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Introduction

Light has profound and diverse effects on the human body, influencing sleep-wake cycles, circadian rhythmicity, immune function, and even mood. In recent decades, scientists have begun exploiting the body's responses to light with photobiomodulation, a non-invasive, light-based therapeutic technique that uses specific wavelengths of light to stimulate biological processes within cells and tissues, triggering a cascade of physiological responses. A growing body of evidence suggests that photobiomodulation has potential applications in medicine, dentistry, cosmetic procedures, and scientific research. This article presents the history and current clinical evidence of photobiomodulation and describes the mechanisms and modalities that drive its effects.

In brief, research demonstrates that photobiomodulation may…

• Promote hair regrowth in people with androgenic alopecia.^[1]
• Enhance collagen production and reduce the appearance of fine lines on the skin.^[2]
• Restore healthy thyroid function in the setting of autoimmune hypothyroidism.^[3]
• Support muscle performance and recovery.^[4]
• Improve symptoms of depression.^[5]
• Reduce pain associated with rheumatoid arthritis and osteoarthritis.^[6]

History

First discovered in the late 1960s by Dr. Endre Mester, a general surgeon and scientist whose early research demonstrated that laser treatment promoted hair regrowth and wound healing in mice,^[7] and later investigated as a means to promote healing processes during space travel,^[8] photobiomodulation is still in its infancy. It is described in various terms, including red light therapy, low-level light therapy, and photodynamic therapy, among others,^[9] potentially contributing to some confusion regarding its uses and effects.

Clinical evidence supporting the use of photobiomodulation

Hair regrowth

An abundance of evidence demonstrates that photobiomodulation has marked effects on hair regrowth, and data supporting photobiomodulation as a treatment for androgenic alopecia are generally promising.^[1] The trials typically used a wavelength in the 655 nanometer (nm) range with either a helmet device in which lasers had very close contact with the scalp or a hair comb where lasers were in close or complete contact with the scalp. Lasers appeared to be more effective than LED light for hair regrowth.^[1]

Skin aging

The data supporting photobiomodulation as a treatment for skin aging are generally promising. One study found that photobiomodulation was particularly effective at increasing collagen and reducing the appearance of fine lines on the face and neck.^[2] The investigators used wavelengths of 611 to 650nm or 570 to 850nm, with better results achieved at 570 to 850nm. A different study found that photobiomodulation using LED applied directly to the skin using wavelengths of 830nm and 633nm reduced signs of photoaging and improved skin tone, smoothness, and skin clarity.^[10]

Thyroid function Promising evidence suggests that photobiomodulation supports healthy thyroid function in people with hypothyroidism. In a study in which an 830nm laser with an output power of 50 mW was applied directly to the skin adjacent to the thyroid gland, photobiomodulation improved chronic autoimmune-induced hypothyroidism, as evidenced by a reduction in the medication dose required for thyroid hormone replacement therapy.^[3] A follow-up study found that the effects of photobiomodulation endured six years later.^[11] Another study demonstrated a reduction in the medication dose required for thyroid hormone replacement therapy nine months after treatment.^[12]

Muscular performance and recovery

The data supporting the use of photobiomodulation to promote muscle performance and recovery have been inconsistent, likely due to differences in the various study protocols. A meta-analysis investigating the effects of photobiomodulation on muscle performance found that photobiomodulation was beneficial, but the quality of the analysis is suspect. However, most of the studies applied wavelengths in the red (630 to 660 nm) and near-infrared (808 to 950 nm) spectral regions and used LEDs, lasers, or both in direct contact with the skin. The positive results were typically observed with an energy dose range of 20 to 60 Joules for small muscle groups and 60 to 300 Joules for large muscle groups and a maximal power output of 200 milliwatts (mW) per diode. ^[4]

Depression

The evidence supporting the use of photobiomodulation for depression is limited and of poor quality, due primarily to flaws in study design. For example, because 50 percent of the patients in the treatment group were taking antidepressants, while only 36 percent of those in the placebo group were, the participants in the photobiomodulation treatment group appeared to be more responsive. In addition, the physicians who interpreted the results were not properly blinded.^[5]

Rheumatoid arthritis and osteoarthritis

The data suggesting that photobiomodulation is beneficial for people with rheumatoid arthritis and osteoarthritis are weak. The authors of a meta-analysis reviewed findings from studies in which one group received a treatment laser and a placebo group received a placebo laser. They also analyzed studies in which people received a treatment laser on one hand and a placebo laser on the other hand. They found that people with rheumatoid arthritis had 70 percent less pain than those who received the placebo laser. However, people who received a treatment laser on one hand and a placebo laser on the other demonstrated improvement in both hands regarding pain and disease, suggesting a robust placebo effect.^[6] The same meta-analysis also found no effect of photobiomodulation on osteoarthritis, and other studies showed the same.^[13]

Commercial photobiomodulation devices

A popular line of commercial photobiomodulation devices uses red and near-infrared wavelengths in the mid-600 and mid-800 nm range, respectively. The devices allow mixing and matching between red and near-infrared or switching each wavelength on and off. Notably, while manufacturers of many clinical and commercially available devices claim to have “FDA approval," they actually have FDA clearance for safety, which does not ensure efficacy.^[14] See the FAQ section below for more information about commercial devices.

Mechanisms

Photobiomodulation's primary mechanism of action involves chromophores, a class of light-sensitive molecules present in cells. The principal chromophores involved in photobiomodulation are cytochrome c oxidase in the mitochondria and light-sensitive ion channels in cell membranes (primarily used in the research setting).

Enhanced mitochondrial function

Photobiomodulation activates cytochrome c oxidase,^[15] a crucial enzyme in the mitochondrial electron transport chain. This activation drives ATP production,^[15] fueling cellular processes and enhancing cellular metabolism. The upregulation of ATP production also promotes the release of reactive oxygen species,^[15] triggering signaling pathways that regulate cell survival, proliferation, and gene expression. The mitochondrial effects of photobiomodulation appear to be context-dependent, however: In healthy mitochondria, photobiomodulation exerts little to no effect.

Anti-inflammatory and immune effects

Photobiomodulation exerts anti-inflammatory effects via modulation of the body's immune responses. For example, it suppresses the production of proinflammatory cytokines while promoting anti-inflammatory cytokines, thereby alleviating inflammatory conditions.^[16],^[17] In addition, photobiomodulation enhances phagocytic activity,^[18] facilitating the clearance of cellular debris and pathogens by immune cells.

New blood vessel formation and tissue repair

Light in the near-infrared range stimulates the cellular release of nitric oxide,^[19] promoting vasodilation and increased blood flow. This, in turn, promotes the formation of new blood vessels, a critical aspect of tissue repair and wound healing. Photobiomodulation also enhances the proliferation and migration of fibroblasts,^[20] accelerating the synthesis of collagen and extracellular matrix proteins.^[21]

A growing body of evidence suggests that photobiomodulation promotes bone formation via the proliferation and recruitment of osteogenic cells,^[22],^[23] which could have applications for healing fractures or promoting bone deposition in people with osteoporosis.

Research applications

In the research setting, photobiomodulation exploits ion channels – proteins embedded in the cell membrane that can undergo conformational changes in response to specific wavelengths of light. This conformational change alters the flow of ions across the cell membrane, leading to various cellular effects.

For example, introducing channel rhodopsin proteins (light-sensitive proteins found in algae) into mammalian cells enables the target cells to respond to light.^[24] When exposed to specific wavelengths of light, channel rhodopsins undergo a conformational change, opening the ion channel and allowing the passage of cations, such as sodium or calcium, to cross the cell membrane. This influx of ions depolarizes the cell, triggering downstream signaling events.^[24] By expressing channel rhodopsins in specific cell types or tissues, researchers can use photobiomodulation to selectively activate or modulate neuronal activity, muscle contractions, or other cellular processes, depending on the target tissue and application.^[25],^[26]

Modalities

Photobiomodulation employs various modalities, including low-level laser therapy (LLLT), light-emitting diode therapy (LEDT), intranasal photobiomodulation, and transcranial photobiomodulation. Several parameters, including wavelength, energy density, power output, and duration of application dictate each.

Low-level laser therapy

LLLT is commonly used for wound healing, pain management, and musculoskeletal disorders.^[27] It uses laser light in the visible to near-infrared spectrum. LLLT devices have different power densities, energy fluences, and wavelengths tailored to target specific tissues and conditions.

Light-emitting diode therapy

LEDT is used for many applications, including skin rejuvenation, acne treatment, and hair regrowth.^[27],^[28] It uses light-emitting diodes, commonly known as LEDs, which produce a broader range of wavelengths that are typically less powerful than lasers. LEDT devices can cover larger treatment areas and are more cost-effective than lasers.^[27]

Intranasal photobiomodulation

Intranasal photobiomodulation involves the delivery of light to the nasal cavity using specialized devices that can reach the blood vessels and nerves in the nasal mucosa, facilitating systemic effects. Intranasal photobiomodulation has demonstrated effects in neurological disorders such as Alzheimer's disease, Parkinson's disease, and depression.^[29],^[30] It has also been used as a strategy to restore olfactory losses associated with COVID-19.^[31]

Transcranial photobiomodulation

Transcranial photobiomodulation delivers light to the brain via the scalp and skull. It can penetrate the brain tissue, influencing neuronal activity and promoting neuroprotective effects. Evidence suggests that transcranial photobiomodulation may benefit various neurological and psychiatric conditions.^[32]

Photodynamic therapy

Photodynamic therapy combines the use of light-sensitive drugs called photosensitizers with specific wavelengths of light to induce therapeutic effects. A light-activated photosensitizer drug generates reactive oxygen species that selectively destroy abnormal cells or pathogens. Photodynamic therapy is commonly used in dermatology to treat certain types of cancer, skin conditions, and localized infections.^[33]

Conclusion

Photobiomodulation is a non-invasive, light-based therapeutic technique that uses specific wavelengths of light to stimulate biological processes within cells and tissues. It is often described in a wide range of terms, potentially contributing to some confusion regarding its uses and effects. In addition, photobiomodulation modalities differ by wavelength and power, influencing the amount of light penetrating the body's tissues. Protocols for studying photobiomodulation vary considerably, making it difficult to conclude its efficacy. Clinical evidence supporting the use of photobiomodulation is limited and of varied quality.

FAQs

Q: Can commercial devices produce the effects of photobiomodulation?

Putting aside issues of heterogeneity and potential conflicts of interest, some of the research seems promising. Therefore, it’s a natural question to speculate what consumer devices might produce some of the effects described above. While some of the power outputs and wavelengths may not be available outside a lab setting, specific effects do seem achievable based on the specifications of consumer devices, such as:

• Regrowing hair

  • Research setting^[1]
  • Wavelength: ~655 nm
    • Irradiance:
    • Combination of LED and laser: ≤22 mW/cm² (LED) and ≤4.6 mW/cm² (laser) to 92.15 mW/cm² (LED + laser)
    • Laser: 2.34 to 3.5 mW/cm²
  • Commercially available devices:
  • iRestore ID-520, WELLMIKE Technology Corp. (LED wavelength 660 nm, irradiance: ≤22 mW/cm²; laser wavelength: 660 nm: ≤4.6 mW/cm²)^[34]
  • Hairmax Lasercomb, Lexington International (laser wavelength: 665 nm, irradiance: not specified (3.7 mW per beam))^[35],^[36]

• Skin aging

  • Research setting:^[2]
  • Wavelength: 570 to 850 nm
  • Irradiance, LED: 10.3 mW/cm² to 70 mW/cm²
  • Commercially available devices:
  • Omnilux Plus, Photo Therapeutics Ltd. (LED wavelength: 830 nm, irradiance 55 mW/cm²) ^[37]
  • Omnilux Revive2, Photo Therapeutics Ltd. (LED wavelength: 633 nm, irradiance: 105 mW/cm²)^[37]
  • Lightstim ProPanel, LED intellectual properties LLC (LED wavelength: combination of 605, 630, 660 and 855 nm, irradiance: 65 mW/cm²)

• Muscular performance and recovery

  • Research setting:^[4]
  • Wavelength: 808 to 950 nm and 630 to 660 nm
  • Energy: 20 to 60 Joules for small muscle groups and 60 to 300 Joules for large muscle groups
  • Commercially available devices:
  • Multi Radiance Medical MR4 (laser wavelength: 905 nm, energy: 0.285 J, irradiance: 2.84 mW/cm²; infrared LED wavelength: 875 nm, energy: 15.96 J, irradiance: 77.76 mW/cm²; red LED wavelength: 640 nm, energy: 13.68 J, irradiance: 66.64 mW/cm²)^[38]
  • THOR Photomedicine LX2 (LED wavelength: 660 nm, irradiance: 51mW/cm2; infrared LED wavelength: 850 nm, irradiance: 150mW/cm2)^[39]

• Increasing bone mineralization

  • Dental socket bone preservation
  • Research setting:
    • Wavelength: 808-940 nm
    • Irradiance LED: 20-2500 mW/cm²
  • Commercially available devices:
    • Multi Radiance Medical MR4 (laser wavelength: 905 nm, irradiance: 2.84 mW/cm²; infrared LED wavelength: 875 nm, irradiance: 77.76 mW/cm²; red LED wavelength: 640 nm, irradiance: 66.64 mW/cm²
    • THOR Photomedicine LX2 (infrared LED wavelength: 850 nm, irradiance: 150 mW/cm2; LED wavelength: 660 nm, irradiance: 51mW/cm2)

• Bone healing after rapid maxillary extension

  • THOR Photomedicine LX2 (LED wavelength: 660 nm, irradiance: 332 mW/cm²)

• Osteoarthritis

  • The World Association for Laser Therapy recommends irradiating the knee joint line/synovia with the following doses per treatment spot: ≥4 J using 5–500 mW mean power 780–860 nm wavelength laser and/or ≥1 J using 5–500 mW mean power (>1000 mW peak power) 904 nm wavelength laser.)^[40]
  • Commercially available devices:
    • Intellect Laser, Chattanooga (laser: 850 nm, 6 Joules/point, 100 mW mean output power)^[41]
    • Irradia MIDCARE 904 (laser: 904nm, 3 Joules/point, 60 mean output power)^[42]

• Depression

  • Research setting:^[5]
  • Wavelength: 823 nm
  • Irradiance, LED: 36.2 mW/cm2
  • Commercially available transcranial-intranasal device:
  • Vielight (LED: 810 nm, 100 mW/cm²)