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Low Level Light Therapy
sponsored by
American Society for Photobiology
Low Level Light Therapy is the application of very low power red or near infrared light for wound healing or other therapeutic purposes.
Controversy and the Need for a Paradigm Shift in Low-Level Laser Therapy
Elizabeth Rodríguez de Santana, M.D. and Luis A. Santana Blank, M.D., Fundalas, Foundation for Interdisciplinary Research and Development.
e-mail: fundalas@mail2science.com, web site
Nearly forty years after Mester's pioneer studies on the biological effects of non-ionizing light [1] often referred to as Low-Level Laser Therapy (LLLT), skepticism continues to surround this type of radiation even though there is currently substantial evidence of its effects [2]. Causes for long-lasting distrust in some circles have been manifold. In a review of a new LLLT modality termed Photo-Infrared Pulsed Biomodulation (PIPBM) [3], we summarized potential sources of discredit as unchecked mercantilism, absence of sound scientific methodology behind numerous studies, scarcity of indisputable clinical effects and a general want of plausible theory for reported findings. Other interpretations exist.
In a careful and well-thought analysis, Hamblin and Demidova [4] attribute the controversy surrounding LLLT to two main reasons: an incomplete understanding of the biochemical mechanisms underlying the positive effects reported and "the complexity of rationally choosing amongst a large number of illumination parameters." Two comments can be made about this:
a. In reference to complexity in the interpretation of negative and positive results due to the diversity of illumination parameters used, we may add that said perceived difficulty is often encouraged by the lack or incompleteness of information on wave and treatment parameters found in numerous publications. Responsibility for this deficiency, which hinders reproducing and interpreting data, falls squarely on authors, reviewers and journals. As recently argued by Smith [5] "it is absolutely necessary to specify the wavelength(s) of light used, the area of irradiation, the dose of radiation (whether incident or absorbed), time, etc." We, consequently, endorse Smith's "plea to phototherapy groups, societies and journals, to raise the standards for running and publishing experiments and clinical trials by learning the basics of photobiology, and thereby accelerating the acceptance of this field into the mainstream of science and medicine."
b. On the other hand, greater understanding of the biochemical and biophysical bases of LLLT can only arise from an objective and open dissemination of all rigorously obtained results and a comprehensive discussion of scientifically-sound mechanistic information. Yet, it seems that, despite the obtuse mentality faced for decades by researchers studying LLLT, some in the field have adopted the same type of frame of mind. For instance, notwithstanding the very positive comments received over the years in reference to our studies, we can personally attest to the irrationality of the opposition given by some to ideas that broaden or redefine existing paradigms.
Hamblin and Demidova summarize LLLT effects and proposed mechanisms as follows:
"This introductory review will cover some of the proposed cellular chromophores responsible for the effect of visible light on mammalian cells, including cytochrome c oxidase (with absorption peaks in the near infrared) and photoactive porphyrins. Mitochondria are thought to be a likely site for the initial effects of light, leading to increased ATP production, modulation of reactive oxygen species and induction of transcription factors. These effects in turn lead to increased cell proliferation and migration (particularly by fibroblasts), modulation in levels of cytokines, growth factors and inflammatory mediators, and increased tissue oxygenation."
In addition to the mechanisms described in the above excerpt, the proposed role of water and carbon dioxide, primary photoacceptors of red to NIR irradiation has been documented and discussed in our group's theoretical [6,7] experimental [8,9] and clinical results [10-15] - all of which have been published by leading peer-reviewed journals- and their mechanistic basis [3]. In addition to the potential benefits of LLLT described by Hamblin and Demidova as "increased healing in chronic wounds, improvements in sports injuries and carpal tunnel syndrome, pain reduction in arthritis and neuropathies, and amelioration of damage after heart attacks, stroke, nerve injury and retinal toxicity," our group has presented results for cancer (backed by a phase I trial in patients with advanced neoplasias that appeared in one of the most highly regarded journals in oncology [12]), ophthalmology, neuroscience and other disciplines.
In his landmark book The Structure of Scientific Revolutions, Thomas Kuhn showed that most breakthroughs in science are initially a rupture from established ideas, a concept he aptly termed a "paradigm shift." It is our opinion that, for LLLT to gain acceptance into the mainstream of science and medicine, novel ideas must be objectively assessed and, if valid, incorporated into a new paradigm that reflects the immense therapeutic potential of light. Consequently, at Fundalas, we have strived to promote cooperation and constructive discussion in the field [16-19].
The history of corneal shaping to correct vision defects - which gave birth to now pervasive laser eye surgery techniques - may provide valuable insights to LLLT researchers about the importance of cooperation and objectivity. Until the early 1980s, surgical techniques investigated in Japan and the former Soviet Union to reduce myopia were regarded, with some justification, as "unorthodox" in the West. The world medical community was only assured of the validity of said approach as a result of joint multi-center studies with ample governmental, institutional and individual support. As a witness and participant of this endeavor, one of us (Rodríguez-Santana) had the opportunity to learn first hand the effectiveness of collective, unbiased, efforts to change an existing paradigm and, ultimately, benefit the general public [20].
Thus, we consider auspicious that the leadership of the American Society for Photobiology has embarked on the worthy venture of dispelling misconceptions on the topic of LLLT. It is certainly hoped that petty differences and well-known shortcomings no longer stand on the way of progress in the field. If so, therapeutic uses of non-ionizing light in medicine may finally shine.
References
1. Mester E., Sellyei, M Tota, GJ. [Laser beam effect on the growth of the Ehrlich ascites tumor] Arch. Geschwulstforsch. 1968;32:201-206.
2. Karu TI, Kolyakov SF. Exact action spectra for cellular responses relevant to phototherapy. Photomed Laser Surg. 2005 Aug;23(4):355-61.
3. Santana-Blank LA, Rodriguez-Santana E, Santana-Rodriguez KE. Photo-infrared pulsed bio-modulation (PIPBM): a novel mechanism for the enhancement of physiologically reparative responses. Photomed Laser Surg. 2005 Aug;23(4):416-24.
4. Hamblin MR, Demidova TN. Mechanisms for Low-Light Therapy. Edited by Hamblin, Michael R.; Waynant, Ronald W.; Anders, Juanita. Proceedings of the SPIE, Volume 6140, pp. 1-12 (2006).
5. Kendric C. Smith. Laser and LED Therapy is Phototherapy. www.pol-us.net/lllt/phototherapy.html
6. González JA, Martin-Landrove M. Solitons in a nonlinear DNA model. Physics Letters 1994; 191:409-415.
7. González JA, Martin-Landrove M, Carbo JR, Chacon M. Bifurcations and Chaos of DNA Solitonic Dynamics. International Centre For Theoretical Physics, ed. International Atomic Energy Agency, Trieste, Italy 1994; 1-29.
8. Santana-Blank LA, Rodriguez-Santana E, Scott-Algara D, Hunger M, Santana-Rodriguez KE, Orellana R. Short-term bioeffects of an infrared pulsed laser device on burned rat skin monitored by transverse relaxation times (NMR). Lasers Surg Med. 2000;27(5):411-9.
9. Rodríguez-Santana E, Santana-Blank LA, Reyes H, Santana-Rodriguez KE, Hunger M, Orellana R, Ortega D. H-NMR spin-lattice and correlation times of burned soft-tissues after treatment with an infrared pulsed laser device. Lasers Surg Med. 2004;34(5):398-406.
10. Santana-Blank LA, Reyes H, Rodríguez-Santana E, Santana-Rodriguez KE. Microdensitometry of T2-weighted magnetic resonance (MR) images from patients with advanced neoplasias in a phase I clinical trial of an infrared pulsed laser device (IPLD). Lasers Surg Med. 2004;34(5):398-406.
11. Rodríguez-Santana, E. (2004). The amazing reparative potential of a novel low-energy laser in ophthalmic diseases: theoretical, experimental and clinical foundations. Presented at the First Diode Laser Technology Workshop, 24th Annual Meeting of the American Society of Laser Medicine and Surgery, Dallas.
12. Santana-Blank LA, Rodríguez-Santana E, Vargas F, Reyes H, Fernandez-Andrade P, Rukos S, Santana-Rodriguez KE. Phase I trial of an infrared pulsed laser device in patients with advanced neoplasias. Clin Cancer Res. 2002;8:3082-91.
13. Santana-Blank LA, Rodríguez-Santana E, Vargas F, Santana-Rodriguez KE. Photo-induced cytomorphologic changes in an advanced cancer phase I clinical trial. Lasers Surg Med. 2002;30:18-25.
14. Santana-Blank LA, Castes M, Rojas ME, Vargas F, Scott-Algara D. Evaluation of serum levels of tumour necrosis factor-alpha (TNF-alpha) and soluble IL-2 receptor (sIL-2R) and CD4, CD8 and natural killer (NK) populations during infrared pulsed laser device (IPLD) treatment. Clin Exp Immunol. 1992 Oct;90(1):43-8.
15. Martín M, Itriago S, Martín R, Santana-Blank LA. Tumor characterization by transversal relaxation rate distribution analysis. World Congress on Medical Physics and Biomedical Engineering 1994, Rio de Janeiro Brazil.
16. Santana-Blank L. Effects of an infrared pulsed laser device (IPLD) over apoptosis in cancer cells. Bioelectromagnetics. 2005 Sep;26(6):523-4.
17. Santana-Blank L. Exchanging ideas about research that is both methodologically sound and scientifically relevant. Photomed Laser Surg. 2004 Oct;22(5):442-3.
18. Santana-Blank L. Contraindications in noninvasive laser therapy: truth and fiction. Photomed Laser Surg. 2004 Oct;22(5):442.
19. Santana-Blank L. Modulated low-energy near-infrared (NIR) lasers and cancer: an invitation to discuss a new treatment approach. Lasers Surg Med. 2003;32(1):1-2.
20. McDonald M, Frantz J, Santana E, Salmeron B, Stephenson G, Klyce S, Beuerman R, Kaufman H Excimer laser surface shaping of the primate for correction of myopia. ARVO Abstract. Invest Ophthalmol Vis. Sci (Suppl) 1988;29:310.