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Red Light Articles Summary

This is a repository for the initial research on red light therapy

Summary: Combine a red light with a near infrared light. Most common combination used seems to be low to mid 600s (around 635) and high 700s to low 800s (780-810). Some websites and studies also seem to like 670-680 as well. From what I’ve seen, the studies with the best results combined the two, and some even included blue/green light which doesn’t penetrate the skin as much as red/infrared light but still has positive effects. I will however say, I attribute the slight differences in preference to the fact that a few nm make it very difficult to determine measurable changes in the body. Also many of the studies were unfortunately small, not double blind, not random, and only tested 1-2 wavelengths, used non-red/infrared light and some used lasers as opposed to LED panels.

Some interesting things involving ATP. Max ATP production occurs 3-6 hours after red light is shone onto the body. Many use a combination of 2 lights in experiments. One paper ties the increase in ATP/other benefits of Red Light Therapy to redox reactions, which you may want to look at.

  • https://academic.oup.com/asj/article/22/5/451/254429
    • “Low-level laser-assisted lipoplasty is a new technique that offers rapid postoperative recovery and highly satisfactory aesthetic results.”
    • Occurred at 635 nm
  • https://www.sciencedirect.com/science/article/abs/pii/S1010518217302974?via%3Dihub
    • “Our analysis showed a 16.5% reduction of edema in the LLLT group and 7.3% in the sham light group. The edema reduction was statistically significantly greater in the LLLT group than in the sham light group (p < 0.047).”
    • Used 590 and 830 nm lights (no in between) to see how it would affect facial bone/cartilage regrowth. Results only slightly significant and they used no lights in between. Also only 40 total ppl (20 in light and 20 in nonlight group).
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5599844/
  • http://erepository.cu.edu.eg/index.php/BFPTH/article/view/455
    • “The results of the present study showed that there was significant different between the pre-post treatment mean value of BMD using LLLT. It has been suggested that LLLT may influence the healing process by affecting various tissue responses such as blood flow, lymphatic flow, inflammation, cellular proliferation and differentiation”
    • Used 904 nm, LLLT better than HLLT
  • https://pubmed.ncbi.nlm.nih.gov/31050946/
    • “Rapid Reversal of Cognitive Decline, Olfactory Dysfunction” using 635 and 810 nm light
  • https://www.liebertpub.com/doi/full/10.1089/pho.2016.4227?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
    • “There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4-week period.”
    • Used 810 nm, only 5 participants, they had AD and dementia
  • https://pubmed.ncbi.nlm.nih.gov/26535475/
    • “Clinical application of these levels of infrared energy for this patient with TBI yielded highly favorable outcomes with decreased depression, anxiety, headache, and insomnia, whereas cognition and quality of life improved. Neurological function appeared to improve based on changes in the SPECT by quantitative analysis. NIR in the power range of 10-15 W at 810 and 980 nm can safely and effectively treat chronic symptoms of TBI.”

This one talks about how in vitro studies involving photobiomodulation are generally flawed in experimental set up

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459822/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926176/

“Broadband polychromatic PBM showed no advantage over the red-light-only spectrum. However, both novel light sources that have not been previously used for PBM have demonstrated efficacy and safety for skin rejuvenation and intradermal collagen increase when compared with controls.”

https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0365-05962014000400616&lng=en&tlng=en

Best red light for atp production

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996814/

  • Talks about how the reason why we see changes like ATP Production from mitochondria is a result of redox reactions, since it results in cellular homeostasis
  • Since you did a lot of redox stuff w/ Heliopatch this might be worth a read

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355185/

  • 630 and 850 nm used; found that peak ATP synthesis occurs 3-6 hours after light is applied to skin (in vitro experiment)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215870/

  • Explores mechanisms behind light affecting ATP production in the mitochondria. One of the leading hypothesis is that the photons dissociate inhibitory nitric oxide from the cytochrome c oxidase enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. 

https://europepmc.org/article/pmc/pmc6462613

  • Interesting take on mitochondria and cytochrome c oxidase. This article says “Mitochondrial cytochrome c oxidase is not the primary acceptor for near infrared light; it is mitochondrial bound water”

https://pubmed.ncbi.nlm.nih.gov/25700769/

  • 6 hours for maximum benefit in LLLT. This is as a result of ATP increases due to mitochondria
  • STUDY DONE ON MICE

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Tiina Karu articles of interest:

https://www.sciencedirect.com/science/article/abs/pii/S1011134414002541?via%3Dihub

“Moreover we also report that a variety of biomolecules localized in mitochondria and/or in other cell compartments including cytochrome c oxidase, some proteins, nucleic acids and adenine nucleotides are light sensitive with major modifications in their biochemistry.”

-Used either laser or narrow band light (in this case both low power He–Ne laser with k = 632.8 nm, and non-coherent red light LED k = 650 ± 20 nm, were used).

There were several tests used to determine how light sensitive these biomolecules were by combining research on this topic from several papers and aggregating/analyzing results (refer to table 1). Most results showed positive correlation with light therapy/photobiomodulation including ATP production, # of mitochondria, mitochondria density, muscle regeneration.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3643261/

“The peak at 620 nm belongs to reduced CuA, and that at 680 nm, to oxidized CuB atoms in cytochrome c oxidase molecule.”

What is CuA and CuB?

In “classical” CcO, CuA accepts electrons from cytochrome c which are then transferred via heme a to the coupled heme a 3-CuB dioxygen-reducing site.

https://pubmed.ncbi.nlm.nih.gov/16125966/

“A similarity is established between the peak positions at 616, 665, 760, 813, and 830 nm in the absorption spectra of the cellular monolayers and the action spectra of the long-term cellular responses (increase in the DNA synthesis rate and cell adhesion to a matrix).”

https://pubmed.ncbi.nlm.nih.gov/15739174/

“The well-structured action spectrum for the increase of the adhesion of the cells, with maxima at 619, 657, 675, 740, 760, and 820 nm, points to the existence of a photoacceptor responsible for the enhancement of this property (supposedly cytochrome c oxidase, the terminal respiratory chain enzyme), as well as signaling pathways between the cell mitochondria, plasma membrane, and nucleus.”

In terms of NO and its affects on light therapy, it seems

https://pubmed.ncbi.nlm.nih.gov/12614475/

“Melatonin modifies the light action spectrum significantly in near IR region (760–840 nm only). Thus, the peak at 820–830 nm characteristic for the light action spectrum is fully reduced.”

We can possibly, according to this paper, extend the in vitro effects of this study to in vivo studies. This means that at wavelengths near-infrared, humans with higher levels of melatonin might be less susceptible to the positive benefits of red light therapy. Thus, especially if we use high wavelengths, we should figure out how one might try to optimize their melatonin levels.

https://pubmed.ncbi.nlm.nih.gov/19099388/?from_term=tiina+karu&from_page=2&from_pos=2

“The experimental results of our work demonstrate that irradiation at 632.8 nm causes either a (transient) relative reduction of the photoacceptor, putatively cytochrome c oxidase, or its (transient) relative oxidation, depending on the initial redox status of the photoacceptor.” 

https://pubmed.ncbi.nlm.nih.gov/15362946/

“The number of cells attached to glass substratum increases if HeLa cell suspension is irradiated with monochromatic visible-to-near infrared radiation before plating (the action spectrum with maxima at 619, 657, 675, 700, 740, 760, 800, 820, 840 and 860 nm).”

https://pubmed.ncbi.nlm.nih.gov/18307393/?from_term=tiina+karu&from_pos=9

“The biological effect (stimulation of cell attachment) of light with lambda = 637 nm on cells in our model system was pronounced, but did not depend on the degree of light polarization.”

https://pubmed.ncbi.nlm.nih.gov/14872239/

“The well-structured relationship between this biological response and the radiation wavelength (action spectrum with maxima at 620, 680, 760, and 820 nm) suggests the existence of a photoacceptor responsible for the enhancement of attachment (presumably cytochrome c oxidase, the terminal enzyme of the respiratory chain) and, secondly, the existence of signaling pathways between the mitochondria, the plasma membrane, and the nucleus of the cell.”

https://pubmed.ncbi.nlm.nih.gov/21796755/

“Cell adhesion and proliferation can be increased by irradiation with light of certain wavelengths (maxima in action spectrum are 619, 675, 740, 760, and 820 nm) or decreased when the activity of photoacceptor (cytochrome c oxidase in mitochondrial respiratory chain) is inhibited by chemicals before the irradiation.”

Summary of above:

Using these papers as a measure for the best wavelengths to irradiated red light on the body for maximum benefit, it seems as though Tiina Karu most commonly found the following wavelengths (in nm) to be most effective and as a result, were cited most commonly in her (looked it up and Tiina is a she) papers:

~620, ~680, ~760, ~820; frequently ~680 as well.

This correlates similarly, but not exactly with general consensus in other papers, which use ~635 nm and ~800 nm.

620-630, 670-680, 825-835

Brain related articles (first 3 copied from above):

https://pubmed.ncbi.nlm.nih.gov/31050946/

  • “Rapid Reversal of Cognitive Decline, Olfactory Dysfunction” using 635 and 810 nm light. 
  • “The patient showed a significant improvement in the Montreal Cognitive Assessment score from 18 to 24 and in the Working Memory Questionnaire score from 53 to 10. The cognitive enhancement was accompanied by reversal of olfactory dysfunction as measured by the Alberta Smell Test and peanut butter odor detection test. Quality-of-life measures improved and caregiver stress was reduced. No adverse effects were reported.”
    • Average Montreal Cognitive Assessment: 0-30 range, with 26+ considered normal
      • In a study, people without cognitive impairment scored an average of 27.4; people with mild cognitive impairment (MCI) scored an average of 22.1; people with Alzheimer’s disease scored an average of 16.2
    • Working Memory Questionnaire: Not a very conventional test, best article can be found here: https://pubmed.ncbi.nlm.nih.gov/22537095/
      • Avg Score is

https://www.liebertpub.com/doi/full/10.1089/pho.2016.4227?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

  • “There was significant improvement after 12 weeks of PBM (MMSE, p < 0.003; ADAS-cog, p < 0.023). Increased function, better sleep, fewer angry outbursts, less anxiety, and wandering were reported post-PBM. There were no negative side effects. Precipitous declines were observed during the follow-up no-treatment, 4-week period.”
  • Used 810 nm, only 5 participants, they had AD and dementia

https://pubmed.ncbi.nlm.nih.gov/26535475/

  • “Clinical application of these levels of infrared energy for this patient with TBI yielded highly favorable outcomes with decreased depression, anxiety, headache, and insomnia, whereas cognition and quality of life improved. Neurological function appeared to improve based on changes in the SPECT by quantitative analysis. NIR in the power range of 10-15 W at 810 and 980 nm can safely and effectively treat chronic symptoms of TBI.”

https://pubmed.ncbi.nlm.nih.gov/31050950/

  • Patients w/ dementia tested with MRIs and the Alzheimer’s Disease Assessment Scale-cognitive (ADAS-cog) subscale and the Neuropsychiatric Inventory (NPI).
  • At baseline, the UC and PBM groups did not differ demographically or clinically. However, after 12 weeks, there were improvements in ADAS-cog (group × time interaction: F1,6 = 16.35, p = 0.007) and NPI (group × time interaction: F1,6 = 7.52, p = 0.03), increased cerebral perfusion (group × time interaction: F1,6 = 8.46, p < 0.03), and increased connectivity between the posterior cingulate cortex and lateral parietal nodes within the default-mode network in the PBM group.
    • Essentially tests showed that subjects with hom PBM (meaning LLLT, self-administration) were still able to see the effects of PBM
  • Wavelength: 810 nm

https://pubmed.ncbi.nlm.nih.gov/31647776/

  • Compilation of several studies including one that was double, blind, placebo-controlled IRB-approved FDA Clinical Trial (all of which is VERY positive)
  • Took patients w/ AD and Parkinsons and showed that they demonstrated gain in memory and cognition by increased clock drawing.
  • Varying wavelengths in each study, some above what were are allowed to have

https://pubmed.ncbi.nlm.nih.gov/31647775/

  • Tested at 830 nm
  • 15 patients with general anxiety disorder tested using Hamilton Anxiety Scale (SIGH-A), the Clinical Global Impressions-Severity (CGI-S) subscale and the Pittsburgh Sleep Quality Index (PSQI) subscales from baseline to last observation carried forward.
  • Results show a significant reduction in the total scores of SIGH-A (from 17.27 ± 4.89 to 8.47 ± 4.87; p < 0.001; Cohen's d effect size = 1.47), in the CGI-S subscale (from 4.53 ± 0.52 to 2.87 ± 0.83; p < 0.001; Cohen's d effect size = 2.04), as well as significant improvements in sleep at the PSQI. t-PBM was well tolerated with no serious adverse events.
    • Basically what this is saying is that there was a significant change is scores from beginning to end of study. Worth noting that only 12 patients finished study, 3 dropped out for whatever reason

https://link.springer.com/chapter/10.1007%2F5584_2018_234

  • Used 635 nm
  • 40 patients with autism, all the participants were evaluated with the Aberrant Behavior Checklist (ABC), with the global scale and five subscales (irritability/agitation, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech), and the Clinical Global Impressions (CGI) Scale including a severity-of-illness scale (CGI-S) and a global improvement/change scale (CGI-C). 
  • ANCOVA analysis found this difference to be statistically significant (F = 99.34, p < 0.0001) compared to the baseline ABC irritability subscale score. The study found that low-level laser therapy could be an effective tool for reducing irritability and other symptoms and behaviors associated with the autistic spectrum disorder in children and adolescents, with positive changes maintained and augmented over time.

https://pubmed.ncbi.nlm.nih.gov/31390288/

  • Used 633 nm
  • 27 patients w/ Binswanger’s disease (BD) were in study. 14 underwent intracerebral transcatheter laser PBMT, and 13 patients-had conservative treatment. The used CT’s MRI’s and measures of blood flow to gauge progress.
  • Good and satisfactory clinical results were obtained in Test group 1 and Test group 2 patients in 49 (92.45%) cases, with a persistent decrease of dementia and motor impairment, and recovery of cognitive functions and daily life activity. Control group 1 and Control group 2 patients showed a satisfactory clinical result in 6 (15.79%) cases. Persistent positive dynamics was not observed. 

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ATP https://pubmed.ncbi.nlm.nih.gov/17603858/ 808nm

ATP lots of wavelengths  https://pubmed.ncbi.nlm.nih.gov/29665018/

ATP superiority of red over blue green 2017 https://pubmed.ncbi.nlm.nih.gov/28798481/

660 was better than 830 at atp production https://pubmed.ncbi.nlm.nih.gov/27857496/ 

Find out why pulsing was bad for the cells https://onlinelibrary.wiley.com/doi/abs/10.1002/adbi.201900227

Lots of wavelengths Fibroblasts grew better with 660-70 while 810 actually reduced growth (fibroblasts make collagen. https://pubmed.ncbi.nlm.nih.gov/15662631/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215870/

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Showing ability to illuminate brain using cadaver 670 and 808 nm https://pubmed.ncbi.nlm.nih.gov/25789711/

Comparison of LED to laser and showed no real difference

https://pubmed.ncbi.nlm.nih.gov/24197518/

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Quote I like -ROS are one of the classic “Janus face” mediators; beneficial in low concentrations and harmful at high concentrations; beneficial at brief exposures and harmful at chronic long-term exposures. ROS are produced at a low level by normal mitochondrial metabolism. The concept of mitohormesis was introduced to describe the beneficial of low controlled amounts of oxidative stress in the mitochondria. However when the mitochondrial membrane potential is altered either upwards or downwards, the amount of ROS is increased. In normal cells, absorption of light by Cox leads to an increase in mitochondrial membrane potential and a short burst of ROS is produced. However when the mitochondrial membrane potential is low because of pre-existing oxidative stress, excitotoxicity, or inhibition of electron transport, light absorption leads to an increase in mitochondrial membrane potential towards normal levels and the production of ROS is lowered.

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