Friday, May 15, 2015

The Therapeutic Effects of Red and Near-Infrared Light (2015)

An edited version has also been published at Perfect Health Diet.

"Penetrating red light is possibly the fundamental anti-stress factor for all organisms. The chronic deficiency of such light is, I think, the best explanation for the deterioration which occurs with aging." - Raymond Peat

1. Preface

About two years ago, I spent a lot time reading Ray Peat's articles, trying to make sense of his various ideas regarding health. In many of his articles, Peat wrote that red light is healthy and even crucial for well-being, because it can activate mitochondrial respiration.

For example, in his article Aging Eyes, Infant Eyes, and Excitable Tissues (2006), he wrote:
"Old observations such as Warburg’s, that visible light can restore the activity of the 'respiratory pigments,' showed without doubt that visible light is biochemically active. By the 1960s, several studies had been published showing the inhibition of respiratory enzymes by blue light, and their activation by red light."
Peat didn't give many references to justify his claims, but after doing some searches on PubMed, I realized that there are literally thousands of papers supporting his views.

2. How could red light improve metabolism?

Certain wavelengths of electromagnetic radiation directly increase energy (ATP) in the tissues, and the activation of cytochrome c oxidase (Cox), the mitochondrial respiratory enzyme discovered by Nobel laureate Otto Warburg, seems to be the main mechanism.[1-6]

On the molecular level, red light seemingly causes the photodissociation of nitric oxide (NO). When the cells are stressed, cells can produce NO which can bind to Cox, inhibiting its ability to bind oxygen.[2,7-11]

The following citations are from a news article on Nature (2006):
"Recent findings suggest that the enzyme [Warburg] identified, cytochrome oxidase, is a key player in a new understanding of how the cell's energy metabolism affects health and disease. And surprisingly they show that light has a profound effect on how the enzyme works — and could even be used to treat degenerative disease." [...]
"According to cell biologist Salvador Moncada of University College London, evolution really has crafted cytochrome oxidase to bind not only oxygen but also NO. 'One effect of slowing respiration in some locations is to divert oxygen elsewhere in cells and tissues,' he says. This prevents oxygen levels sinking dangerously low." [...]
"We have shown that light can indeed reverse the inhibition caused by NO binding to cytochrome oxidase, both in isolated mitochondria and in whole cells," says biochemist Guy Brown, at the University of Cambridge, UK. "And what's more, we found that light can protect cells against NO-induced cell death." [11]

The most relevant wavelengths seem to be 600-1070nm --- in other words, red light and the penetrating shorter wavelengths of near-infrared radiation (NIR).[1,2]

Our eyes are able to see 400-700nm
radiation (blue, green 
and red light).
Therapeutic effects 
come from 600-1070nm
radiation (red and 
near-infrared light).
Within this range, some wavelengths seem to have better effects than others. For example, in one study, 665nm and 810nm rays were beneficial, while 730nm and 980nm were not.[12]

There are important differences in the penetrating power of the different wavelengths. Visible red light doesn't penetrate tissue very well, but near-infrared does that quite well. If near-infrared is directed to the skin, the power seems to decrease 1000-fold by every 2-3 centimetres. However, a worm study shows that even those very small doses seem to have an effect on the cellular level.[13-15]

Later in this article, I will also show that light apparently also has an systemic effect, which probably spreads through the circulation to the whole body.

When it comes to Peat's claims about blue light, high intensities can inhibit the same enzyme (Cox), and this can lead to retinal damage and other problems.[11,16]

3. The health effects of red light and near-infrared radiation: The research history

John H. Kellogg's book (1910) is
freely available on
John Kellogg and incandescent lamp therapy (1910): The therapeutic use of red light is not a new phenomenon. The very earliest reports on the topic have been published in the 19th century, the most well-known article being The Red Light Treatment of Small-Pox (1895) by Niels Finsen, who also got the 1903 Nobel Prize in medicine, for his research regarding the health effects of light (especially ultraviolet radiation).[17]

In 1910, John Harvey Kellogg published his 200-page book Light Therapeutics, which included a large amount of information about the therapeutic usefulness of light therapy with incandescent light bulbs and arc lights. According to his book, light therapy can be effectively used for diabetes, obesity, chronic fatigue, insomnia, baldness, cachexia and many other health problems.[18]

Similar therapeutic usage was also reported in Margaret A. Cleaves' book Light energy, its physics, physiological action and therapeutic applications (1904) and Leopold Freund's book Elements of general radio-therapy for practitioners (1904).

In the next decades after Kellogg's, Cleaves' and Freund's books, the information was apparently forgotten. However, some elderly people have told me that in their youth, some doctors used to recommend infrared lights for some therapeutic purposes (such as pain after dental operations).

The invention of laser light (1960-): In the beginning of 60's, the first red-light emitting lasers were invented. A couple of years after that, Endre Mester from Hungary reported that red laser light could improve hair growth on mice. Quickly after that it was also found that red laser light could accelerate wound healing in animals - and in '70s the first human trials were being done.[2] (At the same time, Marta Fenyo started focusing on polarized light therapy after working with Mester.)

In the '80s and '90s most of the research was conducted in the Soviet Union. There was many kinds of effects studied. For example, some studies reported protective effect against x-rays and other studies focused on heart disease.[19-22]

Modern study of light/LLLT:  In the Western countries, research on red light didn't really start before the 21th century, and most of the interesting studies have been released within the last five years (2010-2015). A dramatic amount of clinical research is being conducted nowadays: In 2014, more than 400 PubMed titles on the topic were published.

In most of the studies on red light or near-infrared therapy, a low-power laser device (output often less than 100mW) has been used, therefore the widely used abbreviation LLLT (low-level laser therapy).

Many studies have also been conducted with LED's or other light sources. One can find also relevant studies by using keywords such as narrow-band light therapy, phototherapy, photobiomodulation, photobiostimulation, low-level light therapy, laser acupuncture, water-filtered infrared-A, near-infrared light, visible light, polarized-light therapy, or light-emitting diode irradiation. Despite different ways of generating the light, the wavelength used in the studies always fits between 600 and 1070 nanometres, because that is the effective range.

The studies have most often been conducted using a monochromatic light source (eg. 630, 633, 660, 670, 780, 808, 810, 890, 904, 940, 1064 or 1072nm). The parameters such as light dose, power output, pulsing or diameter of the light ray usually varies in the different studies because different devices are being used. There is no general consensus on which parameter is the most reliable, but many have yielded positive results.

4. The health effects of red light and near-infrared radiation: The extent of research

Today, PubMed keyword LLLT  returns more than 4000 scientific papers. Hundreds of clinical trials have been conducted, and dozens of systematic reviews can also be found.

Here is a list of some health issues that have been reported to improve by light therapy (usually low-level laser). In some cases, the effects are still disputed, while other results are confirmed by meta-analyses.

Many animal studies have also been conducted:

Photobiomodulation indications (animal studies)
Diabetes (kidney)

5. The health effects of red light and near-infrared radiation: A few examples of the clinical study results

5.1. Age-related macular degeneration

German clinicians conducted a retrospective analysis of 200 elderly subjects with age-related macular degeneration (most of them also had cataracts). The subjects were treated using a LLLT device emitting near-infrared light (780nm). The light was targeted to their eyes, through the conjunctiva.[65]

The subjects were treated four times during two weeks. Placebo group was given a mock treatment.

In the LLLT group, the visual acuity was improved in 95% of the subjects. Most of them were able to see a few rows lower on the Snellen chart. The improved vision was maintained for 3-36 months after treatment. LLLT also appeared to improve edema, bleeding, metamorphosia, scotoma and dyschromatopsia in some patients.

5.2. Knee Osteoarthritis

Hungarian researchers studied the use of near-infrared LLLT in knee osteoarthritis patients, in a double-blinded placebo controlled trial (830nm).[73]

Intervention group got infrared treatment on their affected joint twice a week, over a period of four weeks. The placebo group got a similar treatment of 100-fold lower intensity.

In the intervention group, the pain scores were (on a scale from 1 to 10):
- 5.75 before the treatment
- 1.71 after the last treatment session
- 1.18 two months after completing the therapy

In the placebo group, the pain scores were:
- 5.62 before treatment
- 4.13 after the last treatment session
- 4.12 two months after completing the therapy

Some other studies on this issue haven't been nearly as successful, but as discussed below, it might be related to dose parameters or some other methodological factors in the studies.

5.3. Labial herpes

The researchers of University of Vienna Medical School studied the usage of red light on labial herpes in a double-blind, placebo-controlled trial.[61]

There was a 12-fold difference in the median time until
the recurrence of herpes symptoms between the groups.
(Schindl&Neumann 1999)
The subjects were treated in a recurrence-free period. The intervention group were treated for 10 minutes daily for two weeks with visible red light (low-level laser).

Placebo group got a similar treatment, but the laser wasn't turned on. The subjects wore masks, so that they couldn't see whether they were given the real treatment.

The patients were instructed to return to the department at the time of symptom recurrence. The median recurrence-free interval in the laser-treated group was 37.5 wk compared with 3 wk in the placebo group.

5.4. Wisdom teeth extraction

A 2013 Italian study focused on patients who had their lower third molar removed surgically. The patients were assigned to a LLLT or control group. The active group received near-infrared light to the extraction site and on cheek (980nm).[92]

The pain level and edema were measured 24h after the surgery. The subjects in the active group had much less pain and edema compared to the control group.

The patients receiving low-level laser therapy reported that their
level of pain was 3.75/10 on the next day after surgery.
In the control group, the score was 7.1/10.

A couple of other studies on this issue have been published. If we look at the all of the data critically, it isn't completely conclusive, but still very promising.

5.5. Hypothyroidism

This 2013 randomized, placebo-controlled study involving 43 patients with Hashimoto's thyroiditis-induced hypothyroidism was conducted in São Paolo, Brazil.[37]

The active group received ten treatment sessions (twice a week) involving the near-infrared irradiation of the skin area close to their thyroid glands (830nm). The placebo group received red light treatment of very low intensity[37]

After 10 treatment sessions, the thyroxine (T4) medication was discontinued in both groups. During the next 9 months, the medication was slowly re-introduced if the thyroid hormone levels didn't normalize without medication.

In the control group, hypothyroidism remained after the discontinuation of T4 and the final dosage after the reintroduction of medication was actually higher than before the discontinuation.

However, in the active group, 48% of the patients maintained normal thyroid hormone levels without any medication. The rest also could decrease their dosage a little.

Average T4 dose in the active group (baseline -> 9 months): 93µg -> 39µg
Average T4 dose in the placebo group (baseline -> 9 months): 90µg -> 107µg

In the active group, some other positive changes were also noticed (thyroid volume, TPO antibodies and echogenicity index).

In my personal opinion, this is a very remarkable result. The Brazilian researcher had also conducted a pilot study before this randomized study, with equally positive results. Similar effects have also been reported in some Russian and Ukrainian dissertations (not translated to English).[36-43]

If you are interested in this topic, see also my more recent article Hypothyroidism: Could it be treated with LIGHT?.

6. The systemic anti-inflammatory effect

Usually the red/near-infrared is applied locally to the treatable tissue. If the patient suffers from knee osteoarthritis, then the light is going to be shone on the knee, and so on.

However, light also has systemic effects which seem to be transmitted mainly by circulation of blood. The researcher Natalya Zhevago has conducted an interesting study, in which the patients got some visible light and infrared to the sacral area (low back).[86] The light was quite similar to sunlight, except that it didn't contain UV radiation or blue light, and the infrared portion was polarized. According to one study, polarization of light enchances the metabolic effect slightly.[87]

The subjects' blood was analyzed after the treatment. The results were interesting. Subjects' pro-inflammatory cytokines (TNF-α, IL-6 etc.) were dramatically reduced in the subjects, especially in those with initially high values. Also, the concentrations anti-inflammatory cytokines increased.[86]
A dramatic decrease in the level of pro-inflammatory cytokines TNF-α, IL-6, and IFN-γ was revealed: at 0.5 h after exposure of volunteers (with the initial parameters exceeding the norm), the cytokine contents fell, on average, 34, 12, and 1.5 times[...]

Another research group reported that polarized light protects rabbits from atherosclerosis when targeted on the outside surface of ear.[88]
"Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT [polarized-light therapy] on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. [...] [T]he anti-atherosclerotic activity of PLT was superior to lovastatin: 5-min and 20-min PLT decreased the plaque area to 42.2% and 26.4%, respectively." "Importantly, 5-min PLT also exerted a remarkable efficacy in LDL reduction"

The possible mechanisms of these systemic effects hasn't been studied widely yet. One research group conducted an interesting in vitro study and suggested that the effect might be mediated by some growth factors.[89]
In the present study, increased growth factors by indirect irradiation stimulate the ERK phosphorylation in the presence of LPS. Especially, indirect 635 nm irradiation can affect MAPK activation and is correlated with the inhibition of pro-inflammatory cytokine expression.

The effects observed by Zhevago were quite opposite to the typical effects of UV radiation, which increases TNF-α, IL-6 and other pro-inflammatory cytokines. Sun-exposure is also related to increased IL-6 levels.[90,91]

In human studies, large doses of IL-6 and TNF-α have been demonstrated to suppress peripheral thyroid hormone metabolism by decreasing T3 and increasing rT3.[92,93] We could also speculate, whether lack of sufficient therapeutic light could be one cause of the "rT3 dominance" and hypothyroid symptoms. In two studies, half of the hypothyroid patients getting near-infrared treatment did not require any medication through the 9-month follow-up after the treatment period, somewhat establishing the importance of light for thyroid health.[36,37] Moreover, in a Russian study (Kovalyova 2002), the diabetic patients' total cholesterol was apparently reduced from 7.98 to 5.31 in one month, a change also seen in thyroid treatments.[32-35,94]

7. Light sources (laser, LED, light bulbs, heat lamps, sunlight, therapeutic devices)

"Many people who came to cloudy Eugene to study, and who often lived in cheap basement apartments, would develop chronic health problems within a few months. Women who had been healthy when they arrived would often develop premenstrual syndrome or arthritis or colitis during their first winter in Eugene." - Ray Peat

Laser and LED: Nowadays red light and near-infrared are studied mostly with low-level laser devices (LLLT), but many researchers also use light-emitting diodes (LED) or other light sources.

The coherence and pulsing of light (Laser vs. other sources): Although most of the researchers have been using coherent light (laser), it seems that coherence is not a requirement for the beneficial effects. This is logical considering the studies utilizing light-emitting diodes. The idea is also supported by Kellogg's reports, which were based on the usage of incandescent bulbs and arc lights.[2,95]

However, it is possible that non-coherent light sources might work best with different parameters than laser (power density, total energy, etc.). According to some data I've seen, laser might reach deep tissues better than other types of light.

Laser devices also often emit pulsed light, but it's not clear whether pulsing is very meaningful.[96]

Here are some quotes from an accomplished Estonian LLLT researcher Tiina Karu:

"[T]he stimulative action of various bands of visible light at the level of organisms and cells was known long before the advent of the laser. Also, specially designed experiments at the cellular level have provided evidence that coherent and noncoherent light with the same wavelength, intensity, and irradiation time provide the same biological effect [11-13]. Successful use of LED's in many areas of clinical practice also confirms this conclusion."
-Tiina Karu (2003)

"According to action spectra, optimal wavelengths are 820-830, 760, 680, and 620 nm. Large volumes and deeper layers of tissues can successfully irradiated by laser only (e.g. inner and middle ear diseases, injured siatic or optical nerves, deep inflammations etc.). The LED's are excellent for irradiation of surface injuries."
-Tiina Karu (year?)

Sunlight: When I was writing my Circadian Rhythms essay, I used to think about the possible explanations of the therapeutic effects of walking outdoors. Sunlight can increase the production of vitamin D and it can also suppress melatonin, but now we have a brand new mechanism that could explain why it's good to spend time outdoors.

There is an interesting correlation between latitude
and mean blood cholesterol levels.
(Grimes et al. 1996)
A review article on this subject states that in central Europe, the amount of IR-A radiation is limited to 20mW/cm2, which is actually quite a good amount compared to the power output of usual laser devices. However, the sunlight is not monochromatic, which probably increases the dose requirements.[1]

Especially in Northern countries, it seems that sunlight is correlated to better health. In some countries, the average cholesterol level of population depends largely on the season.

In the Great-Britain, for example, the changing of winter into summer has been shown to decrease cholesterol by 0.8mmol/L (30mg/dl). Also, there seems to be a significant correlation between latitude and cholesterol levels.[97-102]

"In all groups, we found a strong seasonal effect, with 5%–10% higher [total cholesterol] concentrations in winter compared to the summer."[102]

While providing a significant amount of terapeutic wavelengths, sunlight also contains some harmful UV-radiation and blue light, which might decrease the benefits a little bit.

Incandescent, halogen and heat lamps: These types of indoor lamps also provide a significant amount of red light and near-infrared. Some of these lamps have internal reflectors, so the light is targeted at one direction.

Heat lamps by Philips or Osram have quite a good spectrum with low amount of blue light, but a large amount of their power is emitted as warming IR-B radiation, and only ~12% of the power is emitted as the therapeutic wavelengths (600-1070nm). However, the heat lamps are often high power (up to 250W), so they still emit quite a significant amount of therapeutic wavelengths and might have health effects.
4100K halogen lamp seems to be good source of the
therapeutic wavelengths. Sunlight and incandescent/heat
lamps also provide significant amounts of 600-1070nm
light. (Image source: Heelspurs)

Incandescent lamps and especially halogen lights seem to emit quite a significant amount of their energy as therapeutic wavelengths (up to 35%). They are also quite cheap, which might make them a wise choice for light therapy. In my country, the price of Osram halogen lamps (30-40W) with reflector is about 5€ (~5-6 dollars).

However, there is probably no scientific research testing these kinds of lamps, so it's not proven whether they really work. The preliminary reports by Kellogg were very promising, but as I already mentioned, nowadays almost every research group uses either laser or LED, probably because they don't emit any heat and they are monochromatic or at least the bandwidth is quite narrow.

Energy saving lamps: Because of the phase-out of incandescent lamps, it will soon be increasingly difficult to buy incandescent lamps. It's somewhat sad that they are going to be replaced with compact fluorescent lamps (CFL), which emit some UV but only low amounts of protective red and near-infrared light. This is the reason why some of the researchers, such as Richard Funk and Alexander Wunsch, who also appeared in the Bulb Fiction documentary, have stated that increase in the CFL usage might be harmful to eyes.

Infrared saunas: The possible benefits of infrared saunas aren't usually based on this aforementioned mechanism, because even the shortest-wave infrared saunas don't go below 1400nm.

However, the warming effect of far-infrared might also have some beneficial effects.[103]

Infrared lamps:
In theory, a cheap incandescent or halogen
lamp with an internal reflector could
provide all the pro-metabolic effects,
yet nobody has studied the issue
(since Kellogg).
Some lamps are being sold as "infrared lamps". For example, Beurer models IL30 and IL50 seem to be quite popular models in my country. According to one source, they emit 780-1400nm wavelengths, so they might be suitable. However, no scientific data exists on these.

Therapy devices: The good aspect of lasers and LED lights is that the wavelength can be narrowly chosen (monochromatic light). For example, 830nm has proven good in many studies, and the wavelength is invisible to the eyes. Therefore it'd theoretically make a good and non-disturbing therapy device.

Here is a list of some commercial light devices, some of which have been used in LLLT/light therapy studies: AnodyneBioptronHairMax LaserCombOmniluxNoveon NaiLaserBiolightQuantum WarpSyrolight BioBeamHIRO 3.0Picasso LiteHELBO® TheraLite Laser, Super Lizer, BioPhotas CellumaTinniTool EarLaser and Mustang 2000.

The problem with commercial devices is the fact that they are expensive yet a typical halogen spot lamp (eg. Osram Classic Superstar R50 or R63) could theoretically be as good therapeutically, since the lamps also provide a great amount of the healthy wavelengths.

8. Does it really work? Trying to understand the contradictory results:

Negative results:
Even though most of the studies on LLLT have reported positive effects, there have been many studies in which LLLT didn't bring any better results than placebo.

Swedish researchers Jan Tuner and Lars Hode have published an article It's All in the Parameters: A Critical Analysis of Some Well-Known Negative Studies on Low-Level Laser Therapy, in which they explained why, in many cases, the negative results can be explained by the bad parameters used in the study.[104-106]

One typical factor is using a very low dose or power density (eg. 0.004J, 0.005J/cm2), though in some cases too high dose might also block the beneficial effect. Sometimes the problem might arise from targeting the light at the wrong place, using non-effective wavelenghts (eg. 730, 980nm), using the patient as his own control (not taking the systemic effect into account), using an inappropriate control group, or using a malfunctioning device (see below).

One year ago, I tried to discuss some of the LLLT studies with one scientist who works with the doctors who write national recommendations on medical treatments of various diseases. We looked on studies, in which they treated osteoarthritis with LLLT. Most of the results were positive, but in one study condicted in University of Ottawa didn't report a beneficial effect even though the parameters seemed generally "good" on the paper. I couldn't explain this effect to the officer, but later I understood that the light dose they gave to the patients was quite low (0.12J per joint). This is a possible explanation for the negative results of this study.[105,107]

Osmangazi University also conducted a study with negative results.[108] The parameters were similar to the aforementioned Hungarian study with great results.[73] I couldn't find a simple explanation for the negative result, but it could be related to the fact that the diameter of the laser ray was 1mm, and if such a small ray is directed at the wrong point of the joint, then there might be no effect. In one systematic review it was noted that usually the studies using greater ray had better results.[73,108,109]

"Lack of evidence": LLLT isn't still a widely known subject, and therefore many probably think there is no research on the subject. However, a PubMed search with keyword LLLT provides 4000 results, and many meta-analyses have already been published.

Here are some examples of the recent systematic reviews and/or meta-analyses:

Breast cancer-related lymphedema (2015)
Exercise performance and recovery (2015)
Oral mucositis (2014)
Pain relief (2010)
Shoulder tendinopathy (2015)
Temporomandibular disorders (2015)

However, despite the existence of many high-quality RCT trials and good meta-analyses, there is also a really huge amount of problematic research with a high risk of methodological bias. Because of some low-quality studies, some people think that all research on LLLT is bad:

"Like acupuncture, there is a huge literature (4000 on the Pubmeds) of mostly poorly done studies, some showing effect, some not. The Cochrane reviews were not supportive of laser therapy, but note the studies are uniformly lousy."

I think the quality problem is most obvious in the older studies, while nowadays the research has better quality standards. In an 2014 meta-analysis examining the effects LLLT on oral mucositis, most of the studies published after 2011 were of high quality, while older studies had more methodological issues.[72]

"Like acupuncture, better studies demonstrate decreasing effects."

This is also untrue. In a recent meta-analysis on LLLT and shoulder tendinopathy, the average PEDro score of in the studies reporting positive results was 7.5, while the score was 7.6 in the studies reporting negative results.[152]

Also, half of the studies reporting negative results were conducted using a malfunctioning laser device (Roland Pagani) that emitted less than 1% of the output power stated by the manufacturer. Therefore, it can be actually said the studies that reported positive effects were actually better quality.

When I tried to read Wikipedia article on LLLT, I found it difficult to understand the claim that LLLT "may be mildly effective, but in most cases no better than placebo in relieving [...] osteoarthritis, [...] acute and chronic neck pain", since the systematic reviews referenced in Wikipedia article were showing moderate-quality evidence of the beneficial effect.[110-112]

Meta-analyses: When reading meta-analyses on LLLT, some problems might arise. One problem is that so much research is being published nowadays, that there usually exists new data on the subject of the meta-analysis you're reading.

Also, the studies are very heterogenic because the different research groups are using different parameters (wavelength, power, power density, pulsing, dose, treatment time). In one systematic review, in one study patients received 0.3J of light energy per joint, while in another study the dose was 480J per joint (1600-fold difference). Only the latter study reported positive results. However, this doesn't mean that higher energy is better in every case. Some studies have reported a biphasic dose-response curve.[7,113]

In some meta-analyses, there might also be problems related to cherry picking or data synthesis.[114]

9. Light therapy: Animal studies

Red light and near-infrared have also been extensively studied using different animal models. Here is a short list of some research on the subject. The results have been generally very positive:

The 2011 review article is mostly focused on how light
could affect brains. Most of the research data 
is from
 animal studies.
Acute joint inflammation [115]
Bone metabolism [116]
Burns [117-120]
Cortical metabolic capacity and memory retention[121]
Diabetic retinopathy [122]
Diabetic kidney [123]
Heart failure-related inflammation [124]
Hypertension [125]
Kidney injury [126]
Laryngitis [127]
Lung injury [153]
Methanol-induced eye injury [128]
Myocardial infarction (infarct size) [129]
Palatal wound healing [130]
Peripheral nerve regeneration [131]
Reflux laryngitis [132]
Rheumatoid arthritis [133]
Skeletal muscle injury [134]
Tendon healing [135]
Traumatic brain injury [136]
Zymosan-induced arthritis [137]

Encephalomyelitis [138]
Snake venom poisoning [139]
Traumatic brain injury [140]

Hair regrowth (non-inflammatory alopecia) [141]
Myocardial infarction [142]
Recovery from surgery (hemilaminectomy) [143]
Sperm motility [144]

Embolic stroke [145]
Wound healing [146]

10. Conclusions

Nowadays, the knowledge of the physiological effects of light is mainly limited to blue light's effects on circadian rhythm, yet the importance of red and near-infrared light is also likely to be a very important factor.

Research indicates that red light and near-infrared appear to have quite a wide range of therapeutic effects. Light is very cheap to produce, so there is a possibility that in future, red light would be used as a very cost-effective treatment for various wounds, injuries and chronic diseases.

11. Join the new Facebook group!

I recently created a FB group, in which we can discuss all kinds of things related to LLLT and photobiomodulation.

Low Level Laser Therapy (LLLT) and Photobiomodulation (PBM) Discussions


[1] IUBMB Life. 2010 Aug;62(8):607-10. Multiple roles of cytochrome c oxidase in mammalian cells under action of red and IR-A radiation. Karu TI. "This article reviews the current knowledge in photobiology and photomedicine about the influence of monochromatic, quasimonochromatic, and bread-band radiation of red-to-near infrared (IR-A) part on solar spectrum upon mammalian cells and human skin. The role of cytochrome c oxidase as the photoacceptor and photosignal transducer is underlined and its photosensitivity at certain circumstances is discussed. The role of ATP as a critical signaling molecule is discussed."

[2] Ann Biomed Eng. 2012 Feb;40(2):516-33. The nuts and bolts of low-level laser (light) therapy. Chung H, Dai T, Sharma SK, Huang YY, Carroll JD, Hamblin MR. "Within the cell, there is strong evidence to suggest that LLLT acts on the mitochondria to increase adenosine triphosphate (ATP) production, modulation of reactive oxygen species (ROS), and the induction of transcription factors. Several transcription factors are regulated by changes in cellular redox state."

[3] J Photochem Photobiol B. 1995 Mar;27(3):219-23. Irradiation with He-Ne laser increases ATP level in cells cultivated in vitro. Karu T, Pyatibrat L, Kalendo G. "A monolayer of HeLa cells was irradiated with an He-Ne laser (632.8 nm[...]"

[4] Photomed Laser Surg. 2008 Oct;26(5):451-3. Intracellular ATP level increases in lymphocytes irradiated with infrared laser light of wavelength 904 nm. Benedicenti S, Pepe IM, Angiero F, Benedicenti A. "The amount of ATP in irradiated cell cultures was 10.79 +/- 0.15 microg/L (SD; n = 10), and in non-irradiated cell cultures it was 8.81 [...] This significant increase is probably due to laser irradiation; it cannot be attributed to any thermal effect"

[5] Brain Res. 2010 Jan 8;1306:100-5. Transcranial near infrared laser treatment (NILT) increases cortical adenosine-5'-triphosphate (ATP) content following embolic strokes in rabbits. Lapchak PA, De Taboada L. "Transcranial near infrared laser therapy (NILT) improves behavioral outcome following embolic strokes in embolized rabbits and clinical rating scores in acute ischemic stroke (AIS) patients [...] Five minutes following embolization, rabbits were exposed to 2 min of NILT using an 808 nm laser source, which was driven to output either continuous wave (CW), or pulsed wave modes (PW) [...]Embolization decreased cortical ATP content in ischemic cortex by 45% compared to naive rabbits, a decrease that was attenuated by CW NILT which resulted in a 41% increase in cortical ATP content compared to the sham embolized group (p>0.05)."

[6J Alzheimers Dis. 2011;23(3):521-35. Transcranial laser therapy attenuates amyloid-β peptide neuropathology in amyloid-β protein precursor transgenic mice. De Taboada L, Yu J, El-Amouri S, Gattoni-Celli S, Richieri S, McCarthy T, Streeter J, Kindy MS. "TLT showed an increase in ATP levels, mitochondrial function, and c-fos suggesting an overall improvement in neurological function."

[7a] Dose Response. 2009 Sep 1;7(4):358-83. Biphasic dose response in low level light therapy. Huang YY, Chen AC, Carroll JD, Hamblin MR. "The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers." 

[7b] Dose Response. 2011;9(4):602-18. Biphasic dose response in low level light therapy - an update. Huang YY, Sharma SK, Carroll J, Hamblin MR.

[8] Mol Cell Biochem. 1997 Sep;174(1-2):189-92. Nitric oxide inhibition of cytochrome oxidase and mitochondrial respiration: implications for inflammatory, neurodegenerative and ischaemic pathologies. Brown GC. "Nitric oxide (NO) at high levels is cytotoxic, and may be involved in a range of inflammatory, neurodegenerative, and cardiovascular/ischaemic pathologies. The mechanism of NO-induced cytotoxicity is unclear. Recently we and others have found that low (nanomolar) levels of NO reversibly inhibit mitochondrial respiration by binding to the oxygen binding site of cytochrome oxidase in competition with oxygen."

"These results suggest that any cell producing high levels of NO will inhibit its own respiration and that of surrounding cells, and make the respiration rate sensitive to the oxygen level. This inhibition of energy metabolism may contribute to cytotoxicity or cytostasis in some pathologies."

[9] Biochim Biophys Acta. 2001 Mar 1;1504(1):46-57. Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Brown GC. "Cultured cells expressing the inducible isoform of NOS (iNOS) can acutely and reversibly inhibit their own cellular respiration and that of co-incubated cells due to NO inhibition of cytochrome oxidase, but after longer-term incubation result in irreversible inhibition of cellular respiration due to NO or its derivatives."

[10] Nature. 2006 Oct 26;443(7114):901-3. Cell biology: power games. Lane N.

[11] Nick Lane: Are mitochondria the alpha and omega of retinal disease? (2006) "In his Nobel speech of 1931, the great German biochemist Otto Warburg described his insights into the molecular mechanisms of cellular respiration. Warburg had made use of an extraordinary titbit of knowledge, which anyone placing their head in a car’s exhaust fumes might care to reflect on in their final moments: carbon monoxide (CO) doesn’t cause irreversible suffocation – it doesn’t permanently block cell respiration.A flash of light can dissociate CO from the respiratory enzymes and kick-start cellular respiration all over again. But don’t try it at home. Warburg realised that there must be an interaction between light and the (then) unknown enzyme responsible for consuming oxygen in cellular respiration, now labelled cytochrome oxidase."

"Karu and others have shown that NO donors can reverse the effects of NIR phototherapy" [Karu et al. 2005]

[12] Lasers Surg Med. 2012 Mar;44(3):218-26. Low-level laser therapy for closed-head traumatic brain injury in mice: effect of different wavelengths. Wu Q, Xuan W, Ando T, Xu T, Huang L, Huang YY, Dai T, Dhital S, Sharma SK, Whalen MJ, Hamblin MR. "The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT."

[13] Photomed Laser Surg. 2013 Apr;31(4):163-8. Penetration of laser light at 808 and 980 nm in bovine tissue samples. Hudson DE, Hudson DO, Wininger JM, Richardson BD. "Laser light at 808 and 980 nm (1 W/cm(2)) was projected through bovine tissue samples [...] For 808 nm, 1 mW/cm(2) was achieved at 3.4 cm, but for 980 nm, 1 mW/cm(2) was achieved at only 2.2 cm depth of tissue." [See also: Lars Hode: Penetration of light into living tissue]

[14] PLoS One. 2012;7(10):e47460. Transcranial red and near infrared light transmission in a cadaveric model. Jagdeo JR, Adams LE, Brody NI, Siegel DM. "Our results demonstrate that near infrared measurably penetrates soft tissue, bone and brain parenchyma in the formalin preserved cadaveric model, in comparison to negligible red light transmission in the same conditions."

[15] J Photochem Photobiol B. 2011 Feb 7;102(2):156-60. Increased mobility and stem-cell proliferation rate in Dugesia tigrina induced by 880nm light emitting diode. Wu HP, Persinger MA. "The present study indicated that neoblast proliferation [18] can also be reproduced by using non-coherent light NIR (880 nm) sources with power-densities about a 1000-fold less than conventional low-power lasers. This supports the growing number of studies that shows LEDs have photobiostimulation effects comparable to lasers [19–21]. Contemporary photobiostimulation studies using low-power lasers or LEDs have demonstrated numerous effects associated with increased cellular proliferation, maturation, and activity [2,4,10]. These effects have been most consistently observed for fibroblast and osteoblast cultures [4,22] and have been attributed to an increase in mitochondrial activity following light stimulation in the near infrared range [9,10,23]."

"These findings suggest that non-coherent light sources with power-densities about 1000 times lower than contemporary low-power laser settings remain effective in generating photobiostimulation effects and warrants further investigation on stem-cell proliferation induced by near-infrared light emitting diodes."

[16] Br J Ophthalmol. 2006 Feb;90(2):237-41. A hypothesis to suggest that light is a risk factor in glaucoma and the mitochondrial optic neuropathies. Osborne NN, Lascaratos G, Bron AJ, Chidlow G, Wood JP.

[17] Br Med J. 1895 Dec 7;2(1823):1412-4. The Red Light Treatment of Small-Pox. Finsen NR.

[18] John H. Kellogg: Light therapeutics; a practical manual of phototherapy for the student and the practitioner, with special reference to the incandescent electric-light bath (1910)

[19] Bulletin of Experimental Biology and Medicine April 1987, Volume 103, Issue 4, pp 548-550 Stimulation of post-traumatic regeneration of skeletal muscles of old rats after x-ray irradiation N. V. Bulyakova, M. F. Popova 

[20] Sov Med. 1990;(3):12-5. [Helium-neon laser therapy in the combined treatment of unstable stenocardia]. [Article in Russian] Korochkin IM, Kapustina GM, Babenko EV, Zhuravleva NIu. "He-Ne laser therapy included in complex of therapeutic methods for patients with unstable angina pectoris is a highly effective treatment modality; it helps essentially reduce the risk of acute myocardial infarction in these patients." [633nm laser]

[21] Vopr Kurortol Fizioter Lech Fiz Kult. 1996 Mar-Apr;(2):3-5. [The laser therapy of patients with hypertension in combination with coronary insufficiency]. [Article in Russian] Kniazeva TA, Badtieva VA, Zubkova SM. "Hypertensive patients with coronary insufficiency have received infrared (lambda = 0.85 microns) laser radiation to the skin. The treatment is shown to have antianginal, antihypertensive effects, to improve cardiac performance, myocardial contractility, to increase myocardial, coronary and aerobic reserves. This clinicofunctional efficacy is accompanied by positive shifts in lipid metabolism, lipid peroxidation activity, antioxidant defense, hemocoagulation and microcirculation."

[22] Vopr Kurortol Fizioter Lech Fiz Kult. 2002 Jul-Aug;(4):9-11. [Use of infrared laser therapy in patients with ischemic heart disease associated with diabetes mellitus type 2 in health resort]. [Article in Russian] Zin'kovskaia TM, Zavrazhnykh LA, Golubev AD. "Infrared laser therapy (300 Hz) combined with balneotherapy and patients' education is more effective than standard sanatorium rehabilitation in patients with ischemic heart disease associated with diabetes mellitus type 2. 81.8% patients showed good response manifesting in less frequent anginal attacks, episodes of pain and painless ischemia and lower doses of antianginal drugs. Systolic and diastolic arterial pressure lowered by 18 and 10 mm Hg on the average, respectively."

---(the beginning of the removed part)---

[23] Indian J Dermatol. 2012 Mar;57(2):128-30. Comparison of Red and Infrared Low-level Laser Therapy in the Treatment of Acne Vulgaris. Aziz-Jalali MH, Tabaie SM, Djavid GE. "Ten weeks after treatment acne lesion were significantly decreased in the side treated by 630 nm LLLT (27.7±12.7 to 6.3±1.9) [...], but this decrease was not significant in the site treated by 890 nm LLLT (26.9±12.4 to 22.2±8.5) (P>0.05)."

[24] Br J Sports Med. 2006 Jan;40(1):76-80; discussion 76-80. A randomised, placebo controlled trial of low level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous prostaglandin E2 concentrations. Bjordal JM, Lopes-Martins RA, Iversen VV. "Infrared (904 nm wavelength) LLLT (5.4 J per point, power density 20 mW/cm2) and placebo LLLT (0 J) were administered to both Achilles tendons in random blinded order.

[...] Prostaglandin E2 concentrations were significantly reduced 75, 90, and 105 minutes after active LLLT compared with concentrations before treatment (p = 0.026) and after placebo LLLT (p = 0.009). Pressure pain threshold had increased significantly (p = 0.012) after active LLLT compared with placebo"

[25] Photomed Laser Surg. 2010 Feb;28(1):3-16. Low level laser treatment of tendinopathy: a systematic review with meta-analysis. Tumilty S, Munn J, McDonough S, Hurley DA, Basford JR, Baxter GD. "This study found conflicting evidence as to the effectiveness of LLLT in the treatment of tendinopathy. Ten high quality and two low quality RCTs with positive outcomes, compared with ten high quality and three low quality RCTs with negative outcomes, were found. However, there is strong evidence from the 12 positive studies of a correlation between use of recommended dosages and a positive outcome."

[26] Babushkina et al: Results Of 10-Year Use Of Low Intensity Laser Therapy And Conventional Treatment Of Patients With Stenocardia "During the observation period there were 54 deaths: 8,9% in the main and 18,7% in the control group."

[27] J Clin Diagn Res. 2014 Feb;8(2):218-21. Efficacy of low-level laser therapy in treatment of recurrent aphthous ulcers - a sham controlled, split mouth follow up study. Aggarwal H, Singh MP, Nahar P, Mathur H, Gv S. "Complete resolution of the ulcers in the active group was 3.05 ± 1.10 days as compared to 8.90 ± 2.45 days in the sham control group. Immediately, post the LLLT application, complete pain relief was observed in 28 of the 30 patients of the active group." [810nm laser, Picasso Lite 0.5W]

[28] Oral Surg Oral Med Oral Pathol Oral Radiol. 2014 May;117(5):590-4. Recurrent aphthous stomatitis and pain management with low-level laser therapy: a randomized controlled trial. Albrektson M, Hedström L, Bergh H. "A randomized single-blinded placebo-controlled trial was conducted with LLLT (wavelength, 809 nm; power, 60 mW; pulse frequency, 1800 Hz; duration, 80 seconds per treatment; dose, 6.3 J/cm(2)) in 40 patients with RAS. The intervention group was treated with LLLT on 3 occasions, with a 1-day interval. The control group was treated similarly, without any laser power. 

[...] VAS rating decreased (day 0 until day 2) from 84.7 to 31.5 (LLLT) and from 81.7 to 76.1 (placebo) (P < .0001). LLLT also relieved the difficulty of drinking, eating, and brushing teeth."

[29] Lasers Surg Med. 2009 Dec;41(10):799-809. Low-level laser therapy as a non-invasive approach for body contouring: a randomized, controlled study. Jackson RF, Dedo DD, Roche GC, Turok DI, Maloney RJ. "Participants in the treatment group demonstrated an overall reduction in total circumference across all three sites of -3.51 in. (P < 0.001) compared with control subjects who revealed a -0.684 reduction"

[30] Lasers Surg Med. 2013 Jan;45(1):1-7. Independent evaluation of low-level laser therapy at 635 nm for non-invasive body contouring of the waist, hips, and thighs. McRae E, Boris J. "These data further validate the clinical efficacy and safety of LLLT at 635 nm."

[31] Ger Med Sci. 2006 Jul 11;4:Doc05. Influence of water-filtered infrared-A (wIRA) on reduction of local fat and body weight by physical exercise. Möckel F, Hoffmann G, Obermüller R, Drobnik W, Schmitz G.

[32] Jackson et al: Reduction in Cholesterol and Triglyceride Serum Levels Following Low-Level Laser Irradiation: A Noncontrolled, Nonrandomized Pilot Study (2010) [pdf"Participants assigned to the test group were treated with a 5 independent diode laser scanner device, emitting 635 nm (red) laser light, with each diode generating 17 mW output" "The procedure administration phase extended over 2 consecutive weeks, with each participant receiving 6 total procedure administrations" [LDL 103.68 -> 96.53]

[33] Maloney et al: The reduction in cholesterol and triglyceride serum levels following low-level laser irradiation: a non-controlled, non-randomized pilot study (2009) [news


[35Ambulatory Application of Combined Laser Therapy in Patients with Diabetes Mellitus and Dyslipidemia. Laser Partner, 17.5.2002 T.V. Kovalyova

[36] Lasers Surg Med. 2010 Aug;42(6):589-96. Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study. Höfling DB, Chavantes MC, Juliano AG, Cerri GG, Romão R, Yoshimura EM, Chammas MC. "We noted all patients' reduced LT4 dosage needs, including 7 (47%) who did not require any LT4 through the 9-month follow-up. The LT4 dosage used pre-LLLT (96 +/- 22 microg/day) decreased in the 9th month of follow-up (38 +/- 23 microg/day; P < 0.0001)."

[37] Lasers Med Sci. 2013 May;28(3):743-53. Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial. Höfling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC. "The results showed a significant difference in the mean levothyroxine dose required to treat the hypothyroidism between the L group (38.59 ± 20.22 μg/day) and the P group (106.88 [...] These findings suggest that LLLT was effective at improving thyroid function, promoting reduced TPOAb-mediated autoimmunity and increasing thyroid echogenicity in patients with CAT hypothyroidism."

[38] CAOL 2003, 16-20 September 2003, Alushta, Crimea, Ukraine. Effectiveness of using laserotherapy in the treatment of autoimmune thyreoiditis. I. Gopkalova, V. Dubovik, V. Danilevsky "According to ultra-sonic examinations and thermography data decreasing of sizes of gland and centre of lymphoid infiltration was found practially with all patients. [890nm laser]

[39] ДУБОВИК ВІКТОР МИКОЛАЙОВИЧ: ПІСЛЯОПЕРАЦІЙНА РЕАБІЛІТАЦІЯ ХВОРИХ НА АУТОІМУННИЙ ТИРЕОЇДИТ З ВИКОРИСТАННЯМ НИЗЬКОІНТЕНСИВНОГО ЛАЗЕРНОГО ВИПРОМІНЮВАННЯ [Dubovik V. The postoperative rehabilitation of the autoimmune thyroiditis patients with the use of low­intensive laser radiation.] "The dissertation on competition of scientific degree of the medical sciences candidate on speciality 14.01.14" "At performance of the clinical part of work 60 patients with the hypertrophic form of the autoimmune thyroiditis before operation, during two years of the postoperative term and after application of the laser therapy were surveyed. The operation has negative influences on disease: in the remote postoperative term the depression of the thyroid function due to the activization of autoimmune process is observed. The realization of laser treatment after 2 years after operation has allowed to improve function of the thyroid gland, to reduce its volume, to lower indexes of antithyroid autoantibodies and to normalize the cellular parameters of immunodefense. Such changes are found out in one month after end of the laser therapy, reach the maximal exhibiting in three months, and in six months the beginning of inhibition of immunecorrective action is observed. The realization of repeated sessions of the laser therapy allows achieving the clinical- immunological remission of disease and is recommended in six months after the previous course." ["Doses of thyroid hormones in such treatment at (50 - 75)% lower than those commonly used." (Translated from the original language.)]

[40] Proc. SPIE 4166, Laser Florence '99: A Window on the Laser Medicine World, 319 (June 28, 2000); doi:10.1117/12.389505 Use of the immunomodulative influence of low-level laser radiation in the treatment of an autoimmune thyroiditis V. A. Mikhailov ; O. A. Alexandrova ; I. N. Denisov ["Mikhailov et al13 performed a study on patients with Hashimoto’s thyroiditis. Forty two patients were were treated with 10 applications of 2.4 J/cm2 via an 890nm laser and targeted the thymus projection zone, vascular junction, and the thyroid gland. A control group of similar size was given L-thyroxin, 100 mg/day. All laser-treated patients experienced a decrease in the feeling of squeezing in the area around the thyroid and a decrease in facial edema. The thyroid gland became softer on palpation and smaller on ultrasound examination. There was also a decreased number of patients that caught winter colds in the laser group. The immunoregulatory index (Th/Ts) normalized from 7.5 to 4.2%. The laser effects were still noticeable in 78% of the laser patients four months after treatment. This index was only slightly changed in the control group." src: Kneebone 2010]

[41] Vopr Kurortol Fizioter Lech Fiz Kult. 1998 May-Jun;(3):15-6. [The treatment of autoimmune thyroiditis using low-intensity laser radiation]. [Article in Russian] Mikhaĭlov VA, Denisov IN, Aleksandrova OIu, Poliakov AV.

[42] Вера Александровна Кривова: Неинвазивная гемолазеротерапия в системе реабилитации больных аутоиммунным тиреодитом (Диссертация, 2010) [A Russian dissertation]

[43] Александр Вацлавич Поляков: Применение низкоинтенсивного лазерного излучения в комплексном лечении хронического аутоиммунного тиреоидита (Диссертация, 1997) [A Russian dissertation]

[44] Neuroscience. 2013 Jan 29;230:13-23. Transcranial infrared laser stimulation produces beneficial cognitive and emotional effects in humans. Barrett DW, Gonzalez-Lima F. "This treatment consisted of applying light of a specific wavelength (1064 nm) that intersects with the absorption spectrum of cytochrome oxidase, using a laser diode supplied by Cell Gen Therapeutics, LLC (Model CG-5000 laser, HD Laser Center, Dallas, TX, USA)" "The PANAS showed that while participants generally reported more positive affective states than negative, overall affect improved significantly in the treated group due to more sustained positive emotional states as compared to the placebo control group."

[45] Behav Brain Funct. 2009 Dec 8;5:46. Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a pilot study of 10 patients with major depression and anxiety. Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR. "The treatment consisted of applying PBM in the form of a light emitting diode (LED) array (Marubeni America Corp, Santa Clara, CA) with a peak wavelength of 810 nm with a full width half maximum of 40 nm, delivering an irradiance of 250 mW/cm2 when applied at 4 mm from the skin. The treatment consisted of exposure to the light for 4 minutes (total delivered fluence per site of 60 J/cm2) at each of 2 sites on the forehead that correspond to the 10-20 EEG sites, F3, and F4. Based on a penetration of 3.7% of the light to the dura, we calculated that 2.1 J/cm2 was delivered to each of the treated areas of the brain."

"Mean percentage reductions in HAM-D scores were 54.3% ± 26.1 at 2 weeks post-treatment and 23.0% ± 27.1 at 4-weeks post-treatment." [Clinical Psychiatry News]

[46] Biol Psychiatry. 1999 Jul 15;46(2):239-46. Prophylactic treatment of seasonal affective disorder (SAD) by using light visors: bright white or infrared light? Meesters Y, Beersma DG, Bouhuys AL, van den Hoofdakker RH. "Infrared light is just as effective as bright white light. Both are more effective than the control condition."

[47] Arch Gynecol Obstet. 2012 Oct;286(4):947-52. Skin adhesive low-level light therapy for dysmenorrhoea: a randomized, double-blind, placebo-controlled, pilot trial. Shin YI, Kim NG, Park KJ, Kim DW, Hong GY, Shin BC. "The pain reduction rate was 83 % in the active LLLT group, whereas there was only a slight and temporary reduction in pain in the placebo LLLT group."

[48] Rheumatol Int. 2002 Sep;22(5):188-93. Effects of low power laser and low dose amitriptyline therapy on clinical symptoms and quality of life in fibromyalgia: a single-blind, placebo-controlled trial. Gür A, Karakoc M, Nas K, Cevik R, Sarac J, Ataoglu S. "Two physical therapist investigators used standard technique with a Ga-As laser (20 W maximum output per pulse, 904 nm, 200 ns maximum pulse duration, 2.8 kHz pulse frequency, 11.2 mW average power, and 1 cm2 surface (class IIIb Laser Product, Frank Line IR 30, Fysiomed, Belgium)."

"Significant improvements were indicated in all clinical parameters in the laser group (P=0.001) [...] A significant difference was observed in clinical parameters such as pain intensity (P=0.000) and fatigue (P=0.000) in favor of the laser group over the other groups"

[49] Lasers Med Sci. 2002;17(1):57-61. Efficacy of low power laser therapy in fibromyalgia: a single-blind, placebo-controlled trial. Gür A, Karakoç M, Nas K, Cevik R, Saraç J, Demir E. "Our study suggests that laser therapy is effective on pain, muscle spasm, morning stiffness, and total tender point number in fibromyalgia and suggests that this therapy method is a safe and effective way of treatment in the cases with fibromyalgia."

[50] Lasers Med Sci. 2014 Nov;29(6):1815-9. Low-level laser therapy to treat fibromyalgia. Ruaro JA, Fréz AR, Ruaro MB, Nicolau RA. "The LLLT group was treated with a GaAlAs laser (670 nm, 4 J/cm(2) on 18 tender points) three times a week over 4 weeks. [...] After LLLT or sham treatment, the number of tender points was significantly reduced in both groups [...] However, all other fibromyalgia symptoms showed significant improvements after LLLT compared to placebo"

[51] Diabetes Technol Ther. 2012 Sep;14(9):799-803. Low-level lasers as an adjunct in periodontal therapy in patients with diabetes mellitus. Obradović R, Kesić L, Mihailović D, Jovanović G, Antić S, Brkić Z. "A split-mouth design was applied; on the right side of jaws GaAlAs LLLT (670 nm, 5 mW, 14 min/day) (model Mils 94; Optica Laser, Sofia, Bulgaria) was applied for five consecutive days." 

"It can be concluded that LLLT as an adjunct in periodontal therapy reduces gingival inflammation in patients with DM and periodontitis."

[52] Eur J Clin Microbiol Infect Dis. 2012 Aug;31(8):1911-5. Chronic gingivitis: the prevalence of periodontopathogens and therapy efficiency. Igic M, Kesic L, Lekovic V, Apostolovic M, Mihailovic D, Kostadinovic L, Milasin J. "Group A was subjected to basic gingivitis therapy, and group B underwent basic therapy along with adjunctive LLLT. A statistically significant difference between the values of plaque-index (PI) and sulcus bleeding index (SBI) before and after therapy was confirmed in both groups [...], though more pronounced in group B"

[53] Lasers Med Sci. 2013 Jan;28(1):19-24. A histological evaluation of a low-level laser therapy as an adjunct to periodontal therapy in patients with diabetes mellitus. Obradović R, Kesić L, Mihailović D, Antić S, Jovanović G, Petrović A, Peševska S. "All patients received oral hygiene instructions and full-mouth conservative periodontal treatment. In groups 3 and 6, LLLT was applied (670 nm, 5 mW, 2 J/cm(2), 16 min, 5 days). Histologic findings of gingival tissue treated with LLLT showed expressed healing, as is evident by the absence of inflammatory cells. Tissue edema could not be seen, and the number of blood vessels was reduced. In the gingival lamina, propria pronounced collagenization and homogenization were present. It can be concluded that LLLT has shown efficacy in the treatment of periodontitis in diabetics."

[54] Photomed Laser Surg. 2012 Mar;30(3):160-6. Effect of adjunctive low level laser therapy (LLLT) on nonsurgical treatment of chronic periodontitis. Makhlouf M, Dahaba MM, Tunér J, Eissa SA, Harhash TA. "SRP combined with LLLT [830nm] improved radiographic bone density and short-term PPD reduction in patients with chronic periodontitis," [SRP = scaling and root planing]

[55] Clin Drug Investig. 2009;29(5):283-92. HairMax LaserComb laser phototherapy device in the treatment of male androgenetic alopecia: A randomized, double-blind, sham device-controlled, multicentre trial. Leavitt M, Charles G, Heyman E, Michaels D. "The HairMax LaserComb is a hand-held Class 3R lower level laser therapy device that contains a single laser module that emulates 9 beams at a wavelength of 655 nm (+/-5%). The device uses a technique of parting the user's hair by combs that are attached to the device."

"Of the 110 patients who completed the study, subjects in the HairMax LaserComb treatment group exhibited a significantly greater increase in mean terminal hair density than subjects in the sham device group (p < 0.0001)."

[56] Lasers Surg Med. 2013 Oct;45(8):487-95. The growth of human scalp hair mediated by visible red light laser and LED sources in males. Lanzafame RJ, Blanche RR, Bodian AB, Chiacchierini RP, Fernandez-Obregon A, Kazmirek ER. "The active group received a "TOPHAT655" unit containing 21, 5 mW lasers (655 ± 5 nm), and 30 LEDS (655 ± 20 nm), in a bicycle-helmet like apparatus. [...] 

Baseline hair counts were 162.7 ± 95.9 (N = 22) in placebo and 142.0 ± 73.0 (N = 22) and active groups respectively (P = 0.426). Post Treatment hair counts were 162.4 ± 62.5 (N = 19) and 228.7 ± 102.8 (N = 22), respectively (P = 0.0161)" [pics!]

[57] Lasers Surg Med. 2014 Oct;46(8):601-7. The growth of human scalp hair in females using visible red light laser and LED sources. Lanzafame RJ, Blanche RR, Chiacchierini RP, Kazmirek ER, Sklar JA. "The percent hair increase over the duration of the study was 11.05 ± 48.30 (N = 18) for the sham group and 48.07 ± 17.61 (N = 24) for the active group" [655nm laser, 655nm LED]

[58] Am J Clin Dermatol. 2014 Apr;15(2):115-27. Efficacy and safety of a low-level laser device in the treatment of male and female pattern hair loss: a multicenter, randomized, sham device-controlled, double-blind study. Jimenez JJ, Wikramanayake TC, Bergfeld W, Hordinsky M, Hickman JG, Hamblin MR, Schachner LA. "Our results suggest that low-level laser treatment may be an effective option to treat pattern hair loss in both men and women."

[59] Int J Trichology. 2014 Apr;6(2):45-9. doi: 10.4103/0974-7753.138584. Use of low-level laser therapy as monotherapy or concomitant therapy for male and female androgenetic alopecia. Munck A, Gavazzoni MF, Trüeb RM. "Of 32 patients (21 female, 11 male), 8 showed significant, 20 moderate, and 4 no improvement. Improvement was seen both with monotherapy and with concomitant therapy."

[60] Dermatol Surg. 2013 Aug;39(8):1177-83. Low-level light therapy for androgenetic alopecia: a 24-week, randomized, double-blind, sham device-controlled multicenter trial. Kim H, Choi JW, Kim JY, Shin JW, Lee SJ, Huh CH. "After 24 weeks of treatment, the LLLT group showed significantly greater hair density than the sham device group. Mean hair diameter improved statistically significantly more in the LLLT group than in the sham device group." [630+660nm LED & 650nm laser]

[61] SJ Invest Dermatol. 1999 Aug;113(2):221-3. Low-intensity laser therapy is an effective treatment for recurrent herpes simplex infection. Results from a randomized double-blind placebo-controlled study. Schindl A, Neumann R. "In this study we evaluated the influence of low-intensity laser therapy (wavelength 690 nm, intensity: 80 mW per cm2, dose: 48 J per cm2) in 50 patients with recurrent perioral herpes simplex infection (at least once per month for more than 6 mo) in a randomized, double-blind placebo-controlled trial design. [...]

The median recurrence-free interval in the laser-treated group was 37.5 wk (range: 2-52 wk) and in the placebo group 3 wk (range: 1-20 wk)."

[62] Photomed Laser Surg. 2012 Jan;30(1):37-40. The effect of 670-nm low laser therapy on herpes simplex type 1. Muñoz Sanchez PJ, Capote Femenías JL, Díaz Tejeda A, Tunér J. "In the study group, the patients were offered treatment with a Lasermed 670 DL, a 670-nm diode laser [...] The control group was offered indicated treatment with antivirals (acyclovir cream and tablets) and other palliative therapies, such as an anesthetic cream and advice to avoid spicy and hot food."

"After day 7 no patients in the laser group had any visible signs of HSV-1 blisters, whereas in the control group 77 patients still had vesicles, 29 had crust formation, and 10 had secondary infections."

[63] Oncol Nurs Forum. 2013 Jul;40(4):383-93. A pilot randomized trial evaluating low-level laser therapy as an alternative treatment to manual lymphatic drainage for breast cancer-related lymphedema. Ridner SH, Poage-Hooper E, Kanar C, Doersam JK, Bond SM, Dietrich MS. "Treatment was administered using a RianCorp LTU 904, FDA-approved, Class 1 laser." "LLLT with bandaging may offer a time-saving therapeutic option to conventional MLD."

[64] J Surg Res. 2011 Jan;165(1):82-90. Treatment of post-mastectomy lymphedema with laser therapy: double blind placebo control randomized study. Ahmed Omar MT, Abd-El-Gayed Ebid A, El Morsy AM. [904nm]

[65] Photomed Laser Surg. 2008 Jun;26(3):241-5. Low-level laser therapy improves vision in patients with age-related macular degeneration. Ivandic BT, Ivandic T. "LLLT significantly improved visual acuity (p < 0.00001 versus baseline) in 162/182 (95%) of eyes with cataracts and 142/146 (97%) of eyes without cataracts. The prevalence of metamorphopsia, scotoma, and dyschromatopsia was reduced. In patients with wet AMD, edema and bleeding improved. The improved vision was maintained for 3-36 mo after treatment. Visual acuity in the control group remained unchanged. No adverse effects were observed in those undergoing therapy."

[66] Vopr Kurortol Fizioter Lech Fiz Kult. 2009 Sep-Oct;(5):37-9. [Effect of infrared low-intensity laser therapy on orbital blood circulation in children with progressive short sightedness]. [Article in Russian] Shurygina IP, Khadzhieva MR. "Indirect action of LIIRR on the orbital region promoted stabilization of short-handedness in 78.8% of the treated patients." [Irina Petrovna Shurygina: Влияние инфракрасной низкоинтенсивной лазерной терапии на состояние орбитального кровотока у детей с прогрессирующей близорукостью.]

[67] Pain. 2006 Sep;124(1-2):201-10. Epub 2006 Jun 27. The effect of 300 mW, 830 nm laser on chronic neck pain: a double-blind, randomized, placebo-controlled study. Chow RT, Heller GZ, Barnsley L. "The mean VAS pain scores improved by 2.7 in the treated group and worsened by 0.3 in the control group" [In Law et al. meta-analysis, this paper was given PEDro score of 10/10, indicating good methodological quality] 

[68] Lancet. 2009 Dec 5;374(9705):1897-908. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. "We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients with chronic neck pain."

[69] J Pediatr Hematol Oncol. 2009 Jan;31(1):33-7. Low-level infrared laser therapy in chemotherapy-induced oral mucositis: a randomized placebo-controlled trial in children. Kuhn A, Porto FA, Miraglia P, Brunetto AL. "On day 7 after OM diagnosis, 1/9 of patients remained with lesions in laser group and 9/12 of patients in the placebo-control group (P=0.029)."

[70] Radiother Oncol. 2012 Sep;104(3):349-54. Low level laser therapy for concurrent chemoradiotherapy induced oral mucositis in head and neck cancer patients - a triple blinded randomized controlled trial. Gautam AP, Fernandes DJ, Vidyasagar MS, Maiya AG, Vadhiraja BM. "In our study patients in laser group experienced moderate pain, whereas in placebo progressed toward the severe pain during the last 4 weeks of CCRT." [632nm laser]

[71] Radiother Oncol. 2013 Nov;109(2):297-302. Phase III trial of low-level laser therapy to prevent oral mucositis in head and neck cancer patients treated with concurrent chemoradiation. Antunes HS, Herchenhorn D, Small IA, Araújo CM, Viégas CM, Cabral E, Rampini MP, Rodrigues PC, Silva TG, Ferreira EM, Dias FL, Ferreira CG. "A diode InGaAlP (660nm-100mW-1J-4J/cm(2)) was used. [...] A six-fold decrease in the incidence of grades 3-4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%)."

[72] PLoS One. 2014 Sep 8;9(9):e107418. Effect of prophylactic low level laser therapy on oral mucositis: a systematic review and meta-analysis. Oberoi S, Zamperlini-Netto G, Beyene J, Treister NS, Sung L.

[73] Photomed Laser Surg. 2009 Aug;27(4):577-84. The effect of low-level laser in knee osteoarthritis: a double-blind, randomized, placebo-controlled trial. Hegedus B, Viharos L, Gervain M, Gálfi M. "Our results show that LLLT reduces pain in KOA and improves microcirculation in the irradiated area."

[74] Lasers Surg Med. 2003;33(5):330-8. Efficacy of different therapy regimes of low-power laser in painful osteoarthritis of the knee: a double-blind and randomized-controlled trial. Gur A, Cosut A, Sarac AJ, Cevik R, Nas K, Uyar A. "Our study demonstrated that applications of LPLT in different dose and duration have not affected results and both therapy regimes were a safe and effective method in treatment of knee OA." [904nm laser]

[75] J Am Geriatr Soc. 1992 Jan;40(1):23-6. Improvement of pain and disability in elderly patients with degenerative osteoarthritis of the knee treated with narrow-band light therapy. Stelian J, Gil I, Habot B, Rosenthal M, Abramovici I, Kutok N, Khahil A. "Fifty patients with degenerative osteoarthritis of both knees were randomly assigned to three treatment groups: red (15 patients), infrared (18 patients), and placebo (17 patients). Infrared and placebo emitters were double-blinded."

"Pain reduction in the red and infrared groups after the treatment was more than 50% in all scoring methods (P less than 0.05). There was no significant pain improvement in the placebo group. We observed significant functional improvement in red- and infrared-treated groups (p less than 0.05), but not in the placebo group." [probably 660nm and 940nm light, I'm not sure whether narrow-band is a different thing than LED... I guess the product they used was Syrolight BioBeam 940]

[76] Lasers Med Sci. 2014 Mar;29(2):749-55. Effect of low-level laser therapy in patients with chronic knee osteoarthritis: a single-blinded randomized clinical study. Alghadir A, Omar MT, Al-Askar AB, Al-Muteri NK. "The LLLT device used was a Ga-As diode laser with a power output of 50 mW, a wavelength of 850 nm, and a diameter beam of 1 mm. Eight points were irradiated and received dosage of 6 J/point for 60 s, with a total dosage of 48 J/cm(2) in each session. The placebo group was identical but treated without emission of energy. [...] Active laser group showed significant differences in pain intensity at rest and movement, knee function, and ambulation duration when compared with the placebo group"

[77] J Cosmet Dermatol. 2007 Sep;6(3):189-94. The use of light-emitting diode therapy in the treatment of photoaged skin. Baez F, Reilly LR. "Thirteen subjects with wrinkles or fine lines in the periorbital and nasolabial region and those presenting Glogau scale photodamage grade II-III received nine 20-min duration light treatments using the Omnilux LED system. The treatments combined wavelengths of 633 and 830 nm at fluences of 126 and 66 J/cm(2), respectively. Sun-damage reduction was assessed at 6, 9, and 12 weeks by clinical photography and patient satisfaction scores. [...]

The majority of subjects displayed "moderate" (50%) or "slight" (25%) response to treatment at investigator assessment. Treatment of the periorbital region was reported more effective than the nasolabial region. At 12-week follow-up, 91% of subjects reported improved skin tone, and 82% reported enhanced smoothness of skin in the treatment area."

[78] J Cosmet Laser Ther. 2005 Dec;7(3-4):196-200. A study to determine the efficacy of combination LED light therapy (633 nm and 830 nm) in facial skin rejuvenation. Russell BA, Kellett N, Reilly LR. "52% of subjects showed a 25%-50% improvement in photoaging scores by week 12; 81% of subjects reported a significant improvement in periorbital wrinkles on completion of follow-up."

[79] Photodermatol Photoimmunol Photomed. 2001 Feb;17(1):32-8. Effects of phototherapy on pressure ulcer healing in elderly patients after a falling trauma. A prospective, randomized, controlled study. Schubert V. "Both groups were given the same standard ulcer therapy. One group was also given phototherapy with pulsed monochromatic infrared (956 nm) and red (637 nm) light. [...] Patients treated with pulsed monochromatic light had a 49% higher ulcer healing rate, and a shorter time to 50% and to 90% ulcer closure compared with controls. Their mean ulcer area was reduced to 10% after 5 weeks compared with 9 weeks for the controls." [Biolight(TM) International AB, Sweden]

[80] Vojnosanit Pregl. 2008 Dec;65(12):906-12. The effects of polarized light therapy in pressure ulcer healing. Durović A, Marić D, Brdareski Z, Jevtić M, Durdević S. "There were significant differences between the groups at the end of the treatment regarding the surface of pressure ulcer (E: 10.80 +/- 19.18; C: 22,97 +/- 25,47; p = 0.0005)" [Bioptron 2]

[81] J Cosmet Laser Ther. 2004 Jun;6(2):96-102. Defocused diode laser therapy (830 nm) in the treatment of unresponsive skin ulcers: a preliminary trial. Kubota J. "Defocused 830 nm diode laser therapy was well tolerated, and was very effective in the treatment of this small number of compromised skin ulcers of different aetiologies and in a large range of patient ages."

[82] J Athl Train. 2012 Nov-Dec;47(6):673-8. Red light and the sleep quality and endurance performance of Chinese female basketball players. Zhao J, Tian Y, Nie J, Xu J, Liu D. "The red-light treatment participants lay in the supine position, and continuous illumination was performed using noncoherent red light from a whole-body red-light treatment machine (Shanghai Dayou PDT Technology Co, Ltd, Shanghai, China) with an average wavelength of 658 nm and light dose of 30 J/cm2."

"The 14-day whole-body irradiation with red-light treatment improved the sleep, serum melatonin level, and endurance performance of the elite female basketball players"

[83] Lasers Surg Med. 2008 Feb;40(2):106-12. LED photoprevention: reduced MED response following multiple LED exposures. Barolet D, Boucher A. "Thirteen healthy subjects and two patients with polymorphous light eruption (PLE) were exposed to 5, 6, or 10 LED treatments (660 nm) on an EXPERIMENTAL anterior thigh region."

"Reduction of erythema was considered significant when erythema was reduced by >50% on the LED-treated side as opposed to CONTROL side. A significant LED treatment reduction in UV-B induced erythema reaction was observed in at least one occasion in 85% of subjects, including patients suffering from PLE. Moreover, there was evidence of a dose-related pattern in results. Finally, a sun protection factor SPF-15-like effect and a reduction in post-inflammatory hyperpigmentation were observed on the LED pre-treated side."

[see also: J Invest Dermatol. 1998 Oct;111(4):629-33. Non-coherent near infrared radiation protects normal human dermal fibroblasts from solar ultraviolet toxicity. Menezes S, Coulomb B, Lebreton C, Dubertret L. "This study describes the induction by non-coherent infrared radiation (700-2000 nm), in the absence of rising temperature, of a strong cellular defense against solar UV cytotoxicity as well as induction of cell mitosis. [...] Living organisms on the Earth's surface are bathed by infrared radiation every day, before being submitted to solar UV. Thus, we propose that this as yet undescribed natural process of cell protection against solar UV, acquired and preserved through evolutional selection, plays an important role in life maintenance."]

[84] Photomed Laser Surg. 2009 Feb;27(1):21-4. The effect of low-level laser therapy on trismus and facial swelling following surgical extraction of a lower third molar. Aras MH, Güngörmüş M.

[85] Lasers Med Sci. 2013 May;28(3):845-9. Effect of low-level laser therapy after extraction of impacted lower third molars. Ferrante M, Petrini M, Trentini P, Perfetti G, Spoto G. "Group test showed improvement in the interincisal opening and remarkable reduction of trismus, swelling and intensity of pain on the first and the seventh postoperative days."

---(the end of removed part)---

[86] Photomed Laser Surg. 2006 Apr;24(2):129-39. Pro- and anti-inflammatory cytokine content in human peripheral blood after its transcutaneous (in vivo) and direct (in vitro) irradiation with polychromatic visible and infrared light. Zhevago NA, Samoilova KA. "Exposure of a small area of the human body to light leads to a fast decrease in the elevated pro-inflammatory cytokine plasma content and to an increase in the the anti-inflammatory factor concentration, which may be an important mechanism of the anti-inflammatory effect of phototherapy. These changes result from transcutaneous photomodification of a small volume of blood and a fast transfer of the light-induced changes to the entire pool of circulating blood."

[87] Barulin, Nikolai V., and Vitaly Yu Plavskii. "Effect of Polarization and Coherence of Optical Radiation on Sturgeon Sperm Motility." Proceedings of World Academy of Science, Engineering and Technology. No. 67. World Academy of Science, Engineering and Technology, 2012. [Sperm motility: 1) Control group: 120, 2) Circularly polarized radiation: 230, 3) Linearly polarized radiation 250, 4) Unpolarized radiation: 200]

[88] Lab Anim Res. 2012 Mar;28(1):39-46. Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet. Park D, Kyung J, Kim D, Hwang SY, Choi EK, Kim YB. "The PLT equipment is consisted of a 60 W tungsten lamp and a lens coated with polarized film in a stainless tube with 6-cm internal diameter. The polarized film [...] was designed to block ultraviolet and infrared lights, permitting penetration of only 400-760 nm light [...] The distance between light source and polarized-light lens was set at 10 cm to adjust the light intensity and energy density exposed to the skin to be 50 mW/cm2 and 60 J/cm2"

[89] J Oral Pathol Med. 2015 Feb;44(2):94-102. Anti-inflammatory effect of 635 nm irradiations on in vitro direct/indirect irradiation model. Lim W, Choi H, Kim J, Kim S, Jeon S, Zheng H, Kim D, Ko Y, Kim D, Sohn H, Kim O. "Thus, we suggest that not only direct exposure with 635 nm light, but also indirect exposure with 635 nm light can inhibit activation of pro-inflammatory mediators and may be clinically useful as an anti-inflammatory tool."

[90] J Invest Dermatol. 2009 Apr;129(4):994-1001. UVB and proinflammatory cytokines synergistically activate TNF-alpha production in keratinocytes through enhanced gene transcription. Bashir MM, Sharma MR, Werth VP. "In conclusion, TNF-alpha expression in primary keratinocytes is upregulated transcriptionally by UVB and IL-1alpha."

[91] BMC Psychiatry. 2013 Mar 5;13:75. The effect of sunlight exposure on interleukin-6 levels in depressive and non-depressive subjects. Levandovski R, Pfaffenseller B, Carissimi A, Gama CS, Hidalgo MP. "The amount of time that participants are exposed to sunlight is directly related to their IL-6 levels."

[92] J Clin Endocrinol Metab. 1994 Nov;79(5):1342-6. Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans. Stouthard JM, van der Poll T, Endert E, Bakker PJ, Veenhof CH, Sauerwein HP, Romijn JA.

[93] J Clin Endocrinol Metab. 1990 Dec;71(6):1567-72. Tumor necrosis factor: a putative mediator of the sick euthyroid syndrome in man. van der Poll T, Romijn JA, Wiersinga WM, Sauerwein HP.

[94] Lancet. 1959 Aug 22;2(7095):149-52. Prophylaxis of ischaemic heart-disease by thyroid therapy. BARNES BO.

[95] Laser Ther. 2011;20(3):205-15. Is light-emitting diode phototherapy (LED-LLLT) really effective? Kim WS, Calderhead RG.

[96] Lasers Surg Med. 2010 Aug;42(6):450-66. Effect of pulsing in low-level light therapy. Hashmi JT, Huang YY, Sharma SK, Kurup DB, De Taboada L, Carroll JD, Hamblin MR.

[97] QJM. 1996 Aug;89(8):579-89. Sunlight, cholesterol and coronary heart disease. Grimes DS, Hindle E, Dyer T.

[98] J Clin Hypertens (Greenwich). 2008 Feb;10(2):125-9. Seasonality of hypertension. Al-Tamer YY, Al-Hayali JM, Al-Ramadhan EA.

[99] Transplant Proc. 2004 Jan-Feb;36(1):148-9. Seasonal variations of blood pressure in hemodialysis and renal transplant recipients. Argani H, Javanshir MR.

[100] Eur J Epidemiol. 2008;23(9):609-14. Incident solar radiation and coronary heart disease mortality rates in Europe. Wong A. "An analysis of coronary heart disease mortality rates in Europe from a latitudinal gradient perspective has shown to have a close correlation to incident solar radiation."

[101] J Clin Epidemiol. 1988;41(7):679-89. Cyclic seasonal variation in plasma lipid and lipoprotein levels: the Lipid Research Clinics Coronary Primary Prevention Trial Placebo Group. Gordon DJ, Hyde J, Trost DC, Whaley FS, Hannan PJ, Jacobs DR, Ekelund LG. [This research group is from Maryland, so the latitude is probably 37-39 degrees to north]

[102] Chronobiol Int. 2001 May;18(3):541-57. Influence of dietary intake and physical activity on annual rhythm of human blood cholesterol concentrations. Blüher M, Hentschel B, Rassoul F, Richter V. "In all groups, we found a strong seasonal effect, with 5%–10% higher TC concentrations in winter compared to the summer."

[103] Clin Rheumatol. 2009 Jan;28(1):29-34. Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot study showing good tolerance, short-term improvement of pain and stiffness, and a trend towards long-term beneficial effects. Oosterveld FG, Rasker JJ, Floors M, Landkroon R, van Rennes B, Zwijnenberg J, van de Laar MA, Koel GJ. 

[104] J Clin Laser Med Surg. 1998 Oct;16(5):245-8. It's all in the parameters: a critical analysis of some well-known negative studies on low-level laser therapy. Tunér J, Hode L. "A study of 1,200 papers on LLLT has resulted in 85 positive and 35 negative double-blind studies. The negative studies have been scrutinized carefully in an effort to pinpoint possible reasons for the failures. In the following, the majority are double-blind studies, but some non-blinded and animal studies have been included to give typical examples of pitfalls." [Read also: The Cochrane LPT analyses – can they be improved? and Are all the negative lllt studies really negative?]

[105] Lasers Surg Med. 2005 Mar;36(3):210-9. Randomized controlled trial on low level laser therapy (LLLT) in the treatment of osteoarthritis (OA) of the hand. Brosseau L, Wells G, Marchand S, Gaboury I, Stokes B, Morin M, Casimiro L, Yonge K, Tugwell P.

[106] Clin Rheumatol. 2010 Sep;29(9):1075-6. Low-level laser therapy for hand arthritis-fact or fiction? Tunér J, Hode L. "The study by Meireles et al. [1] on the effect of low-level laser therapy (LLLT) on hand arthritis comes to the conclusion that there was no effect at the wavelength, dosage and power used in the study [...] It is obvious that the lack of clinical effect in the Meireles study is due to too low energy. [...] Dose (J/cm2 ) and energy (J) are two separate entities in laser therapy [...] The lack of understanding of these two important parameters is, for instance, shown in the studies by Brosseau et al. [4] and Cruz et al. [5]. Brosseau reported 860 nm, 60 mW, 3 J/cm2 for finger arthritis, but the unreported energy was actually 0.12 J per point. Cruz reported 780 nm, 60 mW, 4 J/cm2 for oral mucositis, in the only negative clinical study on mucositis. The unreported energy per point after 3 s per point is 0.18 J."

[107] Lasers Surg Med. 2006 Apr;38(4):343. Wrong parameters can give just any results. Hode L, Tunér J.  "Is laser therapy no better than placebo in osteoarthritis of the hand? This seems to be the fact after a superficial glance at the contribution by Brosseau et al. in 36:210–219 (2005). But looking closer, there are several alarming details in this study [...] Total energy per finger joint: (calculated with 30 mW and 1 x 4 seconds per finger joint), the energy applied to each joint is 0.12 J and that is very low [...] In short, this study has used a very low energy per point, using a previously rarely tested wavelength (860 nm) at a random pulse frequency and in the discussion failed to pinpoint some very important aspects of laser therapy. Still, the abstract claims that ‘‘LLLT’’ is no better than placebo."

[108] Swiss Med Wkly. 2004 May 1;134(17-18):254-8. Low power laser treatment in patients with knee osteoarthritis. Tascioglu F, Armagan O, Tabak Y, Corapci I, Oner C. 

Photomed Laser Surg. 2012 Aug;30(8):405-17. Meta-analysis of pain relief effects by laser irradiation on joint areas. Jang H, Lee H. "In investigations of knee pain, studies35,37 in which the irradiation size was [equal or greater than] 1 cm2 showed the effectiveness of laser treatments. Among three studies36,38,39 in which the irradiation size was [smaller than] 1 cm2, however, two studies36,38 reported ineffectiveness and one study39 reported effectiveness. In this case, the energy per point of study39 with an improved outcome (6 J) was greater than the energies of the two ineffective studies36,38 ([equal or smaller than] 3 J)."

[the old, incorrect ref: Aust J Physiother. 2003;49(2):107-16. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Bjordal JM Couppé C, Chow RT, Tunér J, Ljunggren EA.]

[110] Wikipedia: Low level laser therapy (Luettu 29.4.2015) "Despite a lack of consensus over its scientific validity, specific test and protocols for LLLT suggest it may be mildly effective, but in most cases no better than placebo, in relieving short-term pain for rheumatoid arthritis,[2] osteoarthritis,[6] acute and chronic neck pain,[7] tendinopathy,[4][8] and possibly chronic joint disorders.[5]"

[111] Phys Ther. 2008 Jan;88(1):123-36. Physical therapy interventions for patients with osteoarthritis of the knee: an overview of systematic reviews. Jamtvedt G, Dahm KT, Christie A, Moe RH, Haavardsholm E, Holm I, Hagen KB. "The meta-analysis of 7 RCTs concluded that laser therapy reduced pain and improved function compared with a placebo intervention. Two major studies in this meta-analysis did not include patients with osteoarthritis of the knee. Therefore, we graded the evidence down to moderate and conclude that there is moderate-quality evidence that low-level laser therapy reduces pain and improves function (Tab. 3)."

[112] Lancet. 2009 Dec 5;374(9705):1897-908. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. "We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients with chronic neck pain."

[113] J Oral Rehabil. 2015 Apr;42(4):291-9. Efficacy of low-level laser therapy in the treatment of TMDs: a meta-analysis of 14 randomised controlled trials. Chen J, Huang Z, Ge M, Gao M. 

[114a] Photomed Laser Surg. 2005 Oct;23(5):453-8. Can Cochrane Reviews in controversial areas be biased? A sensitivity analysis based on the protocol of a Systematic Cochrane Review on low-level laser therapy in osteoarthritis. Bjordal JM, Bogen B, Lopes-Martins RA, Klovning A. "An imbalance of the review group was identified as reviewers tend to favor their own trial conclusions. [...] Five of the seven members of the review group have authored clinical RCTs of LLLT with negative conclusions [...] Three of the reviewers recently published an included LLLT trial with treatment time per point of only 1 sec [...] Two of the authors had also published an industry-sponsored RCT with positive conclusion on topical and oral NSAIDs for knee OA"

"This Cochrane review displays omissions of relevant trial data that contradict the review conclusion. [...] Serious errors in data synthesis, omission of relevant data, and non-inclusion of eligible trials were identified, and nearly all systematically pointed in a negative direction for LLLT efficacy. [...] All of the seven pre-planned, but unperformed, subgroup analyses turned out positive in the sensitivity analysis."

[114bJ Altern Complement Med. 2006 Mar;12(2):181-3. Is quality control of Cochrane reviews in controversial areas sufficient? Bjordal JM, Lopes-Martins RA, Klovning A. "Only clinicians who had performed LLLT trials, and had negative results were invited into the review group. The review was oblivious to findings published after 1993 about physiologic mechanisms and dose response patterns for LLLT. We found 18 questionable selections that favored a negative review conclusion in 17 of 18 cases. These were largely omissions of relevant positive data and selective inclusion of negative data from trials with small, ineffective doses. When existing and omitted data from relevant trials were combined, results changed from negative to significantly positive for continuous and categorical data. Subgrouping trials by location and recommended doses taken from current guidelines, revealed a highly significant effect of LLLT for treating knee OA."

[115] Arthritis Res Ther. 2013;15(5):R116. Effect of low-level laser therapy on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation. Alves AC, Vieira R, Leal-Junior E, dos Santos S, Ligeiro AP, Albertini R, Junior J, de Carvalho P.

[116] Lasers Med Sci. 2014 Jul;29(4):1357-64. The effects of low-level laser irradiation on bone tissue in diabetic rats. Patrocínio-Silva TL, de Souza AM, Goulart RL, Pegorari CF, Oliveira JR, Fernandes K, Magri A, Pereira RM, Araki DR, Nagaoka MR, Parizotto NA, Rennó AC. "[I]t seems that LLLT stimulated bone metabolism, decreased resorptive areas, increased RUNX-2 expression, cortical area, fracture force, BMD, and BMC."

[117] Lasers Med Sci. 2014 Jan;29(1):313-9. Effect of low-level laser therapy on types I and III collagen and inflammatory cells in rats with induced third-degree burns. Fiório FB, Albertini R, Leal-Junior EC, de Carvalho Pde T. "Laser irradiation (both 3 and 4 J/cm(2)) resulted in reduction in the inflammatory process and improved collagen deposition, thereby ameliorating the healing of third-degree burns." [660nm laser]

[118] Photomed Laser Surg. 2010 Oct;28(5):603-11. Low-level laser therapy with a pulsed infrared laser accelerates second-degree burn healing in rat: a clinical and microbiologic study. Ezzati A, Bayat M, Khoshvaghti A. [890nm laser]

[119] J Rehabil Res Dev. 2009;46(4):543-54. Low-level laser therapy with pulsed infrared laser accelerates third-degree burn healing process in rats. Ezzati A, Bayat M, Taheri S, Mohsenifar Z. [890nm laser]

[120] Photomed Laser Surg. 2009 Dec;27(6):959-64. Low-level laser therapy using 80-Hz pulsed infrared diode laser accelerates third-degree burn healing in rat. Vasheghani MM, Bayat M, Dadpay M, Habibie M, Rezaei F. "The paired Student t-test showed that the wound closure rate of laser-treated burns (17.6+/-1.86 days) was significantly longer than that of the control burns (19.6+/-0.81 days) (p=0.007)." [890nm laser]

[121] J Alzheimers Dis. 2012;32(3):741-52. Low-level light therapy improves cortical metabolic capacity and memory retention. Rojas JC, Bruchey AK, Gonzalez-Lima F.

[122] Invest Ophthalmol Vis Sci. 2013 May 1;54(5):3681-90. Low-intensity far-red light inhibits early lesions that contribute to diabetic retinopathy: in vivo and in vitro. Tang J, Du Y, Lee CA, Talahalli R, Eells JT, Kern TS. [670nm LED]

[123] J Photochem Photobiol B. 2010 May 3;99(2):105-10. Effects of low-level light therapy on streptozotocin-induced diabetic kidney. Lim J, Sanders RA, Snyder AC, Eells JT, Henshel DS, Watkins JB 3rd. [670nm LED]

[124] Lasers Med Sci. 2013 May;28(3):1007-16. Low-level laser therapy improves the inflammatory profile of rats with heart failure. Hentschke VS, Jaenisch RB, Schmeing LA, Cavinato PR, Xavier LL, Dal Lago P. "LLLT showed systemic and skeletal muscle anti-inflammatory effects in rats with HF." [660nm laser]

[125] Arq Bras Cardiol. 2014 Aug;103(2):161-4. Hemodynamic effect of laser therapy in spontaneously hypertensive rats. [Article in English, Portuguese] Tomimura S, Silva BP, Sanches IC, Canal M, Consolim-Colombo F, Conti FF, De Angelis K, Chavantes MC. "The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group)." [780nm laser]

[126] Photochem Photobiol. 2013 Jul-Aug;89(4):953-60. Laser therapy in metabolic syndrome-related kidney injury. Ucero AC, Sabban B, Benito-Martin A, Carrasco S, Joeken S, Ortiz A. "The main findings of this study are that the LLLT-treated rats had lower blood pressure after treatment and a better preserved glomerular filtration rate with less interstitial fibrosis upon euthanasia at the end of follow-up. This initial proof-of-concept study suggests that LLLT may modulate chronic kidney disease progression, providing a painless, noninvasive, therapeutic strategy, which should be further evaluated."

[127] J Photochem Photobiol B. 2013 Apr 5;121:86-93. Potentiated anti-inflammatory effect of combined 780 nm and 660 nm low level laser therapy on the experimental laryngitis. Marinho RR, Matos RM, Santos JS, Ribeiro MA, Smaniotto S, Barreto EO, Ribeiro RA, Lima RC Jr, Albuquerque RL Jr, Thomazzi SM. 

[128] Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3439-44. Therapeutic photobiomodulation for methanol-induced retinal toxicity. Eells JT, Henry MM, Summerfelt P, Wong-Riley MT, Buchmann EV, Kane M, Whelan NT, Whelan HT. "Our studies document a significant recovery of rod- and cone-mediated function in LED-treated, methanol-intoxicated rats. We further show that LED treatment protected the retina from the histopathologic changes induced by methanol-derived formate. These findings provide a link between the actions of monochromatic red to near-IR light on mitochondrial oxidative metabolism in vitro and retinoprotection in vivo. They also suggest that photobiomodulation may enhance recovery from retinal injury and other ocular diseases in which mitochondrial dysfunction is postulated to play a role." [670nm LED]

[129] Int J Cardiol. 2001 Sep-Oct;80(2-3):109-16. Impact of low level laser irradiation on infarct size in the rat following myocardial infarction. Ad N, Oron U. "The infarct size (expressed as percent of total left ventricle area) of the LI rats was 10.1+/-5.8, which was significantly lower [...] than the infarct size of NLI rats which was 28.7+/-9.6. [...] LLLI of the infarcted area in the myocardium of experimentally induced MI rats, at the correct energy, duration and timing, markedly reduces the loss of myocardial tissue. This phenomenon may have an important beneficial effect on patients after acute MI or ischemic heart disease."

[130] Photomed Laser Surg. 2013 Jul;31(7):315-21. The effects of low-level laser therapy on palatal mucoperiosteal wound healing and oxidative stress status in experimental diabetic rats. Firat ET, Dağ A, Günay A, Kaya B, Karadede Mİ, Kanay BE, Ketani A, Evliyaoğlu O, Uysal E. 

[131] Photomed Laser Surg. 2007 Jun;25(3):137-43. Efficacy of 780-nm laser phototherapy on peripheral nerve regeneration after neurotube reconstruction procedure (double-blind randomized study). Rochkind S, Leider-Trejo L, Nissan M, Shamir MH, Kharenko O, Alon M.

[132] Lasers Med Sci. 2014 Jan;29(1):239-43. Potential anti-inflammatory effect of low-level laser therapy on the experimental reflux laryngitis: a preliminary study. Marinho RR, Matos RM, Santos JS, Ribeiro MA, Ribeiro RA, Lima RC Jr, Albuquerque RL Jr, Thomazzi SM. "Thereafter, measurement of myeloperoxidase activity and the histopathological procedures were performed. In conclusion, we observed in this study that 105-J/cm(2) infrared laser reduced the influx of neutrophils in rats, and it improved the reparative collagenization of the laryngeal tissues." [780nm laser]

[133] Lasers Med Sci. 2013 Feb;28(2):529-36. Low-level laser therapy in different stages of rheumatoid arthritis: a histological study. Alves AC, de Carvalho PT, Parente M, Xavier M, Frigo L, Aimbire F, Leal Junior EC, Albertini R. "We observed that LLLT both at early and late RA progression stages significantly improved mononuclear inflammatory cells, exudate protein, medullary hemorrhage, hyperemia, necrosis, distribution of fibrocartilage, and chondroblasts and osteoblasts compared to RA group" [780nm laser]

[134] Lasers Med Sci. 2014 Mar;29(2):653-8. What is the best treatment to decrease pro-inflammatory cytokine release in acute skeletal muscle injury induced by trauma in rats: low-level laser therapy, diclofenac, or cryotherapy? de Almeida P, Tomazoni SS, Frigo L, de Carvalho Pde T, Vanin AA, Santos LA, Albuquerque-Pontes GM, De Marchi T, Tairova O, Marcos RL, Lopes-Martins RÁ, Leal-Junior EC. "Therefore, we can conclude that 904 nm LLLT with 1 J dose has better effects than topical application of diclofenac or cryotherapy in acute inflammatory phase after muscle trauma."

[135] Lasers Med Sci. 2014 Mar;29(2):805-11. doi: 10.1007/s10103-013-1406-2. Epub 2013 Aug 28. Pulsed LLLT improves tendon healing in rats: a biochemical, organizational, and functional evaluation. Guerra Fda R, Vieira CP, dos Santos de Almeida M, Oliveira LP, Claro AC, Simões GF, de Oliveira AL, Pimentel ER.

[136] Photomed Laser Surg. 2012 Sep;30(9):523-9. Near-infrared photobiomodulation in an animal model of traumatic brain injury: improvements at the behavioral and biochemical levels. Quirk BJ, Torbey M, Buchmann E, Verma S, Whelan HT. "These results show statistically significant, preclinical outcomes that support the use of NIR treatment after TBI in effecting changes at the behavioral, cellular, and chemical levels." [670nm LED]

[137] Lasers Med Sci. 2014 Mar;29(2):757-63. Protective effect of low-level laser therapy (LLLT) on acute zymosan-induced arthritis. Carlos FP, de Paula Alves da Silva M, de Lemos Vasconcelos Silva Melo E, Costa MS, Zamuner SR. "Treatment with laser significantly inhibited leukocytes influx, the release of IL-1 and IL-6 and also the activity of metalloproteinase-2 and 9, into the joint cavity." [660nm laser]

[138] PLoS One. 2012;7(1):e30655. Amelioration of experimental autoimmune encephalomyelitis in C57BL/6 mice by photobiomodulation induced by 670 nm light. Muili KA, Gopalakrishnan S, Meyer SL, Eells JT, Lyons JA. "670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α) and up-regulation of anti-inflammatory cytokines (IL-4, IL-10) in vitro and in vivo." [670nm LED, bandwidth 25-30nm]

[139] Photomed Laser Surg. 2009 Aug;27(4):591-7. Effect of low-level laser therapy in the myonecrosis induced by Bothrops jararacussu snake venom. Barbosa AM, Villaverde AB, Sousa LG, Munin E, Fernandez CM, Cogo JC, Zamuner SR. "LLLT significantly reduced myonecrosis by 83.5% at 24 h (p < 0.05) but not at 3 h, and [antivenom] therapy alone was ineffective for reducing myonecrosis at 3 and 24 h." [685nm laser]

[140] Lasers Surg Med. 2012 Mar;44(3):218-26. Low-level laser therapy for closed-head traumatic brain injury in mice: effect of different wavelengths. Wu Q, Xuan W, Ando T, Xu T, Huang L, Huang YY, Dai T, Dhital S, Sharma SK, Whalen MJ, Hamblin MR. "The effectiveness of 810 nm agrees with previous publications, and together with the effectiveness of 660 nm and non-effectiveness of 730 and 980 nm can be explained by the absorption spectrum of cytochrome oxidase, the candidate mitochondrial chromophore in transcranial LLLT."

[141] Vet Dermatol. 2015 Feb;26(1):35-9, e11. Efficacy of low-level laser therapy on hair regrowth in dogs with noninflammatory alopecia: a pilot study. Olivieri L, Cavina D, Radicchi G, Miragliotta V, Abramo F. "At the end of the study, coat regrowth was greatly improved in six of seven animals and improved in one of seven. By morphometry, the area occupied by hair follicles was 18% in the treated sample and 11% in the untreated one (11%); haired follicles were (per area) 93% in the treated sample and only 9% in the control sample." [470+685+830nm laser]

[142] Lasers Surg Med. 2001;28(3):204-11. Attenuation of infarct size in rats and dogs after myocardial infarction by low-energy laser irradiation. Oron U, Yaakobi T, Oron A, Hayam G, Gepstein L, Rubin O, Wolf T, Ben Haim S. "In dogs, a 49% [...] reduction of infarct size was achieved." "However, laser applied twice at an energy density of 12 mW/cm2 did not cause a significant reduction in infarct size." [810nm laser]

[143] J Small Anim Pract. 2012 Aug;53(8):465-9. Low-level laser therapy reduces time to ambulation in dogs after hemilaminectomy: a preliminary study. Draper WE, Schubert TA, Clemmons RM, Miles SA. "The time to achieve a modified Frankel score of 4 was significantly lower (P=0.0016) in the low-level laser therapy group (median 3.5 days) than the control group (median 14 days)." [810nm laser]

[144] Lasers Med Sci. 2005;20(1):28-34. Epub 2005 Apr 19. Effect of 655-nm diode laser on dog sperm motility. Corral-Baqués MI, Rigau T, Rivera M, Rodríguez JE, Rigau J. "At these parameters, the 655-nm continuous-wave diode laser improves the speed and linear coefficient of the sperm."

[145] Stroke. 2004 Aug;35(8):1985-8. Transcranial infrared laser therapy improves clinical rating scores after embolic strokes in rabbits. Lapchak PA, Wei J, Zivin JA. "This study shows that laser treatment improved behavioral performance if initiated within 6 hours of an embolic stroke and the effect of laser treatment is durable. Therefore, transcranial laser treatment may be useful to treat human stroke patients and should be further developed."  [808nm laser]

[146] N Am J Med Sci. 2011 Apr;3(4):193-7. Effects of a low level laser on the acceleration of wound healing in rabbits. Hussein AJ, Alfars AA, Falih MA, Hassan AN. "The study found that low level laser therapy (II) was effective in open wounds, which showed better regeneration and faster restoration of structural and functional integrity as compared to the control group." [890nm, 910nm laser]

[147] Biochim Biophys Acta. 1997 Mar 28;1319(1):5-8. Cardiolipin-dependent decrease of cytochrome c oxidase activity in heart mitochondria from hypothyroid rats. Paradies G, Petrosillo G, Ruggiero FM. 

[148] J Cell Biol. 1978 Jun;77(3):887-901. Biochemical and stereological analysis of rat liver mitochondria in different thyroid states. Jakovcic S, Swift HH, Gross NJ, Rabinowitz M. 

[149] Schultze, M. O. "The relation of copper to cytochrome oxidase and hematopoietic activity of the bone marrow of rats." Journal of Biological Chemistry 138.1 (1941): 219-224. 

[150] Am J Clin Nutr. 1998 May;67(5 Suppl):1041S-1045S. Copper intake and assessment of copper status. Milne DB.

[151] Shab‐Bidar, Sakineh, et al. "Dietary intakes of zinc and copper and cardiovascular risk factors in Tehranian adults: Tehran Lipid and Glucose Study." Nutrition & Dietetics 70.3 (2013): 218-226.

[152Physiother Res Int. 2015 Jun;20(2):108-25. The efficacy of low-level laser therapy for shoulder tendinopathy: a systematic review and meta-analysis of randomized controlled trials. Haslerud S, Magnussen LH, Joensen J, Lopes-Martins RA, Bjordal JM.

[153] Lasers Med Sci. 2015 Aug;30(6):1757-62. Effect of low-level laser therapy on lung injury induced by hindlimb ischemia/reperfusion in rats. Ashrafzadeh Takhtfooladi M, Ashrafzadeh Takhtfooladi H, Sedaghatfar H, Shabani S.

[extra] Free Radic Biol Med. 2009 Sep 15;47(6):850-7. Inhibition of mitochondria-dependent apoptosis by 635-nm irradiation in sodium nitroprusside-treated SH-SY5Y cells. Lim W, Kim JH, Gook E, Kim J, Ko Y, Kim I, Kwon H, Lim H, Jung B, Yang K, Choi N, Kim M, Kim S, Choi H, Kim O. "Finally, these results show that 635-nm irradiation, by promoting the scavenging of O(2)(-)" 

[extra] Biomed Tech (Berl). 2014 Dec;59(6):487-93. Red light as a 12-oxo-leukotriene B₄ antagonist: an explanation for the efficacy of intensive red light in the therapy of peripheral inflammatory diseases. Paschke F, Rabong C, Schuster C. "The power balance demonstrates that intensive red light with a power density of 0.4 W/cm2 transfers sufficient energy to 12-Oxo-LTB4 to render it biologically inactive."

[extraJ Mol Cell Cardiol. 2009 Aug;47(2):256-63. Enhancement of nitric oxide release from nitrosyl hemoglobin and nitrosyl myoglobin by red/near infrared radiation: potential role in cardioprotection. Lohr NL, Keszler A, Pratt P, Bienengraber M, Warltier DC, Hogg N. "We show both in purified systems and in myocardium that R/NIR light can decay nitrosyl hemes and release NO, and that this released NO may enhance the cardioprotective effects of nitrite."

[extra] J Neurosci. 2008 Dec 10;28(50):13511-21. Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy. Rojas JC1, Lee J, John JM, Gonzalez-Lima F. "superoxide dismutase activities were also increased in NIL-treated subjects in a dose-dependent manner, suggesting an in vivo transcranial effect of NIL."

[extra] Lasers Surg Med. 2005 Mar;36(3):171-85. Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury. Byrnes KR, Waynant RW, Ilev IK, Wu X, Barna L, Smith K, Heckert R, Gerst H, Anders JJ. "6% of the power of a 150 mW 810 nm laser was transmitted through all of the layers of tissue between the [adult rat] dorsal skin surface and the ventral side of the spinal cord." "PBM resulted in a significant suppression [...] of IL6 expression at 6 hours post-injury, with a 171-fold decrease in expression of IL6."

[extra] Lasers Surg Med. 2015 Apr;47(4):296-305. Effect of low-level laser therapy on chemoradiotherapy-induced oral mucositis and salivary inflammatory mediators in head and neck cancer patients. Oton-Leite AF, Silva GB, Morais MO, Silva TA, Leles CR, Valadares MC, Pinezi JC, Batista AC, Mendonça EF. "One interesting finding in this study was that IL-6 concentrations were lower in the laser group than in the control group throughout the treatment."

[extra] J Invest Dermatol. 1998 Oct;111(4):629-33. Non-coherent near infrared radiation protects normal human dermal fibroblasts from solar ultraviolet toxicity. Menezes S, Coulomb B, Lebreton C, Dubertret L. "Living organisms on the Earth's surface are bathed by infrared radiation every day, before being submitted to solar UV. Thus, we propose that this as yet undescribed natural process of cell protection against solar UV, acquired and preserved through evolutional selection, plays an important role in life maintenance."

[extraThe importance of coherence in phototherapy. TomasHode, Donald Duncan, Sean Kirkpatrick, Peter Jenkins, Lars Hode. "In superficial tissue, where the photon flux is high (less absorption has taken place), it is easy to reach necessary power density thresholds without the benefits of laser speckle. However, in deep tissue where the photon flux is extremely low, the increased probability of photon absorption from individual laser speckles increases the probability of reaching the necessary power density thresholds. Because of the non-coherent nature of radiation from light/IR emitting diodes speckle does not occur in the tissue with LED therapy, which may explain why head-to-head comparisons between lasers and LEDs in deep tissue seem to be in favor of lasers, and super-pulsed lasers in particular"

[extra] Masui. 2012 Jul;61(7):687-92. [Near infrared light irradiator using halogen lamp]. [Article in Japanese] Ide Y.

[extra] Photomed Laser Surg. 2011 Jun;29(6):399-404. Visible light-induced healing of diabetic or venous foot ulcers: a placebo-controlled double-blind study. Landau Z, Migdal M, Lipovsky A, Lubart R.

[extra] Br J Ophthalmol. 2014 Aug;98(8):1013-5. Photobiomodulation in the treatment of patients with non-center-involving diabetic macular oedema. Tang J, Herda AA, Kern TS. "Daily PBM treatment for only 80 s per treatment twice daily caused a significant reduction in focal retinal thickening in all 4 treated eyes. No adverse effects attributable to therapy were noted by the patients or study investigators during the study period.[670nm LED]

[extraExp Eye Res. 2014 May;122:50-3. Recharging mitochondrial batteries in old eyes. Near infra-red increases ATP. Gkotsi D, Begum R, Salt T, Lascaratos G, Hogg C, Chau KY, Schapira AH, Jeffery G. "Near infra-red (670 nm) is thought to be absorbed by cytochrome c oxidase (COX), a key element in mitochondrial respiration and it has been demonstrated that it improves mitochondrial membrane potentials in aged eyes. It also significantly reduces the impact of experimental pathology and ameliorates age related retinal inflammation. We show ATP decline with ageing in mouse retina and brain. Also, in these tissues that ATP is significantly increased by 670 nm exposure in old mice. In the retina this was associated with increased COX and reduced acrolein expression."

[extra] Neurobiol Aging. 2013 Feb;34(2):602-9. Age-related retinal inflammation is reduced by 670 nm light via increased mitochondrial membrane potential. Kokkinopoulos I, Colman A, Hogg C, Heckenlively J, Jeffery G. "These results provide a simple route to combating inflammation in an aging population with declining visual function and may be applicable to clinical conditions where retinal inflammation is a key feature."

[extra] Photomed Laser Surg. 2011 May;29(5):351-8. Improved cognitive function after transcranial, light-emitting diode treatments in chronic, traumatic brain injury: two case reports. Naeser MA, Saltmarche A, Krengel MH, Hamblin MR, Knight JA. 

[extra] J Photochem Photobiol B. 2013 Jun 5;123:13-22. Non-invasive infra-red therapy (1072 nm) reduces β-amyloid protein levels in the brain of an Alzheimer's disease mouse model, TASTPM. Grillo SL, Duggett NA, Ennaceur A, Chazot PL. "Chronic IR1072 treatment of female TASTPM mice elicited significant increases in HSP60, 70 and 105 and phosphorylated-HSP27 (P-HSP27) (50-139%), together with a concomitant profound decrease in αB-crystallin, APP, tau-P, Aβ1-40 and Aβ1-42 (43-81%) protein levels at 7 months of age."

[extra] Lasers Med Sci. 2015 Jan;30(1):339-46. The effects of transcranial LED therapy (TCLT) on cerebral blood flow in the elderly women. Salgado AS, Zângaro RA, Parreira RB, Kerppers II. "TCD parameters showed improvement in the blood flow on the arteries analyzed. TCLT promoted a blood and vasomotor behavior of the basilar and middle cerebral arteries in healthy elderly women."

[extra] Poult Sci. 2014 May;93(5):1289-97. Red light is necessary to activate the reproductive axis in chickens independently of the retina of the eye. Baxter M, Joseph N, Osborne VR, Bédécarrats GY.

[extra] J Dent Res. 2012 Oct;91(10):961-6. Effects of red light-emitting diode irradiation on dental pulp cells. Holder MJ, Milward MR, Palin WM, Hadis MA, Cooper PR. "Light exposure also rescued the inhibition of mitochondrial dysfunction and increased levels of in vitro mineralization compared with control."

[extra] Sci Transl Med. 2014 May 28;6(238):238ra69. Photoactivation of endogenous latent transforming growth factor-β1 directs dental stem cell differentiation for regeneration. Arany PR, Cho A, Hunt TD, Sidhu G, Shin K, Hahm E, Huang GX, Weaver J, Chen AC, Padwa BL, Hamblin MR, Barcellos-Hoff MH, Kulkarni AB, J Mooney D. [810nm laser] "in vivo pulp capping model in rat teeth demonstrated significant increase in dentin regeneration after LPL treatment."

[extra] J Oral Rehabil. 2014 Jul;41(7):523-31. Treatment of dentin hypersensitivity with a low-level laser-emitting toothbrush: double-blind randomised clinical trial of efficacy and safety. Ko Y, Park J, Kim C, Park J, Baek SH, Kook YA.

[extra] J Pain Res. 2015 May 26;8:253-6. Can intractable discogenic back pain be managed by low-level laser therapy without recourse to operative intervention? Ip D, Fu NY. "All of the patients who entered the study had failed response to a combination of nonsteroidal anti-inflammatory agents and had had not less than 3 months of conventional physical therapy. [...] All but one patient had significant improvement in their Oswestry Disability Index score, from a mean of 50% score to a mean of 10% score, at the end of treatment at 12 weeks. In addition, surprisingly, the improvement was found maintained at follow-up assessments 1 year and 5 years later."

[extra] Physiother Theory Pract. 2015 Jan 14:1-8. Muscular pre-conditioning using light-emitting diode therapy (LEDT) for high-intensity exercise: a randomized double-blind placebo-controlled trial with a single elite runner. Ferraresi C, Beltrame T, Fabrizzi F, Nascimento ES, Karsten M, Francisco CO, Borghi-Silva A, Catai AM, Cardoso DR, Ferreira AG, Hamblin MR, Bagnato VS, Parizotto NA. "A LED cluster with 50 LEDs (λ = 850 nm; 50 mW 15 s; 37.5 J) was applied on legs, arms and trunk muscles of a single runner athlete 5 min before a high-intense constant workload running exercise on treadmill. [...] LEDT improved the speed of the muscular VO2 adaptation (∼-9 s), decreased O2 deficit (∼-10 L), increased the VO2 from the slow component phase (∼+348 ml min-1) and increased the time limit of exercise (∼+589 s). LEDT decreased blood and urine markers of muscle damage and fatigue (CK, alanine and lactate levels)."

[extra] Circulation. 2001 Jan 16;103(2):296-301. Low-energy laser irradiation reduces formation of scar tissue after myocardial infarction in rats and dogs. Oron U, Yaakobi T, Oron A, Mordechovitz D, Shofti R, Hayam G, Dror U, Gepstein L, Wolf T, Haudenschild C, Haim SB. "Only 14+/-3% of the mitochondria in the cardiomyocytes in the ischemic zone (4 hours after MI) of LI MI-induced rats were severely damaged, compared with 36+/-1% in NLI rats. Accordingly, ATP content in that zone was 7.6-fold (significantly) higher in LI than in NLI rats." [LI: laser, NLI: sham]

[extra] Ann Allergy Asthma Immunol. 1997 Apr;78(4):399-406. Narrow-band red light phototherapy in perennial allergic rhinitis and nasal polyposis. Neuman I, Finkelstein Y. "Following treatment, improvement of symptoms was reported by 72% of the allergic rhinitis patients and objective improvement was endoscopically demonstrated in 70% of them as compared with 24% and 3%, respectively, in the placebo group."

[extra] Dose Response. 2014 Sep 22;12(4):619-49. Pre-conditioning with low-level laser (light) therapy: light before the storm. Agrawal T, Gupta GK, Rai V, Carroll JD, Hamblin MR. "Recently it has become apparent that LLLT can also be effective if delivered to normal cells or tissue before the actual insult or trauma, in a pre-conditioning mode. Muscles are protected, nerves feel less pain, and LLLT can protect against a subsequent heart attack. These examples point the way to wider use of LLLT as a pre-conditioning modality to prevent pain and increase healing after surgical/medical procedures and possibly to increase athletic performance."

[extra] J Cell Sci. 2014 Jan 15;127(Pt 2):388-99. Light-harvesting chlorophyll pigments enable mammalian mitochondria to capture photonic energy and produce ATP. Xu C, Zhang J, Mihai DM, Washington I. "Here we show that mammalian mitochondria can also capture light and synthesize ATP when mixed with a light-capturing metabolite of chlorophyll."

[extraBiol Lett. 2015 Mar;11(3). pii: 20150073. Near-infrared light increases ATP, extends lifespan and improves mobility in aged Drosophila melanogaster. Begum R, Calaza K, Kam JH, Salt TE, Hogg C, Jeffery G.

[extra] Med Hypotheses. 2015 May;84(5):421-8. Did human hairlessness allow natural photobiomodulation 2 million years ago and enable photobiomodulation therapy today? This can explain the rapid expansion of our genus's brain. Mathewson I.

[extraJournal of Cancer Research, 3(1), 1-5. (2015) Water’s Many Roles in Laser Photobiomodulation. Santana-Blank, L., Rodríguez-Santana, E., Santana-Rodríguez, K. E., Santana-Rodríguez, J. A., & Reyes, H. "We propose that light-water interactions offer a potent, alternate and complementary pathway to activate and modulate tumor suppression and/or proto-oncogenic expression through energy transfer via water and CO2 in multi-fractal regimes, leading to the coupling of spatiotemporal oscillators. Laser photobiomodulation may, thus, offer the possibility of targeting multiple hallmarks of cancer and other complex diseases using fit-for-purpose electromagnetic (light) energy to restore physiologically reparative and regenerative mechanisms that can help reestablish homeostasis-homeokinesis, constituting a new emerging paradigm in the treatment of cancer and other complex diseases"

[extra] Med Hypotheses. 2014 Mar;82(3):275-81. Protein conformational modulation by photons: a mechanism for laser treatment effects. Liebert AD, Bicknell BT, Adams RD. "The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders."

[extra] Ann Thorac Surg. 2012 Apr;93(4):1181-6. Light-induced vasodilation of coronary arteries and its possible clinical implication. Plass CA, Loew HG, Podesser BK, Prusa AM. "Vessels exposed to either light source showed a remarkable as well as comparable photorelaxation at definite energy densities. This effect is mediated by an intracellular nitric oxide-dependent mechanism. 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."

University of Milwaukee - Light as medicine? UWM researchers explain how

SuppVersity - Low Level Laser Therapy (LLLT) Almost Doubles Muscle Gains & Ramps Up Concentric & Eccentric Peak Torque Development During 8-Week Eccentric Training Program

Havelock Ellis: Sexual Education and Nakedness (1909) "The hygienic value of nakedness is indicated by the robust health of the savage throughout the world who go naked. The vigor of the Irish, also, has been connected with the fact that (as Fynes Moryson's Itinerary shows) both sexes, even among persons of high social class, were accustomed to go naked except for a mantle, especially in more remote parts of the country, until the sevcenteeth century. 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.“


Appendix 2: Some extra speculations regarding light, thyroid hormones and copper

The general therapeutic effects of red light remind me of some similar findings related to thyroid hormones. Thyroid hormone also appears to increase the activity of cytochrome c oxidase (Cox), so there might be a common mechanism.[147,148] Also, in one study, dietary copper was associated with a five-fold lower risk of metabolic syndrome. Since Cox is a copper enzyme, it might be hypothetically dependent on dietary intake.[149-151]


  1. Thank you for putting in the time to review that literature and share your knowledge.

    Heel Spurs LED would be a good site to refer readers to (I know you referenced the image).

    I use a cheap spectroscope to measure the lights that I am trying to use therapeutically. However, I do not know how to measure their power and to determine if they are powerful enough to stimulate metabolic changes.

    I do have an LED panel from amazon that is 14 w providing 640nm red light.

    I also have a halogen light bulb in a lamp holder that I taped a red filter in front of in an attempt to make it closer to monochromatic. The spectroscope registers is as in the healing range.

    Any thoughts on how to measure output power or to determine if these could indeed be beneficial would be appreciated.

    1. Hi Elie, and thanks for the comment. :)

      I added the link to!

      Currently, I don't have any good ideas about good ways of measuring the light power. :\ It'd certainly be good to be able to measure it. (From this perspective, the lasers with well-known parameters are really a good thing. If they didn't usually cost thousands of euros, I wouldn't talk so much about LED's or lamps.)


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  2. I'm curious if you've ever looked into the therapeutic effects of moxabustion. I haven't looked closely at the research, but some claim to have verified its anti-inflammatory and immune-stimulating effects. I find it effective in my acupuncture practice, where I mostly use indirect pole moxa on particular acupuncture points. Spectral curves seem hard to find, but this site which sells an "electric" version, shows it to be close to a black body at 850° C.

    It appears to have low output at the frequencies typically investigated and a peak at 2.6 μm, which they consider to be "medium IR."


    1. Hi Greg,

      Thanks for mentioning that type of therapy. I'm currently too busy to investigate moxabustion, but it's still interesting to hear about treatments I didn't know about.

      It would be interesting to know whether the electric device has any beneficial effects unrelated to the heat. The wavelengths are indeed a little bit too long.

  3. Hey Vladimir,

    Thanks for the very detailed post. I am still somewhat struggling to determine what product would be best.

    What do you think of this model:

    I appreciate any help you can provide!

    1. Hello Unknown,

      Since it emits near-infrared, it might provide the beneficial effects. Might be worth a try!

      - It's a little bit more expensive than halogen/incandescent/heat lamps
      - There's no high-quality research on polychromatic (continous spectrum) light, so we can't be sure about the efficacy

      If you try it, I hope it works! :-)


  4. 'would you recommend light therapy for thyroidissues ?

    1. Hi Amir,

      I think that using light therapy for autoimmune thyroiditis and hypothyroidism seems VERY PROMISING according to the research I've read:

  5. Hi,

    What light equipment are you using currently (which can be find here in Helsinki)?

  6. hi! what are your views on phillips infracare series, do they emit the beneficial wavelengths required for benefits?

    thank you!

    1. Hi Anonymous,

      I've used Philips heat lamp, and I guess this product has a similar wavelength spectrum. It probably emits a good amount of near-infrared, and might be therapeutic for this reason. However, I wish there was some research about polychromatic light (continuous spectrum). LLLT studies are basically conducted with monochromatic (single wavelength) devices.

  7. Very informative article. You definitely did your research and you have a convert right here. A lot of this information has been circulating around in many circles and other ideas in the past, I have no doubt this will soon be mainstream. There are a lot of ways one can adapt to using red light and especially IR light.

    Ronni Casillas @ JNH Life Styles

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  12. Hello-

    Can you please give me your opinion as to whether this bulb is safe for treating sun damaged skin and wrinkles? Will this bulb cause skin cancer?

    Thank you very much!

    Product Description
    RubyLux NIR-A Infrared Bulb is a premium incandescent infrared bulb that operates at 850 nm. It is a near infrared/NIR/IR-A light source that emits NO far infrared rays. It has been engineered to fit standard US lamp and light socket sizes. RubyLux NIR-A Infrared Bulb has a multitude of applications and has been designed to provide an intense level of infrared in a simple, easy-to-use light bulb form. In addition to infrared and red light, this bulb also produces a pleasant, relaxing warmth. Most importantly, these genuine RubyLux brand bulbs are guaranteed to be free of toxic mercury, Teflon and fluorinated fumes. RubyLux NIR-A Infrared Bulbs emit NO far infrared waves- only gentle near infrared light. Each bulb is inspected, guaranteed and engineer-certified. As with all RubyLux products, these bulbs are cruelty-free and are not tested on animals. Average bulb life is 5,000 hours. This is the only genuine, authorized seller of RubyLux bulbs on Amazon. Every RubyLux bulb is backed by our 60-day guarantee and Amazon customer service. Delivered directly from Amazon Fulfillment and available for Amazon Prime. Instructions for use and care are delivered electronically immediately upon purchase. Package includes one (1) bulb only. All other items, such as RubyLux Bulb Cover Shields and RubyLux All-in-One Goggles are sold separately.

    1. Hi Anonymous,

      I would say this bulb MIGHT be beneficial to treat skin and wrinkles.

      The problem of LLLT research is that they usually use monochromatic light. This lamp produces polychromatic light, whis has not been extensively studied. Still I think it's possible that these lamps might also work, if you find a right dose (not too much light, but not too little). :-)

      I would say it doesn't cause skin cancer. Usually it's the ultraviolet (UV) that is linked to skin cancers, but this bulb probably produces only negligible amounts of UV.

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