Low-level laser therapy (LLLT), cold laser therapy, or photobiomodulation (PBM) is a photochemical reaction-based medical treatment that applies low-level (low-power) lasers or light-emitting diodes (LEDs) to the surface of the body without damaging tissue. Proponents claim that this treatment stimulates healing, relieves pain, and enhances cell function. Sometimes termed as low-level red-light therapy (LLRL), its effects appear to be limited to a specific range of wavelengths. Its effectiveness is under investigation. Several such devices are cleared by the United States Food and Drug Administration (FDA). The therapy may be effective for conditions such as juvenile myopia,Jiang M.D., Yu, et al., Effect of Repeated Low-Level Red-Light Therapy for Myopia Control in Children, Ophthalmology, American Academy of Ophthalmology, Volume 129, Issue 5P509–519, May 2022. rheumatoid arthritis, and oral mucositis.

Mechanism

LLLT uses lasers, LEDs, or a combination of both to alter biological activity. The light sources expose cells to low levels of red and near infrared light (compared to other forms of laser therapy).

LLLT is subject to the Grotthuss-Draper law, the first law in photochemistry: light must be absorbed by a chemical substance in order for a photochemical reaction to take place. In the generally accepted LLLT theory that chemical substance is represented by the respiratory enzyme cytochrome c oxidase, which is involved in the electron transport chain in mitochondria. Administering LLLT below the dose range does not appear to be effective.

Applications

Human use Musculoskeletal conditions LLLT has been studied for use in treatment of musculoskeletal conditions, including:

osteoarthritis rheumatoid arthritis temporomandibular joint disorders chronic low back pain neck pain tendinopathy chronic joint disorders.

Other wound healing smoking cessation tuberculosis. periodontal disease

Prevention LLLT appears to be effective for preventing:

oral mucositis in recipients of a stem cell transplant with chemotherapy

Brain stimulation Transcranial low level light therapy (or transcranial photobiomodulation) is limited in neuromodulation by several factors:

Excessive radiation can be harmful.Smith KC (2005). Laser (and LED) therapy is phototherapy. Photomed. Laser Surg. 23, 78–80. Therefore, dosing must be strictly controlled to achieve growth stimulation, while avoiding excessive singlet oxygen that may be harmful to cells.Karu, T (1989). Photobiology of low-power laser effects. Health Physics 56, 691–704. LED stimulation cannot pass through the skin, only laser light can penetrate deeper tissues and stimulate brain areas. The penetration depth of white and LED light into the skin increases with increasing wavelength from the ultraviolet to the visible light range, and then decreases again in the infrared range. This depth increases if the thickness of the stratum corneum decreases.Louise Finlayson, Isla RM Barnard, Lewis McMillan, Sally H Ibbotson, C Tom A Brown, Ewan Eadie, Kenneth Wood (2021) "Depth Penetration of Light into Skin as a Function of Wavelength from 200 to 1000 nm". Photochemistry and Photobiology, Volume 98, Issue 4, published by Wiley Periodicals LLC. https://doi.org/10.1111/php.13550. White light and LED radiation can only penetrate 0.0017 mm to 5 mm of tissue. At wavelengths of 450 nm and 650 nm only 1% of the light reaches approximately 1.6 mm and very little reaches 5 mm.Ash, C, M Dubec, K Donne and T Bashford (2017) "Effect of wavelength and beam width on penetration in light-tissue interaction using computational methods". Lasers Med. Sci 32, 1909–1918.

The action spectrum for tissue regeneration and repair consist of more than one wavelength,Calderhead RG (2007). "The photobiological basics behind light-emitting diode (LED) phototherapy". Laser Ther. 16, 97–108. such that laser and LED light sources may offer some disadvantages,Wunsch A and Matuschka K (2014). "A controlled trial to determine the efficacy of red and near-infrared light treatment in patient satisfaction, reduction of fine lines, wrinkles, skin roughness, and intradermal collagen density increase". Photomed Laser Surg, 2014 32(2): p. 93–100.24286286 possibly destroying healthy cells. Links between neuronal activity and mental processes are still research questions as is whether the laser reaches only the neuronal structures that benefit from treatment. Insufficient information from clinical trials compares the effectiveness of different types of devices or device parameters (wavelengths, power output, session time, area of actuation).

Veterinary use Veterinary clinics use cold laser devices to treat a wide variety of ailments, from arthritis to wounds, on dogs and cats.Robinson, Narda G. (2013), "Complementary and Alternative Veterinary Medicine: Laser Therapy", The Merck Veterinary Manual, 11th edition. In spite of this, little research has been done on its effects. According to Brennen McKenzie, president of the Evidence-Based Veterinary Medicine Association, as of 2016 "research into cold laser in dogs and cats is sparse and generally low quality. Most studies are small and have minimal or uncertain controls for bias and error".McKenzie, Brennen (2016), "The Laser Craze: What Is the Evidence for Low-level Laser Therapy?" [SA222]; Western Veterinary Conference, Proceedings of the WVC 88th Annual Conference, Mandalay Bay Convention Center, Resort and Casino, Las Vegas, NV, March 6–10, 2016.McKenzie, Brennen (2016), "WVC 2016: The Laser Craze", The SkeptVet. He allowed that some studies show promising results, while concluding that current evidence is not sufficient to support routine clinical use.

Contraindications Based on the results of a systematic review, there is no evidence to suggest that people with cancer or people who are at risk of getting cancer should avoid photobiomodulation.

Side effects There are some reports of mild pain or skin irritation after red-light therapy. The long-term effects on the skin or the hair are not known. Eye protection is suggested for some devices. For skin applications, different wavelengths of light may result in different biological effects depending on the person's skin type, race, and ethnicity. Clinical guidelines suggest that a dermatologist be consulted before undergoing treatment.

For safety, use should be limited to a device approved for human use by the relevant government authority; for example, in the US, it is suggested that only devices certified by the FDA for dermatologic application be used.

History Faroese physician Niels Finsen is believed to be the father of modern light therapy. He used red light to treat smallpox lesions. He received the Nobel Prize in Physiology or Medicine in 1903. Scientific evidence for some of his treatments is lacking, and later eradication of smallpox and development of antibiotics for tuberculosis rendered light therapy obsolete for these diseases.

Hungarian physician and surgeon Endre Mester (1903–1984) is credited with the discovery of the biological effects of low power lasers, which occurred a few years after the 1960 invention of the ruby laser and the 1961 invention of the helium–neon (HeNe) laser. Mester accidentally discovered that low-level ruby laser light could regrow hair during an attempt to replicate an experiment that showed that such lasers could reduce tumors in mice. The laser he was using was faulty and was not as powerful as believed. It failed to affect the tumors, but in places where the mice had been shaved in order to do the experiments, the hair grew back more quickly on the treated mice than on those among the control group. He published those results in 1967. Mester went on to show that low level HeNe light could accelerate wound healing in mice.

By the 1970s, he was applying low level laser light to treat people with skin ulcers. In 1974, he founded the Laser Research Center at the Semmelweis Medical University in Budapest, and continued working there for the remainder of his life. His sons carried on his work and brought it to the United States.

By 1987, companies selling lasers were claiming that they could treat pain, accelerate healing of sports injuries, and treat arthritis, but there was little evidence for this at that time.

Mester originally called this approach "laser biostimulation", but it soon became known as "low-level laser therapy". With the adaptation of light emitting diodes it became known as "low-level light therapy"; to resolve confusion around the exact meaning of "low level", the term "photobiomodulation" arose as a synonym.

Names Alternative terms for low level light therapy are: LLLT, laser biostimulation, laser phototherapy, low-level laser therapy, low-power laser irradiation, low-power laser therapy, and photobiomodulation therapy. The term photobiomodulation therapy is considered the preferred term by industry professionals.. However LLLT has been marketed and researched under a number of other terms, including red light therapy, low-power laser therapy (LPLT), soft laser therapy, low-intensity laser therapy, low-energy laser therapy, cold laser therapy, bio-stimulation laser therapy, photo-biotherapy, therapeutic laser, and monochromatic infrared light energy (MIRE) therapy.American Cancer Society. Cold Laser Therapy Page archived April 24, 2015 More specific applications sometimes have their own terms, for example when administered to acupuncture points, the procedure is called laser acupuncture. When applied to the head, LLLT may be known as transcranial photobiomodulation, transcranial near-infrared laser therapy (NILT), or transcranial low level light therapy.

Government action The FDA filed a complaint for injunction in 2014, alleging that the company QLaser PMA was marketing its devices as being able to treat "over 200 different diseases and disorders," including cancer, cardiac arrest, deafness, diabetes, HIV/AIDS, macular degeneration, and venereal disease. This case resulted in a permanent injunction against the manufacture, marketing, sale, and distribution of those devices in 2015.

In 2017, the owner of QLaser, Robert Lytle, and two of QLaser's distributors were charged with a criminal conspiracy to commit fraud. Lytle pleaded guilty to one count of conspiracy to introduce misbranded medical devices into interstate commerce with the intent to defraud and mislead, and one count of criminal contempt in January 2018. Lytle was sentenced to serve 12 years in prison and made an initial restitution payment of $637,000. Lytle's conspirators were sentenced to 24 months and 15 months, respectively.

Insurance coverage

Blue Cross Blue Shield Association and Aetna provide coverage for the prevention of oral mucositis, but not any other reason. (Policy reviewed each June; if link is dead try replacing "06-18" with a more recent year.)"Infrared therapy". Aetna clinical policy bulletin 0363, reviewed June 17, 2020. Aetna has additional information in its "Clinical Policy Bulletin on Cold Laser and High-Power Laser Therapies". The Centers for Medicare and Medicaid Services does not provide coverage for LLLT."Decision memo for infrared therapy devices" (CAG00291N). Center for Medicare & Medicaid Services, Oct 24, 2006. Cigna lists LLLT as "experimental, investigational, or unproven for any indication" and provides literature review summaries for a number of conditions.

Research

Musculoskeletal