Introduction

Light has profound and diverse effects on the human body, influencing sleep-wake cycles, circadian rhythmicity, mood, and immune function. In recent decades, scientists have begun exploiting the body's responses to light with photobiomodulation, a non-invasive, light-based therapeutic technique. Photobiomodulation employs specific wavelengths of light (measured in nanometers, nm) 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:

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

Evidence supporting the use of photobiomodulation

Skin health and aging

The skin is a critical barrier between the body and the external environment. As such, it is highly vulnerable to environmental exposures, such as ultraviolet light, humidity, and pollutants. The data supporting photobiomodulation as a means to address aspects of skin health and aging are generally promising. This section presents the findings of several reviews and individual studies investigating these effects.

General skin health and appearance

Researchers conducted a literature review of the evidence supporting the use of low-level laser therapy (LLLT) for various skin concerns such as wrinkles, skin discoloration, acne, wound healing, body contouring, and androgenic alopecia (hair loss). They found that a modest amount of research supports the use of LLLT for these skin concerns; however, some of the studies were small, had gross methodological flaws, and were industry-funded, calling the quality of the evidence into question. They also questioned whether LED sources have the same effects as the laser-based systems used in higher-quality studies. The researchers concluded that despite its popularity and success in the market, LLLT requires more solid clinical evidence to substantiate its effectiveness.^[10]

In a single study investigating the effects of photobiomodulation on skin appearance, texture, and collagen density, 113 people received light therapy twice weekly using either a combination of 611 nm to 650 nm or 570 to 850 nm polychromatic light versus a control group that did not receive light therapy. The light intensity and the treatment duration varied in each group. Participants who received light therapy experienced marked improvements in their skin appearance, texture, and collagen density compared to the control group. Interestingly, using a broad range of light wavelengths did not provide additional benefits compared to using only wavelengths in the red light spectrum only (~700 nm). However, both light sources used in this study effectively and safely rejuvenated the skin and increased collagen levels.^[1]

Wrinkles and skin rejuvenation

Twenty-two people with facial wrinkles received eight light-emitting diode (LED) therapy sessions using wavelengths of 830 nm and 633 nm, delivered over four weeks using the handheld Omnilux LED system. Eight weeks after treatment, 74 percent of the participants reported reduced signs of photoaging and improved skin tone, smoothness, and clarity.^[11]

In a similar study, researchers investigated the effectiveness of LED phototherapy for skin rejuvenation in 76 people, 35 to 55 years old, with facial wrinkles. Participants received one of four treatments: 830 nm alone, 633 nm alone, a combination of 830 and 633 nm, or a sham treatment light, twice a week for four weeks, using the Omnilux plusTM and/or Omnilux reviveTM devices. The researchers measured the participants' skin's elasticity and melanin levels and photographed changes. They found that the treatments reduced wrinkles by up to 36 percent and increased skin elasticity by up to 19 percent compared to baseline. They also observed increased collagen, elastic fibers, and activated fibroblasts in the treated areas. The treatment was well-tolerated with no side effects. They concluded that LED phototherapy at specific wavelengths (830 nm and 633 nm) effectively rejuvenates the skin and improves its appearance.^[12]

Interestingly, a similar study using the Ominlux Revive device (mentioned above) found that 91 percent of participants reported visible changes in their skin, and a blinded photographic evaluation observed a clinical response in 59 percent of the participants. However, objective analyses of the skin's hydration and elasticity did not reveal statistically significant changes.^[13]

One hundred thirty-seven women aged 40 to 65 years with varying skin types and signs of aging received ten sessions of red (660 nm) and amber (590 nm) LED treatments over four weeks, with one side of the face treated with each color, using the Cicatrillux LED device. Researchers measured changes in periocular ("crow's feet") wrinkle volume, skin hydration, and skin elasticity. They found that red LED reduced periocular wrinkle volume by 31.6 percent reduction, and amber LED reduced wrinkle volume by 29.9 percent. However, neither treatment improved skin hydration nor elasticity.^[14]

In a similar study, researchers investigated the effects of LED on reducing periocular wrinkles. The study included 52 women who received one of two LED treatments daily for 12 weeks: red light at 660 nm or white light ranging from 411 to 777 nm. The researchers found that both groups of women experienced improvements in their facial wrinkles after 12 weeks. The red LED group had slightly better results; however, there were no significant differences between the two groups. However, the participants who received the red LED treatment reported greater satisfaction with their results. Notably, there was no control group.^[15]

Thirty-two adults received one of four treatments for 12 weeks: KLOX-001 (a topical photoconverter chromophore gel) and placebo light; a placebo gel and KLOX LED; combined KLOX-001 gel and KLOX LED; and a retinol-based cream (standard care). The combined KLOX-001 gel/KLOX LED treatment was more effective than the standard care and placebo light groups in reducing wrinkles and improving brow positioning. Several participants reported skin tightening and improved pore size, skin texture, and overall appearance. The treatments were safe, well-tolerated, and painless.^[16]

Researchers compared the effectiveness of radiofrequency (using Surgitron Dual RF, which uses electric current to generate heat in the skin's dermis, causing collagen to contract) versus LED (using the Light Active BiMedica device) for skin rejuvenation. The study involved 30 women aged 35 to 65 years with signs of photodamage around their eyes. Researchers assigned the participants to one of three groups: five radiofrequency treatments, spaced ten days apart; eight LED sessions, spaced five days apart; and a combination of one radiofrequency session and two LED sessions, repeated five days apart. The researchers found that the combination of LED and radiofrequency treatments yielded the best results in improving all aspects of skin rejuvenation. The participants reported higher satisfaction levels with skin texture, wrinkle reduction, and firmness when using both treatments together. However, LED alone improved skin texture and reduced wrinkles, while radiofrequency alone enhanced skin texture and firmness.^[17]

Safety, dose, and parameters

A recent review assessed the potential cancer-causing effects of photobiomodulation when used for skin rejuvenation. Reviewers examined data from seven clinical trials, 41 in vitro studies, and nine in vivo studies. They found that within specific parameters, red and near-infrared light used in photobiomodulation primarily promotes healthy cell growth with unclear effects on cell viability. However, it tends to reduce the growth and viability of cancer cells. Although photobiomodulation does not induce abnormal changes in healthy cells, the potential invasiveness of cells exposed to photobiomodulation therapies remains uncertain. Based on current evidence, photobiomodulation appears to be safe for skin rejuvenation and does not appear to be contraindicated for people with a history of cancer treatment.^[18]

Another group of researchers used a dose-escalation study design to determine the maximum tolerated dose in people with different skin colors. A group of 60 healthy participants with varying skin types received red-light LED (160 to 640 Joules per centimeter squared, J/cm2) or mock treatment on their forearms three times a week for three weeks. A group of 55 non-Hispanic Caucasians received red-light LED (480 to 640 J/cm2) or sham treatment for the same frequency and duration. Although some blistering and prolonged redness occurred at 480 J/cm2 for participants with different skin types and at 640 J/cm2 for non-Hispanic Caucasians, these events were rare, and most participants experienced only mild and temporary redness and increased skin pigmentation, the latter of which resolved within three months of treatment.^[19]

Other resources

To learn more about the effects of photobiomodulation on skin, as well as recommendations for its clinical and scientific use, see these reviews and commentaries:

• Light emitting diodes technology-based photobiomodulation therapy (PBMT) for dermatology and aesthetics: Recent applications, challenges, and perspectives^[20]
• Photobiomodulation: The Clinical Applications of Low-Level Light Therapy^[10]
• Photobiomodulation devices for hair regrowth and wound healing: a therapy full of promise but a literature full of confusion^[21]
• The use of lasers and light sources in skin rejuvenation ^[22]
• Light-emitting diodes in dermatology: A systematic review of randomized controlled trials^[23]
• Role of Visible Light on Skin Melanocytes: A Systematic Review^[24]
• The expression of opsins in the human skin and its implications for photobiomodulation: A Systematic Review^[25]

Joint and bone health

Rheumatoid arthritis and osteoarthritis

Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the joints, while osteoarthritis is a degenerative condition caused by joint wear and tear over time. Photobiomodulation therapies target many of the pro-inflammatory processes involved in the pathogenesis and progression of these two conditions. Researchers have conducted many reviews and individual studies on the effects of photobiomodulation on rheumatoid arthritis and osteoarthritis in cell lines, animal models, and humans. However, many of the human trials are small, typically involving fewer than 50 participants, and the overall quality of the data is weak.

A systematic review and meta-analysis of ten randomized controlled trials involving 263 participants investigated the effects of LLLT versus sham, laser, or high-intensity laser treatment on rheumatoid arthritis. The LLLT devices used in these trials used wavelengths of 820 nm to 950 nm, power outputs ranging from 15 milliwatts (mW) to 940 mW, and a total number of sessions ranging from eight to 16. The study durations varied from four to 24 weeks. The reviewers found LLLT to be more effective than the control treatments (sham, laser, high-intensity laser), with little heterogeneity among the studies. It's important to note that only three of the studies assessed the treatment effects in follow-up, potentially limiting the ability to draw conclusions regarding the long-term effects of LLLT. They concluded that LLLT appears to have a beneficial effect compared to sham, laser, and high-intensity laser treatments for rheumatoid arthritis. However, further research with larger sample sizes and longer follow-up periods is needed to strengthen the evidence and better understand the specific conditions in which LLLT may be most effective.^[26]

Knee osteoarthritis

Researchers conducted a systematic review and meta-analysis to assess the efficacy of LLLT for managing pain and disability in people with knee osteoarthritis based on findings from randomized placebo-controlled trials. The analysis included 22 studies involving 1,063 participants whose average age was 60 years. Most participants were female and overweight (average body mass index, 29.55). The LLLT devices used in the trials provided a mean power output of 10 mW to 400 mW and used varied wavelengths. The studies used LLLT as an adjunct to exercise therapy in 11 of the trials, and the average treatment duration was about 3.5 weeks. The number of treatment sessions varied from eight to 16, with sessions conducted two to five times weekly and treating two to 12 areas per session. The findings revealed that LLLT reduced pain and disability better than a placebo in people with knee osteoarthritis when assessed at the end of therapy and during follow-ups one to 12 weeks later. Subgroup analysis indicated that recommended LLLT doses were more effective in reducing disability than non-recommended doses, but only at one of the time points assessed. The reviewers deemed the overall methodological quality of the included trials adequate, with a low risk of bias in most instances. They concluded that LLLT shows promise to reduce pain and disability in people with knee osteoarthritis.^[27]

Another systematic review and meta-analysis investigated the effect of LLLT plus exercise therapy versus a placebo treatment plus exercise in people with knee osteoarthritis. The 14 studies involved 820 people aged 40 years and older, and the treatments were applied twice weekly for five to eight weeks at 4 to 8 Joules, using a wavelength of 640 nm to 905 nm per site. They found that LLLT plus exercise provided better pain relief than a placebo treatment plus exercise at the end of the interventions. During follow-up, LLLT plus exercise demonstrated pain relief benefits over the placebo plus exercise. However, LLLT plus exercise was not superior to the placebo plus exercise in improving range of motion, muscle strength, and function in patients with knee osteoarthritis. They concluded that their findings support the use of LLLT in combination with exercise therapy for pain relief in knee osteoarthritis patients; however, they noted that there was statistically significant heterogeneity among the studies.^[28]

Finally, an individual study investigated the effects of combining an exercise program with photobiomodulation therapy on functional capacity and inflammatory biomarkers in 42 adults with knee osteoarthritis. Participants received one of three interventions: exercise + sham photobiomodulation, exercise + photobiomodulation (infrared, 808 nm), or neither (control group). At the end of the eight-week trial, both exercise groups exhibited greater functional capacity than the control group, but the exercise + photobiomodulation group also showed increased levels of interleukin (IL)-10, an anti-inflammatory molecule.^[29]

Other bone and joint-related conditions

Other studies have investigated the effects of photobiomodulation on various bone- and joint-related conditions. This section provides a sampling of the findings.

Achilles tendinopathy

Investigators analyzed the findings of four trials comparing the effectiveness of laser therapy associated with eccentric exercises (which elongate the tendon, placing a greater load on a tendon) to eccentric exercises alone and sham treatments for 119 participants with Achilles tendinopathy. One of the trials found that, at two months, the combination of laser therapy with eccentric exercises reduced pain slightly compared to the other treatments, with an average difference of fewer than three points on a pain scale of zero to ten. However, the range of differences between the groups at three and 13 months was not large enough to be considered significant. On the other hand, when looking at functional assessment, the placebo group showed better improvement at one month, with an average difference of approximately nine points in function scores compared to the other groups. However, this difference was not statistically significant when comparing the groups at three and 13 months. The investigators concluded that the certainty of the evidence was low to very low, and more robust research is needed to determine the efficacy of laser therapy in treating Achilles tendinopathy.^[30]

Lower extremity tendinopathy and plantar fasciitis

Researchers analyzed the findings of 18 randomized controlled trials involving 784 participants (average age, 43 years) with lower extremity tendinopathy or plantar fasciitis. They grouped the trials according to laser dose recommendations by the World Association of Laser Therapy, which recommends using specific minimum doses for different conditions.^[31] They found that LLLT reduced pain immediately after therapy and at follow-ups four to 12 weeks later. LLLT also reduced disability immediately after therapy and at follow-ups four to nine weeks later. A subgroup analysis revealed that LLLT, when used with exercise, stretching, and corrective insoles, reduced pain better than those interventions alone immediately after therapy and at follow-ups nine weeks later, particularly when using recommended laser doses. The reviewers concluded that LLLT effectively reduces pain and improves disability in the setting of lower extremity tendinopathy or plantar fasciitis; however, some uncertainty remains due to wide margins of error and small sample sizes.^[32]

Shoulder disorders

Researchers analyzed the findings of 11 randomized controlled trials investigating the effects of LLLT on shoulder disorders. The studies included 858 participants, most of whom had impingement syndrome. They found that LLLT, when used with exercise, significantly reduced pain in the short term compared to the control groups. However, they did not observe significant differences between LLLT + exercise and sham LLLT + exercise for pain, shoulder function, or range of motion. The device specifications used in these studies for LLLT used wavelengths between 810 to 904 nm, with an energy density ranging from 1.6 to 5 Joules/cm² (duration: 20 to 150 seconds per spot), applied in 10 to 16 sessions over two to eight weeks.^[33]

Bone tissue regeneration

Researchers delivered a low-level laser treatment (808 nm) to implanted bone marrow stem cells to investigate the effects of LLLT on bone tissue regeneration in mice. They delivered the same treatment to co-cultured human stem cells and endothelial cells to evaluate the effects of LLLT on cell growth, blood vessel development, and bone formation. They found that LLLT promoted the formation of blood vessels, collagen fibers, and bone tissue in the stem cells. It also increased the expression of genes related to blood vessel growth and bone formation in both stem and co-cultured cells. In addition, they found that reactive oxygen species and HIF-1-alpha (a protein involved in bone remodeling) mediated the effects of LLLT on blood vessel formation and bone regeneration.^[34]

Neck pain

Researchers conducted a systematic review and meta-analysis of 16 randomized controlled trials involving 820 people, comparing the effectiveness of LLLT with a placebo or active control in acute and chronic neck pain cases. They rated the participants' pain on a visual analog scale of zero to 100 millimeters. They found that LLLT was 69 percent more effective at reducing acute neck pain and 400 percent more effective at reducing chronic neck pain than a placebo. Among the 11 trials reporting changes in the visual analog scale, LLLT reduced pain intensity by 19.86 millimeters. The benefits of LLLT endured, with seven trials finding that pain relief persisted for up to 22 weeks post-treatment. The reduction in pain intensity at the mid-point follow-up was 22.07 millimeters. Notably, the side effects from LLLT were mild and similar to the placebo's, suggesting that LLLT is well-tolerated and safe for managing neck pain. The investigators concluded that LLLT could be a promising non-pharmacological treatment option for neck pain.^[35]

Fractures

Investigators conducted a systematic review and meta-analysis of the effects of photobiomodulation on fractures. It included two randomized clinical trials with 104 participants aged 24 to 36 years. They found that photobiomodulation was more effective than the placebo in reducing pain, as measured by a visual analog scale, at the end of treatment (between one day and two weeks), with an average difference of 1.19 millimeters on the scale. They did not observe differences in fracture healing between the groups in both analyses. However, after two weeks, the group that underwent photobiomodulation treatment showed marked improvement in physical function. The investigators concluded that photobiomodulation may reduce pain and improve physical function in people with fractures. However, they classified the certainty of evidence as very low and suggested that more high-quality studies are needed to understand the potential benefits of photobiomodulation in fracture treatment.^[36]

Targeting causative factors in bone- and joint-related disorders

Inflammation

Researchers investigated the effects of red LED light on human synoviocytes, a class of cells that promote joint damage by releasing pro-inflammatory molecules. They treated the cells with tumor necrosis factor-alpha (TNF-alpha, a pro-inflammatory molecule) and then administered red LED light therapy (630 nm). They found that red LED light exposure inhibited the synoviocytes' growth and movement, decreased the expression of pro-inflammatory molecules, and increased the expression of the anti-inflammatory molecule IL-10. In addition, the red LED light altered the levels and activation of proteins involved in TRPV4/PI3K/AKT/mTOR – a TNF-alpha-triggered signaling pathway involved in cell growth, movement, and inflammation.^[37]

Oxidative stress

Another team investigated the effects of photobiomodulation combined with exercise on oxidative stress (a driver of inflammation) in an animal model of rheumatoid arthritis. They administered LLLT (808 nm) to the medial and lateral sides of the animals' knees and then exercised them on a treadmill for five weeks. They found that the combined treatment reduced lipid peroxidation (a marker of oxidative damage) and increased the activity of antioxidant enzymes, particularly superoxide dismutase, glutathione peroxidase, and catalase.^[38]

Although the findings presented here are compelling, the data suggesting that photobiomodulation benefits people with bone and joint disorders are weak overall, and some evidence indicates a robust placebo effect.^[2] In addition, many of the human trials also include an exercise component, which could confound the findings due to the anti-inflammatory nature of exercise.

Other resources

To learn more about the effects of photobiomodulation on joint disorders, see these reviews:

• Molecular and Cellular Mechanisms of Arthritis in Children and Adults: New Perspectives on Applied Photobiomodulation^[39]
• Efficacy of low-level laser therapy on pain and disability in knee osteoarthritis: a systematic review and meta-analysis of randomised placebo-controlled trials^[27]
• Effect of low-level laser therapy plus exercise therapy on pain, range of motion, muscle strength, and function in knee osteoarthritis – a systematic review and meta-analysis^[28]
• Effects of Laser Therapy on Rheumatoid Arthritis A Systematic Review and Meta-analysis^[26]

Muscle performance and recovery

During exercise, muscles fatigue and become weak, hindering performance and increasing the risk of injury. 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.

Performance

A meta-analysis of 28 studies investigating the effects of photobiomodulation on muscle performance found that the treatment was beneficial; however, the quality of the analysis is suspect due to how some of the studies were weighted. Most of the studies applied wavelengths in the red (630 nm to 660 nm) and near-infrared (808 nm 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 J to 60 J for small muscle groups and 60 J to 300 J for large muscle groups and a maximal power output of 200 mW per diode.^[3]

Researchers conducted a meta-analysis of randomized controlled trials investigating the effects of LLLT on muscular performance and soreness recovery, primarily in male athletes. Their analysis included 24 studies involving 104 participants, mostly males between 15 and 40 years old. They found that LLLT benefited muscle strength, contract repetition number (the number of times an athlete can perform a specific muscle contraction or exercise before reaching fatigue or exhaustion), and soreness. Specifically, LLLT using wavelengths of 850 nm to 880 nm for various muscle sites increased lower-limb muscle strength at various follow-up periods (24-hour, 48-hour, 96-hour, and eight-weeks) but had little effect on participants that received the therapy postexercise. LLLT using wavelengths of 660 nm to 830 nm increased contract repetition numbers in the pre-exercise laser group compared to the control group. In addition, LLLT using wavelengths of 810 nm to 830 nm reduced soreness after exercise. Participants who received LLLT had lower concentrations of creatine kinase, lactate, and IL-6 (a pro-inflammatory molecule), suggesting reduced muscle damage, inflammation, and lactate accumulation. Wavelengths ranged from 623 nm to 830 nm. However, LLLT did not significantly affect time to fatigue, pro-inflammatory factors, jumping height test, maximal oxygen usage tests, and hamstring strain injury recovery. The reviewers concluded that their meta-analysis suggests that LLLT bolsters athletes' muscle strength, contract repetition number, and soreness recovery. However, the effects on other performance and recovery factors were inconclusive or showed no significant difference compared to the control group.^[40]

Reviewers conducted a systematic review and meta-analysis to analyze the effects of photobiomodulation on exercise performance in 37 crossover, placebo-controlled trials, including 586 participants, primarily young, healthy male athletes. They found that photobiomodulation did not benefit muscle strength performance for single-joint exercises but did improve muscle endurance performance when applied before exercise. In cycling, photobiomodulation using 630 nm to 850 nm wavelengths with a total energy of 42 J to 405 J on the quadriceps femoris increased time-to-exhaustion better than a placebo. However, there were no changes in all-out sprint performance. In running, photobiomodulation using wavelengths of 660 nm to 950 nm with a total energy of 27 J to 60 J on the quadriceps femoris did not improve time to exhaustion, time-trial performance, or repeated-sprint performance. Similarly, in swimming, photobiomodulation using 630 nm to 850 nm with a total energy of 130 J to 152 J on the gluteus maximus did not influence time-trial performance.

The analysis revealed that photobiomodulation may favor the activity of slow-twitch motor units, improving muscle endurance and time-to-exhaustion performances. The researchers posited that highly trained athletes, who often have more muscle mitochondria, may respond better to photobiomodulation. However, photobiomodulation did not enhance muscle strength or performance reliant on fast-twitch motor units, such as all-out sprints and time-trial performances in running and swimming.

Overall, photobiomodulation appears to be effective in improving muscle endurance and time-to-exhaustion in specific forms of exercise but has limited influence on other performance aspects. Their findings suggest that muscle type and individual training levels influence photobiomodulation's effectiveness.^[41]

Exercise-induced fatigue

Researchers analyzed the findings of 20 randomized controlled trials involving 394 participants investigating the effectiveness of laser therapy in reducing exercise-induced fatigue. The laser devices' wavelengths in the studies ranged from 630 nm to 970 nm, with most falling between 800 nm and 850 nm. The energy delivered per site varied from 0.6 J to 50 J, and the power of the lasers ranged from 80 mW/diode to 200 mW/diode. They found that laser therapy did not significantly affect lactate levels (a marker of fatigue), creatine kinase (a marker of muscle damage), workload, maximum voluntary contraction, or the number of repetitions performed. While some individual studies showed beneficial effects of laser therapy on exercise-induced fatigue, the pooled data did not provide strong evidence of its efficacy. The investigators expressed concerns about the studies' heterogeneity and potential publication bias.^[42]

In a small, randomized controlled trial, 27 soccer players received a pre- or post-fatigue infrared laser treatment (830 nm) or a placebo, delivered in two sessions, with a one-week interval between treatments. Researchers measured the participants' lactate and creatine kinase concentrations and assessed their performance. Lactate concentrations were considerably lower among the post-fatigue laser treatment group than the placebo group, an effect that endured for at least 15 minutes. Creatine kinase concentrations were also lower in the post-fatigue laser treatment group. However, performance did not differ markedly between the treatment groups.^[43]

In contrast, 28 male futsal players received various LED treatments (905 nm, 875 nm, and 640 nm) to several lower limb sites 40 minutes before matches. The players' performance (determined by playing time) increased, but the distance covered during the match did not.^[44]

Another study compared the effects of low-level light therapy (LLLT, 850 nm, 40 seconds per site) and neuromuscular electrical stimulation (NMES) on 36 volleyball players' performance. They found that both LLLT and NMES enhanced non-dominant lower limb muscle strength, an effect that endured even after a two-week interruption in training.^[45]

Other resources

To learn more about the effects of photobiomodulation on muscle strength and performance, as well as recommendations for its clinical and scientific use, see these reviews and commentary:

• Deconstructing the Ergogenic Effects of Photobiomodulation: A Systematic Review and Meta-analysis of its Efficacy in Improving Mode-Specific Exercise Performance in Humans^[41]
• Efficacy of laser therapy for exercise-induced fatigue^[42]
• Review of light parameters and photobiomodulation efficacy: dive into complexity^[46]
• Use of Photobiomodulation Therapy in Exercise Performance Enhancement and Postexercise Recovery: True or Myth?^[47]
• Clinical and scientific recommendations for the use of photobiomodulation therapy in exercise performance enhancement and post-exercise recovery: current evidence and future directions^[48]

Conditions and safety concerns associated with pregnancy

The American Society for Laser Medicine & Surgery cautions against using photobiomodulation in pregnancy due to the unknown effects on the fetus. However, some research conducted in animals and humans suggests that photobiomodulation during pregnancy is safe. For example, a study in cell culture found that photobiomodulation mitigated the pathological cellular conditions that drive preeclampsia in pregnancy.^[49] A study in rats found that the application of an 808 nm laser to the abdomens of pregnant females reduced or prevented the risks associated with hypoxic-ischemic injury-induced brain injuries in newborns.^[50] A human study found that photobiomodulation safely and effectively reduced pain during labor.^[51] In addition, a recently completed clinical trial investigated the use of photobiomodulation delivered to the head to treat depression during pregnancy. The results of this trial have not yet been published. Furthermore, some evidence suggests that photobiomodulation improves fertility.^[52]

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.^[4] The trials typically used a wavelength in the 655 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.^[4]

Thyroid function

Promising evidence suggests that photobiomodulation supports healthy thyroid function in people with hypothyroidism. In a study in which an 830 nm 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.^[5] A follow-up study found that the effects of photobiomodulation endured six years later.^[53] Another study demonstrated a reduced medication dose required for thyroid hormone replacement therapy nine months after treatment.^[54]

Spinal cord regeneration

Red-light therapy may benefit spinal cord injury. Researchers investigated the effects of two light-based therapy methods using a rat model of spinal cord injury. One method used transcutaneous (through the skin) laser-light treatment, while the other used an implantable device. They found that both delivery methods produced comparable outcomes, with a daily one-minute dose of 660-nanometer laser light for seven days reducing tissue scarring at the injury site and enhancing functional recovery. They also noted increased levels of proteins associated with nerve cell regeneration and improved connectivity between cells in the injured spinal areas. These findings suggest that photobiomodulation enhances recovery after spinal injury in rats and holds potential for future therapeutic applications in humans.^[55]

Vision

Researchers analyzed the findings of five randomized controlled trials investigating the effects of repeated low-level red-light therapy on myopia versus prescription glasses in children. The studies included 833 participants, about half of whom received red-light therapy. The parameters measured included axial length (distance from the front to the back of the eye), spherical equivalent refraction (the power needed to correct vision), and subfoveal choroidal thickness (thickness of the layer beneath the central part of the retina). They found that repeated red-light therapy improved all vision parameters at multiple follow-up periods during the studies. At the 12-month follow-up assessment, the children experienced a 0.31-millimeter decrease in axial length and a 0.63 increase in spherical equivalent refraction, indicating marked improvements in myopia progression and eye structure. These findings suggest that repeated low-level red-light therapy effectively slows or reduces myopia progression in children, leading to less elongation of the eyeball and improved vision.

Commercial photobiomodulation devices

Many popular commercial photobiomodulation devices use red and near-infrared wavelengths in the mid-600 nm 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.^[10] See the FAQ section below for more information about commercial devices.

Mechanisms

Photobiomodulation's primary mechanism of effects 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,^[56] a crucial mitochondrial electron transport chain enzyme. This activation drives ATP production,^[56] fueling cellular processes and enhancing cellular metabolism. The upregulation of ATP production also promotes the release of reactive oxygen species,^[56] triggering signaling pathways that regulate cell survival, proliferation, and gene expression. However, the mitochondrial effects of photobiomodulation appear to be context-dependent: 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.^[57],^[58] In addition, photobiomodulation enhances phagocytic activity,^[59] 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,^[60] 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,^[61] accelerating the synthesis of collagen and extracellular matrix proteins.^[62] Furthermore, a growing body of evidence suggests that photobiomodulation promotes bone formation via the proliferation and recruitment of osteogenic cells,^[63],^[64] which could have applications for healing fractures or promoting bone deposition in people with osteoporosis.

Red light therapy modalities

Photobiomodulation employs various modalities, including LLLT, LED therapy (LEDT), intranasal photobiomodulation, and transcranial photobiomodulation. Several parameters, including wavelength, energy density, power output, and duration of the application dictate each.

Low-level laser therapy

LLLT is commonly used for wound healing, pain management, and musculoskeletal disorders. It employs 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.,^[65] It uses LEDs, which produce a broader range of wavelengths typically less powerful than lasers. LEDT devices can cover larger treatment areas and are more cost-effective than lasers.^[66]

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.^[67],^[68] It has also been used to restore olfactory losses associated with COVID-19.^[69]

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.^[70]

Photodynamic therapy

Photodynamic therapy combines 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.^[71]

Usage and parameters

In one compelling review, researchers evaluated the range of effective versus ineffective parameters in photobiomodulation therapy. They analyzed studies conducted_ in vitro_ with cultured cells or in vivo with different tissues, categorizing them according to their mitochondrial activity. Tissues with higher numbers of mitochondria (such as muscle, brain, heart, and nerves) tended to respond better to lower light doses. In contrast, tissues with lower mitochondrial activity (skin, tendon, and cartilage) responded better to higher light doses. Interestingly, the studies attributed poor results in tissues with high mitochondrial activity to over-dosing rather than under-dosing. These findings highlight the need for standardized protocols in photobiomodulation therapy to ensure consistent and successful results. By understanding the optimal parameters for different tissue types, researchers can enhance the potential of photobiomodulation therapy for treating various medical conditions.^[46]

It is noteworthy that human tissues (skin, fat, muscle, bone) pose a significant obstacle to the passage of light. Reaching a depth of 50 millimeters into living tissue using light in the red spectrum requires an intensity of at least 100 mW/cm2. As a result, low-power light sources applied over large surface areas achieve low-intensity treatments that may not penetrate deep enough into the muscle tissue to produce a measurable biological effect. In addition, timing is critical when using photobiomodulation for preconditioning before exercise. In vivo experiments demonstrate that the best results for exercise performance and muscle energy production occur within three to six hours after the treatment, contradicting previous research suggesting that a five-minute preconditioning with photobiomodulation was the best strategy.^[47]

In another review, researchers identified the optimal parameters for using photobiomodulation to enhance exercise performance based on the findings of systematic reviews and high-quality research focusing on young, healthy adults. They found that for optimal results, the light source should have a specific wavelength, ranging from 640 nm (red) to 950 nm (infrared). The light dose is crucial and varies depending on the muscle group size. A dose between 20 J and 60 J is recommended for small muscles, like the biceps, while a dose between 60 J and 300 J is best for larger muscles, like the quadriceps. Doses between 120 J and 300 J for large muscle groups and 20 J to 60 J for small muscle groups showed the most favorable outcomes for performance enhancement. When comparing these doses to higher ones (above 300 J), the lower doses within the 120 J to 300 J range had better results.

The researchers determined that light therapy should be applied five minutes to six hours before activity for acute effects. For chronic effects related to strength training, it should be performed immediately before each exercise session, and for endurance training, before and after each session. During irradiation, the light source should directly contact the skin, applied with slight pressure. The light should cover as much of the muscle area as possible, and if using single probes, the distance between irradiation points should be less than 2 centimeters.

The reviewers concluded that these recommendations provide valuable guidance on using light therapy effectively to enhance exercise performance in healthy people, but more research is needed for non-healthy or older adults.^[48]

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 various terms, potentially contributing to 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 draw conclusions regarding its efficacy. Clinical evidence supporting the use of photobiomodulation is limited and of varied quality. Still, it indicates that it may be beneficial for skin, muscle, and joint issues, as well as many other health concerns.

FAQs

Q: Can commercial devices produce the effects of photobiomodulation?

Some of the research seems promising despite study heterogeneity and potential conflicts of interest. 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^[4]
  • 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:
  • Hairmax Lasercomb, Lexington International (laser wavelength: 665 nm, irradiance: not specified (3.7 mW per beam))^[72],^[73]
    • Perspective: The comb form may be challenging from a dosing standpoint. For example, studies on hair regrowth have used durations of 8 to 15 minutes to treat the entire scalp. The manual handling may make it difficult to treat all areas for the same amount of time. Also, the unspecified irradiance poses a challenge to compare this product to studies using other devices and treatment parameters.
  • iRestore ID-520 cap, WELLMIKE Technology Corp. (LED wavelength 660 nm, irradiance: ≤22 mW/cm²; laser wavelength: 660 nm: ≤4.6 mW/cm²)^[74]
  • Capillus272 Pro cap (laser wavelength: 650 nm: 2.34 mW/cm2)^[75]
    • Perspective: Laser and LED caps provide a higher usability because, unlike combs, they do not require active participation of the user during the 30-minute treatment period. However, the caps are more expensive and not suitable for the treatment of hair loss on the sides and back of the scalp because the device does not fully cover them.

• Skin aging

  • Research setting:
  • Wavelength: 570 to 850 nm
  • Irradiance, LED: 10.3 mW/cm² to 105 mW/cm²

• Commercially available devices:

  • Omnilux Plus, Photo Therapeutics Ltd. (LED wavelength: 830 nm, irradiance 55 mW/cm²) ^[12]
  • Omnilux Revive2, Photo Therapeutics Ltd. (LED wavelength: 633 nm, irradiance: 105 mW/cm²)^[12]
  • Lightstim ProPanel, LED intellectual properties LLC (LED wavelength: combination of 605, 630, 660 and 855 nm, irradiance: 65 mW/cm²)
  • Omnilux LED mask (red LED wavelength: 630-680 nm, infrared LED wavelength: 800-880 nm, irradiance: 10-60 mW/cm²)

• Perspective: Commercially available photobiomodulation devices used in skin rejuvenation studies consist of multiple LED panels whose distance to the skin must be adjusted manually. The combined or alternating use of shorter and longer wavelengths allows the treatment of superficial and deeper skin layers, which may provide additional benefits over using either alone. Due to their high price and the significant space requirements, they seem more suitable for professional use than for home use. In contrast, more affordable devices, such as masks and handheld devices, were not used in studies. However, the specifications of the Omnilux LED mask are comparable to those of the LED panels.

• Muscular performance and recovery

  • Research setting:^[3]
  • 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)^[76]
  • THOR Photomedicine LX2 (LED wavelength: 660 nm, irradiance: 51mW/cm2; infrared LED wavelength: 850 nm, irradiance: 150mW/cm2)^[77]
  • Perspective: The Multi Radiance photobiomodulation device, with its longer wavelengths, may be more suitable to treat deeper tissue layers than the THOR LX2.

• 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)
  • Perspective: Research on the effects of photobiomodulation on increasing bone mineralization or improving bone healing is very limited. It focuses primarily on dental applications, possibly because the bones of the oral cavity are only covered by thin layers of soft tissue that can be easily penetrated by the light. Devices that use longer wavelengths are more likely to reach bones that are surrounded by thick layers of tissue, but there is no reliable information on promising treatment parameters for these parts of the skeletal system.

• 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.)^[27]
  • Commercially available devices:
    
    • Intellect Laser, Chattanooga (laser: 850 nm, 6 Joules/point, 100 mW mean output power)^[78]
    • Irradia MIDCARE 904 (laser: 904nm, 3 Joules/point, 60 mW mean output power)^[79]
  • Perspective: The current version of the Intellect laser offers the combination of two to three different wavelengths, allowing for different penetration depths. However, the wavelengths are partly outside the range recommended by the World Association for Laser Therapy (WALT). The same is true for its wide range of mean output power. The specifications of the Irradia laser are more limited but within the WALT recommendations. Moreover, the cordless and compact design promises easier handling than the Intellect laser.
    

• Depression

  • Research setting:^[6]
  • Wavelength: 823 nm
  • Irradiance, LED: 36.2 mW/cm2

• Commercially available transcranial-intranasal device:

  • Vielight (LED: 810 nm, 100 mW/cm²)
  • Mito-Saver Near Infrared Photobiomodulation Helmet (LED wavelength: 1070 nm, 1064 nm, irradiance: not specified (256 diodes, 50 mW/diode))
  • Neuradiant 1070, Neuronic (LED wavelength: 1070 nm, irradiance: 20-40 mW/cm²)

• Perspective: There are major differences between the commercially available devices in terms of wavelengths and irradiance. None of these devices have been tested in peer-reviewed studies for efficacy in treating depression, and comparing them to experimental devices is difficult.
  Vielight’s photobiomodulation device appears to be the only device that combines transcranial and intranasal photobiomodulation.