tunér	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
Age-related macular degeneration	Canada	LumiThera, Inc.	Active	NCT02725762
Androgenetic alopecia	USA	Theradome, Inc.	Active	NCT02528552
Cardiovascular diseases	Brazil	Federal University of Health Science of Porto Alegre	Recruiting	NCT02688426
Chemotherapy-induced peripheral neuropathy	USA	University of Minnesota	Active	NCT02000908
Cognitive enchancement	USA	University of Texas at Austin	Recruiting	NCT02851173
Cognitive function	USA	University of Florida	Recruiting	NCT02582593
Colles’ Fracture	Norway	University of Bergen	Recruiting	NCT02749929
Colles’ Fracture	Norway	University of Bergen	Recruiting	NCT03014024
Dementia	USA	University of California	Recruiting	NCT03160027
Endodontic re-treatment pain	Iran	Shahid Beheshti University	Recruiting	NCT03023761
Failed Back Surgery Syndrome	Brazil	University of Nove de Julho	Active	NCT02529657
Fibromyalgia	USA	University of Texas Southwestern Medical Center	Recruiting	NCT02948634
Gingival recession (connective tissue graft)	Brazil	Uni. Estadual Paulista Júlio de Mesquita Filho	Recruiting	NCT02995070
Gulf War Veterans Illnesses	USA	VA Office of Research and Development	Recruiting	NCT01782378
Hamstring injury	USA	University of North Carolina	Recruiting	NCT03044106
Knee osteoarthritis	Brazil	University of Nove de Julho	Active	NCT02636764
Leprosy neuropathy	Brazil	Federal University of Uberlandia	Recruiting	NCT03072004
Low Back Pain	Brazil	University of Nove de Julho	Recruiting	NCT02529670
Major Depressive Disorder	USA	University of Texas at Austin	Recruiting	NCT02898233
Major Depressive Disorder	USA	Massachusetts General Hospital	Recruiting	NCT02959307
Migraine	USA	The San Francisco Clinical Research Center	Recruiting	NCT02969642
Nonalcoholic Steatohepatitis	USA	Erchonia Corporation	Recruiting	NCT03163810
Onychomycosis	USA	Erchonia Corporation	Recruiting	NCT03066336
Oral mucositis	USA	University of Pittsburgh	Recruiting	NCT02682992
Oral mucositis	USA	Barbara Ann Karmanos Cancer Institute	Recruiting	NCT02723604
Oral mucositis	France	Institut de Cancérologie de la Loire	Recruiting	NCT02696408
Oral mucositis	France	Institut Cancerologie de l'Ouest	Recruiting	NCT01772706
Orthodontic tooth movement	France	Nantes University Hospital	Recruiting	NCT02181439
Orthodontic tooth movement	USA	Biolux Research Ltd.	Recruiting	NCT03202355
Orthodontic tooth movement (w/ Invisalign)	USA	Biolux Research Ltd.	Recruiting	NCT02954133
Osteoarthritis	Brazil	Universidade Cidade de Sao Paulo	Recruiting	NCT02898025
Palatal Wound	Brazil	Uni. Estadual Paulista Júlio de Mesquita Filho	Recruiting	NCT03000426
Pelvic girdle pain	Sweden	Uppsala University	Recruiting	NCT02789735
Periodontitis	Hong Kong	The University of Hong Kong	Recruiting	NCT02352038
Phobias (fear extinction)	USA	University of Texas at Austin	Recruiting	NCT02926352
Plantar Fascitis	Germany	Landstuhl Regional Medical Center	Recruiting	NCT03015116
Pressure ulcer	Brazil	Hospital de Clinicas de Porto Alegre	Recruiting	NCT02296697
Radiodermatitis	Belgium	Hasselt University	Recruiting	NCT02738268
Radiodermatitis	USA	University of Pittsburgh	Recruiting	NCT02384434
Skin rejuvenation	USA	Cutera Inc.	Recruiting	NCT02910492
Spinal Cord Injuries	Brazil	University of Nove de Julho	Recruiting	NCT03031223
Subacromial Impingement	Spain	University of Castilla-La Mancha	Active	NCT02971215
Temporomandibular disorder	Brazil	University of Nove de Julho	Recruiting	NCT02839967
Temporomandibular disorder	Brazil	University of Nove de Julho	Recruiting	NCT03257748
Temporomandibular disorder	Brazil	University of Nove de Julho	Recruiting	NCT02928809
Tooth extraction (third molar)	Brazil	University of Sao Paulo	Recruiting	NCT02602431
Traumatic brain injury	USA	Massachusetts General Hospital	Recruiting	NCT02233413
Traumatic brain injury (and PTSD)	USA	VA Office of Research and Development	Recruiting	NCT02356861
Venous ulcers	Brazil	Hospital de Clinicas de Porto Alegre	Recruiting	NCT03229330
Vulvar Lichen Sclerosus	Brazil	University of Nove de Julho	Active	NCT02416531
Weight Loss	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. Criticisms and obstacles of photobiomodulation

In their article Low level laser (light) therapy and photobiomodulation: The path forward, a group of important photobiomodulation researchers summarized some reasons hampering the application of photobiomodulation in the medical community:

"The reasons for this skepticism and disbelief are many and various and differ depending on who you are talking to. Biomedical scientists often refer to a lack of mechanism, and the absence of agreement on dosimetry and parameters. Physicians often claim there is a lack of large clinical trials and not enough systematic reviews. Hospital and insurance administrators cannot agree on coverage and reimbursement. Finally (and regrettably) there has been marketing hype, over-promising and frank misinformation from some of the companies making devices (lasers, LED arrays, mixed clusters) that are used in the LLLT industry."

Many skeptic websites and blogs also have claimed that photobiomodulation (LLLT) is mostly a form of quackery. These sites include Science-Based Medicine, Skeptic North, SkeptVet, Device Watch and also the Wikipedia page on LLLT. These criticisms present some of the weaknesses of the photobiomodulation (PBM) research fairly, but since most of the PBM research has been published since the 2010, most of these criticisms are outdated and I would trust recent systematic reviews more than these articles that are mostly based on some quick internet searches.

Some skeptics claim that the effects of photobiomodulation might be based on thermal effects of red or near-infrared radiation. This is a question that has also been examined by the scientific community. Thermal effects of low-level light therapy are usually negligible and some experimental temperature-controlled studies also confirm the existence of athermal effects. Therefore, nowadays the biological effects of PBM are considered to be mostly of athermal nature (Lanzafame et al. 2004, Joensen et al. 2011, Jung&Grune 2012, Grandinétti Vdos et al. 2015).

The quality of randomized, blinded and placebo-controlled photobiomodulation studies is currently somewhat poorer than it could be. Especially these aspects could be improved:

• While the application of placebo is common the PBM literature, some minor methodological deficiencies have been revealed (Relf et al. 2008). 
• Treatment parameter reporting also fails somewhat often (Tunér&Jenkins 2016). 
• Regarding the randomisation, most trials apparently fail in the allocation concealment, which is quite an important methodological aspect in the assessment of study quality (risk of bias). These aspects should be improved in the future trials.

Marketing of photobiomodulation devices has also been often somewhat deceptive and has included a lot of empty promises regarding the efficiency of PBM in the treatment of various diseases. Recently a LLLT salesman Larry Lytle pleaded guilty for misleading marketing of "QLaser" devices, agreeing to repay customers more than $16 million.

A major obstacle in the application of PBM in the medical treatments has been the high price of PBM treatment devices. However, since the LED-based devices for in-home usage are becoming more popular, this aspect is probably going to improve a lot in the near future.

16. 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 100 different diseases. Evidence from human studies is also emerging in a fast pace.
   
3. Over 3800 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 at least 71 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

Book recommendations
Author/Editor	Book title
Riegel and Godbold	Laser Therapy in Veterinary Medicine: Photobiomodulation (2017)
Hamblin, de Sousa and Agrawal	Handbook of Low-Level Laser Therapy (2016)
Hode and Tunér	Laser phototherapy: Clinical practice and scientific background (2016)
Hamblin and Huang	Handbook of Photomedicine (2013)

Scientific review articles
Journal	Article title
AIMS Biophysics	Mechanisms and applications of the anti-inflammatory effects of photobiomodulation
Frontiers in Neuroscience	Turning On Lights to Stop Neurodegeneration: The Potential of Near Infrared Light Therapy in Alzheimer's and Parkinson's Disease (2016)
BBA Clinical	Shining light on the head: Photobiomodulation for brain disorders (2016)
Biochemical Pharmacology	Neurological and psychological applications of transcranial lasers and LEDs (2013) (pdf)
Annals of Biomedical Engineering	The nuts and bolts of low-level laser (light) therapy (2012)

News features
Source	Article title
The Australian	Let There Be Light (2017)
Massachusetts General Hospital	Low-level laser therapy may improve treatment of dangerous bleeding disorder (2016)
Wisconsin Academy	Light As Medicine? (2014)
University of Sydney	Shining a (red) light on Parkinson’s disease (2013)
ScienceDaily	Lasers stimulate stem cells and reduce heart scarring after heart attack, study suggests (2011)
Nature	Cell biology: Power games (2006)
Scientific American	Red Light Saves Sight (2003)

Appendix 2: Photobiomodulation on social media

Photobiomodulation on social media
Site	Category	Title
Facebook	Group	Low Level Laser Therapy (LLLT) and Photobiomodulation (PBM) Discussions
Facebook	Page	Photobiomodulation
Facebook	Page	NAALT - North American Association for Photobiomodulation Therapy
Facebook	Page	Shine With Light
Facebook	Page	In Light Medical