Research

Low Level Light Therapy (LLLT) Research Quotes

“So many acronyms are used in this field that it is confusing to readers, e.g., Low-Level Light Therapy (LLLT), Low-Power Laser Irradiation (LPLI), Low-Power Laser Therapy (LPLT), Low-Energy Laser Irradiation (LELI), etc., etc. It would be a great boon to the field if there could be some standardization of nomenclature. Since all these devices just produce light, I would urge the use of the simple and correct term, Low-Level Light Therapy (LLLT) (Smith 2014).

 

“Since life on earth evolved under the sun, who’s terrestrial photon flux (“intensity”) is greatest between 400 nm and 800 nm, it should not be surprising that most biological responses to light are induced by radiation between 400 nm and 800 nm. LLLT delivered at low doses tends to work better than the same wavelength delivered at high levels” (Smith 2004).

 

“Coherent and noncoherent light with the same parameters (i.e., wavelength, dose, intensity) produce the same biological effects on cell monolayers (Karu et al., 1982a, b), and in dilute cell suspensions (Karu et al., 1983; Bertoloni et al., 1993), as well as on tissue surfaces (e.g., the healing of peptic ulcers; Karu et al., 1984; Sazonov et al., 1985). In these cases, the healing effect of irradiation is occurring via absorption of light by photoacceptors (cytochrome-C-oxidase in particular, Karu, 1999, 2003). However, some additional (therapeutic) effects from coherent and polarized radiation, in addition to those caused by light absorption by photoacceptors molecules, can appear in deeper layers of bulk tissue” (Karu 2011).

 

“Each chemical compound has a different absorption spectrum, because of its unique electronic structure. Each of the wavelengths absorbed by a chemical compound will be absorbed to different degrees, again because of the unique electronic structure of the compound” (Smith 2014).

 

“An action spectrum is a plot of the relative effectiveness of different wavelengths of light in causing a particular biological response, and under ideal conditions it should mimic the absorption spectrum of the molecule that is absorbing the light, and whose photochemical alteration causes the biological effect” (Smith 2014).

 

“LLLT delivered at low doses tends to work better than the same wavelength delivered at high levels, which illustrates the basic concept of biphasic dose response or hormesis (Calabrese 2001b). In general, fluences of red or NIR as low as 3 or 5 J/cm² will be beneficial in vivo, but a large dose like 50 or 100 J/cm² will lose the beneficial effect and may even become detrimental. The molecular and cellular mechanisms LLLT suggest that photons are absorbed by the mitochondria; they stimulate more ATP production and low levels of ROS, which then activates transcription factors, such as NF-κB, to induce many gene transcript products responsible for the beneficial effects of LLLT” (Huang, Y.Y.; Chen, A.C.; Carroll, J.D.; Hamblin, M. R. 2009). Retrieved on 6 Oct 14 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790317/

References:

Please follow this link for a list of 3747 papers on Low Level Light Therapy listed on PubMed.

 

MECHANISMS of LOW LEVEL LIGHT THERAPY: EVERYTHING YOU EVER WANTED to KNOW and MORE from HARVARD MEDICAL SCHOOL

Dr Michael R. Hamblin: Department of Dermatology, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, 40 Blossom Street, Boston MA 02114; Retrieved on 14 Sep 2014 from: http://www.photobiology.info/Hamblin.html

 

NASA LIGHT EMITTING DIODE MEDICAL APPLICATIONS – from DEEP SPACE to DEEP SEA

Harry T. Whelan 1a, 5, 7, Ellen V. Buchmann1a, Noel T. Whelan 1a, 7, Scott G. Turner 1a, Vita Cevenini 7, Helen Stinson 7, Ron Ignatius 2, Todd Martin 2, Joan Cwiklinski 1a, Glenn A. Meyer 1c, Brian Hodgson 3, 4, Lisa Gould 1b, Mary Kane 1b, Gina Chen 1b, James Caviness 6. Published on 2 Feb 2001 / DOI: 10.1063/1.1357902. Retrieved on 25 Sep 2014 at http://academic.research.microsoft.com/Publication/5064338

 

WHAT IS PHOTOBIOLOGY?

Dr Smith, Kendric, C., Emeritus Professor, Radiation Oncology (Radiation Biology) Stanford University School of Medicine; 800 Blossom Hill Road, Unit R169, Los Gatos, CA 95032. Published online Retrieved on 25 Sep 2014 kendric@stanford.edu / www.stanford.edu/~kendric/

 

BIPHASIC DOSE RESPONSE in LOW LEVEL LIGHT THERAPY

Dr’s Ying-Ying Huang, Aaron C.-H. Chen, […], and Michael R. Hamblin. Retrieved on 25 Sep 2014 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790317/

 

LIGHT COHERENCE – IS THIS PROPERTY IMPORTANT FOR PHOTOMEDICINE?

Tiina I. Karu Institute of Laser and Information Technologies, Russian Academy of Sciences, Troitsk 142190, Moscow Region, Russian Federation; tkaru@isan.troitsk.ru/ Published online 4 June 2011. Retrieved on 10 July 2014 from http://www.photobiology.info/Coherence.html

 

LOW-LEVEL LASER or LED THERAPY IS PHOTOTHERAPY

Kendric C. Smith (200314); Emeritus Professor, Radiation Oncology (Radiation Biology), Stanford University School of Medicine, 800 Blossom Hill Road, Unit R169, Los Gatos, CA 95032, kendric@stanford.edu

 

LASER AND LED PHOTOBIOLOGY

Kendric C Smith, Stanford School of Medicine, CA, USA. Published online. Retrieved on 1 Oct 2014 from: http://web.stanford.edu/~kendric/PDF/B57.pdf

 

THERAPEUTIC PHOTOBIOMODULATION for METHANOL-INDUCED RETINAL TOXICITY

By J. T. Eells,^*† M. M. Henry,^* P. Summerfelt,^‡ M. T. T. Wong-Riley,^‡ E. V. Buchmann,^§ M. Kane,^§ N. T. Whelan,^§ and H. T. Whelan^§ , Published online 18 Mar 2003 by US National Library of Medicine Acad. Sci. USA. 100(6): 3439–3444. Retrieved on 4 Oct 2014 from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC152311/

 PubMed Abstracts on LLLT

 Photomed Laser Surg. 2006 Apr;24(2):121-8.

Clinical and experimental applications of NIR-LED photobiomodulation.

Desmet KD¹, Paz DA, Corry JJ, Eells JT, Wong-Riley MT, Henry MM, Buchmann EV, Connelly MP, Dovi JV, Liang HL, Henshel DS, Yeager RL, Millsap DS, Lim J, Gould LJ, Das R, Jett M, Hodgson BD, Margolis D, Whelan HT.

Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16706690

Abstract

This review presents current research on the use of far-red to near-infrared (NIR) light treatment in various in vitro and in vivo models. Low-intensity light therapy, commonly referred to as “photobiomodulation,” uses light in the far-red to near-infrared region of the spectrum (630-1000 nm) and modulates numerous cellular functions. Positive effects of NIR-light-emitting diode (LED) light treatment include acceleration of wound healing, improved recovery from ischemic injury of the heart, and attenuated degeneration of injured optic nerves by improving mitochondrial energy metabolism and production. Various in vitro and in vivo models of mitochondrial dysfunction were treated with a variety of wavelengths of NIR-LED light. These studies were performed to determine the effect of NIR-LED light treatment on physiologic and pathologic processes. NIRLED light treatment stimulates the photoacceptor cytochrome c oxidase, resulting in increased energy metabolism and production. NIR-LED light treatment accelerates wound healing in ischemic rat and murine diabetic wound healing models, attenuates the retinotoxic effects of methanol-derived formic acid in rat models, and attenuates the developmental toxicity of dioxin in chicken embryos. Furthermore, NIR-LED light treatment prevents the development of oral mucositis in pediatric bone marrow transplant patients. The experimental results demonstrate that NIR-LED light treatment stimulates mitochondrial oxidative metabolism in vitro, and accelerates cell and tissue repair in vivo. NIR-LED light represents a novel, noninvasive, therapeutic intervention for the treatment of numerous diseases linked to mitochondrial dysfunction.

 

J  Clin Laser Med Surg. 2001 Dec 19 (6):305-14.

Effect of NASA light-emitting diode irradiation on wound healing.

Whelan HT¹, Smits RL Jr, Buchman EV, Whelan NT, Turner SG, Margolis DA, Cevenini V, Stinson H, Ignatius R, Martin T, Cwiklinski J, Philippi AF, Graf WR,Hodgson B, Gould L, Kane M, Chen G, Caviness J.

Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/11776448

Abstract

OBJECTIVE:
The purpose of this study was to assess the effects of hyperbaric oxygen (HBO) and near-infrared light therapy on wound healing.

BACKGROUND DATA:
Light-emitting diodes (LED), originally developed for NASA plant growth experiments in space show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper, we review and present our new data of LED treatment on cells grown in culture, on ischemic and diabetic wounds in rat models, and on acute and chronic wounds in humans.

MATERIALS AND METHODS:
In vitro and in vivo (animal and human) studies utilized a variety of LED wavelength, power intensity, and energy density parameters to begin to identify conditions for each biological tissue that are optimal for biostimulation.

RESULTS:
LED produced in vitro increases of cell growth of 140-200% in mouse-derived fibroblasts, rat-derived osteoblasts, and rat-derived skeletal muscle cells, and increases in growth of 155-171% of normal human epithelial cells. Wound size decreased up to 36% in conjunction with HBO in ischemic rat models. LED produced improvement of greater than 40% in musculoskeletal training injuries in Navy SEAL team members, and decreased wound healing time in crew members aboard a U.S. Naval submarine. LED produced a 47% reduction in pain of children suffering from oral mucositis.

CONCLUSION:
We believe that the use of NASA LED for light therapy alone, and in conjunction with hyperbaric oxygen, will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury/illness level of activity. This work is supported and managed through the NASA Marshall Space Flight Center-SBIR Program.

PMID: 11776448 [PubMed – indexed for MEDLINE]

 

Photomed Laser Surg. 2010 Jun;28(3):291-325. doi: 10.1089/pho.2008.2446.

Laser Photobiomodulation of wound healing: a review of experimental studies in mouse and rat animal models.

Peplow PV¹, Chung TY, Baxter GD.

Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/19995230

Abstract

OBJECTIVES:
This investigation reviewed experimental studies of laser irradiation of wound healing in mice and rats published from 2003 to August 2008, respectively, to assess putative stimulatory effects of this treatment.

BACKGROUND:
Animal models, including rodents, attempt to reflect human wound healing and associated problems such as dehiscence, ischemia, ulceration, infection, and scarring. They have played a key role in furthering understanding of underlying mechanisms involved in impaired wound healing, and in testing new therapeutic strategies including laser irradiation.

METHOD:
Original research papers investigating effects of laser or monochromatic light therapy on wound healing in mice and rats and published from January 2003 to August 2008 were retrieved from library sources, PubMed and Medline databases, reference lists from retrieved papers, and hand searches of relevant journals. Papers were selected for this review with regard to specific inclusion and exclusion criteria. Studies were critically reviewed in terms of study design, methodology, and appropriateness of laser irradiation parameters.

RESULTS:
The literature search identified eight studies in mice and 39 in rats. A variety of wound models were investigated, including acute-wound, impaired-healing, and chronic-wound models. Considerable variation was observed in research design, methodology, and irradiation parameters employed, limiting comparison of research findings between studies. Inadequate reporting of key experimental details, or errors in specification and/or calculation of key irradiation parameters was also found. Evidence from the studies reviewed suggested that use of red or infrared wavelength at a range of dosage parameters (median 4.2 J cm(-2)) results in significant benefits in measured parameters of wound healing. Interestingly, coherence does not seem essential to the photobiomodulatory effects of ‘laser’ phototherapy.

CONCLUSION:
Studies reviewed consistently demonstrated the ability of laser or monochromatic light to photobiomodulate wound healing processes in experimental wounds in rats and mice, and strongly support the case for further controlled research in humans.

PMID: 19995230 [PubMed – indexed for MEDLINE]

J Clin Laser Med Surg. 2003 Apr;21(2):67-74.

 

Effect of NASA light-emitting diode irradiation on molecular changes for wound healing in diabetic mice.

Whelan HT¹, Buchmann EV, Dhokalia A, Kane MP, Whelan NT, Wong-Riley MT, Eells JT, Gould LJ, Hammamieh R, Das R, Jett M.

Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/12737646

Abstract

OBJECTIVE:
The purpose of this study was to assess the changes in gene expression of near-infrared light therapy in a model of impaired wound healing.

BACKGROUND DATA:
Light-Emitting Diodes (LED), originally developed for NASA plant growth experiments in space, show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper we present the effects of LED treatment on wounds in a genetically diabetic mouse model.

MATERIALS AND METHODS:
Polyvinyl acetal (PVA) sponges were subcutaneously implanted in the dorsum of BKS.Cg-m +/+ Lepr(db) mice. LED treatments were given once daily, and at the sacrifice day, the sponges, incision line and skin over the sponges were harvested and used for RNA extraction. The RNA was subsequently analyzed by cDNA array.

RESULTS:
Our studies have revealed certain tissue regenerating genes that were significantly upregulated upon LED treatment when compared to the untreated sample. Integrins, laminin, gap junction proteins, and kinesin superfamily motor proteins are some of the genes involved during regeneration process. These are some of the genes that were identified upon gene array experiments with RNA isolated from sponges from the wound site in mouse with LED treatment.

CONCLUSION:
We believe that the use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process, and more quickly return the patient to a preinjury / illness level of activity. This work is supported and managed through the Defense Advanced Research Projects Agency (DARPA) and NASA Marshall Space Flight Center-SBIR Program.

PMID: 12737646 [PubMed – indexed for MEDLINE]

 

 

 PubMed – published online Sep 1, 2009. doi:  10.2203/dose-response.09-027.Hamblin

Biphasic Dose Response in Low Level Light Therapy

Ying-Ying Huang; Aaron C.-H. Chen; James D. Carroll; Michael R. Hamblin

Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2790317/

Abstract

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. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.